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36,800,841 | An Overview of the Effect of the Wnt Signaling Pathway in Lung Cancer. | Wnt signal is known to play a significant role in many cellular processes such as cell proliferation, survival, self-renewal, and differentiation. This pathway has been linked to various types of cancer after the definition of mutations and various dysfunctions after the discovery of this pathway. Lung cancer is a type of maligned cancer caused by the deterioration of cellular homeostasis due to various reasons, such as the unbalanced proliferation of cells in the lung, gene expression change, epigenetic factors, and mutation accumulation. It is the most common type of cancer among all types of cancer. There are also various intracellular signal transmission pathways known to be active or inactive in cancer. Although the role of the Wnt signaling pathway in lung cancer development has not yet been clearly clarified, its role in the development and treatment of cancer is seen as very important. Active Wnt signaling or Wnt-1 is overexpressed in lung cancer. Therefore, targeting the Wnt signal pathway is important in cancer treatment, especially lung cancer. Because by creating a minimal effect on somatic cells, inhibiting tumor growth, and preventing resistance to classic treatment methods such as chemotherapy, radiotherapy is necessary for the treatment of disease. New treatment methods developed to target these changes will find a cure for lung cancer. In fact, its incidence may be reduced. |
36,800,840 | Antiproliferative Effects of EGFR inhibitor Cetuximab and PARP Inhibitor Combination on Non-Small Cell Lung Cancer Cell Line A549 and Cervical Cancer Cell Line HeLa. | In this study, the efficacy of Cetuximab and Parp inhibitor (Parp 1 inhibitor) used in targeted therapies, alone or in combination, on non-small cell lung cancer cell line A549 and cervical cancer cell line HeLa cells were evaluated. For this purpose different cell kinetic parameters were used. Cell viability, mitotic index, BrdU labelling index and apoptotic index were evaluated in experiments. In single applications Cetuximab at concentrations ranging from 1 mgml to 10 mgml and Parp inhibitor at concentrations 5 µM -7 µM - 10 µM were applied. IC50 concentration of Cetuximab for A549 was 1 mgml, the IC50 concentration of Cetuximab for HeLa was 2 mgml, the IC50 concentration of Parp inhibitor for A549 was 5 µM, and the IC50 concentration of Parp inhibitor for HeLa was 7 µM. In both single and combinations, there was a significant decrease in cell viability, mitotic index, BrdU labelling index and there was a significant increase in apoptotic index. A comparison of cetuximab, PARPi and combination applications showed the superiority of combined applications over single applications in all cell kinetic parameters used. |
36,800,677 | Real-world evaluation of atezolizumab and etoposide-carboplatin as a first-line treatment for extensive-stage small cell lung cancer. | Despite the obvious benefits of adding immune checkpoint inhibitors to platinum-etoposide chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), real-world data remain scarce. This retrospective study included 89 patients with ES-SCLC treated with platinum-etoposide chemotherapy alone (chemo-only group n 48) or in combination with atezolizumab (atezolizumab group n 41) and compared the survival outcomes between these two groups. Overall survival (OS) was significantly longer in the atezolizumab group than in the chemo-only group (15.2 months vs. 8.5 months p 0.047), whereas the median progression-free survival was almost the same (5.1 months vs. 5.0 months) in both groups (p 0.754). Subsequent multivariate analysis revealed that thoracic radiation (hazard ratio HR, 0.223 95% confidence interval CI, 0.092-0.537 p 0.001) and atezolizumab administration (HR, 0.350 95% CI, 0.184-0.668 p 0.001) were favorable prognostic factors for OS. In the thoracic radiation subgroup, patients who received atezolizumab demonstrated favorable survival outcomes and no grade 3-4 adverse events (AEs). The addition of atezolizumab to platinum-etoposide resulted in favorable outcomes in this real-world study. Thoracic radiation was associated with improved OS and acceptable AE risk in combination with immunotherapy in patients with ES-SCLC. |
36,800,626 | Adverse reactions and efficacy of camrelizumab in patients with lung adenocarcinoma with high PD-L1 expression A case report. | Immune checkpoint inhibitors have been rapidly developed for lung cancer therapy and major clinical guidelines have recommended them as the optimal first-line treatment for PD-L1-positive advanced lung cancer. Unfortunately, there is a lack of efficient prediction tools for the occurrence of immune-related adverse events (irAEs) caused by immunotherapy, and there is a lack of real-world data on the processing of irAEs, particularly those occurring in multiple systems simultaneously. We report a 62-year-old male with expectoration who was diagnosed with lung adenocarcinoma with brain and bone metastases. The results of the lung cancer tissue biopsy showed lung adenocarcinoma. Gene detection results of lung cancer tissue biopsy showed that the KRAS gene G12D was mutated and PD-L1 was positive, with a tumor proportion score of 95% (Dako 22C3 IHC platform). The patient initially received 1 cycle of pemetrexed in combination with cisplatin-based chemotherapy. After the results of PD-L1 testing were reported, he received 1 cycle of camrelizumab immunotherapy in combination with pemetrexed plus cisplatin based chemotherapy. Seventeen days after treatment, the patient presented with symptoms such as yellow staining of the sclera and skin, itching throughout the body, dry mouth, and ecchymosis of the skin of the right lower extremity, which continued to worsen. Following treatment with 2 mgkg methylprednisolone, the patients condition continued to deteriorate. IrAEs were controlled after dose escalation to 8 mgkg in combination with plasma exchange therapy and treatment with multiple doses of mycophenolate ester. The patient then received no treatment for almost 2 months, but examination revealed that the tumor still had a persistent shrinkage reaction. Camrelizumab has been well tolerated in several studies, but in patients with high PD-L1 expression and a G12D mutation in KRAS, one should be alert to the development of serious or even multisystem immune-related adverse effects. Timely and individualized selection of the hormone dosage is essential for the treatment of immunotherapy-induced multisystem irAEs. |
36,800,601 | Reverse predictive analysis of Rhizoma Pinelliae and Rhizoma Coptidis on differential miRNA target genes in lung adenocarcinoma. | To use bioinformatics and network analysis to reveal the mechanism of Rhizoma Pinelliae-Rhizoma Coptidis herb pair in the treatment of lung adenocarcinoma. The target and pathway of Rhizoma Pinelliae-Rhizoma Coptidis herb pair in the treatment of lung adenocarcinoma were explored by online databases and network analysis tools, and the potential biomarkers of Rhizoma Pinelliae-Rhizoma Coptidis herb pair in the treatment of lung adenocarcinoma were predicted in reverse. A total of 59 traditional Chinese medicine compounds and 510 drug targets were screened in this study. A total of 25 micro-RNAs and 15,323 disease targets were obtained through GEO2R software analysis. In the end, 294 therapeutic targets and 47 core targets were obtained. A total of 186 gene ontology enrichment assays were obtained, and core therapeutic targets play multiple roles in biological processes, molecular functions, and cellular composition. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the core targets were mainly enriched in cancer-related pathways, immune-related pathways, endocrine-related pathways, etc, among which the non-small cell lung cancer pathway was the most significant core pathway. Molecular docking shows that the compound and the target have good binding ability. Rhizoma Pinelliae-Rhizoma Coptidis herb pair plays a mechanism of action in the treatment of lung adenocarcinoma through multiple targets and pathways. miR-5703, miR-3125, miR-652-5P, and miR-513c-5p may be new biomarkers for the treatment of lung adenocarcinoma. |
36,800,595 | Clear cell sugar tumor of the lung Diagnostic characteristics of a rare pulmonary tumor A case report and review of literature. | Clear cell tumors of the lung (CCTLs), also known as sugar tumors for an abundant cellular glycogen concentration, are an extremely rare type pulmonary neoplasm. Often, they are incidentally found on chest roentgenogram or computed tomography scan during routine examination. CCTLs usually present with nonspecific symptoms that pose a diagnostic challenge to clinicians. Accordingly, histopathology remains the gold standard for diagnosing. Moreover, some of them can present with either appearances or histopathological features similar to other pulmonary neoplasms under the light microscope, including pulmonary malignancy, thereby causing misdiagnosis prior to or after surgery. Accordingly, herein, we describe a rare case of CCTL, review the literature has been published, and then discuss the benign versus malignant nature of this rare tumor. A 59-year-old man presented due to a high-density chest nodule in the left diaphragm. The patients medical history was unremarkable and he also denied smoking in the past. Physical examination, there were no noted signs. A new chest contrast-enhanced computed tomography revealed a 3.2 × 2.5 cm, solitary, circular nodule with a smooth edge located in the beside of the left thoracic aorta. Postoperative pathological and immunohistochemical examinations of the surgical specimens revealed a final diagnosis of CCTLs. The patient underwent video-assisted thoracoscopic surgery. A wedge resection of left lower lung lobe was carried out and the tumor node was successfully removed alongside normal surrounding parenchyma. The operation was successful. Then the patient recovered completely and continued to do well on postsurgical thoracic surgical clinic visits. The tumor was a benign tumor, and the patient did not require any additional treatment. The patient had been followed-up regularly for 4 years after surgery she did not experience any complications and remained disease-free. CCTLs should be considered in the differential diagnosis if a patient shows a solitary, circular chest nodule with a smooth edge. They are extremely rare lung tumors that must be differentiated from other lung tumors, especially the malignant tumors. Although pathological and immunohistochemical findings are important for making the diagnosis, the varying histopathological features on microscope make diagnosis difficult. The current case highlights the importance of physicians being aware of and suspecting CCTLs in similar cases, along with knowing the characteristics of CCTLs for the diagnosis and differential diagnosis. |
36,800,552 | Incremental Health Care Costs of Anxiety and Depression Among Medicare Beneficiaries With Cancer. | Mental health comorbidities are commonplace among patients with cancer and have been associated with adverse health outcomes and elevated health care costs. Given the rapidly evolving cancer care landscape, an updated understanding of the prevalence and costs of mental health conditions among patients with cancer is needed. This study assessed the incremental costs of anxiety and depression among Medicare beneficiaries with cancer. This retrospective cohort study used the SEER-Medicare database. Patients diagnosed with melanoma, breast, lung, prostate, or colorectal cancer between July 2013 and December 2017 were followed for at least 12 months and up to 36 months after cancer diagnosis. Patients were categorized on the basis of anxietydepression (AD) diagnosis (1) predating cancer, (2) onset after cancer, or (3) no AD. Multivariable regression was used to estimate differences in all-cause incremental costs (before Of 230,626 patients, 10% had AD before their cancer diagnosis and 22% were diagnosed after cancer. In the first year after cancer diagnosis, average monthly health care costs were $5,750 in US dollars (USD) for patients with newly onset, $5,208 (USD) for patients with preexisting, and $3,919 (USD) for patients without a diagnosis of AD. The incremental cost of cancer was the greatest among patients with newly onset AD-$1,458 (USD) per month greater than those with no AD. Similar patterns were observed across cancer types and stages. One in three Medicare beneficiaries with cancer in this study had a diagnosis of anxiety or depression. Newly onset AD is associated with an increase in health care costs of $17,496 (USD) per year. Screening and management of mental health conditions for patients with cancer should be part of coordinated oncology care. |
36,800,443 | SGN-CD228A is an investigational CD228-directed antibody-drug conjugate with potent antitumor activity across a wide spectrum of preclinical solid tumor models. | SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of a humanized antibody, hL49, with high specificity and affinity for CD228 that is stably conjugated to 8 molecules of the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via a novel glucuronide linker. We performed comprehensive immunohistochemical studies, which corroborated published RNA-seq data and confirmed low CD228 expression in normal tissues and high expression in several cancers, including melanoma, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer, and pancreatic cancer. SGN-CD228A was efficiently internalized in various tumor cell types, and its cytotoxic activity was dependent on CD228 expression and internalization and intrinsic sensitivity to the MMAE payload. Compared to the valine-citrulline dipeptide linker, the novel glucuronide linker increased the cellular retention of MMAE in vitro and conferred improved antitumor activity against melanoma cell lines in vitro and in vivo. Additionally, SGN-CD228A was active across melanoma, TNBC, and NSCLC cell line- and patient-derived xenograft models with heterogeneous antigen expression. In vivo, CD228 expression was important for response to SGN-CD228A but was not well-correlated across all tumor types, suggesting that other factors associated with ADC activity are important. Overall, SGN-CD228A is a CD228-directed, investigational ADC that employs innovative technology and has compelling preclinical antitumor activity. SGN-CD228A is being investigated in an ongoing Phase I clinical trial (NCT04042480) in patients with advanced solid tumors. |
36,800,412 | Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis. | Neutrophils, the most abundant innate immune cells, function as crucial regulators of the adaptive immune system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions are intrinsic or acquired within the pathological tissue environment. Here, using mouse models of metastatic breast cancer in the lungs, we show that, although neutrophils isolated from bone marrow (BM) or blood are minimally immunosuppressive, lung-infiltrating neutrophils are robustly suppressive of both T cells and natural killer (NK) cells. We found that this tissue-specific immunosuppressive capacity of neutrophils exists in the steady state and is reinforced by tumor-associated inflammation. Acquisition of potent immunosuppression activity by lung-infiltrating neutrophils was endowed by the lung-resident stroma, specifically CD140a |
36,800,306 | Primary Hepatic Inflammatory Myofibroblastic Tumor With Synchronous Primary Squamous Cell Lung Cancer in an Elderly Woman. | The hepatic inflammatory myofibroblastic tumor is a spindle cell tumor of the liver that originates from the mesenchymal tissues. It is a rare benign tumor with the potential to degenerate into a malignant and invasive tumor. It can occur anywhere in the body with the most common sites being the lung, mesentery, and omentum. The most common types are myxoid, vascular pattern, fibrous, or hypocellular fibroid type. Immunohistochemistry staining often indicates vimentin, muscle-specific actin, smooth muscle actin, and cytokeratin. These tumors are positive for CD 68 abundant histiocytes but negative for S100. Half of the inflammatory myofibroblastic tumors contain a clonal cytogenetic aberration that activates the ALK gene expression. We present a rare case of HIMT in an elderly female with active primary squamous lung cancer. |
36,800,249 | Successful neoadjuvant treatment of EGFR exon 19 deletion combined with TP53 mutation in non-small cell lung cancer using aumolertinib after osimertinib-induced myocardial damage a case report and literature review. | The development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) represents a paradigm shift in the treatment of lung cancer with EGFR mutations. Aumolertinib has been shown to be a safe agent in the registry study. However, successful rechallenge with aumolertinib following osimertinib-induced myocardial damage has not been reported. In this article, a case of neoadjuvant therapy for lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was diagnosed with stage IIIA lung adenocarcinoma, and genetic testing revealed EGFR exon 19 deletion mutation combined with Tumor Protein p53 (TP53) mutation. The mutation abundance is 33.5 and 14%, respectively. One month after osimertinib treatment, the patient developed myocardial damage, and abnormal indicators such as myocardial enzyme spectrum showed abnormalities and cardiac insufficiency, followed by pulmonary hypertension and pulmonary edema. Aumolertinib was subsequently used for treatment, following which the myocardial enzyme spectrum returned to normal, and the symptoms of bilateral interstitial edema disappeared. In addition to the disappearance of adverse reactions, the therapeutic effect was excellent the lung lesions and mediastinal lymph nodes were significantly reduced, and the operation was successfully conducted. This is the first report of successful neoadjuvant treatment of EGFR exon 19 deletion combined with TP53 mutation in NSCLC using aumolertinib after osimertinib-induced myocardial damage. The results suggested that aumolertinib had fewer adverse reactions in patients with EGFR exon 19 deletion combined with TP53 mutation, and aumolertinib may be a potential neoadjuvant therapy for stage IIIA lung cancer. |
36,800,243 | Increased 18F-Fluoroestradiol Uptake of Radiation Pneumonitis in a Patient With Metastatic Breast Cancer. | A 42-year-old woman diagnosed with de-novo stage IV breast cancer underwent 18F-fluoroestradiol (FES) PETCT to evaluate the estrogen receptor status of metastatic lesions. The largest pulmonary nodule showed obvious FES uptake, consistent with pulmonary metastases from breast cancer. Interestingly, the images revealed a striking accumulation of FES in ground-glass attenuation in the left lobe of lung, suggestive of radiation pneumonitis. |
36,800,235 | Projections of Lung Cancer Incidence by 2035 in 40 Countries Worldwide Population-Based Study. | The global burden of lung cancer (LC) is increasing. Quantitative projections of the future LC burden in different world regions could help optimize the allocation of resources and provide a benchmark for evaluating LC prevention and control interventions. We aimed to predict the future incidence of LC in 40 countries by 2035, with an emphasis on country- and sex-specific disparities. Data on LC incidence from 1978 to 2012 were extracted from 126 cancer registries of 40 countries in Cancer Incidence in Five Continents Volumes V-XI and used for the projection. Age-standardized incidence rates (ASRs) per 100,000 person-years and the number of incident cases were predicted through 2035, using the NORDPRED age-period-cohort model. Global ASRs of the 40 studied countries were predicted to decrease by 23% (8.235.8) among males, from 35.8 per 100,000 person-years in 2010 to 27.6 in 2035, and increase by 2% (0.316.8) among females, from 16.8 in 2010 to 17.1 in 2035. The ASRs of LC among females are projected to continue increasing dramatically in most countries by 2035, with peaks after the 2020s in most European, Eastern Asian, and Oceanian countries, whereas the ASRs among males will continue to decline in almost all countries. The ASRs among females are predicted to almost reach those among males in Ireland, Norway, the United Kingdom, the Netherlands, Canada, the United States, and New Zealand in 2025 and in Slovenia in 2035 and even surpass those among males in Denmark in 2020 and in Brazil and Colombia in 2025. In 2035, the highest ASRs are projected to occur among males in Belarus (49.3) and among females in Denmark (36.8). The number of new cases in 40 countries is predicted to increase by 65.32% (858,0001,314,000), from 1.31 million in 2010 to 2.17 million in 2035. China will have the largest number of new cases. LC incidence is expected to continue to increase through 2035 in most countries, making LC a major public health challenge worldwide. The ongoing transition in the epidemiology of LC highlights the need for resource redistribution and improved LC control measures to reduce future LC burden worldwide. |
36,800,175 | A Transcriptomic and Reverse-Engineering Strategy Reveals Molecular Signatures of Arachidonic Acid Metabolism in 12 Cancers. | Cancer and arachidonic acid (AA) have important linkages. For example, AA metabolites regulate several critical biological functions associated with carcinogenesis angiogenesis, apoptosis, and cancer invasion. However, little is known about the comparative changes in metabolite expression of the arachidonic acid pathway (AAP) in carcinogenesis. In this study, we examined transcriptome data from 12 cancers, such as breast invasive carcinoma, colon adenocarcinoma, lung adenocarcinoma, and prostate adenocarcinoma. We also report here a reverse-engineering strategy wherein we estimated metabolic signatures associated with AAP by (1) making deductive inferences through transcriptome-level data extraction, (2) remodeling AA metabolism, and (3) performing a comparative analysis of cancer types to determine the similarities and differences between different cancer types with respect to AA metabolic alterations. We identified 77 AAP gene signatures differentially expressed in cancers and 37 AAP metabolites associated with them. Importantly, the metabolite 15(S)-HETE was identified in almost all cancers, while arachidonate, 5-HETE, PGF2α, 14,15-EET, 8,9-EET, 5,6-EET, and 20-HETE were discovered as other most regulated metabolites. This study shows that the 12 cancers studied herein, although in different branches of the AAP, have altered expression of AAP gene signatures. Going forward, AA related-cancer research generally, and the molecular signatures and their estimated metabolites reported herein specifically, hold broad promise for precisionpersonalized medicine in oncology as potential therapeutic and diagnostic targets. |
36,800,099 | Development of a Conceptual Model of the Patient Experience in Small Cell Lung Cancer A Qualitative Interview Study. | Small cell lung cancer (SCLC) is a subtype of lung cancer, the second most common cancer diagnosis worldwide. Currently, there is little published qualitative research that provides insight into the disease-related symptoms and impacts that are relevant to patients living with SCLC as directly reported by patients themselves. This qualitative, cross-sectional, noninterventional, descriptive study included concept elicitation interviews with participants diagnosed with SCLC and the development of a conceptual model of clinical treatment benefit. Concept elicitation interview data from 26 participants with SCLC were used to develop a conceptual model of clinical treatment benefit that organized 28 patient-reported concepts into two domains disease-related symptoms (organ-specific and systemic) and impacts. Organ-specific symptoms included cough, chest pain, and difficulty breathing. Systemic symptoms included pain, fatigue, appetite loss, and dizziness. Impacts included physical functioning, role functioning, reduced movement, impact on sleep, and weight loss. As evidenced by this study, people with SCLC experience considerable and significant symptoms and impacts, including physical and role functioning challenges, that affect their quality of life. This conceptual model will inform the design of a patient-reported outcome (PRO) questionnaire for a future SCLC clinical trial, helping to establish the content validity of the items and questionnaires used in the trial and ensuring that the questionnaires and items selected are appropriately targeted to the population. This conceptual model could also be used to inform future SCLC clinical trials. |
36,800,070 | Severe hyponatraemia (P-Na < 116 mmoll) in the emergency department a series of 394 cases. | To evaluate the significance of severe hyponatraemia presented at the emergency department (ED). A retrospective hospital records study of all patients with plasma sodium levels of < 116 mmoll from 2016 to 2020 in a single tertiary referral centre. A total of 394 visits of 363 individual severely hyponatraemic patients represented 0.08% of all ED visits. The mean age was 68 years and the male-to-female ratio was 11.3. The symptoms and signs were diffuse and varying, while half of the patients had neurologic symptoms. The aetiology of hyponatraemia was often multifactorial. The aetiologies varied by age, and the most common ones were the syndrome of inappropriate antidiuresis (34%), diuretic use (27%), alcohol-related (19%) and dehydration (19%). The mean sodium correction rates were 6.6, 4.9 and 3.8 mmoll24 h at 24, 48 and 72 h, respectively. The mean maximum correction rate over any 24-h time interval was 10.2 mmoll. The vital signs (National Early Warning Score, NEWS) of severely hyponatraemic patients were mostly normal. All-cause mortality was 18% for 1-year follow-up. Malignancies, especially small-cell lung cancer, and end-stage liver disease caused most of the deaths. Osmotic demyelination syndrome (ODS) was diagnosed in five (1.4%) patients. Patients with severe hyponatraemia in the ED presented with non-specific complaints. The aetiology of hyponatraemia was often multifactorial and varied by age. The need for intensive care was poorly predicted by NEWS. The one-year mortality rate was 18% and the incidence of ODS 1.4% after an episode of severe hyponatraemia. |
36,799,899 | Response to Chemoimmunotherapy Is Associated With Expansion of Systemic Antitumor CD4 Th1 Response in Metastatic Non-Small Cell Lung Cancer. | Limited data have reported the evolution of antitumor immune responses under chemoimmunotherapy (chemo-IO) in patients with metastatic non-small cell lung cancer. In this concise study, we performed dynamic monitoring of antitumor CD4 T helper 1 (Th1) response in peripheral blood from 12 patients receiving a first-line chemo-IO. Tumor-reactive CD4 Th1 cells were assessed within blood lymphocytes using interferon-gamma enzyme-linked immunospot assay to detect telomerase (TERT)-specific T cells at baseline, 3 and 12 months after treatment. An induction of circulating anti-TERT CD4 Th1 response were found in 6 of 12 patients at 3 months after chemo-IO. In contrast, 3 patients had a substantial decrease in their preexisting response and 3 remained nonimmune responders. Among patients with chemo-IO-induced immune response, half achieved an objective clinical response and had long-lasting circulating anti-TERT CD4 Th1 cells detected for at least 1 year. In contrast, no objective response was documented in nonimmune responders and a link between the loss of anti-TERT CD4 Th1 responses were observed in patients with progressive disease. This preliminary work supports a relationship between the efficacy of combinatorial chemo-IO and circulating anti-TERT CD4 Th1 responses and highlights the interest to implement blood-based monitoring of tumor-reactive CD4 T cells that could be additional help for patient management. |
36,799,690 | Overview of Adductomics in Toxicology. | Adductomics is epidemiology at the molecular level. Untargeted adductomics compares levels of chemical adducts on albumin, hemoglobin, and DNA between healthy and exposed individuals. The goal is to determine a cause-and-effect relationship between chemical exposure and illness. Chemical exposures are not necessarily due to synthetic chemicals but are often due to oxidation products of naturally occurring lipids, for example, 4-hydroxynonenal and acrolein produced by lipid peroxidation of arachidonic and linoleic acids. The preferred method used in adductomics is ultra-high pressure liquid chromatography coupled to with nanoelectrospray tandem mass spectrometry. The mass of the adduct indicates its structure and identifies the chemical. The advantages of molecular epidemiology include information about the many toxicants to which a person is exposed over a period of weeks or months and the relative exposure levels. The disadvantage is the absence of information about the mechanism of toxicity. Untargeted adductomics examines albumin and hemoglobin adducts, which serve as biomarkers of exposure but do not identify the proteins and genes responsible for the toxicity. Targeted adductomics is used when the origin of the toxicity is known. This can be either an adducted protein, such as the butyrylcholinesterase protein modified by nerve agents, or a toxicant, such as acetaminophen. Untargeted adductomics methods have identified potential protein adduct biomarkers of breast cancer, colorectal cancer, childhood leukemia, and lung cancer. Adductomics is a new research area that offers structural insights into chemical exposures and a platform for the discovery of disease biomarkers. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. |
36,799,689 | MET exon 14 skipping mutation is a hepatocyte growth factor (HGF)-dependent oncogenic driver in vitro and in humanized HGF knock-in mice. | Exon skipping mutations of the MET receptor tyrosine kinase (METex14), increasingly reported in cancers, occur in 3-4% of non-small cell lung cancer (NSCLC). Only 50% of patients have a beneficial response to treatment with MET-tyrosine kinase inhibitors (TKIs), underlying the need to understand the mechanism of METex14 oncogenicity and sensitivity to TKIs. Whether METex14 is a driver mutation and whether it requires hepatocyte growth factor (HGF) for its oncogenicity in a range of in vitro functions and in vivo has not been fully elucidated from previous preclinical models. Using CRISPRCas9, we developed a METex14WT isogenic model in non-transformed human lung cells, and report that the METex14 single alteration was sufficient to drive MET-dependent in vitro anchorage-independent survival and motility and in vivo tumorigenesis, sensitising tumours to MET-TKIs. However, we also show that human HGF (hHGF) is required, as demonstrated in vivo using a humanized HGF knock-in strain of mice and further detected in tumor cells of METex14 NSCLC patient samples. Our results also suggest that METex14 oncogenicity is not a consequence of an escape from degradation in our cell model. Thus, we developed a valuable model for preclinical studies and present results that have potential clinical implication. |
36,799,651 | Modeling Ewing Sarcoma Lung Metastasis. | Ewing Sarcoma (EwS) is the second most common malignant bone tumor in adolescents and young adults. The single-most powerful predictor of outcome in EwS is presence of metastatic burden at the time of diagnosis. Patients with metastatic Ewing Sarcoma have an abysmal 5-year survival rate of 10%-25%, which has not changed over the past 30-40 years. Thus, unraveling underlying mechanisms of EwS metastasis are imperative for developing effective therapeutic measures. Investigations towards this goal are limited by the lack of reliable genetically engineered mouse models and specialized metastatic models. Using two established cell lines, A673 and TC71, we generated lung specific metastatic cell lines by serial orthotopic intra-tibial injection followed by isolation of cells from lung metastases. The lung metastatic lines generated exhibit distinct differential molecular signatures from the parental cells when analyzed using a multi-omics approach. These signatures overlapped with EwS patient primary bone and metastatic lung specimens supporting the clinical relevance of these preclinical models of EwS. © 2023 Wiley Periodicals LLC. Basic Protocol 1 Intra-Tibial injection in NSG mice Basic Protocol 2 Development and characterization of lung metastatic cell line. |
36,799,647 | Commentary Does Covid-19 vaccination disturb menstrual cycling | Inverse associations between dietary fiber (DF) and colorectal cancer risk are well-established. However, evidence is limited in relation to other cancer sites. This study, of 364,856 participants from UK Biobank, aimed to evaluate the associations between total and source-specific partial DF and risk of 17 specific cancers and all cancers combined. Partial DF was derived from baseline touch-screen questionnaire data on cereal, bread, fruit and vegetable intake. The outcomes were incident cancer at 17 sites and all cancers combined. Cox proportional hazard models were applied. Over a median 8.8-year follow-up period, 30,725 people were diagnosed with cancer. After adjusting for sociodemographic and lifestyle factors, those in the highest quintile of DF compared to the lowest quintile (<9.6 vs ≥19.1 gday) had 10% lower risk of cancer overall, with the greatest risk reductions observed for cervical (HR 0.33, 0.14 0.82), esophageal (HR 0.66, 0.52 0.84), lung (HR 0.67, 0.59 0.76), bladder (HR 0.72, 0.56 0.91) and kidney (HR 0.75, 0.61 0.92) cancers. Associations between DF and lung cancer were observed only in current and ex-smokers. Higher dietary fiber intake, in particular cereal fiber and fruit and vegetable fiber, was associated with a lower risk of overall and multiple site-specific cancers. |
36,799,572 | Evaluating the Impact of Physiologically Relevant Oxygen Tensions on Drug Metabolism in 3D Hepatocyte Cultures in Paper Scaffolds. | Oxygen is an essential regulator of cellular function and phenotype. Despite its importance, the incorporation of physiologically relevant oxygen tensions is often overlooked in experimental setups. Ambient oxygen tensions (pO |
36,799,555 | Inferior Pulmonary Ligament Division During Left Upper Lobectomy Causes Pulmonary Dysfunction. | The division of inferior pulmonary ligament (IPL) during upper lobectomy (UL) was believed to be mandatory to dilate the remaining lung sufficiently. However, the benefits, especially postoperative pulmonary function, remain controversial. This study aimed to evaluate whether IPL division leads to pulmonary dysfunction. This retrospective study included 213 patients who underwent UL between 2005 and 2018. They were categorized into an IPL division group (D group, n 106) and a preservation group (P group, n 107). Postoperative dead space at the lung apex, pulmonary function, and complications were assessed using chest X-rays and spirometry. Changes in bronchial angle, cross-sectional area, and circumference of the narrowed bronchus on the excised side were measured on three-dimensional CT. There was no significant difference in the postoperative complication rate, the dead space area, forced expiratory volume (FVC), or forced expiratory volume in one second (FEV1) between the two groups after right UL (FVC P 0.838, FEV1 P 0.693). By contrast, after left UL pulmonary function was significantly better in the P than in the D group (FVC P 0.038, FEV1 P 0.027). Changes in bronchial angle did not significantly differ between the two groups. The narrowed bronchuss cross-sectional area (P 0.021) and circumference (P 0.009) were significantly smaller in the D than in the P group after left UL. IPL division during left UL caused postoperative pulmonary dysfunction and airflow limitation due to bronchial kinking. IPL preservation may have a beneficial impact on postoperative pulmonary function. |
36,799,501 | Changes in Stage at Presentation among Lung and Breast Cancer Patients During the COVID-19 Pandemic. | The COVID-19 pandemic altered access to healthcare by decreasing number of patients able to receive preventative care and cancer screening. We hypothesized that given these changes in access to care, radiologic screening for breast and lung cancer would be decreased, and patients with these cancers would consequently present at later stages of their disease. Retrospective cross-sectional study of 2017-September 2021 UMass Memorial Tumor Registry for adult breast and lung cancer patients. Changes in stage at presentation of breast and lung cancer during the COVID-19 pandemic were measured, defined as prior to and during COVID-19. There were no statistically significant changes in the overall stage of presentation before or during the COVID-19 pandemic for either breast or lung cancer patients. Analysis of case presentation and stage during periods of COVID-19 surges that occurred over the time of this study compared to pre-pandemic data demonstrated a statistically significant decrease in overall presentation of breast cancer patients in the first surge, with no other statistically significant changes in breast cancer presentation. A non-statistically significant decrease in lung cancer presentations was seen during the initial surge of COVID-19. There was also a statistically significant increase in early-stage presentation of lung cancer during the second and third COVID-19 surges. In the two years after the COVID-19 pandemic we were not able to demonstrate stage migration at presentation of breast and lung cancer patients to later stages despite decreases in overall presentation during the initial two years of the COVID pandemic. An increase in early-stage lung cancer during the second and third surges is interesting and could be related to increased chest imaging for COVID pneumonia. |
36,799,341 | Implementable Deep Learning for Multi-sequence Proton MRI Lung Segmentation A Multi-center, Multi-vendor, and Multi-disease Study. | Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton ( Develop a generalizable CNN for lung segmentation in Retrospective. A total of 809 1.5-T and 3-T3D spoiled-gradient recalled and ultrashort echo-time 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance. Kruskal-Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland-Altman analyses assessed agreement with manually derived lung volumes. A P value of <0.05 was considered statistically significant. The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880-0.987), Average HD of 1.63 mm (0.65-5.45) and XOR of 0.079 (0.025-0.240) on the testing set and a DSC of 0.973 (0.866-0.987), Average HD of 1.11 mm (0.47-8.13) and XOR of 0.054 (0.026-0.255) on external validation data. The 3D CNN generated accurate 4. Stage 1. |
36,799,199 | Buddlejasaponin IV induces apoptotic cell death by activating the mitochondrial‑dependent apoptotic pathway and reducing α | Colon cancer is one of the most frequent malignant neoplasms worldwide. Epidemiological studies suggested that the development of colon cancer can be prevented by plant‑derived ingredients. In the present study, the chemopreventive activity of buddlejasaponin IV (BS‑IV), isolated from the aerial part of |
36,799,191 | Effect of DPP4CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m | The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A markerreceptor called Dipeptidyl peptidase 4CD26(DPP4CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The association between DPP4 expression and survival in various tumor tissues was compared using GEPIA 2. The DNMIVD database was used to analyze the correlation between DPP4 expression and promoter methylation in various tumors. On the cBioPortal network, the frequency of |
36,799,172 | Corrigendum METTL3‑mediated m6A modification of Bcl‑2 mRNA promotes non‑small cell lung cancer progression. | Subsequently to the publication of the above paper, the authors have realized, upon reorganizing all their original data, that errors were made during the assembly of the images in Fig. 5 on p. 8. Specifically, in Fig. 5E, the images intended to represent the METTL3 sh‑METTL3 and Bcl‑2 sg‑METTL3 immuno-histochemistry staining experiments were selected incorrectly. The revised version of Fig. 5, showing the correctly assembled data panels for the METTL3 sh‑METTL3 and Bcl‑2 sg‑METTL3 experiments in Fig. 5E, is shown on the next page. The authors sincerely apologize for the errors that were inadvertently introduced during the preparation of this Figure, thank the Editor of |
36,799,061 | Type I Pleuropulmonary Blastoma Incidentally Diagnosed in an Infant with RSV Bronchiolitis. | In summary, PPB, although rare, is the most common primary lung malignancy in children. Early diagnosis and treatment is important in preventing disease progression to a higher-grade lesion. Given its association with the DICER1 cancer predisposition syndrome, children with PPB should undergo DICER1 mutation testing so the appropriate malignancy screening protocols can be instituted. Diagnosing PPB based on symptoms and imaging is challenging as children are often asymptomatic or present with non-specific symptoms, and chest CT is not highly sensitive for predicting malignant lesions. Due to the absence of distinguishing clinical or radiographic features, risk for disease progression and association with the DICER1 cancer predisposition syndrome, it is important to consider PPB in the differential diagnosis for children with cystic lung lesions. This article is protected by copyright. All rights reserved. |
36,799,040 | Immune surveillance of brain metastatic cancer cells is mediated by IFITM1. | Brain metastasis, most commonly originating from lung cancer, increases cancer morbidity and mortality. Although metastatic colonization is the rate-limiting and most complex step of the metastatic cascade, the underlying mechanisms are poorly understood. Here, in vivo genome-wide CRISPR-Cas9 screening revealed that loss of interferon-induced transmembrane protein 1 (IFITM1) promotes brain colonization of human lung cancer cells. Incipient brain metastatic cancer cells with high expression of IFITM1 secrete microglia-activating complement component 3 and enhance the cytolytic activity of CD8 |
36,798,947 | A dose planning study for cardiac and lung dose sparing techniques in left breast cancer radiotherapy Can free breathing helical tomotherapy be considered as an alternative for deep inspiration breath hold | To investigate the possibility to be able to offer left sided breast cancer patients, not suitable for DIBH, an organ at risk saving treatment. Twenty patients receiving radiotherapy for left breast cancer in DIBH were enrolled in the study. Planning CT scans were acquired in the same supine treatment position in FB and DIBH. 3DCRTDIBH plans were designed and optimized using two parallel opposed tangent beams (with some additional segments) for the breast and chest wall and anterior-posterior fields for regional lymph nodes irradiation. Additionally, FB helical tomotherapy plans were optimized to minimize heart and lung dose. All forty plans were optimized with at least 95% of the total CTV covered by the 95% of prescribed dose of 50 Gy in 25 fractions. HTFB plans showed significantly better dose homogeneity and conformity compared to the 3DCRTDIBH specially for regional nodal irradiation. The heart mean dose was almost comparable in 3DCRTDIBH and HTFB while the volume (%) of the heart receiving 25 Gy had a statistically significant reduction from 7.90 ± 3.33 in 3DCRTDIBH to 0.88 ± 0.66 in HTFB. HTFB was also more effective in left descending artery (LAD) mean dose reduction about 100% from 30.83 ± 9.2 Gy to 9.7 ± 3.1. The ipsilateral lung volume receiving 20 Gy has a further reduction of 43 % in HTFB compared with 3DCRTDIBH. For low dose comparison, 3DCRTDIBH was superior for contralateral organ sparing compared to the HTFB due to the limited angle for dose delivery. For patients who cannot be a candidate for DIBH for any reason, HT in free breathing may be a good alternative and provides heart and ipsilateral lung dose sparing, however with the cost of increased dose to contralateral breast and lung. |
36,798,925 | Effects of Methadone on the Toll-like Receptor 4 Expression in Human Non-Small Cell Lung Carcinoma A549 Cell Line Using | In this study, the effects of methadone and naloxone on the expression of toll-like receptor 4 ( Lung cancer A549 cell cultures were stimulated for 24 h with methadone (5, 10, and 20 μM) and naloxone (20 and 40 μM) concentrations. The level of Migration rate of the A549 cells treated with 5 ( According to the present DATA, methadone affects the |
36,798,842 | Pre- and post-intervention survey on lung cancer awareness among adults in selected communities in KwaZulu-Natal, South Africa A quasi-experimental study. | Lung cancer remains the number one cause of cancer mortality estimated at 1.8 million deaths. There are limited studies in resource poor countries regarding knowledge, attitudes and practices towards lung cancer. This study aimed to assess the effects of a lung cancer awareness intervention in selected communities in KwaZulu- Natal, South Africa. A quasi-experimental study design was conducted in the selected communities in KwaZulu-Natal. A community intervention was administered in the communities after a baseline survey. The intervention effects were assessed a month after implementation. There were statistical differences in the mean age (p<0.001) and proportion of males and females (p<0.001) at baseline and post-intervention. There were no differences in terms of smoking status (p0.958), however, there was a reduction in the number of cigarettes smoked per day (p<0.001) and the number of packs smoked per week (p0.026). The mean knowledge score increased from 41.8% (95% CI 35.7 - 47.9) at baseline to 59.9 (95% CI 53.8 - 66.0) post-intervention (p<0.001). The proportion of participants who were aware that lung cancer can be detected early increased from 46.5% (95% CI 39.1 - 53.9) at baseline to 81.1% (95% CI 71.7 - 87.9) post-intervention (p<0.001). The intervention had a statistically significant effect (aOR 4.370, 95% CI 1.477-12.928) on the level of lung cancer knowledge in the selected communities (p<0.001). Interventions increasing the recognition of signs and symptoms, focusing on the importance of early detection and health seeking behaviour (including screening), smoking cessation, and addressing the perceived health system barriers are required. |
36,798,823 | Cancer mortality in 2020 and its trend analysis in Inner Mongolia during four time periods from 1973 to 2020. | Cancer is one of the leading causes of mortality in China and is responsible for placing a major burden on its economic system. Inner Mongolia is located close to the northern border of China and spans more than 2,400 km from east to west. It has a total area of 1,183,000 km |
36,798,818 | Preoperative prognostic prediction for stage I lung adenocarcinomas Impact of the computed tomography features associated with the new histological grading system. | This study aimed to identify the computed tomography (CT) features associated with the new International Association for the Study of Lung Cancer (IASLC) three-tiered grading system to improve the preoperative prediction of disease-free survival of stage I lung adenocarcinoma patients. The study included 379 patients. Ordinal logistic regression analysis was used to identify the independent predictors of IASLC grades. The first multivariate Cox regression model (Model 1) was based on the significant factors from the univariate analysis. The second multivariate model (Model 2) excluded the histologic grade and based only on preoperative factors. Larger consolidation tumor ratio (OR2.15, CTR (cut-off values of <25% and ≥75%) and whole tumor size (cut-off value of 17 mm) could stratify patients into different prognosis and be used as preoperative surrogates for the IASLC grading system. Integrating these CT features with clinical T staging can improve the preoperative prognostic prediction for stage I lung adenocarcinoma patients. |
36,798,816 | A CT-based radiomics approach to predict immediate response of radiofrequency ablation in colorectal cancer lung metastases. | To objectively and accurately assess the immediate efficacy of radiofrequency ablation (RFA) on colorectal cancer (CRC) lung metastases, the novel multimodal data fusion model based on radiomics features and clinical variables was developed. This case-control single-center retrospective study included 479 lung metastases treated with RFA in 198 CRC patients. Clinical and radiological data before and intraoperative computed tomography (CT) scans were retrieved. The relative radiomics features were extracted from pre- and immediate post-RFA CT scans by maximum relevance and minimum redundancy algorithm (MRMRA). The Gaussian mixture model (GMM) was used to divide the data of the training dataset and testing dataset. In the process of modeling in the training set, radiomics model, clinical model and fusion model were built based on a random forest classifier. Finally, verification was carried out on an independent test dataset. The receiver operating characteristic curves (ROC) were drawn based on the obtained predicted scores, and the corresponding area under ROC curve (AUC), accuracy, sensitivity, and specificity were calculated and compared. Among the 479 pulmonary metastases, 379 had complete response (CR) ablation and 100 had incomplete response ablation. Three hundred eighty-six lesions were selected to construct a training dataset and 93 lesions to construct a testing dataset. The multivariate logistic regression analysis revealed cancer antigen 19-9 (CA19-9, p<0.001) and the location of the metastases (p< 0.05) as independent risk factors. Significant correlations were observed between complete ablation and 9 radiomics features. The best prediction performance was achieved with the proposed multimodal data fusion model integrating radiomic features and clinical variables with the highest accuracy (82.6%), AUC value (0.921), sensitivity (80.3%), and specificity (81.4%). This novel multimodal data fusion model was demonstrated efficient for immediate efficacy evaluation after RFA for CRC lung metastases, which could benefit necessary complementary treatment. |
36,798,751 | Identifying the Risk Factors for Postoperative Sore Throat After Endotracheal Intubation for Oral and Maxillofacial Surgery. | To identify risk factors for postoperative sore throat (POST) after general anesthesia in oral and maxillOfacial surgery. This study is a retrospective cohort design study. We enrolled patients with oral and maxillofacial surgery who underwent endotracheal intubation under general anesthesia in the Stomatology Hospital, Zhejiang University School Of Medicine between April 2020 and April 2021. They were divided into the POST group and the without POST group. The distribution Of various characteristics in the two groups was firstly analyzed. Then, logistic regression analysis was performed to explore the independent predictors for POST occurrence. Following this, logistic regression and random forest models were constructed and their performance was evaluated to predict POST occurrence. A total of 891 participants were enrolled in the study. Female gender and cough during extubation were significantly associated with increased POST occurrence in multivariate analysis (all P <0.05). Stratified logistic regression analysis results showed that the female gender was an independent predictor for POST occurrence in the 4≤age≤14 and 14<age≤60 groups after adjusting all the covariates, while cough during extubation independently predicted POST in the age>60 group after adjusting American Society of Anesthesiologists status and throat and lung disease (all P <0.05). The logistic regression model had a similar effect to the random forest model in predicting POST occurrence. Interestingly, the female gender had a higher important weight compared to the cough during extubation. This research reveals female gender and cough during extubation as potential risk factors for POST occurrence, which may provide guidance for the effective prevention of POST in oral and maxillofacial surgery. |
36,798,676 | Tobacco quitline performance Comparing the impacts of early cessation and proactive re-engagement on callers smoking status at follow-up at 12 months. | While tobacco Quitlines are effective in the promotion of smoking cessation, the majority of callers who wish to quit still fail to do so. The aim of this study was to determine if 12-month tobacco Quitline smoking cessation rates could be improved with re-engagement of callers whose first Quitline treatment failed to establish abstinence. In an adaptive trial, 614 adult smokers, who were active duty, retired, and family of military personnel with TRICARE insurance who called a tobacco Quitline, received a previously evaluated and efficacious four-session tobacco cessation intervention with nicotine replacement therapy (NRT). At the scheduled follow-up at 3 months, callers who had not yet achieved abstinence were offered the opportunity to re-engage. This resulted in three caller groups 1) those who were abstinent, 2) those who were still smoking but willing to re-engage with an additional Quitline treatment and 3) individuals who were still smoking but declined re-engagement. A propensity score-adjusted logistic regression model was generated to compare past-7-day point prevalence abstinence at 12 months post Quitline consultation. Using a propensity score adjusted logistic regression model, comparison of the three groups resulted in higher odds of past-7-day point prevalence abstinence at follow-up at 12 months for those who were abstinent at 3 months compared to those who re-engaged (OR9.6 95% CI 5.2-17.8 Bonferroni adjusted p<0.0001), and relative to those who declined re-engagement (OR13.4 95% CI 6.8-26.3 Bonferroni adjusted p<0.0001). There was no statistically significant difference in smoking abstinence between smokers at 3 months who re-engaged and those who declined re-engagement (OR1.39 95% CI 0.68-2.85). Tobacco Quitlines seeking to select a single initiative by which to maximize abstinence at follow-up at 12 months may benefit from diverting additional resources from the re-engagement of callers whose initial quit attempt failed, toward changes which increase callers probability of success within the first 3 months of treatment. This study is registered at clinicaltrials.gov (NCT02201810). |
36,798,672 | FACILITATE A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC. | Accurate testing for epidermal growth factor receptor ( |
36,798,607 | National Patterns of Early Adoption of Magnetic Resonance Imaging-Guided Linear Accelerators in 2018 to 2019. | Adaptive magnetic resonance imaging-guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing forces of the increased cost, knowledge, and staff required for aMRI-LINAC therapy, it is unpredictable how rapidly and for whom aMRI-LINAC therapy is being adopted. Therefore, given that aMRI-LINAC therapy was granted approval from the Food and Drug Administration in late 2017, we evaluated the National Cancer Database (NCDB) to obtain a nationwide view of early aMRI-LINAC adoption in 2018 to 2019. Forty-three disease sites were aggregated. A sample of patients who underwent intensity modulated radiation therapy (IMRT) from 2018 to 2019 were matched 11 by stage for the top 4 cancer sites. We then compared 9 characteristics of interest (age, % White vs non-White, % residing in metro areas, % living in the greatest income quartile, % insured by Medicare, % uninsured or unknown insurance status, % treated at a comprehensive cancer center or academic center, % with no recorded Charlson-Deyo comorbidities, and % residing in an area with highest educational) between the 2 samples (aMRI-LINAC and matched IMRT). Only 171 patients were recorded as having been treated with aMRI-LINACs in the NCDB in 2018 to 2019. Fifty-six percent were male, 89% White, and 54% enrolled in Medicare. The most common sites of disease treated were lung (33 patients), pancreas (30 patients), prostate (29 patients), and breast (23 patients). There were no significant differences between aMRI-LINAC- and IMRT-matched patients except that patients with lung or breast cancer treated with aMRI-LINAC were significantly more likely to be treated at a comprehensive cancer center or academic center. aMRI-LINAC adoption recorded in the NCDB after Food and Drug Administration approval was potentially underreported, slow, and attributed to academic sites of practice. Further longitudinal study will be needed to assess how practice patterns evolve with greater adoption. |
36,798,606 | Estimating Carbon Dioxide Emissions and Direct Power Consumption of Linear Accelerator-Based External Beam Radiation Therapy. | Climate change is one of the direst health threats that humanity faces. We aim to estimate the carbon dioxide (CO We identified patients with the 4 most common cancer types treated with curative-intent EBRT. Beam-on time for each fraction was extracted from the treatment planning system and averaged over each site and treatment modality. The power was multiplied by the beam-on time in hours to yield kilowatt hours (kWh). Using the US Environmental Protection Agency Greenhouse Gas Equivalencies calculator, we converted the kWh into estimates of CO A total of 10 patients were included for each of the following modalities conventionally fractionated for prostate cancer (28 fractions fx), prostate stereotactic body radiation therapy (SBRT) (5 fx), 15- and 5-fx regimens for early-stage breast cancer, 3- and 5-fx SBRT regimens for early-stage lung cancer, conventional EBRT (30 fx) for locally advanced lung cancer, and short- (5 fx) and long-course (25-28 fx) for rectal cancer. The modality with the lowest and highest carbon emissions per course, on average, was prostate SBRT (2.18 kg CO We have estimated CO |
36,798,532 | Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis. | Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balbc mice. D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer. |
36,798,467 | Role of miR‑200 family in brain metastases A systematic review. | Brain metastasis (BM) represents the single most severe neurological complication of systemic cancer. The prognosis of patients with BM is poor, irrespective of the implemented treatment. The present study performed a systematic review of the literature using three online databases (PubMed, Scopus and Web of Science). Recently, a number of small RNA molecules, the microRNAs (miRNAsmiRs), have attracted increasing scientific attention. Members of the miR-200 family, which includes five miRNAs (miR-141, miR-200a, miR-200b, miR-200c and miR-429) appear to play pivotal roles in cancer initiation and metastasis. Indeed, a systematic review of the pertinent literature revealed that miR-200 family members regulate the brain metastatic cascade, particularly by modulating epithelial-to-mesenchymal transition. That holds true for the major representatives of BM, including lung and breast cancer, as well as for other less frequent secondary lesions originating from melanoma and the gastrointestinal tract. Therefore, the miRNAs may serve as potential diagnostic andor prognostic markers, and under specific circumstances, as invaluable therapeutic targets. However, the available clinical evidence is relatively limited. A number of studies have suggested that the miR-200 family members are accurate prognostic markers of survival and resistance to chemotherapy in patients with breast cancer. Similarly, they may prove helpful in differentiating a metastatic lesion from a malignant glioma, or a hemangioblastoma from a renal cell carcinoma in patients with von Hippel Lindau syndrome, based on a cerebrospinal fluid sample. However, currently, there is no known therapeutic role for miR-200 family members in the setting of BM. |
36,798,441 | Endothelial-to-osteoblast transition in normal mouse bone development. | Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal bone formation. We developed an EC and OSB dual-color reporter mouse (DRM) model that marks EC-OSB hybrid cells with red and green fluorescent proteins. We observed EC-to-OSB transition (RFP and GFP co-expression) in both endochondral and intramembranous bone formation during embryonic development and in adults. Co-expression was confirmed in cells isolated from DRM. Bone marrow- and lung-derived ECs underwent transition to OSBs and mineralization in osteogenic medium. RNA-sequencing revealed GATA family transcription factors were upregulated in EC-OSB hybrid cells and knockdown of |
36,798,234 | Inhaled CpG increases survival and synergizes with checkpoint inhibition in lymphangioleiomyomatosis. | Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cancer-like cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. IN lung cancer, TLR agonist, in particular TLR9 agonist CpG has been shown to be effective. Here we investigate the use of TLR9 agonist CpG as LAM immunotherapy in combination with checkpoint inhibitor, anti-PD1 and assess induced changes in anti-LAM immunity. We used a murine model of metastatic LAM to determine survival after intranasal treatment with TLR9 agonist CpG at two doses and in combination the checkpoint inhibitor immunotherapy, anti-PD-1. We used histology and flow cytometry to assess overall inflammation as well as changes in the immune response upon treatment. We found that local administration of CpG enhances survival in a murine model of LAM and that a lower dose more effectively balanced the inflammation induced by CpG with the anti-LAM therapeutic benefits. We also found that CpG reduces regulatory T cell infiltration in LAM lungs and that CD4 helper T cells are skewed toward pro-inflammatory phenotypes. We also found that CpG treatment is effective in both early stage and progressive disease and that CpG is synergistic with previously tested anti-PD1 therapy. We have found that TLR9 agonist CpG can be used as LAM immunotherapy and effectively synergizes with anti-PD1 therapy in LAM. |
36,798,137 | LRRC3B and its promoter hypomethylation status predicts response to anti-PD-1 based immunotherapy. | The leucine rich repeat containing 3B (LRRC3B) gene is a tumor suppressor gene involved in the anti-tumor immune microenvironment. Expression of LRRC3B and DNA methylation at the LRRC3B promoter region may serve as a useful marker to predict response to anti-PD-1 therapy. However, no studies have yet systematically explored the protective role of LRRC3B methylation in tumor progression and immunity. Expression of LRRC3B of 33 cancer types in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (httpxena.ucsc.edu). And, we evaluated the differential expression of LRRC3B according to tumor stage, overall survival, and characteristics of the tumor microenvironment. The immunotherapeutic cohorts included IMvigor21, GSE119144, and GSE72308 which were obtained from the Gene Expression Omnibus database. We conducted pearson correlation analysis of LRRC3B and tumor microenvironment (TME) in pan-cancer. Also, six immune cell types (B cells, CD8 T cells, CD4 T cells, macrophages, neutrophils, and dendritic cells) and tumor purity were analyzed using the Tumor IMmune Estimation Resource (TIMER1.0) (Tumor IMmune Estimation Resource (TIMER2.0). And, a silencing score model base on LRRC3B promoter methylation to predict overall survival (OS) by multivariate Cox regression analysis was constructed. Finally, the model was applied to predict anti-PD-1 therapy in non-small cell lung cancer (NSCLC) and breast cancer (BRCA). LRRC3B expression associated with less tumor invasion, less severe tumor stage, and decreased metastasis. The inactivation of LRRC3B promoted the enrichment of immuneosuppressive cells, including myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), M2 subtype of tumor-associated macrophages (M2-TAMs), M1 subtype of tumor-associated macrophages (M1-TAMs), and regulatory T (Treg) cells. A high silencing score was significantly associated with immune inhibition, low expression of LRRC3B, poor patient survival, and activation of cancer-related pathways. Our comprehensive analysis demonstrated the potential role of LRRC3B in the anti-tumor microenvironment, clinicopathological features of cancer, and disease prognosis. It suggested that LRRC3B methylation could be used as a powerful biomarker to predict immunotherapy responses in NSCLC and BRCA. |
36,798,129 | Gut microbiota A novel and potential target for radioimmunotherapy in colorectal cancer. | Colorectal cancer (CRC) is one of the most common cancers, with a high mortality rate, and is a major burden on human health worldwide. Gut microbiota regulate human immunity and metabolism through producing numerous metabolites, which act as signaling molecules and substrates for metabolic reactions in various biological processes. The importance of host-gut microbiota interactions in immunometabolic mechanisms in CRC is increasingly recognized, and interest in modulating the microbiota to improve patients response to therapy has been raising. However, the specific mechanisms by which gut microbiota interact with immunotherapy and radiotherapy remain incongruent. Here we review recent advances and discuss the feasibility of gut microbiota as a regulatory target to enhance the immunogenicity of CRC, improve the radiosensitivity of colorectal tumor cells and ameliorate complications such as radiotoxicity. Currently, great breakthroughs in the treatment of non-small cell lung cancer and others have been achieved by radioimmunotherapy, but radioimmunotherapy alone has not been effective in CRC patients. By summarizing the recent preclinical and clinical evidence and considering regulatory roles played by microflora in the gut, such as anti-tumor immunity, we discuss the potential of targeting gut microbiota to enhance the efficacy of radioimmunotherapy in CRC and expect this review can provide references and fresh ideas for the clinical application of this novel strategy. |
36,798,090 | Translating an Economic Analysis into a Tool for Public Health Resource Allocation in Cancer Survivorship. | Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users. |
36,798,062 | Small-cell lung cancer metastasis to a meningioma Case report and review of the literature. | Tumor-to-tumor metastasis is a rare event with meningioma as the recipient tumor accounting for 20% of the reported cases. The most common primary cancers showing this phenomenon are lung and breast cancer. Most lung cancers metastasizing to a meningioma are due to lung adenocarcinoma with the literature containing only 3 prior reports of small-cell lung cancer showing this pattern of spread. Herein, we present the case of a 67-year-old-patient with small-cell lung cancer that developed a metastasis to a meningioma. |
36,797,821 | Factors associated with anxiety and depression in cancer patients Demographic factors and the role of demoralization and satisfaction with care. | Anxiety and depression are common in cancer patients and seem to affect quality of life, treatment compliance and even survival. Defining factors related to anxiety and depression and exploring the role of demoralization and satisfaction with care, could contribute to the improvement of patients quality of life and quality of health services as well. A convenience sample of 150 cancer inpatients and outpatients from two oncology centers, with various types of solid tumors, participated in a prospective cross-sectional observational study. The psychometric tools used were the Greek versions of the Hospital Anxiety and Depression Scale (HADS), FAMCARE-Patient Scale and Oncology Palliative Care (FAMCARESCALE) and Demoralization Scale (DEMORALIZATION SCALE II, DS-II). Patients mean age was 62 years (20-85 years) and 89 patients (59.3%) were women. Among patients, 33% had breast, 24% gastrointestinal and 15% lung cancer. Eighty-two patients (54.7%) had metastatic disease. Women showed higher rates of anxiety (p 0.054). Anxiety was inversely related to age (p 0.043) and positively correlated with time since diagnosis (p 0.076). Unmarried patients presented with higher rates of depression (p0.026). Multiple linear regression showed a statistically significant impact of Demoralization factor Meaning and Purpose on anxiety (p <0.001, R2 36.3%) and depression (p <0.001, R2 49%). Moreover, higher educational level (p 0.038, R2 3.1%) is related to higher levels of anxiety and higher scores of FAMCARESCALE factor-Informationinteraction with the health care professionals, is related to lower levels of depression (p0.008, R22.7%). The results highlight the significant impact of demoralization on anxiety and depression in cancer patients. Early recognition of demoralization and early referral to mental health professionals will hopefully alleviate the mental burden of cancer patients. This article is protected by copyright. All rights reserved. |
36,797,820 | Mental Health, Functional Impairment, and Barriers to Mental Health Access Among Cancer Patients in Vietnam. | This study evaluated the prevalence and severity of depression and anxiety symptomatology, barriers to mental health access, and correlates of functional impairment among cancer inpatients. This cross-sectional study recruited adult cancer patients (N300) in June and July 2022 at the largest oncological hospital in Vietnam. Multivariable linear regression analyses examined the association between demographics, clinical characteristics, and patients functional impairment. Approximately 46.3% and 27.0% showed some depression and anxiety symptomatology, while 8.0% and 3.0% experienced major depressive and anxiety symptoms, respectively. Patients reported the most impairment in mobility and capacity for life activities. More functional impairment was identified in patients with gastrointestinal cancers, those receiving radiation therapy alone, and those scoring higher on depression and anxiety than in those with cancers originating in the head, neck, or lung or those receiving chemotherapy alone. Reports of better overall health status were negatively associated with functional impairment. Patients reported extensive perceived barriers to seeking psychiatric care, including not knowing where to get mental health support (86.7%), wanting to manage mental health independently (73.7%), and thinking mental health will resolve on its own (73.7%), and denying mental health concerns (61.0%). High frequency and severity of depression and anxiety symptomatology underscore the importance of integrating mental health services into existing oncological treatment protocols. Increasing mental health literacy and provision of psychoeducation is critical to addressing barriers to mental health service access. Integration of functional impairment evaluations into hospital admission and discharge planning is also needed. This article is protected by copyright. All rights reserved. |
36,797,806 | The reimbursement process in three national healthcare systems variation in time to reimbursement of pembrolizumab for metastatic non-small cell lung cancer. | In this article, we focus on the reimbursement process, and as an example, characterize the time to reimbursement of pembrolizumab, a PD-1 immune checkpoint inhibitor for treatment of metastatic NSCLC from publicly available websites, in three different healthcare systems The National Institute for Health and Care Excellence (NICE) in the UK, the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia, and the National Advisory Committee for the Basket of Health Services in Israel, all who have publicly funded health systems which include drug coverage. Our study found that there are substantial differences in time to reimbursement of pembrolizumab for the same conditions in different countries, with NICE and The National Advisory Committee for the Basket of Health Services in Israel approving one condition at the same time, Israel approving two conditions earlier than NICE, and PBAC lagging behind for every condition. These differences could be due to the differences in health policy systems and the many factors that affect reimbursement. Comparing the reimbursement process between different countries can highlight the challenges facing their health systems in early adoption of new treatments. |
36,797,759 | DNA methylation entropy as a measure of stem cell replication and aging. | Epigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze DNA methylation with age in mouse intestinal stem cells and compare them to nonstem cells. Age-related changes in DNA methylation are identical in stem and nonstem cells, affect most prominently CpG islands and correlate weakly with gene expression. Age-related DNA methylation entropy, measured by the Jensen-Shannon Distribution, affects up to 25% of the detectable CpG sites and is a better measure of aging than individual CpG methylation. We analyze this entropy as a function of age in seven other tissues (heart, kidney, skeletal muscle, lung, liver, spleen, and blood) and it correlates strikingly with tissue-specific stem cell division rates. Thus, DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues. These data have implications for the mechanisms of tissue-specific functional declines with aging and for the development of DNA-methylation-based biological clocks. |
36,797,755 | Lung cancer embolization causing acute limb ischemia a case report. | Acute tumour embolism to the popliteal artery resulting in limb-threatening ischemia is a rare complication of neoplastic disease. Generally, tumors embolize to the pulmonary circulation via the venous system. In this case, the originating tumor was a lung cancer of a large size and advanced stage that had invaded the left atrium of the heart and disseminated in the systemic circulation. The tumor likely fragmented, resulting in showering to the right popliteal artery, superior mesenteric artery, and left renal artery, which is a unique presentation of tumor embolism. We present a case of a 62-year-old Caucasian gentleman with a large left lower lobe squamous cell lung cancer that had invaded into the left atrium via the pulmonary veins. He presented with acute limb threatening ischemia. A computed tomographic angiogram revealed an occlusion of the left popliteal artery as well as embolization to the superior mesenteric artery and the right renal artery. He was started on intravenous heparin and underwent an emergency popliteal embolectomy and calf fasciotomies, which was limb saving. His fasciotomy wounds were closed after 1 week and he was discharged on anticoagulation. This is a rare case of tumor embolism resulting in both an embolectomy and calf fasciotomies. In the light of such cases, we suggest that tumors invading the bloodstream should be considered high risk for embolization and hypothesize that prophylactic antithrombotic therapy may avoid major morbidity. |
36,797,629 | Thoracic Radiotherapy Effect on the Outcome in Extensive Stage Small Cell Lung Cancer. | To evaluate the efficacy of thoracic radiotherapy to primary site in patients with extensive stage small cell lung cancer (SCLC) who had responded completely to systemic chemotherapy. Observational study. Departments of Radiation and Medical Oncology, Baskent University and Dr. Ersin Arslan Research and Training Hospital in Turkey, between the years of 2011 and 2020. The study included 125 patients with extensive stage SCLC. Demographic data and outcomes of chemotherapy and radiotherapy were collected. The efficacy of thoracic radiotherapy to primary site was evaluated in patients who had responded completely to systemic chemotherapy, in terms of progression-free survival and overall survival (OS). The median follow-up time was 12 months and 98 (78.4%) patients died during follow-up. Seventy-three (58.4%) patients had complete response. Progression-free survival (PFS) for complete responder patients was 8 months, and OS for the whole group was found 13 months. Twenty (16%) patients received thoracic radiotherapy to primary site after complete response to platinum etoposide combination treatment. Patients receiving thoracic radiotherapy had better OS than those who did not (19 versus 12 months respectively and p0.002). Patients receiving thoracic radiotherapy had better PFS than those who did not (11 versus 8 months, respectively, and p0.01). Thoracic radiotherapy to primary site may improve the survival outcomes in extensive stage SCLC patients who had complete response to initial systemic chemotherapy. Small cell lung cancer, Thoracic radiotherapy, Complete response, Outcomes, Lung cancer. |
36,797,619 | Peritumoural Oedema as a Predictor of Overall Survival for Patients with Posterior Fossa Metastases. | To analyse the relationship between peritumoural oedema volume and tumour volume in relation to the impact of metastatic posterior fossa tumour survival rates. An observational study. Umraniye Training and Research Hospital, İstanbul, Turkey, from 2011-2021. Fifty-six cancer patients who had been operated upon for cerebellar metastases were analysed retrospectively. To investigate the effect of oedema on survival, patients with a single cerebellar metastasis were evaluated retrospectively. Those patients had a single metastasis located in the cerebellum and did not receive radiotherapy or corticosteroids before surgery. OsiriX MD DICOM viewer was used to calculate the volumes of the tumour and the oedema using fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced magnetic resonance imaging (MRI). The patients were separated into two groups, and the cut-off limit for the oedema to-tumour ratio was set to two. Survival analysis was performed on the two groups. When the primary sites of the tumours were evaluated, 60.7% were located in the lungs (n 34), 10.7% were located in the breasts (n 6), 10.7% were located in the gastrointestinal tract (n 6), 7.1% were located in the renal region (n 4), 5.4% were located in the gynaecologic tract (n 3), and 5.4% were located in other parts of the body (n 3). A univariate analysis showed that overall survival duration was significantly longer in the subgroup with breast cancer (83.3%) and in those patients with a peritumoural oedema volume to tumour volume ratio of less than two (27.6%, p <0.05). Negative prognostic factors were lung cancer and high peritumoural oedema volume. Significant peritumoural oedema was linked to a poor prognosis for cancer patients with a single cerebellar metastasis, especially with lung cancer as the primary source. Cerebellar metastases, Cerebellum, OsiriX MD, Tumour volume. |
36,797,503 | ALK-positive lung cancer a moving target. | Anaplastic lymphoma kinase (ALK) is a potent oncogenic driver in lung cancer. ALK tyrosine kinase inhibitors yield significant benefit in patients with ALK fusion-positive (ALK |
36,797,453 | Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms Past, Present, and Future. | The introduction of Ki67 immunohistochemistry in the work-up of neuroendocrine neoplasms (NENs) has opened a new approach for their diagnosis and prognostic evaluation. Since the first demonstration of the prognostic role of Ki67 proliferative index in pancreatic NENs in 1996, several studies have been performed to explore its prognostic, diagnostic, and predictive role in other neuroendocrine and endocrine neoplasms. A large amount of information is now available and published results globally indicate that Ki67 proliferative index is useful to this scope, although some differences exist in relation to tumor site and type. In gut and pancreatic NENs, the Ki67 proliferative index has a well-documented and accepted diagnostic and prognostic role and its evaluation is mandatory in their diagnostic work-up. In the lung, the Ki67 index is recommended for the diagnosis of NENs on biopsy specimens, but its diagnostic role in surgical specimens still remains to be officially accepted, although its prognostic role is now well documented. In other organs, such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, the Ki67 index does not play a diagnostic role and its prognostic value still remains a controversial issue. In medullary thyroid carcinoma, the Ki67 labelling index is used to define the tumor grade together with other morphological parameters, while in the adrenal cortical carcinoma, it is useful to select patients to treated with mitotane therapy. In the present review, the most important information on the diagnostic, prognostic, and predictive role of Ki67 proliferative index is presented discussing the current knowledge. In addition, technical issues related to the evaluation of Ki67 proliferative index and the future perspectives of the application of Ki67 immunostaining in endocrine and neuroendocrine neoplasms is discussed. |
36,797,416 | KDM6B protects T-ALL cells from NOTCH1-induced oncogenic stress. | T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors. While activating NOTCH1 mutations are the dominant genetic drivers of T-ALL, epigenetic dysfunction plays a central role in the pathology of T-ALL and can provide alternative mechanisms to oncogenesis in lieu of or in combination with genetic mutations. The histone demethylase enzyme KDM6A (UTX) is also recurrently mutated in T-ALL patients and functions as a tumor suppressor. However, its gene paralog, KDM6B (JMJD3), is never mutated and can be significantly overexpressed, suggesting it may be necessary for sustaining the disease. Here, we used mouse and human T-ALL models to show that KDM6B is required for T-ALL development and maintenance. Using NOTCH1 gain-of-function retroviral models, mouse cells genetically deficient for Kdm6b were unable to propagate T-ALL. Inactivating KDM6B in human T-ALL patient cells by CRISPRCas9 showed KDM6B-targeted cells were significantly outcompeted over time. The dependence of T-ALL cells on KDM6B was proportional to the oncogenic strength of NOTCH1 mutation, with KDM6B required to prevent stress-induced apoptosis from strong NOTCH1 signaling. These studies identify a crucial role for KDM6B in sustaining NOTCH1-driven T-ALL and implicate KDM6B as a novel therapeutic target in these patients. |
36,797,158 | Evaluation of electromagnetic navigational bronchoscopic biopsy of lung lesions performed by a thoracic surgical service. | With the increasing use of computed tomography scans for lung cancer screening and surveillance of other cancers, thoracic surgeons are being referred patients with lung lesions for biopsies. Electromagnetic navigational bronchoscopy-guided lung biopsy is a relatively new technique for bronchoscopic biopsy. Our objective was to evaluate the diagnostic yields and safety of electromagnetic navigational bronchoscopy-guided lung biopsy. We conducted a retrospective review of patients who underwent an electromagnetic navigational bronchoscopy biopsy, performed by a thoracic surgical service, and evaluated its safety and diagnostic accuracy. In total, 110 patients (men 46, women 64) underwent electromagnetic navigational bronchoscopy sampling of pulmonary lesions (n 121 median size 27 mm interquartile range 17-37 mm). There was no procedure-related mortality. Pneumothorax requiring pigtail drainage occurred in 4 patients (3.5%). Ninety-three (76.9%) of the lesions were malignant. Eighty-seven (71.9%) of the 121 lesions had an accurate diagnosis. Accuracy increased with increased lesion size (P .0578) with a yield of 50% for lesions <2 cm, increasing to 81% for lesions ≥2 cm. The lesions that demonstrated a positive bronchus sign had a yield of 87% (4552) compared with 61% (4269) in lesions with a negative bronchus sign (P .0359). Thoracic surgeons can perform electromagnetic navigational bronchoscopy safely, with minimal morbidity and with good diagnostic yields. Accuracy increases with the presence of a bronchus sign and increasing lesion size. Patients with larger tumors and the bronchus sign may be candidates for this approach to biopsy. Further work is required to define the role of electromagnetic navigational bronchoscopy in the diagnosis of pulmonary lesions. |
36,797,152 | Liquid Biopsy Screening for Early Detection of Lung Cancer Current State and Future Directions. | Liquid biopsy (LB) is clinically utilized to detect minute amounts of genetic material or protein shed by cancer cells, most commonly cell free DNA (cfDNA), as a noninvasive precision oncology tool to assess genomic alterations to guide cancer therapy or to detect the persistence of tumor cells after therapy. LB is also being developed as a multi-cancer screening assay. The use of LB holds great promise as a tool to detect lung cancer early. Although lung cancer screening (LCS) with low-dose computed tomography (LDCT) substantially reduces lung cancer mortality in high-risk individuals, the ability of current LCS guidelines to reduce the public health burden of advanced lung cancer through early detection has been limited. LB may be an important tool to improve early lung cancer detection among all populations at risk for lung cancer. In this systematic review, we summarize the test characteristics, including sensitivity and specificity of individual tests, as they pertain to the detection of lung cancer. We also address critical questions in the use of liquid biopsy for early detection of lung cancer including 1. How might liquid biopsy be used to detect lung cancer early 2. How accurate is liquid biopsy in detecting lung cancer early and 3. Does liquid biopsy perform as well in never and light-smokers compared with current and former smokers. |
36,797,117 | Role of cellular senescence in inflammatory lung diseases. | Cellular senescence, a characteristic sign of aging, classically refers to permanent cell proliferation arrest and is a vital contributor to the pathogenesis of cancer and age-related illnesses. A lot of imperative scientific research has shown that senescent cell aggregation and the release of senescence-associated secretory phenotype (SASP) components can cause lung inflammatory diseases as well. In this study, the most recent scientific progress on cellular senescence and phenotypes was reviewed, including their impact on lung inflammation and the contributions of these findings to understanding the underlying mechanisms and clinical relevance of cell and developmental biology. Within a dozen pro-senescent stimuli, the irreparable DNA damage, oxidative stress, and telomere erosion are all crucial in the long-term accumulation of senescent cells, resulting in sustained inflammatory stress activation in the respiratory system. An emerging role for cellular senescence in inflammatory lung diseases was proposed in this review, followed by the identification of the main ambiguities, thus further understanding this event and the potential to control cellular senescence and pro-inflammatory response activation. In addition, novel therapeutic strategies for the modulation of cellular senescence that might help to attenuate inflammatory lung conditions and improve disease outcomes were also presented in this research. |
36,796,609 | Short-term association of air pollution with lung cancer mortality in Osaka, Japan. | Long-term air pollution exposure has been linked to increased lung cancer mortality. However, little is known about whether day-to-day fluctuations in air pollution levels are in relation to lung cancer mortality, particularly in low-exposure settings. This study aimed to evaluate the short-term associations between air pollution and lung cancer mortality. Daily data on lung cancer mortality, fine particulate matter (PM |
36,796,505 | Secretoglobin 3A2 protects lung from developing cigarette smoke-induced pulmonary emphysema. | Secretoglobin (SCGB) 3A2 is a bioactive molecule exhibiting various functions such as improving allergic airway inflammation and pulmonary fibrosis and promoting bronchial branching and proliferation during lung development. To determine if and how SCGB3A2 is involved in chronic obstructive pulmonary disease (COPD), a multifactorial disease with both airway and emphysematous lesions, a COPD mouse model was created by exposing Scgb3a2-deficient (KO), Scgb3a2-lung-specific overexpressing (TG), and wild type (WT) mice to cigarette smoke (CS) for 6 months. The KO mice showed loss of lung structure under control condition, and CS exposure resulted in more expansion of airspace and destruction of alveolar wall than WT mouse lungs. In contrast, TG mouse lungs showed no significant changes after CS exposure. SCGB3A2 increased the expression and phosphorylation of signal transducers and activators of transcription (STAT)1 and STAT3, and the expression of α1-antitrypsin (A1AT) in mouse lung fibroblast-derived MLg cells and mouse lung epithelial-derived MLE-15 cells. In MLg cells, A1AT expression was decreased in Stat3- knockdown cells, and increased upon Stat3 overexpression. STAT3 formed a homodimer when cells were stimulated with SCGB3A2. Chromatin immunoprecipitation and reporter assays demonstrated that STAT3 binds to specific binding sites on the Serpina1a gene encoding A1AT and upregulates its transcription in lung tissues of mice. Furthermore, nuclear localization of phosphorylated STAT3 upon SCGB3A2 stimulation was detected by immunocytochemistry. These findings demonstrate that SCGB3A2 protects the lungs from the development of CS-induced emphysema by regulating A1AT expression through STAT3 signaling. |
36,796,393 | Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC) a multicentre, multinational, individual patient data analysis. | p16 In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer data on p16 immunohistochemistry and on HPV testing information on age, sex, tobacco, and alcohol use staging by TNM 7th edition information on treatments received and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r-0·744, p0·0035). The proportion of patients with p16HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5-82·7) for p16HPV, 40·4% (38·6-42·4) for p16-HPV-, 53·2% (46·6-60·8) for p16-HPV, and 54·7% (49·2-60·9) for p16HPV-. 5-year disease-free survival was 84·3% (95% CI 82·9-85·7) for p16HPV, 60·8% (58·8-62·9) for p16-HPV- 71·1% (64·7-78·2) for p16-HPV, and 67·9% (62·5-73·7) for p16HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. Patients with discordant oropharyngeal cancer (p16-HPV or p16HPV-) had a significantly worse prognosis than patients with p16HPV oropharyngeal cancer, and a significantly better prognosis than patients with p16-HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions. European Regional Development Fund, Generalitat de Catalunya, National Institute for Health Research (NIHR) UK, Cancer Research UK, Medical Research Council UK, and The Swedish Cancer Foundation and the Stockholm Cancer Society. |
36,796,178 | CT-derived radiomic analysis for predicting the survival rate of patients with non-small cell lung cancer receiving radiotherapy. | Radiomics provides an opportunity to minimize adverse effects and optimize the efficacy of treatments noninvasively. This study aims to develop a computed tomography (CT) derived radiomic signature to predict radiological response for the patients with non-small cell lung cancer (NSCLC) receiving radiotherapy. Total 815 NSCLC patients receiving radiotherapy were sourced from public datasets. Using CT images of 281 NSCLC patients, we adopted genetic algorithm to establish a predictive radiomic signature for radiotherapy that had optimal C-index value by Cox model. Survival analysis and receiver operating characteristic curve were performed to estimate the predictive performance of the radiomic signature. Furthermore, radiogenomics analysis was performed in a dataset with matched images and transcriptome data. Radiomic signature consisting of three features was established and then validated in the validation dataset (log-rank P 0.0047) including 140 patient, and showed a significant predictive power in two independent datasets totaling 395 NSCLC patients with binary 2-year survival endpoint. Furthermore, the novel proposed radiomic nomogram significantly improved the prognostic performance (concordance index) of clinicopathological factors. Radiogenomics analysis linked our signature with important tumor biological processes (e.g. Mismatch repair, Cell adhesion molecules and DNA replication) associated with clinical outcomes. The radiomic signature, reflecting tumor biological processes, could noninvasively predict therapeutic efficacy of NSCLC patients receiving radiotherapy and demonstrate unique advantage for clinical application. |
36,796,118 | Effectiveness of mindfulness-based interventions on anxiety, depression, and fatigue in people with lung cancer A systematic review and meta-analysis. | Lung cancer is one of the most common cancers and poses a physical and psychological threat to patients. Mindfulness-based interventions are emerging forms of psychotherapy that are effective in improving physical and psychological symptoms, but no review has summarized their effectiveness on anxiety, depression, and fatigue in people with lung cancer. To evaluate the effectiveness of mindfulness-based interventions in reducing anxiety, depression, and fatigue in people with lung cancer. Systematic review and meta-analysis. We searched the PubMed, Web of Science, Embase, China Biology Medicine disc, Wanfang Data, China National Knowledge Infrastructure, and China Science and Technology Journal databases from inception to 13 April 2022. Eligible studies included randomized controlled trials of people with lung cancer receiving mindfulness-based interventions reporting on the outcomes of anxiety, depression, and fatigue. Two researchers independently reviewed the abstracts and full texts, extracted the data and assessed the risk of bias independently by using the Cochrane Risk of bias assessment tool. The meta-analysis was performed by using Review Manager 5.4, and the effect size was calculated by the standardized mean difference and its 95% confidence interval. The systematic review included 25 studies (2420 participants), whereas the meta-analysis included 18 studies (1731 participants). Mindfulness-based interventions significantly decreased levels of anxiety standardized mean difference -1.15, 95% confidence interval (-1.36, -0.94), Z 10.75, P < 0.001, depression standardized mean difference -1.04, 95% confidence interval (-1.60, -0.48), Z 3.66, P < 0.001, and fatigue standardized mean difference -1.29, 95% confidence interval (-1.66, -0.91), Z 6.79, P < 0.001. The subgroup analysis indicated that programs lasting less than eight weeks in length with structured intervention components (e.g., mindfulness-based stress reduction and mindfulness-based cognitive therapy) and 45 min of daily home practice implemented in patients with advanced stage lung cancer showed better effects than programs lasting more than eight weeks in length with less structured components and more than 45 min of daily home practice implemented in patients with mixed stage lung cancer. The overall quality of the evidence was low due to the lack of allocation concealment and blinding and the high risk of bias in most studies (80%). Mindfulness-based interventions might be effective in reducing anxiety, depression, and fatigue in people with lung cancer. However, we cannot draw definitive conclusions because the overall quality of the evidence was low. More rigorous studies are needed to confirm the effectiveness and examine which intervention components may be most effective for improved outcomes. |
36,795,754 | lncRNA | Notch has been implicated in human cancers and is a putative therapeutic target. However, the regulation of Notch activation in the nucleus remains largely uncharacterized. Therefore, characterizing the detailed mechanisms governing Notch degradation will identify attractive strategies for treating Notch-activated cancers. Here, we report that the long noncoding RNA (lncRNA) |
36,795,563 | Circadian regulator CLOCK promotes tumor angiogenesis in glioblastoma. | Glioblastoma (GBM) is one of the most aggressive tumors in the adult central nervous system. We previously revealed that circadian regulation of glioma stem cells (GSCs) affects GBM hallmarks of immunosuppression and GSC maintenance in a paracrine and autocrine manner. Here, we expand the mechanism involved in angiogenesis, another critical GBM hallmark, as a potential basis underlying CLOCKs pro-tumor effect in GBM. Mechanistically, CLOCK-directed olfactomedin like 3 (OLFML3) expression results in hypoxia-inducible factor 1-alpha (HIF1α)-mediated transcriptional upregulation of periostin (POSTN). As a result, secreted POSTN promotes tumor angiogenesis via activation of the TANK-binding kinase 1 (TBK1) signaling in endothelial cells. In GBM mouse and patient-derived xenograft models, blockade of the CLOCK-directed POSTN-TBK1 axis inhibits tumor progression and angiogenesis. Thus, the CLOCK-POSTN-TBK1 circuit coordinates a key tumor-endothelial cell interaction and represents an actionable therapeutic target for GBM. |
36,795,453 | Mitochondria on the move Horizontal mitochondrial transfer in disease and health. | Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria were shown to move between mammalian cells in culture via cytoplasmic bridges. Recent research in animals indicates transfer of mitochondria in cancer and during lung injury in vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial transfer (HMT) in vivo, and its functional characteristics and consequences have been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, mitochondrial trafficking between cells occurs more frequently than previously thought and contributes to diverse processes including bioenergetic crosstalk and homeostasis, disease treatment and recovery, and development of resistance to cancer therapy. Here we highlight current knowledge of HMT between cells, focusing primarily on in vivo systems, and contend that this process is not only (patho)physiologically relevant, but also can be exploited for the design of novel therapeutic approaches. |
36,795,388 | Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials. | Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes. To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non-small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies. IMpower130, IMpower132, and IMpower150 were phase 3, multicenter, open-label, randomized clinical trials to evaluate the efficacy and safety of chemoimmunotherapy combinations involving atezolizumab. Participants were chemotherapy-naive adults with stage IV nonsquamous NSCLC. These post hoc analyses were conducted during February 2022. Eligible patients were randomly assigned 21 to receive atezolizumab with carboplatin plus nab-paclitaxel, or chemotherapy alone (IMpower130) 11 to receive atezolizumab with carboplatin or cisplatin plus pemetrexed, or chemotherapy alone (IMpower132) and 111 to receive atezolizumab plus bevacizumab plus carboplatin and paclitaxel, atezolizumab plus carboplatin and paclitaxel, or bevacizumab plus carboplatin and paclitaxel (IMpower150). Pooled data from IMpower130 (cutoff March 15, 2018), IMpower132 (cutoff May 22, 2018), and IMpower150 (cutoff September 13, 2019) were analyzed by treatment (atezolizumab-containing vs control), irAE status (with vs without), and highest irAE grade (1-2 vs 3-5). To account for immortal bias, a time-dependent Cox model and landmark analyses of irAE occurrence at 1, 3, 6, and 12 months from baseline were used to estimate the hazard ratio (HR) of overall survival (OS). Of 2503 randomized patients, 1577 were in the atezolizumab-containing arm and 926 were in the control arm. The mean (SD) age of patients was 63.1 (9.4) years and 63.0 (9.3) years, and 950 (60.2%) and 569 (61.4%) were male, respectively, in the atezolizumab arm and the control arm. Baseline characteristics were generally balanced between patients with irAEs (atezolizumab, n 753 control, n 289) and without (atezolizumab, n 824 control, n 637). In the atezolizumab arm, OS HRs (95% CI) in patients with grade 1 to 2 irAEs and grade 3 to 5 irAEs (each vs those without irAEs) in the 1-, 3-, 6-, and 12-month subgroups were 0.78 (0.65-0.94) and 1.25 (0.90-1.72), 0.74 (0.63-0.87) and 1.23 (0.93-1.64), 0.77 (0.65-0.90) and 1.1 (0.81-1.42), and 0.72 (0.59-0.89) and 0.87 (0.61-1.25), respectively. In this pooled analysis of 3 randomized clinical trials, longer OS was observed in patients with vs without mild to moderate irAEs in both arms and across landmarks. These findings further support the use of first-line atezolizumab-containing regimens for advanced nonsquamous NSCLC. ClinicalTrials.gov Identifiers NCT02367781, NCT02657434, and NCT02366143. |
36,795,308 | Cardiovascular Toxicities Associated with Tyrosine Kinase Inhibitors. | To provide a detailed overview of cardiovascular adverse events associated with the use of tyrosine kinase inhibitors across different tumor types. Despite an undeniable survival advantage of tyrosine kinase inhibitors (TKIs) in patients with hematologic or solid malignancies, the accompanying off-target cardiovascular adverse events can be life-threatening. In patients with B cell malignancies, the use of Bruton tyrosine kinase inhibitors has been associated with atrial and ventricular arrhythmias, as well as hypertension. Cardiovascular toxic profiles are heterogeneous among the several approved breakpoint cluster region (BCR)-ABL TKIS. Notably, imatinib might be cardioprotective. Vascular endothelial growth factor TKIs, constituting the central axis in the treatment of several solid tumors, including renal cell carcinoma and hepatocellular carcinoma, have strongly been associated with hypertension and arterial ischemic events. Epidermal growth factor TKIs as therapy for advanced non-small cell lung cancer (NSCLC) have been reported to be infrequently associated with heart failure and QT prolongation. While tyrosine kinase inhibitors have been demonstrated to increase overall survival across different types of cancers, special consideration should be given to cardiovascular toxicities. High-risk patients can be identified by undergoing a comprehensive workup at baseline. |
36,795,259 | Ezrin regulates the progression of NSCLC by YAP and PD-L1. | To determine whether ezrin regulates Yes-associated protein (YAP) and programed cell death ligand-1 (PD-L1), which are involved in the invasion and metastasis of non-small cell lung cancer (NSCLC). Immunohistochemistry of 164 NSCLC and 16 para-cancer tissues was performed to detect ezrin, YAP, and PD-L1 expression. Further, H1299 and A549 cells were transfected with lentivirus, and then colony formation, CCK8, transwell, and wound-healing assays were used to assess cell proliferation, migration, and invasion. RT-qPCR and western blotting were used for quantitative analysis of ezrin, PD-L1, and YAP expression. Moreover, the role of ezrin in tumor growth was assessed in vivo, and immunohistochemistry and western blotting were performed to evaluate changes in ezrin expression in mouse samples. The positive protein expression rates of these molecules in NSCLC were as follows ezrin, 43.9% (72164) YAP, 54.3% (89164) and PD-L1, 47.6% (78164) these were higher than those in normal lung tissues. Moreover, YAP and ezrin expression positively correlated with PD-L1 expression. Ezrin promoted proliferation, migration, invasion, and expression of YAP and PD-L1in NSCLC. Inhibition of ezrin expression reduced the effects of ezrin on cell proliferation, migration, invasion, inhibited the expression of YAP and PD-L1, and obviously reduced experimental tumor volume in vivo. Ezrin is overexpressed in NSCLC patients and correlates with PD-L1 and YAP expression. Ezrin regulates YAP and PD-L1 expression. Inhibition of ezrin delayed NSCLC progression. |
36,795,122 | Mean platelet volume, thrombocytosis, and survival in non-small cell lung cancer patients treated with first-line pembrolizumab alone or with chemotherapy. | Patients treated with immune checkpoint inhibitors (ICIs) may not response to treatment and are at risk for immune-related adverse events (irAEs). Platelet function has been linked to both oncogenesis and immune evasion. We studied the association between the change in mean platelet volume (MPV), platelet count, survival, and the risk of developing irAEs in patients with metastatic non-small cell lung cancer (NSCLC) who have received first-line ICI. In this retrospective study, delta (∆) MPV was defined as the difference between cycle 2 and baseline MPV. Patient data were collected via chart review, and Cox proportional hazard and Kaplan-Meier method were used to assess the risk and estimate median overall survival. We identified 188 patients treated with first-line pembrolizumab, with or without concurrent chemotherapy. There were 80 (42.6%) patients received pembrolizumab monotherapy, and 108 (57.4%) received pembrolizumab in combination with platinum-based chemotherapy. Patients whose MPV (∆MPV ≤ 0) decreased had hazard ratio (HR) 0.64 (95% CI 0.43-0.94) for death with p 0.023. Patients with ∆MPV ≤ - 0.2 fL (median), there was a 58% increase in the risk of developing irAE (HR 1.58, 95% CI 1.04-2.40, p 0.031). Thrombocytosis at baseline and cycle 2 was associated with shorter OS with p 0.014 and 0.039, respectively. Change in MPV after 1 cycle of pembrolizumab-based treatment was significantly associated with overall survival as well as the occurrence of irAEs in patients with metastatic NSCLC in the first-line setting. In addition, thrombocytosis was associated with poor survival. |
36,795,001 | MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms. | Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutationsMb), and epigenetic mechanisms drive their development and progression. We aim to comprehensively characterize the microRNA (miRNA) profile of NENs, and explore downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analyzed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N63) and methylomics (N30) were performed to predict miRNA target genes, signaling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas (TCGA) cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signaling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients. |
36,794,726 | Usnic acid as potential inhibitors of BCL2 and P13K protein through network pharmacology-based analysis, molecular docking and molecular dynamic simulation. | Usnic acid (UA) lately piqued the interest of researchers for its extraordinary biological characteristics, including anticancer activity. Here, the mechanism was clarified through network pharmacology,molecular docking and molecular dynamic simulation. Sixteen proteins were selected through network pharmacology study as they are probable to interact with UA. Out of these proteins, 13 were filtered from PPI network analysis based on their significance of interactions ( |
36,794,564 | Afatinib for the treatment of non-small-cell lung cancer with unusual EGFR mutations a plain language summary. | EGFR is a protein on cells that helps control their growth and division. Mutations in the gene for EGFR can cause cancer, including some cases of non-small-cell lung cancer (NSCLC). Afatinib is a medicine that blocks mutated This is a summary of a study reporting findings from a large database of people with non-small-cell lung cancer (also called NSCLC) who have unusual or uncommon changes in a gene called The researchers found that afatinib works well in most people with NSCLC who have unusualuncommon The researchers concluded that afatinib is a treatment option for most people with NSCLC and unusualuncommon |
36,794,455 | Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non-Small Cell Lung Cancer. | Neoadjuvant anti-PD-1 therapy has shown promise for resectable non-small cell lung cancer (NSCLC). We reported the first phase III trial of neoadjuvant nivolumab in resectable NSCLC, finding it to be safe and feasible with encouraging major pathological responses (MPR). We now present 5-year clinical outcomes from this trial, representing to our knowledge, the longest follow-up data for neoadjuvant anti-PD-1 in any cancer type. Two doses of nivolumab (3 mgkg) were administered for 4 weeks before surgery to 21 patients with Stage I-IIIA NSCLC. 5-year recurrence-free survival (RFS), overall survival (OS), and associations with MPR and PD-L1, were evaluated. With a median follow-up of 63 months, 5-year RFS and OS rates were 60% and 80%, respectively. The presence of MPR and pre-treatment tumor PD-L1 positivity (TPS ≥1%) each trended toward favorable RFS HR, 0.61 95% confidence interval (CI), 0.15-2.44 and HR, 0.36 (95% CI, 0.07-1.85), respectively. At 5-year follow-up, 8 of 9 (89%) patients with MPR were alive and disease-free. There were no cancer-related deaths among patients with MPR. In contrast, 611 patients without MPR experienced tumor relapse, and 3 died. Five-year clinical outcomes for neoadjuvant nivolumab in resectable NSCLC compare favorably with historical outcomes. MPR and PD-L1 positivity trended toward improved RFS, though definitive conclusions are limited by cohort size. |
36,794,355 | Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging. | Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii |
36,794,146 | A multicenter-retrospective cohort study of chromosome instability in lung cancer clinical characteristics and prognosis of patients harboring chromosomal instability detected by metagenomic next-generation sequencing. | The usefulness of metagenomic next-generation sequencing (mNGS) in identifying the prognosis of lung cancer with chromosomal instability (CIN) remains unclear. We aimed to analyze clinical characteristics and prognosis of patients in patients harboring CIN. This retrospective cohort study included 668 patients diagnosed with suspected pulmonary infection or lung cancer whose samples underwent mNGS detection from January 2021 to January 2022. Difference between clinical characteristics were calculated by the Students t-test and the chi-square test. The subjects were followed-up from registered to September 2022. Survival curves were analyzed by the Kaplan-Meier method. Of 619 bronchoalveolar lavage fluid (BALF) samples collected by bronchoscopy, 30 CIN-positive samples were confirmed as malignant on histopathology, with a sensitivity of 61.22%, a specificity of 99.65%, and an 83.17% accuracy cut-off values were established by the receiver operating characteristic (ROC) area under the curve (AUC) 0.804. In 42 patients with lung cancer, mNGS detected 24 patients as CIN-positive and 18 as CIN-negative. There were no differences between two groups including ages, pathologic types, stage and metastases. In 25 cases, we detected 523 chromosomal copy number variants (CNVs) with forms including duplication (dup), deletion (del), mosaic (mos), and whole chromosome amplification or loss. A total of 243 duplication variants and 192 deletion variants occurred in all chromosomes. Duplications occurred in most chromosomes except for Chr9 and Chr13, in which CNV tended to delete. The median overall survival (OS) in patients with Chr5p15 duplication was 32.4 months 95% confidence interval (CI), 10.35-54.45 months. The median OS differed significantly between the 5p15dup group and the combined group (32.4 Various forms of CIN detected by mNGS may predict prognosis of patients with lung cancer differentially. CIN with duplication or deletion deserves further study to guide clinical treatment. |
36,794,139 | LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity. | Cisplatin (DDP) is among the most widely used chemotherapeutic drugs for non-small cell lung cancer (NSCLC), yet the frequent emergence of chemoresistance serves as a major barrier to the treatment of this tumor type. Long non-coding RNAs (lncRNAs) have recently been shown to influence the ability of cells to resist particular chemotherapy drugs. The present study was developed to explore the role of the lncRNA SNHG7 as a regulator of NSCLC cell chemosensitivity. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure SNHG7 expression in NSCLC tissues from patients that were sensitiveresistant to DDP, correlations between SNHG7 expression levels and the patients clinicopathological characteristics were assessed, and the prognostic relevance of SNHG7 expression was examined via the Kaplan-Meier approach. In addition, SNHG7 expression was assessed in NSCLC cell lines that were DDP-sensitive or -resistant, while western blotting and immunofluorescence staining were employed to detect autophagy-associated protein expression in A549, A549DDP, HCC827, and HCC827DDP cells. NSCLC cell chemoresistance was quantified via the Cell Counting Kit-8 (CCK-8) assay approach, and flow cytometry was used to detect the apoptotic death of these tumor cells. The chemosensitivity of xenograft tumors Relative to paracancerous tissues, NSCLC tumors exhibited SNHG7 upregulation, and this lncRNA was further upregulated in DDP-resistant patients compared to chemosensitive patients. Consistently, higher SNHG7 expression levels were correlated with worse patient survival outcomes. DDP-resistant NSCLC cells were also found to exhibit higher levels of SNHG7 expression than chemosensitive cells, and knocking down this lncRNA enhanced the sensitivity of these cells to DDP treatment, resulting in impaired proliferation and higher rates of apoptotic death. Knocking down SNHG7 was also sufficient to suppress microtubule associated protein 1 light chain 3 beta (LC3B) and Beclin1 protein levels and promote p62 upregulation SNHG7 can promote malignant behaviors and DDP resistance in NSCLC cells at least partly via the induction of autophagic activity. |
36,794,138 | Bufalin inhibits epithelial-mesenchymal transition and increases radiosensitivity of non-small cell lung cancer via inhibition of the Src signaling. | Epithelial-mesenchymal transition (EMT) is a biological process involved in tumor migration, invasion, and radiotherapy resistance. Bufalin can affect the proliferation, apoptosis and invasion of tumor cells by regulating multiple signaling pathways. Whether bufalin can increase radiosensitivity through EMT deserves further investigation. In this study, we investigated the effect of bufalin on the EMT and radiosensitivity of non-small cell lung cancer (NSCLC) and the underlying molecular mechanism. NSCLC cells were treated with bufalin (at a dose of 0-100 nM) or irradiated with 6 MV X-rays (4 Gymin). The effects of bufalin on cell survival, cell cycle, radiosensitivity, cell migration, and invasion were detected. Western blot was used to analyze the gene expression changes of Src signaling in NSCLC cell induced by Bufalin. Bufalin significantly inhibited cell survival, migration, and invasion and induced G2M arrest and apoptosis. Cells co-treated with bufalin and radiation manifested a higher inhibitory effect compared to those treated with radiation or bufalin alone. Furthermore, the levels of p-Src and p-STAT3 were considerably reduced following bufalin treatment. Interestingly, elevated p-Src and p-STAT3 were observed in cells treated with radiation. Bufalin inhibited radiation-induced p-Src and p-STAT3, whereas the knockdown of Src abrogated the effects of bufalin on cell migration, invasion, EMT, and radiosensitivity. Bufalin inhibits EMT and enhances radiosensitivity through targeting Src signaling in NSCLC. |
36,794,137 | The association of postoperative radiotherapy with survival in resected N2 non-small cell lung cancer. | The current staging system for completely resected pathologic N2 non-small cell lung cancer (NSCLC) treated with chemotherapy is not suitable for distinguishing those patients most likely to benefit from postoperative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized prediction of the net survival benefit of PORT in patients with completely resected N2 NSCLC treated with chemotherapy. A total of 3,094 cases from between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics were included as covariates, and their association with overall survival (OS) with and without PORT was assessed. Data from 602 patients from China were included for external validation. Age, sex, the number of examinedpositive lymph nodes, tumor size, the extent of surgery, and visceral pleural invasion (VPI) were significantly associated with OS (P<0.05). Two nomograms were developed based on clinical variables to estimate individuals net survival difference attributable to PORT. The calibration curve showed excellent agreement between the OS predicted by the prediction model and that actually observed. In the training cohort, the C-index for OS was 0.619 95% confidence interval (CI) 0.598-0.641 in the PORT group and 0.627 (95% CI 0.605-0.648) in the non-PORT group. Results showed that PORT could improve OS hazard ratio (HR) 0.861 P0.044 for patients with a positive PORT net survival difference. Our practical survival prediction model can be used to make an individualized estimate of the net survival benefit of PORT for patients with completely resected N2 NSCLC who have been treated with chemotherapy. |
36,794,135 | Treatment patterns and outcomes in patients with Pancoast tumors a national cancer database analysis. | Pancoast tumors represent 5% of non-small cell lung cancers. Complete surgical resection and no lymph node involvement are important positive prognostic factors. Previous literature has identified neoadjuvant chemoradiation treatment, followed by surgical resection, as the standard of care. But many institutions choose upfront surgery. Our goal was to identify the treatment patterns and outcomes in patients with node-negative Pancoast tumors using the National Cancer Database (NCDB). The NCDB was queried from 2004 through 2017 to identify all patients who had undergone surgery for a Pancoast tumor. Treatment patterns, including the percentage of patients who received neoadjuvant treatment, were recorded. Logistic regression and survival analyses were used to determine outcomes based on different treatment patterns. Secondary analyses were performed on the cohort who received upfront surgery. A total of 2,910 patients were included in the study. Overall 30- and 90-day mortality were 3% and 7% respectively. Only 25% (7172,910) of the group received neoadjuvant chemoradiation treatment prior to surgery. Patients who received neoadjuvant chemoradiation treatment experienced significantly improved 90-day survival (P<0.01) and overall survival (P<0.01). When analyzing the cohort who received upfront surgery, there was a statistically significant difference in survival based on adjuvant treatment pattern (P<0.01). Patients in this group who received adjuvant chemoradiation had the best survival, whereas patients who received adjuvant radiation only or no treatment had the worst outcomes. Patients with Pancoast tumors receive neoadjuvant chemoradiation treatment in only a quarter of cases nationally. Patients who received neoadjuvant chemoradiation treatment had improved survival compared to patients who had upfront surgery. Similarly, when surgery is performed first, adjuvant chemoradiation treatment improved survival compared to other adjuvant strategies. These results suggest underutilization of neoadjuvant treatment for patients with node-negative Pancoast tumors. Future studies with a more clearly defined cohort are needed to assess the treatment patterns being utilized on patients with node-negative Pancoast tumors. It will be beneficial to see whether neoadjuvant treatment for Pancoast tumors has increased in recent years. |
36,794,132 | Lipopolysaccharide and lipoteichoic acid regulate the PI3KAKT pathway through osteopontinintegrin β3 to promote malignant progression of non-small cell lung cancer. | Lung cancer (LC) is a malignancy with one of the highest mortality rates. Respiratory microbiota is considered to play a key role in the development of LC, but the molecular mechanisms are rarely studied. We used lipopolysaccharide (LPS) and lipoteichoic acid (LTA) to study human lung cancer cell lines PC9 and H1299. The gene expression of CXC chemokine ligand (CXCL)16, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell-Counting Kit 8 (CCK-8) was used to analyze cell proliferation. Transwell assays were performed to analyze cell migration ability. Flow cytometry was used to observe cell apoptosis. Western blot and qRT-PCR were used to analyze the expression of secreted phosphoprotein 1 ( We studied that in two cell lines, the expression level of inflammatory factors in LPSLTA group was significantly higher than that in single treatment group (P<0.001). We explored LPS LTA combined treatment group significantly increased the expression of NLRP3 and genes and proteins. LPS LTA Cisplatin group could significantly reduce the inhibitory effect of LPS on cell proliferation (P<0.001), reduce the apoptosis rate (P<0.001) and significantly reduce the expression levels of caspase-39 (P<0.001) compared with Cisplatin group. Finally, we verified that LPS and LTA could increase osteopontin (OPN)integrin β3 expression and activate the PI3KAKT pathway to promote malignant progression of LC This study provides a theoretical basis for further exploration of the influence of lung microbiota on NSCLC and the optimization of LC treatment in the future. |
36,794,128 | High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population. | This study sought to examine the expression and mutation status of fibroblast growth factor receptor 3 (FGFR3) in non-small cell lung cancer (NSCLC) tissues and explore the prognostic potential of FGFR3 in NSCLC. Immunohistochemistry (IHC) was used to evaluate the FGFR3 protein expression of 116 NSCLC tissues. Sanger sequencing was used to examine the mutation status of exons 7, 10, and 15 in FGFR3. A Kaplan‑Meier survival analysis was conducted to evaluate the association between the expression level of FGFR3 and the overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Univariate and multivariate Cox analyses were conducted to examine the association between the risk score and clinical features. FGFR3 was immunoreactive in 26 of the 86 NSCLC cases. Further, FGFR3 was positively expressed in 84.6% of the lung adenocarcinoma (AC) cases and 15.4% of the lung squamous cell carcinoma (SCC) cases. FGFR3 mutations were detected in 2 NSCLC patients (272, 2.8%), who both harbored the T450M mutation, a novel mutation in exon 10 of FGFR3. In NSCLC, a high expression of FGFR3 was positively correlated with gender, smoking, histology type, T stage, and the epidermal growth factor receptor (EGFR) mutation (P<0.05). FGFR3 expression was also correlated with better OS and DFS. The multivariate analysis revealed that FGFR3 served as an independent prognostic factor (P0.024) for the OS of NSCLC patients. This study showed that FGFR3 was highly expressed in NSCLC tissues, and the frequency rate for the FGFR3 mutation at T450 M in NSCLC tissues was low. The survival analysis suggested that FGFR3 may be a useful prognostic biomarker in NSCLC. |
36,794,098 | Evaluating Histological Subtypes Classification of Primary Lung Cancers on Unenhanced Computed Tomography Based on Random Forest Model. | Lung cancer is the leading cause of cancer-related death in many countries, and an accurate histopathological diagnosis is of great importance in subsequent treatment. The aim of this study was to establish the random forest (RF) model based on radiomic features to automatically classify and predict lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), and small cell lung cancer (SCLC) on unenhanced computed tomography (CT) images. Eight hundred and fifty-two patients (mean age 61.4, range 29-87, malefemale 536316) with preoperative unenhanced CT and postoperative histopathologically confirmed primary lung cancers, including 525 patients with ADC, 161 patients with SCC, and 166 patients with SCLC, were included in this retrospective study. Radiomic features were extracted, selected, and then used to establish the RF classification model to analyse and classify primary lung cancers into three subtypes, including ADC, SCC, and SCLC according to histopathological results. The training (446 ADC, 137 SCC, and 141 SCLC) and testing cohorts (79 ADC, 24 SCC, and 25 SCLC) accounted for 85% and 15% of the whole datasets, respectively. The prediction performance of the RF classification model was evaluated by F1 scores and the receiver operating characteristic (ROC) curve. On the testing cohort, the areas under the ROC curve (AUC) of the RF model in classifying ADC, SCC, and SCLC were 0.74, 0.77, and 0.88, respectively. The F1 scores achieved 0.80, 0.40, and 0.73 in ADC, SCC, and SCLC, respectively, and the weighted average F1 score was 0.71. In addition, for the RF classification model, the precisions were 0.72, 0.64, and 0.70 the recalls were 0.86, 0.29, and 0.76 and the specificities were 0.55, 0.96, and 0.92 in ADC, SCC, and SCLC. The primary lung cancers were feasibly and effectively classified into ADC, SCC, and SCLC based on the combination of RF classification model and radiomic features, which has the potential for noninvasive predicting histological subtypes of primary lung cancers. |
36,794,070 | Tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as first-line therapy for advanced non-squamous non-small cell lung cancer. | Tislelizumab is a programmed cell death protein-1 (PD-1) inhibitor. Tislelizumab plus chemotherapy as first-line option for advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy alone, resulted in significantly prolonged survival outcomes however, evidence regarding its relative efficacy and cost is lacking. We aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy compared with that of chemotherapy alone, from the health care perspective in China. A partitioned survival model (PSM) was used for this study. The survival data were obtained from the RATIONALE 304 trial. Cost-effectiveness was defined as incremental cost-effectiveness ratio (ICER) less than the willingness to pay (WTP) threshold. Incremental net health benefits (INHB), incremental net monetary benefits (INMB), and subgroup analyses were also assessed. Sensitivity analyses were further established to assess the model stability. Compared with chemotherapy alone, tislelizumab plus chemotherapy increased by 0.64 quality-adjusted life-years (QALYs) and 1.48 life-years, and yielded an increase of $16,631 in cost per patient. The INMB and INHB were $7,510 and 0.20 QALYs at a WTP threshold of $38,017QALY, respectively. The ICER was $26,162QALY. The outcomes were most sensitive to the HR of OS for tislelizumab plus chemotherapy arm. The probability of tislelizumab plus chemotherapy being considered cost-effective was 87.66% and >50% in most of the subgroups at the WTP threshold of $38,017QALY. At the WTP threshold of $86,376QALY, the probability achieved 99.81%. Furthermore, the probability of tislelizumab plus chemotherapy being considered cost-effective in subgroups of patients with liver metastases and PD-L1 expression ≥50% were 90.61 and 94.35%, respectively. Tislelizumab plus chemotherapy is likely to be cost-effective as a first-line treatment for advanced non-squamous NSCLC in China. |
36,794,022 | A mechanistic study on the cellular uptake, intracellular trafficking, and antisense gene regulation of bottlebrush polymer-conjugated oligonucleotides. | We have developed a non-cationic transfection vector in the form of bottlebrush polymer-antisense oligonucleotide (ASO) conjugates. Termed pacDNA (polymer-assisted compaction of DNA), these agents show improved biopharmaceutical characteristics and antisense potency |
36,793,988 | Hybrid uniportal robotic-assisted thoracoscopic surgery using video-assisted thoracoscopic surgery staplers technical aspects and results. | The clinical efficacy of robot-assisted thoracic surgeries has been explored by numerous recent studies. Nonetheless, since current standard robotic systems (da Vinci Xi system) were intended for multiportal surgical processes and robotic staplers were still unavailable in the developing world, obstacles still remain concerning the feasibility of uniportal robotic surgeries. A hybrid uniportal robotic-assisted thoracoscopic surgery (RATS) modality utilizing video-assisted thoracoscopic surgery (VATS) staplers was investigated in Shanghai Pulmonary Hospital. Clinicopathological characteristics and perioperative outcomes concerning patients receiving hybrid uniportal RATS between August 2022 and September 2022 were collected. A total of 40 patients were included in this study. Most of the patients (2340, 57.5%) received hybrid uniportal RATS lobectomies. One conversion from uniportal RATS to biportal process was encountered due to extensive adhesions discovered intraoperatively. The median procedural duration was 76 min interquartile range (IQR), 61-99 min, and the median blood loss volume was 50 mL (IQR, 50-50 mL). A median stay length of three days (IQR, 2-4 days) was recorded. Eleven patients (27.5%) developed Clavien-Dindo grade I-II postoperative complications, while no grade III-IV complications were observed. Aside from this, none of the patients were readmitted or died within 30 days post-surgery. The feasibility of hybrid uniportal RATS procedures using VATS staplers has been preliminarily validated. For early-stage non-small cell lung cancer patients, such a procedure might clinical efficacy comparable to that of uniportal RATS utilizing robotic staplers. |
36,793,982 | Uniportal robotic versus thoracoscopic assisted surgery a propensity score-matched analysis of the initial 100 cases. | Minimally invasive surgery (MIS) is becoming the standard of care for anatomic lung resections. The advantages of the uniportal approach compared to the conventional multiple incision approach, multiportal video-assisted thoracic surgery (mVATS) and multiportal robotic-assisted thoracic surgery (mRATS), have been previously described. However, no research studies comparing early outcomes between uniportal video-assisted thoracic surgery (uVATS) and uniportal robotic-assisted thoracic surgery (uRATS) have been reported. Anatomic lung resections performed by uVATS and uRATS from August 2010 to October 2022 were enrolled. Early outcomes were compared after propensity score-matched (PSM) analysis by applying a multivariable logistic regression model including gender, age, smoking habit, forced expiratory volume in the first second (FEV1), cardiovascular risk factors (CVRF), pleural adhesions and tumor size. A total of 200 patients who underwent anatomic lung resections by the same surgeon were recruited in this study, including the initial 100 uVATS patients and the initial 100 uRATS patients. After PSM analysis, each group included 68 patients. The comparison of the two groups showed no significant differences according to the TNM stage in patients with lung cancer, surgical time, intraoperative complications, conversion, number of nodal stations explored, opioid usage, prolonged air leak, length of intensive care unit (ICU) and hospitalization, reintervention and mortality. However, there were significant differences concerning the histology and type of resection (anatomic segmentectomies, the proportion of complex segmentectomies and the sleeve technique were significantly higher in the uRATS group), number of resected lymph nodes (significantly higher in the uRATS group), postoperative complications and duration of chest drain (significantly lower in the uRATS group). Judging from the short-term outcomes, our results confirm the safety, feasibility and efficacy of uRATS as a new minimally invasive technique that combines the benefits of the uniportal method and robotic systems. |
36,793,981 | Uniportal fully robotic-assisted sleeve resections surgical technique and initial experience of 30 cases. | Since the first uniportal video-assisted thoracoscopic surgery (uVATS) performed in 2010, the uniportal approach has evolved up to a point where even the most complex cases can be done. This is thanks to the experience acquired over the years, the specifically designed instruments and improvements in imaging. However, in these last few years, robotic-assisted thoracoscopic surgery (RATS) has also shown progress and distinct advantages compared to the uniportal VATS approach, thanks to advanced maneuverability of the robotic arms as well as the three-dimensional (3D) view. Excellent surgical outcomes have been reported and so too, the ergonomic benefits to the surgeon. The main limitation we find of the robotic systems is that they are designed for a multiport approach, requiring between three to five incisions to be able to perform surgeries. With the aim to offer the least invasive approach, using the robotic technology we decided to adapt the Da Vinci Xi |
36,793,937 | Establishment of a Lymph Node Metastasis-Associated Prognostic Signature for Lung Adenocarcinoma. | Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC) with a low 5-year survival rate, which may be associated with the presence of metastatic tumors at the time of diagnosis, especially lymph node metastasis (LNM). This study aimed to construct a LNM-related gene signature for predicting the prognosis of patients with LUAD. RNA sequencing data and clinical information of LUAD patients were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Samples were divided into metastasis (M) and nonmetastasis (NM) groups based on LNM status. Differentially expressed genes (DEGs) between M and NM groups were screened, and then WGCNA was applied to identify key genes. Furthermore, univariate Cox and LASSO regression analyses were conducted to construct a risk score model, and the predictive performance of model was validated by GSE68465, GSE42127, and GSE50081. The protein and mRNA expression level of LNM-associated genes were detected by human protein atlas (HPA) and GSE68465. A prognostic model based on eight LNM-related genes (ANGPTL4, BARX2, GPR98, KRT6A, PTPRH, RGS20, TCN1, and TNS4) was developed. Patients in the high-risk group had poorer overall survival than those in the low-risk group, and validation analysis showed that this model had potential predictive value for patients with LUAD. HPA analysis supported the upregulation of ANGPTL4, KRT6A, BARX2, RGS20 and the downregulation of GPR98 in LUAD compared with normal tissues. Our results indicated that the eight LNM-related genes signature had potential value in the prognosis of patients with LUAD, which may have important practical implications. |
36,793,923 | Fixed right ventricular collapse A loculated pericardial effusion due to metastatic pulmonary adenocarcinoma. | Pericardial effusions can occur as either circumferential or loculated when referencing their anatomic distribution in the pericardium. These effusions can result from multiple different etiologies, including malignancy, infection, trauma, connective tissue disease, acute pericarditis drug induced, or idiopathic. Loculated pericardial effusions can be difficult to manage. Even small loculated effusions can result in hemodynamic compromise. Oftentimes in the acute setting, point of care ultrasound can be used to evaluate pericardial effusions directly at the bedside. We present a case of a malignant loculated pericardial effusion and offer insight into management and clinical evaluation using point of care ultrasound. |
36,793,862 | PLK1-mediated phosphorylation of β-catenin enhances its stability and transcriptional activity for extracellular matrix remodeling in metastatic NSCLC. | null |
36,793,853 | Exosomal STIMATE derived from type II alveolar epithelial cells controls metabolic reprogramming of tissue-resident alveolar macrophages. | null |
36,793,761 | Garlic Extract Participates in the Proliferation and Apoptosis of Nonsmall Cell Lung Cancer Cells Via Endoplasmic Reticulum Stress Pathway. | To investigate the effect of garlic extract (GE) on the proliferation and apoptosis of cell lines A549 and H1299 in lung cancer (LC). A549 and H1299 cells with well-developed logarithmic growth were added with GE at a concentration of 0 Colony formation and EdU assays revealed that Z-ajoene could inhibit cell viability and cell proliferation in NSCLC cells. After 24 h culture, there was no significant difference in the proliferation rate of A549 and H1299 cells with different GE concentrations ( GE could exert toxic effects on A549 and H1299 cells, inhibit cell proliferation, promote apoptosis, and attenuate cell migration. Meanwhile, it might induce apoptosis of A549 and H1299 cells through the caspase signal pathway, which is positively correlated with the mass action concentration and is expected to be a new drug for LC treatment. |
36,793,737 | DSP-0509, a systemically available TLR7 agonist, exhibits combination effect with immune checkpoint blockade by activating anti-tumor immune effects. | TLR7 is an innate immune receptor that recognizes single-stranded RNAs, and its activation leads to anti-tumor immune effects. Although it is the only approved TLR7 agonist in cancer therapy, imiquimod is allowed to be administered with topical formulation. Thus, systemic administrative TLR7 agonist is expected in terms of expanding applicable cancer types. Here, we demonstrated the identification and characterization of DSP-0509 as a novel small-molecule TLR7 agonist. DSP-0509 is designed to have unique physicochemical features that could be administered systemically with a short half-life. DSP-0509 activated bone marrow-derived dendritic cells (BMDCs) and induced inflammatory cytokines including type I interferons. In the LM8 tumor-bearing mouse model, DSP-0509 reduced tumor growth not only in subcutaneous primary lesions but also in lung metastatic lesions. DSP-0509 inhibited tumor growth in several syngeneic tumor-bearing mouse models. We found that the CD8 |
36,793,597 | A new immune signature for survival prediction and immune checkpoint molecules in non-small cell lung cancer. | Immune checkpoint blockade (ICB) therapy has brought remarkable clinical benefits to patients with advanced non-small cell lung carcinoma (NSCLC). However, the prognosis remains largely variable. The profiles of immune-related genes for patients with NSCLC were extracted from TCGA database, ImmPort dataset, and IMGTGENE-DB database. Coexpression modules were constructed using WGCNA and 4 modules were identified. The hub genes of the module with the highest correlations with tumor samples were identified. Then integrative bioinformatics analyses were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of NSCLC. Cox regression and Lasso regression analyses were conducted to screen prognostic signature and to develop a risk model. Functional analysis showed that immune-related hub genes were involved in the migration, activation, response, and cytokine-cytokine receptor interaction of immune cells. Most of the hub genes had a high frequency of gene amplifications. MASP1 and SEMA5A presented the highest mutation rate. The ratio of M2 macrophages and naïve B cells revealed a strong negative association while the ratio of CD8 T cells and activated CD4 memory T cells showed a strong positive association. Resting mast cells predicted superior overall survival. Interactions including protein-protein, lncRNA and transcription factor interactions were analyzed and 9 genes were selected by LASSO regression analysis to construct and verify a prognostic signature. Unsupervised hub genes clustering resulted in 2 distinct NSCLC subgroups. The TIDE score and the drug sensitivity of gemcitabine, cisplatin, docetaxel, erlotinib and paclitaxel were significantly different between the 2 immune-related hub gene subgroups. These findings suggested that our immune-related genes can provide clinical guidance for the diagnosis and prognosis of different immunophenotypes and facilitate the management of immunotherapy in NSCLC. |
36,793,588 | Characterization of Infiltrating Immune Cells and Secretory or Membrane-Associated Proteins in KRAS Lung Adenocarcinoma. | This study identified the expression and prognosis significance of secretory or membrane-associated proteins in KRAS lung adenocarcinoma (LUAD) and depicted the characteristics between the immune cell infiltration and the expression of these genes. Gene expression data of LUAD samples ( Secretory or membrane-associated genes with differential expression ( The research investigated the relationship between the expression of KRAS-related secretory or membrane-associated proteins in LUAD patients with prognostic prediction and immune infiltration characterization. Our study demonstrated that secretory or membrane-associated genes were closely associated with the survival of KRAS LUAD patients and were strongly correlated to immune cell infiltration. |
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