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Development of fatty acid metabolism-related models in lung adenocarcinomaA Review.

Lung adenocarcinoma (LUAD) is 1 of the common malignancy with a poor prognosis. Based on bioinformatics, the fatty acid metabolism model of LUAD was developed. We downloaded LUAD transcriptome data from the cancer genome atlas and gene expression omnibus databases. We used bioinformatics methods to construct a fatty acid metabolism-related predictive risk model to predict the prognosis of LUAD. We further explored the relationship between prognostic models and survival and immunity. We identified 17 prognosis-related fatty acid-associated genes and constructed prognostic models. In the the cancer genome atlas cohort, the prognosis was worse in the high-risk score group compared to the low-risk score group. The ROC curve confirmed its accuracy. Subsequently, we used the gene expression omnibus database to confirm the above findings. There were differences in immune infiltrating cell abundance and immune function between the high-risk score group and low-risk score group. The immune dysfunction and exclusion (TIDE) based algorithm showed that the low-risk score group was more suitable for the immune treatment. Fatty acid metabolic patterns can deepen the understanding of the immune microenvironment of LUAD and be used to guide the formulation of immunotherapy protocols.

Important parameters for cost-effective implementation of lung cancer screening.

It is now widely accepted that lung cancer screening through low-dose computed tomography (LDCT) results in fewer diagnoses at a late stage, and decreased lung cancer mortality. Whilst reducing deaths from lung cancer is an essential prerequisite, this must be balanced against the considerable economic costs accumulated in screening. Multiple health economic models have shown substantial variation in cost per Quality-Adjusted Life Year (QALY), partly driven by the healthcare costs in the country concerned and partly by other modifiable programme components. Recent modelling using UK costs and a targeted approach suggest that most scenarios are within the willingness to pay threshold for the UK. However, identifying the most clinically and cost-effective programme is a priority to minimise the total financial impact. Programme components that influence cost-effectiveness include the method of selection of the eligible population, the participation rate, the interval between rounds of screening, the method of pulmonary nodule management, and the approach to clinical work up. Future research will clarify if a personalised approach to screening, using baseline and subsequent risk to define screening intervals is more cost-effective. The burden of LDCT screening on the medical infrastructure and workforce has to be quantified and carefully managed during implementation.

Lung Cancer Risk Prediction Nomogram in Nonsmoking Chinese Women Retrospective Cross-sectional Cohort Study.

It is believed that smoking is not the cause of approximately 53% of lung cancers diagnosed in women globally. The study aimed to develop and validate a simple and noninvasive model that could assess and stratify lung cancer risk in nonsmoking Chinese women. Based on the population-based Cancer Screening Program in Urban China, this retrospective, cross-sectional cohort study was carried out with a vast population base and an immense number of participants. The training set and the validation set were both constructed using a random distribution of the data. Following the identification of associated risk factors by multivariable Cox regression analysis, a predictive nomogram was developed. Discrimination (area under the curve) and calibration were further performed to assess the validation of risk prediction nomogram in the training set, which was then validated in the validation set. In sum, 151,834 individuals signed up to take part in the survey. Both the training set (n75,917) and the validation set (n75,917) were comprised of randomly selected participants. Potential predictors for lung cancer included age, history of chronic respiratory disease, first-degree family history of lung cancer, menopause, and history of benign breast disease. We displayed 1-year, 3-year, and 5-year lung cancer risk-predicting nomograms using these 5 factors. In the training set, the 1-year, 3-year, and 5-year lung cancer risk areas under the curve were 0.762, 0.718, and 0.703, respectively. In the validation set, the model showed a moderate predictive discrimination. We designed and validated a simple and noninvasive lung cancer risk model for nonsmoking women. This model can be applied to identify and triage people at high risk for developing lung cancers among nonsmoking women.

Occupational exposure to silica dust in Slovenia is grossly underestimated.

As a by-product or material used in various industries crystalline silica contaminates the air many occupational settings. If its fine particles are inhaled, they are deposited in the lungs and may cause the development of silicosis, chronic obstructive pulmonary disease, and lung cancer. The goal of this study was to estimate occupational exposure to respirable crystalline silica (RCS) in Slovenia and the associated health risks. To do that, we ran two cross-sectional studies, one to determine the number of workers at risk of occupational exposure to RCS in Slovene industries and the other to determine and classify changes in the lung radiographs of glass factory workers exposed to RCS, as a means to infer health risks for other RCS exposed workers in Slovenia. However, the first study shows that official public data on occupational exposure to silica in Slovenia are unreliable and incomplete and that company representatives strongly underestimate occupational exposure to silica. Measurements of total and silica dust are made by 8.3 % and 1.8 % of companies working with silica, respectively. The second study shows that about a third of the exposed workers had lung changes associated with silicosis. We have failed to achieve the goal of our study, as the obtained data are grossly underestimated and unreliable, but it has opened our eyes as to what needs to be improved. All companies need to systematically be informed about occupational health risks, field inspections need to be consistent, regular, and intensified, and health surveillance of all exposed workers implemented regularly. Silicijev dioksid v kristalni obliki se uporablja v različnih gospodarskih panogah ali pa je prisoten kot vzporedni produkt. Fini delci se po vdihavanju deponirajo v pljučih in lahko povzročijo nastanek silikoze, kronične obstruktivne bolezni pljuč in pljučnega raka. Cilj študije je bil oceniti poklicno razširjenost izpostavljenosti vdihljivemu silicijevemu dioksidu in stopnjo zdravstvenega bremena zaradi take izpostavljenosti v Sloveniji. Da bi to lahko naredili, smo v prvi raziskavi skušali oceniti število delavcev izpostavljenih vdihljivemu silicijevemu dioksidu v slovenski industriji, v drugi pa smo odčitali in klasificirali spremembe na radiogramih delavcev izpostavljenih vdihljivemu silicijevemu dioksidu. Iz slednje bi lahko posredno sklepali o zdravstvenem tveganju preostalih izpostavljenih delavcev v Sloveniji. Vendar pa je prva študija pokazala, da so javni podatki nezanesljivi in pomanjkljivi in da predstavniki podjetij močno podcenjujejo poklicno izpostavljenost silicijevemu dioksidu. Meritve celokupnega praha je naredilo le 8,3% podjetij, meritve praha silicijevega dioksida pa le 1,8 % sodelujočih podjetih. Druga raziskava je pokazala, da ima ena tretjina izpostavljenih delavcev spremembe na rentgenogramih pljuč, ki bi jih lahko pripisali silikozi. Ker so bili pridobljeni podatki hudo podcenjeni in nezanesljivi, cilj naše študije ni bil dosežen rezultati pa so pokazali, kaj je potrebno storiti za izboljšanje stanja. Vsa podjetja morajo biti sistematično obveščena o poklicnem tveganju, inšpekcija za delo pa mora vztrajno, redno in dosledno izvajati nadzor izpostavljenosti.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer.

To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guanganmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI 12.357-25.643) vs. 9 months (95% CI 5.957-12.043), HR0.43 (95% CI 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI 16.425-20.835), HR0.40 (95% CI 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).

Involvement of ACACA (acetyl-CoA carboxylase α) in the lung pre-metastatic niche formation in breast cancer by senescence phenotypic conversion in fibroblasts.

Reprogramming of metabolism is strongly associated with the development of cancer. However, the role of metabolic reprogramming in the remodeling of pre-metastatic niche (PMN), a key step in metastasis, is still unknown. We aimed to investigate the metabolic alternation during lung PMN formation in breast cancer. We assessed the transcriptomes and lipidomics of lung of MMTV-PyVT mice by microarray and liquid chromatography-tandem mass mass spectrometry before lung metastasis. The validation of gene or protein expressions was performed by quantitative real-time polymerase chain reaction or immunoblot and immunohistochemistry respectively. The lung fibroblasts were isolated from mice and then co-cultured with breast cancer to identify the influence of cancer on the change of lung fibroblasts in PMN. We demonstrated changes in the lipid profile and several lipid metabolism genes in the lungs of breast cancer-bearing MMTV-PyVT mice before cancer spreading. The expression of ACACA (acetyl-CoA carboxylase α) was downregulated in the lung fibroblasts, which contributed to changes in acetylation of proteins lysine residues and the synthesis of fatty acid. The downregulation of ACACA in lung fibroblasts triggered a senescent and inflammatory phenotypic shift of lung fibroblasts in both in vivo and in vitro models. The senescence-associated secretory phenotype of lung fibroblasts enabled the recruitment of immunosuppressive granulocytic myeloid-derived suppressor cells into the lungs through the production of CXCL1 in the lungs. Knock-in of ACACA prevented lung metastasis in the MMTV-PyVT mouse model, further supporting that ACACA was involved in the remodeling of the lung PMN. Taken together, these data revealed a mechanism by which ACACA downregulation directed the formation of an immunosuppressive lung PMN in breast cancer.

Iodine-125 brachytherapy suppresses tumor growth and alters bone metabolism in a H1299 xenograft mouse model.

The present study aimed to investigate the efficacy of Iodine-125 (I-125) brachytherapy in a mouse model of non-small cell lung cancer, to further explore the efficacy and appropriate method of implantation of the I-125 radioactive seed. This study also aimed to determine the impact of brachytherapy on bone metabolism. A total of 18 mice were used to establish H1299 xenograft models, and were randomly assigned to three groups. These included non-radioactive seed implantation (Sham IM), fractionated I-125 seed implantation (Fractionated IM) and single I-125 seed implantation (Single IM) groups. Mice were euthanized after 28 days of implantation. HE staining, Ki67 immunohistochemistry, CD31 morphometric analysis and TUNEL immunofluorescence assays were respectively used to determine the histopathological changes, proliferation, micro-angiogenesis and apoptosis of tumors. In addition, bone volume and microstructure were evaluated using trabecular bone area (Tb.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and cortical thickness. Bone metabolic status was analyzed using histomorphometric staining of tartrate-resistant acid phosphate (TRAP) and alkaline phosphatase (ALP) expression in the femur, and using an ELISA assay to determine the expression of C-telopeptide of type 1 collagen (CTX-1) and procollagen type 1 n-terminal propeptide (P1NP) in the serum. Moreover, reverse transcription-quantitative PCR and western blotting were carried out for the analysis of bone remodeling-related gene expression in the bone tissue. Results of the present study demonstrated that compared with the Sham IM group, both the I-125 seed implantation groups, including Fractionated IM and Single IM, demonstrated significant therapeutic effects in both tumor volume and weight. More specifically, the most significant therapeutic effects on tumor inhibition were observed in the Fractionated IM group. Results of Ki67 and CD31 immunohistochemical staining suggested a notable reduction in tumor cell proliferation and micro-angiogenesis, and results of the TUNEL assay demonstrated an increase in tumor cell apoptosis. Although the cortical bone appeared thinner and more fragile in both I-125 seed implantation groups, no notable adverse changes in the morphology of the cancellous bone were observed, and the index of Tb.Ar, Tb.Th and Tb.n was not significantly different among Sham IM and I-125 implantation groups. However, alterations in bone metabolism were characterized by a decrease in CTX-1 and P1NP expression, accompanied by an increase in TRAP activity and a decrease in ALP activity. Results of the present study also demonstrated the notable suppression of osteocalcin and runt-related transcription factor 2. I-125 seed implantation may be an effective and safe antitumor strategy. Moreover, the use of fractionated implantation patterns based on tumor shape exhibited improved therapeutic effect on tumor suppression when the total number of I-125 seeds was equivalent along with reduced complications associated with bone loss.

Time to Treatment Initiation for Six Cancer Types An Analysis of Data from a Nationwide Registry in Japan.

Delay in the time to treatment initiation (TTI) may adversely affect the survival of patients, but its current status in Japan is unknown. This study aims to describe the TTI for six cancer types lung, breast, colorectal, stomach, head and neck (HN), and cervical. Data for this study were derived from a nationwide registry in Japan. This observational study employed the national database of hospital-based cancer registries (HBCRs) and health services utilization data. Using HBCR data, we identified all patients with cancer who started their cancer therapy at the same hospitals between January 1 and December 31, 2017. We calculated the TTI for each cancer type and treatment option, stratifying the results by age group and geographical region. The overall median TTI was 33 days, with shorter TTIs for colorectal and HN cancers and chemotherapy. The TTI was the shortest for younger patients and the longest for the elderly, especially for lung cancer. When categorized by eight Japanese geographical regions, Tohoku and Kanto had the longest TTI. The result remained the same even after adjusting cancer type, treatment, age, and stage information. For colorectal and HN cancers, in which a longer TTI is associated with a poorer prognosis, TTI was found to be particularly shorter. Although we could not discuss our results in light of the patient survival in this study, future research should explore the best balance between thorough evaluation before treatment and necessary time for that.

Lhermitte-Duclos Disease Related With Cowden Syndrome Mimicking Metastatic Lung Cancer on FDG PETCT.

Cowden syndrome is characterized by multiple hamartomatous and neoplastic lesions including Lhermitte-Duclos disease, which is the main criterion for the diagnosis. Herein, we presented a patient with suspected metastatic disease referred to PETCT, which showed mildly hypermetabolic multinodular thyroid goiter, multiple hamartomatous pulmonary, and breast nodules. Also, intense hypermetabolism was noted on the cerebellar tumor lesion. Lhermitte-Duclos disease was diagnosed based on the characteristic MRI findings, and she was followed up with a diagnosis of Cowden syndrome. Our case indicates that Cowden syndrome should be included as a differential diagnosis of abnormal FDG uptake in the multiple systemic hamartomatous tumors.

Prostate-Specific Membrane Antigen PET Positivity in a Lung Mass Diagnosis of Diffuse Large B-Cell Lymphoma.

An 84-year-old man with nonmetastatic castrate-sensitive prostate cancer was referred for a 68Ga-prostate-specific membrane antigen (PSMA) PETCT scan with a prostate-specific antigen level of 3.6 ngmL for restaging. He was 22 years post-radical prostatectomy and had salvage radiation being managed with intermittent hormonal therapy. Imaging revealed a right lower lobe mass with increased PSMA uptake (SUVmax 6.2). Biopsy and subsequent immunostaining determined the mass to be diffuse large B-cell lymphoma. We report a case of diffuse large B-cell lymphoma diagnosed in the setting of PSMA positivity, highlighting awareness for oncologists and radiologists to know this possibility.

Increased FAPI Activity in Pulmonary Tuberculosis.

A 50-year-old man presented with cough and hemoptysis for 1 month. Chest CT showed an irregular mass in the right lung, with enlarged lymph nodes in the mediastinum and right hilum. These findings were suggestive of lung cancer with lymph node metastases. The patient was subsequently enrolled in a 68Ga-DOTA-FAPI-04 PETCT clinical trial. 68Ga-DOTA-FAPI-04 PETCT revealed a mass in the upper lobe of right lung, with intense tracer uptake. Meanwhile, PETCT showed enlarged lymph nodes in the mediastinum and right hilum, with mild FAPI uptake. However, pathological examination confirmed the mass was tuberculous granuloma.

Comparison of the Detection Performance Between FAP and FDG PETCT in Various Cancers A Systemic Review and Meta-analysis.

18F-FDG is the dominant radiotracer in oncology however, it has limitations. Novel labeled fibroblast activation protein (FAP) radiotracers have been developed and published in several studies. Thus, this meta-analysis aimed to compare the detection rates (DRs) of FDG and FAP, based on previous studies from a systematic review. PubMedMEDLINE and Cochrane library databases were used to perform a comprehensive and systematic search and are updated to April 30, 2022. The DR, relative risk, and the SUVmax were calculated between the FAP and FDG tracers. Finally, the sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve of FAP and FDG were analyzed using gold and reference standards. Thirty studies (1170 patients) were included in the meta-analysis. The relative risks of FAP DR for the primary tumor, recurrent tumor, lymph node metastasis, and distant metastasis were FDG 1.06- to 3.00-fold per patient and per lesion. For the primary tumor, FAP uptake was most intense in pancreatic cancer, followed by head and neck, cervical, colorectal, lung, gastric, and hepatocellular carcinoma, and was higher than FDG except for urological system cancer. The sensitivity (0.84-0.98), diagnostic odds ratio (19.36-358.47), and summary receiver operating characteristic curve (0.94-0.99) of FAP based on patient and lesion were better for primary tumors, LN metastasis, and distant metastasis than FDG. Fibroblast activation protein is an extremely potential radiotracer to replace most of the use of FDG in oncology. It is noteworthy that the FAP tracers for primary tumors had low specificity despite excellent sensitivity and had lower uptake than FDG in urological system cancer. In addition, the difference in detection between FAP and FDG for LN metastasis could not be certain in sarcoma.

Lung nodules sorting the wheat from the chaff.

Pulmonary nodules are a common finding on CT scans of the chest. In the United Kingdom, management should follow British Thoracic Society Guidelines, which were published in 2015. This review covers key aspects of nodule management also looks at new and emerging evidence since then.

Treatment and survival of patients with metachronous colorectal lung metastases.

The lungs are the second most common site for metachronous metastases in colorectal cancer. No treatment algorithm is established, and the role of adjuvant chemotherapy is unclear. This study aimed to map pulmonary recurrences in a modern multimodal treated population, and to evaluate survival depending on management. Retrospective study based on the COLOFOL-trial population of 2442 patients, radically resected for colorectal cancer stage II-III. All recurrences within 5 years were identified and medical records were scrutinized. Of 165 (6.8%) patients developing lung metastases as first recurrence, 89 (54%) were confined to the lungs. Potentially curative treatment was possible in 62 (37%) cases, of which 33 with surgery only and 29 with surgery and chemotherapy combined. The 5-year overall survival (5-year OS) for all lung recurrences was 28%. In patients treated with chemotherapy only the 5-year OS was 7.5%, compared with 55% in patients treated with surgery, and 72% when surgery was combined with chemotherapy. Hazard ratio for mortality was 2.9 (95% confidence interval 1.40-6.10) for chemotherapy only compared to surgery. A high proportion of metachronous lung metastases after colorectal surgery were possible to resect, yielding good survival. The combination of surgery and chemotherapy might be advantageous for survival.

Emulating Randomized Controlled Trials with Hybrid Control Arms in Oncology A Case Study.

This proof-of-concept study retrospectively assessed the feasibility of applying a hybrid control arm design to a completed phase III randomized controlled trial (RCT CheckMate-057) in advanced non-small cell lung cancer using a real-world data (RWD) source. The emulated trial consists of an experimental arm (patients from the RCT experimental cohort) and a hybrid control arm (patients from the RCT and RWD control cohorts). For the RWD control cohort, this study used a nationwide electronic health record-derived de-identified database. Three frequentist statistical borrowing methods were evaluated a two-step Cox model, a fixed Cox model, and propensity score-integrated composite likelihood (Methods 1-3). The experimental treatment effect for hybrid control designs were evaluated using hazard ratios (HRs) with 95% confidence interval (CI) estimated from the Cox models accounting for covariate differences. The reduction in study duration compared to the RCT was also evaluated. All three statistical borrowing methods achieved comparable experimental treatment effects to that observed in the CheckMate-057 clinical trial, with HRs of 0.73 (95% CI 0.59, 0.92), 0.74 (95% CI 0.61, 0.91), 0.72 (95% CI 0.59, 0.88) for Methods 1-3, respectively. Reduction in study duration time was 99-115 days when borrowing 30-38 events for Methods 1-3, respectively. This study demonstrated that it is feasible to emulate an RCT using a hybrid control arm design using three frequentist propensity-score based statistical borrowing methods. Selection of an appropriate, fit-for-use RWD cohort is critical to minimizing bias in experimental treatment effect.

Core fucosylation is required for the secretion of and the enzymatic activity of SOD3 in non-small cell lung cancer cells.

The anticancer function of superoxide dismutases (SODs) is still controversial. Removing superoxide andor producing oxygen and hydrogen peroxide exhibits both pro- and anti-tumor effects. SOD3 is an extracellular superoxide dismutase and contains a single

Safety of Intravenous Administration of an AAV8 Vector Coding for an Oxidation-Resistant Human α1-Antitrypsin for the Treatment of α1-Antitrypsin Deficiency.

α1-antitrypsin (AAT) deficiency is a common autosomal recessive hereditary disorder, with a high risk for the development of early-onset panacinar emphysema. AAT, produced primarily in the liver, functions to protect the lung from neutrophil protease with AAT deficiency, unimpeded neutrophil proteases destroy the lung parenchyma. AAT is susceptible to oxidative damage resulting in an inability to inhibit its target proteases, neutrophil elastase, and cathepsin G. The major sites of oxidative modification on the AAT molecule are methionine residues 351 and 358. We have previously demonstrated that an engineered variant of AAT that resists oxidation by modifying both protein surface methionines (M351V and M358L) provides antiprotease protection, despite oxidative stress. In mice, intravenous delivery of the modified AAT(AVL) variant by AAV serotype 8, AAV8hAAT(AVL), primarily to the liver resulted in long-term expression of an AAT that resists oxidative inactivation. In this study, we evaluated the safety of intravenous administration of AAV8hAAT(AVL) in a dose-escalating, blinded, placebo-controlled toxicology study in wild-type mice. The study assessed organ histology and clinical pathology findings of mice, intravenously administered AAV8hAAT(AVL) at three doses (5.0 × 10

Multistate Pharmacometric Model to Define the Impact of Second-Line Immunotherapies on the Survival Outcome of the IMpower131 Study.

Overall survival is defined as the time since randomization into the clinical trial to event of death or censor (end of trial or follow-up), and is considered to be the most reliable cancer end point. However, the introduction of second-line treatment after disease progression could influence survival and be considered a confounding factor. The aim of the current study was to set up a multistate model framework, using data from the IMpower131 study, to investigate the influence of second-line immunotherapies on overall survival analysis. The model adequately described the transitions between different states in patients with advanced squamous non-small cell lung cancer treated with or without atezolizumab plus nab-paclitaxel and carboplatin, and characterized the survival data. High PD-L1 expression at baseline was associated with a decreased hazard of progression, while the presence of liver metastasis at baseline was indicative of a high risk of disease progression after initial response. The hazard of death after progression was lower for participants who had longer treatment response, i.e., longer time to progression. The simulations based on the final multistate model showed that the addition of atezolizumab to the nab-paclitaxel and carboplatin regimen had significant improvement in the patients survival (hazard ratio 0.75, 95% prediction interval 0.61-0.90 favoring the atezolizumab nab-paclitaxel and carboplatin arm). The developed modeling approach can be applied to other cancer types and therapies to provide a better understanding of efficacy of drug and characterizing different states, and investigate the benefit of primary therapy in survival while accounting for the switch to alternative treatment in the case of disease progression.

Comparative proteomics reveals anticancer compounds from Lansium domesticum against NSCLC cells target mitochondrial processes.

Lansium domesticum is identified as a potential source of anticancer compounds. However, there are minimal studies on its anti-lung cancer properties as well as its mechanism of action. Here, we show the specificity of lanzones hexane (LH) leaf extracts to non-small cell lung cancer cells (A549) compared to normal lung fibroblast cells (CCD19-Lu) and normal epithelial prostate cells (PNT2). Subsequent bioassay-guided fractionation of the hexane leaf extracts identified two bioactive fractions with IC

LINC00173 facilitates tumor progression by stimulating RAB1B-mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma.

An increasing number of studies have found that long non-coding RNA (lncRNA) play important roles in driving the progression of nasopharyngeal carcinoma (NPC). Our microarray screening revealed that expression of the lncRNA long intergenic non-protein coding RNA 173 (LINC00173) was upregulated in NPC. However, its role and mechanism in NPC have not yet been elucidated. In this study, we demonstrate that high LINC00173 expression indicated a poor prognosis in NPC patients. Knockdown of LINC00173 significantly inhibited NPC cell proliferation, migration and invasion in vitro. Mechanistically, LINC00173 interacted and colocalized with Ras-related protein Rab-1B (RAB1B) in the cytoplasm, but the modulation of LINC00173 expression did not affect the expression of RAB1B at either the mRNA or protein levels. Instead, relying on the stimulation of RAB1B, LINC00173 could facilitate the extracellular secretion of proliferation-associated 2G4 (PA2G4) and stromal cell-derived factor 4 (SDF4 also known as 45-kDa calcium-binding protein) proteins, and knockdown of these proteins could reverse the NPC aggressive phenotype induced by LINC00173 overexpression. Moreover, in vivo LINC00173-knockdown models exhibited a marked slowdown in tumor growth and a significant reduction in lymph node and lung metastases. In summary, LINC00173 serves as a crucial driver for NPC progression, and the LINC00173-RAB1B-PA2G4SDF4 axis might provide a potential therapeutic target for NPC patients.

Clinical utilization of radiation therapy in Korea between 2017 and 2019.

This study aimed to evaluate the clinical infrastructure and utilization of radiotherapy (RT) services in Korea between 2017 and 2019. We extracted the data of patients who underwent RT between 2017 and 2019 from the Health Insurance Review and Assessment Service. We further analyzed this data according to the diagnosis and treatment modalities of patients diagnosed with International Classification of Disease 10 (ICD-10) diagnostic codes C00-C97 and D00-D48. In addition, we collected statistics on RT facilities in Korea using a nationwide survey. The total number of patients who received RT in 2017, 2018, and 2019 were 77,901, 81,849, and 87,460, respectively. The number of patients diagnosed with ICD 10 C- and D-codes in 2019 was 86,339, of whom 39,467 were men and 46,872 women. The rate of utilization of RT among cancer patients was 30.4% in 2017 and 2018 and 30.9% in 2019. In 2019, the most common types of cancers treated with RT were breast, lung, prostate, colorectal, and liver cancers. Regarding the RT infrastructure in Korea, there were 95 radiation oncology centers, 237 megavoltage (MV) teletherapy units, 35 brachytherapy units, and two proton accelerators in 2019. There were 4.5 MV teletherapy machines per million. The number of patients treated with RT has increased consistently from 2017 to 2019. As the number of patients with cancer increases, it is expected that the RT infrastructure will be further expanded in Korea.

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10Notch pathway.

Retraction 8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors.

This retracts the article DOI 10.7150jca.30143..

Pemetrexed is an anti-folate agent which is one of the most frequently used chemotherapy agents for non-squamous non-small cell lung cancer (NSCLC) patients. However, clinical response to pemetrexed chemotherapy and survival outcome of patients varies significantly. We evaluated whether the genetic variants in miRNA target sites may affect the treatment outcome of pemetrexed chemotherapy in lung adenocarcinoma patients. One hundred SNPs in miRNA binding regions in cancer-related genes were obtained from the crosslinking, ligation, and sequencing of hybrids (CLASH) and CancerGenes database, and the associations with the response to pemetrexed chemotherapy and survival outcomes were investigated in 314 lung adenocarcinoma patients. Two polymorphisms,

Case report Eosinophilic fasciitis induced by pembrolizumab with high FDG uptake on

Eosinophilic fasciitis (EF) is a rare connective tissue disorder causing inflammation and fibrosing of fascia. In this study, we present a very rare case of an immune checkpoint inhibitor (ICI)-induced EF revealed by

Immunocytochemical Evaluation of TTF-1, Napsin-A, and p-63 for Subtyping of Non-Small Cell Lung Carcinoma and Clinicopathological Correlation.

Carcinoma of lung is the most common cause of cancer-associated mortality worldwide. About 70% of lung cancer cases are unresectable and present in advanced stages. So, cytology and small core needle biopsy specimen are available for diagnostic as well as prognostication workup. Subtyping of non-small cell lung cancer (NSCLC) is essential for the treatment and further workup study. For this, immunocytochemistry (ICC) plays a crucial role that helps in early diagnosis. Subtyping of NSCLC from cytology samples using ICC markers like TTF-1, Napsin-A, and p63 and their clinicopathological correlation are the aims of the study. This ambispective study was conducted in the pathology department of a tertiary care hospital of eastern India for a 2-year period from 2018 to 2020. In our study, 46 cytologically diagnosed cases of NSCLC were included. Subtyping was done by cytomorphology and correlated with ICC expression, histopathology, and clinicopathological parameters. In our study, adenocarcinoma (ADC) was the most common (32.61%) cancer. Most cases of ADC showed positive expression of TTF-1 and Napsin-A, and p63 was positive in most cases of squamous cell carcinoma (SCC). Concordance with cytomorphology and ICC was 87.50% and 81.81% with ADC and SCC, respectively. Cyto-ICC-histo concordance was observed in 85.51% of ADC and 66.66% of SCC cases. Sensitivity was 100%, 93.1%, and 100% for TTF-1, Napsin-A, and p63, respectively. Specificity of both TTF-1 and Napsin-A was 88.2% and for p63 was 93.8%. In small biopsy along with cytology samples, ICC is cost-effective and plays an important role in early diagnosis along with management of NSCLC.

Accuracy of Bronchial Cytological Diagnosis in Lung Lesions in Comparison with Histopathology.

The incidence of lung cancer has been increasing in the recent years. Bronchial cytology using Papanicolaou society of cytopathology (PSC) system is an effective method for triaging patients. The present study attempts to evaluate the bronchial cytological diagnosis with histopathological correlation of lung lesions. i. To study the cytological features of lung lesions. ii. To assess the sensitivity, specificity, and diagnostic accuracy of bronchial cytology of lung lesions in comparison with histopathology. Prospective study at the tertiary care hospital. It included 63 cases of lung lesions, evaluated using the PSC system for reporting respiratory cytology. The cytological diagnosis was correlated with the final histopathological diagnosis. The study was conducted between January 2019 and June 2020. SPSS 20.0 software. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of bronchial cytology was 60%, 89%, 90%, 58.62%, and 71.42%, respectively. Bronchial cytology including bronchial wash, bronchial brush, endobronchial ultrasoundtransbronchial needle aspiration, and computerized tomography-guided fine needle aspiration cytology can be used to increase the sensitivity and specificity for definitive diagnosis and better management.

A case of malignant phyllodes tumor that responded to pazopanib and developed pneumothorax.

Here, we present a 59-year-old female with recurrent malignant phyllodes tumor with multiple lung and lymph node metastases who developed a pneumothorax after the administration of pazopanib. The patient received pazopanib as the second-line chemotherapy. After 2.5 months of the therapy, computed tomography (CT) showed a decrease in the sizes and cavitation of lung lesions however, a left pneumothorax was newly observed. It was difficult to distinguish the pneumothorax by upright chest X-ray. Typical symptom or physical finding of pneumothorax, such as dyspnea, chest pain or decreased breath sound was not observed. As the pneumothorax was small and asymptomatic, the administration of pazopanib was discontinued and follow-up chest X-ray and CT were performed. After 1 week, CT showed an improvement in the pneumothorax. Chemotherapy was switched to eribulin however, a rapid increase in sizes of lung lesions was observed after the first administration of eribulin, pazopanib was reintroduced. Careful follow-up by chest X-ray and CT was performed and the pneumothorax has not recurred.

Systemic chemotherapy for unresectable or recurrent primary thymic adenocarcinoma of enteric type.

Primary thymic adenocarcinoma of enteric type is a very rare subtype of thymic carcinoma. Choosing appropriate systemic chemotherapy for patients with unresectable or recurrent disease remain a big challenge. We present a case of 38-year-old man with primary thymic adenocarcinoma of enteric type. The patient received multiline chemotherapy. Metastatic lesions were effectively controlled by FOLFOX (oxaliplatin5-fluorouracilleucovorin) chemotherapy. According to the present case and the literature review, FOLFOX and XELOX (capecitabineoxaliplatin) regimens are reasonable treatment choice for unresectable or recurrent primary thymic adenocarcinoma of enteric type, even in the first-line chemotherapy.

Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma.

Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.

Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy associated with gastric cancer and response to immediate chemotherapy.

Pulmonary tumor thrombotic microangiopathy is a rare and fatal complication of cancer that features widespread tumor cell-derived embolisms in the small arteries and arterioles of the lung and is often associated with thrombus formation. We describe the case of a 43-year-old woman who was hospitalized with cough and respiratory distress that lasted for 2 months. Computed tomography findings demonstrated multiple areas of interlobular septal thickening and ground-glass opacities in both lungs. Transthoracic echocardiography demonstrated a D-shaped left ventricle suggesting right heart overload, and pulmonary blood flow scintigraphy revealed multiple small, peripheral, and patchy areas of reduced blood flow. Upper gastrointestinal endoscopy revealed a signet-ring carcinoma. The patient was diagnosed with pulmonary tumor thrombotic microangiopathy based on her clinical presentation and treatment with tegafur, gimeracil oteracil potassium, oxaliplatin, and an anticoagulant was initiated on the 3rd day after admission. The symptoms improved rapidly after treatment initiation. The patient was discharged 28 days after initiation of chemotherapy without the need for supplemental oxygen. This case suggests that the immediate use of chemotherapy and anticoagulants for treating pulmonary tumor thrombotic microangiopathy may improve patient survival.

Solitary pulmonary capillary hemangioma mimicking a preinvasive malignant lesion in an asymptomatic middle-aged female patient.

Pulmonary capillary hemangiomatosis (PCH) is a rare disease characterized by a proliferation of capillaries in the alveolar septa, bronchial and venous walls, pleura, and regional lymph nodes. However, the etiology of the disease remains unknown due to its rarity. Therefore, we present a case of a solitary PCH lesion without symptoms in a 38-year-old female patient. According to computed tomography, she was diagnosed with lung carcinoma, indicated by a tiny nodule with ground-glass opacity detected in her right upper lung. However, no other lesions were detected on systemic examination. Consequently, partial lung resection was conducted, since the lesion was suspected of lung adenocarcinoma. Pathologic results showed that the thick alveolar septa were caused by capillary growth without cellular atypia and hardly any infiltration of inflammatory cells. Finally, we diagnosed the pulmonary lesion as PCH, although solitary PCH has previously been reported in a few case reports. Therefore, further case studies are essential to clarify the causes of PCH.

Primary lung cancer treatable with radical resection after complete remission with pembrolizumab therapy following gemcitabine and carboplatin chemotherapy for multiple metastases of bladder cancer.

We report a patient with the complete remission of multiple metastases and primary bladder lesions of bladder cancer who developed primary lung cancer requiring radical resection. A 68-year-old man diagnosed with invasive bladder cancer, right hydroureteronephrosis, and multiple metastases were administered six courses of gemcitabine and carboplatin chemotherapy and thereafter has been receiving pembrolizumab therapy. Bladder cancer and multiple metastases decreased in size, whereas a ground-glass opacity lesion in the lung gradually increased in size. Fluorodeoxyglucose-positron emission tomography revealed the accumulation of fluorodeoxyglucose in the ground-glass opacity lesion only. The patient was diagnosed with primary lung cancer and underwent a thoracoscopic lobectomy. Histopathological findings showed ALK-negative, EGFR L858R mutation-positive invasive adenocarcinoma with a programmed death-ligand 1 tumor proportion score of less than 1%. This is the first case report of patients with the complete remission of multiple metastases of bladder cancer who developed primary lung cancer requiring radical resection.

A case of pseudoprogression in avelumab maintenance therapy for metastatic bladder cancer.

A unique phenomenon of immune therapy is pseudoprogression however, a definite mechanism and predictive factors remain unclear. We herein report a case of pseudoprogression with avelumab maintenance therapy. A 67-year-old male diagnosed with muscle-invasive bladder cancer with lung metastasis was treated with four cycles of gemcitabine and cisplatin chemotherapy immediately after cystectomy and ileal conduit urinary diversion. The response to cisplatin-based chemotherapy was a stable disease. Avelumab maintenance therapy was started after first-line chemotherapy but was interrupted due to his general fatigue after the third administration of avelumab. At that time, computed tomography (CT) revealed an increased size of lung metastases. Two months after the interruption, avelumab maintenance therapy was restarted. At the end of the seventh dose of avelumab administration, CT showed a dramatic reduction of lung metastatic tumors. Pseudoprogression may also occur with avelumab maintenance therapy in metastatic bladder cancer.

A radiological complete response to pembrolizumab in a patient with metastatic upper urinary tract urothelial cancer and Lynch syndrome.

In Lynch syndrome, urothelial cancer is the third most common cancer, following colorectal and endometrial cancers. Little is known, however, about the efficacy of immune checkpoint inhibitors in the treatment of metastatic urothelial cancer in Lynch syndrome. A 49-year-old patient with metastatic urothelial cancer underwent pembrolizumab therapy after platinum-containing chemotherapy. The efficacy of the pembrolizumab therapy was good. Her lung and bone metastatic lesions disappeared in imaging studies and her back pain decreased dramatically. Pathogenic mutations of We report metastatic urothelial cancer in a patient with Lynch syndrome who demonstrated a radiological complete response to pembrolizumab therapy. Accurate genetic diagnosis can provide useful information to both the patient and their relatives.

A focused natural compound screen reveals senolytic and senostatic effects of

Natural products and their derivatives historically represent alternatives to conventional synthetic molecules for pharmacotherapy, ranging from cancer chemotherapeutics to cosmetic ingredients that exert anti-aging activities. Cellular senescence is considered a main driver of skin aging, yet natural products that target skin senescence in a specific manner are not thoroughly explored. Here, we performed a focused compound screen to identify natural products that exert anti-senescence effects. We found that

Apoplexy in pituitary metastasis revealing a lung carcinoma.

Pituitary metastasis (PM) is an uncommon manifestation of systemic malignant tumours. It is the least common site of intracranial metastases. As PM has no clinical or radiological pathognomonic features, their diagnosis is challenging. Herein, we present a rare case of a PM unveiling lung cancer. A 60-year-old male with no medical history of malignancy was admitted with a sudden headache, retro-orbital pain, and a severe loss of both eyes visual acuity. After proper investigations and endoscopic resection of the sellar mass, the diagnosis was confirmed to be pituitary metastasis of lung carcinoma. PM can be the initial presentation of an otherwise unknown malignancy. Their diagnosis and management are complex and depend on many factors. Endoscopic surgical resection provides histopathological proof, helps with symptomatic relief, and improves the quality of life but has no effect on survival.

Obstructive shock due to a spontaneous haemothorax caused by primary lung cancer.

We describe the case of a 67-year-old man with shock and hypoxemia. Chest X-ray showed bilateral lung mass shadows and left pleural effusion with a mediastinal shift, suggesting malignancy. Physical examination and point-of-care ultrasound findings did not suggest obstructive or cardiac shock, but the patient had prolonged shock refractory to fluid and blood transfusion therapy. We inserted a drain into the left thoracic cavity, which enabled the patient to recover from shock. We diagnosed the patient with obstructive and hypovolemic shock due to spontaneous haemothorax caused by primary lung cancer. Tension haemothorax due to malignancy is rare, and when obstructive shock is combined with haemorrhagic shock, it can be very difficult to determine the cause of shock.

Immune-related aseptic meningitis diagnosed by Cube FLAIR on enhanced magnetic resonance imaging for a lung cancer patient administered atezolizumab A case report.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), such as neurological toxicity. A 46-year-old man was diagnosed with squamous cell lung cancer. Lung cancer recurred 3 years after he experienced left segmental lung rejection. Therefore, he received atezolizumab as fourth-line chemotherapy. He experienced fever, headache, and decreased consciousness 10 days after the first dose of atezolizumab. Plain head computed tomography and cerebrospinal fluid examination showed no significant findings. Magnetic resonance imaging (MRI) with a Gadolinium (Gd)-enhanced Cube fluid-attenuated inversion recovery (FLAIR) sequence showed nodular abnormalities with contrast enhancement. Thus, aseptic meningitis caused by ICIs was suspected. His consciousness level gradually improved with glucocorticoid therapy. Moreover, most nodular abnormalities observed on cerebral MRI disappeared concurrently. Thus, Gd-enhanced Cube FLAIR sequence has the unique ability to reveal immune-related aseptic meningitis.

Identification of a transcription factor‑cyclin family genes network in lung adenocarcinoma through bioinformatics analysis and validation through RT‑qPCR.

Lung adenocarcinoma (LUAD) is the predominant pathological subtype of lung cancer, which is the most prevalent and lethal malignancy worldwide. Cyclins have been reported to regulate the physiology of various types of tumors by controlling cell cycle progression. However, the key roles and regulatory networks associated with the majority of the cyclin family members in LUAD remain unclear. In total, 556 differentially expressed genes were screened from the GSE33532, GSE40791 and GSE19188 mRNA microarray datasets by R software. Subsequently, protein-protein interaction network containing 499 nodes and 4,311 edges, in addition to a significant module containing 76 nodes and 2,631 edges, were extracted through the MCODE plug-in of Cytoscape. A total of four cyclin family genes

Discovery of HCD3514 as a potent EGFR inhibitor against C797S mutation

Osimertinib (AZD9291), a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), has significantly improved the survival of non-small cell lung cancer (NSCLC) patients with EGFR

Circulating Tumor DNA correlates with Lactate Dehydrogenase, CYFRA 21-1, and CRP levels in patients with advanced NSCLC.

Optimizing Genomic Control in Hit Network-Target Set Model Associations with Lung Adenocarcinoma.

A Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiotherapy in Patients Treated with Post-Mastectomy Radiotherapy.

Radiotherapy continues to play an important role in the management of breast cancer. This study compared the dosimetric differences between the techniques of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in breast cancer patients who had radiotherapy after mastectomy. Forty post-mastectomy patients (19 right-sided breast and 21 left-sided breast) treated with the IMRT technique using 7-9 fields who were re-planned with VMAT using 2 coplanar arc on the Varian Vital beam linear accelerator between January, 2020 and August, 2021 were included in this study. The patients received 42 Gy in 15 fractions to the chest wall, lymph nodes and supraclavicular nodes. The dosimetric parameter for planning target volume (PTV), organs at risk (OAR) and the integral dose to the body were analysed. Students t-test for two independent means was used to analyse the dosimetric differences between the plans. Clinical goals were achieved for both techniques. In terms of PTV coverage at 95% (IMRT 712.17±233) vs (VMAT 694.9±214) and the homogeneity index (IMRT 0.075±0.04) vs (VMAT 0.104±0.03), IMRT resulted in better dose coverage and homogeneity than VMAT. However, with the conformity index, no significant difference was seen. As regards the OARs, the mean doses, V With IMRT, better PTV coverage, homogeneity and OAR sparing were observed. Additionally, VMAT resulted in a lower delivery time than IMRT. Overall, both techniques offered dosimetric qualities that were clinically acceptable.

Peripheral Tumor Location Predicts a Favorable Prognosis in Patients with Resected Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is an aggressive malignancy. Surgical resection is currently only recommended for clinical stage I patients who have been carefully staged. The clinical outcomes of patients with resected SCLCs vary because the disease is highly heterogeneous, suggesting that selected patients could be considered for surgical resection depending on their clinical andor molecular characteristics. We collected data on a retrospective cohort of 119 limited-stage SCLC patients who underwent lobectomy with mediastinal lymph node dissection from March 2013 to March 2020 at Harbin Medical University Cancer Hospital. Correlations were derived using Fishers exact test. Models of 2-year and 3-year survival were evaluated by deriving the area under receiver operating characteristic curves. Kaplan-Meier and Cox regression analyses were used to evaluate significant differences between the survival curves and hazard ratios. The median disease-free survival (DFS) was 35.9 months (range 0.9-105.3 months), and the median overall survival (OS) was 45.2 months (range 4.8-105.3 months). Univariate analysis showed that TNM stage was significantly correlated with DFS and OS. The 2-year disease-free rates of patients with stage I, II, and III disease were 76.4%, 50.5%, and 36.1%, respectively, and the 3-year OS rates were 75.9%, 57.7%, and 34.4%, respectively. In pN patients, multiple (or multiple-station) lymph node involvement significantly increased recurrence and reduced survival compared with patients with single or single-station metastases. Patients with peripheral SCLCs evidenced significantly better DFS and OS than did patients with central tumors. Multivariate analysis showed that TNM stage and tumor location were independently prognostic in Chinese patients with resected limited-stage SCLC. A combination of TNM stage and tumor location was helpful for prognosis. TNM stage and tumor location were independently prognostic in Chinese patients with resected SCLCs. Patient stratification by tumor location should inform the therapeutic strategy. The role of surgical resection for limited-stage SCLC patients must be reevaluated, as this may be appropriate for some patients.

The value of stereotactic biopsy of primary and recurrent brain metastases in the era of precision medicine.

Brain metastases (BM) represent the most frequent intracranial tumors with increasing incidence. Many primary tumors are currently treated in protocols that incorporate targeted therapies either upfront or for progressive metastatic disease. Hence, molecular markers are gaining increasing importance in the diagnostic framework of BM. In cases with diagnostic uncertainty, both in newly diagnosed or recurrent BM, stereotactic biopsy serves as an alternative to microsurgical resection particularly whenever resection is not deemed to be safe or feasible. This retrospective study aimed to analyze both diagnostic yield and safety of an image-guided frame based stereotactic biopsy technique (STX). Our institutional neurosurgical data base was searched for any surgical procedure for suspected brain metastases between January 2016 and March 2021. Of these, only patients with STX were included. Clinical parameters, procedural complications, and tissue histology and concomitant molecular signature were assessed. Overall, 467 patients were identified including 234 (50%) with STX. Median age at biopsy was 64 years (range 29 - 87 years). MRI was used for frame-based trajectory planning in every case with additional PET-guidance in 38 cases (16%). In total, serial tumor probes provided a definite diagnosis in 230 procedures (98%). In 4 cases (1.7%), the pathological tissue did not allow a definitive neuropathological diagnosis. 24 cases had to be excluded due to non-metastatic histology, leaving 206 cases for further analyses. 114 patients (49%) exhibited newly diagnosed BM, while 46 patients (20%) displayed progressive BM. Pseudoprogression was seen in 46 patients, a median of 12 months after prior therapy. Pseudoprogression was always confirmed by clinical course. Metastatic tissue was found most frequently from lung cancer (40%), followed by breast cancer (9%), and malignant melanoma (7%). Other entities included gastrointestinal cancer, squamous cell cancer, renal cell carcinoma, and thyroid cancer, respectively. In 9 cases (4%), the tumor origin could not be identified (cancer of unknown primary). Molecular genetic analyses were successful in 137 out of 144 analyzed cases (95%). Additional next-generation sequencing revealed conclusive results in 1218 (67%) cases. Relevant peri-procedural complications were observed in 5 cases (2.4%), which were all transient. No permanent morbidity or mortality was noted. In patients with BM, frame-based stereotactic biopsy constitutes a safe procedure with a high diagnostic yield. Importantly, this extended to discerning pseudoprogression from tumor relapse after prior therapy. Thus, comprehensive molecular characterization based on minimal-invasive stereotactic biopsies lays the foundation for precision medicine approaches in the treatment of primary and recurrent BM.

Survival analysis of women breast cancer patients in Northwest Amhara, Ethiopia.

Breast cancer, the most common cause of cancer death and the most frequently diagnosed cancer among women worldwide, ranks as the second cause of death next to lung cancer. Thus, the main objective was to assess the factors that affect the survival time of breast cancer patients using the shared frailty model. A retrospective study design was used to collect relevant data on the survival time of breast cancer patients from the medical charts of 322 breast cancer patients under follow-up at the Felege Hiwot Comprehensive Specialized Hospital (FHCSH). The data were explored using the Cox proportional hazard model, the accelerated failure time model, and shared frailty models. The model comparison was done using AIC and BIC. As a result, the Weibull gamma shared frailty model had a minimum AIC and BIC value. From a total of 322 patients, about 95 (29.5%) died and 227 (70.5%) were censored. The overall mean and median estimated survival times of breast cancer patients under study were 43.7 and 45 months, respectively. The unobserved heterogeneity in the population of clusters (residence) as estimated by the Weibull-gamma shared frailty model was 0.002 (p-value 0.000), indicating the presence of residential variation in the survival time of breast cancer patients. The estimated hazard rate of patients who had not had recurrent breast cancer was 0.724 (95% CI 0.571, 0.917) times the estimated hazard rate of patients who had had recurrent breast cancer. The prevalence of breast cancer was considerably high. Under this investigation, older patients, patients in stages III and IV, anemic and diabetes patients, patients who took only chemotherapy treatment, metastasized patients, patients with an AB blood type, patients with a positive breast cancer family history, and patients whose cancer was recurrent had high death rates. Patient characteristics such as age, stage, complications, treatment, metastasis, blood type, family history, and recurrence were significant factors associated with the survival time of women with breast cancer.

Necroptosis-related lncRNAs Combination of bulk and single-cell sequencing reveals immune landscape alteration and a novel prognosis stratification approach in lung adenocarcinoma.

Necroptosis, which is recently recognized as a form of programmed cell death, plays a critical role in cancer biology, including tumorigenesis and cancer immunology. It was recognized not only to defend against tumor progression by suppressing adaptive immune responses but also to promote tumorigenesis and cancer metastasis after recruiting inflammatory responses. Thus the crucial role of necrosis in tumorigenesis has attracted increasing attention. Due to the heterogeneity of the tumor immune microenvironment (TIME) in lung adenocarcinoma (LUAD), the prognosis and the response to immunotherapy vary distinctly across patients, underscoring the need for a stratification algorithm for clinical practice. Although previous studies have formulated the crucial role of lncRNAs in tumorigenicity, the relationship between necroptosis-related lncRNAs, TIME, and the prognosis of patients with LUAD was still elusive. In the current study, a robust and novel prognostic stratification model based on Necroptosis-related LncRNA Risk Scoring (NecroLRS) and clinicopathological parameters was constructed and systemically validated in both internal and external validation cohorts. The expression profile of four key lncRNAs was further validated by qRT-PCR in 4 human LUAD cell lines. And a novel immune landscape alteration was observed between NecroLRS-High and -Low patients. To further elucidate the mechanism of necroptosis in the prognosis of LUAD from a single-cell perspective, a novel stratification algorithm based on K-means clustering was introduced to extract both malignant and NecroLRS-High subsets from epithelial cells. And the necroptosis-related immune infiltration landscape and developmental trajectory were investigated respectively. Critically, NecroLRS was found to be positively correlated with neutrophil enrichment, inflammatory immune response, and malignant phenotypes of LUAD. In addition, novel ligand-receptor pairs between NecroLRS-High cells and other immunocytes were investigated and optimal therapeutic compounds were screened to provide potential targets for future studies. Taken together, our findings reveal emerging mechanisms of necroptosis-induced immune microenvironment alteration on the deteriorative prognosis and may contribute to improved prognosis and individualized precision therapy for patients with LUAD.

Importance of TAK-1 levels in patients with non-small cell lung carcinoma.

In this study, we aimed to investigate the relationship between survival, tumor dimension, grade and stage in respect to transforming growth factor-β-activating kinase (TAK-1) extensity, severity and total score in patients undergoing resection for Stage 1B-2B non-small cell lung cancer. Between January 2000 and December 2014, a total of 70 patients (64 males, 6 females mean age 63.49.6 years range, 32 to 78 years) who underwent surgery with resectable non-small cell lung cancer in Stage 1-2b were included. The patients were divided into two groups as Group 1 (n35) consisting of patients with squamous cell carcinoma and Group 2 (n35) consisting of patients with adenocarcinoma. The control group consisted of 20 patients (Group 3) who underwent surgery due to non-cancer causes. The relationship between TAK-1 staining (extensity, severity, total scores) and grade, survival time, T factor, N factor, and chemotherapy administration was examined. Pathology specimens of the patients were evaluated for the degree of staining with TAK-1 primary antibody. There was a strong correlation between the tumor grade and TAK-1 primary antibody staining level, independently from histopathological type. A significant correlation was found between dimension, stage, and TAK-1 staining in patients with squamous cell carcinoma. No statistically significant difference was found in the other factors, except for grade factor, in patients with adenocarcinoma. The current study provides precious information about the effects of TAK-1, in clinicopathological behavior and survival of malignant cells, particularly in common histopathological types of lung cancer. We believe that our data can be useful, particularly in evaluating the response to targeted therapies and the prognosis of the disease.

A preliminary study of tracking B-cell kinetics in patients with lung transplantation by monitoring kappa-deleting recombination excision circles.

This study aims to evaluate humoral immune system response by measuring copy numbers of kappa-deleting recombination excision circles (KREC) gene segment from B lymphocytes in patients with lung transplantation. Between September 2015 and November 2016, a total of 11 patients (8 males, 3 females mean age 45.4±12.0 years range, 23 to 59 years) who underwent lung transplantation with different primary indications were included. The copy numbers of KREC gene segment were quantified using real-time polymerase chain reaction method in peripheral blood samples collected pre- and post-transplantation. The samples of the patients were compared with the KREC l evels i n deoxyribonucleic acid extracted from blood samples of healthy children. There was no significant change in KREC levels between pre- and post-operation (p0.594 and p0.657), although the median values indicated that the highest increase in the KREC levels (7x105- 12x105 85-170) was on Day 7 of transplantation. There was a positive correlation between the KREC levels (mL in blood) and lymphocytes at 24 h after transplantation (p0.043) and between KREC copies per 106 of blood and age on Day 7. Our preliminary results suggest that KREC l evels a s an indicator of B lymphocyte production are elevated after lung transplantation. A prognostic algorithm by tracking B cell kinetics after post-transplantation for long-term follow-up can be developed following the confirmation of these preliminary results with more patient samples.

The effects of the degree of pleural invasion on survival in patients with non-small cell lung cancer undergoing surgical resection.

The aim of this study was to evaluate the degree and size of pleural invasion in non-small cell lung cancer patients and to compare its relationship with the survival time. Between January 2008 and June 2019, a total of 164 patients (143 males, 21 females median age 64.65 years range 39 to 92 years) who underwent surgical resection with a diagnosis of non-small cell lung cancer and who were found to have pleural invasion histopathologically were retrospectively analyzed. The control group consisted of 105 patients (95 males, 10 females median age 61.7 years range, 32 to 82 years) who underwent surgical resection but who were not found to have pleural invasion histopathologically during the same time period. Survival time was compared between the groups. Median survival was 52 months in the group with pleural invasion, while it was 70.6 months in the group without pleural invasion. In the pleural invasion group, the patients who underwent sublobar resection had shorter survival. The degree of pleural invasion (p0.028), advanced age (p0.022), and lymph node involvement (p0.011) were found to be poor prognostic factors for survival. In non-small cell lung cancer patients, the increase in the degree and size of pleural invasion is negatively correlated with the survival time and this is thought to be associated with advanced disease stage.

Clinical outcomes of vinorelbine loading CalliSpheres beads in the treatment of previously treated advanced lung cancer with progressive refractory obstructive atelectasis.

Construction and validation of nomograms combined with novel machine learning algorithms to predict early death of patients with metastatic colorectal cancer.

The purpose of this study was to investigate the clinical and non-clinical characteristics that may affect the early death rate of patients with metastatic colorectal carcinoma (mCRC) and develop accurate prognostic predictive models for mCRC. Medical records of 35,639 patients with mCRC diagnosed from 2010 to 2019 were obtained from the SEER database. All the patients were randomly divided into a training cohort and a validation cohort in a ratio of 73. X-tile software was utilized to identify the optimal cutoff point for age and tumor size. Univariate and multivariate logistic regression models were used to determine the independent predictors associated with overall early death and cancer-specific early death caused by mCRC. Simultaneously, predictive and dynamic nomograms were constructed. Moreover, logistic regression, random forest, CatBoost, LightGBM, and XGBoost were used to establish machine learning (ML) models. In addition, receiver operating characteristic curves (ROCs) and calibration plots were obtained to estimate the accuracy of the models. Decision curve analysis (DCA) was employed to determine the clinical benefits of ML models. The optimal cutoff points for age were 58 and 77 years and those for tumor size of 45 and 76. A total of 15 independent risk factors, namely, age, marital status, race, tumor localization, histologic type, grade, N-stage, tumor size, surgery, radiation, chemotherapy, bone metastasis, brain metastasis, liver metastasis, and lung metastasis, were significantly associated with the overall early death rate of patients with mCRC and the cancer-specific early death rate of patients with mCRC, following which nomograms were constructed. The ML models revealed that the random forest model accurately predicted outcomes, followed by logistic regression, CatBoost, XGBoost, and LightGBM models. Compared with other algorithms, the random forest model provided more clinical benefits than other models and can be used to make clinical decisions in overall early death and specific early death caused by mCRC. ML algorithms combined with nomograms may play an important role in distinguishing early deaths owing to mCRC and potentially help clinicians make clinical decisions and follow-up strategies.

Lung Tumor Skin Metastasis Case Report of a Solitary Cutaneous Ulcerated Lesion as Initial Manifestation of Lung Carcinoma.

Lung cancer has the highest cancer incidence, and it is the most common cause of cancer death worldwide. Cutaneous metastases are infrequent compared to hilar nodes, adrenal glands, liver, brain, and bones. However, unusual skin lesions in patients at high risk of lung cancer should be regarded carefully to rule out a metastatic manifestation of an occult primary site tumor. Surgical excision, or incisional biopsy when the former is deemed unfeasible, should be performed to allow histopathological examination in case of occult primary site. In patients affected by advanced lung tumors, surgical excision could be beneficial in terms of pain control and improvement of the quality of life. We report a case of a solitary large skin lesion as an early manifestation of a lung adenocarcinoma.

Successful Dasatinib Treatment of Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinoma and

Dasatinib, a second-generation

A Case of Full Recovery from Prolonged Cardiac Arrest after Infusion with Paclitaxel and Pembrolizumab.

Lung cancer is one of the most common cancers and has the highest risk of mortality in both genders. This devastating cancer is also a significant financial and emotional burden to patients and the healthcare system. Chemotherapy and immunotherapy have become the cornerstone for the treatment of lung cancer. However, treatment may come with severe and sometimes fatal side effects. In this report, we present the case of a 52-year-old Caucasian male who suffered two episodes of prolonged cardiac arrest after the infusion of paclitaxel and pembrolizumab.

Study of epirubicin sustained-release chemoablation in tumor suppression and tumor microenvironment remodeling.

Although intratumoral chemoablation can obtain an impressive therapeutic effect, there is still incomplete ablation and tumor recurrence in some patients. This could be due to the short retention time of the drug in the tumor, the limited distribution of intratumoral drugs, and, beyond that, the immunotolerance caused by the tumor microenvironment (TME). There is still an urgent need to find an optimal drug sustained-release carrier and figure out the impact of regional injection to TME. In this study, we supposed to use polyethylene glycol (PEG) hydrogel as a drug carrier to improve the retention time of the drug to extend the exposure of tumor cells and investigate the feasibility of combination local Epirubicin injection with anti-PD-L1. The results revealed obvious tumor suppression based on the tumor volume and the inhibition time of tumor growth in the A549 lung cancer mouse model after local injection. Furthermore, the enhanced antitumor effects of the combination of systematic anti- programmed death ligand 1 (PD-L1) therapy with local chemoablation (EPI-GELPD-L1) for abscopal tumor reduction in the 4T1 breast model were also observed. Flow cytometry analysis of the tumor and blood samples showed significant variations in the proportions of PD-L1 The combination of local injection of the chemoablation agent with anti-PD-L1 monoclonal antibody (mAb) therapy may strengthen the antitumor activity, and the use of PEG hydrogel as the drug carrier can extend the retention time of the chemoablation agent around the tumor, maintaining a long-term tumor-killing activity.

Cancer risks in rheumatoid arthritis patients who received immunosuppressive therapies Will immunosuppressants work

Exploring the cancer risks of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARDs) can help detect, evaluate, and treat malignancies at an early stage for these patients. Thus, a comprehensive analysis was conducted to determine the cancer risk of RA patients using different types of DMARDs and analyze their relationship with tumor mutational burdens (TMBs) reflecting immunogenicity. A thorough search of PubMed, EMBASE, Web of Science, and Medline was conducted up to 20 August 2022. Standardized incidence ratios (SIRs) were constructed with a random-effect model to determine risks for different types of malignancies in comparison with the general population. We also analyzed the correlation between SIRs and TMBs using linear regression (LR). From a total of 22 studies, data on 371,311 RA patients receiving different types of DMARDs, 36 kinds of malignancies, and four regions were available. Overall cancer risks were 1.15 (SIR 1.15 1.09-1.22 We demonstrated a cancer risk spectrum of RA populations using DMARDs. Additionally, TMBs were not associated with elevated cancer risks in RA patients following immunosuppressive therapy, which confirmed that iatrogenic immunosuppression might not increase cancer risks in patients with RA. Changes were similar in cancer risk after different immunosuppressive treatments, and there was a lack of correlation between SIRs and TMBs. These suggest that we should look for causes of increased risks from the RA disease itself, rather than using different types of DMARDs.

A self-supervised contrastive learning approach for whole slide image representation in digital pathology.

Image analysis in digital pathology has proven to be one of the most challenging fields in medical imaging for AI-driven classification and search tasks. Due to their gigapixel dimensions, whole slide images (WSIs) are difficult to represent for computational pathology. Self-supervised learning (SSL) has recently demonstrated excellent performance in learning effective representations on pretext objectives, which may improve the generalizations of downstream tasks. Previous self-supervised representation methods rely on patch selection and classification such that the effect of SSL on end-to-end WSI representation is not investigated. In contrast to existing augmentation-based SSL methods, this paper proposes a novel self-supervised learning scheme based on the available primary site information. We also design a fully supervised contrastive learning setup to increase the robustness of the representations for WSI classification and search for both pretext and downstream tasks. We trained and evaluated the model on more than 6000 WSIs from The Cancer Genome Atlas (TCGA) repository provided by the National Cancer Institute. The proposed architecture achieved excellent results on most primary sites and cancer subtypes. We also achieved the best result on validation on a lung cancer classification task.

The Mechanism of Quercetin in the Treatment of Lung Squamous Cell Carcinoma Based on a Protein-Protein Interaction Network.

Lung squamous cell carcinoma (LUSC) is characterized by poor prognosis and obvious limitations of therapeutic methods. The molecular target and mechanism of quercetin (QR), a natural anticancer product with extensive pharmacological activities, on lung squamous cell carcinoma is still unclear. The effects of QR on LUSC were examined using cell proliferation, migration, and invasion tests. Key target genes were screened using The Cancer Genome Atlas (TCGA) database, Gene Ontology (GO)Kyoto Encyclopedia of Genes and Genomes (KEGG) database, STRING website, topology, and prognosis analysis, molecular docking, and other bioinformatics methods for further analysis. Finally, the effects of QR on the expression of key targets in LUSC cells were detected using a cell cycle assay and western blotting. Our study demonstrates that QR not only inhibits the proliferation of LUSC but also affects the invasion and metastasis of LUSC. After downloading and analyzing the TCGA database, 2150 differentially expressed genes were identified. PLK1, CDC20, and BUB1B were identified using enrichment analysis, topological network analysis, cluster analysis, and molecular docking screening. Subsequent experiments showed that QR could interfere with the cell cycle and downregulate the expression of the target gene PLK1 at the protein level. We found that QR not only inhibits the proliferation, migration, and invasion but also blocks the cell cycle progression of LUSC. QR downregulated the expression of the LUSC target gene PLK1 at the protein level.

Antitumor Effects of Ononin by Modulation of Apoptosis in Non-Small-Cell Lung Cancer through Inhibiting PI3KAktmTOR Pathway.

Lung cancer is a leading global cause of cancer-related death in both males and females. Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed cancer type that can be difficult to control with conventional chemotherapeutic and surgical approaches resulting in a poor prognosis. Paclitaxel (PTX) is a commonly used chemotherapeutic drug for NSCLC, which can cause tissue injury in healthy cells and affect the quality of life in patients with cancer. In order to treat NSCLC, alternative medications with minimal or no side effects are highly needed. Ononin is an isoflavone glycoside extracted from Astragali Radix (AR) that has various pharmacological activities. Therefore, this study investigated whether ononin inhibits NSCLC progression and promotes apoptosis synergistically with PTX both

Impact of thoracic multidisciplinary tumor boards on the management of patients with cancer A retrospective study at the American university of Beirut medical center.

Multidisciplinary tumor boards (MDT) provide an opportunity for experts from different specialties and expertise to pool and complement each others experience and inputs. Several factors impact the MDT discussions, including the meetings structure, time management, and expert leadership. The process of MDT, their utilization, and efficacy need continuous assessment and improvement. A retrospective study was conducted to review the process of thoracic MDT, their plans of therapy, and changes in diagnosis and treatment plans for patients with cancer at the American University of Beirut Medical Center (AUBMC) over the period of one year. The primary outcome measure was the percentage of patients presented at the thoracic MDT who had a change in their treatment plan after the presentation. A total of 214 cases were scheduled for thoracic MDT during the study period. The majority, 132 (61.7%) did not have a treatment plan before presenting in the MDT. Of the 195 cases presented, only 43 (22.0%) did not have a change in their plan, while 88 (45.2%) of the cases presented had a change in their treatment plan. A total of 64 (32.8%) cases consisted of discussion of the diagnosis during MDT with either confirmation or modification of the patients diagnosis. Of the 195 cases that were presented, the majority, 170 (87.2%), had their recommended treatment plan implemented after the MDT discussion. There was an association between the stage of cancer at the time of presentation and requesting additional tests (P0.021), but there was no association between the stage of cancer and change in treatment plan (P0.177) nor with implementation of recommendation (P0.217). MDT are used to make upfront management decisions. In addition to considering change in management plans as an indicator of the benefit of MDT, it is suggested that making upfront multidisciplinary plans shall be considered an additional component of indicators of the benefit of MDT.

Entrectinib-Induced Heart Failure in a Patient With Metastatic Lung Adenocarcinoma A Case Report.

Entrectinib is a recently approved multikinase inhibitor to treat advanced c-ros oncogene1 (ROS1) positive non-small cell lung cancer (NSCLC). Although molecular targeted therapy is generally well tolerated, cardiovascular adverse events have been described in recent years. We report a case of NSCLC with ROS1 rearrangement where the patient developed drug-induced heart failure after receiving entrectinib. A 74-year-old non-smoker female patient was diagnosed with stage IVB lung adenocarcinoma with ROS-1 positive and right breast cancer stage I. We started on entrectinib as the first-line therapy for lung cancer. Five days after, she developed oral dysesthesia and blood creatinine increased. These findings gradually worsened, so we temporarily discontinued entrectinib. After withholding the drug for 14 days, these findings improved, and we resumed entrectinib at a reduced dose. On day 19 of the reduced entrectinib dose, she presented to the outpatient with shortness of breath and bilateral lower extremity edema, accompanied by respiratory failure. Laboratory evaluation revealed elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), troponin I, creatine kinase (CK), and C reactive protein (CRP), and transthoracic echocardiogram showed congestive heart failure (CHF) with a preserved ejection fraction (HFpEF). She did not complain of chest pain and fever, so we did not consider ischemic heart disease and viral myocarditis in the initial evaluation. There was no other causative cause of CHF. Therefore, we suspected entrectinib-related heart failure. Her symptoms improved and she recovered her cardiac function to baseline within a week of discontinuation of entrectinib and standard heart failure treatment. She developed heart failure after a one-step dose reduction and was prone to cardiotoxicity due to entrectinib. Considering that she could be treated with crizotinib, we decided discontinuation of entrectinib permanently. This case report highlights the potential cardiotoxicity of entrectinib and suggests the need for close monitoring of the cardiac functions of patients receiving entrectinib.

Higher aorta dose increased neutrophil-to-lymphocyte ratio resulting in poorer outcomes in stage II-III non-small cell lung cancer.

This study focused on the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the dose of organs at risk in patients with stage II-III non-small cell lung cancer (NSCLC) receiving intensity-modulated radiotherapy. The clinical characteristics and dosimetric parameters of 372 patients were collected retrospectively. A high NLR was defined as that ≥1.525. Survival analysis was conducted using the Kaplan-Meier and Cox regression analysis. Least absolute shrinkage and selection operator (LASSO) analysis was conducted to select appropriate dosimetric parameters. The risk factors of NLR were evaluated using univariate and multivariate logistic regression analyses. Patients with a high NLR had poorer progression-free survival (PFS) (p 0.011) and overall survival (OS) (p 0.061). A low NLR (<1.525) predicted better PFS (hazard ratio HR 0.676, 95% confidence interval CI 0.508-0.900, p 0.007) and OS (HR 0.664, 95% CI 0.490-0.901, p 0.009). The aorta dose differed between the low and high NLR groups (all <0.1) in the univariate analysis. An aorta V10 was confirmed as a significant risk factor for a high NLR (odds ratio OR 1.029, 95% CI 1.011-1.048, p 0.002). Receiving chemotherapy before (OR 0.428, 95% CI 0.225-0.813, p 0.010) and during (OR 0.491, 95% CI 0.296-0.815, p 0.006) radiotherapy were predictive factors of a low NLR. The aorta dose was significantly associated with a high NLR. Patients with stage II-III NSCLC with a high NLR had poorer prognosis. Receiving chemotherapy before andor during radiotherapy predicted a low NLR.

Alectinib-induced hemolytic anemia.

Alectinib is an oral anaplastic lymphoma kinase tyrosine kinase inhibitor with central nervous system activity. It is currently approved and a preferred first-line option for those with anaplastic lymphoma kinase-positive non-small cell lung cancer. Alectinib has been shown to cause anemia, usually mild. We report a case of alectinib-induced hemolytic anemia in a patient receiving alectinib as first-line treatment for anaplastic lymphoma kinase-positive non-small cell lung cancer. The patients dose was reduced from 600 mg twice daily to 450 mg twice daily and further down to 300 mg twice daily and eventually discontinued. At that point, the hemoglobin normalized. Our case demonstrates objective evidence for hemolytic anemia induced by alectinib.

Proton minibeam radiation therapy for treating metastases A treatment plan study.

Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma-bearing rats compared to conventional proton therapy. Such preclinical results encourage the preparation of clinical trials. In this study, the potential of pMBRT for treating clinical indications candidates for the first clinical trials (i.e., brain, lung, and liver metastases) was evaluated. Four clinical cases, initially treated with stereotactic radiotherapy (SRT), were selected for this study. pMBRT, SRT, and conventional proton therapy (PT) dose distributions were compared by using three main criteria (i) the tumor coverage, (ii) the mean dose to organs-at-risk, and (iii) the possible adverse effects in normal tissues by considering valley doses as the responsible for tissue sparing. pMBRT plans consisted of one fraction and one-two fields. Dose calculations were computed by means of Monte Carlo simulations. pMBRT treatments provide a similar or superior target coverage than SRT, even using fewer fields. pMBRT also significantly reduces the biologically effective dose (BED) to organs-at-risk. In addition, valley and mean doses to normal tissues remain below tolerance limits when treatments are delivered in a single fraction, contrary to PT treatments. This work provides a first insight into the possibility of treating metastases with pMBRT. More favorable dose distributions and treatment delivery regimes may be expected from this new approach than SRT. The advantages of pMBRT would need to be confirmed by means of Phase I clinical trials.

Comparison between functional lung volume measurement and segment counting for predicting postoperative pulmonary function after pulmonary resection in lung cancer patients.

Functional lung volume (FLV) obtained from computed tomography images was a breakthrough for lung imaging and functional assessment. We compared the accuracy of the FLV measurement method and the segment-counting (SC) method in predicting postoperative pulmonary function. A total of 113 patients who underwent two thoracoscopic surgeries were enrolled in our study. We predicted postoperative pulmonary function by the FLV measurement method and the SC method. Novel formulas based on the FLV measurement method were established using linear regression equations between the factors affecting pulmonary function and the measured values. The predicted postoperative forced vital capacity (ppoFVC) and forced expiratory volume in 1 s (ppoFEV1) measured by the 2 methods showed high concordance between the actual postoperative forced vital capacity (postFVC) and the forced expiratory volume in 1 s (postFEV1) r 0.762, P < 0.001 (FLV method) and r 0.759, P < 0.001 (SC method) for FVC r 0.790, P < 0.001 (FLV method) and r 0.795, P < 0.001 (SC method) for FEV1. Regression analysis showed that the measured preoperative pulmonary function parameters (FVC, FEV1) and the ratio of reduced FLV to preoperative FLV were significantly associated with the actual postoperative values and could predict these parameters (all P < 0.001). The feasibility of using these equations postFVC 0.8 × FVC - 0.784 × ΔFLVFLV 0.283 (R The new FLV measurement method is valuable for predicting postoperative pulmonary function in patients undergoing lung resection surgery, with accuracy and consistency similar to those of the conventional SC method.

Transbronchial cryobiopsy in unexplained, severe ARDS a single center retrospective case series.

Acute respiratory distress syndrome (ARDS) deptics an acute form of lung infjury with often severe respiratory impairment that requires invasive mechanical ventilation. Since ARDS can be caused by several distinct etiologies, correct characterization is desired and frequently challenging. Surgical lung biopsy was previously reported to be of additive value. We describe our institutional experience using transbronchial cryobiopsy (TBCB) for further characterization of severe and unexplained ARDS cases. We retrospectively collected data of TBCB in patients with unexplained ARDS, whether with or without ECMO-support. Between 2019 and 2020 TBCB was performed in eight patients. Decision for the intervention was decided in multidisciplinary discussion. Five patients were treated with ECMO. The median duration of invasive ventilation before TBCB was 24 days. TBCB was performed in one segment, that was prophylactically occluded by Watanabe spigot or swab after the procedure. Histology results and their contribution to further therapeutic decisions were analyzed. Histology revealed five diffuses alveolar damage, one acute fibrinoid organizing pneumonia, one cryptogenic organizing pneumonia and one lung cancer. All results contributed to the decision of further management. While no pneumothorax or severe endobronchial bleeding occurred, two delayed hematothoraces needed surgical treatment. No patients died due to TBCB. TBCB is feasible in ARDS even during ECMO treatment. Histologic results can play a significant role in therapeutic and ethic discussion to guide the patients care. Side effects should be considered and monitored.

The efficacy of small molecule anti-angiogenic drugs in previously treated Thymic carcinoma.

Antiangiogenic drugs have shown initial efficacy in the treatment of advanced thymic carcinomas (TCs) however, data are limited. In this study, we provide real-world data relating to the efficacy of antiangiogenic drugs for the treatment of patients with TCs. We retrospectively collected data on clinical progress after first-line chemotherapy in TCs patients who were treated with small molecule antiangiogenic drugs at our institution between January 2010 and December 2021. Tumor response was evaluated according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Progression free survival and overall survival were calculated using the Kaplan-Meier method. Of the 17 patients enrolled, 13 (76.5%) received apatinib and four (23.5%) anlotinib monotherapy with an objective response rate of 23.5%. Eleven (64.7%) patients had stable disease. The median follow-up period was 46.0 months (95% confidence interval CI, 33.0-59.0 months). The median progression survival and overall survival were 7.9 months (95% CI, 6.5-9.3) and 47.0 months (95% CI, 35.4-58.6), respectively. In the 13 patients receiving apatinib, the median PFS was 7.0 months (95% CI, 5.0-9.0), compared with 8.0 months (95% CI, 2.7-13.3 months) for patients in the anlotinib group (P 0.945). The most common grade 3 adverse events (AEs) were hypertension (n 3, 23.1%), followed by proteinuria and hand-foot syndrome (HFS, n 2, 15.4%). There were no grade 4 AEs although eight patients (47.1%) required mid-course discontinuation. For refractory TCs, small molecule antiangiogenic drugs are efficacious as second- or post-line treatments. The toxicity of antiangiogenic therapy is manageable.

Association between psoriasis and lung cancer two-sample Mendelian randomization analyses.

Observational studies reported an association between psoriasis and risk of lung cancer. However, whether psoriasis is causally associated with lung cancer is unclear. Genetic summary data of psoriasis were retrieved from two independent genome-wide association studies (GWAS). Genetic information of lung cancer was retrieved from GWAS of International Lung Cancer Consortium. A set of quality control steps were conducted to select instrumental tools. We performed two independent two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between psoriasis and lung cancer (LUCA) as well as its subtypes, squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD). Between-SNP heterogeneity was present for most MR analyses, whereas horizontal pleiotropy was not detected for all MR analyses. Multiplicative random-effect inverse variance weighted (IVW-MRE) method was therefore selected as the primary MR approach. Both IVW-MRE estimates from the two independent MR analyses suggested that there was no significant causal relationship between psoriasis and LUCA as well as its histological subtypes. Sensitivity analyses using other four MR methods gave similar results. Meta-analysis of the two IVW-MRE derived MR estimates yielded an odds ratio (OR) of 1.00 (95% CI 0.95-1.06) for LUCA, 1.01 (95% CI 0.93-1.08) for LUSC, and 0.97 (95% CI 0.90-1.06) for LUAD. Our results do not support a genetic association between psoriasis and lung cancer and its subtypes. More population-based and experimental studies are warranted to further dissect the complex correlation between psoriasis and lung cancer.

Investigating the functional role of SETD6 in lung adenocarcinoma.

SET domain containing 6 (SETD6) has been shown to be upregulated in multiple human cancers and can promote malignant cell survival. However, expression and function of SETD6 in lung adenocarcinoma (LUAD) remains unaddressed. This study aimed to demonstrate the expression pattern, biological roles and potential mechanisms by which SETD6 dysregulation is associated with LUAD. The expression level of SETD6 was evaluated in LUAD clinical specimens and its correlation with clinical parameters were analyzed. In vitro, gain-of-function and loss-of-function experiments were performed to evaluate the effects of SETD6 on cell proliferation, apoptosis, migration, and colony formation of LUAD cell line A549. Western-blot was performed to investigate the involvement of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways as downstream signaling of SETD6 in LUAD cells. Compared with non-tumorous tissues, SETD6 was overexpressed in tumor tissues, and its overexpression significantly correlates with higher rates of regional lymph node metastasis and poor prognosis in patients with LUAD. In A549 cell line, SETD6 overexpression could promote cell proliferation, migration, colony formation and inhibit cell apoptosis, whereas SETD6 knockdown caused the opposite effects. Furthermore, we demonstrated that the mechanisms underlying the effect of SETD6 on LUAD biological behaviors may be through its interaction with NF-κB and Nrf2 signaling pathways. SETD6, which is highly expressed in LUAD tumor tissues, plays an important role in promoting the malignant behaviors of LUAD via likely the NF-κB and Nrf2 signaling pathways.

LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization.

Long intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD). Biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963HNRNPA2B1Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models. Higher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis. By stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.

OASL phase condensation induces amyloid-like fibrillation of RIPK3 to promote virus-induced necroptosis.

RIPK3-ZBP1-MLKL-mediated necroptosis is a proinflammatory cell death process that is crucial for antiviral host defence. RIPK3 self-oligomerization and autophosphorylation are prerequisites for executing necroptosis, yet the underlying mechanism of virus-induced RIPK3 activation remains elusive. Interferon-inducible 2-5 oligoadenylate synthetase-like (OASL) protein is devoid of enzymatic function but displays potent antiviral activity. Here we describe a role of OASL as a virus-induced necroptosis promoter that scaffolds the RIPK3-ZBP1 non-canonical necrosome via liquid-like phase condensation. This liquid-like platform of OASL recruits RIPK3 and ZBP1 via protein-protein interactions to provide spatial segregation for RIPK3 nucleation. This process facilitates the amyloid-like fibril formation and activation of RIPK3 and thereby MLKL phosphorylation for necroptosis. Mice deficient in Oasl1 exhibit severely impaired necroptosis and attenuated inflammation after viral infection, resulting in uncontrolled viral dissemination and lethality. Our study demonstrates an interferon-induced innate response whereby OASL scaffolds RIPK3-ZBP1 assembly via its phase-separated liquid droplets to facilitate necroptosis-mediated antiviral immunity.

Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis.

Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.

Improving practice in PD-L1 testing of non-small cell lung cancer in the UK current problems and potential solutions.

Programmed cell death ligand 1 (PD-L1) expression, used universally to predict response of non-small cell lung cancer (NSCLC) to immune-modulating drugs, is a fragile biomarker due to biological heterogeneity and challenges in interpretation. The aim of this study was to assess current PD-L1 testing practices in the UK, which may help to define strategies to improve its reliability and consistency. A questionnaire covering NSCLC PD-L1 testing practice was devised and members of the Association of Pulmonary Pathologists were invited to complete this online. Of 44 pathologists identified as involved in PD-L1 testing, 32 (73%) responded. There was good consistency in practice and approach, but there was wide variability in the distribution of PD-L1 scoring. Although the proportions of scores falling into the three groups (negative, low and high) defined by the 1% and 50% cut-offs (38%, 33% and 27%, respectively) reflect the general experience, the range within each group was wide at 23-70%, 10-60% and 15-36%, respectively. There is inconsistency in the crucial endpoint of PD-L1 testing of NSCLC, the expression score that guides management. Addressing this requires formal networking of individuals and laboratories to devise a strategy for its reduction.

Cancer survival in Africa, central and south America, and Asia (SURVCAN-3) a population-based benchmarking study in 32 countries.

Population-based cancer survival is a key measurement of cancer control performance linked to diagnosis and treatment, but benchmarking studies that include lower-income settings and that link results to health systems and human development are scarce. SURVCAN-3 is an international collaboration of population-based cancer registries that aims to benchmark timely and comparable cancer survival estimates in Africa, central and south America, and Asia. In SURVCAN-3, population-based cancer registries from Africa, central and south America, and Asia were invited to contribute data. Quality control and data checks were carried out in collaboration with population-based cancer registries and, where applicable, active follow-up was performed at the registry. Patient-level data (sex, age at diagnosis, date of diagnosis, morphology and topography, stage, vital status, and date of death or last contact) were included, comprising patients diagnosed between Jan 1, 2008, and Dec 31, 2012, and followed up for at least 2 years (until Dec 31, 2014). Age-standardised net survival (survival where cancer was the only possible cause of death), with 95% CIs, at 1 year, 3 years, and 5 years after diagnosis were calculated using Pohar-Perme estimators for 15 major cancers. 1-year, 3-year, and 5-year net survival estimates were stratified by countries within continents (Africa, central and south America, and Asia), and countries according to the four-tier Human Development Index (HDI low, medium, high, and very high). 1 400 435 cancer cases from 68 population-based cancer registries in 32 countries were included. Net survival varied substantially between countries and world regions, with estimates steadily rising with increasing levels of the HDI. Across the included cancer types, countries within the lowest HDI category (eg, CÔte dIvoire) had a maximum 3-year net survival of 54·6% (95% CI 33·3-71·6 prostate cancer), whereas those within the highest HDI categories (eg, Israel) had a maximum survival of 96·8% (96·1-97·3 prostate cancer). Three distinct groups with varying outcomes by country and HDI dependant on cancer type were identified cancers with low median 3-year net survival (<30%) and small differences by HDI category (eg, lung and stomach), cancers with intermediate median 3-year net survival (30-79%) and moderate difference by HDI (eg, cervix and colorectum), and cancers with high median 3-year net survival (≥80%) and large difference by HDI (eg, breast and prostate). Disparities in cancer survival across countries were linked to a countrys developmental position, and the availability and efficiency of health services. These data can inform policy makers on priorities in cancer control to reduce apparent inequality in cancer outcome. Tata Memorial Hospital, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer.

Clinical analysis of inflatable video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopy.

Total flavonoids of Litchi seed attenuate stem cell-like properties in breast cancer by regulating Notch3 signaling pathway.

Breast cancer has been the most commonly-diagnosed cancer worldwide, and the treatment and prognosis of which are often limited by breast cancer stem cells (BCSCs). Litchi seeds have shown good anti-cancer activity in various cancers including prostate cancer, lung cancer and breast cancer. However, the activity and underlying mechanism of Litchi seeds against BCSCs remain unknown. To investigate the activity and mechanism of total flavonoids of litchi seed (TFLS) against BCSCs in vitro and in vivo. Two orthotopic xenograft mouse models were established using HCC1806 cells pretreated or untreated with TFLS to determine whether TFLS could target BCSCs in vivo. Mammosphere formation and flow cytometry assays were employed to evaluate the effect of TFLS on BCSCs in vitro. The underlying mechanism was investigated using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence experiments. TFLS could significantly inhibit the viability of HCC1806, MCF-7 and HCC1937 cells in vitro and suppress the growth of HCC1806 cells in vivo. TFLS attenuated stem cell-like properties of breast cancer through reducing the percentage of CD44 TFLS could suppress the growth of breast cancer and eliminate breast cancer stem cells by inhibiting the Notch3 signaling pathway.

Navigator-based slice tracking for prospective motion correction in kidney vessel architecture imaging.

To apply a navigator-based slice tracking method to prospectively compensate the respiratory motion for kidney vessel architecture imaging (VAI). A dual gradient echo spin echo 2D EPI sequence was developed for kidney VAI. A single gradient-echo slice selection and projection readout at the location of the diaphragm along the inferior-superior direction was applied as a navigator. Navigator acquisition and fat suppression were inserted before each transverse imaging slice. Motion information was calculated after exclusion of the signal saturation in the navigator signal caused by imaging slices. The motion information was then directly sent back to the sequence and slice positioning was adjusted in real-time. The whole sequence was applied during a contrast agent pass-through. VAI parametric maps show the structural heterogeneity of the renal vasculature. The respiratory motion from the navigator signal was precisely calculated and slice positioning was changed in real-time based on the motion information. The vibration amplitude of the signal intensity of the liver tissue at the liver-lung interface in the case of prospective motion correction (PMC) on is about 28% of the PMC off case. Compared to the case of PMC off, the coefficient of variation was reduced 30% of the case of PMC on. This study demonstrates the feasibility of the motion-compensating technique in kidney VAI. The sequence may improve the evaluation of microvasculature in kidney diseases.

Free-breathing BLADE fat-suppressed T2 weighted turbo spin echo sequence for distinguishing lung cancer from benign pulmonary nodules or masses A pilot study.

Diffusion Weighted Imaging (DWI) can be used to differentiate benign and malignant pulmonary nodules or masses, while T2WI is also of great value in the differential diagnosis of them. For example, T2WI can be used to differentiate abscess from lung cancer. The study aims to quantitatively evaluate the efficacy of free-breathing BLADE fat-suppressed T2 weighted turbo spin echo sequence (BLADE T2WI) for differentiating lung cancer (LC) and benign pulmonary nodule or mass (BPNM). A total of 291 patients with LC (197 males, 94 females mean age 63.2 years) and 74 BPNM patients (53 males, 21 females mean age 62.8 years) who underwent BLADE T2WI at 3-T MRI between November 2016 and May 2022were included in this retrospective study. Two radiologists independently blinded observed the MR images and measured the T2 contrast ratio (T2CR). Mann-Whitney U test was used to compare T2CR values between the two groups, ROC curves were used to evaluate the diagnostic efficacy of BLADE T2WI. The two radiologists had good inter-observer consistency for T2CR (ICC 0.958). The T2CR of BPNM was significantly higher than LC (all p < 0.001) the cut-off value of T2CR was 2.135, and the sensitivity, specificity, and accuracy of diagnosis were 75.6%, 63.5%, and 73.2%, respectively. Moreover, T2CR correctly diagnosed 220 LC cases (220291 75.6%) and 47 BPNM cases (4774 63.5%). The T2CR value of MR non-enhanced BLADE T2WI can be easily obtained and can quantitatively distinguish BPNM from LC, thus avoiding misdiagnosis caused by lack of work experience.

A study of non small cell lung cancer (NSCLC) patients with brain metastasis A single centre experience.

Lung cancer is the leading cause of cancer death with the majority of cases being non-small cell lung cancer (NSCLC) 1. A common complication of NSCLC is brain metastasis (BM) 2, 3, where the prognosis remains poor despite new treatments. Real world data complements data gained from clinical trials, providing information on patients excluded from prospective research 4. However, information from patient notes may prove incomplete and difficult to extract. We developed an algorithm to identify patients in our clinical database with brain metastasis from the electronic health record (EHR). We retrospectively extracted data from the EHR of patients managed at a large teaching hospital between 2007 and 2018. Using the ICD-10 code C34, for lung cancer, our algorithm used phrases associated with BMs to search the unstructured text of radiology reports. Summary statistics and univariant analysis was performed for overall survival. 818 patients were identified as potentially having BM and 453 patients were confirmed on clinical review of their records. The median age of patients was 69 years, 50% were female and 66% had a performance status of >2. 12.2% had an identifiable mutation and 11.5% were identified as PD-L1 positive. In the first line setting, 65% of patients received symptomatic treatment, 23% received systemic anticancer therapy (SACT), 6.1% surgery and 10% radiotherapy, of which 6.5% had external beam and 3.5% stereotactic radiosurgery. Regarding those treated with SACT, 35% had an intracranial response to treatment (3% had complete response, 32% had a partial response). Median survival was 2 months (1.9 - 2.4 months 95% CI). The real-world prognosis for NSCLC patients with BMs is poor. By using an algorithm, we have reported outcomes on a comprehensive cohort of patients which helps identify those for whom an active treatment approach is appropriate.

Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM) an academic, multicenter, single-arm, two-stage, phase II study.

Maintaining angiogenesis inhibition and switching the chemotherapy backbone represent the current second-line therapy in patients with RAS-mutant metastatic colorectal cancer (mCRC). Regorafenib, an oral multikinase inhibitor, prolonged overall survival (OS) in the chemorefractory setting. STREAM was an academic, multicenter, single-arm phase II trial, evaluating the activity of regorafenib in RAS-mutant mCRC, in terms of the rate of patients who were progression-free after 6 months from study entry (6mo-PF). Patients were pretreated with fluoropyrimidine, oxaliplatin, and bevacizumab. According to Simons two-stage design, ≥18 patients 6mo-PF were needed in the overall population (N 46). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS), and OS. Early metabolic response by The number of patients 6mo-PF was 822 at the first stage and 1446 in the overall population. The ORR was 10.9%, disease control rate was 54.6%, median (m)PFS was 3.6 months 95% confidence interval (CI) 1.9-6.7 months, mOS was 18.9 months (95% CI 10.3-35.3 months), and mPFS2 (from study entry to subsequent-line progression) was 13.3 months (95% CI 8.4-19.7 months). Long benefiter patients (>6mo-PF) significantly more often had a single metastatic site and lung-limited disease. No unexpected toxicity was reported. Grade ≥3 events occurred in 39.1% of patients, with hand-foot syndrome (13%), fatigue, and hyperbilirubinemia (6.5%) occurring mostly. Baseline metabolic assessment was associated with OS in the multivariate analysis, while early metabolic response was not associated with clinical outcomes. The study did not meet its primary endpoint. However, regorafenib was well tolerated and did not preclude subsequent treatments. Patients with good prognostic features (single metastatic site and lung-limited disease) reported clinical benefit with regorafenib. The exploratory metabolic analysis suggests that baseline

Perspectives of Indonesian Muslim patients with advanced lung cancer on good death A qualitative study.

Lung cancer is the leading cause of cancer-related death. Patients with advanced lung cancer may experience burdensome distress at the end of life. The concept of good death has been shown to be complex, and continues to be expanded by gaining a better understanding of the cultural views of different populations. This study aimed to explore the perspective of Indonesian Muslims patients with advanced cancer on the concept of good death. A qualitative design comprising in-depth interviews was employed. Seven male and 3 female Muslim patients between ages 36 and 68 and diagnosed with advanced lung cancer were recruited from a teaching hospital in Central Java, Indonesia. Content analysis of the interviews revealed five themes dying without physical discomfort, dying in religious ways and in a desirable place, dying without emotional discomfort, receiving help and support, and having a good relationship with medical staff. Indonesian Muslim patient with advanced lung cancer have unique perspectives on good death, especially based on the themes of religious ways of dying and support from family. Health care providers should be aware that good death is not an individual concern and should thus adopt highly sensitive observation skills to assess the physical and emotional state of patients. These providers must also understand their patients preferences and respect their needs, regardless of their own beliefs.

GLIM diagnosed malnutrition predicts clinical outcomes and quality of life in patients with non-small cell lung cancer.

The high prevalence of malnutrition in non-small cell lung cancer (NSCLC) patients has numerous negative consequences on patients outcome when undergoing anti-neoplastic treatment. The Global Leadership Initiative on Malnutrition (GLIM) criteria for diagnosis of malnutrition are currently being verified however, studies validating GLIM criteria in NSCLC patients are lacking. This study aimed to evaluate clinical outcomes and Quality of Life (QoL) in malnourished compared to well-nourished NSCLC patients to determine the predictive validity of GLIM criteria. We collected data on adverse events, survival, and QoL from NSCLC patients undergoing first line anti-neoplastic treatment collected from two prospective trials. Patients were categorized by GLIM criteria as malnourished or well-nourished, based on non-volitional weight loss, low Body Mass Index, reduced muscle mass (Computed Tomography-scans), reduced food intake (24-h recall), and inflammatory condition (modified Glasgow Prognostic Score). Differences in descriptive data, adverse events, survival, and QoL between the malnourished and well-nourished patients were analyzed. Overall, 120 patients were included in the study. Malnourished patients compared to well-nourished patients had significantly worse outcome in terms of treatment cessation (n 21 vs 13, p 0.049), disease progression (n 20 vs 12, p 0.034) and shorter overall survival (HR 2.0, 95% CI 1.2, 3.4, p 0.009). Stratifying by severity, moderately malnourished patients had a shorter overall survival compared to well-nourished patients (HR 2.1, 95% CI 1.2, 3.6, p 0.007). Malnutrition at baseline was associated with poor QoL by lower physical (p < 0.001) and role functioning (p 0.011), more symptoms of fatigue (p 0.001), nausea and vomiting (p 0.009), pain (p < 0.001), dyspnea (p 0.032), appetite loss (p < 0.001), and constipation (p 0.029). No significant differences were found in hospitalization, dose reductions, or treatment postponement. Malnutrition defined by GLIM criteria in NSCLC patients was associated with more frequent early cessation of anti-neoplastic treatment, shorter overall survival, and poorer QoL compared to well-nourished patients.

Efficient improvement in chemophotothermal synergistic therapy against lung cancer using BiAu nano-acanthospheres.

Novel highly hydrophilic and biocompatible bismuth nanospheres with gold nanoparticles growing outside (BiAu nano-acanthospheres, BiAu NASs) were synthesized through a simple procedure, which demonstrated to be a promising photothermal agent owing to the ultrahigh photothermal conversion efficiency (η 46.6 %). The as-prepared BiAu NASs showed excellent blood compatibility and fairly low cytotoxicity to human lung cancer A549 cells, as well as efficient photothermal ablation (PTA) therapy induced by a near-infrared laser. Under the 808 nm laser radiation, the tumour temperature could be elevated by ∼25 °C high enough to kill the cancer cells. Moreover, the anticancer drug doxorubicin hydrochloride (DOX) was successfully loaded in BiAu NASs with a loading content as high as 16.78 % and released under a pH sensitive release profile, a characteristic beneficial for intravenous delivery of DOX into cancer cells for chemotherapy. The presence of the Bi element enabled BiAu NASs to act as a favourable computed tomography (CT) contrast medium for CT imaging-guided tumour treatment. Compared with cancer treatment through either photothermal therapy or chemotherapy, the chemo-photothermal synergistic therapy using BiAu NASs as both a photothermal agent and a drug carrier has efficiently enhanced the in vitro and in vivo therapeutic effects in cancer treatment.

Tumor-promoting roles of HMMR in lung adenocarcinoma.

Searching for differential genes in lung adenocarcinoma (LUAD) is vital for research. Hyaluronan mediated motility receptor (HMMR) promotes malignant progression of cancer patients. However, the molecular regulators of HMMR-mediated LUAD onset are unknown. This work aimed to study the relevance of HMMR to proliferation, migration and invasion of LUAD cells. Let-7c-5p and HMMR levels in LUAD cells and HLF-a cells were assessed, and their correlation was also detected. Their interaction was determined by dual-luciferase experiments and qRT-PCR. Cell proliferation, migration and invasion potentials in vitro were validated through cell counting kit-8 (CCK-8), colony formation, scratch healing, and transwell assays. The expression of HMMR was examined by qRT-PCR and western blot and the expression of let-7c-5p was assayed by qRT-PCR. It was found that HMMR level was increased in LUAD and negatively correlated with let-7c-5p level. Let-7c-5p directly targeted HMMR to repress LUAD cell proliferation, migration and invasion. The above data illustrated that the let-7c-5pHMMR axis may provide certain therapeutic value for LUAD patients.

Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC. This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable n 30) or RT (ie, inoperable n 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N 62). Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic In this cohort of ES-NSCLC,

Synthesis of silver and copper nanoparticle using

The present research displays the green synthesis of stable silver nanoparticles (Ag-NPs) and copper oxide nanoparticles (CuO-NPs). The aqueous solution of

Hydrolysis-Resistant Ester-Based Linkers for Development of Activity-Based NIR Bioluminescence Probes.

Activity-based sensing (ABS) probes equipped with a NIR bioluminescence readout are promising chemical tools to study cancer biomarkers owing to their high sensitivity and deep tissue compatibility. Despite the demand, there is a dearth of such probes because NIR substrates (e.g., BL660 (a NIR luciferin analog)) are not equipped with an appropriate attachment site for ABS trigger installation. For instance, our attempts to mask the carboxylic acid moiety with standard self-immolative benzyl linkers resulted in significant background signals owing to undesirable ester hydrolysis. In this study, we overcame this longstanding challenge by rationally designing a new hydrolysis-resistant ester-based linker featuring an isopropyl shielding arm. Compared to the parent, the new design is 140.5-fold and 67.8-fold more resistant toward spontaneous and esterase-mediated hydrolysis, respectively. Likewise, we observed minimal cleavage of the ester moiety when incubated with a panel of enzymes possessing ester-hydrolyzing activity. These impressive in vitro results were corroborated through a series of key experiments in live cells. Further, we showcased the utility of this technology by developing the first NIR bioluminescent probe for nitroreductase (NTR) activity and applied it to visualize elevated NTR expression in oxygen deficient lung cancer cells and in a murine model of non-small cell lung cancer. The ability to monitor the activity of this key biomarker in a deep tissue context is critical because it is associated with tumor hypoxia, which in turn is linked to drug resistance and aggressive cancer phenotypes.

Quality of life of patients with solid malignancies at 3 months after unplanned admission in the intensive care unit A prospective case-control study.

Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 12 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients median of 54 (interquartile range 42-57) vs. 47 (37-52), respectively (p 0.01). The physical component score of the SF-36 did not differ between groups 35 (31-47) vs. 42 (34-47) (p 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients.

Whole Mitochondrial Genome Analysis in Non-Small Cell Lung Carcinoma Reveals Unique Tumor-Specific Somatic Mutations.

Mitochondria and mitochondrial DNA have been suggested to play a role in cancer initiation and progression. Knowledge of mitochondrial DNA could provide a breakthrough to advance cancer management. To identify the mitochondrial DNA landscape in non-small cell lung carcinoma. The adenocarcinoma set consisted of 365 pairs of adenocarcinomas and normal lung tissues, whereas the metastasis set included 12 primary non-small cell carcinomas, 15 metastatic tumors, and their normal counterparts. Tumor-specific somatic variants were identified, and if a variant showed heteroplasmy, the proportion of minor alleles was evaluated. Variants with greater than 10% change in allele frequency between tumor and normal pairs were identified as heteroplasmic shifts. Tumor-specific variants appeared throughout the whole mitochondrial genome, without a common hot spot. Distinct variant profiles were seen in 289 (79.18%) of all individual adenocarcinomas. The presence of a unique profile and the number and loading of heteroplasmic shifts in tumors increased with higher stage or lymph node metastasis, and were related to shorter survival. In the metastasis set, the primary tumor variants were generally found in metastatic tumors. This study shows that somatic mitochondrial DNA mutations present with diverse locations and unique profiles in each individual tumor, implying their clinicopathologic utility.

Metastatic Pattern of Breast Cancer by Histologic Grade A SEER Population-based Study.

Population-based estimates of the differences -in metastatic pattern, incidence, and prognosis of breast cancer patients by histologic grade at breast cancer diagnosis are lacking. Patients with breast cancer and metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic and Cox regression were performed to determine the effect of histologic grade on the presence of metastases at diagnosis and all-cause mortality. We identified a population-based sample of adult patients diagnosed with invasive breast cancer between 2010 and 2015 for whom the presence or absence of metastases was known. We depicted the landscape of metastatic pattern of breast cancer histologic grade that the percentage of bone metastasis was decreasing with higher histologic grade, while the percentages of lung and brain metastasis were increasing. Higher histologic grade was associated with a greater incidence of all metastatic lesions. Median durations of survival with distant metastasis were 41 months (Grade I), 34 months (Grade II), 21 months (Grade III), 13 months (Grade IV), and 16 months (unknown histologic grade). Grade III and unknown histologic grade represent the most common part of patients with metastatic disease, but not for breast cancer patients without metastasis. In multivariate analysis, Grade II, III, IV, and unknown histologic grade were associated with significantly greater odds of patients with metastatic disease to any distant site, compared with Grade I, but not to bone. Grade III was associated with increased all-cause mortality among patients having metastases to any sites, bone, brain, liver, and lung compared with Grade I, but not Grade II and Grade IV. Breast cancer histologic grades are associated with distinct patterns of metastatic spread and notable differences in survival.

Adoption of Innovative Therapies Across Oncology Practices-Evidence From Immunotherapy.

Immunotherapies reflect an important breakthrough in cancer treatment, substantially improving outcomes for patients with a variety of cancer types, yet little is known about which practices have adopted this novel therapy or the pace of adoption. To assess adoption of immunotherapies across US oncology practices and examine variation in adoption by practice type. This cohort study used data from Medicare fee-for-service beneficiaries undergoing 6-month chemotherapy episodes between 2010 and 2017. Data were analyzed January 19, 2021, to September 28, 2022, for patients with cancer types for which immunotherapy was approved by the US Food and Drug Administration (FDA) during the study period melanoma, kidney cancer, lung cancer, and head and neck cancer. Oncology practice location (rural vs urban), affiliation type (academic system, nonacademic system, independent), and size (1 to 5 physicians vs 6 or more physicians). The primary outcome was whether a practice adopted immunotherapy. Adoption rates for each practice type were estimated using multivariate linear models that adjusted for patient characteristics (age, sex, race and ethnicity, cancer type, Charlson Comorbidity Index, and median household income). Data included 71 659 episodes at 1732 oncology practices. Of these, 264 practices (15%) were rural, 900 (52%) were independent, and 492 (28%) had 1 to 5 physicians. Most practices adopted immunotherapy within 2 years of FDA approval, but there was substantial variation in adoption rates across practice types. After FDA approval, adoption of immunotherapy was 11 (95% CI, -16 to -6) percentage points lower at rural practices than urban practices and 27 (95% CI, -32 to -22) percentage points lower at practices with 1 to 5 physicians than practices with 6 or more physicians. Adoption rates were similar at independent practices and nonacademic systems however, both practice types had lower adoption than academic systems (independent practice difference, -6 95% CI, -9 to -3 percentage points nonacademic systems difference, -9 95% CI, -11 to -6 percentage points). In this cohort study of Medicare claims, practice characteristics, especially practice size and rural location, were associated with adoption of immunotherapy. These findings suggest that there may be geographic disparities in access to important innovations for treating patients with cancer.

Risk of Psychiatric Disorders Among Spouses of Patients With Cancer in Denmark and Sweden.

There is emerging evidence that spouses of patients with cancer may have a higher prevalence of mental illness, but these studies have been limited by pre-post designs, focus on a single mental illness, and short follow-up periods. To assess the overall burden of psychiatric disorders among spouses of patients with cancer vs spouses of individuals without cancer and to describe possible changes in this burden over time. This population based cohort study included spouses of patients with cancer (diagnosed 1986-2016 in Denmark and 1973-2014 in Sweden exposed group) and spouses of individuals without cancer (unexposed group). Members of the unexposed group were individually matched to individuals in the exposed group on the year of birth, sex, and country. Spouses with and without preexisting psychiatric morbidity were analyzed separately. Data analysis was performed between May 2021 and January 2022. Being spouse to a patient with cancer. The main outcome was a clinical diagnosis of psychiatric disorders through hospital-based inpatient or outpatient care. Flexible parametric models and Cox models were fitted to estimate hazard ratios (HRs) with 95% CIs, adjusted for sex, age and year at cohort entry, country, household income, and cancer history. Among 546 321 spouses in the exposed group and 2 731 574 in the unexposed group who had no preexisting psychiatry morbidity, 46.0% were male participants, with a median (IQR) age at cohort entry of 60 (51-68) years. During follow-up (median, 8.4 vs 7.6 years), the incidence rate of first-onset psychiatric disorders was 6.8 and 5.9 per 1000 person-years for the exposed and unexposed groups, respectively (37 830 spouses of patients with cancer 6.9% 153 607 of spouses of individuals without cancer 5.6%). Risk of first-onset psychiatric disorders increased by 30% (adjusted HR, 1.30 95% CI, 1.25-1.34) during the first year after cancer diagnosis, especially for depression (adjusted HR, 1.38 95% CI, 1.30-1.47) and stress-related disorders (adjusted HR, 2.04 95% CI, 1.88-2.22). Risk of first-onset psychiatric disorders increased by 14% (adjusted HR, 1.14 95% CI, 1.13-1.16) during the entire follow-up, which was similar for substance abuse, depression, and stress-related disorders. The risk increase was more prominent among spouses of patients diagnosed with a cancer with poor prognosis (eg, pancreatic cancer adjusted HR, 1.41 95% CI, 1.32-1.51) or at an advanced stage (adjusted HR, 1.31 95% CI, 1.26-1.36) and when the patient died during follow-up (adjusted HR, 1.29 95% CI, 1.27-1.31). Among spouses with preexisting psychiatric morbidity, the risk of psychiatric disorders (first-onset or recurrent) increased by 23% during the entire follow-up (adjusted HR, 1.23 95% CI, 1.20-1.25). In this cohort study of 2 populations in Denmark and Sweden, spouses of patients with cancer experienced increased risk of several psychiatric disorders that required hospital-based specialist care. Our results support the need for clinical awareness to prevent potential mental illness among the spouses of patients with cancer.

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab.

The addition of consolidative durvalumab to chemoradiation has improved disease control and survival in locally advanced non-small cell lung cancer (NSCLC). However, there remains a need to identify biomarkers for response to this therapy to allow for risk adaptation and personalization. To evaluate whether TMB or other variants associated with radiation response are also associated with outcomes following definitive chemoradiation and adjuvant durvalumab among patients with locally advanced unresectable NSCLC. This cohort study included consecutive patients with unresectable locally advanced NSCLC treated with chemoradiation and adjuvant durvalumab between November 2013 and March 2020 who had prospective comprehensive genomic profiling. This study was completed at a multisite tertiary cancer center. The median (IQR) follow-up time was 26 (21-36) months. Statistical analysis was conducted from April to October 2022. Patients were grouped into TMB-high (≥10 mutationsmegabase mtMb) and TMB-low (<10 mtMb) groups and were additionally evaluated by the presence of somatic alterations associated with radiation resistance (KEAP1NFE2L2) or radiation sensitivity (DNA damage repair pathway). The primary outcomes were 24-month local-regional failure (LRF) and progression-free survival (PFS). In this cohort study of 81 patients (46 57% male patients median range age, 67 45-85 years), 36 patients (44%) had TMB-high tumors (≥10 mtMb). Patients with TMB-high vs TMB-low tumors had markedly lower 24-month LRF (9% 95% CI, 0%-46% vs 51% 95% CI, 36%-71% P .001) and improved 24-month PFS (66% 95% CI, 54%-84% vs 27% 95% CI, 13%-40% P .003). The 24-month LRF was 52% (95% CI, 25%-84%) among patients with KEAP1NFE2L2-altered tumors compared with 27% (95% CI, 17%-42%) among patients with KEAP1NFE2L2-wildtype tumors (P .05). On Cox analysis, only TMB status was associated with LRF (hazard ratio HR, 0.17 95% CI, 0.03-0.64 P .02) and PFS (HR, 0.45 95% CI, 0.21-0.90 P .03). Histology, disease stage, Eastern Cooperative Oncology Group status, programmed cell death ligand 1 expression, and pathogenic KEAP1NFE2L2, KRAS, and DNA damage repair pathway alterations were not significantly associated with LRF or PFS. In this cohort study, TMB-high status was associated with improved local-regional control and PFS after definitive chemoradiation and adjuvant durvalumab. TMB status may facilitate risk-adaptive radiation strategies in unresectable locally advanced NSCLC.

New2-((2-(2,4-dinitrophenyl)hydrazineeylidene) derivatives design, synthesis,

A series of novel hydrazone compounds have been synthesized by the condensation of hydrazines and different substituted salicylaldehydes at a molar ratio of 11 in one step reaction and characterized by FT-IR, ESI-MS,

Older age is not a negative factor for video-assisted thoracoscopic lobectomy for pathological stage I non-small cell lung cancer a single-center, retrospective, propensity score-matching study.

Video-assisted thoracoscopic surgery (VATS) has changed the surgical approach to non-small cell lung cancer (NSCLC) dramatically. The current study compares the outcomes of older and younger patients who underwent VATS lobectomy for NSCLC. In total, 424 eligible patients with pathological stage I NSCLC underwent VATS lobectomy between 2007 and 2017. Patients were classified into two groups (< 75 and ≥ 75 years old), after which propensity score-matching was performed. After matching, 143 patients were identified. No significant difference in postoperative complication rates was observed however, the ≥ 75-year-old group had a longer postoperative hospital stay (p 0.001). The 5-year overall survival, relapse-free survival, and lung cancer-specific survival rates of the < 75- and ≥ 75-year-old groups were 87.1% vs. 85.6% (p 0.537), 82.1% vs. 79.0% (p 0.531), and 93.5% vs. 92.7% (p 0.832), respectively. Despite the longer postoperative recovery following VATS lobectomy, the short- and long-term outcomes of older patients did not differ from those of younger patients. Thus, for early-stage NSCLC, older age alone was not a negative factor for lobectomy performed via minimally invasive surgery. Naturally, the systemic condition of this population must be evaluated carefully before surgery.

Group 2 Innate Lymphoid Cells Are Detrimental to the Control of Infection with Francisella tularensis.

Innate lymphoid cells (ILCs) are capable of rapid response to a wide variety of immune challenges, including various respiratory pathogens. Despite this, their role in the immune response against the lethal intracellular bacterium Francisella tularensis is not yet known. In this study, we demonstrate that infection of the airways with F. tularensis results in a significant reduction in lung type 2 ILCs (ILC2s) in mice. Conversely, the expansion of ILC2s via treatment with the cytokine IL-33, or by adoptive transfer of ILC2s, resulted in significantly enhanced bacterial burdens in the lung, liver, and spleen, suggesting that ILC2s may favor severe infection. Indeed, specific reduction of ILC2s in a transgenic mouse model results in a reduction in lung bacterial burden. Using an in vitro culture system, we show that IFN-γ from the live vaccine strain-infected lung reduces ILC2 numbers, suggesting that this cytokine in the lung environment is mechanistically important in reducing ILC2 numbers during infection. Finally, we show Ab-mediated blockade of IL-5, of which ILC2s are a major innate source, reduces bacterial burden postinfection, suggesting that IL-5 production by ILC2s may play a role in limiting protective immunity. Thus, overall, we highlight a negative role for ILC2s in the control of infection with F. tularensis. Our work therefore highlights the role of ILC2s in determining the severity of potentially fatal airway infections and raises the possibility of interventions targeting innate immunity during infection with F. tularensis to benefit the host.

A Rare Case of Primary Malignant Pericardial Mesothelioma Diagnosed with Pericardiotomy.

Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and lethal cardiac tumor. This article presents a 62-year-old man with recurrent pericardial fluid. The patients clinical symptoms and imaging features were nonspecific. Initial diagnosis was constrictive pericarditis. After admission, the patients symptoms worsened, and echocardiography indicated increased pericardial effusion. To diagnose and improve the patients symptoms, pericardiotomy was performed however, the procedure was unsuccessful because the pericardium was densely adherent to the myocardium. Histopathological examination, including immunohistochemical staining of the pericardial specimen revealed malignant mesothelioma. We recommended adjuvant therapy for the patient with cis-platinum and pemetrexed however, the patient and his family refused treatment. The patient was discharged 11 days after surgery. The patient survived for more than 15 months with surgical treatment. In this report, the patients symptoms improved, and the patient survived beyond the median survival after surgical treatment. Conclusion The definitive diagnosis of PMPM mostly has been obtained from specimens obtained by surgery. Surgery is an effective treatment method because it prevents cardiac tamponade and can improve symptoms or prognosis, but complete resection is impossible.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy a case report and literature review.

Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.