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bone cancer

Disparities in Palliative Treatment Utilization in Metastatic Colorectal Cancer Patients.

Patients with metastatic colorectal cancer (mCRC) often require multidisciplinary interventions due to the diversity of symptoms. Palliative treatment offers benefits including improved quality of life, yet sociodemographic disparities influence its utilization. This study aims to characterize these disparities in palliative treatment use among mCRC patients.

bone cancer

The role of disulfidptosis-associated LncRNA-LINC01137 in Osteosarcoma Biology and its regulatory effects on macrophage polarization.

The objective of this research is to investigate the function of long non-coding RNA (lncRNA) associated with disulfidptosis, particularly LINC01137, in osteosarcoma (OS), and its impact on macrophage polarization and the tumor immune microenvironment (TME), with the goal of identifying new prognostic biomarkers and therapeutic targets. Utilizing the OS transcriptome dataset from the TARGET database, differentially expressed lncRNAs related to disulfidptosis were identified. The functional mechanisms of LINC01137, which affect cell proliferation, migration, invasiveness, programmed cell death, and macrophage orientation, were explored using the full suite of analyses provided by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), alongside a diverse array of laboratory experiments, including an in vivo osteosarcoma xenograft model in BALB/c nude mice to assess the impact of LINC01137 knockdown on tumor growth. Among three lncRNAs identified that were distinctly linked to disulfidptosis, LINC01137 showed a notable increase in expression within OS cell lines. Silencing LINC01137 led to a marked decrease in the abilities of cell proliferation, migration, and invasiveness, simultaneously enhancing programmed cell death and facilitating the process of epithelial-mesenchymal transition (EMT). In vivo experiments further confirmed that LINC01137 knockdown significantly suppressed tumor growth in osteosarcoma xenograft models, aligning with the in vitro findings. Associated with disulfidptosis, LINC01137 is pivotal in osteosarcoma development through its enhancement of tumor cell proliferation, migration, and invasiveness, as well as its modification of macrophage orientation within the TME. Given its significance, LINC01137 merits exploration as a prognostic indicator, necessitating detailed studies on its regulatory functions and potential in therapy.

bone cancer

Early osteointegration in "one-step" resection and reconstruction using porous hydroxyapatite custom implants for skull-infiltrating tumors: a monocentric prospective series.

Early reconstruction of the skull represents the gold standard after resection of bone infiltrating cranial tumors. Customized hydroxyapatite porous ceramics are an excellent option for covering skull bone defects. The authors illustrate the surgical technique and investigate the effectiveness of the "one-step" procedure in terms of aesthetic results and early degree of osteointegration.

bone cancer

Key Proteins for Regeneration in

The axolotl, known for its remarkable regenerative abilities, is an excellent model for studying regenerative therapies. Nevertheless, the precise molecular mechanisms governing its regenerative potential remain uncertain. In this study, we collected samples from axolotls of different ages, including 8-year-old individuals and 8-month-old juveniles, obtaining their blastemas 10 days after amputation. Subsequently, we conducted a transcriptomic analysis comparing our samples to a set of previously published experiments. Our analysis unveiled a distinctive transcriptional response in the blastema, characterized by differential gene expression associated with processes such as bone and tissue remodeling, transcriptional regulation, angiogenesis, and intercellular communication. To gain deeper insights, we compared these findings with those from aged axolotls that showed no signs of regeneration 10 days after amputation. We identified four genes-

bone cancer

Case report: Pulmonary Ewing sarcoma disguised as non-small cell lung cancer.

Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. This rare type of cancer is characterized by its high malignancy and therefore high risk of metastases. Typically, Ewing sarcomas originate from bones. However, extraosseous Ewing sarcoma such as pulmonary Ewing sarcoma can also be found. In this case report, we present a 55-year old male patient who was initially diagnosed with non-small cell lung cancer at his local district hospital. However, the diagnosis was changed to one of pulmonary Ewing sarcoma after subsequent histopathological and molecular pathological analysis performed in a reference pathology laboratory. After patient referral to a certified (according to the German Cancer Society) high-volume sarcoma center, multimodal chemotherapy was initiated based on recently published clinical data as opposed to the more commonly used treatment regimen in Europe. The patient responded well to treatment and underwent a complete surgical tumor resection followed by radiotherapy. In summary, this case report highlights the importance of a rigorous and timely histopathological examination of biopsy samples by a specialized cancer center to enable a correct diagnosis of the cancer type. Additionally, molecular pathology plays a crucial part in this analysis and allows the necessary differentiation between cancer types. Up to now, there is no international treatment guideline available for the treatment of Ewing sarcoma. Patients should be referred to specialist centers to allow the best possible treatment of the cancer type in view of current published clinical data. In the case of Ewing sarcoma, and in accordance with the most recent research, patients should be treated with vincristine, doxorubicin and cyclophosphamide plus ifosfamide and etoposide in combination with local treatment such as surgery and/or radiotherapy because this has been demonstrated to be the more effective therapy.

bone cancer

Characterization of sarcoma topography in Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome primarily caused by germline

bone cancer

Impact of bone metastasis on prognosis in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Lung cancer is a leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. While immune checkpoint inhibitors (ICIs) have transformed treatment for advanced NSCLC, the role of bone metastasis in modulating ICI efficacy remains unclear. Bone metastasis, occurring in 30-40% of advanced NSCLC cases, is associated with worse outcomes. However, how this affects the therapeutic benefit of ICIs has not been fully elucidated, highlighting a critical knowledge gap in optimizing treatment for this patient population.

bone cancer

Bone metastasis in differentiated thyroid cancer: Spanish multicenter study of clinical characteristics, survival and prognostic factors.

This study describes the characteristics, survival and prognostic factors in a cohort of patients with bone metastases (BM) from differentiated thyroid carcinoma (DTC).

bone cancer

Osteosarcomas of the hand and foot: A sarcoma‑center case series experience.

Hand and foot osteosarcoma represents ~1% of all diagnosed cases of osteosarcoma. The rarity of osteosarcoma of the hand and foot leads to frequent misdiagnosis, delayed diagnosis or incorrect treatments, which can lead to fatal consequences. Typically, salvaging the affected limb is the treatment of choice, and with the use of chemotherapy, 60-65% of patients with osteosarcoma can be treated without amputation. Due to its rarity, misdiagnosis and treatment delays are common, yet detailed reviews and analyses of such cases are limited. The present retrospective cohort study aimed to review and analyze cases of osteosarcoma located in the hand and foot. From January 2007 to January 2019, 11 patients were treated at the Masaryk Memorial Cancer Institute Sarcoma Center (Brno, Czechia), 5 cases affected the hand and 6 affected the foot. A total of 6 male patients and 5 female patients, with a mean age of 30.9±16.74 years, were diagnosed with hand or foot osteosarcoma. The mean follow-up period was 90.36±66.14 months. The mean tumor size detected during diagnosis was 4.29±1.81 cm. Osteoblastic osteosarcoma was the most common histopathological type, accounting for 4 cases (33.4%). A majority of the osteosarcomas were identified as high grade (81.8%). A total of 5 patients experienced misdiagnoses following their initial biopsy, with 2 patients initially receiving treatment outside the Masaryk Memorial Cancer Institute Sarcoma Center. The most frequently encountered misdiagnosis was giant-cell tumor of the bone. A total of 3 patients underwent limb amputation and 2 patients developed lung metastasis and succumbed to the disease. The disease-free survival period and overall survival rate were calculated using Kaplan-Meier survival analysis. The mean disease-free survival period was 82.83±60.05 months, while the overall survival rate was 72%, with a mean survival time of 90.36±56.73 months. In summary, an examination of a case series involving 11 patients diagnosed with osteosarcoma of the hand and foot was conducted. The treatment approach, clinical characteristics and patient outcomes were described. A total of four case studies of patients with osteosarcoma in the hand or foot were presented. Misdiagnosis of this disease may result in the inappropriate treatment being administered to patients, therefore, the correct and rapid diagnosis of disease is necessary for effective treatment of hand and foot osteosarcomas.

bone cancer

Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib-a case report.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and aggressive subtype of inflammatory myofibroblastic tumor. The disease is associated with rearrangements of the anaplastic lymphoma kinase (ALK). In this paper, we present the clinicopathological features and treatment of a female patient diagnosed with EIMS. In 2019, an 18-year-old female patient was admitted to the hospital with abdominal pain. Radiological examinations confirmed a large pelvic mass which was subsequently resected. After re-evaluation of the initial histologic diagnosis, the final diagnosis of EIMS was established. Consequently, due to the lack of response to chemotherapy and deteriorating clinical condition, she began the therapy with ALK inhibitors. In total, the patient was treated with crizotinib, alectinib, and lorlatinib. As a result, after over 4 years since the initial diagnosis, she is still alive with significantly improved clinical condition and quality of life. This paper demonstrates the clinical benefits of sequential therapy of ALK inhibitors and an exceptionally long response to lorlatinib, a third-generation tyrosine kinase inhibitor.

bone cancer

Unveiling the Link Between Breast Cancer Treatment and Osteoporosis: Implications for Anticancer Therapy and Bone Health.

bone cancer

Cost-effectiveness analysis of additional local prostate radio therapy in metastatic prostate cancer from a medicare perspective.

Metastatic prostate cancer remains a therapeutic challenge. Based on data of the STAMPEDE trial, patients with a low metastatic burden showed prolonged failure-free and overall survival when treated with prostate radio therapy (RT) in addition to standard of care (SOC). The objective of this study was to determine the cost-effectiveness of additional prostate RT compared to SOC alone for following subgroups: non-regional lymph node (NRLN) metastases, up to three bone metastases and four or more bone metastases.

bone cancer

Interdisciplinary care of facial plexiform neurofibroma: a case report.

Neurofibromatosis is considered a rare genetic disorder primarily affecting neural tissues. The most common type is neurofibromatosis type 1, which is characterized by plexiform neurofibromas.

bone cancer

Palliative care of proximal femur metastatic disease and osteolytic lesions: results following surgical and radiation treatment.

Femoral bone metastases (FBM) or lesions (FBL) can lead to loss of mobility and independence due to skeletal-related events (SRE), e.g. pain, deformity and pathological fractures. Aim of this study was to analyze effects of radiotherapy and surgery, different surgical techniques and complications on disease-specific survival (DSS).

bone cancer

Efficacy of Vinblastine and Methotrexate in a Childhood Patient with Progressive Desmoid Fibromatosis of the Lower Jaw: A Case Report.

Desmoid fibromatosis (DF) is defined as a borderline tumor of the soft tissues with a low malignant potential. The most common tumor sites are the extremity, trunk, abdominal cavity, and head and neck. Surgical resection has been the standard treatment for DF. However, there are concerns regarding long-term cosmetic outcomes or functional morbidity associated with surgery particularly in the head and neck. Recently, the use of the front-line wait-and-see strategy and pharmacologic treatment such as chemotherapy for progression has been proposed as tumors can spontaneously stabilize and regress. Herein, we report the efficacy of vinblastine (VBL) and methotrexate (MTX) in a childhood patients with DF. A 21-month-old female patient with a 4-cm tumor at the left lower jaw was diagnosed with DF. She did not initially receive any therapies (wait-and-see) according to the recent treatment guidelines. However, the tumor gradually progressed, and the patient was managed with COX2 inhibitor. Since the tumor was not controlled with such a treatment and tracheal exclusion caused by the mass was a cause of concern, the patient was managed with chemotherapy with VBL and MTX. VBL and MTX were administered weekly for 26 weeks, every other week, and further for 26 weeks. The tumor size gradually decreased with VBL and MTX. Magnetic resonance imaging revealed no evidence of the disease at the end of chemotherapy. Good cosmetic outcomes were achieved, and recurrence was not observed after 24 months of follow-up.

bone cancer

Differential bone morphology and hypoxia activity in skeletal metastases of ER

Bone metastases occur in the majority of advanced breast cancer patients, and the most common complications are osteolytic bone metastases. However, due to the limitations of models and methodologies for bone metastasis studies, the intricacies of bone metastasis have not been fully acknowledged and revealed in prior work. Our earlier study indicated that certain breast cancer cells undergo a pre-osteolytic stage before the establishment of overt metastatic lesions. Here, we further identify a differential bone morphology between ER (estrogen receptor)

bone cancer

Neutrophils in toxicology: a forgotten field.

Neutrophils are the most abundant leukocytes in humans and essential for innate immune responses despite a short lifespan in the bloodstream. A complex and tightly regulated production of neutrophils is required to maintain host defense. This process involves intricate signaling between the bone marrow, blood, and tissue clearance. Deficiency or excessive neutrophil infiltration impairs host defenses. Historically, neutrophils were viewed as initial effectors in innate immune responses. Recent discoveries have expanded our understanding of neutrophil biology, identifying multiple activation states and subsets. These subsets may switch phenotypes based on the composition of the microenvironment and might exhibit reverse migratory behavior, moving from inflamed tissues back into the bloodstream. This versatility poses neutrophils as key players in (1) signaling for host defenses, (2) trained immunity, (3) tissue repair, and (4) cancer biology. Disturbances in neutrophil production, responsiveness, apoptosis, and cell removal significantly affect inflammatory diseases and cancer progression. Environmental factors may directly affect the immune system and trigger the onset of many diseases; however, the precise mechanisms underlying the impact of xenobiotics on neutrophil production and functions remain unclear. This review aimed to summarize the current knowledge on neutrophil ontogeny, plasticity, and roles in inflammation, tissue repair, and cancer, emphasizing their susceptibility to different sources of xenobiotic exposures.

bone cancer

Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial.

Neoadjuvant PD-1 inhibitor is promising in cutaneous melanoma but remains unknown in acral melanoma (AM). This phase Ib trial study (Clinicaltrials.gov NCT04197882) assessed the efficacy and safety of the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable AM. Thirty patients of stage III/IV received neoadjuvant therapy of ori and tori for 12 weeks before surgery, followed by adjuvant treatment with tori for 1 year. Primary endpoints were radiographic and pathological response rates, with secondary endpoints of 1- and 2-year recurrence-free survival (RFS) rates, event-free survival (EFS) rates, and safety. Twenty-seven completed surgery and tori adjuvant treatment and median follow-up was 35.7 months. Radiographic and pathological response rates were 36.7% and 77.8%, with complete response rates of 3.3% and 14.8%, 1- and 2-year RFS rates of 85.2% and 81.5%, and 1- and 2-year EFS rates of 83% and 73%, respectively. Adverse events occurred in all patients, mainly grade 1-2. There was no correlation between PET/CT evaluation and pathological response or progression-free survival/overall survival. Patients with pathological response showed tumor beds with high tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs). Cytokines and chemokines analysis showed the combination therapy significantly increases the secretion of proinflammatory cytokines and chemokines in both responders and non-responders. Therefore, neoadjuvant ori and tori demonstrated promising antitumor activity with high response rates and high 2-year RFS/EFS for AM with acceptable tolerability.

bone cancer

Impact of Lymphatic and Venous Invasion Patterns on Postoperative Prognosis and Distant Metastasis in Esophageal Squamous Cell Carcinoma After Preoperative Chemotherapy.

Lymphovascular invasion (LVI) is reported to correlate with postoperative prognosis in esophageal squamous cell carcinoma (ESCC). However, reports analyzing lymphatic and venous invasion separately are rare, and no studies have examined the correlation in resected specimens after neoadjuvant chemotherapy (NAC). This study evaluated the postoperative prognosis and distant metastatic recurrence patterns in ESCC patients who underwent esophagectomy after NAC.

bone cancer

Advancing precision in CT-guided bone biopsies: exploring the potential of dual-energy CT imaging.

This study aimed to investigate the integration of dual-energy CT (DECT) into CT-guided bone biopsy procedures, comparing it with conventional CT techniques. The focus was on technical aspects, accuracy and radiation dose exposure.

bone cancer

Ibrutinib With Bendamustine and Rituximab for Treatment of Patients With Relapsed/Refractory Aggressive B-Cell Lymphoma.

Therapy for relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (aB-NHL) post autologous stem cell transplantation (ASCT) or in elderly patients can be challenging. In this single-center, single-arm, phase II clinical study, we investigated the efficacy of ibrutinib (560 mg once daily) in combination with bendamustine and rituximab (IBR) given for six 28-day cycles in their standard dose, to patients with R/R aB-NHL who were either transplant ineligible in first or second relapse or post-ASCT for second relapse. The primary endpoint was overall response rate (ORR). Fifty-six patients (54% male, median age 69.7 years) were included. ORR was 49.1% among 55 patients treated with ≥ 1 cycle of IBR and 69.4% among 36 patients treated with ≥ 3 cycles. Patients with relapsed disease had significantly higher ORR compared to those with refractory disease (72.3% vs. 37.8%, p = 0.024). Median overall survival (OS) was 11.6 months (95% CI, 7.1-22.3) and median progression-free survival was 5.3 months (95% CI, 2.5-7.4). Patients with complete and partial responses had significantly longer median OS compared to those with stable and progressive disease (28.1 vs. 5.2 months, p < 0.0001). Adverse events included thrombocytopenia (19.6%), anemia (16.1%), neutropenia (7.1%), fatigue (35.7%), diarrhea (28.6%) and nausea (28.6%). At the first efficacy evaluation 8 patients were referred to transplantation, and 3 more were referred during follow-up. These data indicate that the IBR regimen is a safe and effective treatment option that can also be used for bridging to transplantation in patients with R/R aB-NHL.Trial Registration: ClinicalTrials.gov: NCT02747732.

bone cancer

Nanotube-mediated mitochondrial transfer: power to the T cells!

The success of T cell-based immunotherapies is limited by exhaustion, which is associated with mitochondrial dysfunction. Baldwin and colleagues show that bone marrow stromal cells (BMSCs) use nanotubes to transfer mitochondria to T cells, which increases mitochondria mass and fitness and boosts antitumor efficacy. The results pave the way to organelle-based therapies against cancer.

bone cancer

Reclassifying cT4b buccal mucosa/gingivobuccal complex cancers: do we need to change?

T4b carcinomas are termed as very locally advanced carcinomas of the oral cavity and are deemed borderline resectable or unresectable. The role of surgery for these patients is not well defined. We therefore aimed to relook at the role of surgery for cT4b carcinoma of the oral cavity. We evaluated 596 patients with cT4 oral cancers. A total of 218 patients were staged as cT4b based on clinicoradiological findings. These patients underwent bite composite resection either before or after neoadjuvant chemotherapy. Additional compartmental infratemporal fossa (ITF) clearance was done in patients with involvement of more than two of following structures: medial and lateral pterygoid muscles, pterygoid plates, temporalis at the tip of the coronoid process, high masseter, retroantral fat pad. Oncological outcomes and prognostic factors were estimated. Patients were treated between August 2013 and May 2021. Compartmental ITF clearance was done in 93 patients; the rest had standard surgical clearance. A total of 112 patients had node-positive disease. The median (range) age of the group was 50 (24-84) years. On a median follow up of 54 months (IQR: 1-111 months), 136 (62.4%) were alive and 82 (37.6%) had died. Five-year locoregional control, disease-free survival, and overall survival were 54%, 52%, and 59%, respectively. On multivariate analysis, the presence of nodal disease, perineural invasion, and bone involvement were statistically significant factors affecting overall survival. Surgery for cT4b oral cancer is therefore feasible and associated with acceptable oncological outcomes.

bone cancer

[Clinical application of reconstruction of pelvic floor with pedunculated omentum flap combined with basement membrane biological products in pelvic exenteration with sacrococcygeal bone].

bone cancer

[Analysis of the efficacy of adjusting the dose of imatinib with therapeutic drug monitoring in adjuvant treatment after complete resection of gastrointestinal stromal tumors].

bone cancer

[Prognosis and its influencing factors in patients with non-gastric gastrointestinal stromal tumors at low risk of recurrence: a retrospective multicenter study in China].

bone cancer

IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.

Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).

bone cancer

[Long-Term Response to CDK4/6 Inhibitor for Multiple Metastases of Breast Cancer].

The patient was a 60-year-old woman. She was diagnosed with hypertension, symptomatic epilepsy, renal failure, and cerebral infarction. During follow-up, she was found to have a mass in her left breast and was referred to our department. An irregular mass measuring 5 cm in diameter was palpated in the C region of the left breast. Multiple enlarged lymph nodes, thought to be metastases, were also palpated in the ipsilateral axillary lymph nodes. A needle biopsy revealed invasive ductal carcinoma, ER positive, PgR positive, HER2 negative, Ki-67 12%. A systemic examination revealed bone metastasis. Surgery was not possible due to comorbidities, so fulvestrant(500 mg/month)+denosumab(120 mg/month)was started. Furthermore, as the tumor markers were elevated, abemaciclib(300 mg/day)was added, which resulted in a decrease in the tumor markers. After 1 month of administration, grade 3 neutropenia was observed, so the dosage was reduced to 200 mg/day. During the course of treatment, the tumor markers rose again, so the dose was increased to 250 mg/day, which resulted in a decrease in the tumor markers and good tolerability. At present, 36 months after the start of treatment, long SD has continued, no adverse events of grade 3 or higher have been observed, and the drug has been well tolerated.

bone cancer

[A Case of Late Recurrence of Breast Cancer with Gastric Metastasis 35 Years after Surgery].

An 82-year-old woman, who underwent a mastectomy for right breast cancer 35 years ago, presented to our hospital with a chief complaint of general malaise and dyspnea. A chest CT scan revealed a right pleural effusion and multiple bone metastases. Upper gastrointestinal endoscopy revealed a small bulge in the mid gastric fold, which was diagnosed as a metastatic breast cancer lesion, based on pathological diagnosis and immunostaining findings. The patient had triple-negative breast cancer and was started on docetaxel therapy despite her advanced age. The pleural effusion disappeared, tumor marker levels normalized, and treatment was continued. Here, we report a case of late recurrence of breast cancer with gastric metastasis 35 years postoperatively.

bone cancer

The molecular subtypes of small cell lung cancer defined by key transcription factors and their clinical significance.

Lung cancer, a prevalent and deadly malignancy, is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC is further subdivided into four molecular subtypes-SCLC-A, SCLC-N, SCLC-P, and SCLC-I-based on key transcription factor expression.

bone cancer

Stereotactic Ablative Radiotherapy for Bone-Only Oligometastatic Breast Cancer: On a Quest to Find the Optimum Cohort.

We aimed to evaluate the treatment outcomes and associated prognostic factors in breast cancer (BC) patients who had bone-only oligometastatic disease (OMD) and we tried to determine the subgroup that would benefit most from stereotactic ablative radiotherapy (SABR).

bone cancer

Immunohistochemical study of histone protein 3 modification in pediatric osteosarcoma identifies reduced H3K27me3 as a marker of poor treatment response.

The most common pediatric primary malignant bone tumor, osteosarcoma, is often described as genetically non-recurrent and heterogeneous. Neoadjuvant chemotherapy is typically followed by resection and assessment of treatment response, which helps inform prognosis. Identifying biomarkers that may impact chemotherapy response and survival could aid in upfront risk stratification and identify patients in highest need of innovative therapies for future clinical trials. Relative to conventional genetics, little is known about osteosarcoma epigenetics. We aimed to characterize the methylation and phosphorylation status in osteosarcoma using histone markers found in primary diagnostic biopsies and their paired metastases. We constructed two tissue microarray sets from 58 primary diagnostic samples and 54 temporally-separated but related metastatic or recurrent samples, with tissue blocks available from 2002-2022. Clinical charts were reviewed for post-therapy necrosis response, presence of metastatic disease or recurrence, and overall survival. We evaluated 6 histone H3 residues using immunohistochemistry, including H3K4me3, H3K9me3, H3K27me2, H3K27me3, H3S10T11phos, and H3S28phos. Tumors were scored with low (<25%) or high (≥25%) nuclear staining of tumor cells. Diagnostic biopsies with low H3K27me3 nuclear staining were associated with poor treatment response (≤90% necrosis) at the time of definitive excision (P<0.05). We observed loss of H3S10T11phos expression in metastatic and recurrent resections specimens compared to the primary tumor (P<0.05). Expression patterns for the remaining histone markers did not show significant associations with disease parameters or survival. Although larger cohort studies are needed, these results support the expanded evaluation of histone markers, particularly H3K27me3 and H3S10T11phos, in osteosarcoma biology and risk stratification.

bone cancer

Internal Carotid Artery Injury During the Endoscopic Transsphenoidal Surgery of Pituitary Adenoma: Case Illustration, Introspection, and Systematic Review.

Advances in endoscopic technology have made the endoscopic transsphenoidal approach the preferred approach for most surgeries of pituitary adenoma. The goal of these surgeries is to achieve cure, efficacy, and safety. Ample research has deliberated on the complications of cerebrospinal fluid (CSF) leak, meningitis, visual deterioration and nasal crusting after endoscopic transsphenoidal surgery. Among these, injury to the internal carotid artery (ICA) is not common in transsphenoidal pituitary surgery and has an incidence that ranges from 0.1% to 1%. Though it is rare, the effects are devastating and associated with a high risk of mortality and morbidity. As a result, iatrogenic ICA injury is every neurosurgeon's nightmare. Available literature primarily consists of case reports on these injuries. The literature is lacking on preventive and management options. We present an unusual case of a patient who had a nonfunctioning pituitary macroadenoma and an unexpected injury to the internal carotid artery (ICA) during endoscopic transsphenoidal surgery. We share our successful experience with its management via emergency endovascular treatment with parent vessel occlusion for an iatrogenic ICA injury. We present the article to address the pragmatic questions and challenges faced by neurosurgeons experiencing this complication for the first time.

bone cancer

Venous Compromise/Deep Venous Thrombosis During Parasagittal Meningiomas Resection.

We are reporting the case of JB, a 28-year-old male who presented to our hospital in 2009. The patient reported a progressive increase in a known mass that had been deforming their head since 2005. He had suffered from a first-time seizure four years later (in 2009). Neurological examination revealed a large tumor protruding in the parietal region, which was confirmed by CT. A subsequent MRI demonstrated a hyperostotic contrast-enhancing parasagittal tumor occluding the middle third of the superior sagittal sinus, with cortical veins joining the sinus adjacent to the tumor.The patient was taken to the OR for a craniotomy and a resection of the tumor with cranioplasty in the same setting. The tumor was exposed by using a straight incision on the scalp. A craniotomy was performed around the tumor by using multiple burr holes; now the bone could be separated from the dura and removed. The intradural tumor was exposed, and a cortical vein draining into the tumor could not be preserved. Some residual tumor was left close to the anterior part of the superior sagittal sinus. The dura was reconstructed with pericranium, and the bony defect was closed with titanium mesh. The patient woke up initially paraplegic, but 7 days later, he started with proximal movements in both legs. Unfortunately, he died suddenly in the second postoperative week, due to pulmonary embolism. The case is reviewed in this manuscript to analyze the contributing factors of the complications that were observed and to suggest management strategies to avoid them.

bone cancer

Carotid Complications in Skull Base Surgery.

Carotid artery rupture is a worrisome complication that sometimes occurs during microsurgical or endoscopic skull base procedures. Many identifiable aspects are related to prevention, intraoperative management, and immediate postoperative endovascular treatment. This article deals with microsurgical and endoscopic cases in which the carotid artery or its branches have been damaged in the context of a resection of skull base lesions. Factors related to the anatomy of the skull base and the arteries and their variations are considered, along with intraoperative measures to control the bleeding. Finally, depending on the case, recommendations for immediate postoperative endovascular management are made.

bone cancer

Wide surgical margins may be necessary to reduce recurrence and mortality in patients with localized periosteal chondrosarcoma: retrospective analysis of twenty three patients and literature meta-analysis.

Periosteal chondrosarcoma (PCS) is the rarest subtype of chondrosarcoma and is recognized as a low-grade malignant tumour, reported to have an 88% ten year overall survival rate. The relationship between surgical margins and clinical outcome is inconsistent; some authors claim that PCS can be successfully treated with marginal resection and others report more local recurrence and distant metastasis with marginal compared to wide resection. This study was intended to report the treatment and prognosis of localized PCS patients from the Japanese National Bone and Soft Tissue Tumor Registry database and to perform a systematic review of the literature to determine the relationship between surgical margins and rates of local recurrence, distant metastasis, and mortality.

bone cancer

Dendritic cell activation by iron oxide nanoparticles depends on the extracellular environment.

Nanoparticles can exert immune modulating effects in a host depending on composition, mode of administration, and type of disease. Although the specific mechanisms of nanoparticle-induced immune responses remain unclear, their uptake by macrophages and other phagocytic innate immune cells is considered to be a key event. Our objective here was to ascertain if nanoparticle-mediated activation of dendritic cells (DCs) occurs

bone cancer

Adrenocortical Carcinoma: A Challenging Diagnosis.

Adrenocortical carcinoma (ACC) is a rare malignancy with aggressive behaviour and a poor prognosis. Patients can present with adrenal hormonal excess or with nonspecific symptoms driven by the presence of an abdominal mass or metastatic disease. Many are completely asymptomatic and diagnosed incidentally. ACC can cause considerable morbidity and mortality, mostly due to its ability to invade surrounding tissues, produce hormones, and spread to distant organs. The authors describe a case of a 62-year-old woman who presented with subacute dorso-lumbar pain. A computed tomography (CT) scan revealed osteolytic lesions in her dorsal spine and sacrum, suggesting metastatic disease. Later on, she presented with hypercortisolism and refractory hypokalemia, so an abdominal and pelvis CT was performed, which showed a suspicious mass in the right adrenocortical gland. A CT-guided adrenal biopsy confirmed ACC. Unfortunately, our patient's clinical status rapidly deteriorated, resulting in her death only a few weeks later. ACC is often found at an advanced stage and with distant metastases, most commonly in the liver, lungs, lymph nodes, and bone. The overall prognosis of ACC is generally poor, but it varies depending on the extent of the disease. Multiple factors have been shown to be relevant in the prognostic classification, such as tumor stage, cell proliferation markers, and resection status. Currently, the only curative treatment is complete surgical resection. Adjuvant therapies have often been shown to decrease recurrence rates or as an alternative in patients with advanced disease. Many studies have been conducted to better understand the molecular basis of ACC, thus enabling the classification into molecular subtypes, but more studies are necessary to identify targets amenable to pharmaceutical intervention. With this case report, we want to emphasize that the diagnosis of ACC is not always obvious. Although metastases are infrequent, their presence is by far the strongest indicator of poor prognosis. All patients with proven or suspected ACC benefit from multidisciplinary monitoring, preferably at a specialized center.

bone cancer

A novel hypoxia- and lactate metabolism-related prognostic signature to characterize the immune landscape and predict immunotherapy response in osteosarcoma.

Immunotherapy has shown considerable promise in cancer treatment, yet only a minority of osteosarcoma patients derive benefits from this approach. Hypoxia and lactate metabolism are two predominant characteristics of the tumor microenvironment. These features are crucial for molding the immune landscape and thus have the potential to act as predictive indicators for immunotherapy response.

bone cancer

Statin prescription disparities in patients with breast cancer and diabetes for primary cardiovascular disease prevention.

This brief report examines statin prescription trends for primary cardiovascular disease (CVD) prevention in breast cancer (BC) survivors with diabetes, a large population at particularly high CVD risk.

bone cancer

Acute myeloid leukemia drug tolerant persister cells survive chemotherapy by transiently increasing plasma membrane rigidity, that also increases their sensitivity to immune cell killing.

Resistance to chemotherapy remains a major hurdle to the cure of Acute Myeloid Leukemia (AML) patients. Recent studies indicate a minority of malignant cells, termed drug-tolerant persisters (DTPs), stochastically upregulate stress pathways to evade cell death upon acute exposure to chemotherapy without acquiring new genetic mutations. This chemoresistant state is transient and the cells return to baseline after removal of chemotherapy. Yet, the mechanisms employed by DTPs to resist chemotherapy are not well understood and it is largely unknown whether these mechanisms are also seen in patients receiving chemotherapy. Here, we used leukemia cell lines, primary AML patient samples and samples from patients with AML receiving systemic chemotherapy to study the DTP state. We demonstrated that a subset of AML cells transiently increases membrane rigidity to resist killing due to acute exposure to Daunorubicin and Ara-C. Upon removal of the chemotherapy, membrane rigidity returned to baseline and the cells regained chemosensitivity. Although resistant to chemotherapy, the increased membrane rigidity, rendered AML cells more susceptible to T-cell mediated killing. Thus, we identified a novel mechanism by which DTP leukemic cells evade chemotherapy and a strategy to eradicate these persistent cells.

bone cancer

Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy.

Chimeric Antigen Receptor (CAR) T cells targeting CD19 induce durable remissions in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), but many patients experience treatmentrelated toxicity. Cytokine release syndrome and immune effector cell-associated neurologic syndrome are extensively characterized. However, limited data exist on the burden, predictors, and implications of acute kidney injury (AKI) after CAR T cell therapy. On initial screening of the FDA adverse event reporting system, we identified a disproportionately high rate of renal adverse events among nearly 6,000 CAR T adverse event reports, suggesting it is clinically important in this patient population. In a subsequent single-center analysis of 399 NHL patients treated with CD19 CAR T cells, we found a substantial burden of AKI after CAR T infusion (10% and 5% of any grade and grade ≥2 AKI) with pre-renal causes being predominant (72%). Evolution to chronic kidney disease was rare, however, 3 patients required hemodialysis. Importantly, patients experiencing cytokine release syndrome and/or neurotoxicity as well as those with low serum albumin and high inflammatory cytokines, including IL-6 and TNF-alpha, were more likely to develop AKI. While pre-CAR T renal dysfunction was not associated with adverse outcomes, patients developing post-CAR T AKI had lower overall survival compared to their counterparts. Our findings indicate that renal dysfunction is a common toxicity of CAR T cell therapy with meaningful prognostic impact. Notably, the link between systemic inflammation and renal dysfunction, suggests that readily available biomarkers may inform on renal injury risk after CAR T cell therapy.

bone cancer

Towards Optimal Automated

DOTA-functionalized bisphosphonates can be useful tools for PET imaging of bone metastases when radiolabeled with

bone cancer

Transcriptome Analysis of HNSCC by Aggregatibacter actinomycetemcomitans Extracellular Vesicles.

The role of extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), secreted by oral bacteria in the progression of head and neck squamous cell carcinomas (HNSCCs), is largely unexplored. This study aimed to investigate the influence of bacterial EVs, specifically those derived from Aggregatibacter actinomycetemcomitans (Aa), on the progression of HNSCC.

bone cancer

Treatment-Free Remissions in Children With Chronic Myeloid Leukemia (CML): A Prospective Study From the Tata Memorial Hospital (TMH) Pediatric CML (pCML) Cohort.

Pediatric chronic myeloid leukemia (pCML) is a rare childhood malignancy, representing 2%-3% of all childhood leukemia. Tyrosine kinase inhibitors (TKIs) have greatly improved survival but pose challenges due to their long-term effects on growth and bone health in children. We prospectively studied treatment-free remission (TFR) in 45 children with pCML in chronic phase on imatinib. Eligibility criteria were as per current NCCN guidelines, with a less stringent qPCR monitoring scheduled every 3 months. TFR was successful in 71.1% (32 out of 45) of patients after a median follow-up of 25 (range: 6-42) months. The TFR rates at 12 and 24 months were 70% and 66%, respectively. Children under 5 years had a TFR rate of 88.9%, compared to 61.8% in those over 5 years (p = 0.18). Eleven of the 13 patients who lost MMR did so within 6 months of discontinuation. The cumulative incidence of loss in MMR at 6, 12, and 24 months was 26.4%, 27%, and 33%, respectively. Ten out of 13 (76.9%) patients with discontinuation failure (DF) regained MMR within 3 (2-20) months of restarting imatinib. A significant correlation was found between higher T-regulatory cell levels at baseline and DF (p = 0.005). More than half patients showed improved bone mineral density after 2 years of TFR. Our findings suggest that high TFR rates can be attained in pCML, with added benefits for bone health. Less frequent molecular monitoring was not associated with adverse outcomes and there seems to be a role of the immune system in sustaining TFR. The study is registered in the Clinical Trials Registry-India (CTRI/2020/11/029199).

bone cancer

What are the factors contributing to symptomatic local recurrence in metastatic spinal cord compression after surgery?

Risk factors for local recurrence in patients with metastatic spinal cord compression (MSCC) has not been clearly investigated. So, the purpose of this study was to identify risk factors causing local recurrence following surgeries in patients with MSCC.

bone cancer

Classification of pediatric soft and bone sarcomas using DNA methylation-based profiling.

Pediatric sarcomas present heterogeneous morphology, genetics and clinical behavior posing a challenge for an accurate diagnosis. DNA methylation is an epigenetic modification that coordinates chromatin structure and regulates gene expression, determining cell type and function. DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) was applied to 122 pediatric sarcomas referred to a reference pediatric oncology hospital. The classifiers reported 88.5% of agreement between histopathological and molecular classification confirming the initial diagnosis of all osteosarcomas and Ewing sarcomas. The Ewing-like sarcomas were reclassified into sarcomas with BCOR or CIC alterations, later confirmed by orthogonal diagnostic techniques. Regarding the CNAs profile, osteosarcomas had several chromosomal gains and losses as well as chromothripsis, whereas Ewing sarcomas had few large events, such as amplifications of chromosomes 8 and 12. The molecular classification together with clinical and histopathological assessment could improve the diagnosis of pediatric sarcomas although there are limitations to deal with more rare classes. This study provides an increase in the number of sarcomas evaluated for DNA methylation profiling in the pediatric population.

bone cancer

Machine learning-based prediction model for brain metastasis in patients with extensive-stage small cell lung cancer.

Brain metastases (BMs) in extensive-stage small cell lung cancer (ES-SCLC) are often associated with poor survival rates and quality of life, making the timely identification of high-risk patients for BMs in ES-SCLC crucial. Patients diagnosed with ES-SCLC between 2010 and 2018 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. Four different machine learning (ML) algorithms were used to create prediction models for BMs in ES-SCLC patients. The accuracy, sensitivity, specificity, AUROC, and AUPRC were compared among these models and traditional logistic regression (LR). The random forest (RF) model demonstrated the best performance and was chosen for further analysis. The AUROC and AUPRC were calculated and compared. The findings from the RF model were utilized to identify the risk factors linked to BMs in patients diagnosed with ES-SCLC. Examining 4,716 instances of ES-SCLC, the research conducted an analysis, with brain metastases arising in 1,900 cases. Through evaluation of the ROC curve and PRC concerning the RF Model, results depicted an AUROC of 0.896 (95% CI: 0.889-0.899) and AUPRC of 0.900 (95% CI: 0.895-0.904). Test accuracy measured at 0.810 (95% CI: 0.784-0.833), sensitivity at 0.797 (95% CI: 0.756-0.841), and specificity at 0.819 (95% CI: 0.754-0.879). Based on the SHAP analysis of the RF predictive model, the top 10 most relevant features were identified and ranked in order of relative importance: bone metastasis, liver metastasis, radiation, age, tumor size, primary tumor location, N-stage, race, T-stage, and chemotherapy. The research developed and validated a predictive RF model using clinical and pathological data to predict the risk of BMs in patients with ES-SCLC. This model may assist physicians in making clinical decisions that could delay the onset of BMs and improve patient survival rates.

bone cancer

The diverse roles of neutrophils from protection to pathogenesis.

Neutrophil granulocytes are the most abundant leukocytes in the blood and constitute a critical arm of innate immunity. They are generated in the bone marrow, and under homeostatic conditions enter the bloodstream to patrol tissues and scout for potential pathogens that they quickly destroy through phagocytosis, intracellular degradation, release of granules and formation of extracellular traps. Thus, neutrophils are important effector cells involved in antibacterial defense. However, neutrophils can also be pathogenic. Emerging data suggest they have critical functions related to tissue repair and fibrosis. Moreover, similarly to other innate immune cells, neutrophil cell states are affected by their microenvironment. Notably, this includes tumors that co-opt neutrophils. Neutrophils can undergo transcriptional and epigenetic reprogramming, thus causing or modulating inflammation and injury. It is also possible that distinct neutrophil subsets are generated with designated functions in the bone marrow. Understanding neutrophil plasticity and alternative cell states will help resolve their contradictive roles. This Review summarizes the most recent key findings surrounding protective versus pathogenic functions of neutrophils; elaborating on phenotype-specific subsets of neutrophils and their involvement in homeostasis and disease.

bone cancer

Impact of microgravity and lunar gravity on murine skeletal and immune systems during space travel.

Long-duration spaceflight creates a variety of stresses due to the unique environment, which can lead to compromised functioning of the skeletal and immune systems. However, the mechanisms by which organisms respond to this stress remain unclear. The present study aimed to investigate the impact of three different gravitational loadings (microgravity, 1/6 g [lunar gravity], and 1 g) on the behavior, bone, thymus, and spleen of mice housed for 25-35 days in the International Space Station. The bone density reduction under microgravity was mostly recovered by 1 g but only partially recovered by 1/6 g. Both 1 g and 1/6 g suppressed microgravity-induced changes in some osteoblast and osteoclast marker gene expression. Thymus atrophy induced by microgravity was half recovered by both 1 g and 1/6 g, but gene expression changes were not fully recovered by 1/6 g. While no histological changes were observed due to low gravity, alterations in gene expression were noted in the spleen. We found that in bone and thymus, lunar gravity reduced microgravity-induced histological alterations and partially reversed gene expression changes. This study highlighted organ-specific variations in responsiveness to gravity, serving as an animal test for establishing a molecular-level gravity threshold for maintaining a healthy state during future spaceflight.

bone cancer

The novel developed and validated multiparametric MRI-based fusion radiomic and clinicoradiomic models predict the postoperative progression of primary skull base chordoma.

Local progression of primary skull base chordoma (PSBC) is a sign of treatment failure. Predicting the postoperative progression of PSBC can aid in the development of individualized treatment plans to improve patients' progression-free survival (PFS) after surgery. This study aimed to develop a multiparametric MRI-based fusion radiomic model (FRM) and clinicoradiomic model (CRM) via radiomic and clinical analysis and to explore their validity in predicting postoperative progression in PSBC patients before surgery. In this retrospective study, a total of 129 patients with PSBC from our institution, including 57 patients with progression, were enrolled and randomized to the training set (TS) or the validation set (VS) at a 2:1 ratio. Radiomic features were extracted and dimensionally reduced from 3.0 T/axial T2-weighted imaging (T2WI), T1-weighted imaging (T1WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) sequences for each patient, and the features were used for radiomic analysis. Univariate and multivariate Cox regression analyses were used to screen for key clinical factors. We constructed models on the basis of multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses were performed to evaluate the performance of the clinical model (CM), FRM and CRM. Through analysis, we found that blood supply was the only significantly different clinical factor in the CM. For the FRM, the area under the receiver operating characteristic curve (AUC) of the TS was 0.925, and the calibration curves were consistent across the TS. In the CRM, the AUC of the TS was 0.929, the calibration curve analysis was consistent for both the TS and the VS, and the DCA showed that the net benefit was greater at a threshold probability of > 0% for both the TS and the VS. Our proposed FRM can help clinicians better predict PSBC progression preoperatively, and the use of the CRM can lead to the development of more appropriate protocols to improve patients' PFS after surgery.

bone cancer

Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting.

Fibrinolysis influences the mobilization of hematopoietic stem cells from their bone marrow microenvironment (BMM). Here we show that activation of plasmin, a key fibrinolytic agent, by annexin A2 (ANXA2) distinctly impacts progression of BCR-ABL1

bone cancer

Restoring mobility: roles of percutaneous consolidation for pelvic ring bone lesions-a multicenter study.

This study aimed to assess the early functional rehabilitation outcomes following percutaneous consolidation for pelvic ring tumor lesions.

bone cancer

The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma.

Osteosarcoma, as the most common primary malignant bone tumor, has become one of the main causes of cancer-related deaths in adolescents and children. This study thus proposes new biomarkers for OS based on whole-transcriptome re-analysis and experimental confirmation.

bone cancer

Human and canine osteosarcoma cell lines: How do they react upon incubation with calcium phosphate-coated lipid nanoparticles carrying doxorubicin and curcumin?

Osteosarcoma (OSA) is a bone cancer that affects both humans and animals, with dogs being particularly vulnerable. Standard therapy is often limited by multidrug resistance (MDR), primarily due to the overexpression of P-glycoprotein (P-gp), which expels drugs from the cells, reducing their efficacy. To overcome this challenge, drug delivery systems (DDS) and P-gp modulators have been explored. However, developing DDS that selectively target cancer cells remains difficult, with many current options lacking efficiency. Our research group has recently developed an innovative type of nanoparticle with a lipid core and a calcium phosphate shell (CaP-NPs), which enhances the uptake of doxorubicin (DOXO) in OSA cells. In this study, we loaded a lipophilic ester of doxorubicin (C12DOXO) and curcumin (CURC), a natural P-gp modulator, into CaP-NPs and co-incubated them into human and canine OSA cell lines, including DOXO-resistant cells. The results demonstrated a significant reduction in viability in human OSA cells. Additionally, the combination treatment led to a further increase in C12DOXO retention when cells were also treated with the P-gp inhibitor verapamil, indicating enhanced efficacy against MDR mechanisms. Notably, canine OSA cells exhibited a distinct response pattern, suggesting the presence of species-specific differences that warrant further investigation.

bone cancer

Efficacy of radiotherapy for bone metastasis in breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors.

In patients diagnosed withestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, bone metastasesemerge as theprimary siteofsignificant tumor burden. Cyclin-dependent kinase 4/6 (CDK4/6i) inhibitorsare thegold standard in this clinical scenario, while radiotherapy (RT) represents a valuable addition. However, data on the efficacy of this combination remain scarce. We aimed to evaluate efficacy of RT in bone metastatic breast cancer patients treated with CDK4/6 inhibitors.

bone cancer

[Efficacy of Xihuang capsules as an adjuvant treatment for metastatic colorectal cancer and its impact on immune function].

Objective To investigate the efficacy and safety of Xihuang capsules as an adjuvant treatment for metastatic colorectal cancer and their impact on immune function. Methods A retrospective analysis was conducted on clinical data from 112 patients diagnosed with metastatic colorectal cancer. The patients were categorized into two groups: a control group (n=56) that did not take Xihuang capsules and an observation group (n=56) that did. The efficacy, improvement of quality of life, toxic and side effects and immune function of the two groups were analyzed and compared. Results After treatment, the disease control rate (DCR) and the rate of improvement in quality of life were significantly higher in the observation group compared to the control group. Additionally, levels of carcinoembryonic antigen (CEA) and the incidence of adverse reactions, including bone marrow suppression and liver and kidney function damage, were significantly lower in the observation group. Furthermore, the percentages of CD4

bone cancer

Ewing sarcoma of the thumb presenting in a Hispanic patient: A case report.

Ewing sarcoma (EwS) is an uncommon and highly aggressive cancer primarily affecting children and young adults. This tumor constitutes 10 % to 15 % of all bone sarcomas and often presents in the pelvis, axial skeleton, and femur. Despite its rarity, EwS's rapid progression and early metastatic potential make it a significant concern in pediatric oncology, highlighting the need for effective treatment protocols and further research.

bone cancer

Non-redundant roles of the CCR1 and CCR2 chemokine axes in monocyte recruitment during lung metastasis.

Monocytes and monocyte-derived macrophages facilitate cancer progression and metastasis. Inflammatory monocytes expressing CCR2 are actively recruited to metastatic lungs, where they promote tumor cell extravasation, metastatic outgrowth, and an immunosuppressive environment. The role of CCR1 in this process has remained unclear. We used Ccr1- and Ccr2-deficient mice and two different tumor cells lines, MC38 and LLC1 with and without Ccl2-deficiency in vitro and in vivo. The recruitment of both Ccr1- and Ccr2-deficient monocytes towards the Ccl2 chemokine was significantly impaired, while no substantial recruitment was observed towards Ccl5 in vitro. MC38 and LLC1 Ccl2-deficient tumor cells showed reduced lung metastasis in both Ccr1- and Ccr2-deficient mice when compared to wild-type mice. We detected reduced numbers of macrophages and myeloid cells in both chemokine receptor-deficient mice. Lung metastasis in both Ccr1- and Ccr2-deficient mice could be rescued to the same levels as in wild-type mice by an adoptive transfer of Ccr2-deficient but not Ccr1-deficient monocytic cells. Accumulation of Ccr1-deficient monocytes in the lungs was severely impaired upon intravenous monocyte injection, indicating the importance of this axis in cell recruitment. Moreover, the efficient recruitment of adoptive transferred Ccr2-deficient monocytes to the lungs and the restoration of lung metastasis suggests an involvement of an additional, Ccr2-independent chemokine pathway. This data defines the non-redundant functions of the Ccr1- and Ccr2-chemokine axes in monocyte recruitment and macrophage presence during lung metastasis. While Ccr2 is essential for the release of monocytes from the bone marrow, Ccr1 is primarily responsible for monocyte presence at metastatic sites.

bone cancer

Thrombopoietic agents enhance bone healing in mice, rats, and pigs.

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, has renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte growth factor, thrombopoietin (TPO) and second generation TPO agents using multiple animal models including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (e.g., thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells.

bone cancer

Oral Myeloid Sarcoma as a Marker of Relapse in Acute Myeloid Leukemia.

A 20-year-old woman with acute myeloid leukemia (AML) with monocytic differentiation in remission presented with a recent onset painful indurated swelling on the tongue with fever. Although her peripheral blood picture was normal, the bone marrow biopsy was suggestive of a relapse of AML. A biopsy from the tongue lesion showed diffuse infiltration of lamina propria and submucosa by blast cells, positive for myeloperoxidase and CD11c and suggestive of oral myeloid sarcoma (MS). This presents an uncommon site of occurrence of MS and was a marker of relapse of AML. This case highlights the variable presentation of MS. It should prompt investigation for relapse of hematological malignancy in the bone marrow even in the absence of evidence from peripheral blood.

bone cancer

Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone.

The purpose of this study is to demonstrate the consistency and reproducibility of quantitative SPECT/CT by evaluating the maximum SUV (SUV

bone cancer

Conventional (bone-type) giant cell tumor of the larynx: the first case with proven H3-3A: c.103G >T (p.Gly35Trp) mutation.

This report documents the first case of a conventional (bone-type) giant cell tumor of the larynx, in which the diagnosis was confirmed by molecular genetic analysis. A 50-year-old non-smoking man experienced progressive hoarseness lasting for 3 months. Imaging showed a 40-mm tumor arising from the right thyroid cartilage. The total laryngectomy was performed. Grossly, the tumor was solid and whitish, with areas of hemorrhage. Microscopically, the tumor consisted of a biphasic population with mononuclear cells with round to oval nuclei, small nucleoli, and pale eosinophilic cytoplasm admixed with evenly distributed dispersed osteoclast-like giant cells. Immunohistochemically, the neoplastic mononuclear cells expressed diffusely vimentin and p63 and focally SATB2. Admixed mononuclear histiocytes coexpressed CD68 and CD163, while the osteoclast-like giant cells showed only CD68 expression. Most importantly, all mononuclear tumor cells showed strong nuclear expression of anti-histone H3.3 G34W antibody. Subsequent next-generation sequencing confirmed the missense mutation of gene H3-3A: c.103G>T (p.Gly35Trp).

bone cancer

Severe toxicity, but long-term persistence of CAR T cells after immune checkpoint inhibitors in large B-cell lymphoma.

No abstract found

bone cancer

Identification of the Novel HLA-DPA1*01:214 Allele in a Brazilian Bone Marrow Donor.

A single nucleotide polymorphism, changing Phenylalanine to Leucine, differentiates HLA-DPA1*01:214 from HLA-DPA1*01:03:01:01.

bone cancer

Different impacts of granulocyte colony-stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type.

We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II-IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5-10), early initiation (Days 0-4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II-IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II-IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML.

bone cancer

A Comprehensive Clinico-Pathological Analysis of Osseous Neoplasms: An Observational Study in a Tertiary Care Facility.

Bone neoplasms represent a diverse group of malignancies that significantly impact morbidity and mortality. These tumors primarily affect the appendicular skeleton and, while less common than other malignancies, are particularly notable due to their prevalence in adolescents and young adults. Given their potential for rapid growth and high metastatic potential, these neoplasms can be life-threatening. This study aims to explore the relative frequencies, age, and sex distributions, as well as the anatomical and clinico-pathological characteristics of bone tumors in a tertiary care hospital.

bone cancer

Challenges and practical considerations in the management of blastic plasmacytoid dendritic cell neoplasm: A single-center experience.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and often life-threatening complex hematologic malignancy that can commonly infiltrate the skin, lymph nodes, central nervous system, and bone marrow. In the setting of the infrequency of confirmed diagnoses of BPDCN, and given limited prospective studies, it has been associated with lackluster outcomes with a median overall survival between 9 and 23 months. We herein discuss our experience treating five consecutive patients with BPDCN at our center since the approval of TAG. We also present some of the challenges that face oncology providers treating this disease due to exceptional rarity and aggressive nature of this disease in addition to overall limited experience and effective therapies.

bone cancer

Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer.

Acquired resistance to hormonal therapy, particularly enzalutamide (ENZ), remains a significant obstacle in the treatment of advanced bone metastatic prostate cancer. Here, it is demonstrated that under ENZ treatment, osteoblasts in the bone microenvironment secrete increased levels of extracellular matrix protein 1 (ECM1), which affects surrounding prostate cancer cells, promoting tumor cell proliferation and anti-androgen resistance. Mechanistically, ECM1 interacts with the enolase 1 (ENO1) receptor on the prostate cancer cell membrane, leading to its phosphorylation at the Y189 site. This event further recruits adapter proteins including growth factor receptor-bound protein 2 (GRB2) and son of sevenless homolog 1 (SOS1), which activates the downstream mitogen-activated protein kinase (MAPK) signaling pathway to induce anti-androgen resistance. Furthermore, inhibiting ECM1 or utilizing the ENO1-targeting inhibitor phosphonoacetohydroxamate (PhAH) significantly restores tumor cell sensitivity to ENZ. Taken together, a potential mechanism is identified through which osteoblast-derived ECM1 drives resistance in bone metastatic prostate cancer under ENZ treatment. Additionally, the findings indicate that ECM1 and ENO1 may serve as potential targets for developing therapies for bone metastatic castration-resistant prostate cancer.

bone cancer

Periodontitis and dental quality of life predict long-term survival in head and neck cancer.

Our aim was to investigate oral health in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients in relation to long-term survival. We assessed whether the level of alveolar bone loss due to periodontitis at diagnosis, measured from orthopantomogram (OPG), and reported dental health-related quality of life (HRQoL) scores obtained at diagnosis contain prognostic information for HNSCC patients.

bone cancer

Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study.

In patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) or B-non-Hodgkin's lymphoma (B-NHL) relapsing after allogeneic stem cell transplantation (allo-HCT), it is a standard practice to perform anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. When collected from the patient after allo-HCT, the produced CAR-T cells are likely to be donor T-cell-derived, creating unknown safety risks due to their potential allo-reactivity. We therefore performed an EBMT registry-based study on the incidence of graft-versus-host disease (GvHD) in this setting. We included 257 allo-HCT patients (n = 172 ≥ 18 years) with B-ALL or B-NHL, treated with anti-CD19 CAR T-cells (tisagenlecleucel n = 184, brexucabtagene autoleucel n = 43 and axicabtagene ciloleucel n = 30), between 2018 and 2022. Three patients developed aGvHD, whereas 6 patients developed cGvHD after CAR T-cell. The 100-day cumulative incidence (CI) of new aGvHD was 1.6% and the 12-month CI of new cGvHD was 2.8%. The 1-year GvHD relapse-free survival and non-relapse mortality were 52.1% and 4.7%, respectively. Last, with a median follow up of 18.8 months, the 1-year overall survival was 76.8%. In summary, the GvHD rate in allo-HCT patients treated with CAR T-cell therapy is relatively low. Our data support the view that GvHD is not a major safety issue in this setting.

bone cancer

Polycomb group protein Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of self-renewal and proliferation genes.

Polycomb group (PcG) proteins play important roles in hematopoietic stem cell (HSC) self-renewal. Mel18 and Bmi1 are homologs of the PCGF subunit within the Polycomb repressive complex 1 (PRC1). Bmi1 (PCGF4) enhances HSC self-renewal and promotes terminal differentiation. However, the role of Mel18 (PCGF2) in hematopoiesis is not fully understood and how Mel18 regulates gene transcription in HSCs remains elusive. We found that acute deletion of Mel18 in the hematopoietic compartment significantly increased the frequency of functional HSCs in the bone marrow. Furthermore, we demonstrate that Mel18 inhibits HSC self-renewal and proliferation. RNA-seq studies revealed that HSC self-renewal and proliferation gene signatures are enriched in Mel18

bone cancer

Measurable residual disease testing and allogeneic hematopoietic cell transplantation for AML: adapting Pre-MEASURE to clinical practice.

Measurable residual disease (MRD) testing in patients with acute myelogenous leukemia (AML) represents a heterogenous assessment process designed to quantify leukemia-specific biomarkers that are not ascertainable by routine pathologic evaluation. The most common tools used to assess MRD are multiparameter flow cytometry (MPFC), and polymerase chain reaction (PCR) based tools, including quantitative or digital droplet PCR (qPCR, ddPCR), or next-generation sequencing (NGS) technologies. Collectively, MRD assessments have become an important clinical tool in the management of patients with AML. Despite progress, significant questions remain with respect to the appropriate timing, frequency, and methodology of MRD assessment, and whether or how to adapt therapy based on MRD results. Recent data from the Pre-MEASURE study, a retrospective cohort analysis of error corrected NGS based MRD assessment prior to allogeneic hematopoietic cell transplantation (alloHCT) in patients with AML, provides additional key information with respect to the emerging role of NGS-based technology in MRD assessment. In the context of this review, we evaluate the Pre-MEASURE study as well as other recent, high-quality assessments of MRD in AML. Our focus is to provide a practical assessment of the use of emerging MRD technologies in patients with AML with an emphasis on the role of peri-transplant MRD for the practicing clinician.

bone cancer

Prognostic significance of mutation type and chromosome fragility in Fanconi anemia.

Fanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, and extreme chromosome fragility. To better understand the natural history of FA, identify genetic risk and prognostic factors, and develop novel therapeutic strategies, the Spanish Registry of Patients with FA collects data on clinical features, chromosome fragility, genetic subtypes, and DNA sequencing with informed consent of participating individuals. In this article, we describe the clinical evolution of 227 patients followed up for up to 30 years, for whom our data indicate a cumulative cancer incidence of 86% by age 50. We found that patients with lower chromosome fragility had a milder malformation spectrum and better outcomes in terms of later-onset hematologic impairment, less severe bone marrow failure, and lower cancer risk. We also found that outcomes were better for patients with mutations leading to mutant FANCA protein expression (genetic hypomorphism) than for patients lacking this protein. Likewise, prognosis was consistently better for patients with biallelic mutations in FANCD2 (mainly hypomorphic mutations) than for patients with biallelic mutations in FANCA and FANCG, with the lack of the mutant protein in patients with biallelic mutations in FANCG contributing to their poorer outcomes. Our results regarding the clinical impact of chromosome fragility and genetic hypomorphism suggest that mutant FA proteins retain residual activity. This finding should encourage the development of novel therapeutic strategies aimed at partially or fully enhancing mutant FA function, thereby preventing or delaying bone marrow failure and cancer in patients with FA. Clinical Trial Registration number: NCT06490510.

bone cancer

Interventional Radiology Management of Bone Metastasis Pain: Strategies and Techniques.

Osseous metastases are common in cancer patients, and pain is one of the most frequent associated symptoms. The management of cancer-related pain is still problematic worldwide with 40 to 50% of patients still being undertreated. A significant proportion of cancer patients will require discontinuation of traditional analgesic treatments such as opioids due to unsuccessful pain relief or severe unmanageable toxicity and may, therefore, benefit from alternative treatments. Over the last few decades, several interventional radiology (IR) minimally invasive treatment options have been introduced into the cancer pain management toolbox and can be proposed to cancer patients. This article reviews the main IR treatment options for painful bone metastases which include vertebral augmentation, percutaneous osteosynthesis, tumoral ablation, electrochemotherapy, intra-arterial therapies, and percutaneous neurolysis.

bone cancer

Analysis of cancer multigene panel testing for osteosarcoma in pediatric and adults using the center for cancer genomics and advanced therapeutics database in Japan.

Osteosarcoma (OS) is the most common primary malignant bone tumor. Despite advances in multimodal chemotherapy, prognosis for metastatic or recurrent OS remains poor. Next-generation sequencing (NGS) can uncover new therapeutic options by identifying potentially targetable alterations. This study analyzed NGS data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan, comparing findings with the Memorial Sloan-Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) data from the United States.

bone cancer

Proximal Femoral Intraosseous Schwannoma.

Intraosseous schwannoma is a rare benign nerve sheath tumor comprising < 1% of bone tumors. Relatively common locations for this tumor include the skull and mandible, and, to a lesser degree, the spine and sacrum. Intraosseous schwannoma involving the appendicular skeleton is exceedingly rare. The clinical and imaging presentation, as in this case, is nonspecific and includes pain in the setting of a lytic bone lesion. The first step in management is bone biopsy that often produces greater than expected pain. Definitive management is surgical.

bone cancer

Differential Effector Function of Tissue-Specific Natural Killer Cells Against Lung Tumors.

Natural killer (NK) cells are innate lymphoid cells capable of directly killing target cells while modulating immune effector responses. Despite their multifunctional capacities, a limited understanding of their plasticity and heterogeneity has impeded progress in developing effective NK cell-based cancer therapies. In this study, we investigated NK cell tissue heterogeneity in relation to their phenotype and effector functions against lung tumors.

bone cancer

Role of molecular alterations in transplantation decisions for patients with primary myelofibrosis.

The aim of our study was to analyze the potential survival benefit associated with HSCT according to clinico-biological scores which incorporate molecular data (MIPSS70 and MIPSS70+V2) to facilitate decision-making in this context. One transplant (n=241) and one non-transplant cohorts (n=239) were used to test the hypothesis that PMF patients with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference. Weighted Cox proportional hazard models and logistic regression analyses were performed. 105 non-transplanted patients could be matched to the 239 transplanted patients. Mean age in transplanted and non-transplanted matched patients was 55.5 and 57.9 years. Blood cell count and DIPSS score distribution were similar in both groups. HSCT was associated with a higher 6-year OS rate in intermediate-2 (60.1% versus 41.5%) and high-risk DIPSS patients (44.4% versus 6.55%), high-risk MIPSS70 (46.5 versus 23.9%), high-risk (73.2% versus 39.7%) or very high-risk MIPSS70V2 (51.8% versus 24%). Intermediate MIPSS70 patients have an advantage of survival with HSCT only when their MTSS were low or intermediate. Transplanted patients had an increased mortality risk the first year but a significant benefit with HSCT after the one-year landmark was observed in higher risk patients. This study confirms that similar to DIPSS, MIPSS70 and MIPSS70+V2 risk score in addition to MTSS can be used to determine which patients with primary myelofibrosis have survival benefit from HSCT over non-HSCT strategies.

bone cancer

Bivalent CD47 Immunotoxin for Targeted Therapy of T-Cell Acute Lymphoblastic Leukemia.

CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin-based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique diphtheria toxin-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in vivo efficacy in multiple T-ALL cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Bi-CD47-IT significantly prolonged the median survival of the tumor-bearing mice and highly effectively depleted the T-ALL blast cells in the peripheral blood, spleen, liver, bone marrow, brain, and spinal cord in the T-ALL CDX and PDX mouse models. Bi-CD47-IT cured 60% of tumor-bearing mice in a T-ALL Molt-4 CDX mouse model. Because CD47 is also expressed on normal tissues, including red blood cells and lymphocytes, specificity is a concern. We thus analyzed the in vitro binding avidity and hemagglutination of bi-CD47-IT in human red blood cells, finding no binding or hemagglutination. We further performed a toxicity study of bi-CD47-IT in humanized mice, which showed that bi-CD47-IT transiently depleted the human lymphocytes for ~4 weeks after the 10-day treatment. No clinical adverse events were observed. As a result, bi-CD47-IT appears to possess the "optimal" binding avidity, with effective binding to human CD47+ T-ALL tumor cells, no binding to human red blood cells and weak binding to human lymphocytes. We believe that bi-CD47-IT is a promising and safe therapeutic drug candidate for the targeted therapy of CD47+ cancers.

bone cancer

Development of ALL-Hematotox (ALL-HT): Predicting post CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia.

Immune effector cell-associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. While ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia (>14 days of ANC <500/µl), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC <500/µl) was 13 days (95% CI 10-16), with 83 (53%) experiencing grade >3 ICAHT. Applying CAR-HT, nearly 90% were classified as high-risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and post-infusion neutropenia (r=0.64, p<0.0001), we developed the ALL-Hematotox (ALL-HT) score which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve=0.84, p<0.0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days, p<0.0001), fewer rates of complete response (88% vs 98%, p=0.03), and shorter median overall survival (9.8 vs 24 months, logrank p=0.0002). ALL-HT was also validated in two independent cohorts. The ALL-HT score refines a widely accepted predictive model of post-infusion hematotoxicity, applicable in B-ALL.

bone cancer

An Unusual Histopathological Presentation of Mandibular Osteosarcoma.

Jaw osteosarcoma (JOS) is a rare, distinct variant that differ from long bone osteosarcoma (LBOS) in several aspects. JOS typically appears about twenty years later than LBOS, displays a lower propensity for metastasis to other organs, and exhibits better survival rates. The dissimilarities in clinical and biological behavior between JOS and LBOS are likely due, at least in part, to variations in their respective microenvironments. In this report, we present a case of OS affecting the mandible in a young patient. This case displayed classic radiographic features but a unique histopathological presentation, posing a diagnostic challenge for pathologists, especially if encountered in small biopsies.

bone cancer

Acquired hypophosphatemic osteomalacia: case series from a Peruvian referral center (1999-2023).

Acquired hypophosphatemic osteomalacia (AHO) is a rare metabolic bone disorder characterized by hypophosphatemia and impaired bone mineralization. Tumor-induced osteomalacia (TIO) is the most common cause of AHO, caused by phosphaturic tumors that overproduce fibroblast growth factor 23 (FGF-23).

bone cancer

Impact of cytotoxic therapy on clonal hematopoiesis and myeloid neoplasms in breast cancer patients.

Clonal hematopoiesis (CH), which is characterized by variants of hematopoietic stem cells, increases the risk of subsequent myeloid neoplasms (MNs). This study aimed to investigate the prevalence and characteristics of CH variants in breast cancer (BC) patients treated with cytotoxic therapy (CT), focusing on those who developed MNs after cytotoxic therapy (MN-pCT). We retrospectively analyzed 107 BC patients from a biobank and sequenced peripheral blood and bone marrow samples from 31 CH-associated genes at 2 time points. We analyzed changes in CH for paired samples: T0 to T1 (before and after CT) and T1 to T2 (after CT vs greater CT exposure). Additionally, we compared CH variants in patients with and without MN-pCT. 29% of patients harbored CH variants that were restricted to 8 genes and DNMT3A was the most frequent variant. Among 54 patients with paired samples (T1 to T2), the variant allele frequency (VAF) of CH variants significantly increased after greater CT exposure (P = .02). However, there were no significant changes in VAF before and after CT. Five of the 9 patients who developed MN-pCT harbored CH variants. TP53 was the most frequently mutated gene, but it did not significantly affect MN-pCT risk compared to patients without CH variants. Although the presence of CH did not directly predict MN-pCT development in patients with BC, CT induced changes in CH genes. Further studies are required to determine the role of specific CH variants in the risk of MN-pCT and their potential as predictive biomarkers.

bone cancer

The causal relationship between gut microbiota and 2 neoplasms, malignant and benign neoplasms of bone and articular cartilage: A two-sample Mendelian randomization study.

Previous research has demonstrated a close connection between the development of bone neoplasms and variations in the abundance of specific gut microbiota. It remains unclear, however, how the gut microbiota and bone neoplasms are causally related. Hence, in our study, we aim to clarify this relationship between gut microbiota and 2 neoplasms, malignant neoplasm of bone and articular cartilage (MNBAC) and benign neoplasm of bone and articular cartilage (BNBAC), by employing a two-sample Mendelian randomization (MR) approach. In this study, single nucleotide polymorphisms (SNPs) from genome-wide association studies-pooled data related to bone neoplasms and gut microbiota abundance were evaluated. The inverse variance weighted was employed as the major method for assessing the aforementioned causal relationship. Furthermore, the horizontal multiplicity was evaluated utilizing the Mendelian randomization pleiotropy residual sum and outlier and the MR-Egger intercept test. Finally, inverse MR analysis was performed to assess reverse causality. Inverse variance weighted results indicate a potential genetic relationship between 4 gut microbiota and MNBAC, and 3 gut microbiota and BNBAC. On the one hand, Eubacterium eligens group (OR = 0.16, 95% CI = 0.04-0.67, P = .01), Odoribacter (OR = 0.23, 95% CI = 0.06-0.84, P = .03), Slackia (OR = 0.35, 95% CI = 0.13-0.93, P = .04), and Tyzzerella3 (OR = 0.44, 95% CI = 0.24-0.82, P = .01) exhibited a protective effect against MNBAC. On the other hand, of the 3 gut microbes identified as potentially causally related to BNBAC, Oscillibacter (OR = 0.79, 95% CI = 0.63-0.98, P = .03) and Ruminococcus torques group (OR = 0.62, 95% CI = 0.39-0.98, P = .04) were regarded as protective strains of B, while Eubacterium ruminantium group (OR = 1.24, 95% CI = 1.04-1.47, P = .02) was considered to be a risk factor for increasing the incidence of BNBAC. Additionally, the bone neoplasms were not found to have a reverse causal relationship with the above 7 gut microbiota taxa. Four gut microbiota showed causal effects on MNBAC, and 3 gut microbiota demonstrated causality in BNBAC, providing insights into the design of future interventions to reduce the burden of neoplasms.

bone cancer

Bioinformatics-based screening of hub genes for prostate cancer bone metastasis and analysis of immune infiltration.

Bioinformatics analysis of genes and immune cells that influence prostate cancer (PCa) bone metastases. Using the gene expression omnibus database, we analyzed a PCa bone metastasis dataset. Differentially expressed genes were identified through the utilization of GEO2R and weighted gene co-expression network analysis. Gene set enrichment analysis software was used to identify important pathways. In addition to creating a network of protein-protein interactions, functional enrichment analyses were conducted using Kyoto encyclopedia of genes databases. To screen hub genes, Cytoscape software was used with the CytoHubba plug-in and performed mRNA and survival curve validation analysis of key genes using the cBioPortal website and GEPIA2 database. Immune infiltration analysis was performed using the CIBERSORTx website, and finally, immune cell correlation analysis was performed for key genes according to the TIMER database. A total of 197 PCa bone metastasis risk genes were screened, "G2M_CHECKPOINT" was significantly enriched in PCa bone metastasis samples according to genomic enrichment analysis. Based on the protein interactions network, we have identified 10 alternative hub genes, and 3 hub genes, CCNA2, NUSAP1, and PBK, were validated by the cBioPortal website and the GEPIA2 database. T cells regulatory and macrophages M0 may influence PCa to metastasize to bones, according to CIBERSORTx immune cell infiltration analysis. TIMER database analysis found different degrees of correlation between 3 key genes and major immune cells. PCa bone metastasis has been associated with CCNA2, NUSAP1, and PBK. T cells regulatory and macrophages (M0) may also be involved.

bone cancer

Secondary Osteosarcoma After Carbon-Ion Radiotherapy for Desmoid-Type Fibromatosis: A Case Report.

Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid-type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern.

bone cancer

Basic Techniques and Technical Tips for Ultrasound-guided Needle Puncture.

Ultrasound-guided needle puncture is essential for both vascular and nonvascular interventions. Ultrasound is widely available in various clinical settings, requires no ionizing radiation, offers color Doppler imaging, and enables real-time visualization of the needle position during puncture. However, ultrasound imaging has some limitations, such as signal attenuation in deeper tissues and the inability to penetrate bone or air, and it is a heavily operator-dependent modality. Here, we outline the basic techniques and technical tips for ultrasound-guided needle puncture.

bone cancer

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report of a Rare and Aggressive Hematologic Malignancy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a strikingly unusual, clinically challenging, and rapidly spreading tumor that originates from plasmacytoid dendritic cell (PDC) precursors. It has a high incidence of skin and bone marrow involvement as well as leukemic dissemination. It shows a considerable biologic diversity with overlapping morphologic and immunophenotypic features of various cutaneous hematolymphoid neoplasms. Studies with large series of patients are not available due to low prevalence and short survival of the disease. We report here a rare case of BPDCN in a 30-year-old male patient who primarily came with skin manifestations almost all over the body surface. Skin biopsy revealed monomorphic medium-sized undifferentiated blast-like cells filling the entire dermis sparing the epidermis. The cells were immunopositive for CD45, CD56, CD4, and CD123 with a high Ki-67 labeling index while they were negative for known B-cell and T-cell markers. Radiological evaluation revealed lymphadenopathy at various sites. Peripheral blood smears and bone marrow aspiration smears demonstrated similar blast-like cells. Misdiagnosis or late diagnosis of this clinically heterogeneous BPDCN may lead to systemic spread and poor outcomes. Hence, prompt diagnosis and treatment are essential, with a multidisciplinary approach.

bone cancer

Clinical decision-making in bone cancer care management and forecast of ICU needs based on computed tomography.

This study aimed to evaluate the role of computed tomography (CT) imaging in the diagnosis and management of bone cancer during periods of limited access to histopathological testing. We aimed to determine the correlation between CT severity levels and subsequent patient management and care decisions, adhering to established oncological CT reporting guidelines.

bone cancer

Cisplatin intra-arterial chemotherapy for recurrent maxillary gingival cancer and metastatic lymph nodes without radiation or surgery: A case report.

Most patients with head and neck cancers struggle with their treatment, particularly those with recurrent cancer. However, there is no consensus on effective treatments for recurrent head and neck cancer. Recurrent cases are often challenging to treat because performing both reirradiation and surgical intervention can occasionally be difficult. This report describes the effective cisplatin intra-arterial chemotherapy with oral S-1 for a recurrent case of maxillary gingival cancer (rT4bN1M0, rStage ⅣB). The patient who had undergone chemoradiotherapy 13 years ago and achieved complete response (CR) was referred to us due to recurrence. His recurrent lesions were located on the left maxillary bone, and a metastatic cervical lymph node was detected. We approached the feeder of the locoregional recurrence site using Seldinger's technique and repeated the cisplatin intra-arterial chemotherapy 5 times. As a result, we achieved a complete response, including

bone cancer

Marginal Mandibulectomy in Oral Cavity SCC: Experience in a Tertiary Care Centre.

Marginal mandibulectomy is indicated for oral cavity squamous cell carcinomas that involve floor of mouth, abut or minimally erode the mandible without gross invasion. Successful outcomes after Marginal mandibulectomy is predicated on accurate patient selection and appropriate adjuvant treatment based on specific host and tumor characteristics. To study the onclogical outcomes in terms of loco-regional recurrence free survival and disease specific survival of marginal mandibulectomy done for oral squamous cell carcinomas. Study Design-Retrospective study. Setting-The study was done from January 2018 to January 2021 at our tertiary care centre Madras Medical College, Chennai. Subjects-30 cases were included in our study who underwent Marginal Mandibulectomy for oral cavity SCC. Methods-The decision to perform a marginal mandibulectomy was taken based on preoperative clinical examination, contrast enhanced computed tomography (CECT) findings and intra-operative assessment under anesthesia. Disease-free survival, cause-specific survival, and local control rates were plotted using the Kaplan-Meier method. Oncologic outcomes in terms of Overall survival and Disease-specific survival at the end of 1 year and 3 years for the gingival, buccal, tongue, floor of mouth cancers were analyzed. Independent impacts including the site of tumor, T and N stage, microscopic bony invasion, grade of differentiation, adjuvant radiotherapy on the loco-regional control and cause-specific survival were evaluated using Kaplan meier method. Our study group was comprised of 20(66.67%) males and 10 (33.33%) females of mean age 54 years. None of them had prior radiotherapy to the head and neck region. A total of 7 (23.33%) marginal mandibulectomies were carried out for SCC in the gingival region, 11(36.67%) for buccal mucosa, 8(26.67%) for tongue, 2(6.67%) for floor of mouth SCC, 1(3.33%) involving lip, 1(3.33%) in Retromolar trigone. Clinically 2 (6.67%) patients had T1 cancer, 18 (54.54%) had T2, 6 (18.18%) had T3, 4(13.33%) had T4 tumor. Clinically Neck nodes were not palpable in 17 (56.67%) patients, 10 (33.33%) had N1 disease and 3 (10%) had N2 disease. T and N stage distributions for tongue/floor of mouth and gingival buccal complex cancers are summarized in the table and there were no statistically significant differences between the 2 groups. 19 (63.33%) had selective neck dissection (levels I-III), and 11 (36.67%) had comprehensive neck dissection. Well-differentiated tumors were encountered in 12 (40%) cases, moderately differentiated tumors in 16 (53.33%) cases, and poorly differentiated tumors in 2 (6.67%) cases. Bone was microscopically involved in 4 (13.33%) cases and mucosal margin of excision was less than 5 mm from the tumor in 2 (6.67%) cases. Cumulative hazard of local recurrence was not significantly affected by mandibular involvement. On histopathologic examination, positive nodes were seen in 6(20%) cases that included 3 (10%) with pN1 and the rest with pN2 disease. Adjuvant radiotherapy (56 to 64 Gy) was given to 13 (43.33%) patients. In carefully selected patients, marginal mandibulectomy in oral squamous cancer achieves good oncological outcome in terms of locoregional control and overall survival rates.

bone cancer

Liposarcoma of Maxilla- A Rare Case Report.

Sarcomas of the head and neck region account for less than 10% of soft tissue sarcomas, and comprise less than 1% of head and neck malignancies. Approximately 80% of sarcomas arise from soft tissue, with the remaining originating from bone or cartilage. Head and neck sarcomas typically occur more frequently in men.

bone cancer

Use of Pectoralis Major Myocutaneous Flap for Marginal Mandibulectomy Defects of Oral Cavity Cancers - A 5 Year Institutional Experience.

Segmental resections of the mandible may cause severe functional and aesthetic problems due to continuity loss. The morbidity after mandibular resection can be minimized after microvascular transfer of vascularized bone grafts. Although free flaps have become the gold standard in the past decades for reconstruction of oral cavity defects, regional flaps can also be a reliable option in certain cases, especially for those belonging to the lower socioeconomic corridor and or with coexisting chronic comorbidities which will not allow lengthier procedures. (Milenović A, Virag M, Uglešić V, Aljinović-Ratković N (2006) The pectoralis major flap in head and neck reconstruction: first 500 patients. J Cranio-Maxillofacial Surg 34(6):340-343); (Sabri A (2003) Oropharyngeal reconstruction: current state of the art. Current opinion in otolaryngology & head and neck surgery. 11(4):251-254); (Porcuna DV, Vintró XL, Vilas ML, Olmo AP, Ayala JM, Agustí MQ (2008) Pectoralis major flaps. Evolution of their use in the age of microvascularized flaps. Acta Otorrinolaringologica (English Edition) 59(6):263-268) There are a very few reports of early oral cancers being reconstructed by PMMC flap. In this article, however, we have exclusively reviewed 247 cases of early oral cancer requiring marginal mandibulectomy and their reconstruction with PMMC flap thus justifying the name, the "workhorse flap" even in early oral cancers. This is a retrospective analysis of 5-year patient data collected from our institutional data register of 247 patients undergoing marginal mandibulectomy and reconstruction with PMMC flap between April 2017 to June 2022. No flap loss was reported. No cases were re-explored either for hematoma or for congestion. All patients recovered uneventfully. Although, in this era, free flaps dominate in the soft tissue reconstruction and PMMC is used only in certain advanced oral cancers, our study proves that it can be used safely in effectively in early oral cancer patients as well. Being a quicker procedure, PMMC flap reconstruction should be considered as a valid alternative in early oral cancers requiring marginal mandibulectomy, to overcome the increasing oral malignancy patient load belonging to low socioeconomic regions. To the best of our knowledge, this is the largest data ever published.

bone cancer

Case report: A rare case of breast and multiorgan metastases secondary to papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is generally considered a highly indolent endocrine malignancy, often accompanied by cervical lymph node metastasis and rarely involving distant metastases. We present a rare case of a 37-year-old woman with PTC, who exhibited regional lymph node metastasis, right breast metastasis, and probable right psoas major and multiple bone metastases. Initial symptoms included hoarseness, and subsequent examination revealed a secondary malignant tumor in the right breast, originating from the thyroid gland. This case highlights an unusual pattern of multiple systemic metastasis in PTC, particularly the rare occurrence of breast metastasis.

bone cancer

Artificial intelligence in cytopathological applications for cancer: a review of accuracy and analytic validity.

Cytopathological examination serves as a tool for diagnosing solid tumors and hematologic malignancies. Artificial intelligence (AI)-assisted methods have been widely discussed in the literature for increasing sensitivity, specificity and accuracy in the diagnosis of cytopathological clinical samples. Many of these tools are also used in clinical practice. There is a growing body of literature describing the role of AI in clinical settings, particularly in improving diagnostic accuracy and providing predictive and prognostic insights.

bone cancer

Chondroblastoma of the femoral head: curettage without dislocation.

Chondroblastoma (CBL) of the femoral head is a rare disease, typically encountered in the epiphysis of long bones, with its occurrence in the femoral head being particularly uncommon. The unique location and aggressive nature of this tumor pose substantial challenges in its treatment, leading to ongoing controversies regarding the therapeutic approaches. In this study, we introduce a technique of curettage without surgical dislocation as a treatment option for CBL in this challenging location.

bone cancer

Early clinical efficacy of 3D-printed artificial vertebral body in spinal reconstruction after total en bloc spondylectomy for spinal tumors.

Total en bloc spondylectomy (TES) is a recognized surgical approach for managing spinal tumors. With advancements in three-dimensional (3D) printing technology, the use of 3D-printed prosthetics for vertebral reconstruction post-tumor resection has gained traction. However, research on the clinical implications of these prosthetics remains limited.

bone cancer

Integrated single-cell analysis reveals distinct epigenetic-regulated cancer cell states and a heterogeneity-guided core signature in tamoxifen-resistant breast cancer.

Inter- and intra-tumor heterogeneity is considered a significant factor contributing to the development of endocrine resistance in breast cancer. Recent advances in single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) allow us to explore inter- and intra-tumor heterogeneity at single-cell resolution. However, such integrated single-cell analysis has not yet been demonstrated to characterize the transcriptome and chromatin accessibility in breast cancer endocrine resistance.

bone cancer

The role of allogeneic stem cell transplantation in acute myeloid leukemia with translocation t(8;16)(p11;p13).

Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) represents a rare entity that has been categorized as a disease-defining recurring cytogenetic abnormality with adverse risk in the 2022 European LeukemiaNet classification. This rating was mainly based on a retrospective analysis comprising patients from several large clinical trials, which, however, included only 21 patients treated with allogeneic stem cell transplantation (alloSCT). Therefore, the European Society for Blood and Marrow Transplantation performed a registry study on a larger cohort to evaluate the role of alloSCT in t(8;16) AML. Sixty transplant recipients with t(8;16) AML were identified. Two-year overall and leukemia-free survival (OS/LFS) was 43/39%. Patients transplanted in first complete remission (CR1, n = 44) achieved a 2-year OS/LFS of 48%/48%. Following alloSCT in CR1, the multivariable analysis identified a complex karyotype (CK) as a major risk factor for relapse (HR 4.17, p = .016), lower LFS (HR 3.38, p = .01), and lower OS (HR 3.08, p = .017). Two-year OS/LFS of patients with CK was 19%/19%, in contrast to 67%/67% in patients with t(8;16) outside a CK. Other factors for inferior outcomes were older age and secondary AML. In summary, alloSCT could mitigate the adverse risk of patients with t(8;16) AML not harboring a CK, particularly when performed in CR1.