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Background: Breast cancer remains the most prevalent malignancy and the leading cause of cancer-related mortality among women worldwide. The primary factors contributing to the deterioration and death of patients with breast cancer are metastasis, recurrence, and drug resistance. These phenomena are closely related to the presence of breast cancer stem cells; however, the exact mechanisms regulating stemness remain to be elucidated. Rack1 (Receptor for Activated C Kinase 1), a well-known versatile scaffold protein, has been implicated in tumorigenesis and progression in numerous cancer types; however, its specific role in breast cancer stemness remains to be elucidated. Methods: Using bioinformatic and immunohistochemical approaches, we validated that the expression level of Rack1 is associated with cancer stemness and affects the prognosis of patients. Through a series of experimental methods including mammosphere formation assay, flow cytometry, qPCR, Western blotting, and CHX assays, we validated at the molecular and cellular levels the mechanism by which Rack1 influences cancer stemness via the E2F1/SOX2 axis. Furthermore, by designing and utilizing lentiviral constructs to establish xenograft tumor models in mice, we further confirmed in vivo the impact of the Rack1/E2F1/SOX2 axis on the tumorigenic capacity of breast cancer cells. Results: Our findings indicate that Rack1 plays a critical role in preserving the stemness characteristics of breast cancer cells. Mechanistically, the observed effects of Rack1 are achieved through the modulation of SOX2 expression, a master transcription factor that regulates cancer cell stemness and maintenance. We further demonstrate that Rack1 increases the stability of the E2F1 protein by inhibiting its ubiquitination and subsequent proteasome-mediated degradation, which in turn transcriptionally upregulates SOX2, thereby maintaining breast cancer cell stemness and tumorigenesis. Conclusion: This study thus unveils a novel mechanism through which Rack1 executes its oncogenic function. This study also demonstrates that targeting the Rack1-E2F-SOX2 axis may be a potential strategy to inhibit breast cancer development and progression. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption has been associated with an increased risk of cancer-related mortality. It may also negatively impact oncological therapies, potentially leading to impaired effectiveness or an increased risk of treatment-related toxicities. The aim of this systematic review and meta-analysis was to examine the current evidence regarding the potential effects of alcohol consumption during cancer treatments on both treatment effectiveness and toxicity, irrespective of cancer type. Methods: A comprehensive literature search was performed across three electronic databases (Medline, Web of Science, Cochrane) covering studies from January 1990 to December 2023. Furthermore, a manual search based on the reference lists of the eligible studies was performed to identify additional potentially eligible studies. Studies were eligible if they involved cancer patients and provided data on alcohol consumption during specific oncological treatments, including its effect on treatment outcomes, or compared treatment effectiveness or toxicity between drinkers and non-drinkers. Studies were excluded if they did not meet these criteria, were duplicates, case reports, conference abstracts, or focused only on cancer-specific or overall survival. Only studies using multivariable analyses to examine the association between alcohol consumption and treatment effectiveness or toxicity were included in the pooled analyses. Pooled Hazard Ratios (HRs) or Odds Ratios (ORs) and their corresponding 95% Confidence Intervals (CIs) were calculated using random-effects models. Study quality was assessed by using the Newcastle–Ottawa scale whereas the GRADE approach was applied to rate the certainty of evidence for pooled analyses. Results: Out of 6734 studies identified through searching, 38 met the inclusion criteria for pooled analyses. Alcohol consumption during radiotherapy, with or without concomitant chemotherapy, was associated with worse disease-free survival (pooled HR: 2.05; 95% CI: 1.09 – 3.89), although the numerically increased risk for locoregional recurrence did not reach statistically significance (pooled HR: 2.01; 95% CI: 0.76 – 5.36). The potential impact of alcohol consumption on chemotherapy-induced neurotoxicity and acute / delayed nausea was not statistically significant. However, alcohol consumption was associated with a lower risk of overall chemotherapy-induced nausea (OR: 0.69; 95% CI: 0.57, 0.84). Conclusion: Our findings suggest that alcohol consumption may have a negative impact on radiotherapy, whereas its potential impact on the effectiveness of systemic oncological therapies (chemotherapy, molecular targeted therapy, immunotherapy, endocrine therapy) has not been adequately studied. Similarly, the current evidence on the potential association between alcohol consumption and treatment-related toxicities is weak, highlighting the need for well-designed prospective studies on this topic. [ABSTRACT FROM AUTHOR]

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non‐Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population‐based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30–1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26–1.66 in men; HR = 1.47, 95% CI = 1.22–1.79 in women), and in both never‐smokers and ever‐smokers (HR = 1.43, 95% CI = 1.18–1.73 in never‐smokers; HR = 1.46, 95% CI =1.27–1.67 in ever‐smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36–1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46–2.44), and other non‐small cell LC (HR = 1.94, 95% CI: 1.02–3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. In recent years, circular RNAs (circRNAs), a novel class of non-coding RNA molecules, have emerged as a research focus due to their unique stability and functional roles. CircRNAs regulate tumor-related signaling pathways through interactions with microRNAs (miRNAs) and proteins, playing key roles in tumorigenesis, progression, invasion, metastasis, and chemoresistance. This review summarizes the role of circRNAs in CRC, particularly their mechanisms in cell proliferation, migration, apoptosis, tumor microenvironment (TME) remodeling, and immune evasion. Aberrant expression of circRNAs holds great potential as diagnostic and prognostic biomarkers as well as therapeutic targets for CRC. Additionally, natural products such as flavonoids and glycosides, by modulating circRNA-miRNA-mRNA networks, offer promising therapeutic strategies. The article also discusses the current technical challenges in circRNA research and its future application prospects in CRC, highlighting the need for further investigation into the role of circRNAs in tumor immune microenvironments and drug resistance mechanisms. [ABSTRACT FROM AUTHOR]

Lung cancer, which is on the rise, is the primary reason for mortality among cancer patients. As stated by the World Health Organization, lung tumor is the second-deadliest type of cancer globally. Most lung cancer patients are diagnosed when the illness has already gone this far. Most of these patients receive a diagnosis in stage 3 or 4, as early lung cancer symptoms typically go unnoticed. Lung cancer affects 84 percent of males and 75 percent of women who smoke. We anticipate that early nodule detection will significantly reduce the mortality rate. As a result, it has been shown that early screening using computed tomography (CT) is beneficial in finding early-stage lung cancer. This is because of missed nodules and inaccurate diagnoses. Detecting prospective nodules and eliminating false-positives are crucial components of an excellent pulmonary CAD system. This article provides a thorough comparative analysis of machine learning (ML) and deep learning (DL) techniques used in lung nodule detection and classification. It reviews various algorithms, encompassing both traditional ML methods and advanced DL architectures, and discusses their performance, benefits, and limitations. Additionally, the survey investigates the use of ResNet-50, a deep convolutional neural network, for lung nodule classification. This study provides an in-depth understanding of the ResNet-50 architecture and demonstrates its effectiveness in improving classification accuracy. Finally, it demonstrates that CNN has excellent approaches to identify early detection of lung carcinoma with the help of current difficulties and future possibilities. By examining the relative strengths of different methods, this survey aims to guide future research and advancements in lung nodule detection and classification. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer (LC) has the highest cancer-related mortality rate. Even though genome-wide association studies (GWAS) have identified numerous loci linked to LC risk, the underlying causal genes and biological processes are still mostly unknown. Methods: The LC GWAS summary data comprised 29,863 cases and 55,586 controls of European ancestry. The weight file and related files of plasma protein, multi-tissue, and single-cell were obtained from Zhang's study, Mancuso lab, and Thompson's study, respectively. We conducted transcriptome association studies (TWAS) employing functional Summary-based Imputation (FUSION) from two levels, which were multiple tissues and single cell. We conducted proteome-wide association studies (PWAS) from plasma protein. Conditional and joint (COJO) analysis and multi-marker analysis of genomic annotation (MAGMA) analysis were used to further screen the PWAS/TWAS results. Summary-data-based Mendelian randomization (SMR) and colocalization analysis were utilized to explain the causal association between variables and results. Results: A total of 13, 251, and 16 genes were calculated from the three dimensions, which were plasma protein, multiple tissues, and single cell, respectively. RNASET2 and IREB2 were obtained through intersecting these three sets of genes. COJO analysis and MAGMA analysis were replicated the two genes successfully. Then, RNASET2 was replicated in both eQTL-SMR and mQTL-SMR and following colocalization analysis. Conclusion: In summary, we conducted a multi-omic studies, which integrated three levels to investigate the novel targets for LC. Through a series of verifications, RNASET2 was identified as the key gene for LC in the current research. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with adenocarcinoma as the most common subtype. While metastasis typically occurs in the liver, lungs, and peritoneal cavity, metastasis to the brain, particularly the cerebellum, is exceedingly rare. Case presentation: This report discusses the case of a 50-year-old woman diagnosed with mucinous adenocarcinoma of the descending colon. Over six years, the patient experienced multiple common metastatic sites, including the liver and lungs, before developing a rare cerebellar metastasis. Despite extensive treatment, including surgery and chemotherapy, the disease progressed, ultimately leading to the patient's demise. This case represents the first documented cerebellar metastasis from CRC in Mexico. Conclusion: This case highlights the altered metastatic patterns in CRC due to advanced therapies that extend survival. Clinicians should remain vigilant for metastasis to uncommon sites, such as the cerebellum, especially in patients with prolonged survival. Further research is needed to understand the mechanisms underlying such metastatic behavior and optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Chronic low-grade inflammation is recognized as a significant factor in various health outcomes, including the development and progression of breast cancer. The Systemic Immune-Inflammation Index (SII), a novel marker derived from routine blood counts, has been suggested as a predictor of all-cause mortality and cardiovascular mortality. However, its predictive value in a nationwide representative population, particularly for breast cancer incidence and mortality, is not well-established. Methods: This study aimed to assess the association of SII and the risk of breast cancer incidence and all-cause mortality in breast cancer patients within the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. SII was calculated from complete blood count parameters. We used multifactor regression models to examine the associations between SII and the outcomes of interest. Results: A total of 21,058 female participants were included in the study, of which 557 (2.7%) were identified as having breast cancer. After adjusting for multiple potential confounders, the relationship between SII and the incidence of breast cancer revealed an inverse L-shaped association. The optimal inflection point for SII/100 was determined to be 5.09. Below this threshold, there was a significant increase in the risk of breast cancer (OR=1.05, 95% CI: 1.02-1.09). Within the breast cancer population, SII exhibited a J-shaped relationship with all-cause mortality. The optimal inflection point for SII/100 in this context was 5.22, and above this threshold, there was a marked escalation in all-cause mortality (HR=1.09, 95% CI: 1.04-1.14). Conclusion: The SII, as a novel inflammatory composite index, is significantly associated with the risk of breast cancer incidence and all-cause mortality in breast cancer patients. These findings highlight the importance of monitoring systemic inflammation and suggest that SII could serve as a valuable prognostic tool. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD), the most common type of lung cancer, is a leading cause of cancer-related mortality. NT5E, an ecto-5'-nucleotidase enzyme, has been implicated in cancer progression, particularly in efferocytosis. Despite its potential involvement, the prognostic significance of NT5E and relationship with immune cell infiltration in LUAD have not been extensively explored. In this study, we performed a comprehensive analysis to elucidate the expression patterns of NT5E and its prognostic implications in LUAD using data from diverse public databases. Multiple computational algorithms, including CIBERSORT, ESTIMATE, and xCell, were employed to assess the correlation between NT5E expression and immune cell infiltration. We found that NT5E was significantly overexpressed at both the mRNA and protein levels in LUAD tissues. Elevated NT5E expression was significantly linked to multiple clinicopathological factors, including metastasis and pathological stage, and served as a strong predictor of poor prognosis in LUAD patients. Gene Set Enrichment Analysis (GSEA) indicated that NT5E plays a crucial role in regulating immune responses, as evidenced by differential gene expression associated with NT5E levels. A strong positive correlation was observed between NT5E expression and the presence of immune cells, including dendritic cells, macrophages, and CD4+ T cells, as well as the expression of various immune cell markers, suggesting that NT5E may influence the prognosis of LUAD patients by regulating immune cell infiltration. Additionally, drug sensitivity analysis highlights the potential of selumetinib and PD318088, both MEK1/2 inhibitors, to target NT5E in LUAD treatment, suggesting their use as single agents or in combination with other therapies. Collectively, these findings establish NT5E as a promising prognostic biomarker and therapeutic target in LUAD, particularly in the context of immune cell infiltration. [ABSTRACT FROM AUTHOR]

Cancer therapy-related cardiovascular toxicity (CTR-CVT) is now recognised as one of the leading causes of long-term morbidity and mortality in cancer patients. To date, potential overlapping cardiotoxicity mechanism(s) across different chemotherapeutic classes have not been elucidated. Doxorubicin, an anthracycline, and Carfilzomib, a proteasome inhibitor, are both known to cause heart failure in some patients. Given this common cardiotoxic effect of these chemotherapies, we aimed to investigate differential and common mechanism(s) associated with Doxorubicin and Carfilzomib-induced cardiac dysfunction. Primary human cardiomyocyte-like cells (HCM-ls) were treated with 1 µM of either Doxorubicin or Carfilzomib for 72 h. Both Doxorubicin and Carfilzomib induced a significant reduction in HCM cell viability and cell damage. DNA methylation analysis performed using MethylationEPIC array showed distinct and common changes induced by Doxorubicin and Carfilzomib (10,270 or approximately 12.9% of the DMPs for either treatment overlapped). RNA-seq analyses identified 5,643 differentially expressed genes (DEGs) that were commonly dysregulated for both treatments. Pathway analysis revealed that the PI3K-Akt signalling pathway was the most significantly enriched pathway with common DEGs, shared between Doxorubicin and Carfilzomib. We identified that there are shared cardiotoxicity mechanisms for Doxorubicin and Carfilzomib pathways that can be potential therapeutic targets for treatments across 2 classes of anti-cancer agents. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a significant global health issue and remains one of the leading causes of cancer-related mortality in women. Radiotherapy is a crucial treatment modality for CC; however, tumor heterogeneity and resistance to radiotherapy often result in suboptimal outcomes for some patients, including recurrence and metastasis. Periostin (POSTN), a matricellular protein within the tumor microenvironment, has been implicated in the promotion of tumor progression and treatment resistance, particularly through mechanisms such as epithelial-mesenchymal transition (EMT). Despite this, the role of POSTN in radiotherapy resistance in CC patients remains underexplored. Therefore, in this study, we investigated the prognostic significance of POSTN expression in CC patients undergoing radical radiotherapy and explored potential mechanisms underlying radiotherapy resistance. We analyzed data from 92 CC patients in The Cancer Genome Atlas (TCGA) and 153 patients from our institution, assessing POSTN expression levels through mRNA analysis and immunohistochemistry (IHC). Our findings revealed that high POSTN expression was significantly associated with advanced tumor stages, poorer radiotherapy outcomes, and worse overall survival (OS). Additionally, multivariate Cox regression analysis identified POSTN as an independent prognostic factor for CC patients undergoing radical radiotherapy. A prognostic nomogram integrating POSTN expression and clinicopathological features demonstrated superior predictive accuracy for OS. Drug sensitivity analysis suggested that high POSTN expression may be linked to resistance to multiple chemotherapeutic agents. Furthermore, weighted correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified EMT as a top enriched pathway in patients with high POSTN expression, suggesting it may play a critical role in radiotherapy resistance. Subsequently, in vitro experiments confirmed that POSTN knockdown significantly inhibited HeLa cell proliferation, invasion, and enhanced radiosensitivity, while promoting apoptosis. These findings indicate that high POSTN expression is a risk factor for poor prognosis in CC patients undergoing radical radiotherapy, and targeting POSTN may improve radiotherapy efficacy by reducing tumor proliferation and resistance. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) poses significant challenges globally, ranking fifth in incidence and fourth in cancer-related mortality. SALL4, a stem cell transcription factor with multiple isoforms, includes SALL4-A as its full-length form. This study aims to evaluate the diagnostic potential of SALL4-A isoform expression in GC and its clinical significance. Method: Immunohistochemical (IHC) analysis was conducted on Tissue Micro Array (TMA) slides from 167 GC patients. Clinicopathological parameters were correlated with SALL4-A expression, and survival analysis was performed. Diagnostic performance was assessed using metrics such as sensitivity, specificity, and area under the curve (AUC). Results: SALL4-A exhibited distinct cytoplasmic expression in GC, correlating with lower histological grade (p = 0.003) and TNM stage (p = 0.003), particularly in the intestinal subtype. Diagnostic evaluation showed an AUC of 0.803 for cytoplasmic expression, demonstrating high diagnostic potential. However, SALL4-A expression did not show significant prognostic value. Conclusion: Cytoplasmic SALL4-A expression in GC is associated with less aggressive tumor phenotypes and shows promise as a diagnostic marker. Further research is warranted to elucidate its mechanistic role and potential integration into clinical practice. [ABSTRACT FROM AUTHOR]

Translational control shapes the proteome and is particularly important in regulating gene expression under stress. A key source of endothelial stress is treatment with tyrosine kinase inhibitors (TKIs), which lowers cancer mortality but increases cardiovascular mortality. Using a human induced pluripotent stem cell--derived endothelial cell (hiPSC-EC) model of sunitinibinduced vascular dysfunction combined with ribosome profiling, we assessed the role of translational control in hiPSC-ECs in response to stress. We identified staphylococcal nuclease and tudor domain--containing protein 1 (SND1) as a sunitinibdependent translationally repressed gene. SND1 translational repression was mediated by the mTORC1/4E-BP1 pathway. SND1 inhibition led to endothelial dysfunction, whereas SND1 OE protected against sunitinib-induced endothelial dysfunction. Mechanistically, SND1 transcriptionally regulated UBE2N, an E2-conjugating enzyme that mediates K63-linked ubiquitination. UBE2N along with the E3 ligases RNF8 and RNF168 regulated the DNA damage repair response pathway to mitigate the deleterious effects of sunitinib. In silico analysis of FDA-approved drugs led to the identification of an ACE inhibitor, ramipril, that protected against sunitinib-induced vascular dysfunction in vitro and in vivo, all while preserving the efficacy of cancer therapy. Our study established a central role for translational control of SND1 in sunitinib-induced endothelial dysfunction that could potentially be therapeutically targeted to reduce sunitinib-induced vascular toxicity. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the 4th most prevalent cancer among females globally. In India, approximately 123,907 women are diagnosed with cervical cancer every year, leading to 77,348 deaths annually. However, Indian healthcare system lacks the sufficient information regarding the factors influencing survival and mortality among cervical cancer patients at regional levels. Thus, we aimed to identify the predictors associated with survival outcomes and mortality rates among cervical cancer. Methods: A retrospective cohort study was conducted over 8 months at a tertiary care hospital where 10-year (January 2013–December 2022) data of cervical cancer patients were analyzed from medical record department (MRD). Telephonic interviews were carried out with patients or patient parties to know the survival status of patients. The data was analyzed using descriptive statistics, Kaplan–Meier curve, log-rank test and Cox regression. Results: Out of 330 cervical cancer patients, majority (64.24%) were > 50 years of age followed by 35.76% were < 50 years. Most of the patients had abnormal body mass index (BMI) (46.96%), postmenopausal stage (75.76%), stage II cancer (43.03%), histologically poorly differentiated grade (47.88%) and squamous cell carcinoma (87.88%), with radiation plus chemotherapy being popular treatment choice (48.79%) and with the overall mean age of 56 years. Age, BMI, menopause, stage of cancer, histological grades and types of treatment were found to be significant predictors (p < 0.05) of survival among cervical cancer patients. Using cox regression analysis, advanced age (age > 50 years: hazard ratio (HR): 1.82), underweight (BMI < 18.5: HR:1), postmenopause (HR:1), advanced stage of cervical cancer (Stage I, Stage II, Stage III, Stage IV: HR:1, HR:2.78, HR:10.08, HR:20.81), poorly differentiated cervical cancer (HR:1.70), radiation therapy (HR:4.86), chemotherapy (HR:6.55) or chemoradiation therapy (HR:3.31) and surgery plus chemotherapy (HR: 4.55) were identified to be significant predictors of mortality among cervical cancer patients. Conclusion: We conclude that the 5- and 10-year survival rates for cervical cancer patients were found to be 51.2% and 42.9%, respectively. Advanced age, underweight, postmenopausal status, advanced cancer stage, poor cancer cell differentiation and chemotherapy-based treatment were significant predictor of mortality and vice-versa for survival which might guide clinicians and policymakers in making informed clinical decisions to combat cervical cancer. [ABSTRACT FROM AUTHOR]

Background Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs. Methods We used the Hu-Zelen model, previously used to plan the National Lung Screening Trial (NLST), to estimate mortality reductions, sample size, and power for 9 cancers for different RCT design parameters and MCD test parameters. Results Our base-case RCT with 5 yearly screens and 100 000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87%-89% power to detect a 9%-10% mortality reduction (Number Needed to Screen [NNS] = 578-724) over 7-9 years. The majority of prevented deaths were from lung cancers (base-case [64%-66%] and all sensitivity analyses), 8%-10% from colorectal cancer, and 26% from the other 7 cancers, mostly from stomach or ovary or esophagus (due to excellent stage 1 survival) and less from liver or pancreas (poor stage 1 survival) or head and neck or lymphoma (excellent stage 4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage shifts, and mean sojourn times in the preclinical state (especially for lung cancer), but 90% power could be recovered by recruiting a substantially higher risk population. Conclusions Large-scale MCD RCTs would have 89% power to detect an approximate 10% cancer mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably with mammographic screening. Most prevented cancer deaths in a well-powered MCD RCT would likely be from lung cancer. Non-lung and non-colorectal cancer sites could be a meaningful proportion of prevented cancer deaths, but power is insufficient to isolate non-lung-cancer mortality reductions. [ABSTRACT FROM AUTHOR]

Background Central nervous system cancers are a leading cause of childhood cancer-related mortality. Accurate staging and assessment of leptomeningeal spread, particularly in aggressive neoplasms such as embryonal tumors, is crucial for treatment planning and prognosis. Conventional diagnostic methods, relying on magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology, have limitations, including high false-negative rates and sensitivity issues. In this retrospective study, we aim to compare the diagnostic sensitivity of contrast-enhanced T2-weighted fluid-attenuated inversion recovery (CE-T2W-FLAIR) and 2D and 3D contrast-enhanced T1-weighted imaging (CE-T1WI) for detecting leptomeningeal disease. Methods We retrospectively reviewed 1372 MRI brain studies of 297 patients aged 1–19 years. We included only those MRI examinations adhering to our neuro-oncology protocol while excluding incomplete or suboptimal studies. A control group without leptomeningeal disease was matched for disease and age. Three groups of 2 neuroradiologists each, blinded to case status, reviewed the images using various sequences. The results were compared using the McNemar test and chi-squared test for P -values. Results The sensitivity of CE-T2W-FLAIR sequence was significantly higher compared with that of CE-T1WI (P  = .025). There was no statistically significant difference between the sensitivity of 2D CE-T1WI and 3D CE-T1WI (P  = .3173). The specificity of the 3D CE-T1WI was significantly lower compared with those of CE-T2W-FLAIR and 2D CE-T1WI (P  = .014). The positive predictive values for CE-T2W-FLAIR, 2D CE-T1WI, and 3D CE-T1WI were 100%, 100%, and 68.4%, respectively, whereas the negative predictive values were 100%, 85.7%, and 85.71%, respectively. Conclusions The inclusion of CE-T2W-FLAIR in the MRI protocol improves sensitivity and specificity in diagnosing leptomeningeal spread in pediatric brain tumors. [ABSTRACT FROM AUTHOR]

In Japan, high-quality cancer statistics are collected through cancer registries. However, these data are rarely summarized or reported in research articles. We compiled statistical data on lung cancer in Japan including the COVID-19 pandemic. In 2019, the number of cases of lung cancer in Japan was 126,548. The age-adjusted incidence rate of lung cancer increased from 23.2/100,000 to 42.4/100,000 in males and from 7.2/100,000 to 18.3/100,000 in females between 1975 and 2019. The age-adjusted mortality rate of lung cancer in Japan increased since 2000, after which it decreased. This trend was similar in both males and females. We also investigated statistics on lung cancer worldwide (Australia, Sweden, England, and the United States [USA]). The age-adjusted incidence rate of lung cancer in the data standardized to the world population for males has increased only in Japan; for females, it has decreased only in the USA. Global age-adjusted lung cancer mortality rates have been declining in all countries. In addition, the COVID-19 pandemic has not affected the age-adjusted mortality rate of lung cancer. On the other hand, the number of individuals undergoing lung cancer screening in Japan decreased from 7.92 million in 2019 to 6.59 million in 2020. The COVID-19 pandemic may have affected individuals undergoing lung cancer screening, and its impact on lung cancer needs to be continuously monitored in the future. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between urinary albumin-to-creatinine ratio (uACR) and all-cause/specific-cause mortality among patients with rheumatoid arthritis (RA). Methods: This study included 1354 RA patients in the National Health and Nutritional Examination Surveys (NHANESs) during 1999–2018. The mortality status was assessed by linkage to death certificate data reported in the National Death Index (NDI) until December 31, 2019. Cox proportional hazards models and Kaplan–Meier (K-M) analysis were used to elucidate the relationship between uACR and all-cause/specific-cause mortality. Restricted cubic spline (RCS) was used to visualize the association of uACR with all-cause mortality risk. Stratified analyses were employed to identify patients with higher mortality risk. Results: Over a median of 115 months of follow-up, 298 deaths occurred. Cox proportional hazards models indicated that RA patients with higher uACR had an increased risk of all-cause mortality, but not cardiovascular disease, kidney disease, and cancer mortality. K-M survival curves showed a significant difference (log-rank, p < 0.001) in all-cause mortality among uACR tertiles. RCS analysis revealed an L-shaped association between uACR and all-cause mortality, and patients with uACR above the threshold points (5.96 mg/g) had a 13.2% increased risk of all-cause mortality (HRs 1.132; 95% CI 1.011, 1.267) for each ln unit increase in uACR. The stratified analysis revealed consistent patterns for correlations between uACR and all-cause mortality. Conclusions: High uACR, even in the normal range, was associated with an increased risk of all-cause mortality (not specific-cause mortality) in individuals with RA. Identifying high-risk populations using uACR assessment may contribute to target risk interventions among RA patients in the future. Key points • uACR, even within the normal range, significantly increased the hazard for all-cause mortality among RA patients. • uACR has good performance in identifying populations with different mortality risk levels in RA patients. • uACR, independent of varied well-recognized cardiovascular risk factors, is a predictor of mortality in RA patients. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The accumulation of misfolded proteins and subsequent activation of unfolded protein response (UPR) alters the homeostasis of endoplasmic reticulum (ER) lumen that ultimately causes oxidative stress in ER. The UPR activates stress-detecting proteins such as IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. The ER stress-dependent antitumor activity could be achieved either through suppressing the adaptive UPR to make cells susceptible to ER stress or by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Several herbal drugs trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of fifty-two herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC.Breast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The accumulation of misfolded proteins and subsequent activation of unfolded protein response (UPR) alters the homeostasis of endoplasmic reticulum (ER) lumen that ultimately causes oxidative stress in ER. The UPR activates stress-detecting proteins such as IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. The ER stress-dependent antitumor activity could be achieved either through suppressing the adaptive UPR to make cells susceptible to ER stress or by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Several herbal drugs trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of fifty-two herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC. [ABSTRACT FROM AUTHOR]

Objective: The associations of lean mass distribution with mortality risk are not fully elucidated. We aimed to evaluate the effects of a new lean mass distribution indicator‐android/gynoid lean mass ratio (AGLR) evaluated by dual‐energy x‐ray absorptiometry (DXA) on the risk of all‐cause and specific‐cause mortality in a NHANES cohort. Methods: This was a population‐based cohort study, which included 18 542 subjects aged 20 years and older from the US National Health and Nutrition Examination Survey (US NHANES, 2003–2006 and 2011–2018). The primary outcomes of our study were all‐cause mortality, cardiovascular (CVD) mortality and cancer mortality, which were obtained from the linkage to registries. Cox proportional hazard regression models were used to investigate the association between lean mass distribution and mortality risk among the US NHANES general population. Restricted cubic spline nested in Cox regression was also used to test whether there was a non‐linear association of AGLR as a continuous variable with the risk of mortality. Results: During a median follow‐up of 6.9 years, 1412 participants died, of whom 435 were due to CVD and 340 were due to cancer. The multivariable‐adjusted (Model 4) hazard ratios (HRs) for each SD increase in AGLR were 1.53 (95% confidence interval [CI] 1.40–1.67) for all‐cause mortality, 1.56 (95% CI 1.30–1.87) for cancer mortality and 1.64 (95% CI 1.47–1.84) for CVD mortality. The associations were robust in sensitivity analyses and present in most subgroups. Conclusions: AGLR evaluated by DXA was associated with a higher risk of all‐cause and specific‐cause mortality among the general population from the US NHANES cohort. [ABSTRACT FROM AUTHOR]

Temporal trends demonstrate improved survival for many types of common pediatric cancer. Studies have not examined improvement in very rare pediatric cancers or compared these improvements to more common cancers. In this cohort study of the Surveillance, Epidemiology, and End Results (SEER) registry, we examined patients from 1975 to 2016 who were 0–19 years of age at the time of diagnosis. Cancers were grouped by decade of diagnosis and 3 cancer frequency groups: Common, Intermediate, and Rare. Trends in mortality across decades and by cancer frequency were compared using Kaplan–Meier curves and adjusted Cox proportional hazards models. A total of 50,222 patients were available for analysis, with the top 10 cancers grouped as Common (67%), 13 cancers grouped with Intermediate (24%), and 37 cancers as Rare (9%). Rare cancers had higher rates of children who were older and Black. 5-year survival increased from 63% to 86% across all cancers from the 1970s to the 2010s. The hazard ratio (HR) for mortality decreased from the reference point of 1 in the 1970s to 0.27 (95% CI: 0.25-0.30) in the 2010s in Common cancers, while the HR only dropped to 0.60 (0.49–0.73) over that same period for rare cancers. Pediatric oncology patients have experienced dramatic improvement in mortality since the 1970s, with mortality falling by nearly 75% in common cancers. Unfortunately, rare pediatric cancers continue to lag behind more common and therefore better studied cancers, highlighting the need for a renewed focus on research efforts for children with these rare diseases. [ABSTRACT FROM AUTHOR]

To demonstrate the efficacy of machine learning models in predicting mortality in melanoma cancer, we developed an interpretability model for better understanding the survival prediction of cancer. To this end, the optimal features were identified, ten different machine learning models were utilized to predict mortality across various datasets. Then we have utilized the important features identified by those machines learning methods to construct a new model named NKECLR to forecast mortality of patient with cancer. To explicitly clarify the model's decision-making process and uncover novel findings, an interpretable technique incorporating machine learning and SHapley Additive exPlanations (SHAP), as well as LIME, has been employed, and four genes EPGN, PHF11, RBM34, and ZFP36 were identified from those machine learning(ML). The experimental analysis conducted on training and validation datasets demonstrated that the proposed model has a good performance com- pared to existing methods with AUC value 81.8%, and 79.3%, respectively. Moreover, when combined our NKECLR with PD-L1, PD-1, and CTLA-4 the AUC value was 83%0. Finally, these findings have been applied to comprehend the response of drugs and immunotherapy. Our research introduced an innovative predictive NKECLR model utilizing natural killer(NK) cell marker genes for cohorts with melanoma cancer. The NKECLR model can effectively predict the survival of melanoma cancer cohorts and treatment results, revealing distinct immune cell infiltration in the high-risk group. [ABSTRACT FROM AUTHOR]

Ovarian cancer caused the highest cancer-related mortality among female reproductive system malignancies. Platinum-based chemotherapy is still the footstone of the chemotherapy for ovarian cancer. However, the molecular mechanisms underlying cisplatin insensitivity and resistance remain unclear. SHC SH2 domain-binding protein 1 (SHCBP1) plays critical roles in the progression and drug resistance of different types of cancer. However, the biological function of SHCBP1 in ovarian cancer progression and cisplatin resistance remains obscure. In this study, we found that SHCBP1 was upregulated in ovarian cancer and the upregulated SHCBP1 has growth-promoting effect on ovarian cancer cells. Furthermore, SHCBP1 silencing sensitize ovarian cancer cells to cisplatin (hereafter referred to as CDDP). Mechanism analysis revealed that SHCBP1 activated the Akt/mTOR pathway and further inhibited autophagy in ovarian cancer cells. Meanwhile, autophagy inhibitors combined with SHCBP1 knockdown enhances CDDP sensitivity. In addition, knockdown of SHCBP1 restricted the proliferation of tumors and increased the cisplatin sensitivity in vivo. These findings suggested that upregulated SHCBP1 promoted the proliferation and CDDP resistance of ovarian cancer. The combination of SHCBP1 inhibition and cisplatin treatment might lead to substantial progress in ovarian cancer targeted therapy. [ABSTRACT FROM AUTHOR]

Although leukemia in the Japanese atomic bomb survivor data has long exhibited upward curvature, until recently this appeared not to be the case for solid cancer. It has been suggested that the recently observed upward curvature in the dose response for the Japanese atomic bomb survivor solid cancer mortality data may be accounted for by flattening of the dose response in the moderate dose range (0.3–0.7 Gy). To investigate this, the latest version available of the solid cancer mortality and incidence datasets (with follow-up over the years 1950–2003 and 1958–2009 respectively) for the Life Span Study cohort of atomic bomb survivors was used to assess possible departures from linearity in the moderate dose range. Linear-spline models were fitted, also up to 6th order polynomial models in dose (higher order polynomials tended not to converge). The organ dose used for all solid cancers was weighted dose to the colon. There are modest indications of departures from linearity for the mortality data, whether using polynomial or linear-spline models. Use of the Akaike information criterion (AIC) suggests that the optimal model for the mortality data is given by a 5th order polynomial in dose. There is borderline significant (P = 0.071) indication of improvement provided by a linear-spline model in the mortality data. The low-dose extrapolation factor (LDEF), which measures the degree of overestimation of low-dose linear slope by the linear slope fitted over some specified dose range, is generally between 1.1–2.0 depending on the dose range, with upper confidence limits that sometimes exceed 10; although LDEF < 1 for the lowest dose range (<0.5 Gy), there are substantial uncertainties, with an upper confidence limit that exceeds 1.6. There are generally only modest indications of departures from linearity for the solid cancer incidence data, whether using polynomial or linear-spline models. In contrast to the mortality data, there are much weaker indications of improvement in fit provided by higher order polynomials, and only weak indications (P > 0.2) of improvement provided by linear-spline models. Nevertheless, use of AIC suggests that the optimal model for the incidence data is given by a 3rd order polynomial. LDEF evaluated over various dose ranges is generally between 1.2–1.4 with upper confidence limits that generally exceed 1.6; although LDEF < 1 for the lowest dose range (<0.5 Gy), there are substantial uncertainties, with an upper confidence limit that substantially exceeds 2.0. In summary, the evidence we have presented for higher order powers than the second in the dose response is not overwhelmingly strong, and is to some extent dependent on dose range. A feature of the dose response, which is reflected in the higher-order polynomials fitted to the data, is a leveling off or even a downturn in the response at doses >2 Gy. The linear-quadratic model is very widely used for modeling of dose response, and has been widely used in radiotherapy oncology applications as part of treatment planning. There is a theoretical basis for this model, based on the two-target model, although the data used to validate this has been mainly in vitro; there may be more complicated interactions than are implied by a two-target model, but the contributions made by these, which would contribute to higher order (than quadratic) powers of dose, may not be very pronounced over moderate ranges of dose. [ABSTRACT FROM AUTHOR]

Context There are insufficient data to support a link between serum albumin-to-globulin ratio (AGR) and mortality in individuals with diabetes. Objective This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. Methods This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Hazard ratios (HR) and 95% CIs for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional-hazards models. Results A total of 2415 all-cause deaths, including 688 CV deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (P trend <.0001), cardiovascular mortality (P trend <.001), and cancer mortality (P trend <.01) were 0.51 (0.42-0.60), 0.62 (0.46-0.83), and 0.57 (0.39-0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per 1-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P <.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. Conclusion AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those younger than 60 years and heavy drinkers. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the 12th most common type of cancer, and the sixth leading cause of cancer-related mortality, worldwide. Up-to-date statistics on pancreatic cancer would provide us with a better understanding of epidemiology and identify the causative risk factors for the prevention of this disease. Methods: The degree and change patterns of exposure as well as the attributable cancer burden, including incidence, mortality, disability-adjusted life years (DALYs), and prevalence in global and regional, by sex, age, year, for pancreatic cancer, with the data extracted from the Global Burden of Diseases Study (GBD) 2021. All data analyses were conducted using linear regression analysis and the Joinpoint software (version 5.0.1). Results: In 2021, 508,533 new cases of pancreatic cancer have been reported; the mortality and prevalence rate increased to 5.95, and 5.12 respectively; and the global DALYs rate increased to 130.33 this year. Besides, the pancreatic cancer-associated rates of incidence, mortality, DALYs, and prevalence were higher in males than in females. In addition, these indicators in the high SDI (Sociodemographic index) region were higher than the global mean. To date, the high fasting plasma glucose remained the major risk factor that influenced the incidence, mortality, DALYs, and prevalence of pancreatic cancer, followed by tobacco and high body mass index (BMI). Conclusions: Results of this study suggest that the burden of pancreatic cancer is increasing generally, therefore, more attention and measures should be taken to cope with this situation. [ABSTRACT FROM AUTHOR]

Background: There is still a significant gap in understanding the impact of concomitant or previous cancer diagnoses on clinical outcomes of acute myocardial infarction (AMI) Objective: To provide updated evidence on the effect of concomitant or previous cancer diagnoses on mortality and risk of complications, specifically major bleeding, myocardial reinfarction, and stroke, of patients with AMI. Methods: A literature search was conducted across PubMed, EMBASE, and Scopus databases. English-language cohort studies published in peer-reviewed journals were included. Pooled effect estimates were calculated using random-effects models and reported as odds ratio (OR) or hazards ratio (HR) with 95% confidence intervals (CI). The certainty of the evidence was assessed using the standard GRADE approach. Results: A total of 22 studies were included. AMI patients with previous or concurrent cancer had increased risk of in-hospital mortality (OR 1.44, 95% CI: 1.20, 1.73), in-hospital mortality related to cardiovascular complications (OR 2.06, 95% CI: 1.17, 3.65), mortality at 30-days follow up (OR 1.47, 95% CI: 1.24, 1.74) and mortality at 1 year follow up (HR 2.67, 95% CI: 1.73, 4.11), compared to patients without cancer. The risk of major bleeding (OR 1.74, 95% CI: 1.40, 2.16), reinfarction (OR 1.20, 95% CI: 1.05, 1.37), and stroke (OR 1.16, 95% CI: 0.99, 1.37) was also higher in patients with previous or concurrent cancer. The certainty of evidence was rated as "low" for all outcomes, except for the risk of major bleeding, which was rated as "very low." Conclusion: Based on the low to very low certainty of evidence, we conclude that the presence of previous cancer diagnosis or concurrent cancer may increase the risk of adverse outcomes in patients with AMI. Early interventions, such as close monitoring of cardiac function, lifestyle modifications, and targeted pharmacological therapies, might help mitigate the risk of AMI and improve overall clinical outcomes. However, further methodologically rigorous studies are needed to validate the findings of this review. [ABSTRACT FROM AUTHOR]

Background: To effectively monitor long-term outcomes among cancer patients, it is critical to accurately assess patients' dynamic prognosis, which often involves utilizing multiple data sources (e.g., tumor registries, treatment histories, and patient-reported outcomes). However, challenges arise in selecting features to predict patient outcomes from high-dimensional data, aligning longitudinal measurements from multiple sources, and evaluating dynamic model performance. Methods: We provide a framework for dynamic risk prediction using the penalized landmark supermodel (penLM) and develop novel metrics ( and ) to evaluate and summarize model performance across different timepoints. Through simulations, we assess the coverage of the proposed metrics' confidence intervals under various scenarios. We applied penLM to predict the updated 5-year risk of lung cancer mortality at diagnosis and for subsequent years by combining data from SEER registries (2007–2018), Medicare claims (2007–2018), Medicare Health Outcome Survey (2006–2018), and U.S. Census (1990–2010). Results: The simulations confirmed valid coverage (~ 95%) of the confidence intervals of the proposed summary metrics. Of 4,670 lung cancer patients, 41.5% died from lung cancer. Using penLM, the key features to predict lung cancer mortality included long-term lung cancer treatments, minority races, regions with low education attainment or racial segregation, and various patient-reported outcomes beyond cancer staging and tumor characteristics. When evaluated using the proposed metrics, the penLM model developed using multi-source data ( of 0.77 [95% confidence interval: 0.74–0.79]) outperformed those developed using single-source data ( range: 0.50–0.74). Conclusions: The proposed penLM framework with novel evaluation metrics offers effective dynamic risk prediction when leveraging high-dimensional multi-source longitudinal data. [ABSTRACT FROM AUTHOR]

Background: Evidence is lacking on whether chronic pain is related to the risk of cancer mortality. This study seeks to unveil the association between chronic pain and all-cause, cancer, as well as non-cancer death in cancer patients based on the National Health and Nutrition Examination Survey (NHANES) database. Methods: Cancer survivors aged at least 20 (n = 1369) from 3 NHANES (1999–2004) cycles were encompassed. Chronic pain and cancer were determined through self-report. We employed records from the National Death Index for the determination of death status and reason. All-cause, cancer, and non-cancer deaths were primary outcomes. We used time-dependent ROC curve assessment to evaluate the predictive value of chronic pain for death in cancer patients. Results: Over a median 141-month follow-up (interquartile range: 61–201 months), 884 (64.57%) of 1,369 cancer sufferers died, of which 259 (18.91%) died from cancer, and 625 (45.65%) from other causes. Compared with non-chronic pain survivors, chronic pain correlated with elevated all-cause mortality (Hazard Ratio (HR), 1.40; 95% CI, 1.14–1.72, p = 0.001) and cancer death (HR, 1.75; 95% CI, 1.16–2.64, p = 0.008), primarily in patients with pain lasting 3 months or more. Chronic pain was related to higher non-cancer mortality (HR, 1.38; 95% CI, 1.04–1.82, p = 0.025), and no significant results were found in pain duration. Time-dependent ROC curves showed the area under the curve (AUC) for all-cause mortality at 1, 3, 5, 10, and 20-year survival for chronic pain of 0.71, 0.78, 0.84, 0.89, and 0.96, respectively. The AUCs for cancer mortality at 1, 3, 5, 10, and 20-year for chronic pain were 0.83, 0.87, 0.91, 0.94, and 0.95, respectively, and those for non-cancer mortality at 1, 3, 5, 10, and 20-year for chronic pain were 0.82, 0.86, 0.90, 0.91, and 0.97, respectively. Conclusion: Chronic pain is associated with heightened all-cause and cancer mortality in the cancer population. Clinical staff should focus on chronic pain in this patient population. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) remains a significant cause of cancer-related mortality worldwide. Despite advancements in surgery, chemotherapy, and radiotherapy, the effectiveness of these conventional treatments is limited, particularly in advanced cases. Therefore, transition to novel treatment is urgently needed. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has shown promise in improving outcomes for CRC patients. Notably, patients with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) tumors often benefit from ICIs, while the majority of CRC cases, which exhibit proficient mismatch repair (pMMR) or microsatellite-stable (MSS) status, generally show resistance to this approach. It is assumed that the MSI phenotype cause some changes in the tumor microenvironment (TME), thus triggering antitumor immunity and leading to response to immunotherapy. Understanding these differences in the TME relative to MSI status is essential for developing more effective therapeutic strategies. This review provides an overview of the TME components in CRC and explores current approaches aimed at enhancing ICI efficacy in MSS CRC. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally. Although tumor immunotherapy is widely recognized for treating unresectable CRC, challenges such as ineffective immunotherapy and drug resistance remain prevalent. While intratumor microbiome-derived butyrate has been implicated in promoting lung cancer metastasis, its role in CRC chemoresistance is not well understood. This study aimed to explore the relationship between intratumor butyrate and chemoresistance in CRC. Methods: We performed a comprehensive analysis of the microbiome composition in CRC patients with varying resistance-free survival (RFS) durations, utilizing 16S rRNA sequencing. Furthermore, we assessed the prognostic significance of circulating microbiome DNA (cmDNA) and examined the effects of exogenous butyrate supplementation on the chemosensitivity of CRC cell lines. Results: Our 16S sequencing analysis revealed a reduction in microbial diversity within tumor samples of patients with resistance, as indicated by metrics such as observed taxonomic units, Shannon, and Simpson indices. Notably, Roseburia and Fusobacteria emerged as prominent biomarkers for the resistance group, whereas Bifidobacterium, Helicobacter , and Akkermansia were identified as biomarkers for the non-resistant group. Utilizing a Lasso regression model, we identified six genera-Roseburia, Helicobacter , Gardnerella, Flavonifractor, Coprococcus, and Anaerostipes-that significantly correlated with recurrence-free survival. Furthermore, both the intratumor microbiome signature and circulating microbiome DNA were effective in accurately predicting CRC resistance. Experimental assays, including CCK8 and wound-healing, demonstrated that intratumor microbiome-derived butyrate enhances the proliferation and migration of HCT15 cells in a time- and concentration-dependent manner. Cell survival analysis further indicated that butyrate treatment significantly increased the IC50 value, suggesting heightened drug resistance in HCT15 cells. Mechanistically, this resistance was attributed to butyrate's activation of the PI3K-AKT signaling pathway. Conclusion: Our results suggest that intratumor microbiome-derived butyrate contributes to chemoresistance in colorectal cancer, highlighting the potential prognostic and therapeutic significance of the intratumor microbiome. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequently diagnosed cancer in the UAE and a leading cause of cancer-related mortality. Although early diagnosis contributes to favorable prognoses, novel treatment modalities like antibody-drug conjugates (ADCs) have significantly broadened the therapeutic landscape for patients in metastatic settings. The recognition of "HER2-low" expression as a targetable category has caused a paradigm shift in the management of breast cancer. Although initially developed to target HER2-positive breast cancer, trastuzumab deruxtecan (T-DXd), an ADC, has now also been approved to treat metastatic or unresectable HER2-low breast cancers. Despite the inherent specificity of an ADC, the risk of off-site toxicity exists and is an essential component while assessing the risk-benefit ratio of the treatment. Developing strategies to balance efficacy and safety is crucial, especially for newly approved therapies like T-DXd. Regional perspectives, cultural beliefs, and demographic factors influence treatment decisions and outcomes. The objective of this paper is to establish a UAE-specific consensus among oncologists on practical T-DXd treatment considerations and management of associated side effects. Establishing a consensus on monitoring and managing T-DXd side effects among experts can promote informed decision-making. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is a leading cause of mortality worldwide. The third most prevalent gynecological cancer globally, following cervical and uterine cancer, and the third leading cause of cancer-related mortality among women in Sub-Saharan Africa, including Ethiopia. The time ovarian cancer patients have to wait between diagnosis and initiation of treatment are the indicators of quality in cancer care and influence patient outcomes. Despite extensive studies in the field, little is known about the strength of the association between ovarian cancer survival and waiting time. So, the main purpose of this study is to assess the effect of waiting time on ovarian cancer survival in oncology centers in Addis Ababa, Ethiopia. Methods: A facility-based retrospective cohort study was conducted with a total of 561 study participants included. The main outcome of interest for this study was death due to ovarian cancer. The authors compared the ovarian cancer patients with waiting times ≤ 10 weeks and waiting times > 10 weeks for overall survival rate using the log rank test. The incidence density rate of mortality was calculated for each group variable. The effect of waiting time on ovarian cancer mortality was estimated using the Cox proportional hazards model at the 5% level of significance. Results: The incidence density rate of mortality among ovarian cancer patients for waiting time ≤ 10 weeks was found to be 10.85 (95%CI, 9.10-12.98) per 1,000 person years observation, while for waiting time > 10 weeks the mortality rate was found to be 18.05 (95%CI, 15.33–21.23) per 1,000 person years observation. In the Cox regression analysis after full adjustments for confounder variables, the mortality event risk was 36% higher among waiting time > 10 weeks women (AHR = 1.36; 95%CI = 1.05–1.75) as compared to waiting time ≤ 10 weeks. Conclusions: We have found that the incidence density rate of mortality among ovarian cancer patients was significantly higher in waiting time > 10 weeks groups. Therefore, future policy and clinician programmers should consider the impact of waiting time from diagnosis until to get the first treatment more carefully. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the sixth leading cause of cancer among females and about 97,000 global deaths of endometrial cancer. The changes in the trends of obesity, fertility rates and other risk factors in South Africa (SA) may impact the endometrial cancer trends. The aim of this study was to utilise the age period cohort and join point regression modelling to evaluate the national and ethnic trends in endometrial cancer mortality in South Africa over a 20year period (1999–2018). Methods: Data from Statistics South Africa was obtained to calculate the annual number of deaths, and annual crude and age standardised mortality rates (ASMR) of endometrial cancer from 1999–2018. The overall and ethnic trends of endometrial cancer mortality was assessed using the Join point regression model, while Age-period-cohort (APC) regression modelling was conducted to estimate the effect of age, calendar period and birth cohort. Results: During the period 1999–2018, 4,877 deaths were due to endometrial cancer which constituted about 3.6% of breast and gynecological cancer deaths (3.62%, 95% CI: 3.52%–3.72%) in South Africa. The ASMR of endometrial cancer doubled from 0.76 deaths per 100,000 women in 1999 to 1.5 deaths per 100,000 women in 2018, with an average annual rise of 3.6% per annum. (Average Annual Percentage change (AAPC): 3.6%, 95%CI:2.7–4.4, P-value < 0.001). In 2018, the overall mean age at death for endometrial cancer was was 67.40 ± 11.04 years and, the ASMR of endometrial cancer among Indian/Asians (1.69 per 100,000 women), Blacks (1.63 per 100,000 women) and Coloreds (1.39 per 100,000 women) was more than doubled the rates among Whites (0.66 deaths per 100,000 women). Indian/Asians had stable rates while other ethnic groups had increased rates. The Cohort mortality risk ratio (RR) of endometrial cancer increased with successive birth cohort from 1924 to 1963 (RR increased from 0.2 to 1.00), and subsequently declined among successive cohorts from 1963 to 1998 (1.00 to 0.09). There was strong age and cohort but not period effect among the South African women. Ethnic disparity showed that there was age effect among all the ethnic groups; Cohort effect among Blacks and Coloureds only, while Period effect occurred only among Blacks. Conclusions: The mortality rates of endometrial cancer doubled over a twenty-year period in South Africa from 1999–2018. There was strong ethnic disparity, with age and cohort effect on endometrial cancer trends. Thus, targeted efforts geared towards prevention and prompt treatment of endometrial cancer among the high-risk groups should be pursued by stake holders. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet. Results: Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism. Conclusions: In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species. [ABSTRACT FROM AUTHOR]

Background: Platelet count and function may be closely related to survival and prognosis of stroke and cancer. However, little is known on the impact of platelet count on the patients with a history of stroke and cancer. This study aimed to examine the association between baseline platelet level and all-cause mortality in this population using a cross-sectional analysis. Methods: Participants with a history of stroke and cancer were selected from the database of the National Health and Nutrition Examination Survey from 2007 to 2018. A maximum selected rank statistic was conducted to determine platelet cutoff with the most significant association with mortality. The association between platelet and mortality was characterized visually using restricted cubic spline (RCS). Weighted multivariable Cox regression models were performed to evaluate the association between platelet count and mortality. Time-dependent receiver operating characteristic (ROC) analysis was conducted to assess the accuracy of platelet count in predicting mortality. Results: Forty-three (43/113, 38.05%) stroke patients with cancer were alive at a median follow-up of 42 months (interquartile range, 23–74 months). The RCS analysis demonstrated a linear relationship between platelet and mortality (nonlinear, p = 0.352). Mortality in higher-platelet group (> 209 × 109/L, n = 57) was decreased than lower-platelet group (≤ 209 × 109/L, n = 56) (Model 1 HR 0.43, 95% CI 0.24—0.77, p = 0.005) (Model 2 HR 0.58, 95% CI 0.35—0.96, p = 0.03). Subgroup analyses showed no significant interaction between platelet and age, sex, BMI, WBC and neutrophil. The areas under time-dependent ROC curve of the 1-, 2-, 3-, 4- and 5-year survival rates were 0.54, 0.55, 0.57, 0.53, 0.59 for mortality of stroke patients with cancer. Conclusions: Lower platelet count may be an independent predictor of all-cause mortality in population with a history of stroke and cancer. This result may provide valuable insights for the long-term management in stroke patients with cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the leading causes of cancer-related mortality in the world. Incidence and mortality are predicted to rise globally during the next several decades. When detected early, colorectal cancer is treatable with surgery and medications. This leads to the requirement for prognostic and diagnostic biomarker development. Our study integrates machine learning models and protein network analysis to identify protein biomarkers for colorectal cancer. Our methodology leverages an extensive collection of proteome profiles from both healthy and colorectal cancer individuals. To identify a potential biomarker with high predictive ability, we used three machine learning models. To enhance the interpretability of our models, we quantify each protein's contribution to the model's predictions using SHapley Additive exPlanations values. Three classifiers—LASSO, XGBoost, and LightGBM were evaluated for predictive performance along with hyperparameter tuning of each model using grid search, with LASSO achieving the highest AUC of 75% in the UK Biobank dataset and the AUCs for LightGBM and XGBoost are 69.61% and 71.42%, respectively. Using SHapley Additive exPlanations values, TFF3, LCN2, and CEACAM5 were found to be key biomarkers associated with cell adhesion and inflammation. Protein quantitative trait loci analyze studies provided further evidence for the involvement of TFF1, CEACAM5, and SELE in colorectal cancer, with possible connections to the PI3K/Akt and MAPK signaling pathways. By offering insights into colorectal cancer diagnostics and targeted therapeutics, our findings set the stage for further biomarker validation. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) is characterized by fever, fatigue, dry cough, dyspnea, mild pneumonia and acute lung injury (ALI), which can lead to acute respiratory distress syndrome (ARDS), and SARS-CoV-2 can accelerate tumor progression. However, the molecular mechanism for the increased mortality in cancer patients infected with COVID-19 is unclear. Methods: Colony formation and wound healing assays were performed on Huh-7 cells cocultured with syncytia. Exosomes were purified from the cell supernatant and verified by nanoparticle tracking analysis (NTA), Western blot (WB) analysis and scanning electron microscopy (SEM). Differentially expressed proteins in syncytia-derived exosomes (Syn-Exos) and their functions was analyzed by Proteomic sequencing. Syn-Exo-mediated promotion of hepatocellular carcinoma cells was measured by CCK-8 and Transwell migration assays. The mechanism by which Syn-Exos promote tumor growth was analyzed by Western blotting. A patient-derived xenotransplantation (PDX) mouse model was constructed to evaluate the pathological role of the SARS-CoV-2 spike protein (SARS-2-S). The number of syncytia in the tumor tissue sections was determined by immunofluorescence analysis. Results: Syncytium formation promoted the proliferation and migration of hepatocellular carcinoma cells. Proteomic sequencing revealed that proteins that regulate cell proliferation and metastasis in Syn-Exos were significantly upregulated. Syn-Exos promote the proliferation and migration of hepatocellular carcinoma cells. Animal experiments showed that a pseudotyped lentivirus bearing SARS-2-S (SARS-2-Spp) promoted tumor development in PDX mice. More syncytia were found in tumor tissue from SARS-2-Spp mice than from VSV-Gpp mice. Conclusions: Syn-Exos induced by SARS-2-S can promote the proliferation and metastasis of hepatocellular carcinoma cells. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer is a significant cause of mortality globally, with several factors impacting patient outcomes, including access to healthcare, early detection, and treatment. Despite this, the specific factors affecting incidence of death among colorectal cancer patients in the Amhara region have not been thoroughly investigated. Thus, this study seeks to assess incidence and determinants of mortality among colorectal cancer patients in Amhara Region oncology centers. Results: The mean age of the participants was 48.6 years (SD ± 15). Median survival time was 23.8 months. The overall incidence rate or incidence density of a colorectal cancer mortality rate was 2.9 per 100 person-months (95% CI: 2.5–3.4). Survival rates of colorectal cancer patients 1and 5 year was 69.78% and 16.1%, respectively. The result of the multivariable analysis showed that colorectal cancer patients who had presenting symptoms [AHR = 2.67 (95% CI: 1.95, 3.67)], Base line HGB level < 12.5 mg/dl [AHR = 1.63 (95% CI: 1.12, 2.37)], WHO or ECOG poor performance status [AHR = 2.99 (95% CI: 2.17, 4.12), late stage of cancer [AHR = 2.32 (95% CI: 1.42, 3.79)] and location of tumor on colorectal [AHR = 1.76 (95% CI: 1.20, 2.55)] were significantly associated with mortality of colorectal cancer. Conclusion and recommendation: The study highlights significant findings on the survival and mortality of colorectal cancer patients. The overall mortality rate was 2.9 per 100 person-months. Multivariable analysis identified presenting symptoms, low baseline hemoglobin levels, poor performance status, late-stage cancer, and tumor location as significant predictors of mortality. Highlighting the need for early detection and targeted care strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally, especially in limited-resource countries (LRCs) where access to advanced treatments such as targeted therapy and immunotherapy is constrained. Platinum-based chemotherapy remains a cornerstone of first-line therapy. This study aims to identify prognostic factors influencing survival outcomes and evaluate treatment response to chemotherapy in advanced NSCLC patients in LRCs. Methods: A retrospective cohort study was conducted on 200 advanced NSCLC patients treated with first-line platinum-based doublet chemotherapy at Surin Hospital Cancer Center, Thailand. Prognostic factors were assessed through univariate and multivariate Cox regression analyses. Additionally, restricted mean survival time (RMST) was calculated to compare survival outcomes between responders and non-responders. Results: Independent prognostic factors associated with improved survival included good performance status, ECOG 0–1 (HR 0.50, p = 0.012), serum albumin ≥ 3.5 mg/dL (HR 0.60, p = 0.010), and favorable response to chemotherapy (HR 0.57, p = 0.003). Responders demonstrated significantly longer RMST at 12 months (p < 0.001), 24 months (p < 0.001), and 36 months (p = 0.004) compared to non-responders. Conclusions: Identifying prognostic factors and treatment responses is important for improving outcomes in advanced NSCLC patients, particularly in limited-resource settings where access to novel therapies is restricted. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common malignancies affecting men worldwide and a leading cause of cancer-related mortality, necessitating a deeper understanding of its underlying biochemical pathways. Similar to other cancer types, prostate cancer is also characterised by aberrantly activated metabolic pathways that support tumour development, such as amino acid metabolism, which is involved in modulating key physiological and pathological cellular processes during the progression of this disease. The metabolism of several amino acids, such as glutamine and methionine, crucial for tumorigenesis, is dysregulated and commonly discussed in prostate cancer. And the roles of some less studied amino acids, such as histidine and glycine, have also been covered in prostate cancer studies. Aberrant regulation of two major signalling pathways, mechanistic target of rapamycin (mTOR) and general amino acid control non-depressible 2 (GCN2), is a key driver of reshaping the amino acid metabolism landscape in prostate cancer. By summarising our current understanding of how amino acid metabolism is modulated in prostate cancer, here, we provide further insights into certain potential therapeutic targets for managing prostate cancer through metabolic interventions. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. The discovery of specific driver mutations has revolutionized the treatment landscape of oncogene-addicted NSCLC through targeted therapies, significantly improving patient outcomes. However, immune checkpoint inhibitors (ICIs) have demonstrated limited effectiveness in this context. Emerging evidence, though, reveals significant heterogeneity among different driver mutation subgroups, suggesting that certain patient subsets may benefit from ICIs, particularly when combined with other therapeutic modalities. In this review, we comprehensively examine the current evidence on the efficacy of immunotherapy in oncogene-addicted NSCLC. By analyzing recent clinical trials and preclinical studies, along with an overview of mechanisms that may reduce immunotherapy efficacy, we explored potential strategies to address these challenges, to provide insights that could optimize immunotherapy approaches and integrate them effectively into the treatment algorithm for oncogene-addicted NSCLC. [ABSTRACT FROM AUTHOR]

Background/Objectives: Colon cancer is one of the main causes of cancer-related mortality worldwide. Among its histopathological subtypes, mucinous adenocarcinoma (MAC) is characterized by a more aggressive behavior than non-mucinous adenocarcinoma (non-MAC). This study aimed to compare the clinical outcomes and postoperative recovery between MAC and non-MAC cases in order to better understand the treatment implications and optimize therapeutic strategies. Methods: A retrospective cohort study was conducted on patients diagnosed and treated at the Bihor County Emergency Hospital between January 2019 and December 2022. Data were collected from the medical records. Patients were divided into two groups, based on the histopathological results: mucinous adenocarcinoma and non-mucinous adenocarcinoma. Statistical analysis included descriptive statistics, t-tests, Chi-square tests, and ANOVA where appropriate. Results: A total of 191 patients were enrolled in this study, grouped in 36 cases of MAC and 155 cases of non-MAC. No significant statistical differences were found regarding hematological parameters. However, MAC was associated with higher rates of local invasion and a predominant right-sided colonic location, necessitating more frequent right colectomies. The overall mortality rate was significantly higher for MAC, indicating its aggressive nature. Conclusions: MAC presents higher local invasion rates and overall mortality. The aggressiveness of MAC underscores the need for tailored treatment approaches to optimize patient outcomes. Future large-scale studies are recommended to validate these findings and refine the therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Accurate staging, including the detection of axillary metastases, is vital for treatment planning. This study evaluates the efficacy of MRI relaxometry as a diagnostic tool for axillary lymph node metastases in breast cancer patients. Methods: A prospective study was conducted on 67 consecutive breast cancer patients. Relaxometry parameters, including T2Max, T2Min, and 1HAv, were assessed using 1.5 Tesla MRI. All axillary metastases were histologically confirmed using core-needle biopsy or surgical specimens. Statistical analyses included ROC curves, chi-square tests, and multivariate analysis to determine correlations between imaging findings and pathological results. Results: Significant associations were found between T2Min-ipsilateral (p = 0.018), 1HAv-ipsilateral (p = 0.003), and axillary metastases. ROC analysis demonstrated that T2Min-ipsilateral and 1HAv-ipsilateral have modest to acceptable discriminatory abilities (AUC = 0.681 and AUC = 0.740, respectively). Combined clinical and imaging models enhanced diagnostic accuracy (AUC = 0.749). Conclusions: MRI relaxometry improves the detection of axillary metastases in breast cancer, particularly when integrated with clinical and pathological evaluations. [ABSTRACT FROM AUTHOR]

Background: Smoking is a pivotal modifiable risk factor for lung cancer (LC). Previous studies have indicated that a smoking cessation program might be incorporated into the LC screening program. However, the effects of smoking cessation and its duration with the age at onset (AAO) of LC, all-cause mortality, and LC-specific mortality remain unclear. We aimed to comprehensively investigate the association of smoking cessation-related behaviors on the AAO of LC, LC-specific and all-cause mortality. Methods: A total of 2671 smokers with LC as the primary site from the UK Biobank were included in this study, with a 7:3 ratio assigned randomly to a discovery set (n = 1872) and a validation set (n = 799). Generalized linear regression models were used for AAO of LC outcomes and Cox models for mortality outcomes. Results: Participants over 60 years old could still benefit from smoking cessation to prolong AAOs (β = 1.613 for men, P = 0.003; β = 1.533 for women, P = 0.018). A cessation duration of > 15 years was associated with a later AAO in men (P < 0.001). Moreover, smoking cessation before 60 years old, especially among those under 40 years, was significantly associated with a lower risk of all-cause mortality (men: hazard ratio (HR): 0.65 [95% confidence interval 0.51–0.83]; women: 0.62 [0.47–0.83]) and LC-specific mortality (men: 0.67 [0.51–0.87]; women: 0.68 [0.50–0.92]). Compared with continuous smokers, former smokers who quit smoking for more than 15 years had a lower risk of all-cause mortality (men: 0.70 [0.59–0.84]; women: 0.68 [0.56–0.84]) and LC-specific mortality (men: 0.71 [0.59–0.87]; women: 0.69 [0.56–0.86]). Conclusions: Smoking cessation after 60 years old may still be helpful for a later AAO of LC. Former smokers who quit smoking for more than 15 years have a reduced risk of developing LC and mortality. [ABSTRACT FROM AUTHOR]

Primary malignant bone tumors are the third highest cause of cancer-related mortality among patients under the age of 20. X-ray scan is the primary tool for detecting bone tumors. However, due to the varying morphologies of bone tumors, it is challenging for radiologists to make a definitive diagnosis based on radiographs. With the recent advancement in deep learning algorithms, there is a surge of interest in computer-aided diagnosis of primary bone tumors. Nonetheless, the development in this field has been hindered by the lack of publicly available X-ray datasets for bone tumors. To tackle this challenge, we established the Bone Tumor X-ray Radiograph dataset (termed BTXRD) in collaboration with multiple medical institutes and hospitals. The BTXRD dataset comprises 3,746 bone images (1,879 normal and 1,867 tumor), with clinical information and global labels available for each image, and distinct mask and annotated bounding box for each tumor instance. This publicly available dataset can support the development and evaluation of deep learning algorithms for the diagnosis of primary bone tumors. [ABSTRACT FROM AUTHOR]

Severe obesity is often associated with inflammation and insulin resistance (IR), which expected to increase the risks of mortality and cancers. However, this relationship remains controversial, and it's unclear whether healthy lifestyles can mitigate these risks. The independent and joint associations of severe obesity (body mass index ≥ 35 m/kg2), inflammation (C-reactive protein > 10 mg/L and systemic inflammation markers > 9th decile), and IR surrogates with the risks of all-cause mortality and all-site cancers, were evaluated in 163,008 participants from the UK Biobank cohort. Further analyses were conducted to investigate how these associations were modified by lifestyle. During a median follow-up of 11.0 years, we identified 8844 deaths and 20,944 cancer cases. Severe obesity, inflammation and IR were each independently associated with increased risks of all-cause mortality [HRs(95%CIs) 1.24(1.17–1.30), 1.63(1.55–1.72) and 1.11(1.05–1.17)] and all-site cancers [1.06(1.02–1.10), 1.14(1.10–1.19) and 1.02(0.99–1.06)]. Joint analyses revealed significantly elevated risks of all-cause mortality and all-site cancers due to interaction between severe obesity, inflammation and IR, with the highest HRs(95%CIs) of 1.88(1.67–2.11) and 1.20(1.08–1.34), respectively. Further analyses showed stronger interaction between severe obesity, inflammation, IR and lifestyles, with similar associations observed in both males and females. Additionally, compared with unfavorable lifestyles, favorable lifestyles attenuated the risks of both all-cause mortality [the highest HRs(95%CIs) 2.35(1.75–3.15) vs. 3.72(2.86–4.84) for favorable vs. unfavorable lifestyles] and all-site cancers [1.16(0.89–1.53) vs. 1.63(1.26–2.10)]. Severe obesity interacts with inflammation and IR to exacerbate the risks of all-cause mortality and all-site cancers. Nonetheless, adherence to healthy lifestyles is recommended to mitigate these increased risks. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the major causes of cancer morbidity and mortality. Subtyping of non-small cell lung cancer is necessary owing to different treatment options. This study is to evaluate the value of immunohistochemical expression of glypican-1 in the diagnosis of lung squamous cell carcinoma (SCC). This retrospective study included a total of 68 cases, of which 36 were diagnosed as SCC and 32 as adenocarcinoma (ADC). Furthermore, glypican-1 expression was compared with the expressions of p63, thyroid transcription factor-1 (TTF-1), and napsin A. All cases of SCC except one showed positive immunostaining to glypican-1; 35/36 (97.2%) cases, and predominantly scored 3 +. While only 5 cases of ADC showed positive immunostaining to glypican-1, having a score of 1 + or 2 +. The difference between glypican-1 expression of the two tumor types was highly significant (p value < 0.001). The sensitivity, specificity, and overall accuracy of glypican-1 expression for differentiating lung SCC from ADC were 97.2%, 84.4%, and 91.2%, respectively. The sensitivity of glypican-1 is more than p63 in the diagnosis of lung SCC. Glypican-1 can be added as a new diagnostic marker to help in the accurate discrimination between poorly differentiated lung SCC and solid predominant adenocarcinoma cases. [ABSTRACT FROM AUTHOR]

Cancer-associated thrombosis (CAT) can increase morbidity and mortality for cancer patients. Therefore, guidelines recommend predicting VTE risk and thromboprophylaxis for high-risk patients. Many studies critique oncologists' adherence to thromboprophylaxis guidelines for cancer patients. Meanwhile, most of these studies did not discuss in detail the reasons and facilitators for oncologists' adherence to thromboprophylaxis guidelines. Therefore, the current study aimed to explore in depth the perceptions and practices of oncologists working in oncology centers in Baghdad, Iraq, regarding VTE and its risk assessment among ambulatory cancer patients. A qualitative study with face-to-face individual-based interviews was conducted with oncologists working in four major oncology centers in Baghdad, Iraq using a semi-structured interview guide. The guide was developed based on previous relevant literature and validated by a panel of experts. The interviews were conducted from November 2023 to January 2024. Thematic analysis approach was used for data analysis. Thirty-one oncologists were interviewed in this study. Twenty-two of the interviewed oncologists reported that they detect VTE among their cancer patients. 64% of participating oncologists reported that they did not conduct VTE risk assessments for their cancer patients. Only four oncologists reported assessing VTE risk using the Khorana score. 58% of oncologists reported that they prescribe thromboprophylaxis for high-risk patients; meanwhile, only 11% of them reported prescribing anticoagulants in a dose similar to that reported by thromboprophylaxis guidelines. 77% of participating oncologists reported that pharmacists have a significant role in preventing cancer-related thrombosis by helping physicians prescribe a safe and effective prophylactic anticoagulant and in calculating VTE risk scores. In conclusion, CAT is commonly diagnosed among Iraqi cancer patients. VTE risk assessment for ambulatory cancer patients is rarely conducted by oncologists working at Oncology centers in Baghdad, Iraq. The prophylactic anticoagulants were rarely prescribed in appropriate dose and/or duration for patients at high risk of VTE. Pharmacists can help oncologists follow thromboprophylaxis guidelines by calculating VTE risk score and recommending a safe and effective dose of appropriate prophylactic anticoagulant.Educating and training oncologists about VTE risk assessment is recommended to enhance their practice in thromboprophlaxis. [ABSTRACT FROM AUTHOR]