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Background: Understanding the risk relationship between statin use and immunerelated adverse events (irAEs) in patients undergoing immune checkpoint inhibitors (ICIs) therapy is crucial for optimizing oncological management. Objective: This study aimed to investigate whether the use of statins increases the risk of irAEs in patients receiving ICI therapy. Methods: This study primarily utilized data from FAERS database. Multivariable logistic regression was the principal method of analysis, and the Benjamini-Hochberg procedure was employed to adjust for multiple hypothesis testing. Results: In a group of 145,214 patients undergoing ICI therapy, 9,339 reported using statin medications. Multivariable analysis indicated an increased risk of irAEs among statin users (OR 1.199, 95% CI: 1.141-1.261; FDR p < 0.001) in comparison to those not using statins. Notably, increased risks were observed particularly in patients diagnosed with lung, pancreatic, and renal cancers. The link between statin usage and increased irAEs risk remained consistent across various ICIs treatments. Conclusions: Statin medication usage is linked to an elevated probability of experiencing irAEs in patients enrolled in ICI therapy. In cancer patients receiving immune checkpoint inhibitors, careful consideration of statin use is essential to avoid potentially increased irAEs risk. These findings provide critical guidance for clinicians in developing treatment strategies that balance therapeutic efficacy and safety in oncological management. [ABSTRACT FROM AUTHOR]

Background: The promise of immune checkpoint inhibitors (ICIs) therapy in cancer treatment is tempered by the occurrence of immune-related adverse events (irAEs). Many patients undergoing ICIs also take aspirin, but the association between aspirin and irAEs is not well understood. Methods: This study analyzed adverse reaction data associated with the use of ICIs in the US Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database, from the approval date of each drug until 1 October 2022. Multivariate logistic regression was employed to assess the association of aspirin use with irAEs in patients receiving ICIs. Results: The results indicated that aspirin use was associated with an increased risk of irAEs in a pan-cancer analysis, with a more pronounced association in specific cancer types such as lung cancer, mesothelioma, and pancreatic cancer. However, in lymphoma, aspirin use was associated with a reduced risk of irAEs. Furthermore, aspirin use was associated with an increased risk of certain irAEs, such as anemia, colitis, myocarditis, myositis, pancreatitis, pericarditis, and pneumonia, while it was associated with a reduced risk of rash, Stevens-Johnson syndrome, and thyroiditis. Conclusion: This study has unveiled an association between aspirin use and irAEs in cancer patients receiving ICIs therapy, emphasizing the need for individualized consideration of patients' medication history when devising cancer treatment plans to enhance efficacy and reduce risks. [ABSTRACT FROM AUTHOR]

Background: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. Methods: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-oneout method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. Results: In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. Conclusion: This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients. [ABSTRACT FROM AUTHOR]

Frailty refers to a decline in the physiological functioning of one or more organ systems. It remained unclear whether variations in the trajectory of frailty over time were associated with subsequent cognitive change. The aim of the current study was to investigate the association between frailty trajectories and subsequent cognitive decline based on the Health and Retirement Study (HRS). A total of 15,454 participants were included. The frailty trajectory was assessed using the Paulson-Lichtenberg Frailty Index, while the cognitive function was evaluated using the Langa-Weir Classification. Results showed that severe frailty was significantly associated with the subsequent decline in cognitive function (ß [95% CI] = -0.21 [-0.40, -0.03], p = 0.03). In the five identified frailty trajectories, participants with mild frailty (inverted U-shaped, ß [95% CI] = -0.22 [-0.43, -0.02], p = 0.04), mild frailty (U-shaped, ß [95% CI] = -0.22 [-0.39, -0.06], p = 0.01), and frailty (ß [95% CI] = -0.34 [-0.62, -0.07], p = 0.01) were all significantly associated with the subsequent cognition decline in the elderly. The current study suggested that monitoring and addressing frailty trajectories in older adults may be a critical approach in preventing or mitigating cognitive decline, which had significant implications for healthcare. [ABSTRACT FROM AUTHOR]

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear. Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated. Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results. Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Smoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients. Methods: This study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint. Results: Of the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p < 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p<0.01] had an increased risk of death. However, quitting smoking was not associated with improved survival [HR, 0.90 (95% CI, 0.77-1.04), p = 0.16]. The overall survival increased with the increase of smoking cessation years. Conclusions: In lung cancer patients with brain metastases, smoking was associated with an increased risk of death, but quitting smoking was not associated with improved survival. [ABSTRACT FROM AUTHOR]

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K--Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infectioninduced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions. [ABSTRACT FROM AUTHOR]

Intracranial aneurysm subarachnoid hemorrhage (SAH) is a cerebrovascular disorder associated with high overall mortality. Currently, the underlying mechanisms of pathological reaction after aneurysm rupture are still unclear, especially in the immune microenvironment, inflammation, and relevant signaling pathways. SAH-induced immune cell population alteration, immune inflammatory signaling pathway activation, and active substance generation are associated with pro-inflammatory cytokines, immunosuppression, and brain injury. Crosstalk between immune disorders and hyperactivation of inflammatory signals aggravated the devastating consequences of brain injury and cerebral vasospasm and increased the risk of infection. In this review, we discussed the role of inflammation and immune cell responses in the occurrence and development of aneurysm SAH, as well as the most relevant immune inflammatory signaling pathways [PI3K/Akt, extracellular signal-regulated kinase (ERK), hypoxia-inducible factor-1a (HIF-1α), STAT, SIRT, mammalian target of rapamycin (mTOR), NLRP3, TLR4/nuclear factor-kB (NF-kB), and Keap1/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/ARE cascades] and biomarkers in aneurysm SAH. In addition, we also summarized potential therapeutic drugs targeting the aneurysm SAH immune inflammatory responses, such as nimodipine, dexmedetomidine (DEX), fingolimod, and genomic variation-related aneurysm prophylactic agent sunitinib. The intervention of immune inflammatory responses and immune microenvironment significantly reduces the secondary brain injury, thereby improving the prognosis of patients admitted to SAH. Future studies should focus on exploring potential immune inflammatory mechanisms and developing additional therapeutic strategies for precise aneurysm SAH immune inflammatory regulation and genomic variants associated with aneurysm formation. [ABSTRACT FROM AUTHOR]

Purpose: Current deep learning methods for dose prediction require manual delineations of planning target volume (PTV) and organs at risk (OARs) besides the original CT images. Perceiving the time cost of manual contour delineation, we expect to explore the feasibility of accelerating the radiotherapy planning by leveraging only the CT images to produce high-quality dose distribution maps while generating the contour information automatically. Materials and Methods: We developed a generative adversarial network (GAN) with multi-task learning (MTL) strategy to produce accurate dose distribution maps without manually delineated contours. To balance the relative importance of each task (i.e., the primary dose prediction task and the auxiliary tumor segmentation task), a multi-task loss function was employed. Our model was trained, validated and evaluated on a cohort of 130 rectal cancer patients. Results: Experimental results manifest the feasibility and improvements of our contour-free method. Compared to other mainstream methods (i.e., U-net, DeepLabV3+, DoseNet, and GAN), the proposed method produces the leading performance with statistically significant improvements by achieving the highest HI of 1.023 (3.27E-5) and the lowest prediction error with ΔD95 of 0.125 (0.035) and ΔDmean of 0.023 (4.19E-4), respectively. The DVH differences between the predicted dose and the ideal dose are subtle and the errors in the difference maps are minimal. In addition, we conducted the ablation study to validate the effectiveness of each module. Furthermore, the results of attention maps also prove that our CT-only prediction model is capable of paying attention to both the target tumor (i.e., high dose distribution area) and the surrounding healthy tissues (i.e., low dose distribution areas). Conclusion: The proposed CT-only dose prediction framework is capable of producing acceptable dose maps and reducing the time and labor for manual delineation, thus having great clinical potential in providing accurate and accelerated radiotherapy. Code is available at https://github.com/joegit-code/DoseWithCT [ABSTRACT FROM AUTHOR]

Extramedullary plasmacytoma (EMP) in the vulva is extremely rare. The current study presents, for the first time, a case of EMP in the left labia majora in a 36-year-old patient during pregnancy. A painful 7x4x2-cm mass with ulceration, pus and blood scabs, previously misdiagnosed as vulvar ulcer in a local hosipital, was proven to be an EMP by biopsy. Upon magnetic resonance imaging, the tumor was shown to occur in the left labia majora without lymphadenopathy. A complete multiple myeloma (MM) workup excluded coexistence with MM. The goal of treatment was to eradicate the tumor while synchronously preserving the vulva. Therefore, following the termination of the pregnancy, radiotherapy with a total dose of 4,500 cGy markedly reduced the size of the tumor. An extended local excision of the residual tumor, and anaplasty of the vulva preserved the appearance and function of the vulva to the utmost. No post-operative radiation was administered, as the resection margins were not microscopically involved. There was no relapse, metastasis or progression to MM in a 9-month post-operative follow-up period, but close follow-up and long-term surveillance are required. [ABSTRACT FROM AUTHOR]

Adult pineoblastomas (PBs) are rare central nervous system tumors. Little is known with regard to the clinical features and outcomes of adult PB, and optimal treatment strategies for adult PB remain to be determined. The current report describes a case of PB in a 46-year-old male, who presented with obstructive hydrocephalus due to a large pineal region mass. Considering the potential effect on quality of life, the patient underwent a partial resection. Postoperative radiotherapy, comprising prophylactic craniospinal irradiation at a dose of 34.2 Gy followed by a local 25.3-Gy 'boost' to the tumor site for a total dose of 59.5 Gy, resulted in the complete regression of the tumor without neurological deficits. The patient has remained free of recurrence for 36 months after radiotherapy. This case highlights a minimally invasive strategy to treat a rare pineal region tumor with significant involvement of critical structures that resulted in a favorable response and an excellent neurological outcome. The radiographic and histopathological features of PB are also reviewed, and the various treatment options reported in the literature are discussed. [ABSTRACT FROM AUTHOR]

Oxaliplatin (OX) has been widely used in adjuvant and palliative treatments of advanced colon cancer; however, cancer cells ultimately become resistant in the majority of cases. Therefore, the development of a novel strategy to overcome this resistance is important for the effective treatment of colon cancer. Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer; therefore, the present study used murine CT26 colon carcinoma cells to explore whether inhibition of autophagy by 3-methyladenine (3-MA) is able to enhance OX-induced apoptosis in vitro and OX-suppressed tumor growth in vivo. CT26 cells were treated with 3-MA, OX, or 3-MA plus OX, and the autophagy, apoptosis and proliferation of the CT26 cells was investigated. Additionally, the therapeutic efficiency of the combination of 3-MA and OX treatment was evaluated in vivo by determining the survival time of the tumor-bearing mice and, thus, tumor growth rate. The treatment of CT26 cells in vitro with OX alone increased autophagy as well as apoptosis, whereas treatment with 3-MA plus OX markedly inhibited OX-induced autophagy, but increased OX-induced cell apoptosis. Furthermore, the combination of OX and 3-MA treatment significantly suppressed tumor growth in vivo and prolonged mouse survival time when compared with OX treatment alone. Similarly, 3-MA increased OX-induced cell apoptosis and decreased autophagy in xenograft tumor tissues. Thus, the administration of 3-MA may increase tumor cell sensitivity to OX by reducing its autophagic effects and enhancing its apoptotic effects. Data obtained in the present study indicates that the clinical combination of an autophagy inhibitor with OX may increase the therapeutic effect of OX and improve the clinical outcome of patients with colon cancer. [ABSTRACT FROM AUTHOR]

Background The lung squamous cell carcinoma survival rate is very poor despite multimodal treatment. It is urgent to discover novel candidate biomarkers for prognostic assessment and therapeutic targets to lung squamous cell carcinoma (SCC). Results Herein a two-dimensional gel electrophoresis and ESI-Q-TOF MS/MS-based proteomic approach was used to identify differentially expressed proteins between lung SCC and adjacent normal tissues. 31 proteins with significant alteration were identified. These proteins were mainly involved in metabolism, calcium ion binding, signal transduction and so on. Cathepsin B (CTSB) was one of the most significantly altered proteins and was confirmed by western blotting. Immunohistochemistry showed the correlation between higher CTSB expression and lower survival rate. No statistically significant difference between CTSBshRNA treated group and the controls was observed in tumor volume, tumor weight, proliferation and apoptosis. However, the CTSB-shRNA significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. Moreover, CTSB, Shh and Ptch were up-regulated in patients with metastatic lung SCC, suggesting that hedgehog signaling might be activated in metastatic lung SCC which could affect the expression of CTSB that influence the invasive activity of lung SCC. Conclusions These data suggested that CTSB might serve as a prognostic and therapeutic marker for lung SCC. [ABSTRACT FROM AUTHOR]

This study aimed to explore the mechanism of adriamycin resistance in human chronic myelogenous leukemia cells. Proteomic approach was utilized to compare and identify differentially expressed proteins between human chronic myelogenous leukemia K562 cells and their adriamycin-resistant counterparts. The differentially expressed proteins were analyzed by 2-DE (two-dimensional gel electrophoresis), and protein identification were performed on ESI-Q-TOF MS/MS instrument. Out of the 35 differentially expressed proteins between the two cell lines, 29 were identified and grouped into 10 functional classes. Most of identified proteins were related to the categories of metabolism (24%), proteolysis (13%), signal transduction (21%) and calcium ion binding (6%), suggesting that alterations of those biological processes might be involved in adriamycin resistance of K562 cells. We believe this study may provide some clues to a better understanding of the molecular mechanisms underlying adriamycin resistance. [ABSTRACT FROM AUTHOR]

Platinum-based chemotherapy, such as cisplatin, is the primary treatment for human ovarian cancer. However, overcoming drug resistance has become an important issue in cancer chemotherapy. In this study, we performed 2-DE and ESI-Q-TOF MS/MS analysis to identify differential proteins expression between cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780-CP) ovarian cancer cell lines. Of the 14 spots identified as differentially expressed (±over twofold, P < 0.05) between the two cell lines, ten spots (corresponding to ten unique proteins) were positively identified by ESI-Q-TOF MS/MS analysis. These proteins include capsid glycoprotein, fructose-bisphosphate aldolase C, heterogeneous nuclear ribonucleoproteins A2/B1, putative RNA-binding protein 3, Ran-specific GTPase-activating protein, ubiquitin carboxyl-terminal hydrolase isozyme L1, stathmin, ATPSH protein, chromobox protein homolog3 and phosphoglycerate kinase 1. The proteins identified in this study would be useful in revealing the mechanisms underlying cisplatin resistance and also provide some clues for further research. [ABSTRACT FROM AUTHOR]