Explore the vast range of titles available.

Gastric cancer is a leading cause of cancer-related death worldwide. Recent evidence suggests that gastric cancer is a complex and heterogenous disease with emerging subtypes shown to affect response to treatment and survival. Immunotherapy is an advancing field and immune checkpoint inhibitors have become standard treatment options in numerous tumor types. In this review, we discuss the current and evolving use of checkpoint blockade, focusing on the anti-PD-1 inhibitor, pembrolizumab, for use in advanced gastric and gastroesophageal cancers.

Climate change is intensifying winters in temperate regions, posing a serious threat to Apis mellifera health. The gut microbiome, a distinct community of core bacterial species, is central to overwintering success by supporting immune function, nutrient assimilation, and pathogen resistance, but is highly sensitive to environmental stressors such as cold temperatures and dietary shifts. Stress-induced perturbations can reshape the composition and relative abundance of the gut microbiome in honey bees, leading to adverse effects on host health, physiological functions, and overwinter survival. Cold temperatures and additional stressors further destabilize the microbiome, compounding these effects. This review is the first to synthesize current knowledge on how extrinsic factors, such as diet, antibiotics, and pathogens, and intrinsic factors, including age and strain, influence the composition and function of the honey bee gut microbiota during the overwintering period. Given the increasing severity of winter conditions under climate change, a deeper understanding of microbiome–host–environment interactions is essential for improving honey bee resilience. By integrating evidence on the microbiome’s roles in nutrient utilization, immune modulation, and pathogen defense, this review outlines a framework to guide future research aimed at sustaining pollinator health and nutrition in a changing global climate.

In the United States, hepatocellular carcinoma (HCC) survival varies with tumor characteristics, patient comorbidities, and treatment. The effect of HCC etiology on survival is less clearly defined. The relationship between HCC etiology and mortality was examined using Surveillance, Epidemiology, and End Results–Medicare data. In a cohort of 11,522 HCC cases diagnosed from 2000 through 2014, etiologies were identified from Medicare data, including metabolic disorders (32.9%), hepatitis C virus (8.2%), alcohol (4.7%), hepatitis B virus (HBV, 2.1%), rare etiologies (0.9%), multiple etiologies (26.7%), and unknown etiology (24.4%). After adjusting for demographics, tumor characteristics, comorbidities and treatment, hazard ratios (HRs) and survival curves by HCC etiology were estimated using Cox proportional hazard models. Compared with HBV‐related HCC cases, higher mortality was observed for those with alcohol‐related HCC (HR 1.49; 95% confidence interval [95% CI] 1.25‐1.77), metabolic disorder–related HCC (HR 1.25; 95% CI 1.07‐1.47), and multiple etiology‐related HCC (HR 1.25; 95% CI 1.07‐1.46), but was not statistically significant for hepatitis C virus–related, rare disorder–related, and HCC of unknown etiology. For all HCC etiologies, there was short median survival ranging from 6.1 months for alcohol to 10.3 months for HBV. Conclusion: More favorable survival was seen with HBV‐related HCC. To the extent that HCC screening is more common among persons with HBV infection compared to those with other etiologic risk factors, population‐based HCC screening, applied evenly to persons across all HCC etiology categories, could shift HCC diagnosis to earlier stages, when cases with good clinical status are more amenable to curative therapy.

Honey bee gut microbiota play specific roles in promoting host growth and physiology by regulating the immune system, behavior, metabolism, and neurological processes. While the gut microbiota of honey bee queens, workers, and larvae has been extensively studied, less is known about the composition of gut microbiota in the winter worker bees. This study investigates the dynamics of the gut microbiota in overwintering adult worker bees, focusing on two commercial bee strains: Bolton™ bees and Mann Lake™ bees. These Apis mellifera strains were investigated under different storage conditions (indoor storage at 6 °C and outdoor storage in natural conditions) during the winter months (October, November, and December). Utilizing 16S rRNA gene amplicon sequencing, we characterized the microbial composition of the whole gut. We observed the Lactobacilli dominated in all the overwintering honey bee guts with a significantly higher abundance of unclassified Lactobacillus species in November, while Lactobacillus apis showed significantly higher abundance in October. Bolton bees exhibited significantly higher abundance levels of Bartonella (denoted as uncultured) and Bifidobacterium , along with an unexpected presence of Wolbachia . In contrast, Mann Lake bees demonstrated an increased abundance of Commensalibacter . Our results suggest that Shannon diversity is influenced by the month rather than by the bee strain or storage conditions. We also found significant differences in Bray Curtis diversity index by month. Overall, taxonomical abundance was not affected by whether the hives were stored outside or in constant temperature indoor storage. However, various bacterial species showed differences in abundance across different months, with slight variations observed between bee strains. Given the potential benefits of the honey bee gut microbiome for health and nutrition, our data suggests that the genus Lactobacillus may play a significant role in bee health during winter and overwintering storage.

Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although Helicobacter pylori (H. pylori) is the most significant risk factor for GC, several other gastrointestinal taxa—including Fusobacterium nucleatum (F. nucleatum)—have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. Bifidobacterium and Lactobacillus rhamnosus GG have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management.

Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4–7.4 %), major bleeding was 2.2 % (95 % CI = 0−4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7–23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.

Hepatocellular carcinoma (HCC) is a major cause of cancer-associated mortality worldwide and is expected to rise. Patients with early-stage disease may have a good prognosis with a 5-year survival rate of greater than 70%. However, the majority of patients are diagnosed with late-stage disease with a dismal overall survival rate of less than 16%. Therefore, there is a great need for advances in the treatment of advanced HCC, which for approximately the past decade, has been sorafenib. Immunotherapy is an evolving cancer treatment and has shown promise in treating patients with advanced HCC. In this review, we discuss the current standard of care for advanced HCC and then discuss the evolving role of immunotherapies.

Cancer stem cells (CSCs) are responsible for long-term maintenance of tumors and thought to play a role in treatment resistance. The interaction between stemness and immunogenicity of CSCs in the intrahepatic cholangiocarcinoma (iCCA) is largely unknown. Here, we used single-cell transcriptomic data to study immunogenicity of malignant cells in human iCCA. Using an established computerized method CytoTRACE, we found significant heterogeneity in stemness/differentiation states among malignant cells. We demonstrated that the high stemness malignant cells express much lower levels of major histocompatibility complex II molecules when compared to low stemness malignant cells, suggesting a role of immune evasion in high stemness malignant cells. In addition, high stemness malignant iCCA cells exhibited significant expression of certain cytokine members, including CCL2, CCL20, CXCL1, CXCL2, CXCL6, CXCL8, TNFRSF12A, and IL6ST, indicating communication with surrounding immune cells. These results indicate that high stemness malignant cells retain their intrinsic immunological feature that facilitate the escape of immune surveillance.

Background Current standard of care for advanced biliary tract cancer (BTC) is gemcitabine, cisplatin plus anti‐PD1/PD‐L1, but response rates are modest. The purpose of this study was to explore the efficacy and safety of durvalumab (anti‐PD‐L1) and tremelimumab (anti‐CTLA‐4), with and without an interventional radiology (IR) procedure in advanced BTC. Methods Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab and durvalumab for four combined doses followed by monthly durvalumab alone with and without an IR procedure until the progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6‐month progression‐free survival (PFS). Results Twenty‐three patients with advanced BTC were enrolled; 17 patients were assigned to treatment with durvalumab and tremelimumab (Durva/Treme); and 6 patients were treated with the combination of durvalumab, tremelimumab plus IR procedure (Durva/Treme + IR). The best clinical responses in the Durva/Treme arm were partial response (n = 1), stable disease (n = 5), progressive disease (n = 5), and in the Durva/Treme + IR arm: partial response (n = 0), stable disease (n = 3), progressive disease (n = 3). The median PFS was 2.2 months (95% CI: 1.3–3.1 months) in the Durva/Treme arm and 2.9 months (95% CI: 1.9–4.7 months) in the Durva/Treme + IR arm (p = 0.27). The median OS was 5.1 months (95% CI: 2.5–6.9 months) in the Durva/Treme arm and 5.8 months (95% CI: 2.9–40.1 months) in the Durva/Treme + IR arm (p = 0.31). The majority of AEs were grades 1–2. Conclusion Durva/Treme and Durva/Treme + IR showed similar efficacy. With a manageable safety profile. Larger studies are needed to fully characterize the efficacy of Durva/Treme ± IR in advanced BTC. The purpose of this study was to explore the efficacy and safety of two ICIs, durvalumab and tremelimumab, with and without an interventional radiology (IR) procedure in patients with advanced BTC. Durva/Treme + IR showed no difference in efficacy compared with Durva/Treme alone, but the safety profile of both cohorts was manageable. Larger studies are needed to fully characterize efficacy of Durva/Treme with or without IR in advanced BTCs.