Search Results (694)

Background: Social determinants of health (SDOH) are critical contributors to cancer disparities, influencing prevention, early detection, treatment access, and survival outcomes. Addressing these disparities is essential in achieving equitable oncology care. Artificial intelligence (AI) is revolutionizing oncology by leveraging advanced computational methods to address SDOH-driven disparities through predictive analytics, data integration, and precision medicine. Methods: This review synthesizes findings from systematic reviews and original research on AI applications in cancer-focused SDOH research. Key methodologies include machine learning (ML), natural language processing (NLP), deep learning-based medical imaging, and explainable AI (XAI). Special emphasis is placed on AI’s ability to analyze large-scale oncology datasets, including electronic health records (EHRs), geographic information systems (GIS), and real-world clinical trial data, to enhance cancer risk stratification, optimize screening programs, and improve resource allocation. Results: AI has demonstrated significant advancements in cancer diagnostics, treatment planning, and survival prediction by integrating SDOH data. AI-driven radiomics and histopathology have enhanced early detection, particularly in underserved populations. Predictive modeling has improved personalized oncology care, enabling stratification based on socioeconomic and environmental factors. However, challenges remain, including AI bias in screening, trial underrepresentation, and treatment recommendation disparities. Conclusions: AI holds substantial potential to reduce cancer disparities by integrating SDOH into risk prediction, screening, and treatment personalization. Ethical deployment, bias mitigation, and robust regulatory frameworks are essential in ensuring fairness in AI-driven oncology. Integrating AI into precision oncology and public health strategies can bridge cancer care gaps, enhance early detection, and improve treatment outcomes for vulnerable populations. Full article

Background/Objectives: Cancer is a major public health burden in Serbia and a factor influencing long-term disaster readiness by straining health system capacity. This study examined spatial and temporal trends in incidence and mortality for eight major cancers among women in Central Serbia (1999–2021) to inform targeted prevention and preparedness strategies. Methods: Standardised rates from national datasets were analysed using the Mann–Kendall trend test and Sen’s slope estimator. Geographic disparities were mapped in ArcGIS Pro 3.2. Mortality trends were assessed only for statistically reliable series. Results: Breast cancer incidence increased in six counties, while cervical cancer declined in several areas, likely reflecting screening success. Colorectal, bladder, pancreatic, and lung and bronchus cancers showed rising incidence; lung and bronchus cancer mortality increased in 16 counties, indicating growing demand for chronic respiratory care. These shifts may reduce surge capacity during disasters by increasing the baseline burden on healthcare infrastructure. Regional disparities highlight uneven system resilience. Conclusions: Aligning cancer control measures—especially for high-burden cancers like lung—with emergency preparedness frameworks is essential to strengthen health system resilience, particularly in resource-limited regions. Full article

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

A total of 24 novel steroidal derivatives were synthesized, including 1,3,4-thia(selena)diazolines and structurally unique spirothiadiazolines, obtained through intramolecular cyclization under standard acetylation conditions. This strategy was further extended to the construction of a novel dimeric compound bearing a thiadiazoline linker. Seleno- and thiosemicarbazone precursors were derived from various functionalized steroidal monomers and dimers via straightforward synthetic protocols. Key intermediates included aldehyde 7 and ketones 16, 19, and 24. Rotameric equilibria were observed in certain thiosemicarbazones, attributed to partial double-bond character in the N–CS bond. Cyclization yielded heterocyclic systems as epimeric mixtures, and in some cases, inseparable mixtures of isomers were obtained due to low diastereoselectivity. Full structural elucidation of epimeric pairs was achieved using 2D NMR and IR spectroscopy, with compounds 2, 3, 5, 11, 17, 27, 28a, and 28b further confirmed by single-crystal X-ray diffraction. Preliminary antiproliferative assays against human cancer cell lines revealed GI₅₀ values below 10 µM for compounds 21, 22, and 27. Full article

Gastrointestinal (GI) cancers, particularly colorectal and gastric cancers, majorly contribute to global cancer mortality due to frequent late-stage diagnosis and poor therapeutic response in advanced disease. Earlier detection of GI cancers is needed for a better prognosis. This review examines both traditional and emerging biomarkers that contribute significantly to early detection, prognostication, and prediction of therapeutic resistance or sensitivity. Specifically, we highlight the diagnostic utility of non-invasive liquid biopsy biomarkers such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes. Moreover, we discuss the prognostic and predictive value of conventional genetic alterations, including KRAS, BRAF, and HER2. Although new findings have shown the advantages of liquid biopsy over colonoscopy, there are still limitations to the technique, such as cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. Further studies are required to test the validity and accessibility of liquid biopsy and its biomarkers in order to advance personalized diagnosis and treatments for GI cancers. Such a study will be helpful for clinicians to better manage patients with GI cancers. Full article

The Wntβ-catenin signaling pathway is a key regulator of gastrointestinal (GI) tumorigenesis, modulating cellular processes such as proliferation, differentiation, and epithelial-to-mesenchymal transition (EMT). In this review, we evaluate the expression and mutation profiles of core Wntpathway components in the most common GI malignancies. Our findings outline notable alterations in ligands, receptors, co-receptors, and intracellular effectors across different GI cancers. In gastric cancer tissue, elevated levels of Wnt proteins, FZD7 receptor, and LRP5/6, along with β-catenin accumulation and reduced APC expression, are associated with poor prognosis. In colorectal cancer samples, common APC mutations and Wnt ligand overexpression contribute to β-catenin nuclear localization and EMT. Esophageal cancer specimens exhibit co-overexpression of Wnt2 and Wnt5A, as well as receptors such as FZD2 and FZD6, which are linked to worse prognosis and reduced survival. Liver cancer tissue commonly harbors CTNNB1 mutations, which encode β-catenin and are associated with poor differentiation. In pancreatic cancer samples, overexpression of Wnt ligands, FZD receptors, and β-catenin is associated with the presence of distant metastasis and poor clinical outcomes. In conclusion, this pathway represents a promising avenue for identifying novel diagnostic, prognostic, and therapeutic biomarkers in GI cancers, warranting further clinical investigation. Full article

Helicobacter pylori (H. pylori) is a common gastric pathogen and a leading cause of non-cardia gastric cancers. Known determinants can affect the diagnostic accuracy of invasive clinical methods for H. pylori diagnosis. The objective of this study was to determine the diagnostic accuracy of the CLOtest, a rapid urease test, and the histopathologic examination compared with polymerase chain reaction (PCR) in esophagogastroduodenoscopy patients from a population with high prevalence and other risk factors that may influence diagnostic accuracy. From 2018 to 2022, patients were recruited from a medical care center serving the southwestern Navajo Nation. Summary statistics were calculated using PCR as the comparator to the CLOtest and histopathologic examination. Among the 466 study participants, 27.1% (95% CI 22.9, 31.7%) tested positive for H. pylori using PCR to detect pathogen DNA. Sensitivity was lowest for the CLOtest (57.0%; 95% CI 45.8, 67.6) and highest for the combination the CLOtest and histopathology (72.2%; 95% CI 62.8, 80.4). Patient history of infection or possible GI bleeding influenced sensitivity by over 5%. In high H. pylori prevalence areas, emphasis should be placed on ensuring adequate treatment of suspected positive infections as false-positive results were rare. Including a more sensitive test might reduce the number of individuals falsely classified as H. pylori negative. Full article

Gastrointestinal (GI) cancers represent a major global health burden. Among them, colorectal cancer (CRC) is the most common type, followed by esophagus, stomach, liver, and pancreatic cancer. Since disturbance of the gut microbiota has been directly associated with the development of severe health issues, including cancer, probiotic administration may induce dysbiosis reversion and ameliorate carcinogenesis. Therefore, manipulation of the gut microbiota composition based on probiotic utilization has gradually attained scientific interest as a potent therapeutic modality for GI cancers. This review aims to synthesize the current in vitro and in vivo evidence on probiotics’ effectiveness in GI cancer chemoprevention and treatment. It also provides a classification of the fundamental anticancer features of probiotics, including antiproliferation and cell death induction, anticarcinogenic compound production, reduction in chemotherapy-related toxicity, gut microbiota modulation, intestinal barrier improvement, antioxidant activity, immunomodulatory/anti-inflammatory effects, and carcinogen detoxification. Finally, it underscores the future perspectives and challenges of probiotic administration to individuals. In this regard, it emphasizes the exploitation of advanced encapsulation techniques and the development of novel genetically engineered probiotics and next-generation probiotics as feasible ways to improve their bioavailability, ensure their targeted delivery, and eliminate their mild side effects to the host’s health. Full article

Helminths that inhabit the gastrointestinal (GI) tract represent some of the most significant infectious agents impacting health. The interaction between the human microbiota, GI helminths, and their host occurs through multiple complex pathways, altering the host’s immune system and the dynamics of the commensal gut microbiota (GM). These interactions also largely influence a balanced state of homeostasis and health promotion and robustly activate the immune system, facilitating tumor eradication and mitigating the challenges of drug resistance. Furthermore, incorporating microbial metabolites into radiotherapy and chemotherapy reduces the intense adverse effects of these treatments while enhancing their overall effectiveness. The interplay between GM and helminths, as well as their metabolites, significantly impacts the development, prognosis, and treatment of cancer. The interaction mechanisms between GI helminths and the GM are not fully elucidated. Thus, understanding a beneficial biological relationship can reveal hidden mechanisms for controlling and inhibiting cancer pathways in humans by providing insights into cellular processes and potential therapeutic targets. This knowledge can be applied to develop more effective cancer treatments. This review outlines the existing research on GM metabolites in cancer, intending to offer innovative pathways for future cancer treatment. Full article

Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates of CIT. This complication often leads to treatment delays, dose reductions, and elevated bleeding risk. This review provides a comprehensive overview of the pathophysiology, clinical implications, and management strategies of CIT in GI malignancies. CIT arises from several mechanisms: direct cytotoxicity to megakaryocyte progenitors, disruption of the marrow microenvironment, thrombopoietin dysregulation, and immune-mediated platelet destruction. Platinum agents, antimetabolites, and immune checkpoint inhibitors can contribute to these effects. Oxaliplatin-induced CIT may occur acutely via immune mechanisms or chronically through marrow suppression. CIT affects 20–25% of solid tumor patients, with highest rates in those receiving gemcitabine (64%), carboplatin (58%), and oxaliplatin (50%). Within GI cancer regimens, FOLFOXIRI and S-1 plus oxaliplatin show higher CIT incidence compared to FOLFIRI and CAPIRI. Thrombocytopenia is graded by severity, from mild (Grade 1–2) to severe (Grade 3–4), and often necessitates treatment adjustments, transfusions, or supportive therapies. Current strategies include chemotherapy dose modification, platelet transfusion, and thrombopoietin receptor agonists (TPO-RAs) like romiplostim and eltrombopag. While platelet transfusions help in acute settings, TPO-RAs may preserve dose intensity and reduce bleeding. Emerging agents targeting megakaryopoiesis and marrow protection offer promising avenues for long-term management. Full article

Background: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (≥40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ≥ 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73–10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy. Full article

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, or a combination of these treatments. Emerging modalities within immunotherapy are anticipated to extend the results with conventional therapy by stimulating the patient’s own intrinsic potential for tumor-specific immunologic rejection. Combination regimens of chemotherapy and tumor-infiltrating lymphocyte (TIL) therapy in advanced colorectal cancer and pancreatic cancer, autologous monocyte therapy in advanced gastric cancer, and CAR-T therapy trained against GI-selective tumor antigens such as carcinoembryonic antigen are currently being studied. Clinical trials are underway to study the combination of various chemotherapeutic agents along with immunotherapy in the management of cholangiocarcinoma, hepatocellular carcinoma, and esophageal cancer. Alternative therapies are needed based on the tumor immune microenvironment, which can lead to a personalized approach to treatment. In this review, we discuss the current status of various modalities of immunotherapy in common GI malignancies, along with their mechanisms of immune activation and cancer suppression. We will also discuss the use of immunotherapy in less common solid GI malignancies and touch on recent advancements and clinical trials. Full article

Background: Gastrointestinal (GI) cancer patients face a four-fold higher suicide risk than the general US population. This study explores psychosocial aspects of GI cancer patient experiences, assessing suicidal ideation and behavior, mental distress during treatment phases, and psychosocial factors on mental health. Methods: A two-phase mixed-methods approach involved a web-based survey and follow-up interviews. Quantitative data analysis validated mental health and suicidal ideation constructs, and correlation analyses were performed. The patient journey was charted from diagnosis to treatment. Results: Two hundred and two individuals participated, with 76 from the rural Appalachian region and 78 undergoing treatments. Quantitative analysis showed a higher prevalence of passive suicidal ideation than active planning. The post-treatment recovery period was the most emotionally challenging. Qualitative data emphasized emotional support and vulnerability to isolation. Care quality concerns included individualized treatment plans and better communication. Patients also needed clear, comprehensive information about treatment and side effects. The in-depth interview with four GI cancer patients revealed a healthcare system prioritizing expedient treatment over comprehensive care, lacking formal psychological support. AI emerged as a promising avenue for enhancing patient understanding and treatment options. Conclusions: Our research advocates for a patient-centric model of care, enhanced by technology and empathetic communication. Full article