Search Results (8,401)

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Background: Pancreatic adenocarcinoma (PDAC) with liver oligometastases (LOM) presents a therapeutic challenge, with optimal management strategies remaining uncertain. This study evaluates the long-term outcomes, patterns of disease progression, and potential factors influencing prognosis in this patient subset. Methods: Patients diagnosed with PDAC and LOM were retrospectively analyzed. Disease progression patterns, causes of death, and predictors of long-term outcomes were assessed. Results: Among 1442 patients diagnosed with metastatic PDAC between November 2009 and July 2024, 129 (9%) presented with LOM, defined as ≤3 liver lesions each measuring <2 cm. Patients with LOM had significantly improved overall survival (OS) compared to those with high-burden disease (p = 0.026). The cause of death (local regional disease vs. systemic disease) could be determined in 74 patients (57%), among whom age at diagnosis, history of smoking, and white blood cell (WBC) count differed significantly between groups. However, no significant difference in OS was observed between the two groups (p = 0.64). Sixteen patients (22%) died from local complications of the primary tumor, including 6 patients (7%) who showed no evidence of new or progressive metastases. In competing risk and multivariable analysis, a history of smoking remained the only factor significantly associated with death due to local complications. Conclusions: Approximately one in five patients with PDAC-LOM died from local tumor-related complications—some without metastatic progression—highlighting a potential role for surgical intervention. Further multicenter studies are warranted to refine diagnostic criteria and better identify patients who may benefit from surgery. Full article

As the body of knowledge on feline mammary tumors (FMTs) continues to grow, their histological classification and grading systems have undergone revisions and updates to better reflect the biological behavior of these tumors. In this review, the historical evolution of these frameworks is traced and later revisited in the context of their prognostic relevance. Numerous studies have investigated clinicopathological prognostic factors in feline mammary carcinomas (FMCs); however, the heterogeneity in assessment methods, inclusion criteria for survival analysis, and the clinical endpoints considered can often complicate direct comparisons across different studies and may contribute to seemingly conflicting results. Furthermore, the small cohort size of many studies limits the robustness and transferability of their findings. This paper provides an updated overview of the epidemiological, clinical, and pathological prognostic factors of these tumors, while also highlighting current challenges, methodological limitations, and areas for future improvement. Full article

Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies characterized by a poor prognosis and resistance to conventional therapies. Mounting evidence suggests the pivotal role of epithelial–mesenchymal transition (EMT) in tumor progression, metastasis, and therapeutic resistance in these cancers. Protein induced by vitamin K absence II (PIVKA-II)—a valuable HCC detector—has ultimately emerged as a potentially relevant biomarker in PDAC, serving as both a serum biomarker and a prognostic indicator. This study investigates the putative link between PIVKA-II expression and the EMT process in HCC and PDAC. Using a Western blot analysis and electrochemiluminescence immunoassay (ECLIA), we quantified PIVKA-II serum levels alongside two canonical EMT markers—Vimentin and E-cadherin—in selected cohorts. Emerging data suggest a dual, context-dependent role for PIVKA-II. Beyond its diagnostic value in both malignancies, its co-expression with EMT markers points to a potential mechanistic involvement in tumor invasiveness and phenotypic plasticity. Notably, the selective detection of E-cadherin in HCC implies limited EMT activation and a preservation of the epithelial phenotype, whereas the higher expression of Vimentin in PDAC reflects a more substantial shift toward EMT. We provide a comprehensive analysis of key molecular markers, their involvement in EMT-driven pathophysiological mechanisms, and their potential as novel diagnostic tools. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this context, cancer vaccines have emerged as a promising immunotherapeutic strategy. By activating the host immune system to eliminate tumor cells, cancer vaccines offer high specificity, low toxicity, and the potential to induce long-lasting immune memory. These advantages have positioned them as a focal point in cancer immunotherapy research. This paper provides a comprehensive overview of recent clinical advances in lung cancer vaccines, discusses the major challenges impeding their clinical application, and explores potential strategies to overcome these barriers. Full article

Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article

Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, requiring innovative approaches to evaluate new therapies. Considering the high activity of unsymmetrical bisacridines (UAs) in PC monolayer cultures, we employed multicellular tumor spheroids (MCTS) to assess whether UAs retain pro-apoptotic activity under more physiologically relevant conditions. Ultra-low attachment plates were used to form spheroids from three PC cell lines (Panc-1, MIA PaCa-2, and AsPC-1) with different genotypes and phenotypes. The effects of UA derivatives (C-2028, C-2045, and C-2053) were evaluated using microscopy and flow cytometry (7-AAD for viability and annexin V-FITC/PI for membrane integrity). UAs altered the morphology of the spheroids and reduced their growth. Notably, Panc-1 spheroids exhibited compromised integrity. The increase in 7-AAD⁺ cells confirmed diminished cell viability, and annexin V-FITC assays showed apoptosis as the dominant death pathway. Interestingly, the exact derivative was most active against a given cell line regardless of culture conditions. These results confirm that UAs maintain anticancer activity in 3D cultures and induce apoptosis, with varying efficacy across different cell lines. This underscores the value of diverse cellular models in compound evaluation and supports UAs as promising candidates for pancreatic cancer therapy. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

Purpose: The present study aims to evaluate alterations in the peripapillary retinal nerve fiber layer (RNFL) thickness in pediatric patients following surgical resection of childhood-onset craniopharyngioma (CP) and to identify tumor characteristics and other factors influencing these alterations, including changes in the lesion’s location. Design: retrospective clinical cohort study. Methods: A retrospective analysis was conducted on 73 eyes from 38 patients with CP and 64 eyes from 32 age- and sex-matched healthy controls. The mean age of the CP patients was 10.3 ± 4.2 years (range 4–17), while the control group had a mean age of 10.5 ± 3.1 years (range 4–17). Optical coherence tomography (OCT) was used to assess the peripapillary RNFL thickness in the study and control groups. RNFL thickness was analyzed in the superior, inferior, and average sectors, as well as across eight optic nerve sectors. Tumor characteristics were evaluated to determine their correlation with changes in RNFL thickness in individual sectors. Results: Postoperative thickness of peripapillary RNFL in all individual sectors was significantly reduced in the CP group compared to healthy controls. Location, tumor volume, maximum tumor diameter, calcification, ventriculoperitoneal shunt, surgery technique, total resection, presence of Rosenthal fibers, and reoperation due to progression or recurrence correlated with damage to RNFL. Conclusions: CP is associated with significant reductions in RNFL thickness, indicating the tumor’s impact on optic nerve fibers. OCT is a valuable tool for monitoring visual pathway impairment and postoperative outcomes. Correlations between RNFL thickness in individual sectors and clinical parameters may offer valuable insights for diagnosis and monitoring, underlining their potential role in predicting visual outcomes. Regular RNFL evaluation should be integrated into the long-term care of CP patients to optimize visual prognosis and detect progressive or residual damage. Full article

Cancer remains a major global health challenge requiring the development of diagnostic and therapeutic strategies. Liquid biopsy is considered a promising minimally invasive tool for cancer screening, prognosis and treatment monitoring. Recent studies suggest that neutrophil extracellular traps (NETs) may also be potential liquid biopsy markers. NETs are web-like chromatin structures released by neutrophils in response to various stimuli to trap and neutralize pathogens. However, excessive or dysregulated NET formation has been implicated in tumor progression and metastasis. Elevated levels of NETs have been observed in patients with various types of cancer and correlate with disease stage and prognosis. The presence of NET markers such as citrullinated histone H3 (H3Cit), neutrophil elastase (NE) and myeloperoxidase (MPO) has been associated with higher tumor burden and poorer clinical outcomes. Several studies have shown a positive correlation between NET markers and circulating free DNA (cfDNA) levels, suggesting that NETs may increase the sensitivity of liquid biopsy in detecting and monitoring cancer progression. This review examines the role of NETs in the tumor microenvironment, their contribution to cancer progression and metastasis, and their potential use in liquid biopsy and cancer therapy. Full article

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies. Full article

Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC. Full article

This review delves into the characteristics of lipid metabolism reprogramming in cancer cells and immune cells within the tumor microenvironment (TME), discussing its role in tumorigenesis and development and analyzing the value of lipid metabolism-related molecules in tumor diagnosis and prognosis. Cancer cells support their rapid growth through aerobic glycolysis and lipid metabolism reprogramming. Lipid metabolism plays distinct roles in cancer and immune cells, including energy supply, cell proliferation, angiogenesis, immune suppression, and tumor metastasis. This review focused on shared lipid metabolic enzymes and transporters, lipid metabolism-related oncogenes and non-coding RNAs (ncRNAs) involved in cancer cells, and the influence of lipid metabolism on T cells, dendritic cells (DCs), B cells, tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), and natural killer cells (NKs) within TME. Additionally, the role of lipid metabolism in tumor diagnosis and prognosis was explored, and lipid metabolism-based anti-tumor treatment strategies were summarized, aiming to provide new perspectives for achieving precision medicine. Full article

Malignant gastric outlet obstruction (MGOO) is a serious complication arising from advanced gastric or pancreatic head cancer, significantly impairing patients’ quality of life by disrupting oral intake and inducing severe gastrointestinal symptoms. With benign causes such as peptic ulcer disease on the decline, malignancies now account for 50–80% of gastric outlet obstruction (GOO) cases globally. This review outlines the pathophysiology, evolving epidemiology, and treatment modalities for MGOO. Therapeutic approaches include conservative management, endoscopic stenting, surgical gastrojejunostomy (GJ), stomach partitioning gastrojejunostomy (SPGJ), and endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While endoscopic stenting offers rapid symptom relief with minimal invasiveness, it has higher rates of re-obstruction. Surgical options like GJ and SPGJ provide more durable palliation, especially for patients with longer expected survival. SPGJ, a modified surgical technique, demonstrates reduced incidence of delayed gastric emptying and may improve postoperative oral intake and survival compared to conventional GJ. EUS-GE represents a promising, minimally invasive alternative that combines surgical durability with endoscopic efficiency, although long-term data remain limited. Treatment selection should consider patient performance status, tumor characteristics, prognosis, and institutional resources. This comprehensive review underscores the need for individualized, multidisciplinary decision-making to optimize symptom relief, nutritional status, and overall outcomes in patients with MGOO. Full article