Cancers最新文献

Background/Objectives: Peritoneal carcinomatosis is the leading cause of death in advanced ovarian cancer (AOC). Mesothelial cells lining the peritoneum modulate tumor implantation, yet the role of their apoptosis in metastasis development remains unclear. This study investigated the relationship between mesothelial cell apoptosis and metastatic spread in ovarian cancer (OC). Methods: The study included 26 patients with AOC, 11 with early-stage OC (EOC), and 13 healthy controls. Apoptotic activity in parietal peritoneal wall and omental mesothelial cells was assessed using the TUNEL technique. Metastases were classified as pushing or infiltrating. Associations with the peritoneal cancer index (PCI), BRCA mutation, and homologous recombination deficiency (HRD) status were analyzed. Results: Mesothelial cells adjacent to AOC metastases exhibited significantly higher apoptotic activity compared to controls (p < 0.05). Apoptosis was greater near infiltrating metastases than near pushing ones in both parietal (p < 0.01) and omental (p = 0.04) sites. The infiltration pattern was consistent between omental and parietal metastases (R = 0.588, p < 0.01). No significant differences in apoptosis were found between EOC and healthy controls, or in tumor and stromal cells between invasion types. Mesothelial apoptosis was independent of PCI, BRCA mutation, and HRD status. Conclusions: Our study suggests that mesothelial cell apoptosis may be associated with peritoneal spread in OC. Mesothelial cell apoptosis is more pronounced near infiltrative-type lesions, independent of BRCA/HRD status. These findings highlight mesothelial apoptosis as a relevant process in peritoneal dissemination. Further studies are needed to clarify its role in ovarian cancer progression.

Background: Oncological treatment remains a major clinical challenge. Despite therapeutic advances and the diversity of available approaches, many tumors continue to exhibit limited responsiveness to chemotherapy. In this context, nutrition has emerged as a promising complementary strategy to support cancer therapy. In particular, interventions based on nutritional deprivation have gained prominence due to their ability to modulate tumor metabolism, inducing alterations that may increase the sensitivity of cancer cells to conventional treatments. Accordingly, the present study aimed to evaluate the safety and efficacy of caloric restriction combined with chemotherapy in a Sarcoma-180 model, investigating its effects on immunological and hematological parameters, antioxidant activity, oxidative stress, and tumor and liver morphology, as well as DNA damage. Methods: Mice bearing Sarcoma-180 were randomly assigned to four groups: Ad Libitum (AL), Ad Libitum + Doxorubicin (ALDOX), Caloric Restriction (CR), and Caloric Restriction + Doxorubicin (CRDOX). Assessment included tumor weight and volume, food and caloric intake, hematotoxicity, lipid metabolism, oxidative stress and antioxidant markers, genotoxicity, morphological alterations in the tumor and liver, and overall survival. Results: The data obtained demonstrate that caloric restriction combined with doxorubicin is both safe and feasible, as it preserves body weight and does not induce metabolic disturbances. Importantly, this combined strategy produced a marked reduction in tumor volume and mass while also mitigating the hematotoxicity typically associated with doxorubicin. In peripheral blood, the regimen decreased chemotherapy-induced DNA damage, supporting a systemic protective effect. Consistently, the combination reduced oxidative stress markers (NOx and MDA) and enhanced antioxidant activity within the tumor. Histological analyses further confirmed these outcomes, showing tumor cell death with features compatible with apoptosis and reduced local invasion. Together, these data indicate that caloric restriction enhances the antitumor efficacy of doxorubicin while simultaneously improving treatment tolerance. Conclusions: This study demonstrates that caloric restriction, combined with doxorubicin, is safe, well-tolerated, and enhances the antitumor response in the Sarcoma-180 model.

Background: The prognostic impact of therapy-induced neutropenia in patients receiving definitive chemoradiotherapy for locally advanced thoracic esophageal cancer (EC) remains inadequately characterized. This study aimed to evaluate the association between grade 3-4 neutropenia and survival outcomes following docetaxel-cisplatin-5-fluorouracil (DCF) combined with radiotherapy (DCF-RT). Methods: Fifty patients with locally advanced thoracic EC were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m² (day 1), CDDP at 60 mg/m² (day 1), and 5-FU at 600 mg/m² (days 1 to 4), administered every four weeks for two cycles in combination with radiotherapy (60 Gy in 30 fractions). Toxicities were assessed using the Common Terminology Criteria for Adverse Events. Overall survival (OS), progression-free survival (PFS), locoregional control and distant metastasis-free survival were compared by neutropenia grade. Results: Grade 3-4 neutropenia occurred in 80% (95% CI: 66.3-90.0) of patients. The OS rate was significantly lower in those with grade 3-4 neutropenia than in those with grade 0-2 (p = 0.006). Multivariate analysis identified grade 3-4 neutropenia (HR 3.77; 95% CI: 1.35-10.56) and complete response (CR) (HR 0.47; 95% CI: 0.25-0.87) as independent prognostic factors for OS among patients who received definitive CRT. Among 38 patients with recurrence or residual disease, those with grade 3-4 neutropenia exhibited significantly greater reductions in lymphocyte counts at recurrence versus pretreatment (p = 0.012) compared with those with grade 0-2 neutropenia. Conclusions: Therapy-induced neutropenia is an independent prognostic factor for OS in locally advanced thoracic EC patients undergoing definitive DCF-RT. It may also serve as a predictor of insufficient lymphocyte recovery following chemoradiation.

Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic-catabolic signaling pathways such as mTOR, UPS, NF-κB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1/MuRF-1) through cytokines including IL-6 and TNF-α, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-κB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability.

Background: Skin cancer is known to be associated with aging, oxidative stress, and inflammation. The present study aimed to explore the association between PhenoAge, dietary inflammatory index (DII), and dietary oxidative balance index (DOBS) with skin cancer risk.

Methods: A total of 474 individuals aged over 20 years who had information on DII, DOBS, PhenoAge, socioeconomic and demographic factors, and self-reported skin cancer, and 16,154 without skin cancer were included in the National Health and Nutrition Examination Survey database (2005-2018). The combination of DII/DOBS was categorized into 3 categories: inflammation- and oxidation-promoting diet, inflammation- and oxidation-reducing diet, and composite diet. We applied logistic regression to estimate odds ratios (ORs) for the association of DII/DOBS and PhenoAge with skin cancer risk, after adjusting for covariates and survey year.

Results: PhenoAge was associated with an increased likelihood of skin cancer (OR 1.07, 95% CI 1.06 to 1.08, p < 0.001). DII and DOBS were associated with PhenoAge advancement of OR 1.28 (95% CI 1.20 to 1.36), OR 0.95 (95% CI 0.94 to 0.96), respectively (p < 0.001). After adjusting for all covariates, the comparison between the inflammation-oxidation-promoting diet and the inflammation-oxidation-reducing diet had a positive relationship with skin cancer (OR 2.19, 95% CI 1.29 to 3.72, p = 0.004). PhenoAge mediated 28.06% of the associations between DII/DOBS and skin cancer risk (p < 0.05). The association remained in the subgroup analysis.

Conclusion: Our results suggest that an inflammation- and oxidation-promoting diet is related to increased skin cancer risk and may be partly mediated by PhenoAge.

The intratumoral microbiota, comprising bacteria, fungi, and viruses within the tumor microenvironment, actively influences carcinogenesis. Key mechanisms include the induction of host DNA damage, modulation of critical oncogenic signaling pathways such as WNT-β-catenin, NF-κB, and PI3K, and the orchestration of inflammatory processes. The microbiome's interaction with the host immune system is complex and bidirectional. On one hand, specific microbes can foster a pro-tumorigenic niche by suppressing the activity of cytotoxic T cells and natural killer (NK) cells or by promoting the accumulation of immunosuppressive cell types like tumor-associated macrophages (TAMs). On the other hand, microbial components can serve as neoantigens for T cell recognition or produce metabolites that reprogram the immune landscape to enhance anti-tumor responses. The composition of this microbiome is emerging as a crucial factor influencing the outcomes of immunotherapies. Prospective investigations in cancer immunotherapy ought to prioritize mechanistic inquiry employing integrative multi-omics methodologies. The execution of meticulously designed clinical trials for the validation of microbial biomarkers, and the systematic, evidence-based development of microbiome-targeted therapeutic interventions aimed at enhancing antitumor immune responses.

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Background/objectives: In high-income settings, the incidence of metastatic breast cancer (MBC) at diagnosis has declined, reflecting the impact of effective screening and therapeutic advances. This study examined long-term trends in MBC incidence, mortality, and survival in a province of North Italy, an area characterized by high screening participation and broad access to modern systemic treatments.

Methods: All invasive breast cancer cases (n = 10,966) diagnosed between 2000 and 2022 were retrieved from the Reggio Emilia Cancer Registry (population: 532,000). Metastatic cases were defined "early" if distant metastases occurred within six months of diagnosis. Mortality trends were assessed using joinpoint regression to estimate annual percentage changes (APCs). One-, three-, and five-year survival probabilities were calculated, with follow-up through December 2024.

Results: Overall, 511 cases (4.7%) were "early" metastatic breast cancers at diagnosis. This proportion declined from 6.4% in 2000-2003 to 3.8% in 2019-2022. One-year mortality decreased from 38.4% to 26.7% (APC = -6.6; 95% CI -13.1 to -0.5), and two-year mortality from 54.5% to 34.9% (APC = -7.3; 95% CI -12.3 to -1.4) after 2017. One- and three-year survival increased from 63% to 66% and from 39% to 42%, respectively, while five-year survival improved from 21% to 30%.

Conclusions: Over more than two decades, the incidence of MBC at diagnosis and early mortality both declined, accompanied by improved survival. These trends temporally coincide with the widespread adoption of targeted therapies and sustained high screening coverage, suggesting a possible combined contribution of early detection and advances in precision medicine to the observed outcomes.

Background: Durvalumab combined with gemcitabine-cisplatin (GC) has become the standard first-line treatment for advanced biliary tract cancer (BTC) following the TOPAZ-1 trial. However, real-world effectiveness, safety, and prognostic determinants, particularly in underrepresented populations, remain insufficiently defined. The aim of this study was to evaluate the real-world outcomes of first-line durvalumab plus chemotherapy and identify independent prognostic factors in patients with advanced BTC.

Methods: This multicenter retrospective cohort study included patients with unresectable or metastatic BTC treated with first-line durvalumab plus chemotherapy across 21 tertiary oncology centers in Türkiye. Clinical characteristics, laboratory parameters, biomarker data, and treatment details were collected. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Survival outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression models.

Results: A total of 78 patients were analyzed; 53.8% were male, and the median age was 62 years. Primary tumor sites were intrahepatic (55.1%), extrahepatic (30.8%), and gallbladder (14.1%). After a median follow-up of 12.58 months, median OS was 11.59 months and median PFS was 6.80 months. The ORR was 50.6%, including complete and partial responses in 2.7% and 47.9% of patients, respectively. Treatment-related adverse events occurred in 97.4% of patients, with grade 3-4 events in 37.2%. Immune-related adverse events were observed in 19.2%, including one case of grade 3 pneumonitis. No patient permanently discontinued durvalumab due to toxicity, and no durvalumab-related mortality occurred. In multivariable analysis, ECOG performance status 2 (HR 3.43; 95% CI 1.33-8.80) and ALBI grade 2-3 (HR 2.54; 95% CI 1.24-5.19) independently predicted worse OS, while ECOG performance status 2 also predicted shorter PFS (HR 5.91; 95% CI 2.30-15.17).

Conclusions: In this multicenter real-world Turkish cohort, first-line durvalumab plus chemotherapy showed effectiveness and tolerability comparable to clinical trial data. Baseline ECOG performance status and ALBI grade were independent prognostic factors, supporting their use for risk stratification in advanced biliary tract cancer.

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care.