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Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10−3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan–Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804–6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC. [ABSTRACT FROM AUTHOR]

Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is one of the most aggressive tumors, with poor prognosis and high metastatic capacity. The aggressive behavior may involve inflammatory processes characterized by deregulation of molecules related to the immunological responses in which interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are involved. It is known that calcitriol, the active vitamin D metabolite, modulates the synthesis of immunological mediators; however, its role in the regulation of IL-1β and TNF-α in TNBC has been scarcely studied. In the present study, we showed that TNBC cell lines SUM-229PE and HCC1806 expressed vitamin D, IL-1β, and TNF-α receptors. Moreover, calcitriol, its analogue EB1089, IL-1β, and TNF-α inhibited cell proliferation. In addition, we showed that synthesis of both IL-1β and TNF-α was stimulated by calcitriol and its analogue. Interestingly, the antiproliferative activity of calcitriol was significantly abrogated when the cells were treated with anti-IL-1β receptor 1 (IL-1R1) and anti-TNF-α receptor type 1 (TNFR1) antibodies. Furthermore, the combination of calcitriol with TNF-α resulted in a greater antiproliferative effect than either agent alone, in the two TNBC cell lines and an estrogen receptor-positive cell line. In summary, this study demonstrated that calcitriol exerted its antiproliferative effects in part by inducing the synthesis of IL-1β and TNF-α through IL-1R1 and TNFR1, respectively, in TNBC cells, highlighting immunomodulatory and antiproliferative functions of calcitriol in TNBC tumors. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) has a high rate of anorexia, which negatively affects quality-of-life and prognosis; however prevalence values may vary as per diagnostic test. There is no standard for anorexia diagnosis, currently the anorexia cachexia scale (A/CS) has been proposed as a tool for diagnosing anorexia with a consensus cutoff value of ≤24, nonetheless a validated cutoff value is required. The A/CS was evaluated in advanced Non-Small Cell Lung Cancer (NSCLC) patients to establish a cutoff value. The appetite item from the QLQ-C30 questionnaire and survival served as a standard reference. The cutoff value was associated with clinical and nutritional characteristics along with quality-of-life. Three hundred and twelve (312) NSCLC patients were evaluated. The mean A/CS value was 31 ± 9 and the identified cutoff value was 32.5 (sensitivity: 80.3% and specificity: 85%). The proportion of anorexia accurately diagnosed with the cutoff value of 24 was 26%, while with 32 it was 50%. The A/CS cutoff value of 32 was associated with clinical parameters, nutritional consumption, and quality-of-life, and independently associated with overall survival. A score of ≤32 in the A/CS is proposed for anorexia diagnosis in order to identify patients at risk of complications involving malnutrition related to LC. [ABSTRACT FROM AUTHOR]

Purpose: The immunonutritional status of cancer patients has a profound impact on lifespan. Prognostic Nutritional Index (PNI) evaluates prognosis in operated patients with both neoplastic and non-neoplastic conditions. This study estimates the overall survival (OS) of Mexican patients operated on gastrointestinal stromal tumors (GIST) based on PNI., Methods: Immune-nutritional status was retrospectively analyzed in a cohort of 104 patients operated on GIST. Receiver operating characteristic (ROC) curves and X-tile software were used to estimate the optimal cutoff point and predict OS stratifying patients by PNI. Survival curves were obtained through Kaplan-Meier and log-rank methods. Multivariate analysis of survival was performed by Cox regression., Results: PNI (≥ 36.5) (p = 0.024) and mitotic index (≥ 5) (p = 0.013) were the only independent prognostic scores; the PNI-high group had better survival with 81.5% less risk of death (HR = 0.185). High PNI was correlated with favorable characteristics, i.e., low/intermediate risk (p = 0.046), reduced mitotic index (< 5) (p = 0.001), and younger age (< 55 years, p = 0.047)., Conclusions: PNI ≥ 36.5 entails a better prognosis for Mexican patients with surgically resected GIST. PNI represents a simple, reliable, and cost-effective prognostic tool, besides the pathological approach., Competing Interests: Declarations. Ethics approval: This is an observational study. The Instituto Nacional de Cancerología Ethics on Research Committee has confirmed no ethical approval is required. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Triple-negative breast cancer (TNBC) is one of the most aggressive tumors, with poor prognosis and high metastatic capacity. The aggressive behavior may involve inflammatory processes characterized by deregulation of molecules related to the immunological responses in which interleukin-1 β (IL-1 β ) and tumor necrosis factor- α (TNF- α ) are involved. It is known that calcitriol, the active vitamin D metabolite, modulates the synthesis of immunological mediators; however, its role in the regulation of IL-1 β and TNF- α in TNBC has been scarcely studied. In the present study, we showed that TNBC cell lines SUM-229PE and HCC1806 expressed vitamin D, IL-1 β , and TNF- α receptors. Moreover, calcitriol, its analogue EB1089, IL-1 β , and TNF- α inhibited cell proliferation. In addition, we showed that synthesis of both IL-1 β and TNF- α was stimulated by calcitriol and its analogue. Interestingly, the antiproliferative activity of calcitriol was significantly abrogated when the cells were treated with anti-IL-1 β receptor 1 (IL-1R1) and anti-TNF- α receptor type 1 (TNFR1) antibodies. Furthermore, the combination of calcitriol with TNF- α resulted in a greater antiproliferative effect than either agent alone, in the two TNBC cell lines and an estrogen receptor-positive cell line. In summary, this study demonstrated that calcitriol exerted its antiproliferative effects in part by inducing the synthesis of IL-1 β and TNF- α through IL-1R1 and TNFR1, respectively, in TNBC cells, highlighting immunomodulatory and antiproliferative functions of calcitriol in TNBC tumors.