Peroxisome Proliferator-Activated Receptor-γ Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has currently been considered as molecular target for the treatment of human metabolic disorders. Experimental data from in vitro cultures, animal models, and clinical trials have shown that PPAR-γ ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Tumor angiogenesis constitutes a multifaceted process implicated in complex downstream signaling pathways that triggers tumor growth, invasion, and metastasis. In this aspect, accumulating in vitro and in vivo studies have provided extensive evidence that PPAR-γ ligands can function as modulators of the angiogenic signaling cascade. In the current review, the crucial role of PPAR-γ ligands and the underlying mechanisms participating in tumor angiogenesis are summarized. Targeting PPAR-γ may prove to be a potential therapeutic strategy in combined treatments with conventional chemotherapy; however, special attention should be taken as there is also substantial evidence to support that PPAR-γ ligands can enhance angiogenic phenotype in tumoral cells

Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival

BACKGROUND: Ephrin (Eph) receptors are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate the clinical significance of EphA1, A4, A5 and A7 protein expression in non-small cell lung carcinoma (NSCLC). METHODS: EphA1, A4, A5 and A7 protein expression was assessed immunohistochemically in tissue microarrays of 88 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients’ survival. RESULTS: Elevated EphA4 expression was significantly associated with low histopathological stage and presence of inflammation (p = 0.047 and p = 0.026, respectively). Elevated EphA7 expression was significantly associated with older patients’ age, presence of fibrosis and smaller tumor size (p = 0.036, p = 0.029 and p = 0.018, respectively). EphA1, A5 and A7 expression were positively associated with tumor proliferative capacity (p = 0.047, p = 0.002 and p = 0.046, respectively). Elevated EphA4, A5 and A7 expression were identified as predictors of favourable patients’ survival at both univariate (Log-rank test, 0 = 0.019, p = 0.006 and p = 0.012, respectively) and multivariate levels (Cox-regression analysis, p = 0.029, p = 0.068 and p = 0.044, respectively). CONCLUSIONS: The present study supported evidence that Ephs may be involved in lung cancer progression, reinforcing their utility as clinical biomarkers for patients’ management and prognosis, as also as potential targets for future therapeutic interventions

MCM5 (minichromosome maintenance complex component 5)

Review on MCM5 (minichromosome maintenance complex component 5), with data on DNA, on the protein encoded, and where the gene is implicated

Can bioelectrical impedance analysis and BMI be a prognostic tool in head and neck cancer patients? A review of the evidence

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Background: Malnutrition can significantly affect disease progression and patient survival. The efficiency of weight loss and bioimpedance analysis (BIA)-derived measures in the evaluation of malnutrition, and disease progression and prognosis in patients with head and neck cancer (HNC) are an important area of research. Method: The PubMed database was thoroughly searched, using relative keywords in order to identify clinical trials that investigated the role of BIA-derived measures and weight loss on the disease progression and prognosis of patients with HNC. Twenty-seven studies met the criteria. More specifically, six studies examined the prognostic role of the tissue electrical properties in HNC patients; five examined the role of the tissue electrical properties on identifying malnutrition; four studies looked at the changes in the tissue electrical properties of HNC patients; and 12 examined the prognostic role of weight loss on survival and/or treatment outcomes. Results: Several studies have investigated the role of nutritional status tools on prognosis in HNC patients. Current studies investigating the potential of BIA-derived raw data have shown that phase angle (PA) and capacitance of the cell membrane may be considered prognostic factors of survival. Weight loss may be a prognostic factor for treatment toxicity and survival, despite some conflicting evidence. Conclusions: Further studies are recommended to clarify the role of BIA-derived measures on patients’ nutritional status and the impact of PA on clinical outcomes as well as the prognostic role of weight loss

Coxsackievirus and adenovirus receptor expression in human endometrial adenocarcinoma: possible clinical implications

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications

Adherence to Mediterranean Diet and Nutritional Status in Women with Breast Cancer: What Is Their Impact on Disease Progression and Recurrence-Free Patients’ Survival?

Introduction: Nutritional status impacts the survival of patients with cancer. There are few studies that investigate the role of nutritional status on breast cancer survival in women with breast cancer, and even fewer regarding the impact of adhering to the Mediterranean diet (MD). The present study aims to assess the nutritional status, MD adherence, physical activity levels and health-related quality of life (HRQOL) in women diagnosed with breast cancer and evaluate these parameters regarding recurrence-free survival. Methods: A total of 114 women, aged 35–87 years old, diagnosed with breast cancer in Larissa, Greece, participated in the study. Tumor histopathology was reported, and anthropometric indices were measured by a trained nurse, while questionnaires regarding nutritional status (via mini nutritional assessment), HRQOL via EORTC QLQ-C30, physical activity levels via IPAQ and Mediterranean diet adherence via MedDietScore were administered. The participants were followed-up for a maximum time interval of 42 months or until recurrence occurred. Results: A total of 74% of patients were overweight or obese, while 4% of women were undernourished, and 28% were at risk of malnutrition. After 42 months of follow-up, 22 patients (19.3%) had relapsed. The median time to recurrence was 38 months (IQR: 33–40 months) and ranged between 23 to 42 months. Higher levels of MD adherence were significantly associated with lower body mass index (BMI) values, earlier disease stage, smaller tumor size, absence of lymph node metastases and better physical activity levels (p \u3c 0.05). Normal nutritional status was significantly associated with higher BMI values and better health-related quality of life (p ≤ 0.05). In univariate analysis, patients with higher levels of MD adherence and well-nourished patients had significantly longer recurrence-free survival (p \u3c 0.05). In multivariate analysis, MD adherence and nutritional status were independently associated with recurrence-free patients’ survival after adjustment for several confounding factors (p \u3c 0.05). Conclusions: The impact of MD on time to recurrence is still under investigation, and future interventional studies need to focus on the role of adhering to the MD before and after therapy in survival and breast cancer progression. Furthermore, the present study also highlights the importance of an adequate nutritional status on disease progression, and the need for nutritional assessment, education and intervention in women with breast cancer

Exclusive Breastfeeding for at Least Four Months Is Associated with a Lower Prevalence of Overweight and Obesity in Mothers and Their Children after 2–5 Years from Delivery

INTRODUCTION: Obesity is a current public health concern. Higher body weight is influenced by genetic and environmental parameters, and their interplay and is associated with a greater risk for several chronic diseases. Breastfeeding has been suggested as a preventive measure against obesity, which can further reduce long-term negative health outcomes for both women and children. AIM: The aim of the present study was to evaluate the role of breastfeeding on maternal and childhood overweight and obesity. MATERIALS AND METHODS: This is a cross-sectional study conducted on 2515 healthy mothers and their children, aged 2-5 years, enrolled from nine different Greek rural and urban regions. Validated, standardized questionnaires were administrated that included anthropometric indices, socio-demographic characteristics of mothers and children, as well as breastfeeding practices. RESULTS: Overall, 68% of participated women exclusively breastfed their children for at least 4 months. Mothers that exclusively breastfed showed a significantly lower prevalence of overweight and obesity after 2-5 years from delivery (p \u3c 0.0001). Children that had exclusively been breastfed showed a significantly lower prevalence of overweight and obesity at the age of 2-5 years (p \u3c 0.0001). Using multivariate regression analysis, exclusive breastfeeding for at least 4 months was associated with a two-fold lower risk for maternal and childhood overweight and obesity after 2-5 years from delivery, independent from maternal age, educational and economic status, and smoking habits (p \u3c 0.0001). CONCLUSION: Exclusive breastfeeding for at least 4 months had a positive effect on childhood overweight and obesity, also contributing beneficially to post-natal maternal weight control. The beneficial effects of breastfeeding should be communicated to future and new mothers, while supportive actions for all mothers to initiate and continue breastfeeding their offspring should be implemented

Pre-Pregnancy Excess Weight Association with Maternal Sociodemographic, Anthropometric and Lifestyle Factors and Maternal Perinatal Outcomes

BACKGROUND: Pre-pregnancy excess weight is an important factor for adverse maternal perinatal outcomes; however, data for Greek women remain limited. Therefore, the aim of the present work was to evaluate the relation between pre-pregnant weight status and sociodemographic, anthropometric and lifestyle factors and maternal perinatal outcomes. METHODS: In the present cross-sectional study, 5133 healthy women were enrolled from nine different Greek regions after applying specific inclusion and exclusion criteria. Validated questionnaires were used to assess the sociodemographic characteristics and certain lifestyle factors of the study population. Anthropometric and clinical data were retrieved from medical history files of the women, including measured weight in the first weeks of pregnancy and right before delivery, and maternal perinatal outcomes. Women\u27s weights and heights were also measured 2-5 years postpartum by trained nutritionists. Non-adjusted and adjusted statistical analysis was performed to assess whether pre-pregnancy weight status was associated with sociodemographic, anthropometric and lifestyle factors and maternal perinatal outcomes. RESULTS: In pre-pregnancy, 17.5% of the women were overweight, and 4.9% were classified as obese. These rates were increased 2-5 years postpartum, reaching 21.0% for overweight and 9.6% for obese women. Pre-pregnancy overweight/obesity were associated with older maternal age, higher prevalence of overweight/obesity at 2-5 years postpartum and nonexclusive breastfeeding, as well as increased rates for preterm birth and pregnancy-induced hypertension after multiple adjustments. CONCLUSIONS: Overweight and obesity rates were high among women of childbearing age in Greece. These findings highlight the urgent need for healthy lifestyle promotion and targeted obesity prevention and intervention schemes among women of reproductive age

Expression and clinical significance of concomitant FAK/SRC and p-Paxillin in mobile tongue squamous cell carcinoma.

Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reservedBACKGROUND/AIM: The focal adhesion kinase (FAK)/SRC phosphorylation cascade and its downstream target paxillin have been implicated in malignant transformation, tumor growth and progression, together with metastasis. The present study aimed to evaluate the clinical significance of concomitant FAK/SRC and p-paxillin expression in mobile tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: FAK, SRC and phospho-paxillin expression in 48 mobile tongue SCC tissue samples was assessed immunohistochemically and analyzed with respect to clinicopathological characteristics and patient survival. RESULTS: Concomitant high FAK/SRC expression was significantly associated with high grade of tumor differentiation (p=0.048) and longer disease-free patient survival (log-rank test, p=0.019). High p-paxillin expression was significantly associated with greater depth of invasion (p=0.002), lymph node metastasis (p=0.048) and poorer disease-free patient survival (log-rank test, p=0.021; Cox-regression analysis, p=0.031). CONCLUSION: The present study provides evidence that FAK/SRC and paxillin play a role in the pathophysiological aspects of mobile tongue SCC and could constitute therapeutic targets.Final Accepted Versio