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As people age, their skeletal muscle (SkM) experiences a decline in mitochondrial functionality and density, which leads to decreased energy production and increased generation of reactive oxygen species. This cascade of events, in turn, might determine the loss of SkM mass, strength and quality. Even though the mitochondrial processes dysregulated by aging, such as oxidative phosphorylation, mitophagy, antioxidant defenses and mtDNA transcription, are the same in both sexes, mitochondria age differently in the SkM of men and women. Indeed, the onset and magnitude of the impairment of these processes seem to be influenced by sex-specific factors. Sexual hormones play a pivotal role in the regulation of SkM mass through both genomic and non-genomic mechanisms. However, the precise mechanisms by which these hormones regulate mitochondrial plasticity in SkM are not fully understood. Although the presence of estrogen receptors in mitochondria is recognized, it remains unclear whether androgen receptors affect mitochondrial function. This comprehensive review critically dissects the current knowledge on the interplay of sex in the aging of SkM, focusing on the role of sex hormones and the corresponding signaling pathways in shaping mitochondrial plasticity. Improved knowledge on the sex dimorphism of mitochondrial aging may lead to sex-tailored interventions that target mitochondrial health, which could be effective in slowing or preventing age-related muscle loss. [Display omitted] [ABSTRACT FROM AUTHOR]

Platinum-based drugs are among the most effective anticancer therapies, integrating the standard of care for numerous human malignancies. However, platinum-based chemotherapy induces severe side-effects in cancer patients, such as cachexia. Weight loss, as well as fatigue and systemic inflammation are characteristics of this syndrome that adversely affects the survival and the quality of life of cancer patients. The signalling pathways involved in chemotherapy-induced cachexia are still to be fully understood, but the activity of several mediators associated with muscle wasting, such as myostatin and pro-inflammatory cytokines are increased by platinum-based drugs like cisplatin. Indeed, the molecular mechanisms behind chemotherapy-induced muscle wasting seem to be similar to the ones promoted by cancer in treatment-naive patients. Although some therapeutic agents are under investigation for treating muscle wasting in cancer patients, no effective treatment is yet available. Herein, we review the molecular mechanisms proposed to be involved in chemotherapy-related muscle wasting with a focus on the typical platinum-based drug cisplatin. Therapeutic strategies presently under investigation are also reviewed, providing an overview of the current efforts to preserve muscle mass and quality of life among cancer patients. [ABSTRACT FROM AUTHOR]

Histamine is a biogenic amine, synthetized and released by mast cells, which acts as a vasodilator in several pathologic processes, namely in allergies and conjunctivitis. Its role on cancer is not fully understood. High levels of histamine have been associated with a bivalent behavior in regulation of several tumors ( i . e . cervical, ovarian, vaginal, uterine, vulvar, colorectal cancer, and melanoma), promoting or inhibiting their growth. Histamine receptors (H1, H2, H3 and H4) are present in a vast group of cells, including tumor cells, making them sensitive to histamine variations. In this work, we review the role of mast cells and histamine on cancer development and the possibility of use antihistamines in the clinical management of this disease. [ABSTRACT FROM AUTHOR]

Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24 weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-κB were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-κB canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-κB inhibitors may be useful resources for treating this syndrome. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common cancer in men, affecting approximately 1.1 million men worldwide. In this way, the study of prostate cancer biopathology and the study of new potential therapies is of paramount importance. Several rat models were developed over the years to study prostate cancer, namely spontaneous models, chemically-induced models, implantation of cancer cell lines and genetically-engineered models. This manuscript aimed to provide the readers with an overview of the rat models of prostate cancer, highlighting their advantages and disadvantages, as well as, their applications. [ABSTRACT FROM AUTHOR]

Aims The inhibition of mast cells' degranulation may be an approach to prevent the formation of new vessels during the mammary carcinogenesis. Materials and methods Female Sprague-Dawley rats were randomly divided into five experimental groups. Mammary tumors were induced by intraperitoneal injection of N -methyl- N -nitrosourea (MNU). Animals from group II were treated with ketotifen for 18 weeks immediately after the MNU administration, while animals from group III only received the ketotifen after the development of the first mammary tumor. Mammary tumors vascularization was assessed by ultrasonography (Doppler, B Flow and contrast-enhanced ultrasound) and immunohistochemistry (vascular endothelial growth factor-A). Key findings and significance Similar to what occurs in women with breast cancer, the majority of MNU-induced mammary tumors exhibited a centripetal enhancement order of the contrast agent, clear margin and heterogeneous enhancement. Ultrasonographic and immunohistochemical data suggest that the inhibition of mast cells' degranulation did not change the mammary tumors vascularization. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed. This review aims to summarize the current knowledge on the cardiac signaling pathways modulated by these two antineoplastic drugs highly used in the management of breast cancer, not only focusing on cardiomyocytes but also to broaden the knowledge of the potential impact on other cells found in the heart. [Display omitted] [ABSTRACT FROM AUTHOR]