Dorota Gil

Currently, cancer represents an escalating public health crisis in Africa, ranking as the continent’s fifth leading cause of mortality. According to recent GLOBOCAN 2022 estimates, approximately 1.15 million new cancer cases and 754,500 deaths occurred across Africa in that year alone. On a global scale, there were an estimated 20 million new cases and 9.7 million deaths in 2022, with a disproportionate burden falling on underserved regions. Low- and middle-income countries are projected to account for nearly 75% of global cancer deaths, highlighting a stark geographical inequity in access to timely diagnosis and comprehensive care. This review provides an inclusive presentation of the two most prevalent reproductive malignancies in Africa: prostate cancer in men and breast cancer in women. Set against the backdrop of the continent’s unique socioeconomic landscape, the article explores the complex interplay of prevalence and risk factors, ranging from genetic and phenotypic predispositions to environmental and epigenetic influences. Recognizing the diverse healthcare landscape in Africa, this work addresses the accessibility of conventional medicine while evaluating the supervised integration of potential herbal agents as complementary therapies. This review identifies barriers to effective disease management and discusses the current and future cancer burden across the African continent for non-specialist readers and those seeking to understand oncological care in Africa. Ultimately, the findings underscore an urgent need for targeted policy-making and strategic investment in prevention. Prioritizing timely screening and strengthening treatment infrastructure are essential steps for authorities to mitigate the surging cancer burden and maintain the health of African populations.

As in other mammalian species, the complex and specific interactions between internal biological processes and external factors regulate and impact the male dog reproductive system functions. This comprehensive review integrates physiological and molecular mechanisms underlying the reproductive system maintenance throughout the anatomical and histological structure of reproductive organs and their functions from development to aging. Simultaneously, the presentation of fundamental hormonal regulations and functions of the reproductive system is comprised. Special attention is put on e.g., genetic, developmental, age- and environmental-related disorders. The structural and hormonal status of the reproductive organs in response to single or mixed influences: genetic predispositions (e.g., cryptorchidism, sex chromosome aneuploidy syndrome), developmental courses (e.g., cryptorchidism, uterus masculinus, hypospadias), age-related diseases (e.g., tumors), and environmental stressors: e.g., endocrine-disrupting chemicals, toxins, heat stress (possibly leading to e.g., hypogonadism, cryptorchidism, infertility, tumors, precocious aging) is provided. Such multidirectional and comprehensive associations of grouped, selected, clinically significant pathological processes and diseases are broadly considered and linked here for the first time. Based on both epidemiological and experimental findings, the etiologies, current diagnostic approaches, treatment options, and prognostic assessments of these common male dog disorders are presented. This compendium seems useful for young veterinarians, researchers, breeders, and dog owners, enabling them to integrate knowledge on biological principles and processes with clinical practices and research in recent and future canine andrology.

Bladder cancer (BC) has an extremely low survival rate due to its tendency to metastasize. The antimalarial drug chloroquine (CQ) can inhibit BC progression and invasiveness by targeting basal autophagy. However, the mechanism by which CQ affects BC is not defined. Here, we revealed that although CQ showed an anticancer effect by reducing the migration and proliferation of the analyzed bladder cancer cells, it increased the expression of ICAM-1, a protein whose expression is associated with higher tumorigenic potential. Sulforaphane (SFN), a well-known ICAM-1 inhibitor, significantly contributed to the enhancement of anticancer effect of CQ, through regulation of both AKT/GSK-3β and mTOR/ULK pathways, which led to effective inhibition of autophagy, reduced proliferation level or inhibition of migration of the analyzed bladder cells. Moreover, regulation of pathways related to autophagy contributed to the reduction of mitochondrial membrane potential and regulation of ROS level. Nevertheless, the level of influence of CQ and SFN on the anticancer effects strongly depended on the molecular basis of the analyzed bladder cell lines. Our data indicate that although CQ exerts antitumor effects on bladder cancer cells, it should be noted that activation of some pro-tumor pathways may be associated with subsequent disease relapse or treatment resistance.

Extracellular matrix (ECM) mechanics critically influence cancer progression, yet the interplay between ECM viscoelasticity, architecture, and tumor cell adaptation remains incompletely understood. Here, we engineered collagen-hyaluronan hydrogels with tunable stiffness to mimic soft and stiff tumor microenvironments and studied bladder cancer spheroids representing benign, low-invasive, and highly invasive stages. Using hydraulic force spectroscopy, rheometry, and molecular analyses, we found that matrix stiffness differentially modulates spheroid morphology, migration, and expression of adhesion and metabolic markers. Active ECM remodeling via metalloproteinase MMP-2 facilitated migration in compliant but not rigid matrices, while mechano-metabolic coupling varied with cancer progression stage. These findings reveal how bladder cancer cells adapt to mechanical cues through coordinated biomechanical and metabolic responses, underscoring the importance of integrating cellular and matrix mechanics in modeling tumor invasion and developing targeted therapies.

Melanoma treatments are necessary when surgically curable treatments are limited. The major challenge of targeted therapy for treating malignant melanoma is acquired drug resistance. Translation and autophagy pathways are interconnected and involved in developing cancer drug resistance. We hypothesized that coordinate inhibition of autophagy and translation would lead to a better anticancer effect. In the present study, we used chloroquine combined with two translation inhibitors (NVP-BEZ235 and CGP57380) acting at different signaling pathway levels, activating the translation. Our study was conducted for human melanoma cell lines with similar genomic alteration (BRAFV600E and PTEN loss). The combination of the drugs suppresses cell invasiveness and growth by inducing apoptosis. We showed multiple direct and indirect interactions, indicating the overlap and interaction between the translation machinery and autophagy. These data suggest that coordinated inhibition of translation and autophagy promotes apoptosis and may be a new therapeutic model for melanoma treatment.

Bladder cancer is one of the most prevalent cancers worldwide. Moreover, if not optimally treated, bladder cancer is a significant burden on healthcare systems due to multiple recurrences which often require more aggressive therapies. Therefore, targeted anti-cancer therapies, developed based on an in-depth understanding of specific proteins and molecular mechanisms, are promising in cancer treatment. Here, for the first time, we presented the new approaches indicating that intracellular adhesion molecule-1 (ICAM-1) may play a potential role in enhancing therapeutic effectiveness for bladder cancer. In the present study, we presented that ICAM-1 expression as well as its regulation in bladder cancer is strongly correlated with the high expression of N-cadherin. Importantly, the presence of N-cadherin and its regulator—TWIST-1 was abolished when ICAM-1 was silenced. We identified also that ICAM-1 is capable of regulating cellular migration, proliferation, and EMT progression in bladder cancer cells via the N-cadherin/SRC/AKT/GSK-3β/β-catenin signaling axis. Therefore, we propose ICAM-1 as a novel metastatic marker for EMT progression, which may also be used as a therapeutic target in bladder cancer.

The twofold role of autophagy in cancer is often the therapeutic target. Numerous regulatory pathways are shared between autophagy and other molecular processes needed in tumorigenesis, such as translation or survival signaling. Thus, we have assumed that ILK knockdown should promote autophagy, and used together with chloroquine, an autophagy inhibitor, it could generate a better anticancer effect by dysregulation of common signaling pathways. Expression at the protein level was analyzed using Western Blot; siRNA transfection was done for ILK. Analysis of cell signaling pathways was monitored with phospho-specific antibodies. Melanoma cell proliferation was assessed with the crystal violet test, and migration was evaluated by scratch wound healing assays. Autophagy was monitored by the accumulation of its marker, LC3-II. Our data show that ILK knockdown by siRNA suppresses melanoma cell growth by inducing autophagy through AMPK activation, and simultaneously initiates apoptosis. We demonstrated that combinatorial treatment of melanoma cells with CQ and siILK has a stronger antitumor effect than monotherapy with either of these. It generates the synergistic antitumor effects by the decrease of translation of both global and oncogenic proteins synthesis. In our work, we point to the crosstalk between translation and autophagy regulation.