Advances in cancer biology - metastasis最新文献

High grade serous ovarian carcinoma (HGSOC) is a systemic malignancy characterized by metastatic lesions that spread within the peritoneal cavity. Despite initial sensibility to platinum-based chemotherapy, more than 80% of patients experience a relapse and acquire chemoresistance. From a genomic point of view, HGSOC shows a high level of inter- and intra-tumor heterogeneity. A better understanding of molecular mechanisms of this disease and the identification of driving genetic alterations could provide relevant indications for diagnostic and prognostic evaluation. Here, we accomplished a double-tier omic-analysis by integrating copy number variation data with matched gene expression profiling of multiple lesions in a cohort of 7 patients. We identified potential driver genes contained in amplified regions whose behavior seem to impact on gene expression program. They represent a distinctive signature that can segregate biopsies of different patients. Moreover, a further analysis highlighted ZNF696, ASPSCR1 and RHPN1 as key drivers, whose regulatory program is confirmed in TCGA cohort. In conclusion, exploration of gene expression program in HSGOC by integrating copy number and transcriptomic data from spatially separated samples obtained from seven patients led to the identification of genes whose amplification is significantly correlated to specific gene expression modules and are related to survival.

A potential treatment approach to treat this terminal illness is the mushroom-based lectin carrier system. It has been hypothesized that lectin-induced apoptotic nature causes necrosis, which leads to cell death, in cancer cells. The antibacterial and free radical scavenging capabilities of lectins were examined, according to the findings of our earlier lectin purification research. The goal of the current investigation is to determine whether Pleurotus flabellatus lectin (PFL-L) has any anti-cancer activity against colorectal cancer (HT29) and lung cancer (A549) cell lines. According to the findings of an in vitro cell line investigation, pre-treatment of the HT29 and A549 cell lines with PFL-L (10–100 μg/ml) significantly reduced the induction of apoptosis with an IC₅₀ range of PFL-L (67 & 60 μg/ml). PFL-L protects cells against cancer cells, according to a confocal microscope viability examination of A549 and HT29 cells, and a comet test was used to track induced apoptosis. Our findings imply that PFL-L has promising anti-cancer activity and targets several apoptotic-related processes present in the A549 and HT29 cells. Additionally, when compared to the control, PFL-L increased DNA damage and the potential loss of cancer cells. A549 and HT29 cells also showed signs of the increased apoptosis-related proteins Bcl-Xl, Bcl-2, Procaspase-3, Procaspase-9, MMP-3, MMP-9, B6, N-Cadherin, and E-Cadherin. Western blot examination revealed decreased expression of apoptosis-related proteins. The results of this study demonstrate that PFL-L has anti-cancer properties against induced apoptosis in an in vitro model of A549 and HT29 cells.

Metastatic cancer is responsible for the overwhelming majority of cancer-related deaths, with metastatic tumors being the most common neoplasms affecting the central nervous system. One of the major factors regulating tumor biology is the tumor microenvironment. However, little is known about the cellular and non-cellular composition of metastatic brain tumors and how tumor cell ontogeny influences the metastatic brain tumor microenvironment. By integrating multiplex immunohistochemistry and histopathological analysis to investigate composition and the spatial relationship between neoplastic cells, infiltrating and brain resident immune cells and the extracellular matrix, we demonstrate that metastatic brain tumors exhibit differences in extracellular matrix deposition, compared with the most common primary brain tumor type, glioblastoma, and that the dominant immune cell types in metastatic brain tumors are immunosuppressive macrophages, which preferentially localize to extracellular matrix-rich stromal regions.

Breast cancer (BC) is one of the most frequently diagnosed cancers in women worldwide. It has surpassed lung cancer as the leading cause of cancer-related death. Breast cancer brain metastasis (BCBM) is becoming a major clinical concern that is commonly associated with ER-ve and HER2+ve subtypes of BC patients. Metastatic lesions in the brain originate when the cancer cells detach from a primary breast tumor and establish metastatic lesions and infiltrate near and distant organs via systemic blood circulation by traversing the BBB. The colonization of BC cells in the brain involves a complex interplay in the tumor microenvironment (TME), metastatic cells, and brain cells like endothelial cells, microglia, and astrocytes. BCBM is a significant cause of morbidity and mortality and presents a challenge to developing successful cancer therapy. In this review, we discuss the molecular mechanism of BCBM and novel therapeutic strategies for patients with brain metastatic BC.

Nuclear medicine imaging of neuroendocrine neoplasm (NEN) patients could evidence cancer cell states related to glycolytic hypermetabolism, somatostatin (SST) receptors overexpression or norepinephrine (NE) transport system hyperactivity status of cancer cells profiles, according to the radiolabelled molecular probe used: fluorodeoxyglucose (FDG), octreotide (SST analogue) or the compound metaiodobenzylguanidine (NE analogue), respectively. NEN lesions with positive positron emission tomography with ¹⁸FDG (glucose analogue radiolabelled with fluoride-18) stablished a relationship with tumour aggressiveness and poorly differentiated cell morphology. Otherwise, NEN lesions evidencing somatostatin receptors (SSTR) overexpression or abnormal surface NE transporter system hyperactivity status of cancer cell profiles correlated with well differentiated cell morphology. Theoretically, the apparent correspondence between the triple-positive imaging of glycolytic hypermetabolism, SSTR overexpression and abnormal NE transporter system hyperactivity of overlapping cancer cell states in metastatic site of a NEN patient could be revealing a single tumorigenic subpopulation with a dynamic divergent differentiation potential. The complex events of metastasis progression included transdifferentiation from epithelial-to-mesenchymal to leave the primary neoplastic niche, probable as a collective migration of cancer cells, including cancer stem cells (CSCs), to circulating and reversibly transdifferentiating from mesenchymal-to-epithelial to settle in distant niches. Considering future research perspectives, we argued whether the apparent triple-positive matched correlative imaging with the radiolabelled molecular probes (glucose, SST and NE analogues) in patients’ metastatic niches could indicate potential biopsy sites to further investigation for the potential CSCs properties. We suggested that early treatment planning with lutetium-177-based peptide receptor radionuclide therapy, could provide for the blocking of poorly differentiated cell states at the point of differentiation to well differentiated cell states, and vice versa. In addition, specific individual cases should be considered for targeted-based therapy with radiolabelled-NE analogue, blocking dedifferentiation and transdifferentiation from abnormal NE transporter system hyperactivity status to SSTR overexpression cancer cell profile.

The ketogenic diet (KD) is a low-carbohydrate, high-fat diet that is primarily used to treat childhood epilepsy. The processes through which the ketogenic diet works, on the other hand, have been proposed as a preventative method for oxidative stress and as adjuvant therapy for various disorders, including cancer. The current review aim is to assess the effect of the ketogenic diet on oxidative stress and cancer. A review of the scientific literature on the effects of the ketogenic diet on oxidative stress, cancer, and the mitochondrial metabolism is provided. Furthermore, the review depicts the human research that evaluated the anti-tumour benefits of ketogenic diets on patients with cancer, with a total of 154 subjects. Although preclinical research indicates that KD has anticancer benefits, prolongs longevity, and inhibits cancer growth, human clinical trials are inconclusive. The effects of KD on cancer and as an adjuvant treatment are mostly unclear due to a paucity of high-quality clinical research. We suggest a series of research recommendations for clinical trials exploring the impact of KD on cancer growth and progression.

Breast cancer is the most frequently diagnosed cancer and the leading cause of death by cancer among women worldwide. The prognosis of the disease and patients’ response to different types of therapies varies in different subgroups of this heterogeneous disease. The subgroups are based on histological and molecular characteristics of the tumor, especially the expression of estrogen (ER) and progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Hormone-dependent breast cancer, determined predominantly by the presence of ER, is the most common type of breast cancer. Patients with hormone-dependent breast cancer have an available targeted therapy, however, tumor cells can develop resistance to the therapy, which is a major obstacle limiting the success of treatment and enabling relapse to metastatic disease. The complicated crosstalk of both tumor-intrinsic and exogenous factors may contribute to endocrine resistance, although the underlying molecular details are still enigmatic. For example, the expression of the melanoma antigen genes (MAGE) correlates with a worse clinical prognosis and therapy resistance in many types of cancers, including breast cancer. Recent studies suggested that cancers co-opt MAGEs’ physiological functions to promote therapy resistance and potentially metastasis development. The response to the therapy can be also affected by the concurrent use of alternative therapy, e.g., cannabinoid use is popular among breast cancer patients. Cannabinoids interact with endogenous estrogen function, however, how they interfere with breast cancer therapy is still poorly understood. In this review, we summarize the role of ER, PR, and HER2 in hormone-dependent breast cancer; provide current knowledge of MAGEs and cannabinoid receptors in breast cancer; ultimately discuss the potential interlacement of their signaling paths which may underlay diverse responses to therapies in breast cancer patients simultaneously using cannabinoids. These interactions are poorly understood but critical for the advancement of conventional and complementary treatment options for patients, particularly the ones with metastatic disease.

The most recurrent type of cancer among women is breast cancer which is an intricate disease with high intertumoral and intratumoral heterogeneity. Such variability is a key factor in the failure of current treatments and the emergence of resistance. It is crucial to develop novel therapeutic options to enhance the prognosis for breast cancer patients due to the limitations of current therapy and the unavoidable formation of acquired drug resistance (chemo and endocrine) as well as radio resistance. Poor clinical results in the treatment of breast cancer, that is resistance are associated with deregulated Notch signalling within the breast tumor and its tumor microenvironment (TME). In this research, a bioinformatics approach was used to check the expression pattern, the role, as well as the prognostic and diagnostic significance of the deregulated Notch-related genes in BC patients. The various bioinformatic tools include; UCSC XENA, GEPIA 2, UALCAN, bc Genexminer, KM Plotter, ENRICHR, STRING and Cytoscape. The study demonstrates that highly dysregulated genes (NOTCH4, CCND1, JAG1, DLL1, MAML2, and EGFR) can be used as biomarkers to identify breast cancer patients with poor prognosis and as potential targets for therapeutic intervention. The study found that 6 genes—NOTCH4, CCND1, JAG1, DLL1, MAML2, and EGFR—out of 22 tested genes showed a significant log2 fold change. Our study revealed that Luminal Breast Cancer patients display a high expression of the CCND1 gene in comparison to its expression in normal. The results of our study also depicted that the patients with elevated levels of NOTCH-related gene expression displayed better relapse-free survival with p < 0.05. Moreover, we analysed the deregulated notch genes that play an important role in various cellular and molecular processes. The study shows that these highly deregulated screened genes could be utilized as the Biomarkers that help to reveal poor prognosis and could act as targets for treating BC. However, the identification of these dysregulated genes involved in notch signallibng through insilico approach is not sufficient.

Renal cell carcinoma (RCC) is a heterogeneous group of cancer that reacts inappropriately to recent therapeutic methods and is frequently linked with an uncertain clinical channel. The biology of renal cell carcinoma (RCC) depends on histology, tumor diversity, and the biological mechanism of metastasis. Malignant renal cell carcinoma (RCC) tumors can spread to bones, brain, pancreas, gallbladder, and adrenal gland resulting in metastasis. Medical treatment for renal cell carcinoma (RCC) has transformed from cytokine-based methods to targeted agent therapy against vascular endothelial growth factor (VEGF), and most recently to immunotherapy drugs. This review aims to summarize the biology of renal cell carcinoma and to understand the present and future directions in the treatment of metastasis.

H. pylori infection can lead to gastric diseases by modulating the various cellular processes such as cellular stress, apoptosis, autophagy, and metabolic changes. H. pylori exposed gastric epithelial cells bypass the cell death pathways. However, the underlying molecular mechanisms remain in infancy. Herein, we determined that H. pylori infection on gastric epithelial cells bypass the cell death pathway via the modulation of autophagy-related signaling molecules (LC3B and ATG7) through the host-associated oncoprotein Gankyrin. Upregulated expression of Gankyrin further enhanced the various antioxidant (gclm, gclc, sod2, cat, keap1, ant, and hsf1) and autophagy-associated genes’ transcripts (atg5, atg7, lc3b, beclin, and sqstm1). Elevated expression of Gankyrin also modulates the various downstream signaling proteins such as Akt, Beta-catenin, and NFkB. We also observed altered cancerous properties of gastric epithelial cells viz; apoptosis, wound healing, chemoresistance, biomass and membrane potential of mitochondria. Concisely, the study revealed that H. pylori infection promotes GC via autophagy through the modulation of oncoprotein Gankyrin and cellular reactive oxygen species (ROS). Overall, our study demonstrated the antiapoptotic property of H pylori-infected gastric epithelial cells might govern through Gankyrin-directed autophagy.