Advances in cancer biology - metastasis最新文献

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.

Background

Signal Transducer and Activator of Transcription 3 (STAT3) is an identified critical protein associated with the progression of cancer. Alpha mangostin (α-M), a powerful dietary xanthone found to have anti-cancer properties against various cancers. However, the precise mechanism of its anti-cancer activity is not fully understood. Therefore, the current work hypothesized that targeting STAT3 with α-M inhibits the migration, invasion, and proliferation of breast cancer cells. Firstly, we evaluated the binding affinity of α-M/STAT3 complex using molecular dynamic simulations (MDS) and further we determined the likely underlying mechanism of STAT3 through in-vitro experiments. α-M treatment affected the levels of STAT3 phosphorylation, hnRNP-A1, PKM2, and EMT markers. α-M stimulation in breast cancer cells also resulted in suppressed migratory and invasive behaviour. More importantly, the treatment also affected the Ki67 and BrdU positive cells. In summary, we found the anti-migratory and anti-proliferative actions of α-M in breast cancer cells via STAT3 inhibition. Also, the study significantly adds a new nutraceutical for therapeutic intervention of invasive breast cancer.

Oncoviruses exploit diverse host mechanisms to survive and proliferate. These adaptive strategies overlap with mechanisms employed by malignant cells during their adaptation to dynamic micro-environments and for evasion of immune attack. While the role of individual oncoviruses in mediating cancer progression has been extensively characterized, little is known about the common gene regulatory features of oncovirus-induced cancers. Here, we focus on defining the interplay between several cancer hallmarks, including Epithelial-Mesenchymal Transition (EMT), metabolic alterations, and immune evasion across major oncoviruses by examining publicly available transcriptomics datasets containing both oncovirus-positive and oncovirus-negative samples. We observe that oncovirus-positive samples display varying degrees of EMT and metabolic reprogramming. While the progression of EMT generally associated with an enriched glycolytic metabolic program and suppressed fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS), partial EMT correlated well with glycolysis. Furthermore, oncovirus-positive samples had higher activity and/or expression levels of immune checkpoint molecules, such as PD-L1, which was associated with a partial EMT program. These analyses thus decode common pathways in oncovirus-positive samples that may be used in pinpointing new therapeutic vulnerabilities for cancer cell plasticity.

Pancreatic Ductal Adenocarcinomas (PDAC) is one of the most lethal cancer, shifting it from the fourth highest to the third-highest cause of cancer-related deaths in the United States recently. The majority of the cases are diagnosed when the disease has metastasized and is associated with poor 5-year survival. A long-term survival data of PDAC has not been well reported in the literature. Pancreatic Cancer requires the imminent need of a multidisciplinary approach. The key to an improved long-term outcome involves early diagnosis and curative resection along with chemotherapeutic agents. Gemcitabine has played a positive role as an adjuvant after surgical resection. Regular follow-ups post-resection are mandatory for the detection of neoplastic recurrence. To add to what is already a challenging task, isolated recurrence of PDAC poses greater challenges for the physicians treating the patients because there is no general consensus on how to manage these specific groups of patients. To effectively handle this challenging task, a definite strategy must be adopted. Long-term survival if accomplished must therefore be accompanied by regular follow-up visits including Spiral CT scans and keeping an eye on the serum tumor marker CA19-9, a prognostic survival predictor.

To evaluate a potentially valuable tool to study cancer progression and metastasis, we characterized a novel murine model composed of a parental oncogene-transformed embryonic fibroblast line and five cell lines isolated from progressively advanced tumors. Lines derived from distant metastases displayed significantly greater rates of motility, invasiveness, and extracellular acidification than lines derived from a primary tumor or local metastases. A comprehensive proteomic analysis of these cells showed numerous oncogenes to be upregulated and tumor suppressors to be downregulated in the advanced lines, and provided novel targets for future examination. The first cell line capable of extravasation displayed particularly high proteomic variation, which could provide insight into its epithelial to mesenchymal transition. The proteomic variation was less than that of an established human breast cancer model, indicating that the observed differences are more likely contributive to tumorigenesis. In total, we validated a novel cell model for the study of tumorigenesis, while providing a robust proteomic data set to guide future research.