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Abstract: The gut microbiome, a diverse community of microorganisms in the human body, plays an important role in maintaining health and influences various processes such as digestion, immunity, and protection against pathogens. A person's unique gut microbiome, shaped by factors such as birth method, diet, antibiotics, and lifestyle, contributes to bodily functions such as nutrient metabolism, drug processing, and im-mune regulation. Changes in the gut microbiome are associated with a predisposition to cancer and can influence the effectiveness of cancer treatments. Dysbiosis in the gut microbiome can lead to inflammation, tumor development, and metastasis, highlight-ing its importance in cancer research and prevention. The gut microbiota significantly influences cancer development and treatment outcomes. Certain bacteria enhance the effects of therapies such as cyclophosphamide and contribute to the body's im-mune response against tumors. Microbes produce anti-cancer molecules and probiotic compounds, making them potential tools in cancer prevention and treatment. Future research aims to develop targeted antibiotics and explore fecal microbiota transfer to selectively manipulate the microbiota for improved cancer treatment. Due to genetic and physiological similarities, mouse models are invaluable in biomedical research. However, because the gut microbiome of humans and mice and the composition of the tumor microenvironment differ, direct comparison between these two models can be challenging in research. Bridging these gaps is crucial for comparative medicine, especially in cancer research where the microbiome plays an important role in treat-ment outcomes. One important area where the gut microbiome could offer potential new treatment options is in primary brain tumors such as gliomas. To date, there are no long-lasting effective treatments for this type of cancer, but research in mouse models shows a link between tumor progression and response to treatment with changes in the gut microbiome. Overall, the gut microbiome and its modulation represent an opportu-nity for more efficient future cancer treatment.
Keywords: gut microbiome, cancer, treatment outcome, tumor models, glioma
Published in DiRROS: 03.04.2025; Views: 260; Downloads: 121
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Abstract: Measurement of RNA can be used to study and monitor a range of infectious and non-communicable diseases, with profiling of multiple gene expression mRNA transcripts being increasingly applied to cancer stratification and prognosis. An international comparison study (Consultative Committee for Amount of Substance (CCQM)-P103.1) was performed in order to evaluate the comparability of measurements of RNA copy number ratio for multiple gene targets between two samples. Six exogenous synthetic targets comprising of External RNA Control Consortium (ERCC) standards were measured alongside transcripts for three endogenous gene targets present in the background of human cell line RNA. The study was carried out under the auspices of the Nucleic Acids (formerly Bioanalysis) Working Group of the CCQM. It was coordinated by LGC (United Kingdom) with the support of National Institute of Standards and Technology (USA) and results were submitted from thirteen National Metrology Institutes and Designated Institutes. The majority of laboratories performed RNA measurements using RT-qPCR, with datasets also being submitted by two laboratories based on reverse transcription digital polymerase chain reaction and one laboratory using a next-generation sequencing method. In RT-qPCR analysis, the RNA copy number ratios between the two samples were quantified using either a standard curve or a relative quantification approach. In general, good agreement was observed between the reported results of ERCC RNA copy number ratio measurements. Measurements of the RNA copy number ratios for endogenous genes between the two samples were also consistent between the majority of laboratories. Some differences in the reported values and confidence intervals (‘measurement uncertainties’) were noted which may be attributable to choice of measurement method or quantification approach. This highlights the need for standardised practices for the calculation of fold change ratios and uncertainties in the area of gene expression profiling.
Keywords: RNA copy number ratio, RT-qPCR, gene expression, normalisation, standardisation, molecular diagnostic, transcriptomics, cancer, diagnostics, biomarker identification and validation
Published in DiRROS: 04.03.2025; Views: 171; Downloads: 73
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Abstract: Background In advanced epithelial ovarian cancer (EOC), the peritoneum is the primary site of disease recurrence which occurs in >75% of patients despite complete cytoreductive surgery (CRS) and chemotherapy. Macroscopically undetectable remaining cancer cells are deemed to be a source for recurrent disease. We investigated characteristics of occult disease in biopsies of macroscopically normal peritoneum during CRS. Materials and methods We included 14 patients with advanced stage high grade serous ovarian cancer (HGSOC). Eleven patients had received neoadjuvant chemotherapy (NACT) and three patients were chemotherapy naïve. Each patient underwent three study-related peritoneal biopsies: 1) of a metastasis, 2) adjacent to a metastasis and 3) at distance from metastases. Cryostat sections were immunohistochemically stained for PAX8 and PanCK as markers of EOC cells and for CD31 as a marker for vascular and lymphatic endothelium. The sections were analyzed semi-quantitatively. Results Macroscopically normal peritoneum showed solitary PAX8-positive cells adjacent to and at distance from metastases in all patients. Thirteen percent of these PAX8-positive cells were found to be attached to the mesothelium and are presumably spread through intra-abdominal fluid. Eighty-seven percent of the solitary PAX8-positive cells were found in the stroma underneath the mesothelium, of which 59% were firmly attached to endothelium and 33% were found in the stroma. In most cases, no sign of proliferation of the solitary cells was observed. Only a few clusters of PAX8-positive cells were found. Chemotherapy did not affect these results. Conclusions Solitary PAX8-positive cells are present in the macroscopically healthy-looking peritoneum of all EOC patients investigated, irrespective of the distance to macroscopically-visible metastases and of previous treatment. The majority of these solitary cancer cells were attached to endothelium of capillaries, venules or lymphatic vessels. Their solitary character and lack of proliferation suggests a dormant state, which could explain why these cells are unaffected by neo-adjuvant chemotherapy.
Keywords: ovarian cancer, peritoneal metastasis, translational medical research, human pathology, PAX8, cancer recurrence
Published in DiRROS: 26.02.2025; Views: 210; Downloads: 138
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Keywords: cancer metastasis, therapy, new treatment approaches
Published in DiRROS: 10.02.2025; Views: 155; Downloads: 86
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Abstract: Triple-negative breast cancer (TNBC) accounts for about 10-20% of all breast cancer cases and is associated with an unfavorable prognosis. Until recently, treatment options for TNBC were limited to chemotherapy. A new successful systemic treatment is immunotherapy with immune checkpoint inhibitors, but new tumor-specific biomarkers are needed to improve patient outcomes. Cannabinoids show antitumor activity in most preclinical studies in TNBC models and do not appear to have adverse effects on chemotherapy. Clinical data are needed to evaluate efficacy and safety in humans. Importantly, the endocannabinoid system is linked to the immune system and immunosuppression. Therefore, cannabinoid receptors could be a potential biomarker for immune checkpoint inhibitor therapy or a novel mechanism to reverse resistance to immunotherapy. In this article, we provide an overview of the currently available information on how cannabinoids may influence standard therapy in TNBC.
Keywords: triple-negative breast cancer, breast cancer, cancer treatment, cannabinoids
Published in DiRROS: 18.09.2024; Views: 545; Downloads: 242
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