PubMed

J Ethnopharmacol. 2023 Nov 21:117472. doi: 10.1016/j.jep.2023.117472. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cinobufacini injection, an aqueous extract of the toad, is a commonly used anti-tumor animal herbal medicine in clinical practice. It has the effects of detoxifying, reducing swelling, and relieving pain.AIMS OF THE STUDY: To investigate the effects of Cinobufacini injection on hepatocellular carcinoma progression by regulating lipid metabolism and macrophage polarization in the tumor microenvironment and to identify the potential molecular mechanisms.MATERIALS AND METHODS: To establish the axillary transplantation tumor model of hepatocellular carcinoma Hepa1-6 in C57BL/6 mice, and to evaluate the inhibitory effect of Cinobufacini injection on hepatocellular carcinoma in vivo as well as drug delivery security. Combined metabolomics and transcriptomics analysis of the effect of Cinobufagin Injection on tumor microenvironment. An in vitro mouse co-culture model of peritoneal macrophages and Hepa1-6 cells was established to research the effects of Cinobufacini injection on macrophage polarization, hepatocellular carcinoma cell growth, migration, and changes in lipid metabolism. Cinobufacini injection inhibition of the AMPK/SREBP1/FASN signaling pathway regulating cholesterol metabolism and affecting macrophage polarization was examined using qRT-PCR, lentiviral transfection, immunofluorescence, and Western blot.RESULT: In vivo experiments demonstrated that Cinobufacini injection treatment significantly inhibited the growth of Hepa1-6 hepatomas, along with a reduction in cholesterol content and a decrease in the percentage of M2 macrophages in tumor tissue. In vitro, we found that Cinobufacini injection inhibits IL-4-induced M2 macrophage polarization, reduces the cholesterol content of Hepa1-6 cells in a co-culture system, and inhibits the promotion of hepatocellular carcinoma cells by M2 macrophages. In addition, successful overexpression of SREBP1 in Hepa1-6 cells showed more pronounced cellular activity whereas Cinobufacini injection inhibited this change and reduced intracellular lipid levels.CONCLUSION: Cinobufacini injection inhibits cholesterol synthesis within the tumor microenvironment via the AMPK/SERBP1/FASN signaling pathway, which in turn blocks the M2 polarization of macrophages, leading to the weakening of hepatocellular carcinoma growth and migration, and the promotion of its apoptosis. Our findings provide an important Introduction to understanding the molecular mechanism of Cinobufacini injection's anticancer activity and provide reliable theoretical and experimental support for its clinical application.PMID:37995825 | DOI:10.1016/j.jep.2023.117472

Cancer Cell. 2023 Nov 16:S1535-6108(23)00365-3. doi: 10.1016/j.ccell.2023.10.009. Online ahead of print.ABSTRACTTrans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2. Temporal regulation by groups of transcription factors across developmental stages reveals that cellular reprogramming precedes the induction of neuronal programs. TFAP4 and ASCL1/2 feedback are identified as potential regulators of ASCL1 and ASCL2 expression. Our study provides temporal transcriptional patterns and uncovers pan-tissue parallels between prostate and lung cancers, as well as connections to normal neuroendocrine cell states.PMID:37995683 | DOI:10.1016/j.ccell.2023.10.009

Plant Physiol Biochem. 2023 Nov 20;205:108201. doi: 10.1016/j.plaphy.2023.108201. Online ahead of print.ABSTRACTAlthough microplastic pollution has been widely studied, the mechanism by which they influence plant photosynthesis and carbon and nitrogen metabolism remains unclear. We aimed to explore the effects of polystyrene microplastics (PS) on photosynthesis and carbon and nitrogen metabolism in cucumber using 5 μm and 0.1 μm PS particles. The PS treatments significantly reduced the stability of cucumber mesophyll cells and photosynthetic parameters and increased the soluble sugar content in cucumber leaves. The 5 μm PS affected the photosynthetic pathway by changing the expression of enzyme genes required for the synthesis of NADPH and ATP, which decreased the photosynthetic capacity in cucumber leaves. However, 0.1 μm PS altered the genes expression of phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (PEPC), which affected the intercellular CO2 concentration and attenuated the negative effects on photosynthetic efficiency. Additionally, PS reduced the expression levels of nitrate/nitrite transporter (NRT) and nitrate reductase (NR), reducing the nitrogen use efficiency in cucumber leaves and mesophyll cells damage through increased accumulation of reduced glutathione (GSH), γ-glutamylcysteine (γ-GC), and citrulline. This study provides a new scientific basis for exploring the effects of microplastics on plant photosynthesis and carbon and nitrogen metabolism.PMID:37995577 | DOI:10.1016/j.plaphy.2023.108201

Aquat Toxicol. 2023 Nov 19;265:106770. doi: 10.1016/j.aquatox.2023.106770. Online ahead of print.ABSTRACTTebuconazole is a triazole fungicide widely used in agricultural crops for control of multiple fungal, mainly foliar and soil-borne diseases. Due to its intense use, this pesticide has been detected on aquatic matrices in different countries, which makes it necessary to identify metabolites capable to be used in its exposure monitoring. The aim of this work was to evaluate tebuconazole metabolites in zebrafish water tanks using liquid chromatography coupled to a high-resolution mass spectrometer (LCHRMS) to highlight analytical targets to monitor tebuconazole exposure in aquatic environments. Two Phase I metabolites, TEB-OH and TEB-COOH, and one Phase II metabolite, TEB-S, were identified. Target metabolomics pointed TEB-S as the most important metabolite for discrimination between treatment and negative control group and potential surrogate for detection and monitoring of tebuconazole exposure in aquatic environments. To the best of our knowledge, this is the first study to suggest the sulphation of tebuconazole (TEB-S) by zebrafish metabolism. Moreover, the use of water samples proved to be a promising approach when compared to the usual biological matrices (e.g. plasma) for evaluating the exposure of aquatic animals to tebuconazole because it is a clean and easy to obtain matrix. Water samples presented a higher concentration of metabolites when compared to plasma samples. The results suggest the applicability of this assay model for the identification of potential biomarkers for monitoring the presence of xenobiotics in water.PMID:37995559 | DOI:10.1016/j.aquatox.2023.106770

Sleep Med. 2023 Nov 19;113:95-102. doi: 10.1016/j.sleep.2023.11.024. Online ahead of print.ABSTRACTIn recent years, there has been an increased interest in elucidating the influence of the gut microbiota on sleep physiology. The gut microbiota affects the central nervous system by modulating neuronal pathways through the neuroendocrine and immune system, the hypothalamus-pituitary-adrenal axis, and various metabolic pathways. The gut microbiota can also influence circadian rhythms. In this study, we observed the gut microbiota composition of patients suffering from narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. We did not observe any changes in the alpha diversity of the gut microbiota among patient groups and healthy controls. We observed changes in beta diversity in accordance with Jaccard dissimilarities between the control group and groups of patients suffering from narcolepsy type 1 and idiopathic hypersomnia. Our results indicate that both these patient groups differ from controls relative to the presence of rare bacterial taxa. However, after adjustment for various confounding factors such as BMI, age, and gender, there were no statistical differences among the groups. This indicates that the divergence in beta diversity in the narcolepsy type 1 and idiopathic hypersomnia groups did not arise due to sleep disturbances. This study implies that using metabolomics and proteomics approaches to study the role of microbiota in sleep disorders might prove beneficial.PMID:37995475 | DOI:10.1016/j.sleep.2023.11.024

Best Pract Res Clin Obstet Gynaecol. 2023 Nov 18;92:102427. doi: 10.1016/j.bpobgyn.2023.102427. Online ahead of print.ABSTRACTPreeclampsia is a pregnancy-specific disease that has no known precise cause. Integrative biology approach based on multi-omics has been applied to identify upstream pathways and better understand the pathophysiology of preeclampsia. At DNA level, genomics and epigenomics studies have revealed numerous genetic variants associated with preeclampsia, including those involved in regulating blood pressure and immune response. Transcriptomics analyses have revealed altered expression of genes in preeclampsia, particularly those related to inflammation and angiogenesis. At protein level, proteomics studies have identified potential biomarkers for preeclampsia diagnosis and prediction in addition to revealing the main pathophysiological pathways involved in this disease. At metabolite level, metabolomics has highlighted altered lipid and amino acid metabolisms in preeclampsia. Finally, microbiomics studies have identified dysbiosis in the gut and vaginal microbiota in pregnant women with preeclampsia. Overall, omics technologies have improved our understanding of the complex molecular mechanisms underlying preeclampsia. However, further research is warranted to fully integrate and translate these omics findings into clinical practice.PMID:37995432 | DOI:10.1016/j.bpobgyn.2023.102427

Funct Plant Biol. 2023 Nov 24. doi: 10.1071/FP23145. Online ahead of print.ABSTRACTMetabolomic investigations offers a significant foundation for improved comprehension of the adaptability of plants to reconfigure the key metabolic pathways and their response to changing climatic conditions. Their application to ecophysiology and ecotoxicology help to assess potential risks caused by the contaminants, their modes of action and the elucidation of metabolic pathways associated with stress responses. Heavy metal stress is one of the most significant environmental hazards affecting the physiological and biochemical processes in plants. Metabolomic tools have been widely utilised in the massive characterisation of the molecular structure of plants at various stages for understanding the diverse aspects of the cellular functioning underlying heavy metal stress-responsive mechanisms. This review emphasises on the recent progressions in metabolomics in plants subjected to heavy metal stresses. Also, it discusses the possibility of facilitating effective management strategies concerning metabolites for mitigating the negative impacts of heavy metal contaminants on the growth and productivity of plants.PMID:37995340 | DOI:10.1071/FP23145

Cell Rep. 2023 Nov 21;42(12):113463. doi: 10.1016/j.celrep.2023.113463. Online ahead of print.ABSTRACTBrain metastasis cancer-associated fibroblasts (bmCAFs) are emerging as crucial players in the development of breast cancer brain metastasis (BCBM), but our understanding of the underlying molecular mechanisms is limited. In this study, we aim to elucidate the pathological contributions of fucosylation (the post-translational modification of proteins by the dietary sugar L-fucose) to tumor-stromal interactions that drive the development of BCBM. Here, we report that patient-derived bmCAFs secrete high levels of polio virus receptor (PVR), which enhance the invasive capacity of BC cells. Mechanistically, we find that HIF1α transcriptionally upregulates fucosyltransferase 11, which fucosylates PVR, triggering its secretion from bmCAFs. Global phosphoproteomic analysis of BC cells followed by functional verification identifies cell-cell junction and actin cytoskeletal signaling as modulated by bmCAF-secreted, -fucosylated PVR. Our findings delineate a hypoxia- and fucosylation-regulated mechanism by which bmCAFs contribute to the invasiveness of BCBM in the brain.PMID:37995180 | DOI:10.1016/j.celrep.2023.113463

Environ Health Perspect. 2023 Nov;131(11):117011. doi: 10.1289/EHP13217. Epub 2023 Nov 23.ABSTRACTBACKGROUND: Perfluorohexane sulfonate (PFHxS) is a frequently detected per- and polyfluoroalkyl substance in most populations, including in individuals who are pregnant, a period critical for early life development. Despite epidemiological evidence of exposure, developmental toxicity, particularly at realistic human exposures, remains understudied.OBJECTIVES: We evaluated the effect of gestational exposure to human-relevant body burden of PFHxS on fetal and placental development and explored mechanisms of action combining alternative splicing (AS) and gene expression (GE) analyses.METHODS: Pregnant ICR mice were exposed to 0, 0.03, and 0.3μg/kg/day from gestational day 7 to day 17 via oral gavage. Upon euthanasia, PFHxS distribution was measured using liquid chromatography-tandem mass spectrometry. Maternal and fetal phenotypes were recorded, and histopathology was examined for placenta impairment. Multiomics was adopted by combining AS and GE analyses to unveil disruptions in mRNA quality and quantity. The key metabolite transporters were validated by quantitative real-time PCR (qRT-PCR) for quantification and three-dimensional (3D) structural simulation by AlphaFold2. Targeted metabolomics based on liquid chromatography-tandem mass spectrometry was used to detect amino acid and amides levels in the placenta.RESULTS: Pups developmentally exposed to PFHxS exhibited signs of intrauterine growth restriction (IUGR), characterized by smaller fetal weight and body length (p<0.01) compared to control mice. PFHxS concentration in maternal plasma was 5.01±0.54 ng/mL. PFHxS trans-placenta distribution suggested dose-dependent transfer through placental barrier. Histopathology of placenta of exposed dams showed placental dysplasia, manifested with an attenuated labyrinthine layer area and deescalated blood sinus counts and placental vascular development index marker CD34. Combined GE and AS analyses pinpointed differences in genes associated with key biological processes of placental development, proliferation, metabolism, and transport in placenta of exposed dams compared to that of control dams. Further detection of placental key transporter gene expression, protein structure simulation, and amino acid and amide metabolites levels suggested that PFHxS exposure during pregnancy led to impairment of placental amino acid transportation.DISCUSSION: The findings from this study suggest that exposure to human-relevant very-low-dose PFHxS during pregnancy in mice caused IUGR, likely via downregulating of placental amino acid transporters, thereby impairing placental amino acid transportation, resulting in impairment of placental development. Our findings confirm epidemiological findings and call for future attention on the health risk of this persistent yet ubiquitous chemical in the early developmental stage and provide a new approach for understanding gene expression from both quantitative and qualitative omics approaches in toxicological studies. https://doi.org/10.1289/EHP13217.PMID:37995155 | DOI:10.1289/EHP13217

Environ Sci Pollut Res Int. 2023 Nov 23. doi: 10.1007/s11356-023-31044-z. Online ahead of print.ABSTRACTCadmium (Cd) contamination in soil poses a severe threat to plant growth and development. In contrast, silicon (Si) has shown promise in enhancing plant resilience under Cd-induced stress. In this study, we conducted an integrated investigation employing morphological studies, gene expression analysis, and metabolomics to unravel the molecular mechanisms underlying Cd tolerance in maize plants. Our results demonstrate that Si biofortification significantly mitigated Cd stress by reducing Cd accumulation in plant tissues, increasing Si content, and enhancing maize biomass in Cd-stressed plants resulted in a substantial enhancement in shoot dry weight (+ 75%) and root dry weight (+ 30%). Notably, Si treatment upregulated key lignin-related genes (TaPAL, TaCAD, Ta4CL, and TaCOMT) and promoted the accumulation of metabolites (sinapyl alcohol, phenylalanine, p-coumaryl alcohol, cafeyl alcohol, and coniferaldehyde) essential for cell wall strength, particularly under Cd stress conditions. Si application enriched the signal transduction by hormones and increased resistance by induction of biosynthesis genes (TaBZR1, TaLOX3, and TaNCDE1) and metabolites (brassinolide, abscisic acid, and jasmonate) in the roots and leaves under Cd stress. Furthermore, our study provides a comprehensive view of the intricate molecular crosstalk between Si, Cd stress, and plant hormonal responses. We unveil a network of genetic and metabolic interactions that culminate in a multifaceted defense system, enabling maize plants to thrive even in the presence of Cd-contaminated soil. This knowledge not only advances our understanding of the protective role of Si but also highlights the broader implications for sustainable agricultural practices. By harnessing the insights gained from this research, we may pave the way for innovative strategies to fortify crops against environmental stressors, ultimately contributing to the goal of food security in an ever-changing world. In summary, our research offers valuable insights into the protective mechanisms facilitated by Si, which enhance plants' ability to withstand environmental stress, and holds promise for future applications in sustainable agriculture.PMID:37995035 | DOI:10.1007/s11356-023-31044-z

Plant Mol Biol. 2023 Nov 23. doi: 10.1007/s11103-023-01390-0. Online ahead of print.ABSTRACTIn response to herbivory, Capsicum annuum leaves adapt their specialized metabolome that may protect the plant against herbivore feeding either directly or indirectly through volatile metabolites acting as cues for natural enemies of the herbivore. The volatile blend of spider-mite infested leaves differs from non-challenged leaves predominantly by a higher contribution of mono- and sesquiterpenes. In addition to these terpenoids released into the headspace, the terpenoid composition of the leaves alters upon herbivory. All this suggests an important role for terpenoids and their biosynthetic machinery in the defence against herbivory. Here, we show that the C. annuum genome contains a terpene synthase (TPS) gene family of 103 putative members of which structural analysis revealed that 27 encode functional enzymes. Transcriptome analysis showed that several TPS loci were differentially expressed upon herbivory in leaves of two C. annuum genotypes, that differ in susceptibility towards spider mites. The relative expression of upstream biosynthetic genes from the mevalonate and the methylerythritol phosphate pathway also altered upon herbivory, revealing a shift in the metabolic flux through the terpene biosynthetic module. The expression of multiple genes potentially acting downstream of the TPSs, including cytochrome P450 monooxygenases, UDP-glucosyl transferases, and transcription factors strongly correlated with the herbivory-induced TPS genes. A selection of herbivory-induced TPS genes was functionally characterized through heterologous expression and the products that these enzymes catalysed matched with the volatile and non-volatile terpenoids induced in response to herbivory.PMID:37995005 | DOI:10.1007/s11103-023-01390-0

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):256-262. doi: 10.7417/CT.2023.2496.ABSTRACTBACKGROUND: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema.OBJECTIVE: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema.METHODS: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks.RESULTS: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity.CONCLUSION: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.PMID:37994773 | DOI:10.7417/CT.2023.2496

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):104-118. doi: 10.7417/CT.2023.2477.ABSTRACTBACKGROUND: Human breast carcinoma is a complex disease, affecting 1 in 8 women worldwide. The seriousness of the disease increases when the definite cause of the disease remains obscure, thus making prognosis challenging. Researchers are emphasizing on adapting more advanced and targeted therapeutic approaches to address the multifaceted impacts of the disease. Hence, modern multi-omics systems have gained popularity among clinicians, as they offer insights into the genomic, pharmacogenomic, metabolomic, and microbiomic factors, thus allowing researchers to develop targeted and personalized approaches for breast cancer prevention and early detection, and eventually improving patient outcomes.AIM: The primary focus of this study is to elucidate, through the integration of multi-omics research findings, the inherent molecular origins of diverse subtypes of breast cancer and to evaluate the effectiveness of these findings in reducing breast cancer-related mortalities.METHODS: Thorough investigation was conducted by reviewing reputable and authoritative medical journals, e-books, and online databases dedicated to cancer research. The Mendelian inheritance in man database (OMIM) was used to scrutinize specific genes and their respective loci associated with the development of different types of breast cancer.RESULTS: Our present research revealed the holistic picture of sundry molecular, genomic, pharmacogenomic, metabolomic, and microbiomic features of breast cancer. Such findings, like genetic alterations in highly penetrant genes, plus metabolomic and microbiomic signatures of breast cancer, unveil valuable insights and show great potential for multi-omics research in breast oncology.CONCLUSION: Further research in omics sciences pertaining to breast cancer are at the forefront of shaping precise treatment and bolstering patient survival.PMID:37994754 | DOI:10.7417/CT.2023.2477

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):95-103. doi: 10.7417/CT.2023.2476.ABSTRACTIn the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.PMID:37994753 | DOI:10.7417/CT.2023.2476

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):85-94. doi: 10.7417/CT.2023.2475.ABSTRACTPancreatic cancer is a leading cause of death worldwide, associated with poor prognosis outcomes and late treatment interventions. The pathological nature and extreme tissue heterogeneity of this disease has hampered all efforts to correctly diagnose and treat it. Omics sciences and precision medicine have revolutionized our understanding of pan-creatic cancer, providing a new hope for patients suffering from this devastating disease. By analyzing large-scale biological data sets and developing personalized treatment strategies, researchers and clinicians are working together to improve patient outcomes and ultimately find a cure for pancreatic cancer.PMID:37994752 | DOI:10.7417/CT.2023.2475

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):77-84. doi: 10.7417/CT.2023.2474.ABSTRACTGlioblastoma is a highly aggressive and malignant type of brain cancer with a poor prognosis, despite current treatment options of surgery, radiation therapy, and chemotherapy. These treatments have limitations due to the aggressive nature of the cancer and the difficulty in completely removing the tumor without damaging healthy brain tissue. Personalized medicine, using genomic profiling to tailor treatment to the patient's specific tumor, and immunotherapy have shown promise in clinical trials. The blood-brain barrier also poses a challenge in delivering treatments to the brain, and researchers are exploring various approaches to bypass it. More effective, personalized treatment approaches are needed to improve outcomes for glioblastoma patients. This tumor is studied using genomics, transcriptomics, and proteomics techniques, to better understand its underlying molecular mechanisms. Recent studies have used these techniques to identify potential therapeutic targets, molecular subtypes, and heterogeneity of tumor cells. Advancements in omics sciences have improved our understanding of glioblastoma biology, and precision medicine approaches have impli-cations for more accurate diagnoses, improved treatment outcomes, and personalized preventive care. Precision medicine can match patients with drugs that target specific genetic mutations, improve clinical trials, and identify individuals at higher risk for certain diseases. Precision medicine, which involves customizing medical treatment based on an individual's genetic makeup, lifestyle, and environmental factors, has shown promise in improving treatment outcomes for glioblastoma patients. Identifying biomarkers is essential for patient stratification and treatment selection in precision medicine approaches for glioblastoma, and several biomarkers have shown promise in predicting patient response to treatment. Targeted therapies are a key component of precision medicine approaches in glioblastoma, but there is still a need to improve their effectiveness. Technical challenges, such as sample quality and availability, and challenges in analyzing and interpreting large amounts of data remain significant obstacles in omics sciences and precision medicine for glioblastoma. The clinical implementation of precision medicine in glioblastoma treatment faces challenges related to patient selection, drug development, and clinical trial design, as well as ethical and legal considerations related to patient privacy, informed consent, and access to expensive treatments.PMID:37994751 | DOI:10.7417/CT.2023.2474

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):68-76. doi: 10.7417/CT.2023.2473.ABSTRACTBACKGROUND: Sarcomas are a relatively rare but diverse group of cancers that typically develop in the mesenchymal cells of bones and soft tissues. Occurring in more than 70 subtypes, sarcomas have broad histological presentations, posing significant challenges of prognosis and treatment. Modern multi-omics studies, which include genomics, proteomics, metabolomics, and micro-biomics, are vital to understand the underlying mechanisms of sarcoma development and progression, identify molecular biomarkers for early detection, develop personalized treatment plans, and discover drug resistance mechanisms in sarcomas to upsurge the survival rate.AIM: This study aims to highlight the genetic risk factors responsible for sarcoma-genesis, and to present a comprehensive review of multi-omics studies about sarcoma.METHODS: Extensive literature research was undertaken using reliable and authentic medical journals, e-books, and online cancer research databases. Mendelian inheritance in man database (OMIM) was explored to study particular genes and their loci that are responsible to cause various sarcomas.RESULT: This in-depth research led to the finding out that omics studies provide a more comprehensive understanding of underlying molecular mechanisms of sarcomas. Through genomics, we can reveal genetic alterations that predispose to sarcoma, like mutation in TP53, NF1, and so on. Pharmacogenomics enable us to find molecular targets for specific drugs. Whereas, proteomic and metabolomic studies provide insights into the biological pathways involved in sarcoma development and progression.CONCLUSION: Future advancements in omics sciences for sarcoma are on the cutting-edge of defining precision treatment plans and improved resilience of sarcoma patients.PMID:37994750 | DOI:10.7417/CT.2023.2473

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):55-67. doi: 10.7417/CT.2023.2472.ABSTRACTColon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcrip-tomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research.PMID:37994749 | DOI:10.7417/CT.2023.2472

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):46-54. doi: 10.7417/CT.2023.2471.ABSTRACTIn the last decade, renal carcinoma has become more prevalent in European and North American regions. Kidney tumors are usually categorized based on histological features, with renal cell carcinoma being the most common subtype in adults. Despite conventional diagnostic and therapeutic strategies, a rise in cancer incidence and recurrence necessitates a fresh approach to diagnosing and treating kidney cancer. This review focuses on novel multi-omics approaches, such as genomics, transcriptomics, proteomics, metabolomics, and microbiomics, to better understand the molecular and clinical features of renal cell carcinoma. Studies integrating omics sciences have shown early promise in enhancing prognostic and therapeutic outcomes for various kidney cancer subtypes and providing insight into fundamental pathophysiological mechanisms occurring at different molecular levels. This review highlights the importance of utilizing omics sciences as a revolutionary concept in diagnostics and therapeutics and the clinical implications of renal cell carcinoma. Finally, the review presents the most recent findings from large-scale multi-omics studies on renal cell carcinoma and its associations with patient subtyping and drug development.PMID:37994748 | DOI:10.7417/CT.2023.2471

Clin Ter. 2023 Nov-Dec;174(Suppl 2(6)):37-45. doi: 10.7417/CT.2023.2470.ABSTRACTLung cancer is a complex disease, with a wide range of genetic alterations and clinical presentations. Understanding the natural and clinical history of the disease is crucial for developing effective diagnostic and treatment strategies. Omics approaches, such as genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools for understanding the molecular mechanisms underlying lung cancer and for identifying novel biomarkers and therapeutic targets. These approaches enable researchers to examine the entire genome, transcriptome, proteome, or metabolome of a cell or tissue, providing a comprehensive view of the biological processes involved in lung cancer development and progression. Targeted therapies that address specific genetic mutations and pathways hold promise for improving the diagnosis and treatment of this disease.PMID:37994747 | DOI:10.7417/CT.2023.2470