Colorectal‐cancer (CRC) is the third leading cause of death due to cancer, supporting the need for identification of novel anticancer drug to improve the efficacy of current‐therapy. There is growing ...bodies of data showing the antitumor‐activity of curcumin, although it is associated with low absorption. The aim of current study was explored the therapeutic‐potential of novel phytosomal curcumin as well as its application in combination with 5‐Flurouracil (5‐FU) in a mouse‐model of colitis‐associated colon‐cancer. The anti‐proliferative‐activity of phytosomal curcumin was assessed in 2‐ and 3‐dimensional cell‐culture‐models as well as in a mouse‐model of colitis‐associated colon‐cancer. The expression‐levels of CyclinD1, beclin, E‐cadherin, and p‐GSK3a/b were investigated by qRT‐PCR and/or Western‐blotting. We evaluated the anti‐inflammatory of this agent by pathological‐evaluation and disease‐activity‐index (DAI). Moreover, oxidant/antioxidant activity was examined by malondialdehyde (MDA), total‐thiols (T‐SH), superoxide‐dismutase (SOD), and catalase (CAT) activity parameters. Our data showed that phytosomal curcumin and its combination with 5‐FU inhibited cell growth and invasive behavior of CRC cells through modulation of Wnt‐pathway and E‐cadherin. Combination of curcumin with 5‐FU dramatically reduced the tumor‐number and tumor‐size in both distal and middle parts of colon in colitis‐associated colon cancer followed by reduction in DAI. Also, curcumin suppressed the colonic inflammation and notably recovered the increased levels of MDA, decreased thiol level and reduced activity of CAT. We demonstrated the antitumor‐activity of novel form of curcumin in CRC, supporting further investigations on the therapeutic‐potential of this approach in colorectal‐cancer.
The aim of current study is to explore the therapeutic‐potential of novel phytosomal curcumin against colitis‐associated colon‐cancer. Our results demonstrated the anti‐proliferative effects of phytosomal curcumin is mediated by regulating wnt/b‐catenin signaling pathway, suggesting that curcumin either alone or in combination with 5FU can improve clinicopathological features of colon cancer in patients.
The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in ...cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce stem cell properties, which can contribute to the development of cancer stem cells (CSCs). CSCs promote tumor-initiation and metastasis and play a crucial role in the development of PDAC. Targeting CDK1 showed promising results for PDAC treatment in different preclinical models, where CDK1 inhibition induced cell cycle arrest in the G2/M phase and led to induction of apoptosis. Next to this, PDAC CSCs are uniquely sensitive to CDK1 inhibition. In addition, targeting of CDK1 has shown potential for combination therapy with both ionizing radiation treatment and conventional chemotherapy, through sensitizing tumor cells and reducing resistance to these treatments. To conclude, CDK1 inhibition induces G2/M cell cycle arrest, stimulates apoptosis, and specifically targets CSCs, which makes it a promising treatment for PDAC. Screening of patients for CDK1 overexpression and further research into combination treatments is essential for optimizing this novel targeted therapy.
Crocin is the major component of saffron, which is used in phytomedicine for the treatment of several diseases including diabetes, fatty liver, depression, menstruation disorders, and, of special ...interest in this review, inflammatory diseases. Promising selective anti‐inflammatory properties of this pharmacological active component have been observed in several studies. Saffron has been shown to exert anti‐inflammatory properties against several inflammatory diseases and can be used as a novel therapeutic agent for the treatment of inflammatory diseases either alone or in combination with other standard anti‐inflammatory agents. This review summarizes the protective role of saffron and its pharmacologically active constituents in the pathogenesis of inflammatory diseases including digestive diseases, dermatitis, asthma, atherosclerosis, and neurodegenerative diseases for a better understanding and hence a better management of these diseases.
Saffron has been shown to exert anti‐inflammatory properties against several inflammatory diseases and can be used as a novel therapeutic agent for the treatment of inflammatory diseases either alone or in combination with other standard anti‐inflammatory agents. This review summarizes the protective role of saffron and its pharmacologically active constituents in the pathogenesis of inflammatory diseases including digestive diseases, dermatitis, asthma, atherosclerosis, and neurodegenerative diseases for a better understanding and hence a better management of these diseases.
The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-β), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). ...In the current study, the therapeutic potential of targeting the TGF-β pathway using Pirfenidone (PFD), a TGF-β inhibitor, either alone or in combination with five fluorouracil (5-FU) has been explored in preclinical models of CRC. The anti-proliferative and migratory effects of PFD were assessed by MTT and wound-healing assays respectively. Xenograft models were used to study the anti-tumor activity, histopathological, and side effects analysis. Targeting of TGF-β resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-β induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-β pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.
We have reviewed the potential use of bioactive peptides in the treatment of gastrointestinal (GI) malignancies, which are a significant cause of morbidity and mortality globally. Conventional ...therapies, such as surgery, chemotherapy, and radiotherapy, are associated with numerous side effects that may lead to longterm complications. Bioactive peptides are short-chain amino acids that can be extracted from natural sources or synthesized, and they have various potential health benefits, including anti-inflammatory, anti-hypertensive, antioxidant, antimicrobial, and anti-cancer properties. Bioactive peptides can be acquired from animal or plant sources, and can be classified based on their function, such as ACE-inhibiting, antimicrobial, and electrolyte- regulating peptides. Recent studies have demonstrated the promising role of bioactive peptides in tumor suppression, especially when combined with conventional therapies. In this study, we have reviewed the beneficial properties of bioactive peptides and their role in suppressing tumor activity. The mechanisms of bioactive peptides in tumor suppression are discussed. We have further reviewed the findings of preclinical and clinical studies that have investigated the application of bioactive peptides in the treatment of GI cancers. This review highlights the potential use of bioactive peptides as a promising treatment method for GI malignancies to increase the quality of life of GI cancer patients.
Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the ...gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Saffron, the dried stigmas of Crocus sativus L., is mainly used as a food coloring and flavoring agent. This agricultural product is used in traditional medicine for the treatment of several diseases ...including asthma, liver disease, menstruation disorders, and, of special interest in this review, metabolic syndrome. Saffron and its active components including crocin, crocetin, and safranal are potential therapeutic candidates for attenuating MetS complications including hypertension, hyperglycemia, obesity, and dyslipidemia. This review summarizes the protective role of saffron and its constituents in the pathogenesis of MetS for a better understanding and hence a better management of this disease.
The clinical, histological, and molecular differences between right-sided colon cancer (RCC) and left-sided colon cancer (RCC) have received considerable attention. Over the past decade, many ...articles have been published concerning the association between primary tumor location (PTL) of colorectal cancer and survival outcomes. Therefore, there is a growing need for an updated meta-analysis integrating the outcomes of recent studies to determine the prognostic role of right vs left-sidedness of PTL in patients with colorectal cancer. We conducted a comprehensive database review using PubMed, SCOPUS, and Cochrane library databases from February 2016 to March 2023 for prospective or retrospective studies reporting data on overall survival (OS) and cancer-specific survival (CSS) of RCC compared with LCC. A total of 60 cohort studies comprising 1,494,445 patients were included in the meta-analysis. We demonstrated that RCC is associated with a significantly increased risk of death compared with LCC by 25% (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.19–1.31; I2 = 78.4%; Z = 43.68). Results showed that patients with RCC have a worse OS compared with LCC only in advanced stages (Stage III: HR, 1.275; 95% CI 1.16–1.4;
P
= 0.0002; I2 = 85.8%; Stage IV: HR, 1.34; 95% CI 1.25–1.44;
P
< 0.0001; I2 = 69.2%) but not in primary stages (Stage I/II: HR, 1.275; 95% CI 1.16–1.4;
P
= 0.0002; I2 = 85.8%). Moreover, a meta-analysis of 13 studies including 812,644 patients revealed that there is no significant difference in CSS between RCC and LCC (HR, 1.121; 95% CI 0.97–1.3;
P
= 0.112). Findings from the present meta-analysis highlight the importance of PTL in clinical decision-making for patients with CRC, especially in advanced stages. We provide further evidence supporting the hypothesis that RCC and LCC are distinct disease entities that should be managed differently.
Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper ...gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement. However several important questions remain to be answered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including uppergastrointestinal- cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/ environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers.
Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the ...therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.
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