Berberine, an isoquinoline alkaloid isolated from the Chinese herb Coptis chinensis and other Berberis plants, has a wide range of pharmacological properties. Berberine can be used to treat many ...diseases, such as cancer and digestive, metabolic, cardiovascular, and neurological diseases. Berberine has protective capacities in digestive diseases. It can inhibit toxins and bacteria, including Helicobacter pylori, protect the intestinal epithelial barrier from injury, and ameliorate liver injury. Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis. Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies. In addition, berberine regulates glycometabolism and lipid metabolism, improves energy expenditure, reduces body weight, and alleviates nonalcoholic fatty liver disease. Berberine also improves cardiovascular hemodynamics, suppresses ischemic arrhythmias, attenuates the development of atherosclerosis, and reduces hypertension. Berberine shows potent neuroprotective effects, including antioxidative, antiapoptotic, and anti-ischemic. Furthermore, berberine exerts protective effects against other diseases. The mechanisms of its functions have been extensively explored, but much remains to be clarified. This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive, metabolic, cardiovascular, and neurological diseases.
The epithelial-mesenchymal transition (EMT) is a highly conserved cellular process that transforms epithelial cells into mesenchymal cells; EMT is involved in normal embryogenesis and tissue repair ...and contributes to tumor progression, including tumor metastasis, therapy resistance and disease recurrence. Cancer stem cells (CSCs) represent a fraction of undifferentiated cancer cells that exhibit stem cell-like features. They have the ability to self-renew and can seed new tumors. Thus, CSCs might represent the cellular resource that causes metastases and accounts for therapy resistance. Recent studies have highlighted a link between EMT and CSC formation. EMT is relevant to the acquisition and maintenance of stem cell-like characteristics and is sufficient to endow differentiated normal and cancer cells with stem cell properties. Moreover, CSCs often exhibit EMT properties. This reciprocal relationship between EMT and CSCs might have many implications in tumor progression. In this paper, we review current studies related to EMT and CSCs in tumor progression and therapeutic resistance, with a special focus on the common characteristics and links between these processes, and explore the importance of these links in the development of improved antitumor therapies.
Abstract Multi-drug resistance (MDR) has become the largest obstacle to the success of cancer chemotherapies. The mechanisms of MDR and the approaches to test MDR have been discovered, yet not fully ...understood. This review covers the in vivo and in vitro approaches for the detection of MDR in the laboratory and the mechanisms of MDR in cancers. This study also envisages the future developments toward the clinical and therapeutic applications of MDR in cancer treatment. Future therapeutics for cancer treatment will likely combine the existing therapies with drugs originated from MDR mechanisms such as anti-cancer stem cell drugs, anti-miRNA drugs or anti-epigenetic drugs. The challenges for the clinical detection of MDR will be to find new biomarkers and to determine new evaluation systems before the drug resistance emerges.
Following dramatic success in many types of advanced solid tumors, interest in immunotherapy for the treatment of colorectal cancer (CRC) is increasingly growing. Given the compelling long-term ...durable remission, two programmed cell death 1 (PD-1)-blocking antibodies, pembrolizumab and nivolumab (with or without Ipilimumab), have been approved for the treatment of patients with metastatic colorectal cancer (mCRC) that is mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). Practice-changing results of several randomized controlled trials to move immunotherapy into the first-line treatment for MSI-H metastasis cancer and earlier stage were reported successively in the past 2 years. Besides, new intriguing advances to expand the efficacy of immunotherapy to mCRC that is mismatch-repair-proficient and low microsatellite instability (pMMR-MSI-L) demonstrated the potential benefits for the vast majority of mCRC cases. Great attention is also paid to the advances in cancer vaccines and adoptive cell therapy (ACT). In this review, we summarize the above progresses, and also highlight the current predictive biomarkers of responsiveness in immunotherapy with broad clinical utility.
Medicine has encountered unprecedented problems associated with changes in nature, society, and environment, as well as with new human quests for survival, longevity, and health. In the meantime, the ...development of medicine is facing challenges that resulted from the over-division and specialization of disciplines and the fragmentation of medical knowledge. To construct a new medical system that is more suitable for human health and disease treatment, holistic integrative medicine (HIM), which regards the human body as a holistic entity, organically integrates the most advanced knowledge and theories in each medical field and the most effective practices in various clinical specialties to revise and adjust on the basis of social, environmental, and psychological conditions. HIM is the inevitable and necessary direction for the future development of medicine. In this article, we illustrated the connotation of HIM, the differences between HIM and other medical conceptions, and the practice of HIM in recent years.
The diagnostic and prognostic significance of carcinoembryonic antigen (CEA), carbohydrate associated antigen 19-9 (CA19-9), alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) in early gastric ...cancer have not been investigated yet. Thus, the present study aimed to explore the diagnostic and prognostic significance of the four tumor markers for early gastric cancer.
From September 2008 to March 2015, 587 early gastric cancer patients were given radical gastrectomy in our center. The clinicopathological characteristics were recorded. The association between levels of CEA and CA19-9 and clinicopathological characteristics and prognosis of patients were analyzed.
There were 444 men (75.6%) and 143 women (24.4%). The median age was 57 years (ranged 21-85). The 1-, 3- and 5-year overall survival rate was 99.1%, 96.8% and 93.1%, respectively. The positive rate of CEA, CA19-9, AFP and CA125 was 4.3%, 4.8%, 1.5% and 1.9%, respectively. The positive rate of all markers combined was 10.4%. The associations between the clinicopathological features and levels of CEA and CA19-9 were analyzed. No significant association was found between CEA level and clinicopathological features. However, elevated CA19-9 level was correlated with female gender and presence of lymph node metastasis. Age > 60 years old, presence of lymph node metastasis and elevation of CEA level were independent risk factors for poor prognosis of early gastric cancer.
The positive rates of CEA, CA19-9, APF and CA125 were relatively low for early gastric cancer. Elevation of CA19-9 level was associated with female gender and presence of lymph node metastasis. Elevation of CEA level was an independent risk factor for the poor prognosis of early gastric cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chemoresistance is the main cause of treatment failure in cancer and is associated with distant metastases and epithelial-to-mesenchymal transition (EMT). This study was aimed to explore the ...mechanism of metastases and EMT in chemoresistant gastric cancer.
A key molecular pathway was identified via gene profiling and a bioinformatic analysis in a chemoresistant gastric cancer model. The roles of FOXL2, HMGA2, and ITGA2 were validated via loss-of-function and gain-of-function experiments
and in an orthotopic gastric cancer animal model. The regulation of FOXL2 by HMGA2 was explored via immunoprecipitation and luciferase reporter assays. The expression of these proteins in gastric cancer tissues was examined by IHC.
HMGA2 and FOXL2 directly regulated the metastasis and EMT of chemoresistant gastric cancer. The interaction between HMGA2 and pRb facilitated the transactivation of FOXL2 by E2F1, and ITGA2 was the downstream effector of the HMGA2-FOXL2 pathway. HMGA2, FOXL2, and ITGA2 were associated with the TNM classification and staging of gastric cancer and were increased in metastatic lymph nodes and distant metastases. Increased HMGA2, FOXL2, and ITGA2 levels were associated with reduced overall survival periods of patients with gastric cancer.
This study demonstrated that the transactivation of FOXL2 driven by interactions between HMGA2 and pRb might exert critical effects on the metastases and EMT of chemoresistant gastric cancer. Blocking the HMGA2-FOXL2-ITGA2 pathway could serve as a new strategy for gastric cancer treatment.
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Portal vein thrombosis (PVT) is a fairly common complication of liver cirrhosis. Importantly, occlusive PVT might influence the prognosis of patients with cirrhosis. Evidence from a randomized ...controlled trial has shown that anticoagulation can prevent the occurrence of PVT in patients with cirrhosis without prior PVT. Evidence from several case series has also demonstrated that anticoagulation can achieve portal vein recanalization in patients with cirrhosis and PVT. Early initiation of anticoagulation therapy and absence of previous portal hypertensive bleeding might be positively associated with a high rate of portal vein recanalization after anticoagulation. However, the possibility of spontaneous resolution of partial PVT questions the necessity of anticoagulation for the treatment of partial PVT. In addition, a relatively low recanalization rate of complete PVT after anticoagulation therapy suggests its limited usefulness in patients with complete PVT. Successful insertion of a transjugular intrahepatic portosystemic shunt (TIPS) not only recanalizes the thrombosed portal vein, but also relieves the symptomatic portal hypertension. However, the technical difficulty of TIPS potentially limits its widespread application, and the risk and benefits should be fully balanced. Notably, current recommendations regarding the management of PVT in liver cirrhosis are insufficient owing to low-quality evidence.
Traditional research modes aim to find cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (miRNA) can function as oncogenes or tumor suppressors. ...miRNAs are single-stranded, small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the miRNA expression patterns in gastric carcinoma and the specific role of miR-223 in gastric cancer metastasis. miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature miRNAs. Sixteen miRNAs were upregulated in gastric carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six miRNAs were downregulated in gastric carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic gastric cancer cells and stimulated nonmetastatic gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3'-untranslated regions. Significantly, overexpression of miR-223 in primary gastric carcinomas is associated with poor metastasis-free survival. These findings indicate a new regulatory mode, namely, specific miRNA, which is activated by its upstream transcription factor, could suppress its direct targets and lead to tumor invasion and metastasis.
Multidrug resistance (MDR) is the most common cause of chemotherapy failure in gastric cancer (GC) treatment; however, the underlying molecular mechanisms remain elusive. Long noncoding RNAs ...(lncRNAs) can be involved in carcinogenesis, but the effects of lncRNAs on MDR are poorly understood. We show here that the lncRNA MRUL (MDR-related and upregulated lncRNA), located 400 kb downstream of ABCB1 (ATP-binding cassette, subfamily B, member 1), was significantly upregulated in two multidrug-resistant GC cell sublines, SGC7901/ADR and SGC7901/VCR. Furthermore, the relative expression levels of MRUL in GC tissues were negatively correlated with in vitro growth inhibition rates of GC specimens treated with chemotherapeutic drugs and indicated a poor prognosis for GC patients. MRUL knockdown in SGC7901/ADR and SGC7901/VCR cells led to increased rates of apoptosis, increased accumulation, and reduced doxorubicin (Adriamycin ADR) release in the presence of ADR or vincristine. Moreover, MRUL depletion reduced ABCB1 mRNA levels in a dose- and time-dependent manner. Heterologous luciferase reporter assays demonstrated that MRUL might positively affect ABCB1 expression in an orientation- and position-independent manner. Our findings indicate that MRUL promotes ABCB1 expression and is a potential target to reverse the MDR phenotype of GC MDR cell sublines.
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