Wanghassing8652

Regorafenib is a multikinase inhibitor. It is used for metastatic colorectal cancer (mCRC) treatment. It has a mild effect. Regorafenib outcomes, and side effects may vary across patients. This study was aimed to evaluate the factors that affect regorafenib outcomes in mCRC patients. We conducted a single-center and retrospective study. Fifty-six patients were included. All patients had received regorafenib for mCRC. Some clinical and pathological factors and the effects of these factors on overall survival (OS), progression-free survival (PFS), and disease control rates (DCR) were analyzed. Concomitant amlodipine intake with regorafenib improved OS [14.26 vs. 6.97 months; 95% confidence interval, 4.04-20.84; P = 0.031] and DCR at 12th week (90% vs. 46%; P = 0.012). Hepatic metastasis was found as the poorest prognostic factor in both univariate and multivariate analyses. Patients who received chemotherapy after regorafenib had better OS. Good performance status was the strongest indicator of better OS. Patients taking amlodipine for arterial hypertension at the same time with regorafenib had numerically better OS and PFS and statistically better DCR. Amlodipine itself already has anticancer effects, and it has additive anticancer effects with regorafenib. The presence of hepatic metastases was found to be the most important prognostic factor for OS. There were not any predictive factors of side effects to regorafenib.The incidence of prostate cancer in the world is increasing every year. Death caused by prostate cancer is increased by 13% in men between 1980 and 2005. It is the second leading cause of cancer death in men after lung cancer. Bladder cancer is the second most common of urological malignancies. Most of the bladder cancers are treated with transurethral resection. Even great efforts have been made in the treatment of bladder cancer over the past years, it still remains as a major health problem. New therapeutic approaches are required to prevent the development and metastasis of these diseases. Experimental and clinical studies have shown potential beneficial effects of co-administration of beta-adrenergic receptor antagonists (beta-blockers) during cancer therapy. This study aimed to investigate the anti-tumor activity of beta-blockers on prostate and bladder cancer. Prostate and bladder cancer cell lines were cultured and treated with beta-blocker (propranolol). Then, protein levels and activity of apoptotic pathway mediators and mitogen-activated protein kinase (MAPK) pathway mediators were analyzed by ELISA. Propranolol treatment elevated the activity of caspase-3 and expression of bax, Wee1, GADD153 and apoptosis-inducing factor, but decreased bcl-2 which is an antiapoptotic protein. Propranolol treatment also inhibited ERK and JNK activity. This study showed that propranolol will help to inhibit prostate and bladder cancer by activating apoptotic pathway and by inhibiting MAPK pathway. This is the first study investigating the apoptotic effect of propranolol via MAPK on prostate and bladder cancer.To investigate the effect and potential mechanism of 3,3'-diindolylmethane (DIM) on ferroptosis against gastric cancer, cells proliferation, lipid reactive oxygen species (ROS) and GSH level were measured in the BGC-823 gastric cancer cells after DIM treatment. Western blotting was used to detect the expression of SLC7A11, GPX4, IP3R and BAP1. Results showed that DIM could induce ferroptosis in the BGC-823 gastric cancer cells via upregulating lipid-ROS level and decreasing GSH generation. Besides, DIM also significantly reduced the protein level of SLC7A11 and GPX4, which was an important regulator of ferroptosis. In addition, DIM promoted the protein level of BAP1 and IP3R in a concentration-dependent manner in the BGC-823 gastric cancer cells. The knockdown of BAP1 could reduce IP3R level and DIM-induced ferroptosis of gastric cancer cells. Taken together, these results indicated that DIM could induce ferroptosis to exert anti-cancer effects via BAP1-IP3R axis, suggesting its effective therapeutic potential in gastric cancer.Tongue squamous cell carcinoma (TSCC) has been well-known for its high metastasis and poor prognosis, but the molecular mechanisms of TSCC pathogenesis and chemoresistance are still largely unknown. Thus, the present study aimed to identify the involvement of a classic Hippo/Yes-associated protein 1 (YAP1) pathway in regulating TSCC progression and cisplatin (DDP) resistance. DDP-resistant TSCC cell lines were established by gradual exposure to DDP. Through western blot analysis, the protein expression of Hippo/YAP1 axis in TSCC tissues and cell lines was detected separately. Then, YAP1 was inhibited or overexpressed in TSCC cells. Cell viability and drug resistance were evaluated by cell counting kit-8 method, colony formation assay and Trypan blue staining assay. Cell migration ability was measured by Transwell assay. The Hippo pathway was dysregulated, and YAP1 was upregulated and dephosphorylated in the TSCC tissues or DDP-resistant cell lines, compared with normal tissues or DDP-sensitive cells. YAP1 knockdown inhibited cell proliferation, colony formation ability and migration, whereas overexpression of YAP1 exacerbated these malignant characteristics. YAP1 knockdown increased DDP-sensitivity by reducing the RAD51-mediated DNA damage repair behavior under DDP intervention in the DDP-resistant TSCC cells. Conversely, YAP1 overexpression significantly increased DDP-resistance by enhancing the RAD51-mediated DNA damage repair behavior under DDP intervention in the DDP-sensitive TSCC cells. In a word, upregulation and dephosphorylation of YAP1 caused dysregulation of the tumor-inhibiting Hippo pathway, resulting in the aggressiveness and DDP resistance in TSCC.The key regulatory roles of circular RNAs (circRNAs) in human diseases have been demonstrated, including breast cancer (BC). The purpose of this study is to explore the role of circ_0102273, a newly discovered circRNA, in BC progression. The expression levels of circ_0102273, microRNA (miR)-1236-3p and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) were determined by quantitative real-time PCR. Cell proliferation, migration and invasion were measured using colony formation assay, EdU staining, wound healing assay and transwell assay. Glucose consumption, lactate production and ATP level were detected to evaluate cell glycolysis. The interaction between miR-1236-3p and circ_0102273 or PFKFB3 was confirmed by dual-luciferase reporter assay and RIP assay. Additionally, western blot analysis was utilized for measuring PFKFB3 protein expression. In-vivo experiments were performed to further explore the function of circ_0102273 in BC tumorigenesis. Our data showed that circ_0102273 was highly expressed in BC tumor tissues and cells, and its downregulation could inhibit BC cell proliferation, metastasis and glycolysis. MiR-1236-3p was confirmed to be sponged by circ_0102273, and its inhibitor could reverse the negative regulation of sh-circ_0102273 on BC cell proliferation, metastasis and glycolysis. PFKFB3 could be targeted by miR-1236-3p, and its expression could be positively regulated by circ_0102273. In addition, miR-1236-3p could suppress BC cell proliferation, metastasis and glycolysis, while this effect could be abolished by PFKFB3. Furthermore, circ_0102273 knockdown also had been discovered to reduce BC tumorigenesis in vivo. In summary, our research proposed that circ_0102273 might be a potential target for BC treatment, which could inhibit BC proliferation, metastasis and glycolysis through the miR-1236-3p/PFKFB3 axis.

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder that causes hepatic overproduction of oxalate and, often, nephrocalcinosis, nephrolithiasis, chronic kidney disease, and kidney failure. The purpose of the review is to provide an update on current emerging therapies for the treatment of PH1.

Use of ribonucleic acid interference (RNAi) therapeutics that target the liver to block production of key enzymes along pathways that generate oxalate is a promising approach. Available evidence supports the efficacy of both Lumasiran (targeting glycolate oxidase) and Nedosiran (targeting hepatic lactate dehydrogenase (LDHa)) to reduce urinary oxalate excretion in PH1. The efficacy of alternative approaches including stiripentol (an anticonvulsant drug that also targets LDHa), lanthanum (a potential gastrointestinal oxalate binder), and Oxalobacter formigenes (a bacterium that can degrade oxalate within the gastrointestinal tract and may also increase its secretion from blood) are all also under study. Genetic editing tools including clustered regularly interspaced short palindromic repeats/Cas9 are also in preclinical study as a potential PH1 therapeutic.

Novel treatments can reduce the plasma oxalate concentration and urinary oxalate excretion in PH1 patients. Thus, it is possible these approaches will reduce the need for combined kidney and liver transplantation to significantly decrease the morbidity and mortality of affected patients.

Novel treatments can reduce the plasma oxalate concentration and urinary oxalate excretion in PH1 patients. Thus, it is possible these approaches will reduce the need for combined kidney and liver transplantation to significantly decrease the morbidity and mortality of affected patients.

Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes.

Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Roxadustat Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies.

There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality.

There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality.