Conwaykaae1604

Recently, combination therapy including immune checkpoint inhibition (ICI) has proven to be effective as first-line therapy for patients with metastatic renal cell carcinoma. Although the first-line combination therapies with ICI have shown clinical benefit, a number of patients require second-line treatment. We report a 60-year-old man with metastatic renal cell carcinoma who was treated with pazopanib soon after nivolumab plus ipilimumab combination therapy. He experienced Grade 3 disseminated intravascular coagulation (DIC). We suspect that this was caused by an interaction between pazopanib and nivolumab even though ICI therapy was discontinued. He was treated with thrombomodulin and platelet transfusion and recovered from DIC. Treatment with pazopanib was subsequently restarted. No evidence of DIC was observed thereafter. This severe adverse reaction may have been induced by an interaction between activated proinflammatory immune cells and cytokines from an exacerbated inflammatory state and pazopanib. This report highlights the need to perform careful monitoring of patients who receive molecular targeted therapy after ICI-based immunotherapy.The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.Side effects of afatinib are a problem in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the occurrence of afatinib-induced hypotension. An 81-year-old man with NSCLC had an epidermal growth factor receptor-positive genotype with the p.L861Q mutation in exon 21. He was administered afatinib (40 mg/day) as anticancer therapy. Hypotension occurred twice after afatinib initiation. He suffered from dizziness and nausea. Blood pressure gradually returned to normal after afatinib cessation. Clinicians should be aware of hypotension in patients with NSCLC after afatinib initiation.In our paper, the effects of As4S4 treatments on the growth and migration of gastric cancer (GC) cells were explored, and the potential underlying molecular mechanisms were also identified. Cell viability was evaluated by cell counting kit 8 assay. The expression of Ki-67 was examined using immunofluorescence staining. Cell apoptosis was assessed by flow cytometry. The migratory and invasion abilities of cells were determined using Transwell assay. The mRNA and protein levels of related gene were examined by RT-qPCR and western blotting, respectively. CircRNAs chip was performed to identify the differentiated expression of circRNAs in GC cells following the treatment with As4S4. Our results revealed that the proliferation, migration and invasion of GC cells were remarkably suppressed by the treatment with As4S4, while cell apoptosis was promoted. Furthermore, circRNA_ASAP2 was a novel target of As4S4 in GC, and it is involved in As4S4-modulated biological behavior alterations in GC cells. In addition, the activities of the Wnt/β-catenin signaling in GC cells were affected by the overexpression circRNA_ASAP2 and the treatment with As4S4. Moreover, the behavior changes in GC cells caused by the knockdown of circRNA_ASAP2 were reversed by the treatment with Wnt agonist SKL2001. In summary, As4S4 could function as an antitumor agent in GC through regulating the circRNA_ASAP2/Wnt/β-catenin pathway, which in turn influences the growth and metastasis of GC cells.Loss of P27 expression correlates with clinical progression in a variety of human cancers. Osimertinib research buy However, the correlation between P27 expression and gastric cancer remains controversial. In this meta-analysis, we performed an electronic search based on six databases to select a sufficient number of studies. Pooled hazard ratio (HR) was used as estimates to investigate the association between P27 expression and prognosis of patients with gastric cancer. We identified 19 studies with 2387 gastric cancer patients, ranging between 50 and 316 samples per study. Q and I2 tests demonstrated that the homogeneity among 19 studies (I2 = 47%, P = 0.0004), thus we applied a fixed-effects model to calculate the pooled HR of P27expression and overall survival (OS) of gastric cancer patients was 0.68, and 95% confidence interval (CI) was 0.60-0.78. Next, we conducted a subgroup meta-analysis and found that patients with low P27 expression in Asians (HR = 0.69, 95% CI 0.58-0.82) and non-Asians (HR = 0.57, 95% CI 0.41-0.79) had poor prognosis. In addition, we found the publication bias results of OS in the final included 19 studies showed that this funnel plot presented incomplete symmetry, and then removed three literatures with larger HRs bias, and found that the remaining 16 literatures were homogeneity (I2 = 0%, P = 0.47), the pooled HR was 0.52 with 95% CI of 0.43-0.62, and the publication bias disappeared. These results suggested a strong association between P27 underexpression and poorer prognosis of gastric cancer in patients. P27 may be a tumor suppressor for predicting survival outcome of gastric cancer patients.Accumulating evidence has presented that microRNA-148a/152 (miR-148a/152) acts as the tumor inhibitor in various cancers. In this article, we aimed to probe the inhibition of colon cancer stem cells by miR-148a/152 cluster via regulation of CCT6A. miR-148a/152 and CCT6A expression in colon cancer tissues and cells was detected. The relationship between miR-148a/152 expression and the clinicopathological features of patients with colon cancer was analyzed. Colon cancer stem cells (CD44+/CD133+) were selected and high/low expression of miR-148a/152 plasmids were synthesized to intervene CD44+/CD133+ colon cancer stem cells to investigate the function of miR-148a/152 in invasion, migration, proliferation, colony formation and apoptosis of cells. The growth status of nude mice was observed to verify the in-vitro results. The relationship between miR-148a/152 and CCT6A was analyzed. CCT6A upregulated and miR-148a/152 downregulated in colon cancer tissues. MiR-148a/152 expression was correlated with tumor node metastasis stage, lymph node metastasis and differentiation degree. Upregulated miR-148a/152 depressed CCT6A expression and restrained invasion and migration ability, colony formation and proliferation, induced cell apoptosis, depressed OCT4, Nanog and SOX2 mRNA expression of colon cancer stem cells, and descended tumor weight and volume in nude mice. CCT6A was a target gene of miR-148a/152. Overexpression of CCT6A protected colon cancer stem cells. Functional studies showed that upregulation of miR-148a/152 can suppress the migration, invasion and proliferation of CD44+/CD133+ colon cancer stem cells, advance its apoptosis via inhibition of CCT6A expression.Introduction Overactive bladder syndrome is an endemic phenomenon, which has a significant impact on the quality of life. In cases where conservative treatment fails, intradetrusor onabotulinumtoxinA injection can be used as second-line therapy. Objective To assess the safety and efficacy of onabotulinumtoxinA treatment in the management of non-neurogenic detrusor overactivity among our patients. Also, to examine the influence of perioperative factors on the effects of the efficacy. Method We have retrospectively collected the perioperative data of 33 patients treated with intradetrusor BOTOX®. The assessment of the efficacy and complications was done by the examination of patient files and questionnaires. The results obtained during the statistical analysis were considered significant for p less then 0.05. Results We have not experienced notable complications after the procedures. Only 6 patients had residual urine (p = 0.024), none of them needed to be catheterized. We have observed significant decrease in the incidence of frequency, nocturia, urgency and incontinence, just as in the number of pads needed daily (p less then 0.01). Quality of life and general health were significantly improved (p less then 0.001). We have not found any significant connection between preoperative factors and efficacy (72.7%). Discussion Our results considering the relief of symptoms are well in line with international data. The fact that our rate of complications is - in international comparison - outstanding can be explained by a more careful patient selection and thorough preoperative assessment. Conclusion OnabotulinumtoxinA therapy is a safe and effective solution of therapy-refractory overactive bladder. We could not identify any perioperative factor to predict postoperative efficacy of therapy. Orv Hetil. 2021; 162(36) 1459-1465.

Obesity imposes risk to cardiometabolic health; however, intentional weight loss among older adults with obesity remains controversial.

To explore the influence of exercise plus weight maintenance and exercise plus intentional weight loss by caloric restriction on changes in cardiometabolic risk among older adults with obesity assessed by four risk-scoring tools.

Using longitudinal data from the Calorie Restriction and Changes in Body Composition, Disease, Function, and Quality of Life in Older Adults study (CROSSROADS) (ClinicalTrials.gov identifier NCT00955903; May 2009 to October 2014), scores were calculated using baseline and 12-month data according to criteria from the International Diabetes Federation, National Cholesterol Education Program's Adult Treatment Panel, Framingham Risk Score, and Cardiometabolic Disease Staging.

Participants (39% men, 23% African American, aged 70.2 ± 4.7 years) were randomized to exercise (n= 48), exercise plus nutrient-dense weight maintenance diet (n= 44), or exeroup differences in Cardiometabolic Disease Staging, the exercise plus weight loss group showed significant risk reduction (P= 0.012; r= -0.142) compared with the exercise group.

Among risk scores evaluated, Framingham and Cardiometabolic Disease Staging showed significantly greater sensitivity to change in cardiometabolic risk. Older adults with obesity can significantly lower cardiometabolic risk through exercise plus weight maintenance or exercise plus weight loss by moderate caloric restriction.

Among risk scores evaluated, Framingham and Cardiometabolic Disease Staging showed significantly greater sensitivity to change in cardiometabolic risk. Older adults with obesity can significantly lower cardiometabolic risk through exercise plus weight maintenance or exercise plus weight loss by moderate caloric restriction.