Koefoedhauser9554
portantly, we demonstrated that miR-214-3p inhibition attenuated the protective effects of circ_GRN knockdown on ox-LDL-induced HVSMCs; besides that, miR-214-3p overexpression abolished ox-LDL-triggered HVSMC proliferation, migration, and inflammation, which were counteracted by FOXO1 upregulation. In conclusion, circ_GRN promoted the proliferation, migration, and inflammation of HVSMCs through miR-214-3p/FOXO1 axis in ox-LDL-induced AS model in vitro, suggesting the potential involvement in an AS process, which provided a potential candidate for future clinic intervention in AS.
Black patients with heart failure in the United States are underrepresented in clinical trials relative to their overrepresentation in the heart failure population and in adverse heart failure outcomes. We aim to evaluate historical trends in this space and highlight recent developments.
Multiple landmark heart failure trials published since 2019 have underrepresented Black patients, though several discussed this lack of representation as limitations. A review of large heart failure clinical trials from 2001 to 2016 found persistent underrepresentation of Black patients without significant change over time. Trials enrolling from North America exclusively had more proportional representation, enrolling an average of 31.6% Black participants.
There is a shrinking proportion of Black patients in pivotal heart failure trials despite a higher prevalence of disease and associated adverse outcomes. Dulaglutide There is increasing awareness of these disparities within the heart failure community, potentially leading to improved representation in future studies.
There is a shrinking proportion of Black patients in pivotal heart failure trials despite a higher prevalence of disease and associated adverse outcomes. There is increasing awareness of these disparities within the heart failure community, potentially leading to improved representation in future studies.
Atrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments.
Genome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many implicated genes. Genetic variants at identified loci also help predict individual atrial fibrillation risk and response to different therapies.
Continued advances in the field of genetics and molecular biology have led to significant insight into the genetic underpinnings of atrial fibrillation. Potential clinical applications of these studies include the identification of new therapeutic targets and development of genetic risk scores to optimize management of this common cardiac arrhythmia.
Continued advances in the field of genetics and molecular biology have led to significant insight into the genetic underpinnings of atrial fibrillation. Potential clinical applications of these studies include the identification of new therapeutic targets and development of genetic risk scores to optimize management of this common cardiac arrhythmia.
The relationship between elevated triglyceride levels (i.e. hypertriglyceridemia) and risk of atherosclerotic cardiovascular disease (ASCVD) has been investigated for decades. Recent genetic studies have sought to resolve the decades-old question of a causal relationship.
Genetic studies seem to demonstrate associations between elevated triglyceride levels and ASCVD risk. link2 Mendelian randomization studies suggest this association may be causal. However, simultaneous pleiotropic effects of metabolically linked lipid variables - such as non-HDL cholesterol, apolipoprotein B and HDL cholesterol -- often go unaccounted for in these studies. Complex underlying pleiotropic interactions of triglycerides with these lipid fractions together with unmeasured intercalated nonlipid-related mechanisms, such as inflammation and coagulation, impair the ability of genetic studies to implicate a direct role for triglycerides on ASCVD risk. One potential mechanism seems largely driven by the cholesterol carried within triglyceride-rich lipoproteins and their remnants, rather than their triglyceride content.
Although the exact mechanisms linking elevated triglyceride levels to ASCVD remain to be determined, new therapeutics that reduce triglyceride levels might be advantageous in certain patients. Newer investigational triglyceride-lowering therapies derived from human genetics target key proteins, such as apo C-III and ANGPTL3. Although these treatments clearly lower triglyceride levels, their efficacy in atherosclerotic risk reduction remains unproven.
Although the exact mechanisms linking elevated triglyceride levels to ASCVD remain to be determined, new therapeutics that reduce triglyceride levels might be advantageous in certain patients. Newer investigational triglyceride-lowering therapies derived from human genetics target key proteins, such as apo C-III and ANGPTL3. Although these treatments clearly lower triglyceride levels, their efficacy in atherosclerotic risk reduction remains unproven.
Present highlights from recent research examining the treatment of advanced prostate cancer.
Although debate remains about the optimal sequencing of docetaxel and novel androgen directed therapies in addition to androgen deprivation therapy (ADT) in the treatment of men with new metastatic prostate cancer, the novel LHRH antagonist relugolix seems poised to become an appealing option in a choice of initial ADT. Novel radioisotopes, genomically selected therapies, and immune therapy combinations show progress in opening up new treatment options for men with castration-resistant prostate cancer.
Although no clear consensus has emerged, evolving data continue to refine the selection of systemic therapies in treatment naïve metastatic prostate cancer. With potentially less cardiotoxic androgen deprivation therapies, novel radioisotopes, targeted pharmaceuticals, and immune therapy combinations, progress appears to be on the horizon in improving outcomes for men with advanced prostate cancer.
Although no clear consensus has emerged, evolving data continue to refine the selection of systemic therapies in treatment naïve metastatic prostate cancer. With potentially less cardiotoxic androgen deprivation therapies, novel radioisotopes, targeted pharmaceuticals, and immune therapy combinations, progress appears to be on the horizon in improving outcomes for men with advanced prostate cancer.
Although a standard of care in the treatment of organ-confined prostate cancer, use of radiation for treatment in the high-risk, metastatic and salvage settings is evolving rapidly.
Recent clinical trials have explored the role of increased treatment for high-risk disease with the addition of adjuvant chemotherapy and expanded the role of radiation in settings previously reserved for systemic therapy. Addition of adjuvant chemotherapy for high-risk prostate cancer is controversial and recent evidence is discussed that continues to refine the patient population for further evaluation. Evidence recently published demonstrates that for patients with low burden metastatic disease and those with oligometastatic disease may have a survival benefit with radiation treatment to all sites of known disease. Finally, reirradiation after prior radiotherapy-based treatment offers a potential salvage option for patients with locally recurrent prostate cancer.
As treatment paradigms evolve for prostate cancer, recent evidence continues to demonstrate benefit for the use of local therapy, both in patients with organ-confined disease and, more increasingly, in those with limited metastatic or locally recurrent disease. Further work is needed to identify subgroups of patients who may benefit from available treatment escalation approaches.
As treatment paradigms evolve for prostate cancer, recent evidence continues to demonstrate benefit for the use of local therapy, both in patients with organ-confined disease and, more increasingly, in those with limited metastatic or locally recurrent disease. Further work is needed to identify subgroups of patients who may benefit from available treatment escalation approaches.
Bladder cancer is the 10th most common cancer in the world and the 6th most common cancer among men. In the past few years, several new agents have been approved for the treatment of urothelial tumors. In this paper, we review the evolving treatment landscape of advanced urothelial carcinoma (UC).
Since 2016, the Food and Drug Administration (FDA) has approved five immunotherapies targeting programmed cell death 1/programmed cell death 1 legend, an antinectin-4 antibody drug conjugate (ADC), and a fibroblast growth factor receptor (FGFR) inhibitor for the treatment of patients with advanced UC. Moreover, there are multiple targeted agents, immune checkpoint inhibitors (ICI), ADCs, and their combinations currently being tested in clinical studies with the goal of obtaining FDA approval.
Precision oncology efforts continue to advance our understanding of the UC biology and transform the existing treatment paradigms. An enlarging arsenal of treatment options promises further personalization of UC therapy.
Precision oncology efforts continue to advance our understanding of the UC biology and transform the existing treatment paradigms. An enlarging arsenal of treatment options promises further personalization of UC therapy.
As molecular profiling of renal cell carcinoma (RCC) continues to elucidate novel targets for nonclear cell histologies, understanding the landscape of these targets is of utmost importance. link3 In this review, we highlight the genomic landscape of nonclear cell RCC and its implications for current and future systemic therapies.
Several genomic studies have described the mutational burden among nonclear cell histologies. These studies have highlighted the importance of MET in papillary RCC and led to several clinical trials evaluating the efficacy of MET inhibitors for papillary RCC. The success of immune checkpoint inhibitors, such as ipilimumab and nivolumab, in clear cell RCC has led to ongoing trials evaluating these novel therapeutics in nonclear cell RCC.
Genomic profiling has allowed for the evaluation of novel targets for nonclear cell RCC. This evolving therapeutic landscape is being explored in promising, ongoing trials that have the potential for changing how nonclear cell RCC is managed.
Genomic profiling has allowed for the evaluation of novel targets for nonclear cell RCC. This evolving therapeutic landscape is being explored in promising, ongoing trials that have the potential for changing how nonclear cell RCC is managed.We investigate L1 cell adhesion molecule (L1CAM) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative breast carcinomas. The finding of a potential correlation between high L1CAM expression and recurrent/metastatic disease in luminal A and B breast carcinomas may be helpful for risk stratification and open opportunities for targeted therapies. 304 cases comprising 152 cases of ER-positive, progesterone receptor (PR)-positive/negative, and HER2-negative recurrent/metastatic breast carcinomas and 152 nonrecurrent controls were included. ER, PR, HER-2, Ki-67 status, Nottingham grade, tumor size, tumor stage, number of foci, lymph node status, lymphovascular invasion, phenotype, laterality, age at diagnosis and first distant or local recurrence were recorded. L1CAM positive cases showed increased specificity for recurrence and these patients were significantly younger than L1CAM negative ones. Compared with L1CAM negative recurrent cases, L1CAM positive ones had a noticeably higher Ki-67, tended to be larger and recurred sooner.
