https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

The ubiquitin-proteasome system (UPS) plays an important role in the cellular processes for protein quality control and homeostasis. Dysregulation of the UPS has been implicated in numerous diseases, including cancer. Indeed, components of UPS are frequently mutated or abnormally expressed in various cancers. Since Bortezomib, a proteasome inhibitor, received FDA approval for the treatment of multiple myeloma and mantle cell lymphoma, increasing numbers of researchers have been seeking drugs targeting the UPS as a cancer therapeutic strategy. Here, we introduce the essential component of UPS, including ubiquitinating enzymes, deubiquitinating enzymes and 26S proteasome, and we summarize their targets and mechanisms that are crucial for tumorigenesis. In addition, we briefly discuss some UPS inhibitors, which are currently in clinical trials as cancer therapeutics.

/pdf/ubiquitin-proteasome-system-ups-as-a-target-for-anticancer-2lprz0y6o2.pdf

Ubiquitin–proteasome system (UPS) as a target for anticancer treatment

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases. 

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential

Squamous precursor lesions of the vulva: current classification and diagnostic challenges

Ubiquitination is vital for multiple cellular processes via dynamic modulation of proteins related to cell growth, proliferation, and survival. Of the ubiquitination system components, E3 ubiquitin ligases and deubiquitinases have the most prominent roles in modulating tumor metastasis. This review will briefly summarize the observations and underlying mechanisms of multiple E3 ubiquitin ligases and deubiquitinases to regulate tumor metastasis. Further, we will discuss the relationship and importance between ubiquitination components and tumor progression.

/pdf/the-role-of-ubiquitination-and-deubiquitination-in-tumor-10ntnsy3.pdf

The role of ubiquitination and deubiquitination in tumor invasion and metastasis

Ellagic acid (EA) is a polyphenol found in several fruits and plants. EA has been reported to exert antitumor activity in many types of cancers. However, the effect and potential molecular mechanism of EA in endometrial cancer are still unclear. Therefore, the aim of this study was to explore the underlying antitumor function and targets by which EA inhibits endometrial cancer. By using multiplatform bioinformatics analysis tools, including DrugBank, STRING, WebGestalt and cBioPortal, the core targets of EA were identified as PIK3CA and PIK3R1. In addition, through transwell assays, EA was strongly found to inhibit cell invasion and migration. Based on CCK8 assays and flow cytometry, EA exhibited a suppressive effect on endometrial cancer cell proliferation by causing cell cycle arrest and inducing apoptosis. The results of real-time PCR confirmed that the expression of PIK3CA and PIK3R was decreased by EA. Furthermore, western blotting analysis demonstrated that EA inhibited PI3K phosphorylation, downregulating the expression of MMP9. In vivo, EA suppressed lung metastasis in BALB/c nude mice based on the SUVmax value determined from PET scans and HE staining. According to all these data, it comprehensively demonstrated the inhibitory effect of EA on endometrial cancer through bioinformatics analysis and experimental verification. Our findings suggest that EA may potentially be beneficial for treating endometrial cancer.

/pdf/ellagic-acid-exerts-antitumor-effects-via-the-pi3k-signaling-3mvq8b4263.pdf

Ellagic acid exerts antitumor effects via the PI3K signaling pathway in endometrial cancer.

Introduction This study aimed to evaluate whether endometriosis could disturb the mental health and health-related quality of life (HRQoL) of patients and to provide a new prospective for further treatment of endometriosis. Methods A comprehensive literature review was conducted among 4 international databases (PubMed, Embase, Web of Science, and Cochrane Library) and 2 of the largest Chinese databases (the China National Knowledge Infrastructure and Wangfang). The Newcastle-Ottawa Scale was used to assess the quality of the included articles. Six effect sizes were synthesized through a meta-analysis, and a subgroup analysis was performed to identify potential moderating factors, including types of control groups, methods of assessment, number of study groups, and origin of the study. Potential publication bias was examined using a funnel plot. Results This meta-analysis pooled 44 articles from 4 continents and 13 countries and compared 6 types of main effect sizes (the odds ratio [OR] for depression, the OR for anxiety, the standardized mean difference [SMD] for depression, the SMD for anxiety, the SMD for the physical component summary [PCS] and the SMD for the mental component summary [MCS]) between endometriosis patients and controls. Except for the SMD for depression, all other effect sizes revealed statistically significant differences between the study group and the controls. The main effect size outcomes of the subgroup analysis were also similar. The type of control group (I2 = 35% in non-endometriosis control groups for the SMD of anxiety; I2 = 47% in non-endometriosis control groups for the MCS of the 36-Item Short Form Health Survey) and the continent of origin (I2 = 0% in studies from South America for the OR of depression; I2 = 47% in studies from Europe for the SMD of anxiety) may influence heterogeneity in this analysis. Additionally, depression and anxiety symptoms in patients seemed to be more apparent compared with healthy controls when the sample was smaller and when a questionnaire was used. The publication bias of the articles was acceptable. Conclusion Endometriosis can disturb mental health (specifically depression and anxiety) and decrease both the mental and physical HRQoL of patients. There may be some moderating factors that we were unable to identify in the subgroup analysis, but more research is necessary to develop proper management and improve the prognosis of endometriosis patients.

Does Endometriosis Disturb Mental Health and Quality of Life? A Systematic Review and Meta-Analysis.

The incidence of uterine fibroids, which comprise one of the most common female pelvic tumors, is almost 70-75% for women of reproductive age. With the development of surgical techniques and skills, more individuals prefer minimally invasive methods to treat uterine fibroids. There is no doubt that minimally invasive surgery has broad use for uterine fibroids. Since laparoscopic myomectomy was first performed in 1979, more methods have been used for uterine fibroids, such as laparoscopic hysterectomy, laparoscopic radiofrequency volumetric thermal ablation, and uterine artery embolization, and each has many variations. In this review, we compared these methods of minimally invasive surgery for uterine fibroids, analyzed their benefits and drawbacks, and discussed their future development.

https://journals.viamedica.pl/ginekologia_polska/article/download/GP.2020.0032/50557

Minimally invasive surgery for uterine fibroids.

Primary primitive neuroectodermal tumors (PNETs) are rare and high-grade malignant tumors that mostly occur in children and young adults. The most common sites are the trunk, limbs, and retroperitoneum. Herein, we present a case of a PNET involving the cervix uteri in a 27-year-old woman. The lesion showed characteristic histologic features of a PNET and was positive for the immunohistochemical markers cluster of differentiation (CD) 99, vimentin, neuron-specific enolase, neural cell adhesion molecule 1 (CD56), and CD117 (c-kit), further defining the tumor while helping to confirm PNET. The clinical Stage IIIB tumor was treated with chemotherapy and radiotherapy.

https://www.dovepress.com/getfile.php?fileID=16425

Primary primitive neuroectodermal tumor of the cervix

Gastrointestinal stromal tumors (GISTs) have a rather wide morphologic spectrum. Here, we report a rare variant plexiform GIST in gastric antrum. Microscopically, the tumor showed plexiform or multinodular growth pattern, proliferation of spindle cells, presence of epithelioid cells, and abundant myxoid stroma with thin-walled blood vessels. The histologic features were similar to plexiform fibromyxoma. The typical characteristics of immunohistochemistry (positive for CD34, DOG-1 and CD117) confirmed the final diagnosis of GIST. This is a rare case of myxoid GIST characterized by a plexiform growth pattern.

Plexiform myxoid gastrointestinal stromal tumor: a potential diagnostic pitfall in pathological findings.

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