RAD6 promotes DNA repair and stem cell signaling in ovarian cancer and is a promising therapeutic target to prevent and treat acquired chemoresistance

Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression. Upregulated RAD6 enhances DNA damage tolerance and repair efficiency of OC cells and promotes their survival. Increased RAD6 levels cause histone 2B ubiquitination-mediated epigenetic changes that stimulate transcription of stem cell genes, including ALDH1A1 and SOX2, leading to a cancer stem cell phenotype, which is implicated in disease recurrence and metastasis. Downregulation of RAD6 or its inhibition using a small molecule inhibitor attenuated DNA repair signaling and expression of cancer stem cells markers and sensitized chemoresistant OC cells to carboplatin. Together, these results suggest that RAD6 could be a therapeutic target to prevent and treat acquired chemoresistance and disease recurrence in OC and enhance the efficacy of standard chemotherapy

Chronic nonpuerperal uterine inversion and necrosis: a case report

<p>Abstract</p> <p><b>Introduction</b></p> <p>Inversion of the non-pregnant uterus is rare.</p> <p><b>Case presentation</b></p> <p>A 56-year-old African American woman presented to our emergency center with complaints of a mass protruding from her vagina. She subsequently underwent vaginal myomectomy, abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathologic examination revealed a necrotic fibroid and endometrium. At the time of laparotomy an inverted uterus was diagnosed when a 3 cm dimple containing bilateral round ligaments, infundibulopelvic ligaments and bladder was observed.</p> <p>Conclusion</p> <p>Chronic nonpuerperal inversion of the uterus is rare. Infection should be suspected and appropriate broad spectrum antibiotics begun while planning surgery. An attempt at vaginal restoration and removal is difficult. Abdominal hysterectomy may be necessary taking care to locate the distal urinary collecting system.</p

Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study

Background Feline nonflea hypersensitivity dermatitis (NFHD) is a frequent cause of over-grooming, scratching and skin lesions. Multimodal therapy often is necessary. Hypothesis/Objectives To investigate the efficacy of ultramicronized palmitoylethanolamide (PEA-um) in maintaining methylprednisolone-induced remission in NFHD cats. Animals Fifty-seven NFHD cats with nonseasonal pruritus were enrolled originally, of which 25 completed all study requirements to be eligible for analysis. Methods and materials Cats were randomly assigned to PEA-um (15 mg/kg per os, once daily; n = 29) or placebo (n = 28) while receiving a 28 day tapering methylprednisolone course. Cats responding favourably to methylprednisolone were then administered only PEA-um (n = 21) or placebo (n = 23) for another eight weeks, followed by a four week long treatment-free period. Cats were maintained in the study until relapse or study end, whichever came first. Primary outcome was time to relapse. Secondary outcomes were pruritus Visual Analog Scale (pVAS), SCORing Feline Allergic Dermatitis scale (SCORFAD) and owner Global Assessment Score (GAS). Results Mean relapse time was 40.5 days (+/- 7.8 SE) in PEA-um treated cats (n = 13) and 22.2 days (+/- 3.7 SE) for placebo (n = 12; P = 0.04). On Day 28, the severity of pruritus was lower in the PEA-um treated cats compared to placebo (P = 0.03). Mean worsening of pruritus at the final study day was lower in the PEA-um group compared to placebo (P = 0.04), whereas SCORFAD was not different between groups. Mean owner GAS at the final study day was better in the PEA-um than the placebo-treated group (P = 0.05). Conclusion and clinical importance Ultramicronized palmitoylethanolamide could represent an effective and safe option to delay relapse in NFHD cats

Beyond the Numbers: An Examination of Diverse Interactions in Law School

A concerted effort has been devoted to diversifying law schools. However, the focus has been almost exclusively on increasing the structural diversity of the student body rather than increasing diverse interactions. This study investigates the types of activities and experiences in law school that relate with more frequent diverse interactions. Findings illustrate several other factors, in addition to structural diversity, are related with more frequent diverse interactions. These factors include perceptions of a supportive and friendly law school environment, interactions with faculty members, positive relationships with other students, pro bono work, and being a member of a student organization