Heather Wahl

Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells

BackgroundGinger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro.MethodsThe effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-κB and and production of VEGF and IL-8 was determined in the presence or absence of ginger.ResultsGinger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8.ConclusionGinger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.

Glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells.

OBJECTIVES Upregulation of glycolysis has been demonstrated in multiple tumor types. Glucose deprivation results in diminished intracellular ATP; this is counteracted by AMPK activation during energy deficiency to restore ATP levels. We sought to determine whether glucose deprivation could induce cytotoxicity in ovarian cancer cells through activation of AMPK, and whether AMPK activators could mimic glucose deprivation induced cytotoxicity. METHODS Sensitivity to 2DG induced cytotoxicity and glucose deprivation was determined in a panel of ovarian cancer cells. Cellular growth rate, rate of glucose uptake, and response to glucose deprivation were determined. Expression of Glut-1, HIF1-α, AMPK and Akt was determined by immunoblotting. RESULTS Incubation of ovarian cancer cells with glucose-free media, 2-DG and AMPK activators resulted in cell death. The glycolytic phenotype of ovarian cancer cells was present in both normoxic and hypoxic conditions, and did not correlate with HIF1-α expression levels. Sensitivity to glucose deprivation was independent of growth rate, rate of glucose uptake, and appeared to be dependent upon constitutive activation of Akt. Glucose deprivation resulted in activation of AMPK and inhibition of Akt phosphorylation. Treatment with AMPK activators resulted in AMPK activation, Akt inhibition, and induced cell death in ovarian cancer cells. CONCLUSIONS Ovarian cancer cells are glycolytic as compared to normal, untransformed cells, and are sensitive to glucose deprivation. Because ovarian cancer cells are dependent upon glucose for growth and survival, treatment with AMPK activators that mimic glucose deprivation may result in broad clinical benefits to ovarian cancer patients.

Inhibition of glycolysis enhances cisplatin-induced apoptosis in ovarian cancer cells

OBJECTIVE Up-regulation of glycolysis has been demonstrated in multiple tumor types and is believed to originate as an adaptive response to the selective pressure of the tumor microenvironment. We hypothesized that ovarian cancer cells are dependent on the glycolytic pathway for adenosine triphosphate generation and that this phenotype could be exploited for therapeutic intervention. STUDY DESIGN Expression of glucose transporter 1 (Glut1), phosphorylated protein kinase B (pPKB/pAkt), and phosphorylated mammalian target of rapamycin (pmTOR) was assessed in ovarian carcinoma tumors and cell lines. Cells were incubated with 2-deoxyglucose and rapamycin; growth inhibition, viability, and mechanism of cell death were determined. RESULTS Ovarian carcinoma cells overexpress Glut1, pAkt, and pmTOR compared with benign ovarian epithelial cells. 2-deoxyglucose and rapamycin markedly enhance apoptotic and nonapoptotic cell death in ovarian cancer cells. CONCLUSION The glycolytic phenotype of ovarian cancer cells can be targeted for therapeutic intervention. Combined treatment modalities that target multiple cellular pathways hold promise for the treatment of chemoresistant ovarian cancer cells.

Resveratrol inhibits ovarian tumor growth in an in vivo mouse model

Resveratrol inhibits the growth of ovarian carcinoma cells in vitro through the inhibition of glucose metabolism and the induction of both autophagy and apoptosis. In the current study, we investigated the metabolic and therapeutic effects of resveratrol in vivo.

Effects of intrauterine contraception on the vaginal microbiota

OBJECTIVES There have been conflicting reports of altered vaginal microbiota and infection susceptibility associated with contraception use. The objectives of this study were to determine if intrauterine contraception altered the vaginal microbiota and to compare the effects of a copper intrauterine device (Cu-IUD) and a levonorgestrel intrauterine system (LNG-IUS) on the vaginal microbiota. STUDY DESIGN DNA was isolated from the vaginal swab samples of 76 women using Cu-IUD (n=36) or LNG-IUS (n=40) collected prior to insertion of intrauterine contraception (baseline) and at 6 months. A third swab from approximately 12 months following insertion was available for 69 (Cu-IUD, n=33; LNG-IUS, n=36) of these women. The V4 region of the bacterial 16S rRNA-encoding gene was amplified from the vaginal swab DNA and sequenced. The 16S rRNA gene sequences were processed and analyzed using the software package mothur to compare the structure and dynamics of the vaginal bacterial communities. RESULTS The vaginal microbiota from individuals in this study clustered into 3 major vaginal bacterial community types: one dominated by Lactobacillus iners, one dominated by Lactobacillus crispatus and one community type that was not dominated by a single Lactobacillus species. Changes in the vaginal bacterial community composition were not associated with the use of Cu-IUD or LNG-IUS. Additionally, we did not observe a clear difference in vaginal microbiota stability with Cu-IUD versus LNG-IUS use. CONCLUSIONS Although the vaginal microbiota can be highly dynamic, alterations in the community associated with the use of intrauterine contraception (Cu-IUD or LNG-IUS) were not detected over 12 months. IMPLICATIONS We found no evidence that intrauterine contraception (Cu-IUD or LNG-IUS) altered the vaginal microbiota composition. Therefore, the use of intrauterine contraception is unlikely to shift the composition of the vaginal microbiota such that infection susceptibility is altered.

The role of nonpharmacologic therapies in management of chronic pelvic pain: What to do when surgery fails

Purpose of review To provide an update on nonsurgical and nonpharmacologic strategies for the management of chronic pelvic pain (CPP). Recent findings Effective treatment of patients with CPP requires a multifaceted approach, with thoughtful consideration of surgical, pharmacologic, and nonpharmacologic strategies. Evidence for physical therapy and trigger point injections for treatment of myofascial components of CPP is increasing. Neuromodulation techniques, such as percutaneous tibial nerve stimulation and transcutaneous electrical stimulation, have limited but favorable preliminary data in patients with CPP. Behavioral strategies, such as exercise, cognitive behavioral therapy, and mindfulness, have demonstrated significant improvements in pain, function and quality of life in patients with a variety of chronic pain conditions and are promising avenues for future research in CPP. Summary Nonpharmacologic therapies are important adjuncts to surgical and pharmacologic treatment for CPP and should be considered integral to a comprehensive treatment approach.

Laparoscopic Removal of a Retroperitoneal Hysteroscopic Microinsert Using Fluoroscopy

Perforation during placement of hysteroscopic microinserts for permanent sterilization occurs in approximately .9% to 2.6% of women undergoing the procedure. Most of the time perforation results in intraperitoneal placement of the hysteroscopic microinsert requiring laparoscopy or laparotomy for removal of the device. Herein we present a case of hysteroscopic microinsert perforation with subsequent retroperitoneal identification of the device. This is the first such case to our knowledge of retroperitoneal identification and retrieval of a perforated device that required real-time fluoroscopy during laparoscopy.

Laparoscopic Retrieval of a Retroperitoneal Hysteroscopic Microinsert Using Fluoroscopy

conservatively by percutaneous nephrostomy tube and ureteral stent with relatively poor success rate. We present a 46-year-old female presents 10 days post-laparoscopic total hysterectomy with urinary drainage from the vagina, with a ureterovaginal fistula diagnosed by cystoscopy and intravenous pyelogram, the fistula was successfully treated laparoscopically immediately after the diagnosis was made. This video demonstrates in detail, step by step, our surgical technique of the laparoscopic repair of a ureterovaginal fistula.