The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line.

The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells

Relationships Between Communication, Time Pressure, Workload, Task Complexity, Logistical Issues and Group Composition in Transdisciplinary Teams: A Prospective Observational Study Across 822 Cancer Cases

Introduction: Functional perspective of team decision-making highlights the importance of understanding the relationship between team interaction/communication during a given task, the internal factors that emanate from within a group (e.g., team composition), and the external circumstances (e.g., workload and time pressures). As an underexplored area, we explored these relationships in the context of multidisciplinary team (MDT) meetings (aka tumor boards). Materials and methods: Three cancer MDTs with 44 team members were recruited from three teaching hospitals in the United Kingdom. Thirty of their weekly meetings encompassing 822 case reviews were filmed. Validated instruments were used to assess each case: Bales' Interaction Process Analysis that captures frequency of task-oriented and socio-emotional interactions/communication; and Measure of case-Discussion Complexity that captures clinical and logistic complexities. We also measured team size, disciplinary diversity, gender, time-workload pressure, and time-on-task. Partial correlation analysis controlling for team/tumor type and case complexity was used for analysis. Results: Clinical complexity positively correlated with task-oriented communication, e.g., gives opinion (r = 0.51, p 0.05), however, case reviews with more males present were associated with more tension (r = 0.09, p < 0.01) and less disagreements (r = −0.11, p < 0.01), while when more females present there were more disagreements (r = 0.10, p < 0.01) and less tension (r = −0.11, p < 0.01). Discussion: To the best of our knowledge, this is the first study to assess the relationship between MDT interaction/communication and the external/internal factors. Smaller size, gender balanced teams with core disciplines present, and streamlining workload to reduce time-workload pressure, time-on-task effects, and logistical issues appear more conducive to building and maintain optimal MDTs. Our methodology could be applied to other MDT-driven areas of healthcare

Pelvic mass associated with raised CA 125 for benign condition: a case report

<p>Abstract</p> <p>Background</p> <p>Raised CA 125 with associated pelvic mass is highly suggestive of ovarian malignancy, but there are various other benign conditions that can be associated with pelvic mass and a raised CA 125.</p> <p>Case presentation</p> <p>We present a case of 19 year old, Caucasian British woman who presented initially with sudden onset right sided iliac fossa pain and on imaging was found to have 9.8 × 4.5 cm complex cystic mass in right adnexa with a raised CA 125 of 657, which was initially thought to be highly suspicious of cancer but was subsequently found to be due to pelvic inflammatory disease on histology.</p> <p>Conclusion</p> <p>This case highlights the fact that though a pelvic mass with raised CA 125 is highly suggestive of malignancy, pelvic inflammatory disease should always be considered as a differential diagnosis especially in a young patient and a thorough sexual history and screening for pelvic infection should always be carried out in these patients.</p

The Eag potassium channel as a new prognostic marker in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K⁺) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression.</p> <p>Objectives</p> <p>To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation.</p> <p>Methods</p> <p>The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3).</p> <p>Results</p> <p>We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K⁺channel blockers.</p> <p>Conclusion</p> <p>This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.</p

Eag and HERG potassium channels as novel therapeutic targets in cancer

Voltage gated potassium channels have been extensively studied in relation to cancer. In this review, we will focus on the role of two potassium channels, Ether à-go-go (Eag), Human ether à-go-go related gene (HERG), in cancer and their potential therapeutic utility in the treatment of cancer. Eag and HERG are expressed in cancers of various organs and have been implicated in cell cycle progression and proliferation of cancer cells. Inhibition of these channels has been shown to reduce proliferation both in vitro and vivo studies identifying potassium channel modulators as putative inhibitors of tumour progression. Eag channels in view of their restricted expression in normal tissue may emerge as novel tumour biomarkers

The expression of EAG and HERG potassium channels in ovarian cancer and their role in cell proliferation

Background Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K) channels have shown to be promising therapeutic targets in the treatment of various cancers. We sought to determine the expression of EAG and HERG potassium channels in ovarian cancer and establish their role in cell proliferation. Material and Methods The Trent Research and Ethics Committee granted initial approval for the study. Informed consent was obtained from all patients undergoing surgery for ovarian cancer and oopherectomy for benign causes for their participation in the study. The tissues were prospectively collected and analysed anonymously. Immunoflurescence. Immunohistochemistry, Western blotting and Reverse transcriptase Polymerase chain reaction experiments were used to determine the expression of EAG and HERG potassium channels in ovarian cancer and normal ovaries. The effect of the EAG blockers (imipramine and clofilium) and HERG blockers (E-4031 and ergtoxin) on SK~OV-3 ovarian cancer cell line proliferation was assessed using the MTS assay with further investigation of their role in the cell cycle and apoptosis determined by flow cytometry. Results EAG and HERG potassium channels have significant (P<0.001) higher expression in patients with ovarian cancer compared to normal ovarian cells and high expression of EAG channels is significantly associated with poor survival (P=0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of EAG staining with high tumour grade (p=0.014) and presence of residual disease (p=0.011). Proliferation of SK-OV-3 cells was significantly (p<0.001) inhibited after treatment with voltage gated K+ channel blockers. There was significant inhibition of proliferation of SK-OV- 3 ovarian cancer cells by imipramine (p<0.001) and ergtoxin (p<0.05) at 72 hours of culture. Incubation of cells with ergtoxin led to the accumulation of cells in the S and G2IM phase while cells accumulated in S phase after incubation with E-403 1, with no effect on apoptosis.imipramine did not affect the cell cycle but increased the proportion ofSK-OV-3 cells undergoing early apoptosis. Conclusion Both EAG and HERG channels are expressed in ovarian cancer and have a role in cell proliferation. Higher expression of EAG channel is associated with poor prognosis suggesting its role as a poor prognostic marker in patients with ovarian cancer. HERG channels affect the cell cycle while EAG channels are implicated in the inhibition of apoptosis of ovarian cancer cells. EAG channels have the potential to be used as new therapeutic targets in patients with ovarian cancer with use of anti-EAG monoclonal antibody.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Does the Performance of Splenectomy as Part of Cytoreductive Surgery Carry a Worse Prognosis Than in Patients Not Receiving Splenectomy? A Propensity Score Analysis and Review of the Literature

Background & Objectives Ultra-radical (UR) procedures, including splenectomy, are utilized to increase complete cytoreduction rates during Cytoreductive Surgery (CRS) performed with the aim of complete macroscopic clearance of disease. The purpose of this study was to investigate if splenectomy negatively impacts survival when undertaken during CRS for advanced ovarian cancer (AOC) and compare published splenectomy and cytoreduction rates. Methods A retrospective review of all consecutive patients who underwent cytoreductive surgery for AOC between 16/05/2013-28/01/2019. Survival, baseline patient characteristics, complications and surgical parameters were recorded. Propensity scored matching (PSM) was performed to reduce bias. Results 154 patients identified over 71 months. 97 underwent standard, 57 underwent UR surgery, 27 patients received splenectomy (17.5%) No difference was seen in overall survival (OS) between all patients (median OS 34 months (95%CI 25.9–41.1) and patients who underwent splenectomy (median OS not yet reached) (p = >0.05). After PSM for various baseline covariates, no significant difference in splenectomy versus non-splenectomy patients (3-year survival 54% compared to 56%) (P > 0.05). Three splenectomy specific complications occurred; one each of pancreatic tail injury, left pleural effusion and streptococcal pharyngitis during chemotherapy. We found wide variation in utilization of splenectomy in published case series; from 9% to 35%. Conclusions Splenectomy performed as part of CRS is not detrimental to survival in AOC. There is a wide variation in utilization of splenectomy in published case series with little correlation with cytoreduction rates

Comparing the experience of enhanced recovery programme for gynaecological patients undergoing laparoscopic versus open gynaecological surgery: a prospective study

Abstract Background Enhanced recovery has been shown to improve patients’ experience after surgery. There are no previous studies comparing patients’ experience between those undergoing laparoscopic and open gynaecological surgery. Therefore, the aim of this prospective study is to compare patients’ functional recovery based on milestones set by the enhanced recovery programme and patients’ satisfaction between the two groups. Methods All eligible patients undergoing gynaecological surgery within an enhanced recovery after surgery (ERAS) programme from March to August 2014 were involved in this study. All patients received the questionnaires on admission which were then collected prior to discharge. They were followed up by telephone within 7 days. Results Two hundred sixty-three patients were involved. One hundred forty-four questionnaires were returned (54% response rate). Fifty-one percent (n = 74) were from the laparoscopic group and 49% (n = 70) were from the laparotomy group. In terms of achieving milestones, more patients in the laparotomy group performed the deep breathing exercises (laparoscopic versus open; 66.2% versus 87.1% (p = 0.003). The laparoscopic group were more able to eat on day 0, but by day 1, there was no difference between the groups. Both groups were similar in their ability to drink (p = 0.98), mobilise (p = 0.123) and sit out in a chair (p = 0.511). In the laparoscopic group, the patients’ experience was better for pain control (p < 0.0001) and nausea control (p = 0.003) from recovery to day 1, and they were more able to put on their own clothes (p = 0.001) and were more confident in mobilising (p < 0.0001) and in going home (p < 0.0001). The laparoscopic group had greater patient satisfaction with their pain always being well controlled (p < 0.0001) whilst more patients in the laparotomy group reported being satisfied to very satisfied with their overall care on the gynaecology ward (p = 0.04). Both groups were equally satisfied with their care from nursing staff (p = 0.709) and doctors (p = 0.431). Conclusion The two groups were in general equally able to achieve the majority of the milestones despite differences in symptoms such as pain, nausea and confidence in mobilising and going home. Pre-operative education can empower patients to engage in their recovery. There is a high level of patient satisfaction in both groups