Abstract:In this review, we summarized 14 major clinical advances in gynecology which occurred in 2008. For cervical cancer, clinical impact of HPV vaccine, prognostic value of imaging during radiotherapy, and oncologic/obstetric outcomes of fertility-sparing surgery were chosen. For uterine cancer, optimal method of adjuvant radiotherapy in intermediate-risk patients, extent of lymph node dissection, outcome of robot-assisted staging surgery, new standard chemotherapy regimen for leiomyosarcoma were selected. For ovar… Show more
“…Patients generally receive adjuvant therapy in the case of positive lymph nodes, large tumor size, deep stromal invasion and positive surgical margins. Standard chemotherapeutic agents such as cisplatin which are used for adjuvant therapy have been associated with several side effects 41 . Hence, in order to prevent recurrence of cervical cancer after surgery, TALEN based adjuvant therapy could therefore be an option to enhance the effectiveness of primary surgery or radiotherapy for cervical cancer.Figure 7Schematic representation of Necrosis induced by TALEN editing of cervical cancer cells and possible activation of immune cells leading to cell death.…”
Human Papillomavirus E7 and E6 oncoproteins have been considered as suitable candidate anti-viral targets since they cause malignant conversion in cervical cancers. Transcription Activator-Like Effector Nucleases (TALENs) are recent editing tools to knockout genes by inducing double stranded breaks at specific sites in the genome. In here, we have designed specific TALENs to target E7 and analyzed their efficiency in inducing cell death in cervical cancer cells. We found that designed TALENs could yield about 10–12% editing activity as observed from T7E1 and nuclease resistance assays. Down-regulation of E7 and E6 was further evident at the transcript as well as proteins levels indicating that the selected TALENs were effective. TALEN-mediated E7 editing led to cell death as ascertained by cell cycle and Annexin V assays. Annexin profiling suggested that cell death could be due to necrosis as observed by upregulation of necrotic markers such as LDH A, Rip-1, and Cyclophilin A. Necrosis appears to be a better therapeutic response as it could further activate pro-inflammatory cytokines to attract immune cells to eliminate HPV-integrated cells and therefore TALEN editing strategy has the potential to be a promising tool as an adjuvant therapy in cervical cancer along with surgery.
“…Patients generally receive adjuvant therapy in the case of positive lymph nodes, large tumor size, deep stromal invasion and positive surgical margins. Standard chemotherapeutic agents such as cisplatin which are used for adjuvant therapy have been associated with several side effects 41 . Hence, in order to prevent recurrence of cervical cancer after surgery, TALEN based adjuvant therapy could therefore be an option to enhance the effectiveness of primary surgery or radiotherapy for cervical cancer.Figure 7Schematic representation of Necrosis induced by TALEN editing of cervical cancer cells and possible activation of immune cells leading to cell death.…”
Human Papillomavirus E7 and E6 oncoproteins have been considered as suitable candidate anti-viral targets since they cause malignant conversion in cervical cancers. Transcription Activator-Like Effector Nucleases (TALENs) are recent editing tools to knockout genes by inducing double stranded breaks at specific sites in the genome. In here, we have designed specific TALENs to target E7 and analyzed their efficiency in inducing cell death in cervical cancer cells. We found that designed TALENs could yield about 10–12% editing activity as observed from T7E1 and nuclease resistance assays. Down-regulation of E7 and E6 was further evident at the transcript as well as proteins levels indicating that the selected TALENs were effective. TALEN-mediated E7 editing led to cell death as ascertained by cell cycle and Annexin V assays. Annexin profiling suggested that cell death could be due to necrosis as observed by upregulation of necrotic markers such as LDH A, Rip-1, and Cyclophilin A. Necrosis appears to be a better therapeutic response as it could further activate pro-inflammatory cytokines to attract immune cells to eliminate HPV-integrated cells and therefore TALEN editing strategy has the potential to be a promising tool as an adjuvant therapy in cervical cancer along with surgery.
“…Despite significant advances in diagnosis and treatment, ovarian carcinoma remains the most lethal gynecologic tumor, and more than 70% of affected women are diagnosed with advanced disease [1][2][3]. Although many patients respond initially to combinations of cytoreductive surgery and chemotherapy, many patients will subsequently experience recurrence [4,5].…”
“…On the other hand, vaginal intraepithelial neoplasia (VAIN) may develop in the vaginal vault after hysterectomy although VAIN is 100 times less frequent than CIN [2]. Previous studies demonstrated that 83.3% of patients with VAIN have been reported to have at least one of the predisposing factors such as human papillomavirus (HPV) infection, radiation therapy and immunosuppression [2][3][4][5]. CIN or vulvar intraepithelial neoplasia (VIN) is found in 33.…”
Laser vaporization may be a feasible method for the treatment of VAIN in the vaginal vault after hysterectomy. However, age (< or =48 years) and VAIN III in the vaginal vault before laser vaporization should be considered as risk factors for recurrence after laser vaporization.
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