76 research outputs found
sj-docx-1-tam-10.1177_17588359231157633 – Supplemental material for A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer
No full textSupplemental material, sj-docx-1-tam-10.1177_17588359231157633 for A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer by Anna V. Tinker, Neesha C. Dhani, Prafull Ghatage, Deanna McLeod, Vanessa Samouëlian, Stephen A. Welch and Alon D. Altman in Therapeutic Advances in Medical Oncology</p
Abstract 3149: Identification of genes associated with the cisplatin resistance in cervical cancer cells expressing E545K mutation
No full textAbstract
The phosphatidylinositol-3 kinase (PI3K)/AKT/ mTOR signaling pathway is activated in several human cancers and activation is frequently mediated by “hotspot” mutations including E542K, E545K and H1047R in the PIK3CA gene. Approximately 30% of cervical cancer patients have the PIK3CA-E545K mutation. Cisplatin with radiotherapy (RT) is the standard treatment of cervical cancer world-wide, used in both the radical and post-operative adjuvant settings. However, details of the molecular mechanisms responsible for cisplatin resistance remain unclear. We previously reported PIK3CA mutation in patients with earlier stage (IB/II) cervical cancer was associated with poor survival (McIntyre et al. Gynecol Oncol. 2013, PMID:23266353), and in our recent study we observed that PIK3CA-E545K mutation renders cervical cancer cells more resistant to cisplatin or cisplatin plus RT and results in a more migratory phenotype than isogenic cell lines with wild type-PIK3CA. Moreover, these phenotypes are reversed by the PI3K inhibitor GDC-0941/Pictilisib (Wani et al. Oncotarget. 2016, PMID:27489350). The aim of the present study is to identify the expression of genes related to cisplatin resistance in cervical cancer cells engineered to express PIK3CA-E545K. Microarray analysis identified 161 genes that were up-regulated and 189 that were down-regulated in the cervical cancer cells stably expressing PIK3CA-E545K, some of which are involved in well-characterized mechanisms that could be relevant to cisplatin resistance. We are currently validating some of those genes by Real-time PCR that will help us to determine the mechanism of PIK3CA-E545K induced cisplatin resistance and enhanced migration in cervical cancer cells expressing PIK3CA-E545K and extending our in vitro findings to animal models. Together, our data will provide a useful basis for screening candidate targets for risk stratification and provide valuable information for potential targeted intervention in patients whose tumors harbor cisplatin-resistant molecular characteristics.
Citation Format: Wani Arjumand, Nicholas Jette, Jb McIntyre, Prafull Ghatage, Corinne M. Doll, Susan P. Lees-Miller. Identification of genes associated with the cisplatin resistance in cervical cancer cells expressing E545K mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3149. doi:10.1158/1538-7445.AM2017-3149</jats:p
Etiology, Clinical Features, and Diagnosis of Vulvar Lichen Sclerosus: A Scoping Review
No full textObjective. Vulvar lichen sclerosus (VLS) is a chronic inflammatory disorder, which affects women of all ages. With numerous controversies as regards to the nomenclature, diagnosis and its association with neoplastic conditions, we decided to conduct a scoping review on this subject. Data Source. A review protocol was developed, and the Knowledge Resource Services website was used to do a search of articles pertaining to VLS with keywords “Vulvar,” “Vulval,” “diagnosis,” “lichen sclerosus et atrophicus,” “kraurosis,” “vulvar dystrophy,” and “Lichen Sclerosus”. Study Selection. The search was limited to published data from the last ten years, i.e., from July 2009 onwards and in the English language. A total of 338 articles pertaining to VLS were obtained. Older data were accessed if particular information was sought for. Results & Conclusion. The presentation is bimodal, i.e., one in prepubertal girls (average age: 7.6 years) and the other in peri- and postmenopausal women (average age: 52.6 years). However, many cases also present during reproductive years. Studies suggest a multifactorial origin as far as etiology is concerned, including a genetic, autoimmune, hormonal, and local infectious background. It affects the genital labial, perineal, and perianal areas and manifests as a patchy, thin, glistening, ivory-white area. Diagnosis is mainly based on clinical features. Biopsy is seldom required. It has been well established as a precursor lesion of dVIN and vulvar carcinoma
Mucinous Cancer of the Ovary: Overview and Current Status
No full textMucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease
Low-Grade Serous Carcinoma – The Clinical Challenge
No full textLow-grade serous carcinoma is one of the five major histological types of ovarian carcinoma associated with a specific biology. We reviewed three cases from our institution to demonstrate the variable clinical course and provide a brief review on this disease entity
Low-Grade Serous Carcinoma of the Ovary: The Current Status
No full textLow-grade serous carcinoma (LGSC) of the ovary is a rare histological subtype of epithelial ovarian carcinoma. It has distinct clinical behavior and a specific molecular profile. Compared with high-grade serous carcinoma, this tumor presents at a younger age, has an indolent course, and is associated with prolonged survival. LGSC can arise de novo or originate following a serous borderline tumor (SBT). Pathological differentiation between LGSC and other ovarian carcinoma histological subtypes is fundamental. Several factors might influence the overall outcome, such as the age at diagnosis, current smoking, elevated body mass index, mutational status, hormonal receptors’ expression, and Ki-67 proliferation index. Surgery is the main treatment option in LGSC, and efforts must be maximized to achieve a microscopic residual in metastatic disease. Despite being relatively chemo-resistant, adjuvant platinum-based chemotherapy remains the standard of care in LGSC. Hormonal maintenance therapy after adjuvant chemotherapy results in improved outcomes. Treatment options for disease recurrence include secondary cytoreductive surgery, chemotherapy, hormonal therapy, targeted therapy, and clinical trials. Advancements in genomic studies and targeted therapies are expected to change the treatment landscape in LGSC
Ten years experience in the management of borderline ovarian tumors at Tom Baker Cancer Centre
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