scholarly journals Therapeutic Targeting of Collective Invasion in Ovarian Cancer

2019 ◽  
Vol 20 (6) ◽  
pp. 1466 ◽  
Author(s):  
Laura Moffitt ◽  
Nazanin Karimnia ◽  
Andrew Stephens ◽  
Maree Bilandzic
Keyword(s):  
Ovarian Cancer ◽  
Primary Tumour ◽  
Survival Rates ◽  
Cell Types ◽  
Target Tissue ◽  
Multicellular Spheroids ◽  
Epithelial Cancers ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy ◽  
Collective Invasion

Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed “leader cells”. Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.

scholarly journals Emerging Role of Inhibin as a Biomarker for Ovarian Cancer

2005 ◽  
Vol 1 (1) ◽  
pp. 51-57 ◽  
Author(s):  
David M Robertson ◽  
Martin K Oehler
Keyword(s):  
Ovarian Cancer ◽  
Granulosa Cell ◽  
Early Stage ◽  
Clinical Stage ◽  
Survival Rates ◽  
Ovarian Carcinomas ◽  
Gynecological Malignancy ◽  
Granulosa Cell Tumors ◽  
Ovarian Cancers ◽  
Specificity And Sensitivity

Ovarian cancer is the most lethal gynecological malignancy as it is diagnosed at a late clinical stage in more than 80% of patients. The development of diagnostic tests that can detect all types of ovarian cancers with high specificity and sensitivity, and at an early stage would improve survival rates. Serum inhibin is an ovarian hormone involved in the regulation of fertility, decreasing to undetectable levels after menopause. Certain ovarian malignancies, such as mucinous carcinomas and granulosa cell tumors, continue to produce inhibin, which is detectable in serum. A test for serum inhibin has been developed which is able to diagnose granulosa cell tumors and mucinous carcinomas with high accuracy. When the inhibin assay is used in conjunction with the CA125 test, which detects epithelial ovarian carcinomas, the two tests detect the majority of ovarian cancers with high sensitivity (95%) and specificity (95%). This article discusses the application of the inhibin test in ovarian cancer.

Ki67 as a prognostic factor in low grade serous ovarian cancer (LGSOC): A retrospective analysis of the Tumor Bank Ovarian Cancer (TOC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5562-5562 ◽  
Author(s):  
Jalid Sehouli ◽  
Helmut Plett ◽  
Rolf Richter ◽  
Carsten Denkert ◽  
Silvia Darb-Esfahani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcome ◽  
Hot Spot ◽  
Survival Rates ◽  
Histological Evaluation ◽  
Low Grade ◽  
Ki 67 ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
The Impact

5562 Background: LGSOC is a rare and distinct entity characterized by younger age, lower response to chemotherapy and better clinical outcome. Aim of this study was to evaluate the impact of Ki67, estrogen and progesterone receptors (ER and PR) on platinum response and survival in primary LGSOC patients. Methods: 80 primary LGSOC patients with available FFPEs were identified within TOC. The histology was confirmed at a second histological evaluation. For Ki67 analysis conventional immunohistochemical staining was performed with the Mib-1 clone on Ventana. Slides were explored with a light microscope camera. A representative field for Ki-67 evaluation was selected, in case of heterogeneous staining a hot spot was chosen. The software classified detected cells into non-tumor, negative and positive cells. When necessary, a correction of tumor and non-tumor areas was performed by an experienced pathologist. The counted cells ranged between 175 and 2398. Overall the method allows a precise, continuous and standardized means to quantify Ki-67. ER and PR status was determined on scanned IHC TMA slides. ER and PR positive tumors were defined if the percentage of stained tumor cells was at least 10%. Statistical analysis was performed using IBM SPSS Statistics. Results: Median age at diagnosis was 56 years (range: 20-81), 81.3% of patients presented in advanced stage and 96.3% received platinum based chemotherapy. Ki67 median value was 5.09 (IQR: 1.56-10.5). 93.1% and 47.9% of the patients showed ER and PR positive tumors, respectively. Median overall survival (OS) was 45.5 months (range: 0.1-182.8). Our analysis showed that platinum free interval (PFI) was significant longer in patients with lower Ki67 (p = 0.006). Higher proliferation rates were significant associated with poorer progression free (p = 0.011, HR = 1.039, 95%CI: 1.009-1.070) and OS rates (p = 0.001, HR = 1.059, 95%CI: 1.025-1.095). No differences in clinical outcome were seen in patients with different ER and PR status. Conclusions: This is the first study showing that higher Ki67 values correlate with shorter PFI and poorer survival rates in LGSOC, underlying the heterogeneous character of this disease.

Weekly carboplatin and paclitaxel is safe, active, and well tolerated in recurrent ovarian cancer cases of Japanese women previously treated with cisplatin-containing multidrug chemotherapy

2005 ◽  
Vol 15 (1) ◽  
pp. 45-49 ◽  
Author(s):  
A. Kikuchi ◽  
H. Sakamoto ◽  
T. Yamamoto
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Index ◽  
Complete Response ◽  
Japanese Patients ◽  
Japanese Women ◽  
Toxicity Profile ◽  
Term Survival ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy ◽  
Multidrug Chemotherapy

The safety and efficacy of weekly carboplatin and paclitaxel administration in recurrent ovarian cancers after platinum-containing multidrug chemotherapy were tested. Japanese patients who achieved complete response with surgery and adjuvant platinum-based chemotherapy and who had a recurrence after at least 6 months were included in the case – control study. Twenty-seven cases received the weekly TJ (WTJ) regime (cohort 1: T = 80 mg/m2, J = AUC 2, median course = 13, range = 3–26) and 41 received other regimens [cohort 2: CAP = 37, monthly TJ (MTJ) = 4]. Toxicity profile, response rate, therapeutic index (TI), and survival were analyzed. Neutropenia, thrombocytopenia, and peripheral neuropathy (grades 3 and 4) in cohorts 1 and 2 were 1.7% and 90%, 5.1% and 14.3%, and 0% and 4.8%, respectively. Response rates were 77.8% and. Thus, TI of the two cohorts was 3.9 and 1.9, respectively. The median survival of cohort 1 was 48.3 months (95% CI 11.5–85.0) whereas that of cohort 2 was 17.8 months (95% CI 5.3–30.3, P < 0.005). WTJ has better toxicity profile and TI than monthly platinum-based multidrug regimens for recurrent ovarian cancers in Japanese women. As second-line treatment of ovarian cancer should primarily provide high TI, WTJ regimen appears a better candidate, but its long-term survival benefit should be tested against MTJ.

Functional profiling of clear cell ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5035-5035
Author(s):  
Rowan Miller ◽  
Rachel Brough ◽  
Ilirjana Bajrami ◽  
Stanley B. Kaye ◽  
Christopher J. Lord ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Screening ◽  
Clear Cell ◽  
Integral Functional ◽  
Therapeutic Targets ◽  
Molecular Profiling ◽  
Loss Of Function ◽  
Ovarian Carcinomas ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy

5035 Background: Clear cell ovarian cancer represents up to 15% of epithelial ovarian cancers. In comparison to other subtypes, clear cell ovarian carcinomas have a poorer prognosis and are relatively resistant to standard platinum based chemotherapy. Recently, loss of function mutations in the tumour suppressor gene ARID1A were identified in up to 50% of ovarian clear cell carcinomas. We have adopted an integral functional and molecular profiling approach as a route to identify new genetic dependencies and therapeutic targets for this disease. Methods: Clear cell ovarian cancer cell lines were functionally profiled using high throughput screening with chemical and siRNA libraries. This has been integrated with molecular profiling data generated from exome and transcriptome sequencing to aid the discovery of novel targets. Results: Using functional screens we have now identified critical gene dependencies and potential therapeutics in a series of clear cell ovarian cancer models. The comparison of functional viability profiles for models characterized by ARID1A loss of function mutations is now enabling an analysis of synthetic lethal effects that could be used to target clear cell ovarian cancers carrying these mutations. Conclusions: The work undertaken so far provides the framework for the discovery of therapeutic targets for clear cell ovarian cancer using an integrated approach. Revalidation of these preliminary results is now underway to characterize new genetic dependencies for this disease.

Phase III Trial of Observation Versus Six Courses of Paclitaxel in Patients With Advanced Epithelial Ovarian Cancer in Complete Response After Six Courses of Paclitaxel/Platinum-Based Chemotherapy: Final Results of the After-6 Protocol 1

2009 ◽  
Vol 27 (28) ◽  
pp. 4642-4648 ◽  
Author(s):  
Sergio Pecorelli ◽  
Giuseppe Favalli ◽  
Angiolo Gadducci ◽  
Dionyssios Katsaros ◽  
Pierluigi Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
Free Survival ◽  
Consolidation Treatment ◽  
Platinum Based Chemotherapy ◽  
Advanced Epithelial Ovarian Cancer

Purpose To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum–based chemotherapy. Patients and Methods Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum–based chemotherapy were randomly allocated to either observation (ie, control) or six courses of paclitaxel 175 mg/m2 every 3 weeks (ie, maintenance). Results Two hundred patients were randomly assigned from March 1999 to July 2006. Because of the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3% and 28.0% of the paclitaxel-arm patients, respectively. After a median follow-up of 43.5 months, 107 patients (53%) had experienced relapse, and 48 patients (24%) had died. Two-year progression-free survival rates were 54% (95% CI, 43% to 64%) and 59% (95% CI, 49% to 69%; P = not significant) in the control and maintenance arms, respectively. Corresponding 2-year overall survival rates were 90% (95% CI, 84% to 97%) and 87% (95% CI, 80% to 94%; P = not significant), respectively. The Cox model showed that residual disease after initial surgery (macroscopic v no macroscopic residuum; hazard ratio [HR], 1.91; 95%CI, 1.21 to 3.03) and stage (IIIc to IV v others; HR, 3.10; 95% CI, 1.13 to 8.48) were independent prognostic factors for progression-free survival, whereas the treatment arm (maintenance v control) had no prognostic relevance. Conclusion A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum–based regimens.

scholarly journals The Role of Cancer Stem Cells and Mechanical Forces in Ovarian Cancer Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1008 ◽  
Author(s):  
Bregenzer ◽  
Horst ◽  
Mehta ◽  
Novak ◽  
Repetto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Ovarian Tumor ◽  
Cancer Metastasis ◽  
Survival Rates ◽  
Careful Consideration ◽  
Mechanical Stimuli ◽  
Ovarian Cancers

Ovarian cancer is an extremely lethal gynecologic disease; with the high-grade serous subtype predominantly associated with poor survival rates. Lack of early diagnostic biomarkers and prevalence of post-treatment recurrence, present substantial challenges in treating ovarian cancers. These cancers are also characterized by a high degree of heterogeneity and protracted metastasis, further complicating treatment. Within the ovarian tumor microenvironment, cancer stem-like cells and mechanical stimuli are two underappreciated key elements that play a crucial role in facilitating these outcomes. In this review article, we highlight their roles in modulating ovarian cancer metastasis. Specifically, we outline the clinical relevance of cancer stem-like cells, and challenges associated with their identification and characterization and summarize the ways in which they modulate ovarian cancer metastasis. Further, we review the mechanical cues in the ovarian tumor microenvironment, including, tension, shear, compression and matrix stiffness, that influence (cancer stem-like cells and) metastasis in ovarian cancers. Lastly, we outline the challenges associated with probing these important modulators of ovarian cancer metastasis and provide suggestions for incorporating these cues in basic biology and translational research focused on metastasis. We conclude that future studies on ovarian cancer metastasis will benefit from the careful consideration of mechanical stimuli and cancer stem cells, ultimately allowing for the development of more effective therapies.

scholarly journals Somatic Mutations in BRCA1 and BRCA2 Could Expand the Number of Patients That Benefit From Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer

2010 ◽  
Vol 28 (22) ◽  
pp. 3570-3576 ◽  
Author(s):  
Bryan T.J. Hennessy ◽  
Kirsten M. Timms ◽  
Mark S. Carey ◽  
Alexander Gutin ◽  
Larissa A. Meyer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Positive Association ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Parp1 Inhibitors ◽  
Expression Loss

Purpose The prevalence of BRCA½ mutations in germline DNA from unselected ovarian cancer patients is 11% to 15.3%. It is important to determine the frequency of somatic BRCA½ changes, given the sensitivity of BRCA-mutated cancers to poly (ADP ribose) polymerase-1 (PARP1) inhibitors and platinum analogs. Patients and Methods In 235 unselected ovarian cancers, BRCA½ was sequenced in 235, assessed by copy number analysis in 95, and tiling arrays in 65. 113 tumors were sequenced for TP53. BRCA½ transcript levels were assessed by quantitative polymerase chain reaction in 220. When available for tumors with BRCA½ mutations, germline DNA was sequenced. Results Forty-four mutations (19%) in BRCA1 (n = 31)/BRCA2 (n = 13) were detected, including one homozygous BRCA1 intragenic deletion. BRCA½ mutations were particularly common (23%) in high-grade serous cancers. In 28 patients with available germline DNA, nine (42.9%) of 21 and two (28.6%) of seven BRCA1 and BRCA2 mutations were demonstrated to be somatic, respectively. Five mutations not previously identified in germline DNA were more commonly somatic than germline (four of 11 v one of 17; P = .062). There was a positive association between BRCA1 and TP53 mutations (P = .012). BRCA½ mutations were associated with improved progression-free survival (PFS) after platinum-based chemotherapy in univariate (P = .032; hazard ratio [HR] = 0.65; 95% CI, 0.43 to 0.98) and multivariate (P = .019) analyses. BRCA½ deficiency, defined as BRCA½ mutations or expression loss (in 24 [13.3%] BRCA½–wild-type cancers), was present in 67 ovarian cancers (30%) and was also significantly associated with PFS in univariate (P = .026; HR = 0.67; 95% CI, 0.47 to 0.96) and multivariate (P = .008) analyses. Conclusion BRCA½ somatic and germline mutations and expression loss are sufficiently common in ovarian cancer to warrant assessment for prediction of benefit in clinical trials of PARP1 inhibitors.

scholarly journals Histopathological Pattern and Age Distribution, of Malignant Ovarian Tumor among Sudanese Ladies

2018 ◽  
Vol 6 (2) ◽  
pp. 237-241 ◽  
Author(s):  
Sumeya A. Khieri ◽  
Abdelillah Kunna ◽  
Ali Yousif Babiker ◽  
Sultan A. Alsuhaibani ◽  
Rami Yousif Ahmed ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Age Distribution ◽  
Case Fatality ◽  
Ovarian Tumour ◽  
Induction Treatment ◽  
Epithelial Cancers ◽  
Ovarian Cancers ◽  
Malignant Ovarian Tumor ◽  
Epithelial Tumour ◽  
Age Of Menarche

INTRODUCTION: Ovarian cancer is the cause of a high case-fatality ratio, and most of the cases are diagnosed in late stages.OBJECTIVES: To determine the histopathological types, age distribution, and ovarian tumour stages among diagnosed with ovarian cancer at Al - Amal Tower a multi-referral polyclinic of Radiology & Isotope Center Khartoum (RICK), Sudan.METHODS: All histopathology reports patients' case from January to June 2015 were reviewed. The cancers classified according to federation international of Obstetrics and Gynecology (FIGO).RESULTS: There were 127 cases of ovarian cancers. Surface epithelial cancers were the most common 77.7% ( n = 98), followed by sex cord-stromal cancers 11.23% (n = 14), Germ cell tumor 1.6% (n = 2). Metastatic cancers were seen from colon and breast in 6.3% and 3.9 % of cases respectively. Few cases (14%) of ovarian cancers were reported before 40 years of age, after the age of 50 is a sharp increase in the incidence of a tumour. The mean age at presentation was 52.36 ± 14.210 years, there is mean age of menarche 13.59 ± 2.706 years. Very few patients used HRT (1.6%) or had been on ovulation induction treatment (8.7%). Most of patients 39 (30.7%) presented in stage IIIC, and stage 1V 32 (25.2%) indicating a poor prognosis.CONCLUSION: The incidence of different types of ovarian cancers in the present study is similar to worldwide incidence. The surface epithelial tumour is the commonest ovarian cancer, of which serous adenocarcinoma is the commonest and most of our patients present in late stages.

Ultrastructural Changes in Three Different Mammalian Cells Following Ultraviolet Laser Irradiation

1972 ◽  
Vol 30 ◽  
pp. 350-351
Author(s):  
K. Shankar Narayan ◽  
Kailash C. Gupta ◽  
Tohru Okigaki
Keyword(s):  
Ultraviolet Light ◽  
Mammalian Cells ◽  
Biological Effects ◽  
Survival Rates ◽  
Chinese Hamster ◽  
Cell Types ◽  
Differential Sensitivity ◽  
Ultrastructural Changes ◽  
Ultraviolet Laser

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.

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