Insilico investigation of TNFSF10 signaling cascade in ovarian serous cystadenocarcinoma
Published on: 2nd July, 2019
OCLC Number/Unique Identifier: 8259199051
The ovarian serous Cystadenocarcinoma shared large number of deaths in gynecologic carcinoma. It has various numbers of molecular events from initiation to progression and at advance stage, surgery is the end product of such molecular signaling. We assess in this study the whole mechanistic view of TNFSF10 network which has the ideal apoptotic causing identity. We used fresh insilico strategy to uncover the secrets and inter-links from its protein-protein interaction complex. We retrieved the TNFSF10 signaling network from STRING database (www.string-db.org). The network contains 25 nodes and 152 edges with clustering presentation. After retrieval, we performed gene enrichment and characterization analysis of network from WebGestalt toolkit (www.webgestalt.com). Finally, we examined the participation of whole network in ovarian cancer progression from cBioPortal, a cancer genomic data portal (www.cbioportal.org). Our results showed that majority of cases have loss of function of death receptors (DR4 and DR5) that are the main unit of initiation of apoptotic signaling. Most of downstream signaling members showed amplification that regulates cell proliferative pathways including NFkB pathway. TNFSF10 cluster has loss of function and in future it gain attention for further research studies to discover its interactome level view for valuable therapy. FAS cluster has large number of members and majority showed amplification rendering them as co-targets for combinational drug designing.
Immunohistochemical expression of p53 and Fox A1 in epithelial ovarian cancer
Published on: 20th May, 2022
Background: Ovarian cancer (OC) is the fifth cause of cancer mortality in females. There were an estimated 300,000 new cases of OC diagnosed worldwide in 2018, corresponding to 3.4% of all cancer cases among women. The high mortality rate of OC attributed to asymptomatic growth of the tumor leads to its diagnosis at advanced stages. About 85% - 90% of OC are epithelial including serous, endometrioid, clear cell, and mucinous carcinoma. Aim: To study the immunohistochemical (IHC) expression of FOXA1 and p53 in epithelial OC and its association with prognostic indicators such as age, tumor size, stage, grade, and histological type.Materials and methods: The study included 52 cases with EOC from the pathology department, faculty of medicine, Aswan, and Sohag Universities, in the period from January 2017 to December 2019. This study involved 52 patients with OC and a median age of 53 years. Different histological types were included as 37 serous, 12 mucinous, 1 case endometroid 2 cases clear cell OC. The study cases were classified into 22 Grade I, 16 Grade II, and 20 Grade III. About 22 cases were at stage I, 9 at stage II, 11 at stage III, and 10 at stage IV. Tissue sections were stained using the IHC technique with FOX A1 at a dilution of 1:100 and p53 at 1:100. Results: A statistically significant correlation was found between FOX A1 expression and advanced patient's age, high grade, advanced stage, ruptured capsule, and ascites, regardless of tumor laterality. No significant association was found between p53 immunoexpression and the same clinic-pathological parameters although p53 was associated with serious type. Conclusion: FOXA1 immunoexpression in EOC is considered a poor prognostic factor in EOC. FOXA1 could be a potential therapeutic target and prognostic marker in EOC.
Cost-analysis comparison of clinical risk assessment with and without ROMA for the management of women with pelvic masses
Published on: 17th August, 2022
Objective: Pelvic masses can be classified as low risk (likely benign) and high risk (likely malignant) based on an initial clinical risk assessment, which involves a detailed history, physical exam, basic laboratory tests, and imaging. In recent years, the Risk of Ovarian Malignancy Algorithm (ROMA), which combines CA125, HE4 and menopausal status, has emerged as a powerful tool in the classification of pelvic masses and triage of patients to either a generalist gynecologist or a gynecologic oncologist for management. The objective of this study was to evaluate whether the use of ROMA, alone or in combination with Initial Clinical Risk Assessment (ICRA), provides cost savings compared to triage based on ICRA alone.Methods: A health-economic decision model was developed to assess clinical and cost differences associated with three different clinical pathways of risk assessment for a pelvic mass: ICRA alone, ROMA alone, or ICRA + ROMA in combination. Using previously reported accuracy rates and patient characteristics from a prospective, multicenter, blinded clinical trial, total healthcare costs were modeled for each clinical pathway using the Medicare 2020 reimbursement rates.Results: A total of 461 patients with pelvic masses were included with 10.4% ultimately diagnosed with epithelial ovarian cancer. Total healthcare costs for patients with benign disease, EOC, or low malignant potential tumors (LMP) (n = 441) triaged using ROMA alone were 3.3% lower than when triaged using ICRA alone. While lab costs increased 55% using ROMA, the use of ROMA alone resulted in a 4% decrease in laparoscopy costs and a 3.1% decrease in laparotomy costs compared with ICRA alone. Similarly, total costs associated with a combination of ICRA + ROMA were 3.9% lower than total costs associated with ICRA alone. The model also predicted a 63% reduction in repeat surgeries resulting from false negative ICRA when using ROMA to triage patients.Conclusion: Triage of women with pelvic masses using the more sensitive ROMA score lowers overall healthcare costs compared to ICRA alone. With fewer false negative results than ICRA alone, the ROMA score improves initial detection of malignancy and reduces second surgical treatments in women with pelvic masses.
New insights of liquid biopsy in ovarian cancer
Published on: 29th September, 2022
Through the development of new analysis technologies, many issues regarding the approach to tumoral diseases have been elucidated. With analytical assays developed in the last years, various omics technologies have evolved in such a manner that the characteristics of tumor cells and products can be evaluated (assessed) in the bloodstream of cancer patients at different times. Ovarian Cancer (OC) is one of the most difficult to diagnose umors, with low survival rates due to the high heterogeneity of these diseases that are distinct in terms of etiology and molecular characteristics, but which simply share an anatomical appearance. Recent findings have indicated that several types of ovarian cancer classified into different histotypes are in fact derived from non-ovarian issues and share few molecular similarities. Within this context, ovarian cancer screening and diagnosis can be made through the evaluation of circulating tumor cells in peripheral blood using liquid biopsy technologies. Advances in the study of various molecules analyzed by liquid biopsy have shown that elucidation of intratumoural and intertumoural heterogeneity and spatial and temporal tumor evolution could be traced by serial blood tests rather than by histopathological analyses of tissue samples from a primary tumor. Therefore, evaluation of some molecules such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA), circulating cell-free RNA (non-coding and mRNA, extracellular vesicles), tumor-educated platelets or different miRNAs using liquid biopsy could lead to improvement of patient management.
Meigs syndrome: About an uncommon case report
Published on: 6th January, 2023
Background: Ovarian fibroma is a very unusual epithelial tumor representing less than 1% of all ovarian tumors. It can be asymptomatic and discovered during surgery or be associated with a pleural effusion preferentially located on the right side and a more or less abundant free ascites in the framework of the so-called Meigs syndrome. The challenge of management then lies in distinguishing benign from malignant since clinically, radiologically, and biologically everything points towards malignant which requires radical surgical treatment. We report here the case of a 69-year-old postmenopausal patient with a clinical form of Meigs' syndrome that strongly suggested ovarian cancer.Case presentation: We hereby report here the case of a 69-year-old patient, menopausal, gravida 4 para 3 with 3 live children delivered vaginally and one miscarriage. She presented with ascites, hydrothorax, and a solid tumor of the ovary. Serum CA 125 and HE 4 levels were very high. ROMA score was highly suggestive of malignancy. A hysterectomy with adnexectomy was performed. It was only the histological evidence of ovarian fibroma and the rapid resolution of its effusions that confirmed Meigs syndrome.Conclusion: Meigs syndrome is an anatomical-clinical entity that associates a benign tumor of the ovary, ascites, and hydrothorax. Highly elevated CA 125 and HE-4 tumor markers often point clinicians toward a malignant tumor and compel radical surgical treatment. This case report reminds us once again that only histology confirms the diagnosis of cancer.
Effects of Pleiotrophin (PTN) on the resistance to paclitaxel in ovarian cancer cells
Published on: 23rd February, 2023
The pathogenesis of an ovarian disease is connected with PTN and its receptor protein tyrosine phosphatase receptor Z1 (PTPRZ1). Paclitaxel is the first-line drug for the therapy of ovarian cancer. With the increment of paclitaxel chemotherapy, paclitaxel obstruction happens in the late phase of therapy frequently. By treating A2780 and SKOV-3 cells with PTN, we found the development of the two cell lines was enhanced. Different concentrations of PTN were added to A2780 and SKOV-3 cells treated with paclitaxel and the results of MTT showed that the inhibitory effect of paclitaxel on these two cell lines was weakened. The results of apoptosis assays showed that PTN could slow down the rate of apoptosis and its concentration dependence in both cell lines. To further investigate the impact of PTN on the paclitaxel responsiveness of ovarian malignant growth cells, A2780 and SKOV-3 cells were transfected with sh-PTN-1, sh-PTN-2 and sh-NC plasmids. The results of PCR and Western Blot showed that both RNA-interfering plasmids could inhibit PTN in A2780 and SKOV-3 cells. The results of MTT showed that the inhibitory effect of paclitaxel on cells transfected with sh-PTN-1 expanded compared with the benchmark group. Apoptosis assays showed that the complete apoptosis pace of A2780 and SKOV-3 cells with sh-PTN-1 plasmid induced by paclitaxel was accelerated obviously compared with the benchmark group. To summarize, the results suggested that PTN could enhance the resistance to paclitaxel in ovarian cancer cells, which provides a groundwork for studying on drug resistance of cancer cells to paclitaxel and a new perspective for ovarian cancer therapy.
Minimally invasive cytoreductive surgery in advanced ovarian cancer: A nonselected consecutive series of robotic-assisted cases
Published on: 28th April, 2023
The gold standard for advanced-stage ovarian cancer surgery entails exploration via a midline vertical laparotomy. Studies have shown that minimally invasive surgery (MIS) can be a safe and effective method for the surgical management of early ovarian cancer. In some cases, MIS can also be selectively used for cytoreductive surgery in cases with advanced-stage ovarian cancer. The robotic platform has the potential to provide similar outcomes to the laparotomy-based standard of care in advanced complex surgery while accelerating recovery, minimizing morbidity, and reducing perioperative complications. The primary objective of this study was to evaluate surgical and perioperative outcomes in patients with advanced ovarian carcinoma who underwent robotic-assisted cytoreduction. A chart review of a nonselected consecutive series of all patients undergoing surgical management of advanced ovarian cancer between 7/1/2017 and 12/31/2021 was conducted. All patients that were diagnosed with Stage III to IV ovarian cancer between the timeframe underwent robotic-assisted cytoreductive surgery at two urban community teaching hospitals in Los Angeles. Twenty-five patients were identified and included in this study. All surgeries were performed by a single surgeon. Optimal or complete CRS was achieved in 96% of the patients (24 of 25 cases). Seven (28%) underwent primary cytoreduction (PCRS) and 18 (72%) underwent interval cytoreduction (ICRS). The estimated median blood loss was 100 mL (25-500 mL), the median operative time was 5.9 hours (3.1-10.5 hours), and the conversion rate to open laparotomy was 0%. There were no intraoperative complications and the readmission rate within 30 days was 4% (1 patient) for ileus, which was managed conservatively. Currently, 64% of the patients in the case series remain alive. The median survival has not been reached. The median follow-up is 4.08 years. Results presented from this nonselected, consecutive case series illustrate how a minimally invasive robotic approach can be safely used in place of the standard exploratory laparotomy for ovarian cytoreduction.
A Perplexing Case of Genito-urinary Tuberculosis in an 83-Year-Old Woman with Increased Levels of Tumor Markers: A Case Report
Published on: 5th December, 2023
Background: Tuberculosis (TB) is a significant global health problem, and extrapulmonary TB can present with no specific clinical or radiographic findings. Genito-urinary TB is often associated with elevated tumor markers and can be misdiagnosed as ovarian/fallopian tube carcinomas, especially in elderly female patients, as genitourinary TB commonly affects women of reproductive age.Objective: We present a rare case of genito-urinary TB in an elderly female patient who was initially misdiagnosed with ovarian cancer with metastasis.Case presentation: An 83-year-old woman with a medical history of diabetes and hypertension presented with complaints of abdominal distension. Diagnostic imaging revealed lesions in the ovaries and omentum and tumor markers were elevated, leading to a suspicion of ovarian cancer with metastases to the omentum. The patient underwent a diagnostic laparotomy and surgical removal of ovaries, fallopian tubes, and the lesion of the greater omentum. However, no malignancy was found during the morphological evaluation. Further histopathological examination confirmed the final diagnosis of genito-urinary tuberculosis, and the patient received anti-TB drugs. The postoperative period was uneventful, and tumor marker levels decreased.Conclusion: As the clinical presentation of genito-urinary TB can mimic ovarian cancer, a histopathological examination should be performed for differential diagnosis, thereby reducing the possibility of inaccurate treatment. This case report highlights the importance of considering genito-urinary TB as a differential diagnosis in elderly female patients presenting with elevated tumor markers, abdominal distension, and suspected genital malignancy. It is crucial to carefully evaluate these cases and explore the possibility of genital TB as an alternative diagnosis, given the overlapping clinical presentation. This highlights the importance of a comprehensive diagnostic approach that includes considering TB in addition to malignancy, even in the context of elderly female patients.
Germline BRCA1 Mutation inSquamous Cell Carcinoma of Oesophagus: Driver versus Passenger Mutation
Published on: 2nd July, 2024
We report a rare case of 62-year-old South Asian women who visited the Molecular Pathology and Genomics Department for hereditary germline cancer genetic testing after being diagnosed with oesophageal cancer, reported as invasive keratinizing squamous cell carcinoma metastasized to the lymph nodes. Her personal history revealed that she was diagnosed with triple-negative breast cancer five years before oesophageal cancer. Germline cancer testing showed pathogenic variants in BRCA1 gene c.68_69delAG, which proved it a hereditary breast and ovarian cancer syndrome. She was started on PARP inhibitors but developed some secondary respiratory failure and succumbed to death. Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.
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