scholarly journals Molecular Alterations in Metastatic Ovarian Cancer From Gastrointestinal Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Chao Chen ◽  
Xiaoxu Ge ◽  
Yamei Zhao ◽  
Da Wang ◽  
Limian Ling ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gastrointestinal Cancer ◽  
Abdominal Cavity ◽  
Circulatory System ◽  
Hematogenous Spread ◽  
Molecular Alteration ◽  
Molecular Alterations ◽  
Metastatic Pathway ◽  
Metastatic Process ◽  
Distant Metastatic Site

Reports indicate that most metastatic ovarian cancer (MOC) originates from gastrointestinal cancer (GIC). Notably, GICs metastasize to the ovary frequently via 3 main routes including hematogenous spread, lymphogenous spread, and transcoelomic spread. Nonetheless, the mechanism of the progression remains unknown, and only a handful of literature exists on the molecular alteration implicated in MOC from GIC. This work collected existing evidence and literature on the vital molecules of the metastatic pathway and systematically analyzed them geared toward exploring the mechanism of the metastatic pathway of MOC. Further, this review described dominating molecular alteration in the metastatic process from cancer cells detaching away from lesions to arrive at the ovary, including factors for regulating signaling pathways in epithelial-interstitial transformation, invading, and surviving in the circulatory system or abdominal cavity. We interrogated the basis of the ovary as a distant metastatic site. This article provides new insights into the metastatic pathway and generates novel therapeutic targets for effective treatment and satisfactory outcomes in GIC patients.

Targeting Tumour Metastasis: The Emerging Role of Nanotechnology

2020 ◽  
Vol 27 (8) ◽  
pp. 1367-1381 ◽  
Author(s):  
Sarah Visentin ◽  
Mirela Sedić ◽  
Sandra Kraljević Pavelić ◽  
Krešimir Pavelić
Keyword(s):  
Cancer Progression ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Metastatic Progression ◽  
Therapeutic Concept ◽  
Molecular Alterations ◽  
Tumour Metastasis ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Underlying Mechanisms

The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.

scholarly journals Coincidence of Intra-Abdominal Splenosis in a Patient with Advanced Ovarian Cancer: Case Report and Review of the Literature

2021 ◽  
Vol 07 (02) ◽  
pp. e116-e120
Author(s):  
Tatjana Braun ◽  
Amelie De Gregorio ◽  
Lisa Baumann ◽  
Jochen Steinacker ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Case Report ◽  
Diagnostic Imaging ◽  
Medical History ◽  
Rare Disease ◽  
Metastatic Cancer ◽  
Abdominal Cavity ◽  
Advanced Ovarian Cancer ◽  
Splenic Tissue ◽  
Tumor Spread

AbstractSplenosis is a rare disease, which is often discovered incidentally years after surgical procedures on the spleen or traumatic splenic lesions. Through injury of the splenic capsule, splenic cells are able to spread and autoimplant in a fashion similar to the process of metastatic cancer. Here we present the case of a 62-year-old female patient with a palpable tumor of the lower abdomen. Her medical history was unremarkable, except for splenectomy after traumatic splenic lesion in her childhood. Clinical examination and diagnostic imaging raised the suspicion of advanced ovarian cancer, which was further substantiated by the typical presentation of adnexal masses and disseminated peritoneal metastases during the following staging laparotomy. Surprisingly, we also found peritoneal implants macroscopically similar to splenic tissue. Microscopic examination of tissue specimens by intrasurgical frozen section confirmed the diagnosis of intra-abdominal splenosis. The patient then underwent cytoreductive surgery with complete resection of all cancer manifestations, sparing the remaining foci of splenosis to avoid further morbidity. This case demonstrates the rare coincidence of intra-abdominal carcinoma and splenosis, which could lead to intraoperative difficulties by misinterpreting benign splenic tissue. Therefore, splenosis should be considered in patients with medical history of splenic lesions and further diagnostic imaging like Tc-99m-tagged heat-damaged RBC scan could be used for presurgical distinguishing between tumor spread in the abdominal cavity and disseminated splenosis. The presented case report should not only raise awareness for the rare disease splenosis, but also emphasize the need to consider the possibility of simultaneous incidence of benign and malignant intra-abdominal lesions, as to our knowledge this is the first published case of simultaneous peritoneal carcinomatosis and splenosis.

Stem-like tumor cells and proinflammatory cytokines in the ascitic fluid of ovarian cancer patients

2021 ◽  
Vol 66 (5) ◽  
pp. 297-303
Author(s):  
S. O. Gening ◽  
T. V. Abakumova ◽  
I. I. Antoneeva ◽  
A. A. Rizvanov ◽  
T. P. Gening ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Blood Serum ◽  
Tumor Cells ◽  
Ascitic Fluid ◽  
Early Stage ◽  
Abdominal Cavity ◽  
Disease Stage ◽  
Cell Populations ◽  
Benign Ovarian Tumors ◽  
Number Of Cells

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

scholarly journals A Dynamic Culture Method to Produce Ovarian Cancer Spheroids under Physiologically-Relevant Shear Stress

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 277 ◽  
Author(s):  
Timothy Masiello ◽  
Atul Dhall ◽  
L. Hemachandra ◽  
Natalya Tokranova ◽  
J. Melendez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Abdominal Cavity ◽  
Culture Method ◽  
Experimental Conditions ◽  
Dynamic Cell ◽  
Screening Platform ◽  
Cancer Spheroids

The transcoelomic metastasis pathway is an alternative to traditional lymphatic/hematogenic metastasis. It is most frequently observed in ovarian cancer, though it has been documented in colon and gastric cancers as well. In transcoelomic metastasis, primary tumor cells are released into the abdominal cavity and form cell aggregates known as spheroids. These spheroids travel through the peritoneal fluid and implant at secondary sites, leading to the formation of new tumor lesions in the peritoneal lining and the organs in the cavity. Models of this process that incorporate the fluid shear stress (FSS) experienced by these spheroids are few, and most have not been fully characterized. Proposed herein is the adaption of a known dynamic cell culture system, the orbital shaker, to create an environment with physiologically-relevant FSS for spheroid formation. Experimental conditions (rotation speed, well size and cell density) were optimized to achieve physiologically-relevant FSS while facilitating the formation of spheroids that are also of a physiologically-relevant size. The FSS improves the roundness and size consistency of spheroids versus equivalent static methods and are even comparable to established high-throughput arrays, while maintaining nearly equivalent viability. This effect was seen in both highly metastatic and modestly metastatic cell lines. The spheroids generated using this technique were fully amenable to functional assays and will allow for better characterization of FSS’s effects on metastatic behavior and serve as a drug screening platform. This model can also be built upon in the future by adding more aspects of the peritoneal microenvironment, further enhancing its in vivo relevance.

Emerging molecular alterations leading to histology-specific targeted therapies in ovarian cancer beyond PARP inhibitors

2021 ◽  
Vol 101 ◽  
pp. 102298
Author(s):  
M. Bartoletti ◽  
L. Musacchio ◽  
G. Giannone ◽  
V. Tuninetti ◽  
A. Bergamini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Targeted Therapies ◽  
Parp Inhibitors ◽  
Molecular Alterations

scholarly journals Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1554
Author(s):  
Enrica Calura ◽  
Matteo Ciciani ◽  
Andrea Sambugaro ◽  
Lara Paracchini ◽  
Giuseppe Benvenuto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Stage I ◽  
Molecular Heterogeneity ◽  
Low Grade ◽  
Multicentric Study ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Signaling Axis ◽  
Tumor Biopsies

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

scholarly journals Algorithms Used in Ovarian Cancer Detection: A Minireview on Current and Future Applications

2018 ◽  
Vol 3 (2) ◽  
pp. 290-299
Author(s):  
Vishaal Gupta ◽  
Marcus Q Bernardini
Keyword(s):  
Ovarian Cancer ◽  
Survival Rates ◽  
Ca 125 ◽  
Cellular Origin ◽  
Molecular Alterations ◽  
Screening Algorithm ◽  
The Us ◽  
Risk Of Malignancy ◽  
Future Potential ◽  
Single Disease Entity

Abstract Background Ovarian cancer is the 5th most common cause of cancer death among women in the US. Currently, there is no screening algorithm for asymptomatic women that has been shown to lower mortality rates. Screening is currently not recommended and has been shown to increase harm. Epithelial ovarian cancer (EOC) detection is reviewed, with a focus on high-grade serous, clear-cell, and endometrioid histotypes. Content A review of current literature surrounding tools used in detection of ovarian cancer will be presented. CA 125, HE4, risk of ovarian cancer algorithm (ROCA), risk of malignancy algorithm (ROMA), risk of malignancy (RMI), OVA1, and future potential biomarkers are reviewed. Summary Screening and early identification of EOC is currently managed as a single disease entity. However, recent evidence has shown ovarian cancer varies with relation to cellular origin, pathogenesis, molecular alterations, and prognosis, depending on histotype. There is a clear need for future studies identifying histotype-specific preclinical tumor markers to aid in detection and improvement of survival rates.

scholarly journals OncoKB: A Precision Oncology Knowledge Base

2017 ◽  
pp. 1-16 ◽  
Author(s):  
Debyani Chakravarty ◽  
Jianjiong Gao ◽  
Sarah Phillips ◽  
Ritika Kundra ◽  
Hongxin Zhang ◽  
...  
Keyword(s):  
Knowledge Base ◽  
Cancer Genomics ◽  
Precision Oncology ◽  
Level Of Evidence ◽  
Molecular Alteration ◽  
Support Tool ◽  
Molecular Alterations ◽  
Web Resource ◽  
Clinical Support ◽  
Cancer Network

Purpose With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, an urgent need exists for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base. Methods OncoKB annotates the biologic and oncogenic effects and prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response on the basis of US Food and Drug Administration labeling, National Comprehensive Cancer Network guidelines, disease-focused expert group recommendations, and scientific literature. Results To date, > 3,000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5,983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public Web resource ( http://oncokb.org ) and are incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers. Conclusion OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.

scholarly journals Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

BMJ ◽  
2019 ◽  
pp. l1580 ◽  
Author(s):  
Yan Xie ◽  
Benjamin Bowe ◽  
Yan Yan ◽  
Hong Xian ◽  
Tingting Li ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gastrointestinal Cancer ◽  
Circulatory System ◽  
Upper Gastrointestinal Cancer ◽  
Circulatory System Diseases ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Upper Gastrointestinal

AbstractObjectiveTo estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).DesignLongitudinal observational cohort study.SettingUS Department of Veterans Affairs.ParticipantsNew users of PPIs (n=157 625) or H2 blockers (n=56 842).Main outcome measuresAll cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).ResultsThere were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).ConclusionsTaking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

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