- Gastric-type Adenocarcinoma of the Cervix: Tumor With Wide Range of Histologic Appearances. [Journal Article]
- AAAdv Anat Pathol 2018 Sep 18
- Gastric-type endocervical adenocarcinoma (GAS) is a recently described diagnostic entity originally characterized as a tumor with (1) voluminous cytoplasm that is (2) clear or pale eosinophilic, and ...
Gastric-type endocervical adenocarcinoma (GAS) is a recently described diagnostic entity originally characterized as a tumor with (1) voluminous cytoplasm that is (2) clear or pale eosinophilic, and (3) cells showing distinct cell borders. Since the initial tumor description there has been accumulating experience that the neoplasm, in addition to classic features, may show a wide spectrum of morphologic appearances. This paper describes and illustrates cases of GAS with focal or diffuse findings that include: densely eosinophilic cytoplasm, foamy cytoplasm, goblet cells, glands with elongated, stratified nuclei, glands with small cuboidal cells, glands with flattened cells, papillary growth, single cell infiltration and infiltration with microcystic elongated and fragmented pattern. All these patterns may bring up a differential diagnosis with other cervical malignancies such as usual, intestinal, endometrioid, clear cell, serous, and mesonephric adenocarcinoma. The paper describes the patterns of immunostaining of respective lesions that may aid in the diagnostic process and summarizes the main points of the differential diagnosis. GAS is associated with somatic and germline STK11 mutations and TP53 mutations but is invariably negative for human papilloma virus when tumor only is tested. It shows variation in incidence between countries. Awareness of the spectrum of morphologic appearances in GAS is important for accurate and confident diagnosis. Correct identification of GAS is important due to its propensity for ovarian and other distant metastases, markedly worse prognosis as compared with usual endocervical adenocarcinoma, and its relative resistance to chemotherapy.
- Prevalence of Homologous Recombination-Related Gene Mutations Across Multiple Cancer Types. [Journal Article]
- JPJCO Precis Oncol 2018; 2018
- CONCLUSIONS: HR-DDR mutations were seen in 17.4% of tumors across 21 cancer lineages, providing a path to explore the role of HRD-directed therapies, including poly-ADP ribose polymerase inhibitors, DNA-damaging chemotherapies, and newer agents such as ATR inhibitors.
- Breast metastasis from ovarian cancer: A case report. [Journal Article]
- RCRadiol Case Rep 2018; 13(6):1166-1169
- Breast metastasis from ovarian cancer is a rare event, with vary clinical and imaging presentations, depends on the form of dissemination of the disease and may mimic primary benign and malignant les...
Breast metastasis from ovarian cancer is a rare event, with vary clinical and imaging presentations, depends on the form of dissemination of the disease and may mimic primary benign and malignant lesions.Confirmation of the diagnosis is of pivotal importance to choice an adequate therapeutic planning, allowing to avoid unnecessary surgeries and to provide appropriate systemic therapy. In this manuscript, we present a case of breast metastasis from ovarian cancer. The patient presented to our Institute with a localized, palpable mass in the upper outer quadrant of the right breast. Mammography and breast sonography showed a singular, round, and homogenous mass with regular borders. No suspicious axillary node was observed. Lesion biopsy revealed the presence of epithelial malignant tumor cells, compatible with a tube-ovarian serous histotype. So, although it could be rare, secondary malignant neoplasm should be considered in the differential diagnosis of breast lesions in patients with a personal history of ovarian cancer.
- SPARCL1 suppresses the proliferation and migration of human ovarian cancer cells via the MEK/ERK signaling. [Journal Article]
- ETExp Ther Med 2018; 16(4):3195-3201
- Ovarian cancer is the most lethal gynecological malignancy worldwide and is one of the five leading causes of cancer-associated mortality in women. There is an urgent requirement to obtain a greater ...
Ovarian cancer is the most lethal gynecological malignancy worldwide and is one of the five leading causes of cancer-associated mortality in women. There is an urgent requirement to obtain a greater understanding of the molecular mechanism underlying ovarian cancer progression in order to identify novel drug targets and biomarkers. Secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) has been suggested as a candidate tumor suppressor in various types of human cancers. However, the potential role of SPARCL1 for ovarian cancer has not yet been clearly established. In the present study, lower protein expression levels of SPARCL1 were detected in ovarian cancer tissues when compared with adjacent normal tissues. Overexpression of SPARCL1 significantly suppressed the proliferation and migration of cells from the ovarian cancer cell line SKOV-3, whereas knockdown of SPARCL1 significantly increased cell growth and migration. Furthermore, the results revealed that SPARCL1 overexpression significantly suppressed the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway. Collectively, these results indicated that SPARCL1 may suppress the proliferation and migration of ovarian cancer cells by downregulating signaling via the MEK/ERK pathway.
- Is there a role for HIPEC in ovarian cancer? [News]
- AGArch Gynecol Obstet 2018 Sep 20
- Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack o...
Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack of robust data supporting this. Publicly available evidence addressing the value of HIPEC in EOC is rather inconclusive, revealing contradictory and inconsistent results while some studies even report harm to the patients from a higher morbidity. On this ground, we cannot recommend the implementation and use of HIPEC outside of a randomized clinical trial setting.
- Histone deacetylase inhibitors synergizes with catalytic inhibitors of EZH2 to exhibit anti-tumor activity in small cell carcinoma of the ovary, hypercalcemic type. [Journal Article]
- MCMol Cancer Ther 2018 Sep 19
- Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal malignancy that mainly impacts young women. SCCOHT is characterized by a diploid genome with loss of SMAR...
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal malignancy that mainly impacts young women. SCCOHT is characterized by a diploid genome with loss of SMARCA4 and lack of SMARCA2 expression, two mutually exclusive ATPases of the SWI/SNF chromatin-remodeling complex. We and others have identified the histone methyltransferase EZH2 as a promising therapeutic target for SCCOHT, suggesting that SCCOHT cells depend on the alternation of epigenetic pathways for survival. In this study, we found that SCCOHT cells were more sensitive to pan-HDAC inhibitors compared to other ovarian cancer lines or immortalized cell lines tested. Pan-HDAC inhibitors, such as quisinostat, reversed the expression of a group of proteins that were deregulated in SCCOHT cells due to SMARCA4 loss, leading to growth arrest, apoptosis and differentiation in vitro and suppressed tumor growth of xenografted tumors of SCCOHT cells. Moreover, combined treatment of HDAC inhibitors and EZH2 inhibitors at sub-lethal doses synergistically induced histone H3K27 acetylation and target gene expression, leading to rapid induction of apoptosis and growth suppression of SCCOHT cells and xenografted tumors. Therefore, our preclinical study highlighted the therapeutic potential of combined treatment of HDAC inhibitors with EZH2 catalytic inhibitors to treat SCCOHT.
- Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer. [Review]
- CCancers (Basel) 2018 Sep 18; 10(9)
- Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high...
Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies to interfere with oxidative phosphorylation should be considered for the treatment of ovarian tumors. Here, we review the literature that supports this hypothesis and describe potential agents and critical control points in the oxidative phosphorylation pathway that can be targeted using small molecule agents. In this review, we also discuss potential barriers that can reduce the efficacy of the inhibitors of oxidative phosphorylation.
- Moving From Mutation to Actionability. [Journal Article]
- ASAm Soc Clin Oncol Educ Book 2018 May 23; (38):495-503
- The diffusion of high-throughput next-generation sequencing technologies has sustained massive parallel sequencing of tumor tissue providing a deep insight into tumor biology and advancement of perso...
The diffusion of high-throughput next-generation sequencing technologies has sustained massive parallel sequencing of tumor tissue providing a deep insight into tumor biology and advancement of personalized medicine. A substantial number of targeted agents have been investigated in gynecologic cancer and some have received U.S. Food and Drug Administration approval, like PARP inhibitors in ovarian cancer, bevacizumab in ovarian and cervical cancers, and pembrolizumab in microsatellite-unstable or mismatch repair-deficient endometrial cancer. To improve effectiveness of targeted therapy, identification of predictive biomarkers able to guide the selection of the correct drug for the correct patient is crucial. Different limitations must be addressed to favor a more rapid implementation of a genotyping approach in treatment selection, such as the possibility to easily assess tumor heterogeneity and clonal evolution along the disease trajectory and the need for innovative trial designs like adaptive or basket trials incorporating molecular features as selection criteria. A deep dive into the genomic features of exceptional responders may also favor better understanding of tumor biology, mechanism of action of a specific target agent, and identification or predictive biomarkers for subsequent tailored studies.
- The Epigenetic Landscape in the Treatment of Gynecologic Malignancies. [Journal Article]
- ASAm Soc Clin Oncol Educ Book 2018 May 23; (38):480-487
- The care of patients with advanced-stage or recurrent endometrial, ovarian, and cervical cancer remains clinically challenging. Despite the identification of novel therapeutics and advancements in su...
The care of patients with advanced-stage or recurrent endometrial, ovarian, and cervical cancer remains clinically challenging. Despite the identification of novel therapeutics and advancements in supportive care, survival outcomes have been relatively unchanged over the past decade. In addition to established genomic alterations and the contributions of the tumor microenvironment to cancer progression, epigenetic mechanisms have emerged as important contributors to gynecologic cancer progression. DNA methylation, histone modification, and noncoding RNA expression may be important contributors to disease initiation and progression and may represent novel therapeutic targets. This article reviews the epigenetic landscape of endometrial, ovarian, and cervical cancer, describing the state of the science and discussing potential clinical applications. To date, the role of epigenetic drugs in the treatment of gynecologic cancers remains unclear, although continued progress may inform future treatment modalities.
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- Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells. [Journal Article]
- MCMol Carcinog 2018 Sep 19
- Ras/Raf/MEKs/ERKs and PI3K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the t...
Ras/Raf/MEKs/ERKs and PI3K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the therapeutic potential of magnolin using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE mutaome analysis for relevant mutation information. The results showed that magnolin efficacy on cell proliferation inhibition were lower in TOV-112D ovarian cancer cells than that in SKOV3 cells by G1 and G2/M cell cycle phase accumulation. Notably, magnolin suppressed colony growth of TOV-112D cells in soft agar, whereas colony growth of SKOV3 cells in soft agar was not affected by magnolin treatment. Interestingly, phospho-protein profiles in the MAPK and PI3K signaling pathways indicated that SKOV3 cells showed marked increase of Akt phosphorylation at Thr308 and Ser473 and very weak ERK1/2 phosphorylation levels by EGF stimulation. The phospho-protein profiles in TOV-112D cells were the opposite of those of SKOV3 cells. Importantly, magnolin treatment suppressed phosphorylation of RSKs in TOV-112D, but not in SKOV3 cells. Moreover, magnolin increased SA-β-galactosidase-positive cells in a dose-dependent manner in TOV-112D cells, but not in SKOV3 cells. Notably, oral administration of Shin-Yi fraction 1, which contained magnolin approximately 53%, suppressed TOV-112D cell growth in athymic nude mice by induction of p16Ink4a and p27Kip1 . Taken together, targeting of ERK1 and ERK2 is suitable for the treatment of ovarian cancer cells that do not harbor the constitutive active P13K mutation and the loss-of-function mutations of the p16 and/or p53 tumor suppressor proteins. This article is protected by copyright. All rights reserved.