The American Journal of the Medical Sciences

Right adrenal cystic mature teratoma: Masquerading as high density mass

An Update on Screening and Prevention for Breast and Gynecological Cancers in Average and High Risk Individuals

Breast and gynecological cancers affect almost 900,000 women and therefore most health care providers will be involved at some point in the management of women with cancer. As the prognosis of all cancers is much more favorable when diagnosed in early stages, it is imperative that all health care providers are familiar not only with current screening guidelines for the average population, but also with the identification of high risk individuals who may benefit from more intense screening as well as available interventions to prevent disease or decrease risk. The purpose of this review article is to provide relevant information to physicians and other health care providers to aid in identifying patients that are classified as "high risk" for developing breast or a gynecologic cancer, outlining what interventions exist for adequate screening and risk reduction strategies, and to provide an update on current screening guidelines for individuals at average and high risk.

Ivermectin Augments the In Vitro and In Vivo Efficacy of Cisplatin in Epithelial Ovarian Cancer by Suppressing Akt/mTOR Signaling

The poor outcomes in epithelial ovarian cancer necessitate new treatments. In this work, we systematically analyzed the inhibitory effects of ivermectin and the molecular mechanism of its action in ovarian cancer. The effects of ivermectin alone and its combination with cisplatin on growth and survival were examined using cultured ovarian cancer cells and a xenograft mouse model. The molecular mechanism of action of ivermectin, focusing on Akt/mTOR signaling, was elucidated. Ivermectin arrested growth in the G2/M phase and induced caspase-dependent apoptosis in ovarian cancer, regardless of specific cellular and molecular differences. Ivermectin significantly augmented the inhibitory effect of cisplatin on ovarian cancer cells in a dose-dependent manner. Mechanistically, ivermectin suppressed the phosphorylation of key molecules in the Akt/mTOR signaling pathway in ovarian cancer cells. In addition, overexpression of constitutively active Akt restored ivermectin-induced inhibition of Akt/mTOR, growth arrest and apoptosis. In an ovarian cancer xenograft mouse model, ivermectin alone significantly inhibited tumor growth. In combination with cisplatin, tumor growth was completely reversed over the entire duration of drug treatment without any toxicity. Furthermore, the concentrations of ivermectin used in our study are pharmacologically achievable. Our work suggests that ivermectin may be a useful addition to the treatment armamentarium for ovarian cancer and that targeting Akt/mTOR signaling is a therapeutic strategy to increase chemosensitivity in ovarian cancer.

Growing teratoma syndrome - ovarian germ cell tumor

More than meets the eye: Duodenal metastasis of cervical squamous carcinoma

Comprehensive analysis of the exocytosis pathway genes in cervical cancer

Cervical cancer (CC) is the fourth most common gynecological malignancy globally. This suggests the need for improved markers for prognosis, better understanding of the molecular mechanism, and targets for therapy. The defective exocytosis pathway is proposed as bona fide drivers of carcinogenesis. This study aimed to identify the exocytosis pathway network and its contribution to CC. We screened exocytosis genes from the The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) dataset and performed differential expression and methylation, Kaplan-Meier survival, and pathway enrichment analysis. We constructed the protein-protein interaction networks (PPIN), predicted the possible metastatic genes, and identified FDA approved drugs to target the exocytosis network in CC. Integrated bioinformatics analysis identified 245 differentially methylated genes, including 153 hypermethylated and 92 hypomethylated genes. Further, 89 exocytosis pathway genes were differentially expressed, including 60 downregulated and 29 upregulated genes in CC. The overlapping analysis identified 39 genes as methylation regulated genes and showed an inverse correlation between methylation and expression. The HCMDB database identified nine of the identified genes (GRIK5, PTPN6, GAB2, ATP8B4, HTR2A, SPARC, CLEC3B, VWF, and S100A11) were linked with metastasis in CC. Moreover, the Kaplan-Meier survival analysis identified that high expression of PTPN6 and low expression of CLEC3B were significantly linked with poor overall survival (OS) in patients with CC. The KEGG pathway enrichment analysis identified differentially expressed genes that were mainly involved with proteoglycans in cancer, TGF-beta signaling, PI3K-Akt signaling, MAPK signaling pathway, and others. The PPIN identified 89 nodes, 192 edges with VWF, MMP9, THBS1, IGF1, CLU, A2M, IGF2, SPARC, VAMP2, and FIGF as top 10 hub genes. The drug-gene interaction analysis identified 188 FDA approved drugs targeting 32 genes, including 5 drugs that are already in use for treating CC. In summary, we have identified the exocytosis pathway networks, candidate genes, and novel drugs for better management of CC.

The expression and clinical significance of cytokines Th1, Th2, and Th17 in ovarian cancer

This study was to analyze the levels of Th1, Th2 and Th17 cytokines in peripheral blood samples from ovarian cancer (OC) patients. Ninty-five OC patients including 45 OC and 50 benign ovarian disease (BOD) were selected at Zhejiang Cancer Hospital from October 2021 to March 2022; 46 healthy participants were simultaneously selected at Taizhou Municipal Hospital as healthy controls (HC). The expressions of Th1, Th2 and Th17 were compared in all participants. Marker levels were analyzed with age, histological type, tumor size, ovarian number and clinical stage of OC. The IL6 and IL8 levels were significantly higher in OC compared to BOD and HC (p 0.05). In peripheral blood from OC patients, the immune system was more dysregulated and immune cells produced more cytokines with contrasting actions. These data showed significant clinical implications for the diagnosis of OC.

Mixed glandular neuroendocrine carcinoma of the endometrium with hypercalcemic crisis

To explore the ideas and research progress in diagnosing and treating hypercalcemic crisis in patients with cancer. We reviewed the clinical data, diagnosis and treatment of hypercalcemic crisis in a patient with mixed glandular neuroendocrine carcinoma of the endometrium. The patient had gastrointestinal symptoms and acute renal impairment as the main manifestations, and the blood biochemical indexes suggested a hypercalcemic crisis with elevated parathyroid hormone (PTH). No lesions were seen in the parathyroid glands on imaging and nuclide imaging, but an abnormal pelvic mass was seen in the pelvis and the biopsy of the uterine cervix tissue suggested that it was an adenocarcinoma. Surgery was performed to remove the mass, and postoperative findings suggested endometrial large-cell neuroendocrine carcinoma with endometrioid adenocarcinoma. The calcium and PTH decreased to normal after surgery and chemotherapy. The condition of the hypercalcemia crisis is dangerous, so it is necessary to think from different aspects of the clinical diagnosis and treatment.

Primary signet ring cell carcinoma of the appendix: An interesting case

MiR-628–5p Inhibits Cervical Carcinoma Proliferation and Promotes Apoptosis by Targeting VEGF

It has been reported that the dysregulation of microRNAs (miRNAs) is implicated in the biological processes of diverse diseases, including the tumorigenesis of human cancers. MicroRNA-628-5p (miR-628-5p) is differentially expressed and plays a critical role in several cancers, but the role of miR-628-5p in cervical cancer has not been well studied. The TCGA database and RT-qPCR were used to evaluate the expression profile of miR-628-5p in cervical cancer tissues. Transfection efficiency of synthetic miRNAs was detected using RT-qPCR. The biological effects of miR-628-5p on cervical cancer cells were assessed by the CCK-8 assay, flow cytometry, western blot analysis, and the tube formation assay. The expression levels of key proteins involved in cell apoptosis, the cell cycle and the PI3K pathway were analyzed by western blot analysis. Bioinformatic analysis and the luciferase reporter assay were performed to investigate the targeted relationship between miR-628-5p and vascular endothelial growth factor (VEGF). MiR-628-5p was downregulated and negatively correlated with Ki-67 expression in cervical cancer tissues, and its low level predicted poor survival of patients. Functional assays indicated that miR-628-5p inhibited cell proliferation and promoted cell apoptosis. Mechanically, VEGF was verified to be a downstream target of miR-628-5p. Moreover, overexpression of VEGF could reverse the effects of miR-628-5p on VEGF/PI3K/AKT signaling, cell proliferation, apoptosis, the cell cycle and angiogenesis in cervical cancer. MiR-628-5p inhibited cervical cancer cell proliferation and promoted apoptosis by targeting VEGF.

Metastatic Intrahepatic Cholangiocarcinoma Presenting as Vulvar Carcinoma Erysipeloides

AC074117.1/miR-193a-3p axis regulates the malignant progression of uterine corpus endometrial carcinoma via the m6A-related gene ALKBH5

Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies, with an annually increasing incidence and a poor prognosis. lncRNAs and microRNAs regulate the progression of UCEC through ceRNA networks. Additionally, m6A modification plays various roles in UCEC, and abnormal regulation of it can directly affect tumor progression. However, the role of m6A-associated ceRNA networks in UCEC remains unclear. Bioinformatics methods were used to construct the ceRNA regulatory network of m6A related genes in UCEC. MeRIP assays, dual-luciferase reporter assays and other experiments were used to prove the conclusions. This study showed that the AC074117.1/miR-193a-3p axis promoted the malignant progression of UCEC through ALKBH5, an m6A demethylase. MeRIP assay indicated that ALKBH5 regulated m6A modification in UCEC. Gene set enrichment analysis and cell proliferation and migration assays showed that the AC074117.1/miR-193a-3p/ALKBH5 axis regulated the proliferation and migration of UCEC cells. With regard to mechanistic analysis, dual-luciferase reporter assay demonstrated that AC074117.1 acted as a ceRNA for miR-193a-3p, influencing the expression of ALKBH5. Furthermore, rescue experiments validated that the regulatory effects of miR-193a-3p on the malignant progression of UCEC relied on ALKBH5 to some extent. Altogether, this study revealed an m6A-related ceRNA network in UCEC, which may serve as a target for early diagnosis and treatment.

Endometrial cancer metastatic to the transverse colon mimicking colorectal cancer