Hepatosplenic actinomycosis in an immunocompetent patient

Hepatosplenic abscess caused by Actinomyces is rare and often misdiagnosed as malignancy. Herein, we report a case of hepatosplenic actinomycosis in a 37-year-old immunocompetent man with a 2-month clinical history of intermittent fever and upper left abdominal pain. Physical examination revealed a mildly ill-appearing man with a low-grade fever (38°C) and upper left quadrant abdominal tenderness. Abdominal sonographic examination showed the presence of a 6.3 cm × 6.5 cm heterogeneous abscess with a hypoechoic center and honeycomb appearance in an enlarged spleen (8 cm × 5 cm). Computerized tomography of the abdomen revealed a multiloculated splenic lesion, and laparotomy showed multiple hepatic nodules and a splenic abscess. Histopathological examination of the biopsy revealed filamentous branching bacilli and sulfur granules in the hepatosplenic abscess. The patient successfully underwent splenectomy accompanied by intravenous and oral penicillin treatment. Proper and prompt diagnosis of hepatosplenic actinomycosis is important because the therapeutic plan and prognosis of this pathogen are quite different from other microorganisms and malignancies

BHLHE22 Expression Is Associated with a Proinflammatory Immune Microenvironment and Confers a Favorable Prognosis in Endometrial Cancer

Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC

Additional file 1: Figure S1. of DEF6 expression in ovarian carcinoma correlates with poor patient survival

Kaplan-Meier curves for overall survival in four histological subtypes of ovarian carcinoma patients according to DEF6, p16 and p53 expressions. A, Patients with high DEF6 expression (scores 2 and 3; n = 60) versus low DEF6 expression (scores 0 and 1; n = 15) in high-grade serous carcinoma. (H: high DEF6 expression; L: low DEF6 expression). B, Patients with high p16 expression (scores 2 and 3; n = 56) versus low p16 expression (scores 0 and 1; n = 18) in high-grade serous carcinoma. (H: high p16 expression; L: low p16 expression). C, Patients with aberrant p53 expression (scores 0 and 3; n = 62) versus insignificant p53 expression (scores 1 and 2; n = 12) in high-grade serous carcinoma. D, Patients with high DEF6 expression (scores 2 and 3; n = 20) versus low DEF6 expression (scores 0 and 1; n = 16) in mucinous carcinoma. (H: high DEF6 expression; L: low DEF6 expression). E, Patients with high p16 expression (scores 2 and 3; n = 32) versus low p16 expression (scores 0 and 1; n = 3) in mucinous carcinoma. (H: high p16 expression; L: low p16 expression). F, Patients with aberrant p53 expression (scores 0 and 3; n = 17) versus insignificant p53 expression (scores 1 and 2; n = 19) in mucinous carcinoma. G, Patients with high DEF6 expression (scores 2 and 3; n = 6) versus low DEF6 expression (scores 0 and 1; n = 22) in endometrioid carcinoma. (H: high DEF6 expression; L: low DEF6 expression). H, Patients with high p16 expression (scores 2 and 3; n = 17) versus low p16 expression (scores 0 and 1; n = 11) in endometrioid carcinoma. (H: high p16 expression; L: low p16 expression). I, Patients with aberrant p53 expression (scores 0 and 3; n = 9) versus insignificant p53 expression (scores 1 and 2; n = 19) in endometrioid carcinoma. J, Patients with high p16 expression (scores 2 and 3; n = 30) versus low p16 expression (scores 0 and 1; n = 11) in clear cell carcinoma. (H: high p16 expression; L: low p16 expression). K, Patients with aberrant p53 expression (scores 0 and 3; n = 10) versus insignificant p53 expression (scores 1 and 2; n = 31) in clear cell carcinoma. (ZIP 195 kb

Epigenomic Analysis Reveals the KCNK9 Potassium Channel as a Potential Therapeutic Target for Adenomyosis

Adenomyosis is linked to dysmenorrhea and infertility. The pathogenesis of adenomyosis remains unclear, and little is known of the genetic and epigenetic changes in the eutopic endometrium in adenomyosis, which may predispose patients to the invasion and migration of endometrial tissues into the myometrium. Transcriptome studies have identified genes related to various cell behaviors but no targets for therapeutic intervention. The epigenetics of the eutopic endometrium in adenomyosis have rarely been investigated. Endometrial tissue was obtained from premenopausal women with (n = 32) or without adenomyosis (n = 17) who underwent hysterectomy aged 34–57 years at a tertiary hospital. The methylome and transcriptome were assessed by using a Methylation 450 K BeadChip array and Affymetrix expression microarray. Protein expression was examined by immunohistochemistry. Differential methylation analysis revealed 53 lowly methylated genes and 176 highly methylated genes with consistent gene expression in adenomyosis, including three genes encoding potassium ion channels. High expression of KCNK9 in the eutopic and ectopic endometria in patients with adenomyosis but not in normal controls was observed. Hormone-free, antibody-based KCNK9 targeting is a potential therapeutic strategy for adenomyosis-related dysmenorrhea, menorrhagia, and infertility

Complete remission of heavily treated ovarian clear cell carcinoma with ARID1A mutations after pembrolizumab and bevacizumab combination therapy: a case report

Abstract Background Patients with ovarian clear cell carcinoma (OCCC) have a poor prognosis because they show low sensitivity to platinum-based chemotherapy. New treatments for refractory OCCC are urgently needed. Case presentation We present a patient with refractory OCCC in whom conventional chemotherapy failed. Cachexia was induced by the disseminating recurrent tumors. Tumor tissue staining and genomic analysis revealed PD-L1 negativity, a low tumor burden, stable microsatellite instability, and two mutations in ARID1A. The patient was administered pembrolizumab combined with bevacizumab triweekly. Her serum CA-125 level decreased dramatically after the first cycle. A computerized tomography scan showed marked regression of the recurrent masses after 3 cycles, and the patient reached complete remission after 9 cycles. She showed good recovery from cachexia. We observed no marked side effects except for mild polyarthritis of the small joints. Conclusions The therapeutic effect of checkpoint inhibitors combined with angiogenesis inhibitors is very promising in our patient with OCCC. Further clinical trials of tumors including ARID1A mutations are warranted