Expression and clinical significance of PD-1 in UCEC and its Impact on tumor.

Programmed death 1 (PD-1) plays an important role in the immune escape, occurrence and development of tumors by inhibiting the function of immune cells. However, its prognostic value in uterine corpus endometrial carcinoma (UCEC) and its impact on the tumor microenvironment remain to be further explored. Transcriptional datasets were retrieved from the GEPIA, TIMER and TCGA databases. "edgeR" package was used for the identification of differentially expressed genes (DEGs) between two groups of patients (PD1-high and PD1-low group). Gene set enrichment analysis (GSEA) was performed to identify underlying pathways between betweenPD1-high and PD1-low groups functioning in UCEC. Gene Correlation Analysis was used to further confirm the associations of PD1 expression with T-cell-related genes. Cytoscape software was used to identify hub genes in DEGs. Kaplan-Meier analysis was performed to validate the prognostic value of hub genes. Mutational characteristics of UCEC patients according to PD1 levels were depicted and analyzed. We found that the transcriptional expression of the PD1 gene in UCEC tumor tissues markedly increased in cohorts from the GEPIA and TCGA databases. PD1 expression was negatively correlated with gene signatures associated with the T-cell receptor signaling pathway and primary immunodeficiency. GESA confirmed that PD1 expression was negatively correlated with gene signatures associated with the T-cell receptor signaling pathway. T-cell receptor complex-related genes, ZAP70, TRAC, CD3D, CD3E, CD8A, TRBC2, TRBV28 and CD247, showed significant positive associations with PD1 expression. The results of the Kaplan-Meier OS analysis indicated that PD1, TIGIT, FASLG, ICOS and TNFRSF9 are the protective factor for patients with UCEC. The top 5 genes of mutations in the low expression group, included PTEN (56%), PIK3CA (43%), TP53 (41%), TTN (39%), and ARID1A (37%). The genes with a higher proportion of mutations in the PD1-high group are PTEN (67%), TTN (62%), PIK3CA (53%), ARID1A (52%), and MUC16 (12%). The prognosis of UCEC patients with PD1 overexpression phenotype is worse than that of the PD1 low group, which is due to the involvement of the PD1 gene in the T-cell receptor signaling pathway. This study provides a further theoretical basis and reference for targeted therapy against PD1.

Circ-0000979 promotes the development of gastric carcinoma by sponging miR-136 and modulating SP1 mRNA expression level.

Circular RNAs (circRNAs) are a new class of non-coding RNAs that play pivotal biological roles in several types of cancer cells. However, the role of circ-0000979 in gastric cancer (GC) has never been explored. Therefore, the current study aims to examine the functional effects of circ-0000979 in GC development and progression. The expression level of circ-0000979 was validated using qRT-PCR analysis. We found that circ-0000979 is significantly upregulated in GC samples. Using AGS and HGC27 GC cell line, we examined the biological functions and regulatory mechanisms of circ-0000979 in GC in vitro and in vivo by knocking down circ-0000979. We found that circ-0000979 is sub-cellularly localized in the cytoplasm of GC cells. Functionally, silencing circ-0000979 leads to a significant reduction in GC cell proliferation and migration. In vivo assays showed that circ-0000979 knockdown markedly reduced GC tumor growth. CircRNA interactome predicted miR-136 as circ-0000979 targeting miRNA, while starbase prediction result showed that miR-136 targeted the 3'UTR region of SP1 mRNA. Taken together, our results demonstrated that circ-0000979, as a carcinogenic circRNA, promotes the progression of GC by regulating the miR-136/SP1 pathway. Circ-0000979 is a potential RNA-based therapeutic target for GC treatment.

The role of slingshot-1L (SSH1L) in the differentiation of human bone marrow mesenchymal stem cells into cardiomyocyte-like cells.

Adult cardiomyocytes (CMs) have very limited capacity to regenerate. Therefore, there is a great interest in developing strategies to treat infarcted CMs that are able to regenerate cardiac tissue and promote revascularization of infarcted zones in the heart. Recently, stem cell transplantation has been proposed to replace infarcted CMs and to restore the function of the affected tissue. This area of research has become very active in recent years due to the huge clinical need to improve the efficacy of currently available therapies. Slingshot (SSH) is a family of protein phosphatases, which can specifically dephosphorylate and reactivate cofilin and inhibit the polymerization of actin filaments and actively involved in cytoskeleton rearrangement. In this study, we found that SSH1L promoted morphology changes of microfilaments during differentiation but was inhibited by the inhibitors of actin polymerization such as cytochalasin D. Overexpression of SSH1L could promote cardiac-specific protein and genes expression. 5-Aza can induce the differentiation of hMSCs into cardiomyocyte-like cells in vitro. We also observed that SSH1L efficiently promotes hMSCs differentiation into cardiomyocyte-like cells through regulation and rearrangement of cytoskeleton. Our work provides evidence that supports the positive role of SSH1L in the mechanism of stem cell differentiation into cardiomyocyte-like cells.

Castleman Disease of the Kidney in Computed Tomography Urography.

BACKGROUND: Castleman Disease (CD) of the kidney is extremely rare. In this study, we have presented a case of CD of the left kidney and comprehensively described the findings of computed tomography urography. CASE PRESENTATION: The case involved unusual imaging characteristics of the focal central cystic area. CONCLUSION: The small and regular cyst-like structures and the hyperdense mass relative to the renal parenchyma in plain scans might help distinguish the CD of the kidney from other hypervascular tumors.

Overexpression of LIMK1 promotes migration ability of multidrug-resistant osteosarcoma cells.

Multidrug resistance (MDR) to chemotherapy is a major obstacle in the treatment of cancer and the resistance process is multifactorial. Studies on multidrug resistance mechanisms relied on the availability of cancer multidrug resistance cell lines that have been established. In this study we successfully established a multidrug resistance cell line MG63/VCR derived from human osteosarcoma cell line MG63 based on the induction by vincristine. MG63/VCR cells exhibited high resistance to vincristine and other anticancer drugs, accompanied by upregulated expression of MDR-associated genes MDR1, MRP1, and Bcl-2. Notably, we found that MG63/VCR cells exhibited higher migration ability compared to parental MG63 cells. Moreover, we demonstrated that LIMK1, a key regulator of actin cytoskeleton, was overexpressed at both mRNA and protein levels in MG63/VCR cells and the higher LIMK1 protein level was correlated with higher level of phosphorylated cofilin. In addition, knockdown of LIMK1 abolished the higher migration ability of MG63/ VCR cells. These results suggest that LIMK1 overexpression contributes to the invasion and metastasis of drug-resistant osteosarcoma and reveal LIMK as a novel therapeutic target for drug resistant osteosarcoma.

Follicular dendritic cell sarcoma of the tonsil: case report and review of literature.

OBJECTIVE: To explore the clinicopathologic features, immunophenotype, differential diagnosis, and prognosis of tonsil follicular dendritic cell sarcoma (FDCS). METHODS: In the Department of Pathology, the affiliated Yantai Yuhuangding Hospital of Qingdao University, in 2019, a case of tonsil FDCS was diagnosed and retrospectively analyzed to summarize its clinical and pathologic characteristics. Relevant literature was reviewed. RESULTS: The patient was a 71-year-old man. The tumor occurred in the right tonsil with a maximum diameter of 3.5 cm. Microscopically, the tumor cells were spindle-shaped or oval-shaped, arranged in bundles or swirls, and some areas formed concentric circles around blood vessels. Small lymphocytes were distributed in the background. The nucleus was oval-shaped or round, with nuclear chromatin and small central nucleoli. Mitoses were up to 5/10 HPF at the highest. Immunohistochemistry showed positive expression of CD21, CD23, CD68, vimentin, and D2-40 in tumor cells, and Ki67 proliferation index was about 20%. CXCL13 was positive only in scattered background lymphocytes. In situ hybridization for EBER was negative. After surgical resection of the tumor, without radiotherapy or chemotherapy, the patient has been followed up for 4 months until now, without recurrence or metastasis. CONCLUSION: FDCS is a rare tumor, especially in extranodal sites. The pathogenesis, treatment and prognosis of FDCS still need further exploration.

Collision tumor of carcinoma and lymphoma in the cecum: case report and review of literature.

Collision tumors that occur in the gastrointestinal tract, especially the intestine, are rare, and collisions of carcinoma and lymphoma are even more rare. We report a case of collision tumor with adenocarcinoma and non-Hodgkin's diffuse large B-cell lymphoma in the cecum of an elderly male patient. Literature was reviewed to explore the clinicopathologic features, differential diagnosis, treatment, and prognosis of collision tumors with carcinoma and lymphoma involving the gastrointestinal tract, to enhance the understanding of this rare tumor, and improve diagnosis and treatment.

The clinicopathological features of combined primary hepatic adenosquamous-hepatocellular carcinoma.

OBJECTIVE: To explore the pathological features of combined primary hepatic adenosquamous carcinoma (ASC) and hepatocellular carcinoma (HCC). METHODS: The clinicopathological data of one case of cASC-HCC was collected, and the features were analyzed through a literature review. RESULTS: The male patient was 59 years old and had suffered from inconsistent, upper abdominal pain without any obvious cause for one year. MRI and B-Mode ultrasound images of the upper abdomen showed abnormal signals in the posterior segment of the right lobe of the liver, measuring 12.2 × 7.7 cm. A right hepatectomy was performed. A gross examination revealed an irregular, gray-white infiltrating growing mass, with a partially grayish-yellow area. The histological morphology and immunohistochemical results showed that the tumor was composed of ASC in the gray-white area, accounting for about 80%, and HCC in the grayish yellow area, accounting for about 20%. CONCLUSION: cASC-HCC is a rare, malignant tumor with high rates of recurrence and metastasis. It mainly occurs in the right lobe of the liver, especially in older men with a history of hepatitis or intrahepatic cholangiolithiasis. Surgery is the main treatment method.

High-grade serous carcinoma of fallopian tube with yolk sac tumor differentiation in a postmenopausal patient.

Yolk sac tumors (YSTs) are the second most common germ cell malignancy of the ovaries, generally presenting in children and young women. However, they rarely occur in the fallopian tubes of postmenopausal patients. The current rare case is composed of yolk sac tumor differentiation within high-grade serous carcinoma (HGSC) arising in the fallopian tube of a 68-year-old woman. Serum α-fetoprotein was much higher than normal level. This case exhibited some areas of glandular architecture with positivity for SALL4, AFP, and Glypican-3 and negative staining for PAX8, supporting a germ cell tumor differentiation. By reviewing the published literature, we believe that YSTs, whether or not associated with an epithelial component detected histologically in older patients, constitute a single entity that is different from YSTs in younger patients. Above all, the pathologist must check carefully tissue stained with hematoxylin-eosin especially in postmenopausal women with ovarian, fallopian tube, or endometrial mass and an elevated serum α-fetoprotein level. Neoplasms of this type should be treated aggressively, and should respond to platinum-based chemothotherapy.

LIM kinase 1 is required for insulin­dependent cell growth of osteosarcoma cell lines.

Osteosarcoma is a type of malignant bone tumor with high metastasis and poor prognosis. Previous studies have demonstrated the involvement of LIM kinase 1 (LIMK1) in the proliferation of osteosarcoma cells. LIMK1 is overexpressed in human osteosarcoma tissues and cell lines. To further study LIMK1-associated mechanisms, we used shRNA targeted to the LIMK1 gene to block its expression in the osteosarcoma cell lines MG63 and U2OS. Insulin promoted the proliferation of MG63 cells in a time- and dose-dependent manner, however, this insulin induced proliferation was significantly inhibited by transfection of shRNA targeted to the LIMK1 gene, as well as by the PI3K inhibitor LY294002, but not by the mitogen­activated protein kinase (MAPK) inhibitor PD98059. The level of cofilin phosphorylation was increased significantly following stimulation of insulin for 24 h, indicating the activation of LIMK1. MG63 cell proliferation was also significantly inhibited by 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in a time-dependent manner. Furthermore, 1,25(OH)2D3 negated the inhibitory effect of LIMK1 shRNA, indicating that LIMK1 is important in the inhibitory pathway of 1,25(OH)2D3. The present study confirms that LIMK1 is important in regulating osteosarcoma cell proliferation via the insulin/PI3K/LIMK1 signaling pathway, thus the development of gene therapy for osteosarcoma targeting LIMK1 is warranted.

Regulation of cofilin activity by CaMKII and calcineurin.

Cofilin promotes actin filament turnover by severing and depolymerizing actin filaments. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase1 (LIMK1) and is activated when protein phosphatase Slingshot-1L (SSH1L) dephosphorylates this residue. The authors have shown that Ca-induced cofilin dephosphorylation is mediated by calcineurin (Cn)-dependent activation of SSH1L. In this study, Ca/calmodulin-dependent protein kinase II (CaMKII) is shown to negatively regulate SSH1L activity and bind to SSH1L in a complex with 14-3-3. Phosphorylation of LIMK1 by CaMKII and its subsequent activation regulates the subcellular localization of SSH1L. Based on these findings, the authors suggest that CaMKII and Cn provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization.