DDX60 Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker

DDX60, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of DDX60 in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, P < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of DDX60 in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. DDX60 expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = −0.24). Furthermore, DDX60 expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like CTLA-4, PD-L1, EGF, CD96, and CD226, were all positively related with DDX60 (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, P < 0.0001) and GBM cells. These results indicated that DDX60 might have important clinical significance in glioma and could serve as a potential immune therapeutic target

Congenital Hepatic Fibrosis in Children and Adults: Clinical Manifestations, Management, and Outcome—Case Series and Literature Review

Background. Congenital hepatic fibrosis is a hereditary fibropolycystic disease caused by ductal plate malformation. It is characterized by portal hypertension, but the manifestations, management, and outcome vary in children and adults. To raise awareness of medical staff, we have comprehensively compared the clinical features of congenital hepatic fibrosis between children and adults. Methods. We retrospectively enrolled all patients diagnosed with congenital hepatic fibrosis at the Huashan Hospital from August 2015 to August 2017 and analyzed their familial, clinical, laboratory, imaging, treatment, and follow-up data in detail. In addition, we reviewed cases with congenital hepatic fibrosis reported in the past 20 years in China and analyzed them according to the patients’ age. Results. A total of eight patients were diagnosed with congenital hepatic fibrosis in the study, including four children and four adults. The onset age of the children, who suffered from severe complications of portal hypertension and needed liver transplantation, ranged from 1 to 15 years old. The disorder developed in adults aged 26 to 60 years old. Three adults complained of recurrent abnormal liver function at the onset of illness, and they mainly received conservative treatments. The literature review included 30 children and 33 adults. In comparison, hepatomegaly was more common in children than in adults (57% vs. 21%, p=0.004). Malformation of kidneys and bile duct abnormalities were common, and multisystem involvement included eyes, other digestive organs, and genital and central nervous systems. Conclusions. Serious complications of portal hypertension developed in children requiring liver transplantation, while adults often had mild-to-moderate liver injuries upon onset. Adults with CHF varied a lot in clinical manifestations. Multiorgan involvement and unusual course are helpful to make a diagnosis. Timely histological assessment by liver biopsy and multidisciplinary cooperation are crucial for definitive diagnosis and early intervention

Primitive neuroectodermal tumor of the kidney: case report and review of literature

Abstract Background Renal primitive neuroectodermal tumor (rPNET) as a member of Ewing’s sarcoma family is extremely rare and usually occurs in children and young adults. Most literature about rPNET was isolated case reports. Case presentation We reported a case of 45-year-old man with the complaint of right flank pain. Computerized tomography (CT) scan demonstrated a large substantive tumor involving the lower pole of the right kidney. Then the patient underwent radical nephrectomy. Pathologic characteristics and immunohistochemical analysis confirmed the diagnosis of rPNET. Additionally, the patient received three cycles of chemotherapy, and was still alive without metastasis at 15-months follow-up. Conclusion rPNET is rare and presents aggressive clinical behavior and worse prognosis. We expect that further awareness and study of this rare tumor can be had by presenting our case.</p

FOXP3+ lymphocyte density in pancreatic cancer correlates with lymph node metastasis.

To determine if the density of FOXP3+ lymphocytes in primary tumors and lymph nodes in pancreatic cancer correlates with the presence of lymph node metastases.FOXP3+ lymphocyte density in primary pancreatic cancer tissue and draining lymph nodes was measured using immunohistochemistry. We analyzed the clinical and pathological aspects associated with the accumulation of FOXP3+ lymphocytes in pancreatic cancer. We also analyzed the correlation of density of FOXP3+ lymphocytes in lymph nodes with the nodal status and distance from the primary tumor.FOXP3+ lymphocyte density in pancreatic cancer was significantly higher than in paratumoral pancreatic tissue. The density of FOXP3+ lymphocytes in local tumor tissue correlated significantly with the histological grade and overall lymph node status. Furthermore, FOXP3+ lymphocyte density was significantly higher in positive lymph nodes than in negative ones, while it had no correlation with the distance of the lymph node from the primary tumor.FOXP3+ lymphocyte density in primary tumor tissue in patients with pancreatic cancer correlates with lymph node metastasis. Lymph nodes containing metastases having higher FOXP3+ lymphocyte densities than do negative lymph nodes

Targeting a Sirt5-Positive Subpopulation Overcomes Multidrug Resistance in Wild-Type Kras Colorectal Carcinomas

Summary: A major obstacle for successful management of patients with colorectal carcinoma (CRC) is resistance to anti-cancer cytotoxic treatments. Here, we identified a mechanism of multidrug resistance in wild-type Kras CRCs based on the survival of a cell subpopulation characterized by Sirt5 expression. Sirt5+ cells in wild-type Kras CRCs are resistant to either chemotherapeutic agents or cetuximab and serve as a reservoir for recurrence. Sirt5 demalonylates and inactivates succinate dehydrogenase complex subunit A (SDHA), leading to an accumulation of the oncometabolite succinate. Succinate binds to and activates a reactive oxygen species-scavenging enzyme, thioredoxin reductase 2 (TrxR2), to confer chemotherapy resistance. In contrast, Sirt5+ cells exhibit an elevated succinate-to-aKG ratio that inhibits aKG-dependent dioxygenases to maintain cetuximab resistance. Our findings suggest that Sirt5 inhibitors in combination with chemotherapeutic agents and/or cetuximab may represent a therapeutic strategy for CRC patients harboring wild-type Kras. : Du et al. show that a Sirt5+ subpopulation represents a critical driving force behind the development of multidrug resistance in wild-type Kras colorectal carcinomas and that Sirt5-mediated SDHA inactivation has implications for this process. Keywords: Sirt5, colorectal carcinomas, wild-type Kras, drug resistance, SDH

Adult primary retroperitoneal cavernous hemangioma: a case report

<p>Abstract</p> <p>Primary retroperitoneal cavernous hemangioma (PRCH) in an adult is extremely rare. We report on the diagnosis and treatment of a patient with PRCH with subtle clinical features and atypical findings on imaging scans. A 38-year-old man was admitted to hospital with a 5-day history of epigastralgia after alcohol drinking. Using various imaging methods, we found a giant cyst-like retroperitoneal mass compressing the surrounding organs. Surgical resection of the tumor was performed, and the mass was found to be a cavernous hemangioma measuring 90 × 80 × 60 mm, with a thick fibrotic wall and extensive intracystic hemorrhage. Physicians should be aware that PRCH may mimic a cystic neoplasm, and that a large tumor size probably indicates intracystic hemorrhage. Surgical resection is a curative approach for PRCH.</p

Univariate and multivariate analysis of relevant factors correlated with lymph node metastases of pancreatic cancer.

<p>Univariate and multivariate analysis of relevant factors correlated with lymph node metastases of pancreatic cancer.</p