Ischemic Colitis Due to Idiopathic Myointimal Hyperplasia of the Mesenteric Veins.

Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare and poorly understood noninflammatory ischemic colitis. First reported by Genta and Haggitt in 1991, the disease typically presents with chronic abdominal pain, weight loss, and diarrhea with or without hematochezia in middle-aged men. IMHMV is frequently misdiagnosed as an inflammatory bowel disease. The pathophysiology of IMHMV involves the proliferation of the intimal smooth muscle in mesenteric veins leading to bowel ischemia. The etiology of this process remains unknown. There are no good medical therapies for IMHMV, and surgical resection, a curative intervention, is typically required to make the diagnosis. We present the case of a 66-year-old man with IMHMV diagnosed with endoscopic biopsies.

TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion.

Diffuse invasion is an important factor leading to treatment resistance and a poor prognosis in gliomas. Herein, we found that expression of the tripartite motif containing 56 (TRIM56), a RING-finger domain containing E3 ubiquitin ligase, was markedly higher in glioma than in normal brain tissue, and was significantly correlated with malignant phenotypes and a poor prognosis. In vitro and in vivo experimental studies revealed that TRIM56 promoted the migration and invasion of glioma cells. Mechanistically, TRIM56 was transcriptionally regulated by SP1 and promoted the K48-K63-linked poly-ubiquitination transition of IQGAP1 at Lys-1230 by interacting with it, which in turn promoted CDC42 activation. This mechanism was confirmed to mediate glioma migration and invasion. In conclusion, our study provides insights into the mechanisms through which TRIM56 promotes glioma motility, i.e., by regulating IQGAP1 ubiquitination to promote CDC42 activation, which might be clinically targeted for the treatment of glioma.

Sequential Development of JAK2V617F Mutation and BCR-ABL1 Fusion in Individual Patients With Myeloproliferative Neoplasms.

CONTEXT.­: Concomitant BCR-ABL1 and JAK2V617F in myeloproliferative neoplasms (MPNs) is rare, and its pathogenesis and clinical significance are unclear. OBJECTIVE.­: To investigate the clonal relationship between the 2 genomic alterations, as well as the clinicopathologic impact. DESIGN.­: Retrospective analysis of MPNs with sequential development of BCR-ABL1 and JAK2V617F. RESULTS.­: Of 6 cases, 5 had JAK2V617F-positive MPN diagnosed before acquiring BCR-ABL1 years later, and 1 had BCR-ABL1+ chronic myeloid leukemia before JAK2V617F-positive myelofibrosis completely replaced the BCR-ABL1+ clone 1 year after tyrosine kinase inhibitor therapy. Among the former group, treatment for the initial MPN involved hydroxyurea, ruxolitinib, and/or supportive care, and the latency to the development of JAK2V617F ranged from 4 to 13 years (median of 9 years). Four cases showed retention of JAK2V617F, whereas BCR-ABL1 emerged as the major clone, including 2 cases that exhibited parallel increases in JAK2V617F and BCR-ABL1 burdens, with both genomic markers exceeding 50%. Three patients received stem cell transplants and demonstrated sustained engraftment, with the genomic markers below detectable levels. CONCLUSIONS.­: Most MPNs with concomitant JAK2V617F and BCR-ABL1 are actually composite MPNs with a "second hit" residing on a different clone. Rare cases demonstrate a subclone harboring a "double-hit" in a background of a JAK2V617F-positive stem line clone. The probability of a "double-hit" with a BCR-ABL1+ stem line clone is probably reduced by effective tyrosine kinase inhibitor treatment. The treatment often involves combined kinase inhibitors and/or hydroxyurea, but the outcome is unpredictable; hematopoietic stem cell transplantation may be the ultimate therapeutic option for this complicated disease.

Intra-tumoral angiogenesis correlates with immune features and prognosis in glioma.

Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.

Advances in the Diagnosis and Management of Neonatal Sarcomas.

Neonatal sarcomas comprise a heterogeneous group of rare soft tissue neoplasms that present unique diagnostic and therapeutic challenges. Recent advances in molecular profiling have improved diagnostic capabilities and reveal novel therapeutic targets. Clinical trials demonstrate differences in behavior between sarcoma subtypes that allow for better clinical management. Surgical resection has been replaced with a multimodal approach that includes chemotherapy and radiotherapy. Despite these advances, neonates with sarcoma continue to fare worse than histologically similar sarcomas in older children, likely reflecting differences in tumor biology and the complexities of neonatal medicine. This review focuses on recent advances in managing neonatal sarcomas.