Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-γ (IFN-γ) and tumor necrosis factor- (TNF-), which play a role in GVHD pathophysiology. We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 expression after stimulation correlated with reduced cytoplasmic IFN-γ and TNF- production in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.
Gastric cancer is a leading cause of cancer-related deaths worldwide and is associated with an overall 5-year survival rate of less than 20%. The most common histologic subtype of gastric cancer is adenocarcinoma. Imaging techniques for evaluating gastric adenocarcinoma include endoscopic US, fluoroscopic upper gastrointestinal imaging, CT, PET/CT, and MRI. Hydrodynamic multiphasic contrast material-enhanced CT is the imaging modality of choice for preoperative clinical staging of regional, nodal, and metastatic involvement. Radiologic manifestations of gastric adenocarcinoma at double-contrast upper gastrointestinal imaging and CT include polyps, ulceration, indistensibility, wall thickening, and abnormal enhancement. There are multiple pathways of disease spread. These pathways include lymphatic dissemination; subperitoneal dissemination along the perigastric ligaments, mesentery, or omentum; direct invasion into adjacent organs; transperitoneal seeding; and hematogenous dissemination. The spread of disease is affected by the location of the tumor in the stomach, and the ligamentous and lymphatic anatomy. Key imaging features that affect clinical staging with use of the TNM classification system for gastric adenocarcinoma, as described in the eighth edition of the AJCC Cancer Staging Manual, are briefly discussed. Accurate radiologic assessment of gastric adenocarcinoma requires identification of perigastric ligament infiltration, regional and metastatic nodal disease, and direct and metastatic organ involvement, all of which directly affect tumor staging, treatment, and prognosis. ©
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