Massive portal vein tumor thrombus from colorectal cancer without any metastatic nodules in the liver parenchyma

Metastatic lesions in the liver derived from colorectal cancer rarely invade the portal vein macroscopically. Portal vein tumor thrombus is commonly associated with hepatocellular carcinoma. Colorectal liver metastases are usually accompanied by microscopic tumor invasion into the intrahepatic portal vein, and the incidence of macroscopic tumor thrombus in the trunk of the portal vein is rare. Here, we provide unique appearance of metastatic colorectal cancer. To the best of our knowledge, macroscopically, the right portal vein filled with the tumor thrombus without any tumor in liver parenchyma has been quite rare

Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells

Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. This report first describes the effectiveness of a novel HSP90 inhibitor NVP-AUY922 to adult T-cell leukemia-lymphoma (ATL) cells

Induction of apoptosis by HBI-8000 in adult T-cell leukemia/lymphoma is associated with activation of Bim and NLRP3

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell lymphotropic virus 1. Treatment options for acute ATL patients include chemotherapy, stem cell transplantation, and recently the anti-chemokine (C-C motif) receptor 4 antibody, although most patients still have a poor prognosis and there is a clear need for additional options. HBI-8000 is a novel oral histone deacetylase inhibitor with proven efficacy for treatment of T-cell lymphomas that recently received approval in China. In the present study, we evaluated the effects of HBI-8000 on ATL-derived cell lines and primary cells obtained from Japanese ATL patients. In most cases HBI-8000 induced apoptosis in both primary ATL cells and cell lines. In addition, findings obtained with DNA microarray suggested Bim activation and, interestingly, the contribution of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome pathway in HBI-8000-induced ATL cell death. Further investigations using siRNAs confirmed that Bim contributes to HBI-8000-induced apoptosis. Our results provide a rationale for a clinical investigation of the efficacy of HBI-8000 in patients with ATL. Although the role of NLRP3 inflammasome activation in ATL cell death remains to be verified, HBI-8000 may be part of a novel therapeutic strategy for cancer based on the NLRP3 pathway

Successful Surgical Treatment of a Spontaneous Rupture of the Esophagus Diagnosed Two Days after Onset

Esophageal perforation is a relatively uncommon disease with a high rate of mortality and morbidity. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40–60%. Primary repair is generally considered the gold standard for patients who present within the first 24 h following perforation of the esophagus. In this paper, we present a case of successful surgical treatment of spontaneous rupture of the esophagus that was diagnosed 2 days after onset. The patient was a 42-year-old man admitted to internal medicine with a diagnosis of pleuritis and complaining of chest and back pain. The next day, computed tomography revealed left-sided pleural effusion and mediastinal emphysema. An esophagogram revealed extravasation of the contrast medium from the lower left esophagus to the mediastinal cavity. These results confirmed a rupture of the esophagus, and an emergency left thoracotomy was performed. The perforation was repaired with a single-layered closure and was covered with elevated great omentum obtained by laparotomy. The patient was discharged 23 days after the first surgery. In conclusion, primary repair surgery must be selected as the best treatment beyond 24 h if the patient's general state was stable and there was no evidence of clinical sepsis

Serum Cytokines Usefulness for Understanding the Pathology in Allergic Bronchopulmonary Aspergillosis and Chronic Pulmonary Aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are important fungal infections caused by Aspergillus species. An overlap of ABPA and CPA has been reported; therefore, it is critical to determine whether the main pathology is ABPA or CPA and whether antifungals are required. In this study, we investigated whether the serum cytokine profile is useful for understanding the pathology and for differentiating between these diseases. We compared the various serum cytokine levels among healthy subjects and patients diagnosed with asthma, ABPA, or CPA at Nagasaki University Hospital between January 2003 and December 2018. In total, 14 healthy subjects, 19 patients with asthma, 11 with ABPA, and 10 with CPA were enrolled. Interleukin (IL) -5 levels were significantly higher in patients with ABPA than in those with CPA, and IL-33 and tumor necrosis factor (TNF) levels were significantly higher in patients with CPA than in those with asthma (p < 0.05, Dunn’s multiple comparison test). The sensitivity and specificity of the IL-10/IL-5 ratio (cutoff index 2.47) for diagnosing CPA were 70% and 100%, respectively. The serum cytokine profile is useful in understanding the pathology of ABPA and CPA, and the IL-10/IL-5 ratio may be a novel supplemental biomarker for indicating the pathology of CPA

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements