Summary Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N=114), myeloid (N=49) and solid tumor (N=856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor.
Aim: The present study aimed to identify the changes on the bladder mucosa in rats after intravesical infusion of Super-oxidized solution (SOS) (Mycrodacyn60® Mexico). Design: Eighteen Wistar Albino rats weighing 250-300 g were randomly categorized into three groups. Rats in Group 1 were infused with a single dose of 1.5 ml of 0.9% saline solution (SS) whereas those in group 2 were administered a single dose of 1.5 ml pH neutral SOS. Control rats in Group 3 did not undergo any procedure. Results: The absence of bacteria was verified before and after the administration of the solution, performing urine cultures and amplifying the 16S rRNA fragment by PCR and histopathological examinations for each bladder. The absence of bacterial DNA in the uroepithelium was demonstrated, histopathological examination revealed, that irrigation with SOS, in histological observation, no structural alterations were identified in the urothelial mucosa. Limitations: It was not possible to analyze the effect of SOS absorption indamage to the uroepithelium secondary to traumatic infection or injury. The effect of irrigation at different times and volumes with SOS was also not analyzed. Originality: It is known that SOS is useful as disinfectant in skin and serosa bacterial infections, lacking toxicity and it is effective against Escherichia coli. The use of superoxide solutions in cavities such as the bladder, has not been investigated yet. Conclusion: The pH-neutral SOS infused transurethral in the bladder of rats has no adverse effects on the uroepithelium, which was supported by histopathological evidence.
Background:Nonmycosis fungoides/Sézary syndrome (non-MF/SS) primary cutaneous lymphomas (PCL) are currently categorized under the 2005-World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for PCL. These differ in behavior from secondary cutaneous lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid neoplasms.Aims:This study aims to report the first series of non-MF/SS PCL, SCL, and POL in a Mexican cohort, examine the applicability of current classification systems and compare our findings with those from foreign cohorts.Materials and Methods:Eighteen non-MF/SS PCL, four SCL, and two POL with available tissue for morphology and immunophenotypic assessment were reclassified according to the 2005-WHO/EORTC and 2016-WHO classifications.Results:Non-MF/SS PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative disorders predominated, followed by Epstein–Barr virus-induced lymphomas, and peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell lymphomas (BCL) were primarily of follicle center cell origin followed by postgerminal lymphomas of the diffuse large BCL variety.Conclusions:Most non-MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases. The relative frequencies in our cohort hold closer similarities to Asian registries than from those of Europe/USA, supporting the concept of individual and/or racial susceptibility, and the notion of geographical variances in the rate of lymphomas. In particular, such disparity may arise from viral-induced lymphomas which might show partial geographical restriction.
5132 There is a well- recognized correlation between cancer and aberrant hemostasis. Venous thromboembolism (VTE) in individuals with solid epithelial tumors has been associated with a poor prognosis, with more than three-fold higher risk of early death as compared to cancer patients without thrombosis. The expression of tissue factor (TF), a cell-surface membrane glycoprotein that triggers the activation of coagulation by cancer cells, is one of the main underlying mechanisms linking thrombosis and aggressive tumor behavior. TF is expressed in a variety of solid tumors in association with genetic events affecting oncogenes and tumor suppressor genes. However, the mechanisms of thrombosis in individuals with hematological malignancies may differ from those with solid tumors. We have previously shown that despite the high rate of thrombosis in multiple myeloma, malignant plasma cells only rarely express TF. We sought to determine TF gene (F3) and protein expression in hematological neoplasias. F3 expression profiling was studied on a variety of cell lines established from lymphoid and myeloid neoplasias available at Glaxo Smith Kline (GSK) Cancer Cell Line Genomic Profiling Dataset (https://array.nci.nih.gov/caarray/project/woost-00041). Interestingly, F3 expression was absent in all lymphoid neoplasias studied, in sharp contrast to acute myeloid leukemias (AML) and solid tumors, of which 30 and 90% expressed F3, respectively. Immunohistochemistry (IHC) confirmed the absence of TF protein expression in all indolent and high-grade B-cell lymphomas (99 patients, including germinal center and activated B-cell phenotype diffuse large B-cell lymphomas) and in all T-cell lymphomas/leukemias (20 patients) studied. IHC for TF was also negative in AML (11 patients) but positive in representative solid tumors (breast, pancreas, prostate), except for renal cell carcinoma which has been previously shown to lack TF. We propose that the pathogenesis of VTE associated with hematological neoplasias differs from that of solid tumors. Though TF from non-neoplastic cell sources may still be important for the prothrombotic state often seen in these patients, we show there is no evidence for a role of tumor-derived TF in the development of DVT, nor in neoplastic behavior. Thus, treatments directed against TF may not impact on prognosis in lymphoid, and non TF-expressing myeloid neoplasias. Disclosures: No relevant conflicts of interest to declare.
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