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[en] A radiochemical ligand binding assay for methotrexate is provided. A binder factor comprising a partially purified dihydrofolic acid reductase preparation is employed. The binder factor is conveniently prepared by homogenizing a factor containing animal organ such as liver, and extracting with isotonic saline and ammonium sulfate. A binder cofactor, NADPH2, is also employed in the binding reaction. The procedure contemplates both direct and sequential assay techniques, and it is not interfered with by vast excesses of many natural folate derivatives. 12 claims, 6 drawing figures
[en] The methods of treatment of squamous carcinoma of the oesophagus in a hospital are briefly discussed: the administration of Methotrexate, pre- and post-operative irradiation and surgery. The results of different combinations of the three treatments are mentioned
[en] The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% (±9%) and the overall 3-year survival 78% (±9%). (author)
[en] Highlights: • LncRNA LUCAT1 and ABCB1 protein are both up-regulated in osteosarcoma methotrexate-resistant cells. • LncRNA LUCAT1 knockdown suppress the expression levels drug resistance related genes, proliferation, invasion and tumor growth of osteosarcoma cells in vitro and vivo. • Bioinformatics predictive tools and luciferase assay reveal the LUCAT1/miR-200c/ABCB1 pathway. • Rescue experiments confirm the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma methotrexate resistance. Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate (MTX) resistant phenotype and discover the potential regulatory mechanism. Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX, HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein expression levels were both up-regulated when induced by different concentration of methotrexate. In vitro and vivo, LUCAT1 knockdown decreased the expression levels drug resistance related genes (MDR1, MRP5, LRP1), proliferation, invasion and tumor growth of osteosarcoma cells. Bioinformatics tools and luciferase assay reveled that miR-200c both targeted the 3′-UTR of LUCAT1 and ABCB1 mRNA, suggesting the modulation of LUCAT1 on ABCB1 through sponging miR-200c. Rescue experiments confirmed the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma proliferation, invasion and methotrexate resistance. Overall, results indicate the vital role of LUCAT1 in the methotrexate resistance regulation through miR-200c/ABCB1 pathway, providing a novel insight and treatment strategy for osteosarcoma drug resistance.
[en] The advantages of laparoscopic surgery used in the treatment of ectopic pregnancy is wellknown; however, the efficacy of uterine manipulators remains unknown. In this study, we aimed to investigate the efficacy of uterine manipulators in the laparoscopic treatment of ectopic pregnancy. Methods: Overall, 118 patients who underwent laparoscopy due to ectopic pregnancy in Department of Obstetrics and Gynaecology at Tepecik Education and Research Hospital between January 2010 and January 2018 and who met the inclusion criteria were included in the study. Groups of patients undergoing surgery with or without the use of a uterine manipulator were compared in terms of demographic data, operative and postoperative results. Results: No difference was noted between the groups in terms of age, parity, body mass index, smoking, side of ectopic pregnancy mass, previous operations and pregnancy type. However, the size of ectopic pregnancy mass measured by ultrasonography was significantly larger (p = 0.006) and the operation time was significantly shorter (p<0.001) in the group where uterine manipulators were not used than in the uterine manipulator group. Conclusion: We concluded that not using a uterine manipulator in laparoscopic procedures for ectopic pregnancy did not increase operative complications and that operation time was higher in procedures using uterine manipulators. (author)
[en] Highlights: • Tannin and 3-Aminopropyltriethoxysilane (APTES) functionalized magnetic nanoparticles (Ta-A-MNP (was successfully synthesized. • Loading of methotrexate (MTX) drug on Ta-A-MNP was investigated. • Proper distribution of tannin and APTES on the surface of Fe3O4 were observed. • Maximum adsorption capacity of 55.55 mg/g was achieved. • Drug adsorption was spontaneous and endothermic, followed pseudo second order kinetic model.
[en] Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (≥1 g/m2) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose (<3 g/m2 vs.≥3 g/m2), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose (<40 Gy vs. ≥40 Gy) was assessed in 70 irradiated complete responders. Results: No difference in overall survival (OS) was detected between mono-CHT and combination CHT (p=0.38). MTX ≥3 g/m2 (p=0.04), thiotepa (p=0.03), and intrathecal CHT (p=0.03) improved the OS, and nitrosoureas (p 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX ≥3 g/m2, only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of ≥40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX ≥3 g/m2 seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders
[en] Highlights: • LPAR2 and LPAR5 expressions were elevated by long-term anticancer drug treatment in HT1080 cells. • Highly invasion HT1080-M6 cells were generated from HT1080 cells using Matrigel-coated filters. • HT1080-M6 cell invasion was shown to be 4.5 times higher than that of HT1080 cells. • The cell motile and invasive activities of HT1080-M6 cells were reduced by LPA2 inhibition. • LPA signaling via LPA2 is a potent target for the regulation of tumor progression in HT1080 cells. Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) regulate a variety of malignant properties in cancer cells. In the present study, we investigated the roles of LPA receptors in the promotion of cellular functions during tumor progression in fibrosarcoma cells. To obtain long-term anticancer drug treated cells, human fibrosarcoma HT1080 cells were treated with methotrexate (MTX) and cisplatin (CDDP) for 6 months. LPAR2 and LPAR5 expressions were significantly higher in MTX-treated (HT-MTX) cells than in HT1080 cells. The cell motile and invasive activities of HT-MTX cells were significantly elevated compared with HT1080 cells. Although LPAR5 expression was increased in MTX and CDDP treated (HT-M-C) cells, no change of LPAR2 expression was observed. The cell motile and invasive activities of HT-M-C cells were lower than those of HT1080 cells. Moreover, to evaluate whether LPA receptors promote cell invasive activity, highly invasion (HT1080-M6) cells were established from HT1080 cells. The cell invasive activity of HT1080-M6 cells was approximately 4.5 times higher than HT1080 cell invasion. LPAR2 expression was markedly elevated in HT1080-M6 cells compared with HT1080 cells. The high cell invasion activity of HT1080-M6 cells was significantly suppressed by an antagonist of LPA2, H2L5186303. These results suggest that LPA2 acts as a key regulator of malignant properties in HT1080 cells.
[en] Background: SEC is an undifferentiated tumour used in tumour studies. MTX is an antimetabolite used in treatment of cancer, autoimmune diseases and induction of abortion. VPA is used as anticonvulsant and is under investigation for treatment of cancer. The aim of this work was to compare between the effect of each of MTX and VPA on solid Ehrlich tumour in mice. Methods: Forty albino mice were divided into 4 equal groups: control untreated group, SEC group, SEC + MTX group, and SEC + VPA group. Tumour volume, tissue CAT, tissue GR, tissue MDA, tissue cholesterol and tissue TNF-α were determined. A part of the tumour was examined for histopathological and immunohistochemical study. Results: MTX alone or VPA alone induced a significant increase in tissue CAT and GR with a significant decrease in the tumour volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with a significant increase in p53 expression compared to SEC group. This effect was more significant in MTX treated group compared to VPA treated group. Conclusion: MTX has more antitumour effect than VPA against SEC