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41.
Saleem Farooq Fahad A. Alharthi Ali Alsalme Aashiq Hussain Bashir A. Dar Abid Hamid S. Koul 《RSC advances》2020,10(69):42221
A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by “HPA-Montmorillonite-KSF” as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz. colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC50 values. Of the synthesized analogs, 16a showed the best activity with IC50 of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode.The general method for the preparation of DHPM analogs; cytotoxic activity and binding mode of the most active derivative against PI3Kγ and CDK2 targets. 相似文献
42.
D. P. Fyhrie C. Milgrom S. J. Hoshaw A. Simkin S. Dar D. Drumb D. B. Burr 《Annals of biomedical engineering》1998,26(4):660-665
Muscular fatigue in the training athlete or military recruit has been hypothesized to cause increased bone strain that may contribute to the development of a stress fracture. Under normal circumstances, muscles exert a protective effect by contracting to reduce bending strains on cortical bone surfaces. In vivo strain studies in dogs show that muscle fatigue following strenuous exercise elevates bone strain and changes strain distribution. However, a similar experiment has yet to be performed in humans. The purpose of this work was to test the hypothesis in humans that strenuous fatiguing exercise causes an elevation in bone strain. It was also hypothesized that this elevation is greater in younger people than in older people due to the decline in muscle strength and endurance that normally occurs with age. To test these hypotheses, strain in the tibiae of seven human volunteers was measured during walking before and after a period of fatiguing exercise. Neither hypothesis was sustained. Post-hoc analysis of the strain data suggests that strain rate increases after fatigue with a greater increase in younger as opposed to older persons. Although not conclusive, this suggests that it is strain rate, rather than strain magnitude, that may be causal for stress fracture. © 1998 Biomedical Engineering Society.
PAC98: 8745Dr, 8745Bp, 0180+b 相似文献
43.
Genotypes of CYP1A1, SULT1A1 and SULT1A2 and risk of squamous cell carcinoma of esophagus: outcome of a case–control study from Kashmir,India 下载免费PDF全文
Studies on associations of various polymorphism in xenobiotic metabolizing genes with different cancers including esophageal squamous cell carcinoma (ESCC) are mixed and inconclusive. To evaluate the association of CYP1A1*4, SULT1A1*2 and SULT1A2*2 genotypes with ESCC risk and their modifying effects on different risk factors of ESCC, we conducted a case–control study in Kashmir, India, an area with relative high incidence of ESCC. We recruited 404 histopathologically confirmed ESCC cases, and equal number of controls, individually matched for sex, age and district of residence to respective case. Information was obtained on various dietary, lifestyle and environmental factors in face‐to‐face interviews, using a structured questionnaire, from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and direct sequencing. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A higher risk was observed in the subjects who harbored variant genotype of CYP1A1*4 (OR = 2.06; 95% CI: 1.28–3.32); and the risk was further enhanced in ever smokers (OR = 3.47; 95% CI: 1.62–7.42), adobe dwellers (OR = 6.71; 95% CI: 3.02–14.89), and biomass fuel users (OR = 5.11; 95% CI: 1.34–19.50). We did not find any significant differences in the polymorphic variants of SULT1A1*2 and SULT1A2*2 between cases and controls. The study indicates that, unlike SULT1A1*2 and SULT1A2*2, the polymorphism of CYP1A1*4 is associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate our findings. 相似文献
44.
Mohammad A. Bhat Zahoor A. Naikoo Tufail A. Dass Riyaz A. Lone Abdul M. Dar 《Saudi Journal Of Gastroenterology》2010,16(3):168-173
Background/Aim:
Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. This study aims to investigate the feasibility and accuracy of detection of SLN using methylene blue dye in patients with carcinoma of the esophagus and assess its potential role in determining the rational extent of lymphadenectomy in esophageal cancer surgery.Materials and Methods:
Thirty-two patients of esophageal cancer diagnosed on endoscopic biopsy were enrolled in this prospective study. After laparotomy, patent methylene blue was injected into the subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes within a period of 5 min. Standard radical esophagogastrectomy with lymphadenectomy was performed in all the patients. All the resected nodes were examined postoperatively by routine hematoxylin and eosin stain for elucidating the presence of metastasis, and the negative SLNs were examined further with cytokeratin immunohistochemical staining.Results:
SLNs were detected in 26 (81.25%) patients out of 32 patients who were studied. The number of SLNs ranged from 1 to 4 with a mean value of 1.7 per case. The SLNs of esophageal cancer were only found in N1 area in 21 (80.77%) cases, and in N2 or N3 area in only 19.33%. The overall accuracy of the procedure was 75% in predicting nodal metastasis. SLN had a sensitivity of 85.71% in mid esophageal tumors and 93.33% in lower esophageal tumors. The SLN biopsy had sensitivity of 87.5% in the case of squamous cell carcinoma and 92.86% in the cases of adenocarcinoma of the esophagus. The accuracy of the procedure for squamous cell carcinoma and adenocarcinoma was 60% and 76.47%, respectively.Conclusion:
SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with esophageal cancer and may indicate rational extent of lymphadenectomy in these patients. SLN mapping provides “right nodes” to the pathologists for detailed analysis and appropriate staging, thereby helping in individualizing the multi-modal treatment for esophageal cancer. 相似文献45.
Sanz DE 《Physics in medicine and biology》2002,47(17):3073-3085
A mathematical approach is developed to evaluate the accuracy of the equivalent field method using basic clinical photon beam data. This paper presents an analytical calculation of dose errors arising when field equivalencies, calculated at a certain reference depth, are translated to other depths. The phantom scatter summation is expressed as a Riemann-Stieltjes integral and two categories of irregular fields are introduced: uniform and multiform. It is shown that multiform fields produce errors whose magnitudes are nearly twice those corresponding to uniform fields in extreme situations. For uniform field shapes, the maximum, local, relative dose errors, when the equivalencies are calculated at 10 cm depth on the central axis and translated to a depth of 30 cm, are 3.8% and 8.8% for 6 MV and cobalt-60 photon beams, respectively. In terms of maximum dose those errors are within 1-2%. This supports the conclusion that the equivalencies between rectangular fields, which are examples of uniform fields, are applicable to dose ratio functions irrespective of beam energy. However, the magnitude of such errors could be of importance when assessing the exit dose for in vivo monitoring. This work provides a better understanding of the influence of the irregular field shapes on the accuracy of the equivalent field method. 相似文献
46.
Early Involvement of Death-Associated Protein Kinase Promoter Hypermethylation in the Carcinogenesis of Barrett's Esophageal Adenocarcinoma and Its Association with Clinical Progression 总被引:8,自引:3,他引:8 下载免费PDF全文
47.
Michael J Robertson John M Kirkwood Theodore F Logan Kevin M Koch Steven Kathman Lyndon C Kirby William N Bell Linda M Thurmond Jill Weisenbach Mohammed M Dar 《Clinical cancer research》2008,14(11):3462-3469
PURPOSE: Interleukin-18 (IL-18) is an immunostimulatory cytokine with antitumor activity in preclinical models. A phase I study of recombinant human IL-18 (rhIL-18) was done to determine the toxicity, pharmacokinetics, and biological activities of rhIL-18 administered at different doses in two different schedules to patients with advanced cancer. EXPERIMENTAL DESIGN: Cohorts of three to four patients were given escalating doses of rhIL-18 as a 2-h i.v. infusion either on 5 consecutive days repeated every 28 days (group A) or once a week (group B) for up to 6 months. Toxicities were graded using standard criteria. Blood samples were obtained for safety, pharmacokinetic, and pharmacodynamic measurements. RESULTS: Nineteen patients (10 melanoma and 9 renal cell cancer) were given rhIL-18 in doses of 100, 500, or 1,000 microg/kg (group A) or 100, 1,000, or 2,000 microg/kg (group B). Common side effects included chills, fever, headache, fatigue, and nausea. Common laboratory abnormalities included transient, asymptomatic grade 1 to 3 lymphopenia, grade 1 to 4 hyperglycemia, grade 1 to 2 anemia, neutropenia, hypoalbuminemia, liver enzyme elevations, and serum creatinine elevations. No dose-limiting toxicities were observed. Biological effects of rhIL-18 included transient lymphopenia and increased expression of activation antigens on lymphocytes. Increases in serum concentrations of IFN-gamma, granulocyte macrophage colony-stimulating factor, and IL-18-binding protein were observed following dosing. CONCLUSIONS: rhIL-18 can be given in biologically active doses by either weekly infusions or daily infusions for 5 days repeated every 28 days to patients with advanced cancer. Toxicity was generally mild to moderate, and a maximum tolerated dose of rhIL-18 by either schedule was not determined. 相似文献
48.
Laura M. Vargas-Roig F. Darío Cuello-Carrión Nicolás Fernández-Escobar Pedro Daguerre Marcela Leuzzi Jorge Ibarra Francisco E. Gago Silvina B. Nadin Daniel R. Ciocca 《Molecular oncology》2008,2(1):102-111
We have analyzed the predictive/prognostic value of Bcl‐2 protein in breast cancer patients treated with neoadjuvant chemotherapy. One hundred and ten patients were submitted to two different chemotherapeutic regimens: a) 5‐fluorouracil, adriamycin or epirubicin, and cyclophosphamide (FAC/FEC) during 2–6 cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery (n=40) and b) doxorubicin (D) 75mg/m2 or epirubicin (E) 120mg/m2 during 4 cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) after surgery (n=70). Bcl‐2 expression, evaluated by immunohistochemistry, did not change significantly after chemotherapy and was not related to clinical/pathological response. In FAC/FEC group, Bcl‐2 positive expression after chemotherapy correlated with better disease free survival (DFS) and overall survival (OS) (P=0.008 and P=0.001). In D/E group, Bcl‐2 also correlated with better DFS and OS (P=0.03 and P=0.054) in the post‐chemotherapy biopsies. An unusual nuclear localization of Bax was observed in some biopsies, but this localization did not correlate with the tumor response or outcome of the patients. We found that a high Bcl‐2 expression had no predictive value but had prognostic value in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy. 相似文献
49.
PURPOSE: To report a patient in whom the finding of hemiretinal vein occlusion led to the diagnosis of membranous glomerulonephritis. DESIGN: Interventional case report. METHODS: A 44-year-old tennis instructor presented with a 1-week history of blurred vision in the left eye. Examination of the left eye demonstrated a best-corrected visual acuity of 20/40 and an inferior hemiretinal vein occlusion. RESULTS: Blood pressure was normal, and the patient was referred for a medical examination, which revealed membranous glomerulonephritis. The patient was treated with oral prednisone and cyclosporine. Four months after presentation, the left eye demonstrated resolution of the vascular abnormalities and had a best-corrected visual acuity of 20/20. CONCLUSION: Retinal vein occlusion may be associated with membranous glomerulonephritis. Treatment of the systemic disease may be associated with regression of the retinal vascular abnormalities. 相似文献
50.