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921.
Ebru B Ozkan Altan A Ozcan Hande Taylan Sekeroglu Yurdun Kuyucu Hulya Ozgun Sait Polat 《Indian journal of ophthalmology》2013,61(7):329-333
Purpose:
To investigate the ultrastructural changes of the rabbit retina induced by intravitreal methotrexate injection.Materials and Methods:
Ten New Zealand white rabbits were enucleated bilaterally at different time periods after intravitreal methotrexate injection. One rabbit was used as control group and one rabbit was used as intact group. Histopathological examinations were performed under light and electron microscopy. Early (within first three days after injection) and long-term (one month after serial injections) effects of intravitreal methotrexate on the retina were investigated.Results:
Retinal edema, vacuolization, and disintegration of mitochondria of the retinal cells were observed as early changes. The main long-term effects after serial injections were edema in the photoreceptor, inner nuclear, and ganglionic cell layers. Cellular disorganisation was seen on light microscopy. Electron microscopic examination revealed mitochondrial degeneration and vacuole formation in retinal cells, nuclear degeneration in outer nuclear layer, and membranous whorl formation in photoreceptor and nerve fiber layers.Conclusions
High dose intravitreal methotrexate injection may cause significant ultrastructural changes in the rabbit retina in varying severity. This finding may highlight the potential side effects of methotrexate on human retina in higher doses. 相似文献922.
Aksu S Beyazit Y Haznedaroglu IC Canpinar H Kekilli M Uner A Sayinalp N Büyükaşik Y Goker H Ozcebe OI 《Leukemia & lymphoma》2006,47(5):891-896
Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34+ hematopoietic stem cells. Angiotensin II stimulates the proliferation of bone marrow and umbilical cord blood hematopoietic progenitors. There are preliminary data that local RAS might also be involved in leukemogenesis. ACE hyper-function may lead to the acceleration of negative hematopoietic regulator peptide, AcSDKP, metabolism, which in turn lowers its level in the bone marrow micro-environment, finally removing the anti-proliferative effect of AcSDKP on the hematopoietic cells and blasts. Renin expression could have a role on the leukemia development and angiotensin may act as an autocrine growth factor for acute myeloid leukemia (AML) cells. The aim of this study is to search ACE (CD 143) surface antigen by flow-cytometric analyses on the leukemic blast cells taken from the bone marrow of the patients with AML. Bone marrow aspiration materials and peripheral blood samples were obtained from 11 patients with AML (eight males, three females; aged 46 (range 26-67) years) and six patients with non-malignant hematological disorders (four males, two females; aged 56 (range 22-71) years). ACE (CD 143) surface antigen was shown to be over-expressed in leukemic myeloid blast cells. ACE is positively correlated with bone marrow blast count. Elucidation of the pathological activity of the local RAS-mediated regulation of the leukemogenesis is both pathobiologically and clinically important, since the angiotensin peptides represent a molecular target in the disease management. 相似文献
923.
Choy H Devore RF Hande KR Porter LL Rosenblatt P Yunus F Schlabach L Smith C Shyr Y Johnson DH 《International journal of radiation oncology, biology, physics》2000,47(4):931-937
PURPOSE: We conducted a prospective phase II study to determine the response rate, toxicity, and survival rate of concurrent weekly paclitaxel, carboplatin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC). The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. METHODS AND MATERIALS: Forty-three patients with unresectable stage IIIA and IIIB NSCLC from the Vanderbilt Cancer Center and Affiliate Network (VCCAN) institutions were entered onto the study from June 1996 until May 1997. Weekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplatin (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) were delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). RESULTS: Forty-two patients were evaluable for response and toxicities. Three patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. (66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rates of all 43 patients were 61.6% and 35% respectively, with a median survival time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (26%). There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary toxicities. CONCLUSIONS: Weekly paclitaxel, carboplatin, plus concurrent hyperfractionated RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more toxic chemoradiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/carboplatin/HFX RT in a phase III study. 相似文献
924.
Choy H DeVore RF Hande KR Porter LL Rosenblatt PA Slovis B Laporte K Shyr Y Johnson DH 《Clinical lung cancer》2000,1(Z1):S27-S31
Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel with concurrent thoracic radiation therapy (TRT) to patients with unresectable stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study. Docetaxel was administered as a 1-hour intravenous (I.V.) infusion, repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were escalated in 10 mg/m2 increments in successive cohorts of three new patients, if tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG) toxicity criteria. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). At the first dose level (20 mg/m2/week), one patient developed grade 4 hyperglycemia and accrual was expanded to five patients. At the second level (30 mg/m2/week), two out of six patients developed grade 3 esophagitis. At the third level (40 mg/m2/week), two out of four patients developed grade 3 esophagitis and one patient developed grade 3 pulmonary toxicity. The weekly docetaxel MTD with concurrent radiation therapy (RT) was found to be 30 mg/m2. The DLT was esophagitis and pulmonary toxicity. Other toxicities encountered included skin reaction, nausea and vomiting, as well as diarrhea. Additionally, there were no treatment-related mortalities or late-occurring toxicities. Esophagitis was the principal DLT of concurrent weekly docetaxel and thoracic radiation in the outpatient setting. The MTD of concurrent weekly docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This study is still open to accrual with weekly docetaxel and TRT in locally advanced NSCLC patients. 相似文献
925.
Hande Beklen Esra Yildirim Medi Kori Beste Turanli Kazim Yalcin Arga 《World journal of gastrointestinal oncology》2021,13(7):638-661
Colorectal cancer (CRC) is the most commonly diagnosed fatal cancer in both women and men worldwide. CRC ranked second in mortality and third in incidence in 2020. It is difficult to diagnose CRC at an early stage as there are no clinical symptoms. Despite advances in molecular biology, only a limited number of biomarkers have been translated into routine clinical practice to predict risk, prognosis and response to treatment. In the last decades, systems biology approaches at the omics level have gained importance. Over the years, several biomarkers for CRC have been discovered in terms of disease diagnosis and prognosis. On the other hand, a few drugs are being developed and used in clinics for the treatment of CRC. However, the development of new drugs is very costly and time-consuming as the research and development takes about 10 years and more than $1 billion. Therefore, drug repositioning (DR) could save time and money by establishing new indications for existing drugs. In this review, we aim to provide an overview of biomarkers for the diagnosis and prognosis of CRC from the systems biology perspective and insights into DR approaches for the prevention or treatment of CRC. 相似文献
926.
用(+)-FLEC手性试剂自动柱前衍生高效液相色谱法拆分麻黄碱类药物对映体 总被引:1,自引:0,他引:1
报道了以(+)-FLEC作为手性衍生化试剂,用反相高效液相色谱技术分离麻黄碱类药物对映异构体的方法。dl-麻黄碱、dl-伪麻黄碱、dl-去甲麻黄碱、dl-去甲伪麻黄碱先与(+)-FLEC形成衍生物后,经过一ODSHypersil柱分离,以水和乙腈为流动相梯度洗脱.二极管阵列检测器在266nm检测。该法从样品衍生化到最终报告全部自动完成。上述各对对映体均达到基线分离,分离度R均大于1.5,方法灵敏度高,最低检出限达10pmo1,保留时间和峰面积的上现性较好,RSD分别为1.1/和3.0%。 相似文献
927.
Hollstein M; Bartsch H; Wesch H; Kure EH; Mustonen R; Muhlbauer KR; Spiethoff A; Wegener K; Wiethege T; Muller KM 《Carcinogenesis》1997,18(3):511-516
The p53 gene was examined for point mutations in archived, alpha-
radiation-associated lung and liver cancers. Lung tumors of 50 uranium
miners in Germany were screened by restriction fragment length analysis for
the putative hotspot mutation at codon 249 (Arg-->Met) previously
detected in a significant fraction of miners from the Colorado Plateau,
USA. This mutation has been proposed as a marker of radon exposure. None of
the tumors we examined harbored the hotspot mutation. Five of the 50
tumors, however, did indeed harbor exon 7 mutations, as determined by
subsequent mutation analysis of exon 7. These mutations were dispersed
among various codons and may be attributable to heavy tobacco smoking in
this cohort. In support of this interpretation, we found no mutations in
exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by
injection of Thorotrast, an alpha-emitting radiocontrast agent. We propose
that if the p53 tumor suppressor gene is a target for the carcinogenic
action of alpha-particle radiation, loss of suppressor function may occur
preferentially by mechanisms such as intrachromosomal deletions, rather
than by base substitution mutations.
相似文献
928.
İncekalan Tuğba Kurumoğlu Taktakoğlu Derya Şimdivar Göksu Hande Naz Öztürk İlker 《International ophthalmology》2022,42(8):2501-2509
International Ophthalmology - To investigate vascular density (VD) changes in the superficial (SCP) and deep capillary plexus (DCP), radial peripapillar capillary plexus (RPCP), Foveal avascular... 相似文献
929.
Potential utility of serum neuron-specific enolase levels in small cell carcinoma of the lung 总被引:1,自引:0,他引:1
D H Johnson P J Marangos J T Forbes J D Hainsworth R Van Welch K R Hande F A Greco 《Cancer research》1984,44(11):5409-5414
To assess the value of neuron-specific enolase (NSE) as a possible biomarker of small cell lung cancer, serum levels were determined by radioimmunoassay in 93 newly diagnosed untreated patients and were compared to the NSE levels of 20 healthy adult controls [9.6 +/- 0.7 (S.E.) ng/ml]. Serum NSE was elevated (greater than 20 ng/ml) in 73% of all patients including 23 of 39 (59%) with limited-stage disease and 45 of 54 (83%) with extensive-stage disease. The mean serum NSE was significantly higher in extensive-stage disease (94.5 +/- 13.8 ng/ml) compared to the mean value for limited-stage disease (33.7 +/- 4.7 ng/ml) (p less than 0.001). NSE was elevated in all patients with three or more sites of metastatic disease. Serial NSE determinations were obtained on 57 small cell lung cancer patients. NSE levels fell in 40 of 50 (80%) of patients responding to treatment, increased in 5 of 7 (71%) of patients with progressive disease, and increased in 30 of 35 (86%) of patients who relapsed. A persistent rise in serum NSE occurred as many as 12 weeks before the clinical recognition of relapse in 15 of 23 (65%) of patients for whom adequate serial NSE data were available. These findings indicate that serum NSE may be a useful marker for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer. 相似文献
930.