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101.
Focusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mechanisms of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [3H-6] FUra (4 h exposure, 100 M) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT-8/FU4hR cells as compared to parental HCT-8 cells.Given the lack of cross resistance between the two schedulesin vitro, a pilot trial was done on patients with colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirmng a certain degree of activity of CI FUra in patients clinically resistant to bolus FUra.Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with FUra continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect).Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial responses were obtained among these 33 patients (RR=48%, 95% confidence limis, 31–66%). After a median follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3% and 6% respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.In conclusion, this experimental and clinical project has generated a novel regimen of schedule oriented biochemical modulation that is twice as active and half as toxic compared to bolus FU+LV given with either the daily x 5 or the weekly schedule. This high clinical activity is very encouraging, especially considering that 1) consecutive patients were entered, 2) the responses were independently reviewed, 3) the progression free survival and survival were much longer than those actually reported for this disease, 4) the toxicity of the program, in particular the bolus regimen, was relatively low allowing further intensification. 相似文献
102.
The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients
with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were
dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin-2 (IL-2) production,
the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated
that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic
activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4+) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented
in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions
of the regional lymph node in patients with head and neck cancer. 相似文献
103.
An efficient impedance method was developed for rapid evaluation of cosmetic preservatives. The method used decimal reduction time or D-value to assess preservative efficacies. The D-value, which was calculated from the plot of Log CFU ml–1 versus time by linear regression analysis, could be obtained within 48 h. Thus, the time required for the challenge test was reduced from 4–8 weeks with the standard procedures (eg US Pharmacopeia), to 2 days with the current method. A calibration curve (r=-0.95) was established by plotting the Log CFU ml–1 versus capacitance detection time (DT) of 108 samples. With the calibration, CFU can be estimated directly from the impedance test without plating. Two commercial biocides and several other chemicals were evaluated in a shampoo by the impedance procedure againstPseudomonas aeruginosa. The D-values obtained from the impedance test were not significantly different from those produced by the conventional plate count method. The technique was found to be particularly useful when screening a large number of compounds to find novel preservatives and synergistic preservative combinations. 相似文献
104.
朱明华 《中国组织化学与细胞化学杂志》1995,(1)
应用免疫组化方法,对32例乳腺癌组织中肿瘤抑制基因p53蛋白的表达和雌激素受体的状态分别进行了检测。结果32例中p53蛋白阳性18例,阳性率56.3%,18例伴有同侧腋下淋巴结转移者阳性13例(72.2%)3而14例无转移者阳性5例(35.7%)二组阳性率差异显著(PMO.05)。32例中雌激素受体阳性17例,18例伴转移者阳性8例(44.4%);14例无转移者阳性9例(64.3%)。结果表明,p53蛋白的异常表达与乳腺癌的浸润转移有关,结合雌激素受体的检查,可作为临床预后判断一个有价值的标志。 相似文献
105.
以人胃癌细胞BGC-823为模型,研究了毛喉萜(forskolin)对胃癌细胞中蛋白激酶C活性及其亚类基因表达的作用,同时也观察了毛喉萜对癌基因c-jun及抑癌基因p53表达的影响.结果表明,2×10~(-5)mol/L毛喉萜处理BGC-823细胞72h,细胞质、膜和细胞核PKC活性下降,PKC亚类β,γ基因表达被抑制,癌基因c-jun的表达也明显降低,而抑癌基因p53表达升高,上述变化可能是毛喉萜抑制胃癌细胞增殖等生理效应的重要分子事件。 相似文献
106.
107.
Study of trace elements in blood of cancer patients by proton-induced X-ray emission (PIXE) analysis
Durosinmi M. A. Ojo J. O. Oluwole A. F. Akanle O. A. Spyrou N. M. 《Biological trace element research》1994,(1):351-355
Proton-induced X-ray emission (PIXE) analysis was employed to determine the concentrations of six elements in the plasma and
erythrocytes of 18 cancer subjects (15 males and 3 females) with neoplastic disorders and in 70 controls (35 males and 35
females). It was found that the concentrations of Br, K, and Zn were significantly elevated in the erythrocytes of the cancer
subjects compared to the controls, whereas the concentration of Fe was significantly depressed, but with no difference observed
in the concentration of Ca. In the plasma, the concentrations of Br, Cu, Ca, and K were significantly elevated, whereas the
concentrations of Fe and Zn were found to be significantly depressed compared to the controls. 相似文献
108.
Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer 总被引:1,自引:0,他引:1
Tsunehiro Oyama Koji Matsuno Toshihiro Kawamoto Tetsuya Mitsudomi Takayuki Shirakusa Yasushi Kodama 《Biological trace element research》1994,42(2):115-127
We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were
seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with
no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p<0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly
clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen
that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator
characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a
paragraph of methods.The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the
high-risk patients for LC. 相似文献
109.
An important new artefact in cytopathology is described. the initial observation of the artefact followed contamination of a breast fine needle aspiration (FNA) sample by ultrasound gel which was used to localize the lesion. the changes proved reproducible ex vivo. the changes varied depending on the conditions and degree of contamination, and ranged from cell swelling to leakage of nuclear chromatin and cell lysis. This artefact is discussed in the context of other major sources of cytology artefact. Pathologists and radiologists should beware of the detrimental effects of ultrasound gel on cytology specimens. 相似文献
110.
Two methods of storing fine needle aspirates were compared in 14 patients with breast cancer. the methods of storage were: (1) as a Cytospin slide prepared immediately from the aspirated material and stored at −80°C; (2) as a suspension of cells in tissue culture medium, stored at −80°C. the effect of storage on the cells was assessed by means of an oestrogen receptor immunocytochemical assay (ER-ICA). an ER positivity of 100% was obtained by ER-ICA staining of cells after storage method 1, whilst all of the specimens stored by method 2 were ER-negative. the data demonstrate that cells stored in tissue culture medium at −80°C are not suitable for ER measurement. the storage method of choice for specimens intended for ERICA is as a Cytospin slide. the ER status of cells deposited on Cytospin slides prepared immediately and stored at −80°C for 2 years could be demonstrated despite the delay in processing the specimen. 相似文献