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191.
192.
Pelvic insufficiency fractures in postmenopausal woman with advanced cervical cancer treated by radiotherapy. 总被引:3,自引:0,他引:3
Ichiro Ogino Naoyuki Okamoto Yoshimi Ono Tatsuo Kitamura Hiroki Nakayama 《Radiotherapy and oncology》2003,68(1):61-67
PURPOSE: To assess the predisposing factors and clinical characteristics of pelvic insufficiency fractures (PIF) in postmenopausal women with pelvic irradiation. MATERIAL AND METHODS: A total 335 postmenopausal patients with cervical cancer of the intact uterus treated with radiation therapy between 1983 and 1998 were reviewed. Total external dose was delivered between 45 and 50.4 Gy with parallel opposed anteroposterior portals. Total brachytherapy dose at point A was delivered between 10 and 36 Gy. PIF were diagnosed by bone scintigraphy and confirmed by computed tomography. The cumulative incidence of symptomatic PIF was estimated by actuarial methods. Potential risk factors (age, weight, type II diabetes, delivery, menopause, total external dose, total brachytherapy dose) were assessed. RESULTS: Fifty-seven (17.0%) of 335 patients were diagnosed as having PIF. Forty-seven patients were symptomatic and ten were asymptomatic. Parameters carrying a significant association with PIF were body weight 49 kg or below (P=0.044) in stepwise logistic regression analysis. The cumulative incidence of symptomatic PIF at 5 years was 17.9% calculated by the Kaplan-Meier method. A body weight of 49 kg or below and more than three deliveries were identified as having a significant effect on symptomatic PIF in univariate analysis (P=0.021, P=0.003, log-rank test) and Cox life table regression analysis (P=0.038, P=0.013). Five patients required narcotic agents and eight patients required hospital admission. CONCLUSIONS: We should consider reducing the dose contribution to the sacrum and sacroilac joints, without underdosing the tumor, especially in postmenopausal women with many deliveries or low body weight. 相似文献
193.
194.
Higashikawa K Furuki K Takada S Okamoto S Ukai H Yuasa T Ikeda M 《Industrial health》2000,38(2):181-188
The present study was initiated to examine the quantitative relationship between blood lead (Pb-B) and urinary delta-aminolevulinic acid (ALA-U) among Pb-exposed workers, and to find a threshold Pb-B level to induce an increase in ALA-U. For this purpose, pairs of venous blood and spot urine samples were collected from 8,274 men and 5,856 women (14,130 workers in total) who were occupationally exposed to inorganic lead. The blood and urine samples were analyzed for Pb-B and ALA-U by atomic absorption spectrometry and colorimetry, respectively, and the correlation between pairs of measures were subjected to statistical analysis. The assumption of the 3rd degree regression for correlation gave a substantially greater correlation coefficient (0.645 for men and 0.619 for women) than 1st or 2nd degree regression, whereas only very small improvement in the coefficient was achieved with 4th to 6th degree ones. Logarithmic conversion of the parameters was not effective in improving the correlation. The assumption of the 3rd degree regression followed by calculation of the local minimum gave 22, 29 and 23 micrograms/100 ml Pb-B for men, women, and men + women, respectively, as the threshold Pb-B to induce ALA-U increase. Pb-B to elevate ALA-U to the 95% upper normal limit (8 mg/l, common to men and women) was 62, 50 and 58 micrograms/100 ml for men, women and men + women, respectively. The validity of the 3rd degree regression assumption as a tool to calculate a threshold from experimental or epidemiological data is discussed. 相似文献
195.
Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells 总被引:2,自引:1,他引:2
p53 mutation is commonly associated with high-grade, high-stage human
urothelial carcinomas. Recent studies suggest that p53 mutation in low-
grade, low-stage bladder carcinomas may be correlated with the progression
of the disease. In the present study, we used antisense RNA methodology in
vitro to evaluate the significance of the loss of p53 function at an early
stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat
urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was
transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA
in antisense orientation. The transfection resulted in a significant
reduction in p53 mRNA expression and protein synthesis, in stimulation of
anchorage- dependent growth, and in acquisition of anchorage-independent
growth potential. Three such clones, when tested in athymic nude mice, all
formed muscle-invasive, high-grade transitional cell carcinomas at s.c.
injection sites. When cells were inoculated into an orthotopic site
(urinary bladder), one of two antisense transfectants tested formed bulky
tumors in the bladder in all seven nude mice and metastases to lungs in
three of the seven mice. Analysis of these cells revealed a decrease in the
expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene
product. Phosphorylation of Rb protein was not inhibited when the cells
were starved. No significant difference was observed in the expression of
p16 protein. In cell cycle analysis, all antisense transfectants tested
escaped from G1 arrest by starvation. Furthermore, secretion of interleukin
(IL)-6 into culture medium was increased significantly. Treatment with
anti-IL-6 antibody suppressed anchorage-dependent growth. This study
directly demonstrates that the loss of p53 function at an early stage of
urothelial carcinogenesis may result in acquisition of a malignant
phenotype by regulating IL-6 production as well as cell cycle related
genes.
相似文献
196.
Hiroaki Okamoto Akira Nagatomo Hideo Kunitoh Hiroshi Kunikane Koshiro Watanabe 《Cancer chemotherapy and pharmacology》1998,42(4):307-312
Purpose: Carboplatin doses can be individualized using the formula of Calvert et al. (Calvert formula) dose (mg) = area under the
plasma concentration versus time curve (AUC) · [glomerular filtration rate (GFR) + 25]. Creatinine clearance (Ccr), either
measured by the 24-h method or calculated by the formula of Cockcroft and Gault [Cockcroft-Gault (CG) formula], is often substituted
for the GFR. The CG formula is based on patient weight, age and sex, and the serum creatinine (Cr) concentration. Another
method for predicting carboplatin clearance (CL) using patient characteristics has also been proposed by Chatelut et al. (Chatelut
formula). This study was undertaken to evaluate the performance of the three formulae in predicting standard- and low-dose
carboplatin pharmacokinetics. Methods: A total of 52 patients with advanced lung cancer were enrolled in this pharmacokinetic study; 37 received standard-dose
carboplatin and 25 received low-dose carboplatin. The Cr concentration was measured using an enzymatic assay. The three formulae
were used to predict carboplatin CL. The median absolute percent error (MAPE) for each formula was evaluated by comparing
the calculated and observed CL. For comparison of AUCs, free platinum plasma concentrations were measured at intervals up
to 24 h after carboplatin administration. AUCs were determined and compared with predicted values. Results: In the standard-dose carboplatin group, the MAPEs for the prediction of carboplatin CL from the 24-h Calvert, CG-Calvert
and Chatelut formulae were 13%, 12% and 23%, respectively. In the low-dose carboplatin group, the corresponding MAPEs were
27%, 18% and 44%, respectively. Observed standard-dose carboplatin AUCs after aiming for target AUCs of 5 and 6 mg · min/ml
using the Calvert formula based upon the 24-h Ccr were 5.3 ± 0.8 and 5.9 ± 0.8, respectively, indicating a small and acceptable
bias compared with that predicted from the dosing formula. Conclusions: The pharmacokinetics of standard-dose carboplatin were accurately predicted by the Calvert formula based upon either 24-h
or CG-calculated Ccr, but not by the Chatelut formula. Either CG-calculated or 24-h Ccr can be substituted for the GFR in
the Calvert formula for the determination of individual doses. The poor predictability of the Chatelut formula found in this
study might be the result of a differences in either the Cr assay or the patient population. Therefore, formulae which attempt
to estimate GFR are not necessarily valid if either the Cr assay or the patient population is changed.
Received: 23 July 1997 / Accepted: 16 December 1997 相似文献
197.
198.
Leptin is one of the key afferent signals that regulate food intake and energy expenditure by acting on specific receptors in the hypothalamus. Recently, leptin was reported to activate the peripheral immune system by acting directly on lymphocytes. To elucidate the brain-mediated participation of leptin in the modulation of peripheral immune functions, we examined the effects of intracerebroventricular (icv) injection of murine recombinant leptin on the proliferative response to Concanavalin A (ConA response) of splenic lymphocytes in rats. The ConA response of splenic lymphocytes was markedly reduced 30 min after icv injection of leptin. The suppressive effect of leptin was abolished completely either by surgical severing of the splenic nerves or by icv injection of an antibody against corticotropin-releasing hormone (CRH), but only partially by an anti-urocortin antibody. Icv injection of CRH and urocortin also suppressed the ConA response of splenic lymphocytes, and the effect of urocortin was prevented by the anti-CRH antibody, while that of CRH was not prevented by the anti-urocortin antibody. These results suggest that leptin suppresses peripheral lymphocyte functions, in contrast to the direct activating effects, indirectly through the activation of the CRH (urocortin)-sympathetic nervous system. 相似文献
199.
Kase M Sakamoto K Yamagata T Watanabe K Kunikane H Okamoto H Nagatomo A 《Kyobu geka. The Japanese journal of thoracic surgery》2000,53(12):1055-1057
A 29-year-old woman was referred to our hospital for an abnormal shadow on chest roentgenogram. She had no symptom but its shadow was pointed out about 20 years ago. Chest CT scan showed a sharply demarcated homogenous mass measured 10 x 10 mm in the S4 segment. The tumor was resected with video-assisted thoracoscopic surgery under CT-guided marking wire inserted. Microscopic examination suspected cavernous hemangioma. Immunohistological staining demonstrated most lining cells of the cavernous structure stained positively for von Willebrand factor antibody, which suggests that this tumor was associated with endothelium. Then we decided that this tumor was pulmonary cavernous hemangioma. 相似文献
200.
Takaomi Sanda Shinsuke Iida Hiroka Ogura Kaori Asamitsu Toshiki Murata Kevin B Bacon Ryuzo Ueda Takashi Okamoto 《Clinical cancer research》2005,11(5):1974-1982
Involvement of nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation of multiple myeloma has been well established. In this study we observed that NF-kappaB is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. In addition, we found the phosphorylation of p65 subunit of NF-kappaB in addition to the phosphorylation of IkappaBalpha and the activation of NF-kappaB DNA binding and that various target genes of NF-kappaB including bcl-x(L), XIAP, c-IAP1, cyclin D1, and IL-6 are up-regulated. We then examined the effect of a novel IkappaB kinase inhibitor, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP). When myeloma cells were treated with ACHP, the cell growth was efficiently inhibited with IC(50) values ranging from 18 to 35 mumol/L concomitantly with inhibition of the phosphorylation of IkappaBalpha/p65 and NF-kappaB DNA-binding, down-regulation of the NF-kappaB target genes, and induction of apoptosis. In addition, we observed the treatment of ACHP augmented the cytotoxic effects of vincristine and melphalan (l-phenylalanine mustard), conventional antimyeloma drugs. These findings indicate that IkappaB kinase inhibitors such as ACHP can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of NF-kappaB. 相似文献