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991.
992.
Choi YH Lee U Suh JH Kim YG Lee M Oh E Lee MG 《Xenobiotica; the fate of foreign compounds in biological systems》2011,41(5):409-415
After both the intravenous and oral administration of zinc acexamate [ZAC; ion-pairing between zinc and ?-acetamidocaproic acid (AACA)] and cimetidine together, the areas under the curve (AUCs) of AACA were significantly greater [by 28.2 and 98.9% after the intravenous and oral administration, respectively, for control rats and 13.5 and 16.9% for indomethacin-induced acute gastric ulcer (IAGU) rats, respectively] than those of ZAC alone due to the significantly slower renal clearance (CL(R)). The significantly greater AUCs of AACA after both the intravenous and oral administration of ZAC and cimetidine together in control and IAGU rats could have been due to the inhibition of active renal tubular secretion of AACA by cimetidine. After the intravenous and oral administration of both drugs together, the AUCs of cimetidine in control and IAGU rats were not different compared with those with cimetidine alone. 相似文献
993.
Suh YA Post SM Elizondo-Fraire AC Maccio DR Jackson JG El-Naggar AK Van Pelt C Terzian T Lozano G 《Cancer research》2011,71(23):7168-7175
p53 levels are tightly regulated in normal cells, and thus, the wild-type p53 protein is nearly undetectable until stimulated through a variety of stresses. In response to stress, p53 is released from its negative regulators, mainly murine double minute 2 (Mdm2), allowing p53 to be stabilized to activate cell-cycle arrest, senescence, and apoptosis programs. Many of the upstream signals that regulate wild-type p53 are known; however, limited information for the regulation of mutant p53 exists. Previously, we showed that wild-type and mutant p53R172H are regulated in a similar manner in the absence of Mdm2 or p16. In addition, this stabilization of mutant p53 is responsible for the gain-of-function metastatic phenotype observed in the mouse. In this report, we examined the role of oncogenes, DNA damage, and reactive oxygen species, signals that stabilize wild-type p53, on the stabilization of mutant p53 in vivo and the consequences of this expression on tumor formation and survival. These factors stabilized mutant p53 protein which oftentimes contributed to exacerbated tumor phenotypes. These findings, coupled with the fact that patients carry p53 mutations without stabilization of p53, suggest that personalized therapeutic schemes may be needed for individual patients depending on their p53 status. 相似文献
994.
Il Hwan Lee Soon Chul Heo Sang Hun Shin Eun Su Jeon Yoon Ji Choi Dong‐Soo Suh Man‐Soo Yoon Jae Ho Kim 《International journal of cancer. Journal international du cancer》2011,128(2):332-342
Lysophosphatidic acid (LPA) is a bioactive lipid crucial for the initiation and progression of ovarian cancer. Identification of LPA‐induced biomarkers is necessary for predicting prognosis of ovarian cancer patients. Here we report periostin, an extracellular matrix protein, as an LPA‐induced protein in stromal cells and as a prognostic marker in patients with epithelial ovarian cancer (EOC). In human EOC tissues, periostin was mainly expressed in cancer‐associated stromal fibroblasts, but not in cancer cells. The expression levels of periostin highly correlated with poor survival and tumor recurrence of ovarian cancer patients. Treatment of human adipose tissue‐derived stromal cells with LPA or conditioned media from human ovarian adenocarcinoma cell lines, such as SK‐OV‐3 and OVCAR‐3, induced expression of periostin. The periostin expression induced by cancer‐conditioned media was abrogated by silencing of the LPA receptor 1 expression using small hairpin RNA lentivirus. Recombinant periostin stimulated adhesion and invasion of SK‐OV‐3 human ovarian adenocarcinoma cells and induced expression of matrix metalloprotease‐2 in the cancer cells. These results suggest that LPA is associated with the expression of periostin in cancer‐associated fibroblasts of EOC. 相似文献
995.
McHaffie DR Chabot P Dagnault A Suh JH Fortin MA Chang E Timmerman R Souhami L Grecula J Nabid A Schultz C Werner-Wasik M Gaspar LE Brachman D Mody T Mehta MP 《Journal of neuro-oncology》2011,105(2):301-308
To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤ 6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥ 4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥ 3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost. 相似文献
996.
Minkyu Jung Joong Bae Ahn Jong Hee Chang Chang Ok Suh Soojung Hong Jae Kyung Roh Sang Joon Shin Sun Young Rha 《Journal of neuro-oncology》2011,101(1):49-55
Brain metastases from colorectal carcinoma (CRC) are rare. The objectives of this study are to assess the natural history,
outcome, and possible prognostic factors in CRC patients with brain metastases. Between 1995 and 2008, 8,732 patients with
CRC were treated at Yonsei University Health System. Brain metastases were found in 1.4% of these patients. Retrospective
review and statistical analysis of these 126 patients were performed. Median time from diagnosis of metastatic CRC (mCRC)
to brain metastases was 9.0 months (range 0–85 months), and 14 patients (11.1%) had brain involvement as their initial presentation.
Among the 126 patients, 91.3% had other systemic metastases; the most common extracranial metastatic site was lung (72.2%).
Median follow-up duration was 6.1 months (range 0.1–90.3 months), and median survival after diagnosis of brain metastases
was 5.4 months [95% confidence interval (CI) 3.9–6.9 months]. Median survival time after diagnosis of brain metastases was
1.5 months for patients who received only steroids (15.9%), 4.0 months for those who received whole-brain radiation therapy
(37.5%), 9.5 months for those who received gamma-knife surgery (GKS) (32.5%), and 11.5 months for those who underwent surgery
(20%) (P < 0.001). On multivariate analysis, recursive partitioning analysis (RPA) class and amount of chemotherapy before brain metastasis
were independent prognostic factors for survival. Overall prognosis of patients with brain metastases from CRC is poor. Nevertheless,
patients with low RPA class, or those with previous less chemotherapy showed good prognosis, indicating that proper treatment
may result in improved survival time. 相似文献
997.
998.
Pentamidine is an aromatic diamine used for the treatment of human protozoa infections. Recently, pentamidine has been reported to exhibit anticancer properties. In this study, we report that pentamidine inhibits expression of hypoxia-inducible factor (HIF)-1α in cancer cells. Pentamidine decreased HIF-1α protein translation and enhanced its protein degradation in DU145 prostate cancer and MDA-MB-231 breast cancer cells. In parallel with reduction of de novo synthesis of HIF-1α, pentamidine was able to suppress global protein translation, an effect accompanied by the reduction of eIF4F complex formation and also the induction of eIF2α phosphorylation. These results show that pentamidine is a potential inhibitor of HIF-1α and its potential as a cancer therapeutic reagent warrants further study. 相似文献
999.
Dae Ho Lee Sang-We Kim Cheolwon Suh Yun Hee Han Jung-Shin Lee 《Cancer chemotherapy and pharmacology》2011,67(1):35-39
Purpose
This phase II study evaluated efficacy of single-agent erlotinib for chemotherapy-na?ve patients with advanced/metastatic NSCLC who were ineligible for platinum doublets.Methods
Chemotherapy-naive patients but ineligible for platinum doublets (aged 18?C75 with an ECOG performance status [PS] 2?C3; or aged 76 or older with an ECOG PS 1?C3) were enrolled and treated with erlotinib 100?mg once daily till disease progression, unacceptable toxicity or patient??s refusal.Results
Out of 24 patients enrolled, 5 reached a PR, giving an overall response rate of 21%, but all responders were never-smokers with adenocarcinoma. According to EGFR mutation status, PR was observed in two of three patients having mutant EGFR (67%) but in one of nine having wild-type EGFR (11%). With a median follow-up of 22.6?months, the median progression-free and overall survival was 1.5?months and 3.2?months, respectively. All responders to post-erlotinib chemotherapy had responded to prior erlotinib.Conclusions
For unselected chemotherapy-na?ve Asian patients with NSCLC but ineligible for platinum doublets, empirical use of upfront erlotinib could not be recommended because of poor survival outcome. However, this can be given to selected subsets based on molecular or clinical predictors. 相似文献1000.
Kyung Hoon Kim Byoung Kuk Jang Woo Jin Chung Jae Seok Hwang Young Oh Kweon Won Young Tak Heon Ju Lee Chang Hyeong Lee Jeong Ill Suh 《Clinical and molecular hepatology》2011,17(3):220-225