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41.
42.
Anthony T C Chan Qian Tao Keith D Robertson Ian W Flinn Risa B Mann Barbara Klencke Wing Hong Kwan Thomas Wai-Tong Leung Philip J Johnson Richard F Ambinder 《Journal of clinical oncology》2004,22(8):1373-1381
PURPOSE: To determine whether therapy with a DNA methyltransferase inhibitor is effective in achieving demethylation and gene re-expression in tumor DNA in patients. METHODS: Biopsy specimens were obtained from patients with Epstein-Barr virus-associated tumors, enrolled on a clinical trial of 5-azacitidine, within 72 hours of the conclusion of the last infusion of the first cycle of therapy, and compared to pretreatment specimens. Methylation-specific polymerase chain reaction, bisulfite genomic sequencing, and immunohistochemistry were used to assess demethylation and gene re-expression. RESULTS: Substantial degrees of demethylation were detected in all latent and lytic Epstein-Barr virus promoters examined. Immunohistochemistry suggested activation of a previously silent viral antigen expression in one instance. CONCLUSION: Pharmacologic reversal of dense CpG methylation in tumor tissue can be achieved in patients. 相似文献
43.
Anthony T C Chan Brigette B Y Ma Y M Dennis Lo S F Leung W H Kwan Edwin P Hui Tony S K Mok Michael Kam Lisa S Chan Samuel K W Chiu K H Yu K Y Cheung Karen Lai Maria Lai Frankie Mo Winnie Yeo Ann King Philip J Johnson Peter M L Teo Benny Zee 《Journal of clinical oncology》2004,22(15):3053-3060
PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC. 相似文献
44.
Anthony T. C. Chan Thomas W. T. Leung Wing H. Kwan Tony S. K. Mok Winnie Yeo Maria Lai Philip J. Johnson 《Cancer chemotherapy and pharmacology》1998,42(3):247-249
Purpose: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal
carcinoma was undertaken to determine the efficacy and safety of the drug in this population. Methods: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study.
One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m2 daily on days 1–5 every 28 days. Results: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease
after 2 (84.6%) or 4 (15.4%) courses. Conclusion: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma.
Received: 9 January 1998 / Accepted: 4 February 1998 相似文献
45.
Delayed Administration of the K+ Channel Activator Cromakalim Attenuates Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage 总被引:12,自引:0,他引:12
Summary ? Background. Delayed cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage
(SAH). Recent evidence indicates that the potassium channel activator cromakalim is capable of limiting cerebral vasospasm
in rabbits when administered immediately after experimental SAH (i.e. before spastic constriction has been initiated). However,
the ultimate clinical value of cromakalim for treating vasospasm will depend in part on its effectiveness when administered
after SAH-induced constriction has already been initiated. The present study examined the effects of cromakalim on vasospasm
when treatment was initiated after SAH-induced constriction was underway.
Methods. New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. Cromakalim
(0.03, 0.1 or 0.3 mg/kg) or vehicle was injected intravenously at 8 hour intervals beginning 24 hours post-SAH. Animals were
killed by perfusion fixation 48 hours after SAH. Basilar arteries were removed and sectioned, and cross-sectional area was
measured.
Findings. The average cross sectional areas of basilar arteries were reduced by 64% and 68% in the SAH-only and SAH+vehicle groups,
respectively. Treatment with cromakalim dose-dependently attenuated SAH-induced constriction. The groups treated with 0.03,
0.1, and 0.3 mg/kg cromakalim exhibited average decreases in cross-sectional area of 57%, 42%, and 19%, respectively.
Interpretation. These findings indicate that cromakalim dose-dependently attenuates cerebral vasospasm when administered 24 hours after experimental
SAH in the rabbit. The results suggest KATP channel activators, such as cromakalim, could be of benefit for reversing cerebral vasospasm after aneurysmal SAH. 相似文献
46.
Bayani J Zielenska M Marrano P Kwan Ng Y Taylor MD Jay V Rutka JT Squire JA 《Journal of neurosurgery》2000,93(3):437-448
OBJECT: Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of the central nervous system are malignant, invasive embryonal tumors with predominantly neuronal differentiation that comprise 20% of pediatric brain tumors. Cytogenetic analysis has shown that alterations in chromosome 17, particularly the loss of 17p and the formation of isochromosome 17q, as well as the gain of chromosome 7 are the most common changes among this group of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel regions of gain, loss, and amplification. The advent of more sophisticated multicolored fluorescence in situ hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits complete recognition of all aberrations including extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinations of classic banding analysis, FISH, CGH, and SKY to examine comprehensively the chromosomal aberrations present in this tumor group and to attempt to identify common structural rearrangement(s). METHODS: The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the tumors studied, which confirms data reported in the current literature. However, the authors have also combined the results of all three molecular cytogenetic assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal rearrangement (gained, lost, or involved in structural rearrangement). CONCLUSIONS: The combined results indicate that chromosomes 7 and 17 are the most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, followed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identified in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally, desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher karyotype heterogeneity, amplification, and aneusomy than classic medulloblastomas. 相似文献
47.
48.
Yoon Jin Choi Yong Chan Lee Jung Mogg Kim Jin Il Kim Jeong Seop Moon Yun Jeong Lim Gwang Ho Baik Byoung Kwan Son Hang Lak Lee Kyoung Oh Kim Nayoung Kim Kwang Hyun Ko Hye-Kyung Jung Ki-Nam Shim Hoon Jai Chun Byung-Wook Kim Hyuk Lee Jie-Hyun Kim Hyunsoo Chung Sang Gyun Kim Jae Young Jang 《Gut and liver》2022,16(4):535
Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier ). NCT03317223相似文献
49.
50.
Viral infections in pregnancy 总被引:1,自引:0,他引:1
Viral infections are a common complication of pregnancy and in some cases, can have profound effects for the unborn fetus. The human herpesvirus family is composed of large, enveloped DNA viruses that have close structural similarity. The family includes the herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types 6, 7 and 8. These viruses all share the ability to establish latency and reactivate at a later time. Structural fetal abnormalities can result from intrauterine infection and transmission of the infection during the pregnancy or at the time of delivery can result in important neonatal disease. Human parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and infection during pregnancy can result in fetal hydrops and stillbirth. The causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C, D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical transmission of maternal infection with hepatitis B and C can result in significant long term sequelae. 相似文献