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101.
Characterization of xenobiotic-metabolizing enzymes and nitrosamine metabolism in the human esophagus 总被引:5,自引:2,他引:5
Smith TJ; Liao A; Wang LD; Yang GY; Starcic S; Philbert MA; Yang CS 《Carcinogenesis》1998,19(4):667-672
Esophageal cancer has been associated with tobacco smoking, and
nitrosamines are possible causative agents for this cancer. The present
study investigated the metabolism of the tobacco carcinogens N'-
nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone
(NNK), and N-nitrosodimethylamine (NDMA), as well as the presence of
xenobiotic-metabolizing enzymes in human esophageal tissues from
individuals in the United States and Huixian, Henan Province, China (a
high-risk area for esophageal cancer). All esophageal microsomal samples
activated NNN and the metabolic rate was 2-fold higher in the esophageal
samples from China than the USA. All microsomal samples activated NDMA.
However, most of the microsomal samples did not activate NNK.
Troleandomycin (an inhibitor of cytochrome P450 3A) decreased the formation
of NNN-derived keto acid by 20-26% in the esophageal microsomes. The
activities for NADPH: cytochrome c reductase, ethoxycoumarin O-deethylase,
NAD(P)H: quinone oxidoreductase and glutathione S-transferase were present
in the esophageal samples. Coumarin 7-hydroxylase (a representative
activity for P450 2A6) activity was not detected in the esophageal
microsomal samples. The activities for nitrosamine metabolism and
xenobiotic- metabolizing enzymes were decreased (by 30-50%) in the squamous
cell carcinomas compared with their corresponding non-cancerous mucosa. The
presence of activation and detoxification enzymes in the esophagus may play
an important role in determining the susceptibility of the esophagus to the
carcinogenic effect of nitrosamines. Our results suggest that P450s 3A4 and
2E1 are involved in the activation of NNN and NDMA, respectively, in the
human esophagus.
相似文献
102.
Liu JM; Chen YM; Chao Y; Liu SM; Tiu CM; Wu HW; Chiou TC; Hsieh RK; Chen LT; Whang-Peng J 《Japanese journal of clinical oncology》1998,28(7):431-435
BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide
continuous infusion chemotherapy for cancer of unknown primary site in
Taiwan, a region with a high prevalence of endemic viral infections.
METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis
of CUPS were treated, including 15 males and five females, of average age
63.3 years (range 41-83 years). Continuous intravenous infusion of
etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3
weeks. Pretreatment tumor marker and viral serology studies were performed
for baseline evaluation. Nearly two-thirds of the patients had poorly
differentiated carcinoma. The average number of metastatic sites was 2.65
(range 1-4), with liver and lymph node involvement predominating. RESULTS:
The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly
differentiated cancers and 25% for well differentiated cancers. Median
survival was 4 months (range 1-12 months), 4.8 months for patients
attaining partial response. Toxicity was moderate, grade 3 and 4
neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%;
other toxicities were mild. CA125 and CA199 were elevated in more than 50%
of patients. Viral serology studies were not significantly different from
those of the indigenous population. CONCLUSION: Etoposide and cisplatin
combination chemotherapy has modest activity in patients with extensive
CUPS and, at the schedule and dosage given, it is associated with moderate
toxicity.
相似文献
103.
Wang WS; Hsieh RK; Chiou TJ; Liu JH; Fan FS; Yen CC; Tung SL; Chen PM 《Japanese journal of clinical oncology》1998,28(9):551-554
A 54-year-old man was treated with weekly 24-h infusion of high-dose
5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon
cancer. At first, he tolerated the treatment well and no significant
toxicity was identified. After a total of eight courses of treatment, a
stable disease was observed, but mild shortness of breath was found on
occasion. The patient had no previous history of cardiac disease and the
heart performance assessed by left ventricular ejection fraction before
treatment was normal. Unfortunately, acute pulmonary edema with lethal
cardiogenic shock occurred during the ninth course of treatment, in spite
of intensive medical treatment. The chest X-ray showed extreme
cardiomegaly. Repeated assessment of his heart function by echocardiogram
and ventricular ejection fraction revealed a very poor cardiac performance.
Toxic cardiogenic shock during weekly 24-h infusion of high-dose
5-fluorouracil and leucovorin is extremely rare. To the best of our
knowledge, no case has been reported in the English literature. We report a
case and the relevant literature about the incidence, clinical picture and
possible pathophysiology on 5-fluorouracil-related cardioxicity is
reviewed.
相似文献
104.
Yao-Yuan Hsieh Chi-Chen Chang Chien-Chung Lee Horng-Der Tsai Cheng-Chieh Lin Chang-Hai Tsai 《Archives of gynecology and obstetrics》1998,261(3):163-166
We present a report on a case of conjoined twin/s (cephalothoracopagus janiceps monosymmetros) diagnosed by ultrasonography
and X-ray at 27 weeks' gestation.
Accepted: 29 December 1997 相似文献
105.
Teresa Pekol J Scott Daniels Jason Labutti Ian Parsons Darrell Nix Elizabeth Baronas Frank Hsieh Liang-Shang Gan Gerald Miwa 《Drug metabolism and disposition》2005,33(6):771-777
Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore. 相似文献
106.
To investigate synaptic mechanisms underlying information processing in auditory cortex, we examined cholinergic modulation of synaptic transmission in a novel slice preparation containing thalamocortical and intracortical inputs to mouse auditory cortex. Extracellular and intracellular recordings were made in cortical layer IV while alternately stimulating thalamocortical afferents (via medial geniculate or downstream subcortical stimulation) and intracortical afferents. Either subcortical or intracortical stimulation elicited a fast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive, monosynaptic EPSP followed by long-duration, polysynaptic activity. The cholinergic agonist carbachol suppressed each of the synaptic potentials to different degrees. At low concentrations (5 μM) carbachol strongly reduced (>60%) the polysynaptic slow potentials for both pathways but did not affect the monosynaptic fast potentials. At higher doses (10–50 μM), carbachol also reduced the fast potentials, but reduced the intracortically-elicited fast potential significantly more than the thalamocortically-elicited fast potential, which at times was actually enhanced. Atropine (0.5 μM) blocked the effects of carbachol, indicating muscarinic receptor involvement. We conclude that muscarinic modulation can strongly suppress intracortical synaptic activity while exerting less suppression, or actually enhancing, thalamocortical inputs. Such differential actions imply that auditory information processing may favor sensory information relayed through the thalamus over ongoing cortical activity during periods of increased acetylcholine (ACh) release. 相似文献
107.
Jane Dimmitt Champion PhD FNP CS ; Pat Kelly PhD FNP ; Rochelle N. Shain PhD ; Jeanna M. Piper MD 《The Journal of rural health》2004,20(3):279-285
CONTEXT: There is a need for community-based, culturally sensitive, cognitive-behavioral interventions to reduce sexual risk behavior among minority adolescents. Studies of adolescent risk and protective behaviors have focused on identifying modifiable psychosocial variables that predict differential outcomes for subsequent intervention efforts. Research has been scarce in studies of rural minority adolescent women. PURPOSE: To examine the protective and risk behaviors of these rural Mexican-American adolescent women and their relationship to physical or sexual abuse. METHODS: Mexican-American adolescent women aged 14-19 years were recruited through a rural health clinic and administered a self-report assessment for protective and risk behavior and sexual, physical, and psychological abuse. FINDINGS: Rural minority adolescent women endured high levels of psychological distress and many risk behaviors yet experienced few protective behaviors. Barriers to health care included access and confidentiality. Physically or sexually abused adolescents endured relatively greater risk and fewer protective behaviors than nonabused. CONCLUSIONS: Rural Mexican-American adolescent women may benefit from confidential identification and assessment of abuse history and risk and protective behaviors so that appropriate psychological treatment can accompany accessible medical treatment. The prevalence of risk behaviors and abuse among these women presents a need for development of behavioral interventions for risk reduction and promotion of health protective behaviors. 相似文献
108.
PURPOSE: We report our experience with preserving the thin distal urethra lacking corpus spongiosum for the treatment of hypospadias. MATERIALS AND METHODS: From January 1997 to October 1999 we treated primary hypospadias in 77 boys with a mean age of 4 years 10 months. After degloving the penile skin a segment of thin distal urethra lacking corpus spongiosum was noted in 18 patients (23.4%) with a mean age of 3 years 5 months. The thin distal urethra was preserved and incorporated as part of urethroplasty (group 1). The procedure was primarily completed by tubularized incised plate urethroplasty. We also performed tubularized incised plate urethroplasty in 31 boys (40.3%) with a mean age of 5 years 2 months who had normal coverage of the corpus spongiosum of a hypospadiac urethra (group 2). We compared the results of treatment in these 2 groups. The remaining 28 patients (36.4%) treated with other methods were excluded from study. RESULTS: In group 1 the distance from the original meatus to the urethra covered by healthy corpus spongiosum was 4 to 20 mm. (mean 8.2). If the thin distal urethra had been excised, the urethral meatus would have been relocated more proximal in these boys. Mean followup in groups 1 and 2 was 9.9 and 7.6 months, respectively. Postoperatively there were 2 (11.1%) urethrocutaneous fistulas in group 1 and 4 (12.9%) in group 2. Tubularized incised plate repair was successful in all 10 cases (100%) of distal hypospadias in group 2, and in 15 of 18 (83.3%) and 17 of 21 (81%) of proximal hypospadias cases in groups 1 and 2, respectively. There was no statistically significant difference in the success rate of hypospadias repair in the groups. CONCLUSIONS: We noted a significantly thin distal urethra in 23.4% of our cases of primary hypospadias. Mean length of the thin distal urethra was 8.2 mm. Preserving the thin distal urethra may simplify the operative procedure without compromising the surgical results of tubularized incised plate urethroplasty. 相似文献
109.
Offering sperm cryopreservation to preserve the fertility of male cancer patients is a relatively recent service in Asia. This study analyzed the types of cancer, timing of collection, sperm quality, and utilization for reproductive services by patients during a 10-year period at a medical center in Taiwan. A total of 75 oncology patients elected to freeze sperm for fertility preservation at our medical center during the initial 10 years of the availability of this service. The mean age of the patients was 25.7 years. Storage was discontinued in 13 (17%) patients and their survival duration was 13.1 +/- 11.1 months. The utilization rate of sperm cryopreservation was 2.8% (75/2642). The types of cancer varied, with leukemia (35%), lymphoma (25%), and testicular cancer (13%) comprising the largest groups. A significantly lower sperm count was found in patients with chronic myelogenous leukemia, suggesting the need for earlier sperm collection after initiation of cancer treatment. Only three (4%) patients utilized their specimens for reproductive purposes. There was no clinical pregnancy during the study period, although one biochemical pregnancy was achieved. The low rates of sperm cryostorage for fertility preservation in cancer patients in this study suggest that there is a need for greater emphasis of this option for male oncology patients whose fertility is likely to be affected by chemotherapeutic treatment. 相似文献
110.
BACKGROUND: Sarcoidosis is still considered a rare multisystem disorder in Taiwan, and data on the disease course and outcome are limited. We analyzed the clinical manifestations, disease course and complications in Taiwanese patients with sarcoidosis. METHODS: A retrospective cohort design was used. Fifty-six patients with sarcoidosis diagnosed between 1985 and 2004 were included. Their clinical features, laboratory findings at initial presentation, disease course, and complications were analyzed. RESULTS: Forty-three patients (76.8%) were female. The mean age at symptom onset was 47 years. The most common clinical symptoms were pulmonary (82.1%), cutaneous (23.2%), ophthalmic (19.6%), and articular (17.8%). Only two patients presented with L?fgren's syndrome. There was a seasonal variation in disease onset, with higher incidence in winter and early spring. No advanced pulmonary involvement was noted. Elevated levels of serum angiotensin converting enzyme (sACE) were found in 72.5% (29/40) of patients with active sarcoidosis, and significantly higher levels of sACE were found in patients with lung involvement (27.98+/-1.71 IU/L vs. 18.2+/-2.76 IU/L; p<0.01). In 50% (20/40) of patients, sACE levels declined significantly in parallel with clinical remission (24.75+/-1.53 IU/L vs. 16.33+/-1.21 IU/L; p<0.05). Spontaneous complete remission was found in 20.7% of patients, whereas 39.6% of patients with multiple extrapulmonary involvement responded poorly to intensive corticosteroids plus various immunosuppressants. CONCLUSION: In this series, the mean age of disease onset was in middle age (mean, 47 years old), there was a low incidence of L?fgren's syndrome (3.6%), and no patients had advanced pulmonary syndrome. The results of this study also suggest that sACE might be a marker of pulmonary involvement that is also useful in monitoring disease activity. 相似文献