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Biomedical subjects

Z F Zhang

Publications and source records attributed to Z F Zhang.

At least 55 records · Page 3Linked to original sources
PubMed1998

Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation.

Uroplakins (UPs) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-II gene and localized it on chromosome 11q23. A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36) of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.

Amino Acid Sequence↗
PubMed1998

Female urethral carcinoma: an analysis of treatment outcome and a plea for a standardized management strategy.

OBJECTIVE: To evaluate our experience with primary carcinomas of the female urethra, by analysing the impact of tumour variables and treatment on overall, disease-specific, local recurrence- and metastasis-free survival. PATIENTS AND METHODS: Between 1958 and 1994, 72 women (median age 60 years, mean 59, range 21-84) with primary urethral carcinoma were identified. They were followed for a median (range) of 85 (0-384) months. The patients were stratified by stage, nodal status, histology, treatment, type of surgery, site of disease, year of diagnosis and smoking habit. RESULTS: In a univariate analysis, stage, nodal status, type of surgery and site of the disease were important factors for survival and recurrence. In a multivariate analysis, primary stage, nodal status and site of disease were independent predictors of survival. CONCLUSION: Current modalities of treatment are ineffective for local control and survival; new treatment strategies are needed for female urethral cancers.

Adult↗
PubMed1998

Aspirin use and p53 expression in colorectal cancer.

p53 protein overexpression indicates loss of tumor suppressor activity and is the most common genetic alteration in colorectal neoplasms. Epidemiologic and experimental studies suggest that regular use of aspirin may reduce colorectal cancer risk. We set out to determine whether p53 overexpression of the colorectum was associated with a patient's history of aspirin use. Self-administered questionnaires, including information on aspirin use, were obtained from 163 patients with nonfamilial colorectal cancer and from 326 healthy controls. Nuclear p53 protein overexpression using anti-p53 CM-1 polyclonal antibody was observed in 44.8% (73/163) of patients' tumors. A nonsignificant inverse association was observed between use of aspirin and colorectal cancer. Compared with that for nonusers, the odds ratio (OR) for individuals who took aspirin at least twice weekly was 0.68 (95% confidence interval [95% CI]: 0.39-1.18). The odds ratio for those individuals who used aspirin for less than 5 years was 0.54 (95% CI: 0.24-1.23), and 0.80 (95% CI: 0.42-1.51) for those who used aspirin for 5 years or more, when compared with nonusers. An inverse association of regular aspirin use (two times per week or more) was found both for cases with p53 overexpression (OR: 0.79; 95% CI: 0.39-1.59), and for cases without p53 overexpression (OR: 0.56; 95% CI: 0.25-1.22). There was little evidence of a difference in the effect of aspirin use on cancer risk between cases with and without p53 overexpression, even after adjustment for potential confounders.

Adenocarcinoma↗
PubMed1998

Cigarette smoking and cervical dysplasia among non-Hispanic black women.

This is the first case-control study to determine whether smoking is associated with cervical dysplasia, after adjustment for human papillomavirus (HPV) infection, among a group of non-Hispanic black women. Subjects were interviewed and asked questions about smoking and other risk factors for cervical cancer. HPV infection was determined by hybrid capture. Thirty-two women with histologically confirmed incident dysplasia and 113 control women with normal cytologic smears were enrolled; all women were HIV negative. Smoking was more strongly associated with dysplasia among women with high-grade lesions than among all case women combined. After adjustment, women with high-grade lesions were roughly four times more likely to be ever (odds ratio [OR]: 3.8; 95% confidence interval [CI]: 0.76-18.4) or current (OR: 4.3; 95% CI: 0.83-21.9) smokers, compared with control women. Larger studies among black women that control for HPV infection are needed to confirm these findings and to explore associations among black women with low-grade lesions.

Adult↗
PubMed1998

Dietary intake and blood levels of lycopene: association with cervical dysplasia among non-Hispanic, black women.

We examined whether elevated levels of retinoids, carotenoids, folate, and vitamin E protected against cervical dysplasia among non-Hispanic, black women. We enrolled 32 women with incident cervical dysplasia, including cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III/carcinoma in situ, and 113 control women with normal cervical cytology in case-control study. Micronutrient levels were estimated from a food-frequency questionnaire (FFQ) and measured from blood samples. Information on risk factors for cervical neoplasia was elicited by interview. Hybrid capture was used to determine infection with human papillomavirus. After adjustment for potential confounders, analysis of micronutrient levels estimated from the FFQ suggested that women in the upper tertile of lycopene and vitamin A intake were one-third (odds ratio = 0.32, 95% confidence interval = 0.8-1.3) and one-fourth (odds ratio = 0.24, 95% confidence interval = 0.05-1.2) as likely, respectively, to have dysplasia as women in the lower tertile. Borderline protective trends (p < or = 0.10) were apparent. Elevated levels of serum lycopene also suggested some protection against dysplasia. Results were not significant at alpha = 0.05 because of the small number of case women enrolled. Overall, correlations between estimates from the FFQ and serum levels were poor. This study indicates that, among black women, lycopene and perhaps vitamin A may play a protective role in the early stages of cervical carcinogenesis.

Adolescent↗
PubMed1998

p53 immunostaining as a significant adjunct diagnostic method for uterine surface carcinoma: precursor of uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is a biologically aggressive carcinoma that causes a disproportionate number of endometrial cancer deaths because of its dismal clinical outcome. Although the precursor lesion of UPSC has been suggested both morphologically and molecularly, diagnosis continues to represent a challenge to surgical pathologists, particularly in biopsy specimens, largely in part because of its multiple histologic patterns and many benign morphologic mimics. In this study, we used p53 immunohistochemical staining as an adjunct test to correctly identify six cases of uterine surface carcinoma (USC) prospectively and three cases retrospectively. Both sensitivity and specificity for this immunostaining method approached 100% when the cutoff score of p53 overexpression was 7 or higher. The precision estimated by receiving operating characteristic curve was 100%, indicating that the diagnostic value of the score for p53 overexpression was very high. p53 immunohistochemical staining was considered a significant adjunct diagnostic method for the probable precursor lesion of UPSC. The probable precursor lesion of UPSC, previously referred to as endometrial intraepithelial carcinoma or endometrial carcinoma in situ, appears to represent the early phase of UPSC. However, unlike its names would suggest, this lesion is often multicentric and behaves in a more aggressive fashion than regular in situ carcinomas. For this reason, we prefer the term uterine surface carcinoma, a term that is more descriptive and less restrictive, to emphasize the unique aggressive nature of the UPSC precursor lesion. The reason we postulate using the term uterine surface carcinoma rather than endometrial intraepithelial carcinoma or endometrial carcinoma in situ is that the latter terms would seem define a neoplastic process confined to the endometrial epithelium without potential for metastasis. In reality, the precursor lesion of UPSC has a tendency to stromal and vascular space involvement as seen by the presence of stromal and vascular invasion in one of the prospectively identified USC cases. Therefore, the term uterine surface carcinoma is selected to alert clinicians that this early carcinoma has features of carcinoma in situ, but still carries a potential for metastasis.

Aged↗
PubMed1998

Prognostic significance of peripheral blood and bone marrow tyrosinase messenger RNA in malignant melanoma.

The objectives of this study were to evaluate the prognostic significance of reverse transcription PCR (RT-PCR) detection of tyrosinase mRNA in the peripheral blood (PB) and bone marrow (BM) of patients with stage II-IV malignant melanoma (MM). Seventy-three PB samples and 109 BM aspirates from 123 assessable patients with stage II-IV MM were analyzed for tyrosinase mRNA using nested RT-PCR. Twenty-five controls without MM were also evaluated. The RT-PCR results were correlated with overall survival (OS) and clinical stage. Overall, 23 of the 123 patients with MM (19%) had tyrosinase mRNA in their blood and/or BM. RT-PCR positivity was present in the PB of 9 of 73 patients (12%), whereas 18 of 109 (16.5%) had tyrosinase mRNA in their BM. All controls were tyrosinase PCR negative. There was no correlation between RT-PCR results and clinical stage. Within stage II, BM PCR-positive patients had a shorter median survival (24 months) than BM PCR-negative individuals (median not reached), with a P approaching significance (P = 0.06). There was a statistically significant correlation between blood PCR positivity and decreased overall survival (P = 0.03) in all patients. Blood PCR positivity was associated with a significantly decreased OS in stage II and III (P = 0.01 and 0.02, respectively) and was not a predictor of OS in stage IV. In multivariate analysis, blood RT-PCR for tyrosinase mRNA was found to be an independent predictor of survival (P = 0.03; risk ratio, 2.87). RT-PCR can specifically detect tyrosinase mRNA in the PB and BM of patients with MM. Blood RT-PCR is an independent predictor of overall survival in stage II-III MM. Additional studies are needed to define the potential role of this assay in the management of patients with advanced melanoma.

Adult↗
PubMed1997

The role of dietary factors in the intestinal and diffuse histologic subtypes of gastric adenocarcinoma: a case-control study in the U.S.

BACKGROUND: The decline of gastric adenocarcinoma in the U. S. and the parallel decrease in the predominance of the intestinal type of gastric adenocarcinoma may reflect, in part, changes in diet over the last 60 years. Because the intestinal and diffuse types of gastric adenocarcinoma may be epidemiologically distinct, the authors hypothesized that different nutritional factors are associated with the different subtypes of gastric adenocarcinoma. METHODS: Ninety-one incident cases with a pathologic diagnosis of gastric adenocarcinoma and 132 cancer free controls were included in this study. All cases were defined as being either the intestinal or diffuse type of gastric adenocarcinoma. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Nutritional and dietary factors were analyzed using a logistic regression model. RESULTS: Several dietary factors were significantly associated with both subtypes of gastric adenocarcinoma, including dietary intakes of fiber, oleic acid, potassium, and fruits. Almost all dietary factors and food groups unique to intestinal gastric adenocarcinoma were protective in nature (vitamin B6, folate, niacin, iron, noncitrus fruits, and raw fruit), except for a high intake of dietary calories, which was a risk factor for intestinal gastric adenocarcinoma. The unique factors found to be protective for diffuse disease were carbohydrate and vitamin C intake. CONCLUSIONS: This study suggests that dietary factors contribute to the carcinogenesis of gastric adenocarcinoma. It also appears that although dietary risk and protective factors are common to both the intestinal and diffuse types of this malignancy, protective dietary factors may play a more important role in preventing the intestinal type of gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Chromosome 16 in primary prostate cancer: a microsatellite analysis.

Cytogenetic and molecular genetic analyses of prostate cancer specimens have revealed nonrandom chromosomal deletions, affecting chromosomes 7q, 8p, 10q and 16q. Based on these data, we designed this study to further characterize the altered region(s) on chromosome 16 by evaluating 16 microsatellite markers on a population composed of 32 paired normal and primary prostatic tumor samples. The 16 microsatellites selected mapped to 11 distinct loci on 16q and 5 loci on 16p. No alterations were identified affecting 16p. However, 16 of 31 (51%) informative cases showed molecular alterations in at least one of the loci analyzed on 16q, consisting of 18 deletions and 11 bandshifts. Moreover, most of the deletions clustered at 6 microsatellite loci, mapping to the 16q22.1-23.1 region. Our results suggest that microsatellite alterations on the long arm of chromosome 16 are frequent events in prostate cancer, and that the 16q22.1-23.1 region might harbor a tumor suppressor gene involved in prostate cancer.

Adenocarcinoma↗
PubMed1997

Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors.

Altered patterns of p53 and pRB expression have been reported to be frequent events and to have prognostic significance in bladder cancer. To assess the potential adverse consequences of having altered patterns of both p53 and pRB proteins in patients with bladder neoplasms compared with having one or neither abnormality, we have studied a cohort of superficial transitional cell carcinomas of the urinary bladder by immunohistochemical analysis. The present study included 59 well-characterized superficial transitional cell carcinomas (Ta, n = 28; T1, n = 31) for which clinicopathological variables were available. Nuclear overexpression of p53 was identified in 22 cases (37%). A statistically significant association was observed between the p53-positive phenotype and disease progression (P < 0.001), as well as reduced survival (P < 0.001). Undetectable levels of pRB were observed in 11 cases (19%). Patients with a pRB-negative phenotype had a more frequent disease progression (P = 0.014) and decreased overall survival (P = 0.014). We also observed a significant association between altered p53 and undetectable pRB expression patterns (P = 0.001). Nine tumors showed both a p53-positive and a pRB-negative phenotype. There was an even more marked increase in progression (P = 0.00005) and decreased overall survival (P = 0.0004) in patients whose tumors had both alterations after controlling for tumor stage, tumor grade, and suspicion of vascular invasion. These data suggest that alterations of p53 and pRB have a cooperative negative effect on both progression and survival in primary bladder cancer. It may be postulated that aberrant p53 and pRB expression deregulates cell cycle control at the G1 checkpoint and engenders tumor cells with reduced response to programmed cell death. The imbalance produced by an enhanced proliferative activity and a decreased apoptotic rate may determine the aggressive clinical course of the bladder tumors harboring both p53 and pRB alterations.

Carcinoma, Transitional Cell↗
PubMed1997

Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube.

The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood. Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9-28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.

Aged↗
PubMed1997

Prognostic significance of detection of prostate-specific antigen transcripts in the peripheral blood of patients with metastatic androgen-independent prostatic carcinoma.

OBJECTIVES: To evaluate the prognostic significance of reverse transcriptase polymerase chain reaction (RT PCR) detection of prostate-specific antigen (PSA) mRNA in relation to survival in patients with metastatic androgen-independent prostatic carcinoma (AIPC). METHODS: Peripheral blood from 122 men (64 from Memorial Sloan-Kettering Cancer Center [MSKCC] and 58 from the Dana Farber Cancer Institute [DFCI]) with metastatic (Stage D2) AIPC was analyzed for PSA mRNA using RT PCR. Forty-one controls without prostatic carcinoma were also evaluated. RESULTS: RT PCR positivity for PSA mRNA was present in 24 of the 64 (38%) patients seen at MSKCC and in 26 of the 58 (45%) patients followed at DFCI. All control individuals were PSA PCR negative. There was a significant correlation between RT PCR positivity and decreased survival in each of the Memorial and Dana Farber population (P = 0.028 and 0.039, respectively). Serum PSA (at time of blood collection for PCR) was not predictive of survival as a continuous variable in the MSKCC [P = 0.31] and the DFCI (P = 0.09) groups. RT PCR for PSA mRNA was found to be independent from and superior to serum PSA in predicting survival in both the MSKCC and DFCI populations (P = 0.048 and P = 0.027, respectively). CONCLUSIONS: The detection of PSA mRNA in the peripheral blood by RT PCR is a predictor of survival in patients with metastatic AIPC, and PCR is superior to a single serum PSA measurement. Further studies are needed to test the value of this factor in comparison to and coupled with other prognostic parameters.

Adult↗
PubMed1997

Adenocarcinomas of the esophagus and gastric cardia: the role of diet.

The incidence of adenocarcinomas of the esophagus and gastric cardia (ACEGC) has been increasing for the past 10-15 years in the United States. The reason for this increase is unknown. This hospital-based case-control study was conducted to assess the effects of dietary and nutritional factors on the risk of ACECG. A total of 95 incident cases with pathological diagnosis and 132 cancer-free controls were included in the study. Patients were recruited at Memorial Sloan-Kettering Cancer Center from 1 November 1992 to 1 November 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Nutritional and dietary factors were analyzed using a logistic regression model. Increased risk of ACEGC was significantly related to higher intake of dietary calories and fat after controlling for several potential confounding factors. Decreased risk of ACEGC was significantly associated with high ingestion of dietary fiber, lutein, niacin, vitamin B6, iron, and zinc. Higher intakes of vitamin A, beta-carotene, vitamin E, folate, phosphorus, and potassium were associated with a decreased risk of the disease, but these were not statistically significant. The study suggests that ACEGC can be preventable through dietary interventions.

Adenocarcinoma↗
PubMed1997

The treated natural history of high risk superficial bladder cancer: 15-year outcome.

PURPOSE: The long-term outcome of patients with high risk superficial bladder cancer is unknown. We report the results of 15 years of followup of high risk patients treated initially with aggressive local therapy, including transurethral resection alone or combined with intravesical bacillus Calmette-Guerin. MATERIALS AND METHODS: Between 1978 and 1981, 86 high risk patients enrolled in a randomized study of transurethral resection alone or with intravesical bacillus Calmette-Guerin for superficial bladder cancer. Of these patients 81% had diffuse carcinoma in situ and 44% had stage T1 tumors before entry into the study. Patients were followed until death (61%) or until the present time (median followup 184 months). RESULTS: Disease stage progressed in 46 patients (53%) and 31 (36%) eventually underwent cystectomy for progression (28) or refractory carcinoma in situ (3), while 18 (21%) had upper tract tumors at a median of 7.3 years. The 10 and 15-year disease specific survival rates were 70 and 63%, respectively. At 15 years 34% of patients overall were dead of bladder cancer, 27% were dead of other causes and 37% were alive, including 27% with an intact functioning bladder. CONCLUSIONS: Despite aggressive local therapy patients with high risk superficial bladder cancer are at lifelong risk for development of stage progression and upper tract tumors. A third of patients are at risk for death from bladder cancer, justifying careful and vigilant long-term followup. These results support the use of initial aggressive local therapy in patients with high risk superficial bladder cancer.

Disease Progression↗
PubMed1997

Genetic susceptibility to head and neck cancer: interaction between nutrition and mutagen sensitivity.

The development of head and neck cancer may depend not only on exposure to environmental carcinogens but also on a genetically based susceptibility to carcinogen-induced damage. This thesis presents a case-control study that demonstrates the significance of mutagen sensitivity, a measure of an individual's intrinsic DNA repair capacity against free radical damage, as a risk factor for the disease. As part of the case-control analysis, 167 previously untreated patients and 177 age- and sex-matched healthy controls were assessed for various lifestyle factors including tobacco and alcohol habits, occupational exposures, and diet. Mutagen sensitivity expressed by each individual was determined by quantifying bleomycin-induced chromosomal breaks within peripheral blood lymphocytes in vitro. Consistent with our initial observations and those of others, mutagen hypersensitivity was strongly associated with increased risk of head and neck cancer (odds ratio, 4.95; 95% confidence interval, 2.67 to 9.17) after adjusting for age, sex, and race. Low intake of vitamins C and E was also associated with an increased risk of disease and was interactive with mutagen sensitivity in risk estimates. Individuals with both a low intake of various antioxidants and increased chromosomal sensitivity to oxidant-induced DNA damage were at greatest risk. This study supports the concept that the risk of head and neck cancer is determined by a balance of factors that either enhance or protect against free radical oxygen damage, including innate capacities for DNA repair.

Adult↗
PubMed1997

Cigarette smoking and chromosome 9 alterations in bladder cancer.

Epidemiological studies suggest that bladder cancer may be caused by carcinogens in tobacco and certain occupational exposures. Molecular studies have shown that chromosome 9 alterations and TP53 mutations are the most frequent events in bladder cancer. To date, the relationships between epidemiological risk factors and genetic alterations have not been fully explored in bladder cancer. The purpose of this study was to explore the association between smoking and chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for smoking history, occupational history, and chromosome 9 alterations. The epidemiological data were abstracted from medical charts. Patients' tumor tissues were analyzed using RFLP and microsatellite polymorphism assays for detection of chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9 alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence interval, 1.02-17.0) after controlling for age, sex, race, occupational history, and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per day and 5.8 for those smoking > 20 cigarettes per day. No association was found between occupational history and chromosome 9 alterations. This study supplies evidence suggestive of the link between smoking and chromosome 9 alterations in the etiology of bladder cancer and indicates that potential tumor suppressor genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.

Chromosome Aberrations↗
PubMed1997

Cigarette smoking and large cell carcinoma of the lung.

Large cell carcinoma is the fourth most common histological type of lung cancer in the United States. Cigarette smoking causes large cell lung cancer, but it is uncertain whether the effect varies with the amount and duration of smoking. This uncertainty stems from ambiguity in the histopathological classification of large cell cancer, especially before 1971, and the relatively infrequent occurrence of large cell cancer in epidemiological studies. The present case-control investigation demonstrates that the risk of large cell cancer increases with both the frequency and number of years of cigarette smoking. The odds ratio associated with smoking two or more packs/day was 37.0 (95% confidence interval, 16.4-83.2) in men and 72.9 (35.4-150.2) in women. It is concluded that cigarette smoking is the predominant cause of large cell lung cancer.

Adult↗