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Biomedical subjects

F X Bosch

Publications and source records attributed to F X Bosch.

At least 109 records · Page 6Linked to original sources

[Salivary duct cyst of the parotid gland and adenocarcinoma].

The progression of benign cystic lesions of the parotid gland to malignant tumors is an extremely rare event and has been described only for cystadenolymphomas. Here we present a case of malignant transformation to an adenocarcinoma occurring in ductal cells forming the wall of a parotid retention cyst. In addition to clinical and histological findings, we describe the results of immunohistochemical and molecular analyses providing evidence that the cells undergoing neoplastic transformation were latently infected by Epstein-Barr virus (EBV). These results suggest a possible causal relationship between latent EBV infection and malignant progression.

Adenocarcinoma↗

Human papillomavirus-related serological markers of invasive cervical carcinoma in Brazil.

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm > 6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II-IV and 31.0% in cases with stage I (P < 0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serologic response in human papillomavirus-associated invasive cervical cancer.

Human papillomavirus (HPV) transforming proteins E6 and E7 are uniformly expressed in HPV-associated cervical cancer. Our objective was to measure antibodies to HPV-16 E6 and E7 proteins in cervical cancer patients using an assay which would detect antibodies to conformational epitopes. Serum specimens obtained from two case-control studies of HPVs and cervical cancer were tested. The studies were performed in Cali, Colombia, South America and in 9 provinces of Spain. Cases consisted of women with invasive cervical cancer associated with HPV-16 or other HPV types and women with HPV-16-associated high-grade cervical intra-epithelial neoplasia (CIN-3). Controls for invasive cases and CIN-3 cases were women who had no cytologic abnormalities and who were matched for age and country of residence. Serum antibodies to HPV-16 E6 and E7 proteins were detected by radio-immunoprecipitation of in vitro translated proteins. Antibodies to the E6 and E7 protein were observed among 56% and 43%, respectively, of invasive cases and 1.7% and 4.1%, respectively, of controls. Antibodies to either protein were detected in 72% of sera from invasive cases and 5.8% of sera from controls. High antibody reactivity and antibodies to both proteins were found almost exclusively in invasive cases. The frequency of antibodies to the E6 protein and the E7 protein among CIN-3 cases did not differ significantly from the CIN-3 controls. Five women with HPV-18-associated invasive cervical cancer were negative for serum antibody to HPV-16 E6 and E7 proteins. Antibodies to HPV-16 E6 and E7 proteins appear to be partially virus-specific and disease state-specific markers of HPV-associated cervical cancer.

Antibodies, Viral↗

Expression of mutated p53 occurs in tumor-distant epithelia of head and neck cancer patients: a possible molecular basis for the development of multiple tumors.

As in most other tumor types, expression of mutated or phenotypically altered p53 is a common occurrence in head and neck carcinogenesis. Since the prognosis for many head and neck tumor patients is severely affected by the occurrence of multiple primary and secondary tumors, we have analyzed the phenotype and genotype of p53 in squamous and respiratory epithelia either adjacent to or at significant distance from the primary tumors. Many tumor patients showed multifocal overexpression of the p53 protein in a variety of these epithelia. Overexpression of p53 correlated with increased proliferation and dedifferentiation, as demonstrated by immunohistochemistry and in situ hybridization using histone H3 and cytokeratin-specific probes. Polymerase chain reaction-single-strand conformation polymorphism analysis and sequencing of p53 DNA, amplified from these biopsies after immunostaining and microdissection, confirmed and extended these findings. We have identified different mutations in p53 in different tumor-distant epithelia from the same patients. The data indicate that mutation of p53 is an early event in head and neck carcinogenesis, preceding signs of overt neoplasia, and that different mutations in p53 in multiple foci may provide a molecular basis for the development of multiple tumors.

Base Sequence↗

Diet and colorectal adenomas: a case-control study in Majorca.

A case-control study on dietary factors and colorectal adenomas was conducted in the island of Majorca, Spain, from April 1987 to February 1990. Subjects were interviewed using a food frequency questionnaire. Nutrient and caloric intake was estimated using local food composition tables. The risk of colorectal adenomas was related to the consumption of sugar and pastries. Consumption of vegetables was highly protective, irrespective of the cooking procedures. Analyses by nutrients identified as protective factors fiber from fruits and vegetables, magnesium and zinc, and vitamins C, B6 and folic acid. No excess risk was found for alcohol drinking, intake of saturated fats or animal protein. Of the non-dietary factors, sedentariness in the work-place and urban residence were the only risk factors identified.

Adenoma↗

Expression of the histone H3 gene in benign, semi-malignant and malignant lesions of the head and neck: a reliable proliferation marker.

To search for a reliable proliferation marker in epithelial head and neck lesions, we have analysed the expression of the histone H3 gene by in situ hybridisation and compared this with the immunoreactivity of the widely used monoclonal antibody Ki-67. In many lesions, the Ki-67 staining failed to delineate proliferation. In contrast, the H3 hybridisation signals were in accordance with the histopathology of the biopsies: in hyperplastic epithelia, significant H3 mRNA levels were only seen in areas with inflammation. Dysplastic cells showed distinctly elevated H3 expression. Benign and semi-malignant tumours, i.e. basal cell carcinomas, showed moderate H3 signals at the periphery. In squamous cell carcinomas, H3 expression was always high at the expanding zone of the tumour and was most extensive in undifferentiated carcinomas. Thus, the expression of the histone H3 gene closely reflected the dynamics of neoplastic growth within and around head and neck tumours.

Biomarkers, Tumor↗

[Human papilloma virus in the etiology of cervicouterine cancer].

The objectives of this study were to confirm the hypothesis that invasive carcinoma of the uterine cervix and the precursors of that condition are most often caused by human papilloma virus (HPV) infections, and to determine whether or not other risk factors are involved in the neoplastic process. For this purpose, four concurrent case-control studies were carried out. Two included cases of invasive cervical cancer and population-based controls. The other two included cases of in situ carcinoma and controls. Research was carried out in nine provinces of Spain and in Cali, Colombia. The identification of cases took place between June 1985 and June 1988. The studies included 436 incident cases of invasive carcinoma and 387 controls, selected at random from the corresponding populations, and 525 cases of in situ carcinoma and 512 controls paired by age, place of recruitment, and date that cytological specimens were taken from the women participating in cytological screening programs. Exposure to HPV was detected through hybridization tests after amplification by polymerase chain reaction (PCR) in exfoliated cervical cells from cases and controls. Exposure to HPV was the principal risk factor in the four studies. For invasive carcinoma, the relative risk and 95% confidence interval were 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Colombia. For in situ carcinoma, the figures were 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Colombia. This strong association was specific for types 16, 18, 31, 33, and 35 as well as still-unclassified HPV types.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma in Situ↗

[Significance of aberrant p53 protein in head-neck tumors and its effect on proliferation and differentiation].

Mutation of the tumor suppressor gene p53 is the most frequent genetic alteration of human tumors. Our systematic immunohistochemical analysis of the p53 phenotype and the comparison to proliferation and differentiation has revealed that over 50% of the squamous cell carcinomas of the head and neck show p53 accumulation of aberrant p53 protein. Normal epithelia did not show p53 accumulation and benign lesions only in exceptional cases. Expression of aberrant p53 was invariably confined to dysplastic cells in close vicinity to the tumor and to invasive, dedifferentiated tumor cells with high proliferative potential, as revealed by expression of the histone H3 gene and of the simple epithelial type cytokeratins. We discuss the possible clinical value of the immunohistochemical screening of tumor patients for the status of the p53 gene.

Adenocarcinoma↗

The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain.

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.

Carcinoma, Squamous Cell↗

Risk factors for cervical cancer in Colombia and Spain.

A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.

Age Factors↗

Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16-associated invasive cervical cancer.

Transforming proteins E6 and E7 of human papillomaviruses (HPVs) are consistently expressed in HPV-associated cervical cancers. In ELISA with four HPV-16 E6-E7 peptides, patients with HPV-16-associated invasive cervical cancer (group 1) had a greater seroreactivity than all other groups, which included patients with HPV-16-associated cervical intraepithelial neoplasia, invasive cervical cancer patients without HPVs, and unaffected controls. A larger proportion of group 1 sera, as compared to sera of all other groups, was reactive with at least one peptide (49% vs 17-27%), and with two or more peptides (22% vs 0-6%). A clear difference between group 1 and all other groups was also found for high ELISA absorbance values to at least one peptide (22% vs 0-8%). This high seroreactivity of group 1 sera was confirmed by a radioimmunoprecipitation assay with in vitro transcribed and translated HPV-16 E7 protein. Sera from 50% of group 1 but only 3% of controls were reactive in this test. Antibodies to HPV-16 E6 and E7 proteins appear to be virus-specific and disease state-specific markers of HPV-associated cervical cancer.

Amino Acid Sequence↗

Comparison of ViraPap, Southern hybridization, and polymerase chain reaction methods for human papillomavirus identification in an epidemiological investigation of cervical cancer.

In order to provide a reliable diagnosis for the presence and type of human papillomavirus (HPV) DNA in a case-control study of cervical cancer in Colombia and Spain, 926 cervical scrapes from female subjects were examined by ViraPap (VP) and Southern hybridization (SH), and 510 of these (263 cases and 247 controls) were also tested by polymerase chain reaction (PCR) using the HPV L1 consensus primers. HPV DNA prevalence was much higher in cases than in controls by each of the three tests. There was complete agreement between the results of the three tests for 64.9% of the 510 specimens; 53.5% were negative and 11.4% were positive (regardless of type) by all tests. An additional 29.0% of the specimens were positive by PCR: 19.4% by PCR alone, 6.7% by PCR and VP, and 2.9% by PCR and SH. SH and/or VP gave positive results for 6.0% of the specimens for which the PCR finding was negative: 2.7% by SH alone, 2.5% by VP alone, and 0.8% by both VP and SH. When specimens which were positive by VP alone or only by SH at low-stringency conditions were excluded, PCR confirmed all but four specimens which were positive by other tests. The concordance between type-specific diagnosis by SH and PCR was 86% when HPVs were typed in both tests. HPV-16 accounted for over 80% of the typed HPVs in each test. The presence of blood in case specimens did not appear to inhibit HPV positivity by VP or by PCR at the dilution tested. Low amounts of cellular DNA of specimens resulted in some underestimation of HPV positivity by VP and SH but not by PCR. Compared with that of PCR, the sensitivities for case specimens were 38% by SH and 50% by VP; the sensitivity for control specimens, although it could not be measured precisely because there were few positive specimens, appeared to be lower than for case specimens. It was concluded that PCR-based tests are best suited for epidemiological investigation of HPVs.

Adult↗

HPV and cervical neoplasia: review of case-control and cohort studies.

Epidemiological studies on the association between human papillomavirus (HPV) and cervical cancer are reviewed. Studies using HPV DNA hybridization methods to assess the presence of viral markers have yielded compelling evidence that HPV has a causal role in the disease: the association is strong, consistent and specific to a limited number of viral types. A dose-response relationship has been reported between increasing estimated viral load and risk of cervical cancer. Indirect evidence suggests that HPV DNA detected in cancer cells is a good marker of HPV infection occurring before cancer development. An increased risk for progression to more advanced CIN lesions has been reported among HPV 16/18-positive women as compared to women with other HPV types or to women without any viral DNA.

Case-Control Studies↗

HPV types in women with normal cervical cytology.

PCR-based hybridization methods have been used to show that some women with normal cytology are carriers of HPV DNA of the types strongly related to cervical cancer. How these women should be managed remains unclear. This chapter selectively reviews reports which have estimated type-specific HPV prevalence in relation to the presence or absence of morphological signs of HPV infection. Overall, these reports indicate that among women who were identified as carriers of HPV DNA (by PCR-based methods) and who also had a normal cytological smear, the HPV type detected in the majority of instances was a high-risk viral type for cervical cancer (HPV types 16/18 = 44.7%; HPV types 31/33/35 = 8.1%; other and unknown types = 37.9%). This suggests that screening programmes which include PCR-based HPV detection could reduce the false negative rates currently reported by screening programmes based on cytology alone.

Adult↗

Nutritional factors in colorectal cancer risk: a case-control study in Majorca.

The relationship between energy intake, selected nutrients and colorectal cancer was investigated in the population of Majorca, a Spanish island in the Mediterranean basin. A population-based case-control study using food frequency questionnaires was conducted during the period 1984-1988 and included 286 cases of colorectal cancer, 295 population controls and 203 hospital controls. Food composition tables and ad-hoc estimates of portion sizes were used to derive intake estimates of 29 nutrients and of total calories. Relative risks were calculated for quartiles of consumption of each specific nutrient after adjustment for total calorie intake. Colorectal cancer was found associated with dietary intake of total calories (RRs = 1.0, 1.6, 1.6, 2.6) and cholesterol (RRs = 1.0, 0.9, 1.7, 1.7) and a protective effect was associated with the intake of fibre from legumes (pulses) and folic acid. The associations and the trends were statistically significant. Among the main energy-supplying nutrients, after adjustment for calories from other sources, increased risks were found for protein (RRs = 1.0, 1.1, 1.7, 2.5), notably animal protein, and carbohydrates (RRs = 1.0, 1.5, 1.4, 2.2), whereas no effects were found for increased consumption of lipids or saturated fats.

Case-Control Studies↗

Inverse relationship between human papillomavirus (HPV) type 16 early gene expression and cell differentiation in nude mouse epithelial cysts and tumors induced by HPV-positive human cell lines.

Two human papillomavirus type 16 (HPV 16)-immortalized human keratinocyte cell lines (HPK) were shown to have retained the ability for differentiation after subcutaneous injection into nude mice. These properties were maintained even at late passage. HPK cells gave rise to transiently growing cysts which exhibited an epitheliumlike architecture. Moreover, differentiation-specific markers such as cytokeratin 10, involucrin, and filaggrin were shown to be expressed in an ordered succession. RNA-RNA in situ hybridization revealed heterogeneous and low levels of HPV 16 E6-E7 RNA in the basal layer of the cysts. In contrast, in progressively growing tumors induced by HPK cells containing an activated ras oncogene (EJ-ras) or in tumors induced by the cervical carcinoma cell line CaSki, high levels of E6-E7-specific RNA could be detected. Irrespective of the growth potential of these cell lines in nude mice, viral transcription was always more evident in the basal layer and in proliferatively active cells rather than in differentiated cells. This contrasts with viral gene expression in HPV 16 positive low-grade cervical dysplasia, in which abundant viral transcriptional activity was mapped to the upper third of the epithelium. It is suggested that the physical state of the viral DNA, i.e., integrated viral DNA in the cell lines as opposed to extrachromosomal DNA in low-grade cervical dysplasia, may influence viral gene regulation.

Animals↗