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F X Bosch

Publications and source records attributed to F X Bosch.

At least 55 records · Page 3Linked to original sources
PubMed1999

Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.

A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.

Antibodies, Viral↗
PubMed1999

[Prognostic significance of cell-cycle regulatory proteins for outcome after primary radiochemotherapy in patients with advanced head and neck cancer].

BACKGROUND: Primary radiochemotherapy is gaining increasing importance for the treatment of advanced head and neck squamous cell carcinomas. However, there is a lack of clinical factors concerning prognostic information in relation to treatment. In this pilot study, we examined whether molecular factors can provide such information. PATIENTS AND METHODS: The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p53, p21(WAF/CIP1), Rb, p16(INK4A), CDK4 and Cyclin D1, MIB1 (Ki-67) and BCL-2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx (n = 26), hypopharynx (n = 10) and larynx (n = 7) by applying immunohistochemistry to paraffin sections of tumor specimens. All patients were treated by the same method of an accelerated "concomitant boost" radiochemotherapy with carboplatin in a phase II study. Median followup time was 56 months. RESULTS: No correlation was found between any of the markers and the remission rate, T-stage, N-stage, rate of loco-regional recurrences and distant metastases. However, independent of the tumor stage, patients with CDK4/cyclin-D1 overexpressing tumors had a significantly shortened overall survival (P = 0.014 and 0.026, respectively). CONCLUSION: The results of this pilot study indicate that CDK4 and cyclin D1 over-expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients.

Adult↗
PubMed1999

[The role of oncogenic human papillomaviruses in tonsillar squamous cell carcinomas with functional inactivation of the retinoblastoma protein].

In order to identify squamous cell carcinomas of the head and neck (HNSCC) with common biological and clinical features, we investigated the incidence and properties of carcinomas lacking retinoblastoma protein (pR6) cell cycle control. Of 208 HNSCC investigated, 23 (11%) showed a lack of pRb expression. The majority of these tumors (65%) were tonsillar carcinomas. The pRb-negative tonsillar tumors were all stage IV, had metastasized to lymph nodes at the time of diagnosis and were in general poorly differentiated or undifferentiated. Very significantly, the pRb-negative phenotype was strongly associated with the presence of oncogenic human papilloma viruses, implying a viral etiology and functional inactivation of pRb by the viral E7 oncoprotein. Despite the very adverse histopathological factors, patients with pRb-negative tonsillar carcinomas had a better clinical outcome, which was consistent with a uniform favorable responsiveness of these tumors to postoperative radiation therapy.

Carcinoma, Squamous Cell↗
PubMed1999

Defects of basement membrane and hemidesmosome structure correlate with malignant phenotype and stromal interactions in HaCaT-Ras xenografts.

Benign and malignant HaCaT-ras clones, derived from immortalized HaCaT cells were grown as nude mouse surface transplants rendering a human tumor progression model. Searching for malignancy-related alterations, the deposition, localization and mRNA of basement membrane and hemidesmosome components were analysed by immunofluorescence, in situ hybridization and electron microscopy. Initially, at 1 week epithelia of benign and malignant cells revealed a similarly low polarity and an enlarged 'activated basal' compartment, reflected by partial dislocation and extended pericellular staining of the hemidesmosome constituent integrin alpha 6 beta 4 seen by immunofluorescence. Whereas benign grafts eventually normalized, closely resembling grafts of HaCaT cells, malignant growth was correlated with a persisting epithelial activation state and continuing higher expression of alpha 6 (by immunofluorescence and in situ hybridization). The basement membrane components bullous pemphigoid antigen 1, laminin-5 and collagen IV exhibited a largely linear distribution at 1 week. However, in the malignant cell transplants initially minor basement membrane discontinuities became more severe at around 2 weeks, associated with close stromal cell contacts, angiogenesis and invasion. Most striking were basement membrane alterations seen by electron microscopy. At 1 week stretches of basement membrane had developed in malignant transplants, though to a much lesser extent than in benign specimens. With invasion these basement membrane structures mostly disappeared despite persistent although variable immunofluorescence, suggesting high turnover without ultrastructural assembly. The hemidesmosome structures were defective throughout, completely lacking anchoring plaques with keratin filaments, whereas they were still associated with basement membrane deposits. Thus, malignant HaCaT-ras transplants, while initially resembling regenerating wounds, revealed an increasing loss of tissue polarity and basement membrane structures, which seemed to be accelerated upon stromal cell contacts.

Animals↗
PubMed1999

Epidemiology of primary liver cancer.

Liver cancer (LC) ranks fifth in frequency in the world with an estimated number of 437,000 new cases in 1990. In developing countries, incidence rates are two- to three-fold higher than in developed countries. The geographic areas at highest risk are located in Eastern Asia, with age-adjusted incidence rates (AAIRs) ranking from 27.6 to 36.6 per 100,000 in men; Middle Africa, with AAIRs ranking from 20.8 to 38.1 per 100,000 in men; and some countries of Western Africa, with AAIRs ranking from 30 to 48 per 100,000 in men. The geographic areas at lowest LC risk are Northern Europe, Australia, New Zealand, and the Caucasian populations in North and Latin America, with AAIRs below 5.0 per 100,000 in men. Excess of LC incidence among men compared to women is universal, with sex ratios between 1.5 and 3.0. Significant variations in LC incidence among different ethnic groups living in the same geographical area and among migrants of the same ethnic groups living in different areas have been extensively described. The variability of LC incidence rates between countries and within countries, strongly suggests differences in exposure to risk factors. The role of chronic infection with the Hepatitis B and hepatitis C viruses (HBV and HCV) in the etiology of LC is well established. The attributable risk estimates for LC for each of these hepatotropic viruses vary among countries but the combined effects of persistent HBV or HCV infections account for well over 80% of LC cases worldwide. Other documented risk factors such as aflatoxin exposure in diets, cigarette smoking, alcohol consumption, and oral contraceptives may explain the residual variation between and within countries. Interactions between some risk factors have been postulated, and are subject of active research. New laboratory techniques and biological markers such as polymerase chain reaction detection of HBV DNA and HCV RNA, as well as specific mutations related to aflatoxin exposure may help to provide quantitative estimates of the risk related to each these factors.

Aged↗
PubMed1999

Serum antibodies to human papillomavirus 16 proteins in women from Brazil with invasive cervical carcinoma.

Serum samples from 194 cases and 217 controls participating in a case-control study of invasive cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 virus-like particles (VLPs) by ELISA. The prevalence of antibody in cases and controls was 47.4 versus 24.4% (P < 0.001). The prevalence was higher in women who had HPV-16 DNA in the genital tract (54.2%) than in those with other HPVs (36.8%) or no HPVs (44.8%), but the differences were not statistically significant. Among cases and controls, HPV-16 VLP antibodies were associated with a greater number of lifetime sexual partners (chi2 for trend, P < 0.001). Among controls, age was inversely associated with HPV-16 VLP seroreactivity (chi2 for trend, P = 0.019). The sera were previously tested for antibodies to HPV-16 E6 and E7 oncoproteins; there was no correlation between antibody titers to HPV-16 E6 or E7 and VLPs. The HPV-16 serological assays were compared as screening tests for invasive cervical cancer. The sensitivity and specificity estimates were 47.4 and 75.6% for HPV-16 VLP serology, 63.4 and 89.9% for either HPV-16 E6 or E7 serology, and 53.6 and 93.6% for high titers of either HPV-16 E6 or E7 or VLP antibodies. The utility of HPV-16 VLP ELISA as a screening test for invasive cervical cancer is limited by a high seroprevalence in women with probable prior exposure to HVP 16 but without disease.

Adult↗
PubMed1998

TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer.

Recent studies have suggested that different mutation types within the core domain of the tumour suppressor protein p53, i.e. DNA contact mutations and structural mutations, confer different biological properties. We have analysed in 86 head and neck squamous cell carcinomas (HNSCC), whether these p53 mutation types have a differential clinical impact. Thirty-seven missense mutations were identified. Thirteen of these (36%) were DNA contact mutations, occurring in the L3 loop, in the H2 loop sheet helix motif, in the S10 beta strand and in Zinc binding residues. Microsatellite marker analysis revealed a selective association between these mutations and the loss of wild-type alleles (100% LOH vs 50% LOH in tumours with structural mutations; P=0.0034, Fisher's exact, 2-tailed). In comparison to structural mutations or to the absence of mutations in the core domain, DNA contact mutations were associated with higher tumour stages (84.6% vs 62%), a higher incidence of lymph node metastasis (91.7% vs 56%; P=0.014, Fisher's exact, 2-tailed), a shortened recurrence-free survival (8.1 months vs 23.7 months, P=0.047, log rank test) and overall survival (11 months vs 29.2 months; P=0.003, log rank test). The latter was also the case when only stage IV tumours were analysed (P=0.0055, log rank test). These data indicate that in HNSCC, TP53 DNA contact mutations confer a strong selection pressure to eliminate wild-type alleles, and that they result in an accelerated tumour progression and reduced therapeutic responsiveness.

Adult↗
PubMed1998

International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas.

Time trends in the incidence of cervical adenocarcinoma and adenosquamous cell carcinomas during the period 1973-1991 were examined using data provided by 60 population-based cancer registries from 32 defined populations in 25 countries. Three components of the incidence trend were studied: age, calendar period of diagnosis and birth cohort. Cumulative incidence rates per 1,000 for 2 groups with age ranges 25-49 and 50-74 years were calculated from the model that best described the incidence data. There was a significant increase in the cumulative incidence of cervical adenocarcinomas in women born in the mid-1930s and in successive cohorts thereafter in some populations in the United States (whites and Hispanic women), Australia, New Zealand (non-Maori), England, Scotland, Denmark, Slovenia, Slovakia and Japan (Osaka) and among Chinese women in Singapore, with a general decline in the incidence in women born in earlier periods. In Sweden and Slovenia there is a suggestion of an increasing trend in both age groups. A decrease in incidence in both age groups was apparent in Finland, France and Italy. There were no changes in incidence in 24 registries covering other European, Asian and black populations in the United States. Part of the increase may be attributable to an increasing prevalence of human papillomavirus infection, and part to improvements in screening.

Adenocarcinoma↗
PubMed1998

The viral origin of cervical cancer in Rabat, Morocco.

In Northern Africa, cervical cancer is the second most common cancer among women. The diagnosis is usually made in advanced stages, and mortality is high, yet few studies have investigated the role of human papillomavirus (HPV) and other risk factors in the etiology of cervical cancer. A hospital-based case-control study was completed at the Institut National d'Oncologie (INO) in Rabat, Morocco. The study included 214 cases of invasive cervical cancer and 203 controls. A structured questionnaire was used to investigate known and suspected risk factors for cervical cancer. A GP 5+/6+ polymerase chain reaction system was used to detect the presence of HPV DNA and HPV type distribution. Probes for 30 HPV types were used in one research laboratory. HPV DNA was the central risk factor and accounted for the large majority of the cases. The adjusted odds ratio (ORa) for any HPV was 61.6 (95% CI, 29.2-130) and the corresponding HPV attributable fraction (AF) was 92%. Among cases of cervical cancer, HPV 16 was the most common type (67.7%) followed by HPV 18. The HPV type-specific prevalence was similar for squamous cell carcinomas and adenocarcinomas. In multivariate adjusted or HPV-stratified analyses, in addition to the strong effect of HPV, other risk factors identified were sexual intercourse with multiple partners before the age of 20 and low socio-economic status. Use of oral contraceptives for 5 or more years and high parity were also found to be related to cervical cancer. Screening was rare in this population but offered substantial protection against cervical cancer. In Morocco, cervical cancer is a late sequel of a viral infection with certain HPV types. Developing screening programs for preneoplastic cervical lesions is a public health priority. When available, HPV vaccination would offer a relevant alternative for preventing cervical cancer.

Adenocarcinoma↗
PubMed1998

[Risk of developing and dying from cancer in Catalonia, Spain].

BACKGROUND: Cumulative risk reflects the lifetime probability that a person will develop a disease or will die from a disease. In this paper we estimate the cumulative risk of developing cancer and dying from cancer during the period 1988-1992 in Catalonia (Spain). MATERIAL AND METHODS: Data from the Tarragona Cancer Registry and Catalonia Mortality Registry are used. Cancer incidence from Tarragona is extrapolated to the total Catalan population. Cumulative risk is estimated from cumulative rate and with a life table method, which takes into account competing risks. The change in risk with age is also studied. RESULTS: Lifetime risk of developing cancer in Catalonia is 38.9% for men and 28.0% for women. Risk of dying from cancer is 26.3% for men and 17.2% for women, that is, a 67.6% and a 61.5% of incident cases, respectively. One in 14 men will develop lung cancer and nearly all of them will die from the disease. One in 14 women will develop breast cancer and 45% of them will die from the disease. CONCLUSION: Cancer is an important health problem in Catalonia because its high impact at the individual level shown by the cumulative risk. More than one in 3 men and one in 4 women are diagnosed of cancer during their lives and, among them, two thirds die because the disease.

Adolescent↗
PubMed1998

5-Lipoxygenase expression in Langerhans cells of normal human epidermis.

We studied expression of the 5-lipoxygenase (5-LO) pathway in normal human skin. In situ hybridization revealed a 5-LO mRNA-containing epidermal cell (EC) population that was predominantly located in the midportion of the spinous layer, in outer hair root sheaths, and in the epithelial compartment of sebaceous glands. Examination of skin specimens by immunohistochemistry and of primary ECs by flow cytometry mapped the 5-LO protein exclusively to Langerhans cells (LCs). The LC 5-LO protein was largely found in the nuclear matrix, in nuclear envelopes, and perinuclear regions as indicated by in situ confocal laser scan microscopy. Reverse transcription-PCR and immunoblot analyses of purified primary EC populations further indicated that LCs are major 5-LO expressing cells. Enriched primary LCs were also found to contain 5-LO activating protein (FLAP), leukotriene (LT) C4 synthase, and LTA4 hydrolase. By contrast, 5-LO, FLAP, and LTC4 synthase were undetectable or largely reduced, but LTA4 hydrolase transcripts and protein were identified in ECs depleted of LCs. These data show that naive LCs are major, and possibly the sole, 5-LO pathway expressing cells in the normal human epidermis.

Arachidonate 5-Lipoxygenase↗
PubMed1998

Causes of cervical cancer in the Philippines: a case-control study.

BACKGROUND: Among the numerous human papillomavirus (HPV) types, only types 16 and 18 have been formally classified as human carcinogens. To evaluate the associations of 33 HPV types and other risk factors with squamous cell carcinoma and adenocarcinoma of the cervix, we performed a hospital-based, case-control study in the Philippines. METHODS: The study included 356 case subjects who had histologically confirmed cervical cancer (323 incident cases of squamous cell carcinoma and 33 incident cases of adenocarcinoma/adenosquamous carcinoma) and 381 control subjects. Information on risk factors was obtained by personal interview. HPV DNA was detected in exfoliated cervical cells and biopsy specimens by use of a polymerase chain reaction assay. RESULTS: HPV DNA was detected in 93.8% of case subjects with squamous cell carcinoma and in 90.9% of case subjects with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control subjects, giving age-adjusted odds ratios of 156 (95% confidence interval [CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were detected in squamous cell carcinoma, and six different HPV types were detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other than types 16 and 18, the associations of HPV with risk of squamous cell carcinoma were strongest for HPV45. In addition to HPV, high parity, low socioeconomic status, and smoking were also associated with both types of cervical cancer. CONCLUSIONS: As has been shown for squamous cell carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous carcinoma of the uterine cervix. The observed associations of less prevalent HPV types with cervical cancer have important implications for cervical cancer prevention strategies.

Adenocarcinoma↗
PubMed1998

Risk factors for cervical cancer in Thailand: a case-control study.

BACKGROUND: Human papillomaviruses (HPV) types 16 and 18 are clearly involved in the etiology of cervical cancer, but the evidence for the carcinogenicity of other HPV types is limited. Cofactors involved in the progression from infection with HPV to high-grade precursors and cancer have not been clearly defined by the results of previous studies. METHODS: We conducted a hospital-based, case-control study of invasive cervical cancer to investigate risk in relation to HPV infection and its epidemiologic cofactors in Hat-Yai, Thailand. A total of 338 patients with squamous cell carcinoma, 39 patients with adenocarcinoma/adenosquamous carcinoma, and 261 control subjects were included in the study and were interviewed to obtain information with regard to cervical cancer risk factors. HPV DNA presence in cervical exfoliated cells or frozen biopsy specimens was determined by a polymerase chain reaction assay. RESULTS: HPV DNA was detected in 95% of patients with squamous cell carcinoma, 90% of those with adenocarcinoma/adenosquamous carcinoma, and 16% of control subjects. For patients with squamous cell carcinoma, the most common types of HPV found were type 16 (60% of the positives), type 18 (18%), type 58 (3%), type 52 (3%), and type 31 (2%). For patients with adenocarcinoma/adenosquamous carcinoma, the most common HPV types found were type 18 (60% of the positives), type 16 (37%), and type 45 (3%). The risk factors that remained associated with risk of both histologic types after adjustment for HPV and their mutual confounding effects were limited education, increasing number of sexual partners, history of venereal diseases, and interval since last Pap smear (i.e., cytologic) test. Among patients with squamous cell carcinoma, some association with smoking was also observed. CONCLUSION: New preventive strategies for cervical cancer will require the consideration of multiple HPV types.

Adenocarcinoma↗
PubMed1998

Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control.

Two hundred eight primary squamous cell carcinomas of the head and neck have been analyzed with respect to the presence of the retinoblastoma tumor suppressor protein, pRb. Of these, 23 tumors (11%) that preferentially localized to the tonsils revealed complete absence or dramatic reduction in the amount of pRb. Other cell cycle components, cyclin D1 and p16INK4A, which are intimately related to pRb through an autoregulatory loop, were also dramatically decreased or overexpressed, respectively, in these pRb-defective tumors. On the other hand, the majority of the pRb-defective tumors contained the wild-type p53 gene. No evidence was found for genetic defects at the Rb locus in these tumors. Very significantly, in 11 of 12 pRb-defective tonsillar tumors, but in none of 9 pRb-positive tonsillar tumors (P < 10[-7]), DNA of oncogenic human papillomavirus types was identified, providing a strong indication for a human papillomavirus-associated etiology of these tumors and suggesting the functional inactivation of the pRb protein by the viral E7 gene product. In comparison to all head and neck squamous cell carcinomas studied, the pRb-defective tonsillar tumors were in general more poorly differentiated (P = 0.0059), and they were all metastatic at the time of resection. Of particular clinical interest, despite these adverse histopathological factors, the clinical outcome for these patients was relatively favorable, strongly implying that the pRb-defective tumors responded uniformly well toward postoperative radiation therapy.

Carcinoma, Squamous Cell↗
PubMed1998

Oral leukoplakias show numerical chromosomal aberrations detected by fluorescence in situ hybridization.

To examine at which stage in the multistep process of head and neck tumorigenesis numerical chromosomal alterations can be detected by fluorescence in situ hybridization (FISH), biopsies and cell smear preparations of clinically healthy oral tissue, premalignant lesions (leukoplakias), and tumors were analyzed by FISH using chromosome-specific centromeric probes. Aberrations found in tumor biopsies and in tumor cell smears consisted of trisomy of chromosomes 1, 7, 10, and 17 and monosomy of chromosomes 1, 7, 9, 10, and 17. In five of eight dysplastic oral leukoplakia biopsies, aberrations were seen consisting of trisomy of chromosome 1, 7, and 17, and monosomy of chromosome 9. No aberrations were found in biopsies of hyperplastic lesions (n = 8), or in oral cell smears of persons at risk. Because numerical chromosomal aberrations seem to be highly specific for malignant cells, FISH may help to identify leukoplakias that have a high risk of malignant conversion.

Adolescent↗
PubMed1998

[Detection of human papillomavirus DNA by PCR in high-risk women. Validation of a protocol].

OBJECTIVE: To validate a protocol for HPV DNA detection using PCR (polymerase chain reaction). METHOD: HPV was investigated in cervical exfoliative specimens from 93 women at high risk for HPV infection Blind comparisons of HPV DNA detection using two PCR protocols were carried out in our laboratory and a widely accepted reference laboratory. RESULTS: HPV DNA prevalence varied according to the different protocols. A good agreement with the reference protocol was reached when a reduction of the cellular amount for DNA extraction was carried out. The prevalence of HPV DNA in this population was 50.5%. All cases with dysplasia were HPV DNA positive. The HPV type distribution was as follows: 29.8% HPV 16, 17% HPV 33, 12.7% HPV 11/6, 12.7%, HPV 18, 23.4% HPV 31, 3.6% HPV 39 y 4.3% HPV 51. An underestimation of the prevalence of HPV 51 was detected by our procedure in relation to the reference laboratory. CONCLUSIONS: HPV DNA detection by PCR may increase with simple protocol modifications. Regular validation studies are important to reach good sensitivity levels.

Adult↗