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F X Bosch

Publications and source records attributed to F X Bosch.

At least 37 records · Page 2Linked to original sources
PubMed2001

Metastatic growth of squamous cell carcinomas is correlated with upregulation and redistribution of hemidesmosomal components.

Bullous pemphigoid antigen-1 (BPA1) and alpha(6)beta(4)-integrin colocalize at the hemidesmosomes in basal-layer keratinocytes of normal squamous epithelia. The expression of these genes was analyzed during the process of tumor cell invasion and metastasis on frozen sections of head and neck biopsies, and the structural appearance of hemidesmosomes was analyzed by electron microscopy. Despite a diminution of hemidesmosomal structures as revealed by electron microscopy, gene expression of BPA1 and alpha(6)beta(4)-integrins was distinctly upregulated with the onset of invasive growth, demonstrated at the mRNA level by in situ hybridization. The upregulated gene expression extended to the entire proliferative zone of invasive tumors, including the tumor cells which have lost contact with the basement membrane and no longer display hemidesmosomes. The polarized localization of the BPA1 and alpha(6)beta(4) proteins to the basal aspect of the peripheral tumor cells was largely retained in invasive but nonmetastatic lesions, but was lost upon progression to metastatic growth of head and neck squamous cell carcinomas (SCC), in which pericellular staining extended into many tumor cell layers. The results of this study confirm that expression of BPA1 and alpha(6)beta(4)-integrins is elevated in carcinoma cells but is not directed to intact hemidesmosomes. Importantly, this loss of directed localization is an indicator of the capacity to metastasize.

Antigens, Surface↗
PubMed2001

Evidence that wild-type p53 in neuroblastoma cells is in a conformation refractory to integration into the transcriptional complex.

Neuroblastoma (NB) cells reportedly accumulate wild-type p53 exclusively in the cytoplasm. However, immunofluorescence assays with five different antibodies showed that p53 accumulates in the nucleus of up to 10% of NB cells. PAb1801 detected cytoplasmic 'punctate structures' which were also found in p53-null cells, rendering this antibody unsuitable for p53 detection. A comparison of DO-1 and PAb1801 staining in NB tissue sections confirmed the results obtained with NB cells. Nuclear accumulation of p53 was induced in NB cells using substances which disturb p53's tertiary structure at its zinc finger motif, or by treatment with mitomycin C. Constitutive nuclear accumulation was observed in an SK-N-SH variant, AW-1, which has a point mutation in p53 at Cys176>Ser, disturbing the same motif. Even though p53 showed DNA-binding capability after mitomycin C treatment of NB cells, the target gene products MDM2 and p21(WAF1,CIP1,SDI1) were not synthesized and no p53 transactivating activity measured in a reporter gene assay. Therefore we suggest that p53 in NB cells might be predominantly in a conformation refractory to integration into the transcriptional complex, resulting in at least partial transcriptional inactivity, hyperactive nuclear export and resistance to degradation by exogenously expressed MDM2.

Animals↗
PubMed2001

[Incidence and survival of leukemias according to the different histologic subsets, in Tarragona, Spain, between 1980-1994].

BACKGROUND: To study the incidence and survival of leukemias according to the different histologic types in Tarragona, Spain. MATERIAL AND METHOD: Analysis of the information obtained from the Cancer Registry of Tarragona (Spain) between 1980-1994. The leukemias were classified in: acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphoid leukemia (CLL) and chronic myeloid leukemia (CML). The estimated incidence rates have been adjusted to the worldwide population, the percentage of the incidence annual change through Poisson regression models and the relative survival using the registry of death rate of Catalonia. RESULTS: The adjusted rate for leukemias between the period 1990-1994 was 8.0 per 100,000 inhabitants in men and of 5.2 in women, being the CLL the most frequent subtype. Regarding the trend of incidence an increase of the CLL of 2.2% annual (CI 95%, 0.1-6.6) in men and of 7.7% (CI 95%, 1.4-14.4) in women was observed. In the remaining subtypes, there was no trend, but the non-classified leukemias decreased a -10.8% annual (CI 95%, -15.0 to -6.4) in men and a -9.9% annual (CI 95%, 15.4 to -4.0) in women. 5-year relative survival (RS5y) for the total leukemias was 37.7% in men and 45.3% in women. It stands out the CLL with a RS5y of 64.8% in men and of 75.7% in women and childhood ALL with a RS5y of 83.0% in boys and of 84.9% in girls. CONCLUSIONS: In Tarragona, Spain, an increase of the CLL incidence has been observed suggesting an improvement in the diagnosis, parallel to a decrease of the non-classified leukemias. The survival in this cohort of patients was similar to the that reported in other european registries.

Adolescent↗
PubMed2001

Adeno-associated virus seropositivity and HPV-induced cervical cancer in Spain and Colombia.

Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-based controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.

Adult↗
PubMed2001

Detailed gene expression analysis but not microsatellite marker analysis of 9p21 reveals differential defects in the INK4a gene locus in the majority of head and neck cancers.

The INK4a gene locus on chromosome 9p21 encodes two proteins, p16(INK4a) and p14(ARF), which influence cell cycle control regulated by pRb and p53. The objective of this study was to use different methods for the analysis of the incidence of changes at the INK4a locus in head and neck cancer (HNSCC). Primary tumours were analysed for allelic imbalances (AI) with microsatellite markers for chromosome 9, by immunohistochemistry (IHC) and IHC with enhanced sensitivity by tyramide signal amplification (TSA-IHC), and by RT-PCR. No homozygous deletions at 9p21 were detected. AI at 9p21, which was found in approximately 60% of the tumours, completely failed to indicate the functional inactivation of the two INK4a gene products. Immunostaining of normal squamous epithelia revealed very low levels of p16(INK4a), whereas p14(ARF) was readily detectable. In 160 tumours, IHC suggested a loss of p16(INK4a) expression in 90%. However, by TSA-IHC, only 53.7% showed loss of p16(INK4a) expression, and this was consistent with the RT-PCR analyses. In 100 tumours analysed for both proteins, selective loss of p16(INK4a) occurred in 37%; loss of p14(ARF) was found in only 15%, and selective loss in only 4%; 11% of the tumours had lost both proteins. We conclude that only IHC with high sensitivity and the combined expression analysis of mRNAs and proteins is suitable for studying the role of INK4a in HNSCC. The INK4a gene expression defects are frequent but not universal and primarily affect p16(INK4a). Their clinical impact is still not clear.

Carcinoma, Squamous Cell↗
PubMed2001

Prevalence and risk factors for herpes simplex virus type 2 infection among middle-age women in Brazil and the Philippines.

BACKGROUND: Data comparing type-specific herpes simplex virus type 2 (HSV-2) seroprevalence and risk factors between comparable populations are largely unavailable, particularly from less-developed countries. GOAL: To examine the seroprevalence of HSV-2 infection and the risk factors for this infection among women in São Paulo, Brazil, and Manila, the Philippines. STUDY DESIGN: Altogether, 552 middle-aged women participating as control subjects in two cervical cancer studies were screened for type-specific HSV-2 antibodies. RESULTS: Herpes simplex virus type 2 seroprevalence was higher in Brazil (42%) than in the Philippines (9.2%). The mean ages of Brazilian (n = 181) and Filipino (n = 371) women were 52.4 and 46.6 years, respectively. Brazilian participants had more lifetime sexual partners, less education, and more often a husband with other sexual partners than Filipino women. Herpes simplex virus type 2 was independently associated with younger age at first intercourse in both countries. More than one lifetime sexual partner, a husband with other sexual partners, urban/semi-urban residence, and no history of condom use were HSV-2 risk factors in Brazil, but not in the Philippines, where long-term hormonal contraceptive use was associated with increased risk. CONCLUSIONS: The higher HSV-2 seroprevalence in Brazil than in the Philippines may be explained largely by differences in the sexual behavior of women and their husbands. Herpes simplex virus type 2 seroprevalence data may be used as a marker of past sexual behavior for the direct comparison of different population groups.

Antibodies, Viral↗
PubMed2001

Prevalence of anti-human papillomavirus type 16, 18, 31, and 58 virus-like particles in women in the general population and in prostitutes.

Genital human papillomavirus (HPV) infection is sexually transmitted. The aim of the study was to characterize serological responses to HPV types 16, 18, 31, and 58 by exploring type-specific virus-like particles (VLPs) in two groups of women with very distinct sexual behaviors. Anti-VLP antibodies for types 16, 18, 31, and 58 and HPV DNA in cervical cells were investigated with 177 prostitutes and 283 age-matched controls from the female general population in Spain. Anti-VLP positivity increased with number of lifetime sexual partners in women from the general population, and no seroresponse was found in virgins. However, in prostitutes HPV infection was characterized by higher multireactivity to three or four VLPs (25%) than the general population (3%) and by a more frequent antibody response to HPV-58 than in the general population. About 75% of the women seropositive for type 58 had been born in a Latin American country. Seroprevalence of HPV and cervical HPV DNA in prostitutes were 14 and 10 times higher than observed in women in the general population (prevalence odds ratio [POR] of HPV seropositivity, 14.04 [95%; CI = 8.4 to 23.6] and POR for HPV DNA, 10.4 [95% CI = 3.9 to 27.6). Our results indicate that prostitutes are at an increased risk of oncogenic HPV infections, and they confirm the validity of anti-VLPs as markers of present or past HPV infection, that the number of sexual partners is the major determinant in acquisition of oncogenic HPV, and that anti-VLPs could be used as a marker of repeated infection in prostitutes.

Adolescent↗
PubMed2001

Increased rectal cell proliferation following alcohol abuse.

BACKGROUND: Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers. METHODS: Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell proliferation, including proliferative compartment size, was measured by immunohistological staining for proliferative cell nuclear antigen (PCNA) and Ki67, and by in situ hybridisation for histone H3. Quantification of cell proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12 controls. In addition, immunohistology was performed for cytokeratins and gene products of Rb1, bcl-2, and p53. RESULTS: Heavy drinking resulted in increased cell proliferation of the rectal mucosa, as shown by increased detection of different proliferation markers. However, cell differentiation regarding cytokeratin expression patterns was unchanged as well as regulatory factors involved in carcinogenesis and/or apoptosis. CONCLUSION: Chronic alcohol abuse leads to rectal mucosal hyperproliferation in humans, a condition associated with an increased cancer risk.

Adult↗
PubMed2001

Papillomavirus research update: highlights of the Barcelona HPV 2000 international papillomavirus conference.

The 18th international papillomavirus conference took place in Barcelona, Spain in July 2000. The HPV clinical workshop was jointly organised with the annual meeting of the Spanish Association of Cervical Pathology and Colposcopy. The conference included 615 abstracts describing ongoing research in epidemiology, diagnosis/screening, treatment/prognosis, immunology/human immunodeficiency virus, vaccine development/trials, transformation/progression, replication, transcription/translation, viral protein functions, and viral and host interactions. This leader summarises the highlights presented at the conference (the full text of the abstracts and lectures can be found at www.hpv2000.com). Relevant material in Spanish can be found at www.aepcc.org.

Female↗
PubMed2001

Overexpression of p53 in tumor-distant epithelia of head and neck cancer patients is associated with an increased incidence of second primary carcinoma.

Second primary carcinoma is a peculiar feature of head and neck cancer and represents a form of treatment failure distinct from the recurrence of the primary tumor. Whether altered p53 expression in tumor-distant epithelia at the time of diagnosis is of clinical value as a biomarker for second primary carcinoma development has not been rigorously answered because of the lack of long-term follow-up studies involving a sufficiently large patient cohort. In this prospective study, we have investigated p53 expression in tumor-distant epithelia and in the corresponding primary tumors of 105 head and neck cancer patients by immunohistochemistry on frozen sections. After a median follow-up of 55 months, the clinical course of disease parameters, i.e., local recurrences, lymph node and distant metastasis, incidence of second primary carcinoma, and survival, was evaluated. Overexpression of p53 in tumor-distant epithelia was found in 49 patients (46.7%), and it was independent of the p53 protein status of the primary tumor and of the tumor site, size, stage, and grading. Mucosal p53 overexpression was not associated with local primary recurrences, lymph node or distant metastases, or overall survival. Importantly, mucosal p53 overexpression, but not overexpression in the primary tumors, was significantly associated with an increased incidence of second primary carcinomas (P = 0.0001; Fisher's exact test). When the times to second primary tumor occurrence were analyzed by the Kaplan-Meier method, the difference remained significant (P = 0.005; log rank test). We conclude that IHC staining for p53 overexpression in tumor-distant epithelia provides a simple and rapid tool to identify head and neck cancer patients at increased risk of developing second primary tumors. Because p53 overexpression in these epithelia in our patient cohort was specifically associated with second primary cancer but not with recurrences, at least a fraction of the second primary cancers appears to have resulted from genetic events in the mucosa ("field cancerization").

Carcinoma, Squamous Cell↗
PubMed2000

Somatic mutations of fibroblast growth factor receptor 3 (FGFR3) are uncommon in carcinomas of the uterine cervix.

Germline mutations of the gene encoding human fibroblast growth factor receptor 3 (FGFR3) have been shown to be responsible for several related autosomal dominant forms of syndromic craniosynostosis and short limb dwarfism. Somatic activating mutations of FGFR3 were recently reported to occur in three of 12 (25%) uterine cervical carcinomas and nine of 26 (35%) bladder carcinomas, suggesting that constitutive activation of FGFR3 may be an important mechanism underlying the development and/or progression of these common epithelial malignancies. In order to investigate further a possible role for FGFR3 mutations in cervical carcinogenesis, we performed sequence-based mutational analysis of FGFR3 in 51 primary cervical carcinomas and seven cervical carcinoma-derived cell lines. The regions analysed (exons 7, 10, 13, 15, and 19) encompassed all previously described FGFR3 mutations. A single nucleotide substitution at codon 249, predicting a serine to cysteine amino acid substitution (S249C) in the FGFR3 extracellular domain, was identified in one primary tumor. Only wild type FGFR3 alleles were identified in the remaining tumors and cell lines. The S249C mutation is the only FGFR3 mutation described to date in cervical carcinomas. These findings suggest that while activating mutations of FGFR3 occur in cervical cancer, they may not be as common as initially reported.

Blotting, Northern↗
PubMed2000

[Human papillomavirus and human immunodeficiency virus infections as risk factors for cervix cancer in women prisoners].

BACKGROUND: The identification of high risk groups for genital human papillomavirus (HPV) infection may contribute to cervical cancer prevention. The study was designed to estimate the prevalence of HPV infection and the related risk of cervical cancer among imprisoned women. PATIENTS AND METHODS: 157 women were visited at the Medical Office of a prison in Barcelona, Spain. Women underwent a structured interview, determination of HIV serostatus and detection of HPV cervical infection by means of PCR. RESULTS: The prevalence of HPV infection was 46%. Prostitution was reported by 38.2% and intravenous drug use by 64.3%. HIV infection was detected in 56.1%. Cervical cytology revealed 19 women with ASCUS and 28 with squamous intraepithelial lesions (SIL) (all grades). HPV infection was associated with an increased risk of intravenous drug use for more than 10 years (prevalence odds ratio [POR] = 2.9) and seropositivity to HIV (POR = 4.7). The increase in risk for SIL related to HIV was explained by the presence of HPV. HIV positive women with low CD4 counts may increase the risk for SIL independently of HPV. CONCLUSION: HIV positive women are at high risk for HPV infection and as a consequence, for developing SIL. HIV positive women should be closely monitored for cervical cancer.

Adolescent↗
PubMed2000

International trends in incidence of cervical cancer: II. Squamous-cell carcinoma.

Time trends in the incidence of squamous-cell carcinomas of the cervix 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 person-years for 2 groups, age ranges 25-49 and 50-74 years, were calculated from the model that best described the incidence data. A significant decline in incidence was noted in the American populations (except for US Hispanic), Australia, the non-Maori women of New Zealand, northern and western Europe (except Italy and Spain, where the rates remain stable) and Asian populations (except Malay women of Singapore, who have stable rates). These trends were of similar magnitude for the whole age range studied (25-74 years). An increasing trend, mainly restricted to younger women, was found for Slovakia, Jewish women born in Israel and the United Kingdom. In Slovenia, the increasing trend was observed for all age groups. The predominant pattern shown by cancer registries in developed countries is of a reduction in the incidence of squamous cervical cancer. This could be, at least partially, attributed to the widespread practice of screening for cervical lesions. The major exception to the pattern is observed in the United Kingdom, though the increasing incidence in young women has changed to a decrease in recent years. There are only a few series covering a long period of time in developing countries, but there is little evidence for a major impact of screening.

Adult↗
PubMed2000

[Detection of numerical chromosome aberrations in leukoplakia and squamous epithelial carcinomas of the head-neck area using fluorescence in situ hybridization].

The tumorigenesis of head and neck squamous cell carcinoma (HNSCC) has been proposed to represent a multistep process characterized by an accumulation of genetic alterations. To study numerical chromosomal aberrations and chromosomal imbalances, biopsies of 11 malignant tumours and biopsies of 16 oral premalignant lesions (leukoplakias) were analyzed by fluorescence in situ hybridization (FISH) using centromeric probes for chromosomes, 1, 7, 9, 10 and 17. The comparison of the alterations observed in simple leukoplakias (group 1, n = 8), dysplastic leukoplakias (group 2, n = 8) and malignant tumours (group 3, n = 11) by the Cochran-Armitage Trend Test revealed an increasing number of numerical chromosomal abberations. This difference was statistically highly significant (p < 0.001). The data open up the possibility that FISH analysis might help to better characterize the progression of premalignant oral leukoplakias.

Biopsy↗
PubMed2000

Loss of fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease.

Allelic losses involving chromosome 3p are frequently observed in cervical cancers. Deletion mapping studies of primary cervical carcinomas have localized common regions of deletion to 3p14.2 and 3p21. The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Fhit protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas. To expand these observations to preinvasive cervical epithelial lesions and to determine whether loss of Fhit protein expression might be associated with tumor progression, immunohistochemical methods were used to examine Fhit expression in 95 invasive cervical carcinomas, 33 high-grade squamous intraepithelial lesions (HSILs) associated with concurrent invasive cancer, 38 HSILs unassociated with invasive cancer, 24 low-grade squamous intraepithelial lesions, and 22 normal cervix samples. All normal cervical epithelia and low-grade squamous intraepithelial lesions exhibited diffuse cytoplasmic immunostaining of moderate to strong intensity. Fhit protein expression was markedly reduced or absent in 67 of 95 (71%) invasive cancers, 17 of 33 (52%) HSILs associated with invasive cancer, and 8 of 38 (21%) HSILs without associated invasive cancer. The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression. Moreover, absent or reduced Fhit protein is observed at a significantly higher frequency in HSILs associated with progression to invasive cancer than in HSILs with unknown risk for progression (P = 0.012). These findings suggest that loss of Fhit expression in HSILs could serve as a useful marker of high-grade preinvasive lesions that have an increased likelihood of progression to invasive carcinoma.

Acid Anhydride Hydrolases↗