Biomedical subjects

Teresa Cabral

Publications and source records attributed to Teresa Cabral.

4 recordsLinked to original sources

PubMed2006

Structure-activity studies with cytotoxic anthrapyrazoles.

Anthrapyrazoles have been investigated as cancer chemotherapeutic agents. The mechanism of action of these compounds is thought to involve inhibition of DNA topoisomerase II. A structure-activity study was carried out to determine the in vitro cytotoxic activity of nine novel anthrapyrazoles against human breast carcinoma, head and neck squamous cell carcinoma and leukemia cells, and against Chinese hamster ovary cells. The activity of these anthrapyrazole analogues was compared with that of two clinically tested anthrapyrazoles, losoxantrone and piroxantrone. Inhibition of topoisomerase II as a mechanism of action for the analogues was also investigated. The cytotoxic activity of the analogues was determined in vitro by MTT cell growth inhibition assay and inhibition of catalytic topoisomerase II activity by each compound was measured using a fluorometric DNA decatenation assay. All of the anthrapyrazole analogues inhibited the growth of the four cell lines with IC50 values that ranged from 0.1 to 45.2 microM. Losoxantrone was the most potent of the anthrapyrazole analogues studied. A tertiary amine in the basic side chain at N-2 increased the cytotoxic activity compared with a secondary amine in this side chain for many of the analogues, but not if there was a basic side chain at the C-5 position. A chlorine substituent on the basic side chain at N-2 did not have a consistent effect on activity. Moving the position of a chlorine substituent from C-5 to C-7 or introducing a basic side chain at C-5 did not have a consistent effect on cytotoxic activity. Anthrapyrazole analogues showed a broad range of activity for inhibiting topoisomerase II decatenation activity. Losoxantrone and piroxantrone were the most potent inhibitors of topoisomerase II activity. There was no significant correlation between the cytotoxic activity of the anthrapyrazole analogues and their ability to inhibit decatenation by topoisomerase II.

Animals↗

PubMed2005

Identification of networks of sexually transmitted infection: a molecular, geographic, and social network analysis.

BACKGROUND: Despite widespread efforts to control it, Chlamydia trachomatis remains the most frequently diagnosed bacterial sexually transmitted infection (STI). Analysis of sexual networks has been proposed as a novel tool for control of and research into STI. In the present study, we combine molecular genotype data, analysis of geographic clusters, and sociodemographic descriptors to facilitate analysis of large sexual networks. METHODS: Individual chlamydia genotypes found in Manitoba, Canada, were analyzed to identify geographic clusters, and the identified clusters were further characterized by statistical analysis of sociodemographic variables. RESULTS: A total of 10 geographic clusters of chlamydia-genotype infection were identified. Clusters in Winnipeg showed no or little geographic overlap and could be further differentiated on the basis of the sociodemographic characteristics of the individuals within a cluster. Several clusters in northern Manitoba overlapped geographically but, nonetheless, could be differentiated on the basis of the sociodemographic characteristics of the infected individuals. CONCLUSIONS: On the basis of results of the combined analyses, each geographic cluster appeared to represent a relatively distinct transmission network within the larger sexual network. The geographic analysis of the molecular data provided a basis for establishment of potential epidemiological connections between small groups of unlinked individuals. Analytic approaches of the type described here would help to decipher the patterns that exist within large social network data sets and would be applicable to many types of infectious agents.

Adolescent↗

PubMed2005

Role of NQO1 polymorphisms as risk factors for squamous cell carcinoma of the head and neck.

A case: control study was carried out to determine if inactivating polymorphisms of the NQO1 gene at bases 609 and 465 are associated with altered risk of developing squamous cell carcinoma of the head and neck (SCCHN). Genotyping was carried out by PCR RFLP analysis on whole blood samples. The frequency of the inactive 609T and active 609C forms, and the inactive 465T and active 465C forms, of NQO1 were compared in patient and control groups by a logistic regression analysis and odds ratios (ORs) were calculated. Participants were stratified by tobacco and alcohol use, and genotype distributions in these sub-groups were compared. There were no significant differences in genotype distribution between SCCHN patients and the control population for the base 609 or 465 polymorphisms. There were also no significant differences in genotype distributions between patient and control groups for tobacco and/or alcohol users and non-users. Genotype distributions were similar for SCCHN patients at all disease sites with the exception of the nasopharynx where there was a higher incidence of the 609C:609T and 609T:609T genotypes. These results suggest that individuals having either 609T or 465T alleles generally do not have an altered risk of developing SCCHN.

Adult↗

PubMed2003

Chlamydia trachomatis omp1 genotypic diversity and concordance with sexual network data.

Sexual and social network analysis have been proposed as novel sexually transmitted disease control and research tools. Here, the concordance between chlamydia genotype data and a large sexual network constructed from routinely collected contact tracing data was examined. A sexual network was constructed for Manitoba, Canada, from province-wide contact tracing data. Positive chlamydia specimens from the same time period were collected and genotyped by omp1 DNA sequencing. A high degree of concordance was found between transmission events, on the basis of molecular data, and proposed transmission events, on the basis of sexual network data. Discordant results appeared to occur when a portion of the network contained potential core group members or in areas where contact tracing is difficult to carry out. The agreement between the molecular and epidemiologic data suggests that the use of routine contact tracing data is a valid approach for the construction of sexual networks.

Chlamydia Infections↗