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Biomedical subjects

Guillermo Tortolero-Luna

Publications and source records attributed to Guillermo Tortolero-Luna.

At least 19 recordsLinked to original sources

Human papillomavirus-related cellular changes measured by cytometric analysis of DNA ploidy and chromatin texture.

BACKGROUND: Image cytometry has provided two highly sensitive markers for the identification of the malignant potential of squamous lesions. Aneuploidy and chromatin texture have been investigated as quantitative measures of nuclear damage in premalignant lesions and carcinoma. Real-time PCR methods have evolved to yield highly specific measurements of mRNA expression in very sparse cellular samples. METHODS: Human papillomavirus (HPV) 16 and 18 E7 mRNA expression was measured using quantitative RT-PCR. DNA index and chromatin measures were taken from image cytology samples. The chromatin features, through discriminant analysis, were aggregated into a score, and both measurements were related to mRNA expression. RESULTS: mRNA level and DNA index show an increasing trend over increasing histological grades. However, DNA index and chromatin score were not correlated to mRNA levels in these samples. Chromatin score differed by mRNA type found with HPV 18 infected samples having a higher score than those with HPV 16. Samples infected with HPV 16 and HPV 18 had even higher chromatin scores. CONCLUSIONS: DNA index and chromatin score were not directly correlated with mRNA levels. However both mRNA and DNA index were related to histological grade, and chromatin score was associated with HPV type. Therefore, DNA index and mRNA levels could be independent predictors of cervical dysplasia, and chromatin score could be related to the viral integration process in cells infected with HPV 18 or dual infections.

Adult↗

Association between adiponectin, insulin resistance, and endometrial cancer.

BACKGROUND: Obesity is a well known risk factor for the development of endometrial cancer; however, weight alone does not account for all cases. The authors hypothesized that insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose cells and has been shown to be a surrogate marker for insulin resistance, with low levels of adiponectin correlated with hyperinsulinemia and degree of insulin resistance. The purpose of the current study was to determine whether there was an independent association between adiponectin level and endometrial cancer. METHODS: A case-control study was performed on 117 endometrial cancer patients (cases) and 238 women with no history of cancer (controls). Serum adiponectin levels were measured using enzyme-linked immunoadsorbent assay and examined for their association with endometrial cancer. Univariate and multivariate logistic regression analyses were performed with adjustment for confounding factors. RESULTS: The mean serum adiponectin levels were significantly lower among cases (88.8+/-63.3 ng/mL) than among controls (148.2+/-68.3; P<.001). This inverse correlation continued to be observed after controlling for age, body mass index, diabetes, and hypertension. Cases were significantly more likely to have serum adiponectin levels in the lowest (odds ratio [OR] of 10.5; 95% confidence interval [95% CI], 4.49-24.57 [P<.001]) and intermediate tertiles (OR of 2.5; 95% CI, 1.01-6.21 [P=.05]) when compared with controls. CONCLUSIONS: Adiponectin level was found to be independently and inversely associated with endometrial cancer. Women with endometrial cancer were more likely to have low adiponectin levels than controls, even after adjusting for body mass index. This suggested that insulin resistance is independently associated with endometrial cancer.

Adiponectin↗

Advanced cervical cancer treatment in Harris County: pilot evaluation of factors that prevent optimal therapy.

OBJECTIVE: To document obstacles to completing outpatient treatment faced by indigent patients with cervical cancer and compare treatment costs. METHODS: A retrospective pilot case series study assessed all indigent Harris County residents referred from Lyndon Baines Johnson Hospital (LBJ) to The University of Texas M. D. Anderson Cancer Center (M. D. Anderson) for advanced cervical cancer treatment between February 2001 and April 2004. Twenty-seven patients required hospital admission during the expected course of outpatient treatment and were identified as the study group. Nine patients, drawn from the same cohort but able to successfully complete the expected course of treatment as outpatients, were selected as the control group. RESULTS: The median total treatment costs per patient in the study group (n = 27) was 28,892 US dollar more than the median treatment costs for the patients in the control group (n = 9) (P = 0.01). Median number of inpatient days in the study group was 19.6. Social factors identified as significantly different between the study and control groups included transportation difficulties (P = 0.006) and lack of social support (P = 0.08). Additional factors identified in the study group may have social significance such as accessible local housing (11% vs. 0%, P = 0.56) and noncompliance with treatment (37% vs. 11%, P = 0.22). CONCLUSION: A combination of the lack of adequate methods of transportation and social support may contribute to the high cost of treating indigent patients with cervical cancer in Harris County, Texas.

Adult↗

Cervical cancer survival by socioeconomic status, race/ethnicity, and place of residence in Texas, 1995-2001.

OBJECTIVE: The current study explored whether socioeconomic status (SES), race/ethnicity, and rural residence may be linked to poorer cervical cancer survival by stage at diagnosis. METHODS: Data from 7,237 cervical cancer cases reported to the Texas Cancer Registry from 1995-2001 were used to address the association by stage at diagnosis and cause of death. Zip code-level census data were used to classify residence and to develop a composite variable for SES. Multilevel Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Late stage at diagnosis was a strong predictor of cervical cancer mortality (HR = 6.2, 95% CI 5.5-7.2). SES and race/ethnicity were independently associated with stage at diagnosis. Women residing in areas with lower SES had significantly shorter survival times when diagnosed at an early stage (HR = 3.0, 95% CI 2.1-4.3). Hispanic women had a lower probability of dying from cervical cancer during the follow-up period (HR = 0.7, 95% CI 0.6- 0.8) after adjusting for confounders. The association between lower SES and poorer survival was consistent across all racial/ethnic groups, suggesting the effect of SES may be more important than race. CONCLUSIONS: SES and race/ethnicity were independently associated with poorer cervical cancer survival in this large Texas sample. Further research is needed to investigate the role of optimal treatment and comorbid conditions in the association between SES and cervical cancer survival.

Adult↗

Correlates of cervical mucosal antibodies to human papillomavirus 16: results from a case control study.

BACKGROUND: While the cervical mucosal immune response to human papillomavirus (HPV) infection is believed to be central to viral clearance, it is not well characterized. We performed this analysis to determine correlates of HPV-16-specific mucosal antibody response in women at high risk for infection with HPV. METHODS: Cervical mucosal and serum samples were obtained from participants in a case control study that measured demographic risk factors of cervical disease and HPV infection. An HPV-16 L1-virus-like particle ELISA was used to detect HPV-16-specific IgA and IgG. Antibody level results were correlated with demographic characteristics, sexual history, cervical disease, and HPV detection. RESULTS: Cervical anti-HPV-16 IgA and IgG inversely correlated with HPV DNA, HPV-16 DNA, and cervical disease. CONCLUSIONS: These findings suggest that mucosal antibodies may protect against HPV infection and cervical disease. However, additional longitudinal studies evaluating serum and mucosal antibody correlates of incident, persistent, and clearing HPV infection are needed. In addition, standardization of mucosal sample collection and testing methods are required.

Adolescent↗

Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study.

BACKGROUND: Epidemiological studies have clearly established that human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Most cervical cancers and pre-cancers are HPV-positive. Not all pre-cancers progress to cancer; a significant number regress. The immunological basis for either spontaneous or treatment-mediated recovery from HPV-associated CIN is not clear. Currently, prophylactic vaccines are successfully inducing antibody responses in HPV negative patients. Therapeutic vaccines for HPV-positive patients with disease are needed. There is a need to understand the immunologic basis for the Cell-Mediated Immune (CMI) response and for histological regression to help the formulation of therapeutic vaccines. MATERIAL AND METHODS: Four groups of women were identified for this cross-sectional study of CMI. Group 1 consisted of six women without cytological or histological diagnosis of CIN and with an HPV negative test (CIN((-))/HPV((-))). Group 2 included 31 women with a new histological diagnosis of CIN and HPV positive test (CIN((+))/HPV((+))). Groups 3 and 4 were selected from women who had undergone ablative or excisional treatment for CIN at the colposcopy clinic at least 6 months before the study. The women in groups 3 and 4 were (CIN((+))/HPV((+))) before CIN treatment. Group 3 consisted of 22 women without evidence of recurrence of CIN (Recur((-))), and group 4 included 10 with histological diagnosis of recurrent CIN (Recur((+))). In particular, we investigated CMI responses to synthetic peptides from the E6 and E7 oncoproteins of HPV-16. RESULTS: Compared to patients with disease recurrence (Recur((+)), n = 10), the majority of individuals who remained recurrence-free post-treatment (Recur((-)), n = 22) exhibited significant proliferative responses to synthetic peptides from the E6 (P = 0.001) and the E7 (P = <0.001). In particular, significant responses were observed with the E6 peptide Q15L (aa 43-57, P = 0.006) and the E7 peptide Q19D (aa 44-62, P = 0.002) in Recur((-)) patients but not Recur((+)) individuals. Additionally, PBMC from women in the Recur((-)) group, but not the Recur((+)) group, produced predominantly TH1 cytokines upon stimulation with the peptides Q15L or Q19D. CONCLUSIONS: These results indicate an association between significant cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 and recurrence-free survival in HPV patients treated for CIN. We predict that these peptides may be useful as indicators of protective immunity for recovery from CIN and also for potential inclusion in designing immunotherapeutic and immunoprophylactic reagents for HPV-associated CIN.

Adolescent↗

Clinical, sociodemographic, and local system factors associated with a hospital death among cancer patients.

OBJECTIVE: The study was conducted to examine factors associated with hospital deaths among a group of cancer patients. PATIENTS AND METHODS: A retrospective chart review of the M. D. Anderson Cancer Center Tumor Registry was conducted. Participants were all adult cancer patients, residents of the State of Texas diagnosed and treated since January 1, 1990, and who died during the years 1999 and 2000. The study outcome was the site of death. MAIN RESULTS: The inclusion criteria were met by 866 patients of whom 504 (58%) died in a hospital. The group included 489 (56%) men. A number of 641 (74%) were White, 104 (12%) Hispanic, 92 (11%) Black, and 29 (3%) of other origin. The majority, 501 (58%), had been diagnosed with stage IV disease, and the median survival time was 14 months. Multivariate logistic regression analysis showed patients diagnosed with hematologic cancers to be significantly more likely (p<0.001) of dying in hospitals, odds ratio [OR 2.88] and confidence interval [95% CI 1.79-4.63], women diagnosed with breast and gynecological cancers were significantly less likely (p=0.03) of dying at hospitals odds ratio [OR 0.64] and confidence interval [95% CI 0.42-0.96], when compared with patients diagnosed with other cancers. Lower household income per zip code of residency was marginally associated (p=0.06) with hospital deaths. CONCLUSIONS: The study identified groups of cancer patients at risk of hospital death. These results should account when planning the allocation of hospital palliative care services as well as when informing policy decisions about health care financing and delivery of these services.

Adult↗

Wood dust exposure and the association with lung cancer risk.

BACKGROUND: Wood dust was designated as a human carcinogen based on increased sinus and nasal cancer rates among exposed workers. However, data on an association with lung cancer have been inconclusive. METHODS: Self-reported wood dust exposure was compared between 1,368 lung cancer patients and 1,192 cancer-free adults, in a lung cancer case-control study. Epidemiological information was collected through a detailed personal interview. RESULTS: Using several definitions of wood dust exposure we consistently observed statistically significant elevated adjusted risk estimates; for example, the adjusted odds ratio (OR) for combined wood dust related occupations and industries was 3.15 (95% confidence intervals (CI) 1.45-6.86) and for an overall summary exposure measure it was 1.60 (95% CI 1.19-2.14). The association was maintained when stratified by histopathological type. Among those exposed to cigarette smoke and wood dust, 21% of the cases were attributable to biologic interaction. CONCLUSIONS: Wood dust exposure is a potential risk factor for lung cancer.

Air Pollutants, Occupational↗

Human papillomavirus type 16 E2 and E6/E7 variants.

OBJECTIVES: Polymorphisms in human papillomavirus (HPV) type 16 have been shown to be related to geographic areas and are broadly classified as European (E), African (Af), Asian (As), or Asian-American (AA). Certain variants have been reported as being more likely to cause cervical disease; our objectives were to identify new HPV16 polymorphisms, to determine the linkage of the E2 and E6/E7 regions and to determine the minimum sequence necessary to classify variants. METHODS: We sequenced the complete E2, E6, and E7 regions in all HPV16-positive cervical samples identified in a case-control study of pre-invasive cervical disease. RESULTS: In the 100 samples analyzed, only one new polymorphism was identified, a synonymous change, T3205A, in region E2. The frequency distribution of variants in the sample set was 37 European prototypes and 27 E-G350, 16 AA, 5 Af1, 2 Af2, 8 E-C109G, 3 E-G131G, and 2 As. As shown by others, region E7 varied much less than E6 and E2. CONCLUSIONS: In each case, E2 changes were linked to the expected E6/E7 changes, and there was no evidence for recombination. The linkage between E2 and E6/E7 allows variant classification to be based on a short E6 sequence (nt 109-350).

Base Sequence↗

Correlation of human papillomavirus type 16 and human papillomavirus type 18 e7 messenger RNA levels with degree of cervical dysplasia.

Infection with certain types of human papillomavirus (HPV) is a necessary event in the development of cervical carcinoma; however, not all women who become infected with HPV will progress to cancer. Much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation. Little is known about the additional factors needed to drive the process. Quantitative real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, low-grade squamous intraepithelial lesions (LSIL), and high-grade squamous intraepithelial lesions (HSIL). Prevalence of mRNA transcripts was lower among normal women (27%) than for women with LSIL (40%) and HSIL (37%). Mean levels ranged from 2.0 (ln scale per 20 ng cDNA) among normal women to 4.2 among those with HSIL, with a significant trend (P=0.008). This trend was only significant for HPV 18 transcripts if separately analyzed by HPV type. The transcriptional activity of HPV 18 is higher than that of HPV 16 and increases with increasing level of dysplasia. This is in concert with the findings of other studies, and reinforces the notion that HPV 18 is a more aggressive viral type. Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from a cervical swab, thus providing a way to better screen women who may progress to higher grade lesions or invasive carcinoma from those who will spontaneously regress.

Adult↗

Acculturation and mammography screening among Hispanic women living in farmworker communities.

The relationship between acculturation and mammography screening practices among Hispanic women is unclear due to inconsistent study findings. The purpose of this research was to further investigate the effect of acculturation on mammography screening practices among Hispanic women and to explore the effect of biculturalism on mammography screening. Hispanic female farmworkers (N = 716) who were 50 years of age and older living in communities in Texas, New Mexico, and California were interviewed at their homes. Data collection was conducted from November 2001 to February 2002. Logistic regression models showed no significant effect for acculturation for the entire sample. Post hoc stratified analysis found that bicultural study participants in California were 3 times more likely to be adherent to screening compared to those with low acculturation. Study findings suggest that distinct differences might exist for Hispanic women living in farmworker communities in California, and perhaps other communities not on the United States-Mexico border. Women in such communities with low levels of acculturation can be targeted for interventions to increase mammography adherence.

Acculturation↗

Correlates of mammography screening among Hispanic women living in lower Rio Grande Valley farmworker communities.

Factors contributing to the underuse of mammography screening by female Hispanic farmworkers aged 50 years and older in the Lower Rio Grande Valley were determined through home-based, Spanish-language personal interviews (N = 200). Questions covered adherence to screening mammography guidelines (mammogram within 2 years), healthcare access, sociodemographic characteristics, and theoretical constructs related to breast cancer screening in the literature. Multivariate findings indicated that adherent women were 3.6 times more likely to have health insurance. Self-efficacy for obtaining a mammogram and decisional balance were also significantly related to adherence; age, income, and education variables were not associated, perhaps because of restricted variation. Results indicate continuing efforts are needed to ensure that medically underserved migrant farmworker women have access to health care services. In addition, efforts to increase their self-efficacy in obtaining a mammogram and to counter negative attitudes and opinions by stressing the positive prognosis associated with early detection are warranted.

Aged↗

Using intervention mapping to develop a breast and cervical cancer screening program for Hispanic farmworkers: Cultivando La Salud.

This article describes the development of the Cultivando La Salud program, an intervention to increase breast and cervical cancer screening for Hispanic farmworker women. Processes and findings of intervention mapping (IM), a planning process for development of theory and evidence-informed program are discussed. The six IM steps are presented: needs assessment, preparation of planning matrices, election of theoretic methods and practical strategies, program design, implementation planning, and evaluation. The article also describes how qualitative and quantitative findings informed intervention development. IM helped ensure that theory and evidence guided (a) the identification of behavioral and environmental factors related to a target health problem and (b) the selection of the most appropriate methods and strategies to address the identified determinants. IM also guided the development of program materials and implementation by lay health workers. Also reported are findings of the pilot study and effectiveness trial.

Adolescent↗

Characteristics of recurrence in patients who underwent lymphatic mapping for vulvar cancer.

OBJECTIVE: To evaluate patients with vulvar cancer who experienced a recurrence after undergoing lymphatic mapping and sentinel lymph node (SLN) biopsy. METHODS: We reviewed the records of 52 patients who underwent vulvectomy and lymphatic mapping with blue dye for treatment of vulvar cancer at our institution from 1993 to 1999 and identified patients who experienced recurrent disease. RESULTS: Fourteen (27%) of 52 patients experienced a recurrence. The patients' median age was 60 years (range 35-84 years). Nine patients had squamous lesions, four patients had melanoma, and one patient had Paget's disease with stromal invasion. Four tumors were stage T1, seven were T2, and three were T3. Eight lesions were located at the midline and six were lateral. Thirteen patients underwent superficial inguinal lymphadenectomy while one patient underwent SLN biopsy only. Postoperatively, seven patients underwent no further treatment, six underwent radiation therapy, and one patient underwent chemotherapy. The median follow-up was 46 months and the median disease-free interval was 21 months. Primary recurrence was in the vulva in eight patients (57%), in the groin in three patients (21%), and distant in three patients (21%). Nine of 32 (22%) squamous lesions recurred, four (57%) of seven melanomas recurred, and the sole patient with invasive Paget's recurred. Patient weight was found to be significantly different between patients who experienced a recurrence and those who did not (P = 0.05). At least one SLN was identified in 46 (88%) of the 52 patients. One (17%) of six patients in whom no SLN was identified experienced a recurrence, and 13 (28%) of 46 patients in whom a SLN was identified experienced a recurrence (P = 0.5). In the 41 patients with negative SLNs and negative non-SLNs, the recurrence rate was 24%; in the six patients with positive SLNs and negative non-SLNs, the recurrence rate was 40%; and in the five patients with positive SLNs and positive non-SLNs, the recurrence rate was 40% (P = 0.6). No patients had a negative SLN and positive non-SLN. Of the three patients who experienced a recurrence in the groin, one had a negative SLN and negative non-SLN, one had a positive SLN and positive non-SLN, and one had no SLN identified and a negative non-SLN. CONCLUSIONS: . This heterogeneous group of patients who underwent lymphatic mapping with blue dye had similar patterns of recurrence to reported series of patients who did not undergo lymphatic mapping. Groin relapse following a negative SLN biopsy is of concern and suggests that long-term follow-up data are required before lymphatic mapping and SLN biopsy alone can be considered standard treatment for patients with vulvar cancer.

Adult↗

Increased plasma levels of insulin-like growth factor 2 and insulin-like growth factor binding protein 3 are associated with endometrial cancer risk.

Circulating insulin-like growth factors (IGFs) and their binding proteins have been associated with increased risk of breast, prostate, colon, and lung cancer. To examine the association of IGFs and endometrial cancer risk, we measured the plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with endometrial cancer and 80 age-matched control subjects with no history of cancer. Mean plasma levels of IGF-2 were significantly higher in women with cancer versus controls (670 ng/ml versus 380 ng/ml, P < 0.001). In contrast, significantly lower mean plasma levels of IGF-1 (155 mg/ml versus 185 ng/ml, P < 0.01) and IGFBP-3 (1703 ng/ml versus 2170 ng/ml, P < 0.001) were observed among cases compared to the control group. Women in the highest quartile of IGF-2 were found to have 9.67 (95% confidence interval 3.29-28.43) times the risk of endometrial cancer than women in the lowest quartiles. Women in the highest quartile of IGFBP-3 were associated with a significantly decreased risk for developing endometrial cancer (odds ratio = 0.23, 95% confidence interval 0.09-0.60). These data suggest that increased plasma levels of IGF-2 and decreased levels of IGFBP-3 are associated with an increased risk of endometrial cancer. Further validation of these results is needed to determine the potential usefulness of risk assessment.

Adult↗

Innovations in understanding the biology of cervical cancer.

Revelation of the connection between the human papillomavirus (HPV) and cervical neoplasia and invasive cervical cancer is prompting new investigations to expand that understanding and promote vaccines, gene therapy, and other interventions. At the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), laboratory and clinical researchers reported advances in new studies meant to increase understanding of the natural history of HPV and cervical intraepithelial neoplasia, to evaluate new cervical cancer screening techniques, and to promote new therapies. Using K14-HPV type 16 transgenic mice, researchers are investigating the effects of estrogen on cervical cancer carcinogenesis, and results are lending support to epidemiological theories showing a difference in HPV infection rates and the development of cervical lesions in women using oral contraceptives. Other work involves investigating genes that are up-regulated by HPV infection and the role of the p53 homologue, p63, in cervical neoplasia evolution. Telomerase also is under investigation as a biomarker in high-risk populations. Gene therapy that replaced p53 in cervical cancer cell lines in vitro and a nude mouse model inhibited cell and tumor growth, confirming previous findings in squamous epithelial carcinomas of the head and neck. Furthermore, research in intracellular targeting of antigens to subcellular locations shows promise for treating cervical cancer preclinically. Identification of molecular changes in cervical cancer and knowledge about the importance of HPV infection in cervical cancer can lead to new therapies to treat existing cervical cancer and, in the long term, prevent the disease.

Animals↗

Serum levels of insulin-like growth factor I and risk of squamous intraepithelial lesions of the cervix.

Squamous intraepithelial lesions (SILs) are areas of precancerous growth in the cervix that can be indicative of future cervical cancer. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been implicated in cancer development. Recent studies have demonstrated that elevated plasma IGF-I levels are associated with increased risk of prostate, lung, colon, and breast cancers. In this case-control study, we analyzed the relationship between serum levels of IGF-I and IGFBP-3, and SILs of the cervix. The case patients were comprised of 267 women treated at The University of Texas M. D. Anderson Cancer Center Colposcopy Clinic in Houston, Texas for abnormal Pap smears. The clinic serves minority and economically disadvantaged women referred from the County Health Department clinics of Harris County, Texas. The control subjects were 238 healthy women receiving family planning and screening services at two Harris County Health Department clinics. Case patients with either high-grade or low-grade SILs had significantly higher serum levels of IGF-I, IGFBP-3, and molar ratios of IGF-I:IGFBP-3 than the control subjects did. IGF-I levels in the highest quartile were associated with significantly higher risk of SILs compared with the lowest quartile, independent of IGFBP-3 levels. The odds ratio for the fourth quartile of IGF-I level, relative to the first quartile, was 8.54 (95% confidence interval, 4.15-17.60; P < 0.0001) after adjustment for age, ethnicity, smoking status, and IGFBP-3 level. There was a dose-response relationship between risk of SILs and the level of IGF-I: as the level of IGF-I increased, so did the risk of SILs. In addition, the serum level of IGFBP-3 was significantly higher in case patients than in control subjects. However, after adjustment for IGF-I, no relationship was evident between IGFBP-3 level and risk of SILs. Serum levels of IGF-I may be a useful biomarker for assessing risk of SIL development.

Adult↗