Biomedical subjects

Thomas Richards

Publications and source records attributed to Thomas Richards.

6 recordsLinked to original sources

PubMed2005

Comparison of normalization methods for CodeLink Bioarray data.

BACKGROUND: The quality of microarray data can seriously affect the accuracy of downstream analyses. In order to reduce variability and enhance signal reproducibility in these data, many normalization methods have been proposed and evaluated, most of which are for data obtained from cDNA microarrays and Affymetrix GeneChips. CodeLink Bioarrays are a newly emerged, single-color oligonucleotide microarray platform. To date, there are no reported studies that evaluate normalization methods for CodeLink Bioarrays. RESULTS: We compared five existing normalization approaches, in terms of both noise reduction and signal retention: Median (suggested by the manufacturer), CyclicLoess, Quantile, Iset, and Qspline. These methods were applied to two real datasets (a time course dataset and a lung disease-related dataset) generated by CodeLink Bioarrays and were assessed using multiple statistical significance tests. Compared to Median, CyclicLoess and Qspline exhibit a significant and the most consistent improvement in reduction of variability and retention of signal. CyclicLoess appears to retain more signal than Qspline. Quantile reduces more variability than Median in both datasets, yet fails to consistently retain more signal in the time course dataset. Iset does not improve over Median in either noise reduction or signal enhancement in the time course dataset. CONCLUSION: Median is insufficient either to reduce variability or to retain signal effectively for CodeLink Bioarray data. CyclicLoess is a more suitable approach for normalizing these data. CyclicLoess also seems to be the most effective method among the five different normalization strategies examined.

Algorithms↗

PubMed2005

Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: long-term follow-up.

OBJECTIVE: To evaluate the long-term effects of the combination of isotretinoin, interferon alfa-2a, and vitamin E in locally advanced squamous cell carcinoma of the head and neck. DESIGN: Phase 2 prospective study. SETTING: Tertiary care academic medical centers. PATIENTS: Forty-five patients entered this study. All patients had stage III or IV squamous cell carcinoma of the head and neck and had been treated with surgical resection, radiation, or both. All patients were then treated with bioadjuvant chemopreventive treatment for 12 months. We previously reported a 24-month median follow-up of this phase 2 trial of the combination of isotretinoin, interferon alfa-2a, and vitamin E as bioadjuvant therapy after definitive local therapy. In that study, all 45 patients completed treatment, but 1 patient was excluded from analysis of recurrence and development of second primary tumors. Main Outcome Measure Longer-term (49.4-month median) follow-up. RESULTS: Among the 45 patients treated under the protocol, only 7 patients (16%) had died. Nine (20%) of 45 patients experienced progressive disease. Only 1 second primary tumor (acute promyelocytic leukemia) occurred during follow-up, and no aerodigestive second primary tumors occurred among the 45 patients. The 5-year progression-free survival and overall survival percentages were 80% (95% confidence interval, 65.1%-89.1%) and 81.3% (95% confidence interval, 63.7%-90.9%), respectively. These results are significantly better than the historical 5-year overall survival for advanced squamous cell carcinoma of the head and neck (approximately 40%). CONCLUSION: The bioadjuvant combination is highly effective in preventing recurrence and second primary tumors, and its role as standard therapy in advanced squamous cell carcinoma of the head and neck is being investigated in a randomized phase 3 study.

Antineoplastic Agents↗

PubMed2005

A phase I/II study of trimetrexate and capecitabine in patients with advanced refractory colorectal cancer.

OBJECTIVE: We tested the hypothesis that the combination of trimetrexate (TMTX) and capecitabine (CAP) would be active in patients with previously treated metastatic colorectal cancer (CRC). Because the optimum dose of this combination was unknown, we used a phase I/II design. METHODS: In the phase I cohort, patients received 110 mg/m2 TMTX intravenously weekly x6 and CAP starting at 750 mg/m2 orally twice daily from days 2 to 15 and 23 to 36 (one cycle). Cycles were repeated every 8 weeks. The phase II doses were 110 mg/m2 TMTX and 1000 mg/m2 CAP orally twice daily. RESULTS: Thirty-two patients were entered. All patients had prior 5-fluorouracil therapy and 94% had prior exposure to irinotecan. Grade 3/4 toxicities included abdominal pain in 4 patients (12.5%) and vomiting in 3 patients (9.4%). Twenty-seven patients were evaluable for response: one patient each had a complete response and a partial response for an overall response rate of 7.4%. The median time to progression was 3.3 months (95% confidence interval [CI], 1.6-3.7 months) and the median overall survival was 5.9 months (95% CI, 5.2-10.2 months). CONCLUSIONS: The combination of TMTX and CAP is well tolerated. However, recent studies have shown more active regimens in the second- and third-line metastatic setting.

Adult↗

PubMed2002

Breast, cervical, and colorectal carcinoma screening in a demographically defined region of the southern U.S.

BACKGROUND: The "Southern Black Belt," a term used for > 100 years to describe a subregion of the southern U.S., includes counties with high concentrations of African Americans and high levels of poverty and unemployment, and relatively high rates of preventable cancers. METHODS: The authors analyzed data from a state-based telephone survey of adults age >or= 18 years to compare the cancer screening patterns of African-American and white men and women in nonmetropolitan counties of this region, and to compare those rates with those of persons in other southern counties and elsewhere in the U.S. The primary study groups were comprised of 2165-5888 women and 1198 men in this region interviewed through the Behavioral Risk Factor Surveillance System. The respondents lived in predominantly rural counties in 11 southern states with sizeable African-American populations (>or= 24.5% of county residents). The main outcome measures were recent use of the Papanicolau (Pap) test, mammography, test for fecal occult blood in the stool (FOBT), and flexible sigmoidoscopy or colonoscopy. RESULTS: Between 1998-2000, 66.3% (95% confidence interval [95% CI] +/- 2.7%) of 1817 African-American women in the region age >or= 40 years had received a mammogram within the past 2 years, compared with 69.3% (95% CI +/- 1.8%) of 3922 white women (P = 0.066). The proportion of African-American and white women who had received a Pap test within the past 3 years was similar (85.7% [95% CI +/- 1.9%] vs. 83.4% [95% CI +/- 1.5%]; P = 0.068]. In 1997 and 1999, 29.3% of African-American women in these counties reported ever receiving an FOBT, compared with 36.9% in non-Black Belt counties and 42.5% in the remainder of the U.S. Among white women, 37.7% in Black Belt counties, 44.0% in non-Black Belt counties, and 45.3% in the remainder of the U.S. ever received an FOBT. Overall, similar patterns were noted among both men and women with regard to ever-use of FOBT, flexible sigmoidoscopy, or colonoscopy. Screening rates appeared to vary less by race than by region. CONCLUSIONS: The results of the current study underscore the need for continued efforts to ensure that adults in the nonmetropolitan South receive educational messages, outreach, and provider recommendations concerning the importance of routine cancer screening.

Black or African American↗

PubMed2002

Immunomodulatory effects of high-dose and low-dose interferon alpha2b in patients with high-risk resected melanoma: the E2690 laboratory corollary of intergroup adjuvant trial E1690.

BACKGROUND: The clinical antitumor activity of recombinant interferon alpha2b (IFNalpha2b) has been well documented in patients with advanced and high-risk melanoma; however, its mechanism of action remains conjectural. Trial E2690 evaluated the immunomodulatory effects of IFNalpha2b in vivo during treatment at high doses (the HDI arm; n = 51 patients) and at low doses (the LDI arm; n = 54 patients) in relation to standard observation (OBS; n = 43 patients). METHODS: This study evaluated peripheral blood lymphocytes (PBLs) for phenotypic markers and cytotoxic functions at 1 month, 3 months, and 12 months in the HDI arm, the LDI arm, and the OBS arm and examined correlations between changes observed in PBLs or in tumors with regard to treatment dosage and disease outcome. Tumor biopsy samples were studied for response to IFNalpha2b at a range of concentrations in vitro. RESULTS: Baseline blood phenotypic and functional assays did not predict disease outcome; however, modulation of these immunologic assays by IFNalpha2b treatment was observed and was associated with IFNalpha2b dosage. Tumor cell class II major histocompatibility antigen expression (human leukocyte/lymphocyte antigen DR) and adhesion molecule expression (ICAM-1) were modulated by exposure to IFNalpha2b in a dose dependent manner. Blood natural killer (NK) cell function, T-cell function, and subset distribution were modulated early by patients in the HDI arm and later by patients in the LDI arm. None of the variables tested in these studies predicted recurrence free survival. The numbers of patients studied were smaller than may be needed to detect potentially clinically significant changes. CONCLUSIONS: These data demonstrate changes in immunologic parameters associated with IFNalpha2b treatment and dosage that may account for some of the differences in the clinical efficacy of this modality. The current results also suggest the need for further study of newer molecular intermediates of IFNalpha2b and T-cell response to specific antigens of melanoma.

Adult↗

PubMedDate not supplied

Breast and cervical cancer screening practices among Hispanic and non-Hispanic women residing near the United States-Mexico border, 1999-2000.

This study examined the breast and cervical cancer screening practices of Hispanic and non-Hispanic women (n = 3,568) in counties that approximate the US southern border region. According to the Health Resources Services Administration (HRSA), border counties are those in which any part of the county is within 100 kilometers (62.14 miles) of the border. The study used data from Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults aged > or = 18 years conducted in 1999 and 2000. The study looked at recent use of mammography and the Papanicolaou (Pap) test. Hispanic women were less likely to have had a recent mammogram or Pap test as compared with non-Hispanic women in border counties, and as compared with Hispanic and non-Hispanic women in nonborder counties of Texas, New Mexico, Arizona, and California combined, and with other women in the United States. Results underscore the need for continued efforts to ensure that medically underserved women who live in the border region have access to cancer screening services.

Adolescent↗