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Biomedical subjects

David S Alberts

Publications and source records attributed to David S Alberts.

At least 55 records · Page 3Linked to original sources
PubMed2004

Wheat bran fiber supplementation and bone loss among older people.

OBJECTIVE: The purpose of this study was to investigate the effect of wheat bran fiber (WBF) supplementation on bone loss in older people. METHODS: Two hundred thirty-seven men and women ages 40 to 80 y were included in this study. They constituted a subgroup of participants from a 3-y WBF intervention trial for preventing recurrence of colorectal adenomas. These participants were randomized into a high (13.5 g/d) or a low (2 g/d) WBF supplementation group. Bone mineral density at the forearm was measured by single photon absorptiometry at baseline and yearly during the intervention to monitor possible toxic effects of fiber supplementation on bone metabolism. RESULTS: Baseline characteristics of this subgroup of participants from the WBF trial were similar between the high and low supplementation groups. The annual amounts of bone loss at the radial third site were -0.017 +/- 0.018 g/cm2 and -0.013 +/- 0.021 g/cm2, respectively, for the low and high WBF groups; and the annual bone losses at the ultra-distal site were was -0.005 +/- 0.020 g/cm2 and -0.006 +/- 0.027 g/cm2, respectively, for the low and high WBF groups. After controlling for confounding factors, we found no significant differences in bone loss between groups (P > 0.05). CONCLUSION: WBF supplementation at the level given in this study may not have a significant effect on bone loss among older people.

Absorptiometry, Photon↗
PubMed2004

Randomized Phase II trial of two high-dose chemotherapy regimens with stem cell transplantation for the treatment of advanced ovarian cancer in first remission or chemosensitive relapse: a Southwest Oncology Group study.

OBJECTIVES: To evaluate response rates, progression-free survival (PFS), overall survival (OS), and toxicity of two high-dose chemotherapy regimens with stem cell rescue used to treat patients with recurrent or persistent stage III/IV ovarian cancer, with the goal of taking one forward into a Phase III comparison with conventional therapy. METHODS: Patients under 65 with clinically or pathologically persistent disease after initial chemotherapy or those relapsing >6 months after a complete remission (CR) were randomized to CMC carboplatin (1500 mg/m(2)), mitoxantrone (75 mg/m(2)), and cyclophosphamide (120 mg/kg)], or CTC: [cisplatin (165 mg/m(2)), thiotepa (600 mg/m(2)), and cyclophosphamide (5625 mg/m(2))] with stem cell rescue. RESULTS: Of 67 randomized, the 32 and 26 eligible in the CMC and CTC arms were matched including age (median 49), maximum tumor diameter, and disease status at transplant. Low-risk disease (maximum diameter disease <or= 0.5 cm and platinum sensitivity) was demonstrated in only approximately one-half of the patients. There were two treatment-related deaths in each arm. The median PFS was 13 and 8 months, respectively, for the CMC and CTC arms. The median OS was 29 and 22 months for the CMC and CTC arms. In a multivariate analysis of PFS, normal CA125 at transplant and CR to primary therapy were significant; for OS, normal CA125 and platinum sensitivity were significant. CONCLUSIONS: The CMC regimen was the superior regimen. However, few patients were long-term progression-free survivors. A clinical CR to primary therapy and a normal CA125, seen in a minority of patients, were requirements for a favorable outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Recombinant human erythropoietin as an adjunct to radiation therapy and cisplatin for stage IIB-IVA carcinoma of the cervix: a Southwest Oncology Group study.

OBJECTIVE: The survival of cervix cancer patients is associated with their hemoglobin (Hgb) level during radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase II trial to determine whether recombinant human erythropoietin (rHuEPO) safely corrects anemia during chemoradiotherapy for cervix cancer. METHODS: Patients had stage IIB-IVA cervix cancer and a Hgb between 8.0 and 12.5 g/dl. All patients received rHuEPO thrice weekly and oral iron starting 10-15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin followed by intracavitary brachytherapy. RESULTS: Fifty-three patients from 26 institutions received the protocol treatment. The mean Hgb was 10.4 +/- 1.3 g/dl on the first day of rHuEPO administration (baseline), 11.0 +/- 1.6 g/dl on the first day of chemoradiotherapy, 11.6 +/- 1.9 g/dl at the midpoint of chemoradiotherapy, and 11.8 +/- 2.2 g/dl at the end of chemoradiotherapy. The target Hgb level of 12.5 g/dl was achieved in 40% of patients (95% CI 26-56%) by the midpoint of Chemoradiotheraphy. Change in Hgb was associated with baseline serum iron (P = 0.008) and transferrin saturation (P = 0.05) levels, but not with baseline Hgb or serum ferritin, or patient age. Seven patients developed deep vein thrombosis. Two-year progression-free survival (PFS) was 43% and overall survival (OS) was 51%. Survival was significantly associated with Hgb level at the end of chemoradiotherapy, but not with the baseline Hgb level. CONCLUSIONS: rHuEPO and iron gradually increased Hgb levels in anemic women with local advanced cervix cancer during chemoradiotherapy. There was a higher than expected incidence of deep vein thrombosis. The progression-free and overall survival rates were lower than reported for women with normal Hgb levels.

Adult↗
PubMed2004

Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study.

OBJECTIVES: To assess the activity of vinorelbine in women with recurrent or resistant epithelial ovarian cancer following treatment with platinum and paclitaxel in terms of survival rate at 6 months, objective response rate (in the subset of patients with bidimensionally measurable disease), and health-related quality of life. METHODS: Seventy-nine evaluable patients with progressive ovarian cancer following platinum and taxane therapy received vinorelbine 30 mg/m(2) days 1 and 8 of a 21-day treatment cycle. RESULTS: Six-month survival rate for the entire group was 65% (95% CI: 54-75%) and median survival was 10.1 months (95% CI: 7.7-13.6 months). In the 71 women with measurable disease, 0 complete and 2 partial responses were observed (RR = 3%) (95% CI: 0.3-10%). Patients reported substantial symptom-related distress at baseline, which persisted, but did not worsen, during treatment. Patients also had impaired physical functioning at baseline and this continued to decline during treatment. CONCLUSIONS: The 6-month survival rate achieved with salvage vinorelbine is comparable to the results obtained with other salvage therapies in patients with relapsed ovarian cancer. During the initial 10 weeks of treatment, vinorelbine did not appear to be effective in alleviating the symptom-related distress or progressive impairment of physical functioning associated with this disease.

Adult↗
PubMed2004

Accuracy of self-reported smoking status among participants in a chemoprevention trial.

BACKGROUND: Exposure to tobacco products is readily assessed through self- or interview-administered questionnaires. Degree of misreporting among participants in chemoprevention trials is unknown. We assessed the level of discrepancy between self-reported smoking exposure and plasma cotinine among participants in a chemoprevention trial. METHODS: Analyses were conducted among 824 men and women who participated in a dietary trial of adenoma recurrence. Smoking exposure was ascertained through self-administered questionnaires at three time-points. Plasma cotinine was measured by gas chromatography among 283 never, 446 former and 95 current self-reported smokers. Sensitivity and specificity were assessed using various plasma cotinine cut-points. RESULTS: Degree of misclassification for self-reported current smokers was minor (0-3%), regardless of cotinine cut-point used. Using a cut-point of 20 ng/ml, which takes into account exposure to environmental tobacco smoke among nonsmokers, sensitivity and specificity were 98.9% and 80.2%, respectively. CONCLUSIONS: These data indicate that degree of misreport for current smokers is extremely low; however, approximately 20% of self-reported never smokers misreport their exposure, suggesting that validation of self-report is needed for these individuals.

Adenoma↗
PubMed2004

Dietary change in an intervention trial of wheat bran fiber and colorectal adenoma recurrence.

PURPOSE: The objectives of this study were to determine whether participants in the Wheat Bran Fiber (WBF) trial exhibited changes in diet over time, and whether these changes were differential by assigned treatment group. METHODS: The WBF trial was a randomized trial with participants assigned to one of two groups: a low-fiber (2.0 g/d) or high-fiber (13.5 g/d) wheat bran fiber cereal supplement. A total of 685 participants from both treatment groups completed the Arizona Food Frequency Questionnaire (AFFQ) at baseline, year one, and year three of the trial. Means were calculated for nutrient intake, change in nutrient intake, number of food group servings, and change in number of food group servings. RESULTS: For both treatment groups combined, significant increases were observed for most micronutrients and vitamins at years one and three, while fat intake significantly decreased. Participants from both groups significantly increased their consumption of cereals, breads, and crackers, but decreased the number of servings from the meat, poultry, and egg group, the fats group, and the salty snacks group. The only differential changes in intake between the treatment groups were for sugar and iron, which increased to a lesser extent among those assigned to the high-fiber treatment as compared with the low-fiber group. CONCLUSIONS: Although differential dietary intake was not appreciable in the WBF trial, participants exhibited longitudinal changes. Future intervention studies should carefully monitor dietary changes during the trial with multiple dietary assessment tools to assess potential secular and treatment-related diet changes.

Adenoma↗
PubMed2004

Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.

Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.

Antibiotics, Antineoplastic↗
PubMed2004

Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence.

BACKGROUND: The results of epidemiologic studies indicate that higher intakes or blood concentrations of folate are associated with a lower risk of colorectal neoplasia; however, only one study assessed the role of homocysteine. OBJECTIVE: We assessed the relation between biochemical and dietary markers of folate status and colorectal adenoma recurrence. DESIGN: Analyses were conducted in 1014 men and women aged 40-80 y who had undergone removal of all colorectal polyps. Diet and supplement use were ascertained through a food-frequency questionnaire administered at study entry. Blood collected at baseline was used to measure plasma folate and homocysteine concentrations. Unconditional logistic regression was used to assess the odds of recurrence associated with the intakes of folate, methionine, and vitamins B-6 and B-12 and with plasma folate and homocysteine. RESULTS: Relative to subjects in the highest quartile of plasma homocysteine, those in the lowest quartile had an odds ratio (OR) of adenoma recurrence of 0.69 (95% CI: 0.47, 1.02; P for trend = 0.02) after adjustment for confounding factors. Lower odds of recurrence were shown for higher plasma folate (OR: 0.66; 95% CI: 0.46, 0.97) and higher total intakes (dietary plus supplemental) of folate (OR: 0.61; 0.42, 0.89) and vitamin B-6 (OR: 0.65; 0.45, 0.94). Slightly weaker and nonsignificant associations were shown for dietary folate, methionine, and total vitamin B-12. CONCLUSIONS: A lower recurrence of colorectal adenomas was shown in subjects with higher intakes and plasma concentrations of folate. Additional markers involved in folate metabolism, including lower homocysteine and higher vitamin B-6 intake, were also associated with lower odds of recurrence.

Adenoma↗
PubMed2004

Effects of a high-selenium yeast supplement on celecoxib plasma levels: a randomized phase II trial.

A combination of celecoxib and selenium was used in a randomized double-blind Phase II trial as a preliminary study to a multicenter Phase III colorectal cancer chemoprevention trial using these two agents together. The purpose of this trial was to determine whether high-selenium baker's yeast [(Saccharomyces cerevisiae) 200 microg once daily] in combination with celecoxib (400 mg once daily) altered the steady-state plasma concentration of celecoxib or produced clinically significant toxicities. Seventy-three healthy subjects (ages 40-75 years) were recruited to the 6-week study from the general local population and were randomized to either the celecoxib plus selenized baker's yeast group or the celecoxib plus placebo group after a 2-week run in period of celecoxib only. Blood samples were taken at baseline (to document that there was no evidence of celecoxib intake), after the 2-week run-in period on celecoxib to verify steady-state blood levels of this agent, and at end of study (4 weeks postrandomization). Toxicities were monitored at 2 weeks after initiation of celecoxib, at 4 weeks after initiation, and at the end of the study. Blood level concentrations of celecoxib did not differ between the two groups as determined by high-performance liquid chromatography analysis nor were there significant differences in blood chemistry values between the two groups. Subjects' self-report of general physical toxicities was uncommon and limited to National Cancer Institute toxicity grade 2 or less; however, 2 female participants (3%) were removed from the study medications because of grade 2 edema and significant weight gain after 2 and 2.5 weeks of celecoxib administration. In conclusion, high-selenium yeast and celecoxib can be taken at the described doses with minimum short-term negative effects. In future Phase III chemoprevention trials of celecoxib, weight gain should be carefully monitored, and participants should be made aware of this potential side effect before study entry.

Administration, Oral↗
PubMed2004

Results of a phase I multiple-dose clinical study of ursodeoxycholic Acid.

BACKGROUND: The hydrophilic bile acid, ursodeoxycholic acid (UDCA), may indirectly protect against colon carcinogenesis by decreasing the overall proportion of the more hydrophobic bile acids, such as deoxycholic acid (DCA), in aqueous phase stool. In the AOM rat model, treatment with UDCA resulted in a significant decrease in adenoma formation and colorectal cancer. It was hypothesized that there is a dose-response relationship between treatment with the more hydrophilic bile acid, UDCA, and a reduction in the proportion of the more hydrophobic bile acid, DCA, in the aqueous stool phase, suggesting the potential of UDCA as a chemopreventive agent. METHODS: Eighteen participants were randomized to 300, 600, or 900 mg/day UDCA for 21 days in this multiple-dose, double-blinded study. Seventy-two-hour stool samples were collected pretreatment and on days 18-20 of UDCA treatment for bile acid measurements. Pharmacokinetics were performed and blood bile acids were measured at days 1 and 21 of UDCA treatment. RESULTS: There were no serious adverse events associated with UDCA treatment. There was a dose-response increase in the posttreatment to baseline ratio of UDCA to DCA from the 300 mg/day to the 600 mg/day group, but not between the 600 and the 900 mg/day groups, in both aqueous and solid phase stool. This posttreatment increase was statistically significant in aqueous phase stool for the 300 and 600 mg/day treatment groups (P = 0.038 and P = 0.014, respectively), but was only marginally significant in the 900 mg/day treatment group (P = 0.057). Following the first dose administration, a dose-dependent increase in plasma ursodeoxycholic concentrations was observed in fasting subjects; however, when these levels were measured postprandially following 3 weeks of treatment, the areas under the plasma concentration-time profile (AUC) were not statistically different and remained relatively unchanged over time. CONCLUSIONS: UDCA treatment did not decrease the quantity of DCA in fecal water or solids; however, it did decrease the proportion of DCA in fecal water and solids in relation to UDCA. Thus, 3 weeks of UDCA treatment resulted in an overall increase in hydrophilicity of bile acids in the aqueous phase stool, with a peak effect observed with a daily dose of 600 mg/day. Much larger studies are needed to determine the effect of ursodeoxycholic administration on deoxycholic concentration, overall hydrophilicity of stool bile acids, and the long-term effects on intermediate biomarkers of cellular damage.

Administration, Oral↗
PubMed2004

Karyometric image analysis for intraepithelial and invasive cervical lesions.

OBJECTIVE: To derive an objective, numeric measure for the progression of intraepithelial and invasive squamous cell cervical lesions. STUDY DESIGN: Thin-layer cervical cytology preparations from colposcopically confirmed normal cervix, low grade squamous intraepithelial lesions, high grade squamous intraepithelial lesions and carcinoma were identified from a cross-sectional study. Fifty-nine cases representing 4 diagnostic categories were selected, and 2,375 nuclei from epithelial cells representative of the diagnostic category were randomly selected for imaging and measurement from these cases. Additionally, 1,378 visually normal appearing intermediate cells from low and high grade squamous intraepithelial lesions, as well as from carcinoma cases, were identified for analysis. The nuclei were quantitatively characterized, and discriminant analyses were performed to derive a progression curve from normal cytology to carcinoma. RESULTS: The lesion signatures show a clear increase in nuclear abnormality with increasing progression. A progression curve was derived based on mean discriminant function scores for each diagnostic category and on the mean nuclear abnormality values for the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. CONCLUSION: A numeric assessment of lesion progression for cervical precancerous and cancerous lesions based on karyometric measurements is possible and may provide an objective, precise characterization of each lesion as well as a basis for improved performance in automated cytology-based cervical cancer screening.

Cell Nucleus↗
PubMed2004

Karyometric analysis of actinic damage in unexposed and sun-exposed skin and in actinic keratoses in untreated individuals.

OBJECTIVE: To assess the ability of karyometric analysis to demonstrate progression of actinic damage as a function of sun exposure in individuals with actinic keratoses (AKs) and to evaluate the stability of that assessment over a 3-month period. STUDY DESIGN: Biopsies from subjects with AKs were obtained from unexposed skin, sun-exposed skin and AK lesions. Subjects used an SPF 50 sunscreen, and 3 months later additional biopsies were taken from sun-exposed and AK sites. A total of 13,300 nuclei were recorded from 31 subjects. RESULTS: Measures of nuclear abnormality (NA) and effects of sun damage based on discriminant function (DF) scores were derived. Actinic damage levels varied significantly across biopsy site, demonstrating the method's sensitivity. Accrual of actinic damage was demonstrated in sun-exposed skin and AK lesions when all nuclei were examined over 3 months but only for sun-exposed skin when the worst-damaged nuclei were examined. This suggests a ceiling effect of nuclear damage in the progression to abnormality. Within-subject variability was similar for both NA and DF when all nuclei were considered. Among the worst-damaged nuclei (as defined by high DF), DF showed lower within-case variability than NA, perhaps due to a reduction in nuclear heterogeneity. CONCLUSION: Karyometry's ability to detect subtle levels of actinic damage in nuclear chromatin patterns may make it useful in screening agents for possible use in cancer chemoprevention.

Actins↗
PubMed2004

Preneoplastic changes in ovarian tissues.

OBJECTIVE: To test whether histologically normal epithelium within ovarian inclusion cysts and stroma exhibit changes in nuclear chromatin pattern that indicate the presence of occult ovarian lesions. STUDY DESIGN: Ovaries were collected from 10 low-risk women,from 7 high-risk women and from 3 women with ovarian cancer. Histologic sections were cut at 5 microm and hematoxylin and eosin stained. High-resolution images were recorded from the epithelium lining inclusion cysts and from the underlying stroma of ovaries from these 20 subjects. A total of 2860 epithelial nuclei and 3610 stromal nuclei were recorded. Karyometric features and nuclear abnormality were computed. Discriminant analyses and unsupervised learning algorithms defined deviations from normal that were designated "above threshold" and used to compute average nuclear abnormality of a second nuclear phenotype. RESULTS: Histologically normal epithelium from inclusion cysts of ovaries harboring a malignant lesion was shown to exhibit changes in the nuclear chromatin pattern that were statistically significant using quantitative image analysis procedures. Similar changes were seen in the inclusion cyst epithelia of high-risk ovaries. A subpopulation of cells representing a new phenotype was detected in the underlying stroma of women harboring a malignant ovarian lesion and in women at high risk of ovarian cancer. CONCLUSION: The karyometric changes observed in the epithelia lining inclusion cysts and in the underlying stroma of ovaries either with ovarian cancer or at high risk of ovarian cancer suggest the presence of preneoplastic changes in histologically normal tissue.

Cell Nucleus↗
PubMed2004

Circulating endogenous retinoic acid concentrations among participants enrolled in a randomized placebo-controlled clinical trial of retinyl palmitate.

Retinoids have been studied extensively for their chemopreventive properties. The biological activity of retinoids is acquired through their conversion to retinoic acid (RA). Characterization of endogenous circulating RA concentrations after supplementation with vitamin A over longer time periods has not been done previously. Our investigation was conducted to determine whether vitamin A (retinyl palmitate) supplementation significantly increases circulating RA concentrations of all-trans-, 9-cis-, and 13-cis-RA. Using plasma samples from 41 participants enrolled in a randomized clinical trial of placebo, 25,000, 50,000, or 75,000 IU supplemental retinyl palmitate daily, high-performance liquid chromatography analyses were conducted for concentrations of three RA isomers. Seven plasma samples were analyzed for each participant over a 16-month period. Based on an intention-to-treat analysis, results obtained using linear mixed models showed that supplementation with retinyl palmitate statistically significantly increased concentrations of all three RA isomers from baseline levels. This study suggests that supplementation with retinyl palmitate is an effective means to increase circulating all-trans, 9-cis-, and 13-cis-RA concentrations among humans.

Aged↗
PubMed2003

Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a gynecologic oncology group study.

PURPOSE: To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity. MATERIALS AND METHODS: A total of 251 patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%) were ineligible following centralized pathology review. Of the 229 patients included in the analysis, 110 received 32P, and 119 received CP. RESULTS: The cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP. Patients receiving CP had a recurrence rate 29% lower than that of those receiving 32P (P =.15, two-tail test). The death rate for patients treated with CP was 17% lower than that for patients treated with 32P (difference not significant). Combining both arms, the 10-year cumulative incidence of recurrence for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI, 32% to 56%) for stage II patients (P =.01). Both regimens were reasonably well tolerated, but problems with inadequate distribution (7%) and small-bowel perforation (3%) make the otherwise less toxic 32P less acceptable. CONCLUSION: Although there are no statistically significant differences in survival, the lower cumulative recurrence seen with CP and complications of 32P administration make platinum-based combinations the preferred adjuvant therapy for early ovarian cancer patients at high-risk for recurrence.

Adenocarcinoma, Mucinous↗
PubMed2003

Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients.

PURPOSE: The Cu efflux transporter ATP7A is overexpressed in some cisplatin-resistant ovarian carcinoma cell lines. We examined the expression of ATP7A in the major normal human organs and in several types of human malignancies and sought to determine whether ATP7A expression changed during treatment of ovarian carcinomas with Pt-containing regimens. EXPERIMENTAL DESIGN: ATP7A expression was quantified by immunohistochemical staining using microarrays containing normal and malignant tissues, and standard sections of 54 paired tumor samples obtained from ovarian carcinoma patients before and after at least two cycles of platinum-based therapy. RESULTS: ATP7A was expressed in normal endometrium, prostate, testis, and kidney but was not detected in the other major organs. ATP7A was expressed in some of the most common human malignancies, including prostate (7 of 7), breast (10 of 10), lung (8 of 8), colon (5 of 8), and ovary (6 of 7), as well as in a wide variety of other types of malignancy. ATP7A staining was detected in 28 of 54 ovarian carcinomas before treatment. Patients with increased ATP7A expression after treatment (18 of 54) exhibited poorer actuarial survival (P<0.0057 by log-rank test). Expression of ATP7A either before or after treatment was not associated with other clinical factors. CONCLUSIONS: Although ATP7A is not detectable in most normal tissues it is expressed in a considerable fraction of many common tumor types. Enrichment of the tumor for ATP7A-expressing cells during platinum drug-based treatment of ovarian cancers is associated with poor survival. These findings are in agreement with results of in vitro studies from this laboratory demonstrating that increased expression of ATP7A renders cells resistant to cisplatin and carboplatin.

Adenosine Triphosphatases↗