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Biomedical subjects

N Natarajan

Publications and source records attributed to N Natarajan.

At least 19 recordsLinked to original sources

The syntheses and in vivo biodistribution of novel boronated unnatural amino acids.

A series of boronated, unnatural amino acids were prepared and their biodistribution determined in melanoma bearing mice. The unnatural amino acids were prepared utilizing recently developed borylation. The majority of the syntheses utilize metal catalyzed additions of diboron agents to unsaturated carbonyl compounds. Biodistribution studies in mice bearing melanoma tumors indicated that all the boronated amino acids were taken up by the melanoma tumors. The data for the cyclic five-membered ring analogue, 1-amino-3-boronocyclopentanecarboxylic acid, was most striking, exhibiting a nearly 22:1 ratio of boron concentration for tumor to brain at the 2 h time point, dropping to 7.3 after 6 h. The tumor to blood and tumor to skin ratios were also quite high. It is important to note that all of the amino acids were synthesized as racemic and diastereomeric mixtures. Thus there is a high probability that a single enantiomer of 1-amino-3-boronocyclopentanecarboxylic acid might exhibit far higher selectivity.

Amino Acids↗

MCM2 is an independent predictor of survival in patients with non-small-cell lung cancer.

PURPOSE: Minichromosome maintenance protein 2 (MCM2) is a component of the prereplicative complex. It is essential for eukaryotic DNA replication and is only expressed in proliferating cells. The prognostic utility of MCM2 compared with Ki-67, another marker of proliferating cells, on survival of patients with non-small-cell lung cancer (NSCLC) was studied. PATIENTS AND METHODS: We examined the immunohistochemical expression of MCM2 and Ki-67 in primary pathologic tumor specimens from 221 NSCLC patients. For each marker, the fraction of tumor cells with positive staining was assessed as a percentage and categorized into four groups: 0% to 24%, 25% to 49%, 50% to 74%, and > or = 75%. MCM2 and Ki-67 immunoreactivities were compared with each other, and associations with pathologic and clinical parameters predictive of survival were analyzed with the chi(2) test. Cox regression models were used to assess associations between MCM2 and Ki-67 and survival while controlling for confounders. RESULTS: Independent variables significantly associated with survival were tumor stage, performance status, and staining category. Patients with less than 25% MCM2 immunoreactivity had a longer median survival time than patients with > or = 25% MCM2 immunoreactivity (46 v 31 months; P =.039) and a lower relative risk (RR) of death (RR, 0.55, 95% confidence interval, 0.34 to 0.88). There was no significant association between survival and Ki-67 expression. CONCLUSION: Immunostaining of tumor cells for MCM2 is an independent prognostic parameter of survival for patients with NSCLC. Interpretable results can be obtained on more than 96% of paraffin-embedded specimens, and approximately 35% will be in the favorable subgroup, with less than 25% positively stained tumor cells. Whether MCM2 is predictive of response to therapy needs to be studied.

Adenocarcinoma↗

Epidemiologic differences between women with colorectal cancer and women with ovarian cancer.

BACKGROUND AND OBJECTIVES: The difference between the epidemiologic features of women with colorectal cancer and those with ovarian cancer has not been thoroughly studied. The aim of this study is to review the epidemiologic features of women with colorectal cancer and compare them with those of women with ovarian cancer. METHODS: The epidemiologic features of 705 women with colorectal cancer were compared with those of 503 women with primary epithelial ovarian cancer. Both groups included all women with the confirmed respective histologic diagnoses admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a voluntary self-administered epidemiologic questionnaire. RESULTS: Women with ovarian cancer were significantly younger, had higher education and income, had fewer children, and were more likely to have never been married and nulligravid than those with colorectal cancer. There was a significant difference in the contraceptive history between both groups among women > or = 45 years of age. More women with ovarian cancer had a family history of ovarian cancer and more women with colorectal cancer had a family history of colorectal cancer. CONCLUSIONS: The epidemiologic features of women with colorectal cancer are different from those with ovarian cancer. The difference between both groups might indicate difference in the environmental or genetic etiology of both cancers.

Colorectal Neoplasms↗

Regular use of analgesic drugs and ovarian cancer risk.

Analgesics have been shown to reduce risk for colorectal cancer. Results from three recent reports (D. W. Cramer et al., Lancet, 351: 104-107, 1998; C. Rodriguez et. al., Lancet, 352: 1354-1355, 1998; L. Rosenberg et al., Cancer Epidemiol. Biomark. Prev., 9: 933-937, 2000) suggest that these drugs might be associated with decreased risk for ovarian cancer. In this hospital-based case-control study, we compared 547 patients with ovarian cancer to 1094 age-matched patients with nonneoplastic conditions. All of the participants received treatment at the Roswell Park Cancer Institute between 1982 and 1998 and completed a comprehensive epidemiological questionnaire that included information on demographics, life-style factors, and reproductive characteristics as well as frequency and duration of aspirin and acetaminophen use. Women who reported that they had used one or more of these agents at least once a week for at least 6 months were classified as analgesic users. Logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Aspirin users were not at reduced risk of ovarian cancer compared with nonusers (adjusted OR, 1.00; CI, 0.73-1.39). There was also no evidence of a decrease in risk as a function of greater frequency of use or prolonged duration of use. Regular acetaminophen use was associated with a reduced risk (adjusted OR, 0.56; 95% CI, 0.34-0.86), and risk reductions were observed for women with the greatest frequency of use (adjusted OR, 0.32; 95% CI, 0.09-1.08) and longest duration of use (adjusted OR, 0.51; 95% CI, 0.27-0.97). These data suggest that regular use of acetaminophen, but not aspirin, may be associated with lower risk of ovarian cancer.

Acetaminophen↗

Comparison of CA 125 after three courses of chemotherapy and results of second-look surgery.

OBJECTIVE: To compare CA 125 levels after three courses of cisplatin-based chemotherapy and the results of second-look surgery. METHODS AND MATERIALS: From January 1990 to December 1996, the medical records of 72 patients diagnosed with epithelial ovarian cancer were reviewed. After initial staging surgery, all patients received cisplatin-based chemotherapy. Prior to each course of chemotherapy, patients underwent physical exams and serum CA 125 was obtained. After 6 courses of chemotherapy, if CA 125 levels were normal (< or = 35 IU/ml) and there was no clinical evidence of disease, the patient was offered second-look surgery. The sensitivity, specificity, and negative predicative value of CA 125 levels after 3 courses of chemotherapy and results of second-look surgery were calculated. Survival curves were constructed using Kaplan-Meier actuarial methods. RESULTS: Seventy-two patients were enrolled in the study. After completing 3 courses of chemotherapy, 43 out of 72 patients were reported to have normal CA 125 levels and were offered second-look surgery. Forty-six out of 72 patients underwent second-look surgery, 28 patients (60%) were reported to have positive second-look surgery. Of the patients with normal CA 125 levels after 3 courses of chemotherapy, 23 patients (57.5%) had a positive second-look surgery. The sensitivity and specificity of CA 125 values after 3 courses of chemotherapy were 17.9% and 94.7%, respectively and the negative predicative value was 43.9%. Patients with normal CA 125 values after 3 courses of chemotherapy had a significantly improved survival compared to those who failed to normalized their CA 125 levels after three courses of chemotherapy. CONCLUSION: Normalization of CA 125 after 3 courses of chemotherapy is a poor predicator of findings at second-look surgery.

Antineoplastic Agents↗

Epidemiologic differences between women with borderline ovarian tumors and women with epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to study the relationship between borderline ovarian tumors (BLOT) and epithelial ovarian cancer (EOC) by comparing the epidemiologic features of women with BLOT with those of women with EOC of similar histology. MATERIAL AND METHODS: The epidemiologic features of 32 women with serous and mucinous BLOT were compared with those of 273 women with primary serous or mucinous EOC. We included all women with the documented respective histologic diagnoses admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a self-administered epidemiologic questionnaire which contained 44 items pertaining to reproductive, contraceptive, medical, social, dietary, occupational, and family histories of cancer. Individual variables between both groups were compared using the Student t test, chi2 analysis, the Mantel-Haenszel test, and the Wilcoxon nonparametric test. Two-tailed P < 0.05 was considered significant. RESULTS: The response rate to the questionnaire was 63% in the BLOT group and 60% in the EOC group. There was no significant difference between the two groups in geographic location, race, education, income, smoking, marital status, age at first pregnancy, age at first birth, history of hysterectomy, history of infertility, history of tubal surgery, use of hormone replacement therapy, or history of diaphragm or intrauterine contraceptive device use. There were no significant differences in family history of malignancy between women with BLOT and those with EOC. Women with BLOT were significantly younger than those with EOC (mean age 47 +/- 14.0 versus 56 +/- 13.7, P < 0.01). There was an apparent difference in oral contraceptive pill use between both groups. However, when we adjusted for age by stratification this difference was not significant (P = 0.089). CONCLUSIONS: The epidemiologic features of women with BLOT are similar to those of women with EOC with the exception of an earlier age of onset. These findings might be consistent with one etiology for both conditions.

Adenocarcinoma, Mucinous↗

Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study.

OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.

Case-Control Studies↗

Epidemiologic differences between women with extraovarian primary peritoneal carcinoma and women with epithelial ovarian cancer.

OBJECTIVE: To describe the epidemiologic features of women with extraovarian primary peritoneal carcinoma and compare them with those of women with primary epithelial ovarian cancer. METHODS: The epidemiologic features of 50 women with extraovarian primary peritoneal carcinoma were compared with those of 503 women with primary epithelial ovarian cancer. We included all women with the respective diagnoses admitted to the Roswell Park Cancer Institute between October 1982 and October 1996 who returned an epidemiologic questionnaire. Epidemiologic features of the study and control groups were extracted from a database compiled from a self-administered questionnaire that has been given to patients as part of the admission process since 1982. Individual variables between the study and control groups were compared using Student t test, chi2 analysis, and Wilcoxon nonparametric test. Two-tailed P < .05 was considered significant. RESULTS: We found few significantly different epidemiologic features between women with extraovarian primary peritoneal carcinoma and those with primary epithelial ovarian cancer. Women with extraovarian primary peritoneal carcinoma were significantly older (mean age 63.8 versus 55.0 years, P < .001), had later menarche (13.3 versus 12.8 years, P = .024), and were less likely to have used perineal talc powder (26.0% versus 48.1%, P = .003). There were no significant differences with respect to reproductive history, contraceptive use, or use of hormone replacement therapy. A larger proportion of ovarian cancer patients reported a family history of breast cancer, but the numbers were too small to reach statistical significance. CONCLUSION: The epidemiologic features of women with extraovarian primary peritoneal carcinoma compared with women with primary epithelial ovarian cancer show few differences. The observed areas of difference warrant further research to determine whether they suggest the occurrence of distinct disease entities.

Epidemiologic Factors↗

A prospective study of microvascular free-flap surgery and outcome.

Over a 6-month period, 23 members of the International Microvascular Research Group participated in a prospective survey of their microvascular free-flap practice. Data were recorded with each case for 60 variables covering patient characteristics, surgical technique, pharmacologic treatment, and postoperative outcome. A total of 493 free flaps were reported with a representative demographic distribution for age, sex, indications for surgery, risk factors, flap type, surgical technique, and pharmacologic intervention. Mixed effects logistic regression modeling was used to determine predictors of flap failure and associated complications. The overall incidence of flap failure was 4.1 percent (20 of 493). Reconstruction of an irradiated recipient site and the use of a skin-grafted muscle flap were the only statistically significant predictors of flap failure, with increased odds of failure of 4.2 (p = 0.01) and 11.1 (p = 0.03), respectively. A postoperative thrombosis requiring re-exploration surgery occurred in 9.9 percent of the flaps. The incidence of this complication was significantly higher when the flap was transferred to a chronic wound and when vein grafts were needed, with increased odds of failure of 2.9 (p = 0.02) and 2.5 (p = 0.02), respectively. There was a lower incidence of postoperative thrombosis when rectus/transverse rectus abdominis muscle (TRAM) flaps were used, where odds of failure decreased by 0.36 (p = 0.04), and when subcutaneous heparin was administered in the postoperative period, where odds decreased by 0.27 (p = 0.04). There was an overall 69-percent salvage rate for flaps identified with a postoperative thrombosis. Intraoperative thrombosis occurred in 41 cases (8.3 percent) and was observed more frequently in myocutaneous flaps or when vein grafts were needed (5.5 and 5.0 greater odds, respectively; p < 0.001) but was not associated with higher flap failure (2 of 41 cases; 4.9-percent failure rate). The incidence of a hematoma and/or hemorrhage was increased in obese patients and when vein grafts were needed [2.7 (p = 0.02) and 2.6 (p = 0.03) greater odds, respectively], whereas this complication was significantly decreased in muscle flaps (myocutaneous or skin-grafted muscle), in tobacco users, when a heparinized solution was used for general wound irrigation, and when the attending surgeon performed the arterial anastomosis (in contrast to the resident or fellow on staff) (p < 0.05 for each factor). With the multivariable analysis, many factors were found not to have a significant effect on flap outcome, including the recipient site (e.g., head/neck, breast, lower limb, etc.); indications for surgery (trauma, cancer, etc.); flap transfer in extremes of age, smokers, or diabetics; arterial anastomosis with an end-to-end versus end-to-side technique; irrigation of the vessel without or with heparin added to the irrigation solution; and a wide spectrum of antithrombotic drug therapies. These results present a current baseline for free-flap surgery to which future advances and improvements in technique and practice may be compared.

Adolescent↗

Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study.

OBJECTIVE: To evaluate the role of hormone replacement therapy (HRT) as a risk factor for the development of epithelial ovarian cancer. METHODS: A case-control study was performed that used 491 patients with epithelial ovarian cancer frequency matched for age at diagnosis (+/-5 years) with a control population of 741 patients with malignancies of nonestrogen-dependent tissues. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, and education. RESULTS: One hundred of 491 patients (20.4%) in the study population had ever used HRT, and 160 of 741 patients (21.6%) in the control population had ever used HRT (OR 0.85; 95% confidence interval [CI] 0.62, 1.2). A significant association between HRT and specific histologic subtypes of epithelial ovarian cancer was not demonstrable for serous cystadenocarcinoma (OR 1.2, 95% CI 0.8, 1.7), Clear cell carcinoma (OR 1.1, 95% CI 0.4, 3.4), or endometrioid carcinoma (OR 0.4; 95% CI 0.2, 1.2). A significant association between duration of use of HRT and the risk of developing epithelial ovarian cancer was not demonstrable for under 5 years (OR 0.8; 95% CI 0.5, 1.2), 5-9 years (OR 0.6; 95% CI 0.3, 1.1), or 10 or more years (OR 0.6; 95% CI 0.3, 1.4). CONCLUSION: A significant association between the use of HRT and the risk of developing epithelial ovarian cancer, even with prolonged exposure, is not demonstrable.

Case-Control Studies↗

Tubal ligation and the risk of ovarian carcinoma.

To assess the relationship of tubal ligation and risk of ovarian carcinoma, we conducted a case-control, retrospective analysis of 300 ovarian carcinoma cases and 606 nonmalignant disease controls, seen between 1982 and 1988 at Roswell Park Cancer Institute, Buffalo, New York. Women who had a tubal ligation had reduced risk for the development of ovarian cancer. This relative risk was 0.52, with a 95% confidence interval 0.31 to 0.85 (p = 0.0076). Controls were matched by age. Multivariate analysis adjusted for socioeconomic level, marital status, parity, age at first pregnancy, menarche age, menopause age, irregular menses, breast-feeding duration, body habitus, and oral contraceptive use. Suggested explanations for this observation are offered.

Age Factors↗

Characteristics of familial ovarian cancer: a report of the first 1,000 families in the Gilda Radner Familial Ovarian Cancer Registry.

BACKGROUND: To determine the demographics of the first 1,000 families in the Gilda Radner Familial Ovarian Cancer Registry. METHODS: Any woman with a family history of two or more first or second degree relatives with ovarian cancer who was referred to the Registry was entered into a database. The demographics of the Registry population were analyzed, including total number of ovarian cancer cases, cases per family, age at diagnosis, prevalence of other malignancies, and histology. Comparisons were made to expected norms in the general population using the most recent surveillance, Epidemiology, and End Results data from the National Cancer Institute. RESULTS: There were 2,425 reported cases of ovarian cancer among the 1,000 registered families. The number of cases per family ranged from 2-10 with 72.4% of the families having two cases of ovarian cancer and 27.6% with three or more cases of ovarian cancer. The mean age at diagnosis was 53.5 years, significantly younger than the 60.8 years reported in the general population (p < 0.1). The mean age at diagnosis was even younger, 52.1 years, in the subset of patients with a family history of three or more cases of ovarian cancer. Moreover, in the mother/daughter pairs of ovarian cancer where age of onset of ovarian cancer was known, the mean age of the mothers was 58.8 compared to a mean age of 50.2 among the daughters (p < 0.01). There was a significantly larger proportion of serous adenocarcinoma (40%) and a significantly smaller proportion of mucinous adenocarcinoma (3%) and stromal cell tumor (0%) when compared to the general population (p < 0.01). Breast and colon cancer were the two most common other cancers reported. CONCLUSIONS: given the limits of the study due to the voluntary nature of the Registry, the data suggests that familial ovarian cancer occurs at a younger age than the general population, daughters of mothers with ovarian cancers develop ovarian cancer at an age significantly younger than their mothers, mucinous and stromal tumors occurred significantly less often than in the general population, and the most common associated other cancers are female breast cancer and female and male colon cancer.

Adolescent↗

Nutritional insult and recovery in the neonatal rat cerebellum: insulin-like growth factors (IGFs) and their binding proteins (IGFBPs).

Alterations in growth caused by neonatal malnutrition may be mediated in part by changes in insulin-like growth factor (IGF) and IGF binding protein (IGFBP) expression. Since the neonatal rat cerebellum undergoes a transient, proliferative growth phase in the first two weeks of life, this structure was used to determine whether alterations in circulating and tissue IGFs and IGFBPs may mediate effects of impaired nutrition on the developing central nervous system. Gravid rats were placed on a 4% (protein-calorie deprived, D) or 20% (control, C) protein diets one day prior to delivery and allowed to nurse their pups postpartum. Pups nursing from D mothers received a limited volume of milk and were calorically deprived. Some litters of D pups were foster fed by C mothers from day 8 to day 13 to constitute a recovery group (R). Cerebellar weight, protein, and DNA content in D pups were less than C, p < 0.001. In R pups, DNA and protein returned to C levels by day 13. Between days 6 and 13, serum IGF-I levels rose from 158 +/- 18 to 210 +/- 18 ng/ml in C but remained low in D (47 +/- 6 ng/ml and 25 +/- 3 ng/ml), respectively. In R pups, serum IGF-I partially recovered during this time, and increased from 49 +/- 5 to 110 +/- 7 ng/ml. In cerebellar extracts, IGF-I levels in both C and D were lower at 13 days than at 6 days, p < 0.05 and p < 0.005, respectively. IGF-I levels in C were similar at day 9 and day 11 and were consistently higher than D (11.84 +/- 0.83 vs 8.56 +/- 0.92 ng/g, p < 0.02 C vs D). In R, IGF-I was reduced on day 11, but was similar to C on day 13. Serum IGF-II in D was lower than C, p < 0.01, and did not increase in the R group. Cerebellar IGF-II was virtually undetectable in either group. Immunoprecipitation and ligand blotting studies of serum demonstrated that circulating levels of 32-34 K IGFBPs were increased 3-4 fold in D vs C, reflecting high levels of IGFBP-1 and/or -2, while levels of 24 K IGFBP-4 were lower in D vs C. By contrast, immunoprecipitation and ligand blotting of cerebellar extracts detected IGFBP-2 and -4, but did not detect IGFBP-1. Further, tissue levels of IGFBP-2 were not increased in D vs C, and levels of IGFBP-4 also were not markedly affected by nutritional deprivation. These results suggest that alterations in tissue content and the availability of IGF-I only modestly contributed to the effects of impaired nutrition in the developing central nervous system.

Animals↗

Proliferative growth of neonatal cerebellar cells in culture: regulation by male and by maternal serum in late gestation.

Neonatal cerebellar cells were utilized as a model system to examine the effect of 20 day pregnant rat serum on proliferative growth in the CNS. Cells were prepared by mechanical dissociation and cultured as mixed cells or populations enriched in astrocytes or oligodendrocytes. Cell proliferation was estimated by measurement of DNA, protein, and/or mitochondrial reductase activity (MTT). When mixed cells were incubated with 10% male rat serum, both total DNA and protein content increased after 6 days of culture. By contrast, neither of these parameters were altered in cultures incubated with 10% pregnant serum. When cells were incubated with either male or pregnant sera, changes in MTT activity paralleled changes in protein content. Graded concentrations of pregnant serum (5-20%) added to mixed cell cultures produced consistently lower MTT values when compared with identical concentrations of male serum. In addition, MTT activity was diminished in both astrocytes and oligodendrocytes incubated with graded concentrations of pregnant sera when compared with similar concentrations of non-pregnant sera. When potential effects of these different sera on the cell cycle were examined, an increase in the number of cells in the S and G2/M phase was similar, and DNA doubling began to increase at 96 hrs in the presence of either male or 20 day pregnant sera. Thus the inhibition of cell growth by pregnant serum was not likely a result of either cytotoxicity or a delay of entry of cells into the cell cycle. To examine whether this inhibition of cell growth may reflect the effect of pregnant serum on endogenous growth factor production, we tested the production of IGF-II by cerebellar cells. production of an endogenous source of IGF-II was apparent using an RNAse protection assay and was noted using Slot Blot analysis of mRNA extracted at sequential times during cell incubation. Mixed cell cultures also secreted immunologically defined IGF-II. These observations are consistent with the previous demonstration that the fraction of pregnant serum which bound IGF-II also inhibited cell growth. The inhibitory effect of pregnant serum was diminished by preincubating aliquots of sera with graded concentrations of IGF-I prior to adding sera to tissue culture medium. Pregnant serum inhibition was also diminished by prolonging incubation times beyond 6 days. The blunting of pregnant serum inhibition may have been consequent to either a continuing production of endogenous growth factors or to the potential emergence of resistant cells due to prolonged tissue culture incubation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Adaptation of the diphenylamine (DPA) assay to a 96-well plate tissue culture format and comparison with the MTT assay.

A simple spectrophotometric method for measuring DNA in proliferating cells is described. The method is an adaptation of the widely used diphenylamine (DPA) reaction to examine DNA in cells grown in a 96-well plate. This assay was capable of detecting as little as 10 ng DNA and could be used to measure DNA in stored as well as viable tissue samples. The DPA assay paralleled the MTT (3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay of mitochondrial reductase in A549 cells, a human lung cancer cell line; in EMT6 cells, a mouse breast cancer cell line; and in a primary cell culture of neonatal rat astrocytes. Over several days of proliferative growth in tissue culture, the ratio of MTT to DPA remained constant. Since the DPA assay and MTT assay measured different parameters of the same cells, they could be employed as complementary spectrophotometric assessments of cell growth on a 96-well plates using the same automated enzyme-linked immunosorbent assay plate reader.

Animals↗

Early and late survival in Hodgkin disease among whites and blacks living in the United States.

BACKGROUND: The independent effect of race on response to treatment and prognosis in Hodgkin disease is unclear. METHODS: The study included 9482 patients with histologically confirmed Hodgkin disease reported by 1084 different hospitals and institutions in the United States. The independent effect of race on response to treatment and recurrence was estimated using the logistic model. Cox proportional hazard model was applied to determine the independent effect of race and other covariables on risk of death. RESULTS: Complete remission occurred in more white patients (67.3%) than black patients (58.2%). Recurrences were reported more often in black patients than in white patients (40.3% and 30.9% respectively). Controlling for confounding variables, race has a significant independent effect on remission and recurrence (P < 0.05). In the first 5 years after diagnosis of Hodgkin disease, the patient age at diagnosis, clinical stage, and histologic type were significant predictors for the risk of death. At 5-10 years after a diagnosis of Hodgkin disease, age, clinical stage, and race of the patient were found to be significant risk factors (whites versus blacks: RR = 0.56; P < 0.05). CONCLUSIONS: Race is a significant predictor for remission, recurrence and survival in Hodgkin disease. Black patients have a more unfavorable prognosis than do white patients.

Adolescent↗

Familial ovarian cancer. A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry 1981-1991.

BACKGROUND: Because of the small number of cases (five) reported between 1929 and 1969 and a significant increase reported in the decade of the 1970s, the Familial Ovarian Cancer Registry was established in 1981 to study the occurrence of familial ovarian cancer in the United States. METHODS: Any woman (with or without ovarian cancer herself) who contacted the Registry and demonstrated a familial history of ovarian cancer was added to the Registry as an index case. RESULTS: From 1981 through May 31, 1991, 658 families for a total of 1568 cases of familial ovarian cancer were accessioned into the Registry. Of the 219 mothers and 251 daughters with familial ovarian cancer, the mean (58.5 years) and median (57.0 years) age at diagnosis of the mothers was significantly older than the mean (49.8 years) and median (49.0 years) ages of their daughters with ovarian cancer. Significantly more index cases without ovarian cancer had used oral contraceptives as compared to index cases with ovarian cancer (P < 0.001). Significantly more index cases with ovarian cancer used other estrogens as compared to index cases without ovarian cancer (P < 0.001). The Registry cases exhibited a higher proportion of serous adenocarcinoma, poorly differentiated adenocarcinoma, borderline carcinoma, and gonadoblastoma as compared to the 1978 SEER data. Mother and a minimum of one daughter was the most common relationship and was represented in 49.5% of the families with familial ovarian cancer. Sister-sister relationships were the second most frequent and accounted for 38.5% of the 658 families. CONCLUSIONS: Familial ovarian cancer occurs most frequently in mother-daughter relationships followed by sister-sister and appears to be an autosomal dominant inheritance with variable penetrance.

Adult↗

Patterns of presentation in brain tumors in the United States.

This study included 11,111 cases with confirmed primary brain tumors reported by 679 different hospitals in the United States in 1980 and in 1985. The combinations of symptoms and signs in relation to the site of the brain tumors, supratentorial vs infratentorial, were studied. Only one symptom was present in 32.9% and 26.7% of cases with supratentorial and infratentorial tumors. No neurologic sign was detected at the time of diagnosis in 20% and 14.6% of cases with supratentorial and infratentorial tumors, respectively. Considering the clinical stage at diagnosis, no neurologic sign was detected in 21.4% of patients presenting in stages I and II: compared with 11.5% in those presenting in late clinical stages (III & IV). The study confirmed the importance of meticulous history taking for early referral for diagnosis of brain tumors.

Brain Neoplasms↗