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Biomedical subjects

H A Fritsche

Publications and source records attributed to H A Fritsche.

At least 37 records · Page 2Linked to original sources
PubMed1997

The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model.

We studied the effects of different hormones on the epithelial cells of the ovaries of 11 guinea pigs. Three received testosterone, two received estrone, three megestrol, and three chorionic gonadotropin. Three control guinea pigs received sterile water. Benign epithelial cysts larger than 1.5 mm were found in six guinea pigs, three who received testosterone, one who received megestrol, and two who received chorionic gonadotropin. In one of the three guinea pigs who received testosterone, 2.5-cm bilateral cysts were grossly identified. Papillary excrescences were found on the ovarian surface in four guinea pigs, three who received testosterone and one who received megestrol. The proliferating epithelial cells also formed benign glands in the ovarian stroma in two guinea pigs who received testosterone, the most exuberant epithelial proliferations, including large bilateral cystadenomas, papillary excrescence that formed a small papillary neoplasm, and glands in the ovarian stroma that formed adenomatous areas, were seen in the guinea pig who received an intermediate dose of testosterone for the longest time. By radioimmunoassay, the serum level of testosterone was 22 ng/dL in one of the controls and 10,000, 12,000, and 15,000 ng/dL in the three guinea pigs who received testosterone. In the guinea pig with the most exuberant epithelial proliferation, the level of testosterone in the uterus was similar to that in the serum (13,860 ng/mg), but in the wall of the ovarian epithelial cyst, it was three times higher than it was in the serum (44,000 ng/mg). Our study shows that testosterone stimulates the growth of epithelial cells in the ovaries of guinea pigs, resulting in benign cysts, small adenomas in the ovarian parenchyma, and papillomas on the ovarian surface. The study also shows that guinea pigs can be used as an animal model for epithelial tumors of the human ovary.

Animals↗
PubMed1996

Bivariate RNA and DNA content analysis in breast carcinoma: biological significance of RNA content.

Flow cytometric studies of mammary carcinoma have been limited to DNA content analysis. Simultaneous analysis of DNA and RNA has been applied to hematological and certain solid neoplasms and has been shown to provide valuable information in the clinical assessment of these tumors. To determine whether measuring RNA content during flow cytometric analysis provides additional information in the clinical assessment of breast carcinoma, dual-parameter analysis of DNA and RNA content on freshly disaggregated breast carcinoma specimens was performed. RNA content, divided along the mean (</=1.6 and >1.6), correlated with tumor grade, histological type, hormonal status, and patient survival. DNA aneuploidy was noted in 247 (69.2%) neoplasms and correlated significantly with tumor grade and stage but not with clinical outcome. The proliferative fraction, defined as S + G2-M and dichotomized along the mean value (</=10% and >10%), correlated significantly with tumor grade, size, hormonal status, lymph node involvement, and survival. Cox's proportional hazard analysis revealed that RNA content, proliferative fraction, and tumor stage are independent prognostic indicators. Our results indicate that measurement of cellular RNA content provides additional biological information that may be useful in the clinical assessment of breast carcinoma.

Adult↗
PubMed1995

Risk classification for large cell lymphoma using lactate dehydrogenase, beta-2 microglobulin, and thymidine kinase.

We have previously proposed a staging system for large cell lymphoma using the two serum markers beta-2-microglobulin (B2M) and lactate dehydrogenase (LDH). We recently tested this model in a different cohort of patients with large cell lymphoma and also examined the possible contribution of thymidine kinase (TK), a previously reported serologic prognostic factor. Using an inclusion criteria in the multivariate analysis for both forward and backward selection of p < 0.15, only LDH, B2M, and TK were significant independent prognostic factors for both time to treatment failure (TTF) and survival. Inclusion of TK in the serologic model resulted in three significantly different risk groups for both TTF and survival. Corresponding endpoints at three years were: 1) good risk (no markers elevated, n = 43): 78%, 91%; 2) intermediate risk (1 or 2 markers elevated, n = 47): 41%, 36%; 3) poor risk (3 markers elevated, n = 11): 0%, 0%. This analysis extends the observation of the independent prognostic significance of B2M and LDH. The addition of TK permits a more precise estimate of risk, contributing to the utility of a serological staging system for large cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Serum levels of transforming growth factor alpha in gastrointestinal cancer patients.

Transforming growth factor alpha (TGF alpha), a polypeptide growth-stimulating factor, has been implicated to play a role in the progression of gastrointestinal (GI) cancer. It has been suggested that TGF alpha expression in tumors or TGF alpha in the biological fluids of cancer patients may have tumor marker value. The serum levels of TGF alpha in GI cancer patients have not been reported. In this study, the serum TGF alpha levels of 100 GI cancer patients, as well as 74 healthy individuals, were determined by a TGF alpha-specific RIA kit. All of the cancer patient sera and 67% of the normal sera had detectable levels of TGF alpha. The TGF alpha concentrations in GI cancer patients ranged from 119 to 760 pg/ml, with a mean value of 269 +/- 102 pg/ml. Fifty normal individuals had detectable levels of TGF alpha, and their levels ranged from 120 to 207 pg/ml, with a mean value of 147 +/- 18 pg/ml. Differences in serum TGF alpha concentration between cancer patients and healthy individuals were found to be statistically significant, as evaluated by Mann-Whitney and Student's t tests. Serum TGF alpha levels were found to be significantly elevated in all disease stages of gastric, pancreas, colon, and rectal cancers, and only in the late stages of esophageal cancer. Serum carcinoembryonic antigen levels were significantly elevated only in the late stages of these diseases. The potential of serum TGF alpha as a tumor marker for GI malignancy, therefore, warrants further investigation.

Adult↗
PubMed1994

Elevated serum levels of transforming growth factor-alpha in breast cancer patients.

Previous studies suggest that transforming growth factor-alpha (TGF alpha) may have the potential of a tumor marker. Since the levels of serum TGF alpha in cancer patients and healthy individuals have not been reported, we determined the serum TGF alpha levels of 83 breast cancer patients and 74 healthy individuals by using a TGF alpha radioimmunoassay kit. All of the cancer patients' sera were positive for TGF alpha; their TGF alpha concentrations ranged from 210 to 740 pg/ml, with a mean of 353 +/- 98 pg/ml. Sixty-seven percent (50 cases) of normal sera were positive for TGF alpha; the levels ranged from 120 to 207 pg/ml, with a mean of 144 +/- 17 pg/ml. The difference in serum TGF alpha levels between cancer patients of different disease stages and healthy individuals was found to be statistically significant by Student t-test and the Mann-Whitney test. No correlation was found between serum carcinoembryonic antigen and TGF alpha levels. The potential of serum immunoreactive TGF alpha as a marker for breast cancer warrants further investigation.

Adult↗
PubMed1994

Nonspecific cross-reacting antigen 50/90 is elevated in patients with breast, lung, and colon cancer.

A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the management of patients with a variety of cancers.

Animals↗
PubMed1994

Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.

PURPOSE: The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients. PATIENTS AND METHODS: Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days. RESULTS: The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed. CONCLUSION: Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.

Adolescent↗
PubMed1994

Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia.

PURPOSE: Retinoids have proven chemopreventive efficacy in both preclinical and clinical studies. This trial was designed to confirm the finding of an earlier uncontrolled trial that the synthetic retinoid etretinate had major activity in reversing squamous metaplasia found in the bronchial epithelium of chronic smokers. PATIENTS AND METHODS: We prospectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 mg/kg isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of treatment. RESULTS: In the group as a whole, the metaplasia index decreased over time from a mean +/- SE of 35.8% +/- 2.7% at baseline to 28.1% +/- 3.3% at the completion of treatment (P = .01) by repeated measures analysis of variance [ANOVA]); a reduction in the metaplasia index (> 8%) was noted in both isotretinoin and placebo groups (19 of 35 [54.3%] and 20 of 34 [58.8%], respectively). Complete reversal of squamous metaplasia was noted in nine subjects from each group. However, the magnitudes of the mean metaplasia index changes did not differ significantly in the two treatment groups. In both groups, smoking cessation resulted in significant declines in the extent of squamous metaplasia, whereas no significant change in metaplasia index was found among those who continued to smoke. CONCLUSION: Squamous metaplasia was frequently observed in bronchial biopsy samples from chronic smokers. From this study, we conclude that isotretinoin has no effect on squamous metaplasia, a potential intermediate end point of bronchial carcinogenesis. Although determining the exact role of isotretinoin in lung cancer prevention requires further study, the finding that there was a significant decrease in squamous metaplasia in the placebo group emphasizes the critical importance of a placebo-controlled study design in chemoprevention trials using intermediate end points.

Adult↗
PubMed1993

Analytical performance goals for measuring prostate-specific antigen.

We have assessed the feasibility of using fixed-limit criteria based on medical relevance and biological variation for evaluating the analytical performance of the prostate-specific antigen (PSA) test. The estimated within-subject variation of serum PSA is on the order of 10-20% at clinical decision points. The calculated performance goals of 5-10% CV are attainable with current immunoassay technology and agree with precision goals based on clinical experience and the current clinical use of the test. However, new clinical applications of PSA may require a degree of analytical performance that current methods may not be able to provide. The PSA model demonstrates the need for biologically based fixed-limit criteria for all tumor-marker tests.

Biomarkers, Tumor↗
PubMed1993

Serum tumor markers for patient monitoring: a case-oriented approach illustrated with carcinoembryonic antigen.

The effectiveness of patient monitoring with serum tumor markers is improved when the patient's pretreatment baseline is established, regular serial testing is performed, and a clinically significant change of the marker is determined on the basis of objective criteria. Attention must be directed to (a) ensuring long-term assay precision, (b) timing specimen collection to avoid misinterpretation of paradoxical increases (induced by chemotherapy, surgery, or radiation), (c) noting changes in the production or clearance mechanisms of the marker, and (d) recognizing the variability of site-response in patients who have multiple locations of metastatic disease. Clinical decisions to alter therapy should not be based only on tumor marker measurements. In the absence of other clinical data, a tumor marker abnormality should be confirmed with serial samples collected at a time interval dictated by the half-life of the marker. Serial tumor marker testing can improve cancer patient care, especially when effective salvage therapies are available.

Biomarkers, Tumor↗
PubMed1991

Sequentially administered ethinyl estradiol and medroxyprogesterone acetate in the treatment of refractory epithelial ovarian carcinoma in patients with positive estrogen receptors.

The activity of sequentially administered hormonal therapy was investigated over 25 days in 25 patients with epithelial ovarian carcinoma who had estrogen receptor (ERc)-positive tumors. Patients received ethinyl estradiol (EE) (50 micrograms/d) on days 1 to 7 and medroxyprogesterone acetate (MPA) (400 mg/d) on days 8 to 25. Twenty-three patients completed one or more courses of treatment. There were no complete responses (CR). Four partial responses (PR) with durations of 9, 4, 3, and 1 months were seen. Two incomplete responses with durations of 6 and 4 months were also seen. Six patients had stable disease (SD), and 11 patients had progression. The overall response rate was 17% and may represent a modest improvement in response over those in previously published studies conducted with MPA alone. No significant toxic effects were noticed, and some patients reported an improved sense of well-being. However, two patients experienced depression with this treatment. The mean ERc values in responders, patients with SD, and nonresponders were 70.0, 36.7, and 47.9 fmol/mg cytosolic protein, respectively. Future studies of hormonal therapy in patients with ovarian carcinoma should attempt to identify more reliable indices for determining sensitivity to these agents.

Administration, Oral↗
PubMed1991

Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis.

Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity.

Adult↗
PubMed1991

Monoclonal prostate-specific antigen in untreated prostate cancer. Relationship to clinical stage and grade.

The authors evaluated 440 men with clinically staged and untreated prostate cancer with a monoclonal prostate-specific antigen (PSA) assay. The serum PSA value correlated significantly with both the stage and grade of disease (P less than 0.00005). The relationships between PSA and consecutive Stages A, B, C, and D2 (alpha = 0.15) and between progressive Gleason's scores 2 to 4, 5 to 7, and 8 to 10 (alpha = 0.15) were statistically significant. Also statistically significant was the correlation between serum PSA level and intracapsular versus extracapsular disease (P less than 0.00005), although no one value can be used to differentiate reliably between patients in these two categories. The probability of clinically detectable metastasis (Stage D2) is 85% if the serum PSA level is greater than 30; however, 12% of patients without clinical evidence of metastases (Stages A, B, and C) have such a serum PSA value. Despite the statistically significant association between PSA and tumor differentiation and volume as reflected by tumor grade and clinical stage, this marker cannot be used to determine either for an individual patient.

Aged↗
PubMed1991

Ratio of polyclonal-monoclonal prostate-specific antigen levels. Discrimination of nodal status in prostate tumors that produce low marker levels.

The preliminary data we present in this report suggest that the ratio of polyclonal-monoclonal serum prostate-specific antigen levels may add clinically useful information to that obtained using serum prostate-specific antigen levels alone. We hypothesize that the diversity of prostate-specific antigen ratios observed in our data reflects a diversity in the antigenic and structural attributes of prostate-specific antigen molecules found in the sera of patients with prostate cancer. Further, this heterogeneity of molecules is a reflection of the diverse and altered metabolic state of human prostate cancer and appears to be related to biologic behavior in individual patients.

Antibodies↗
PubMed1991

Plasma protein-bound sialic acid in patients with colorectal polyps of known histology.

Protein-bound sialic acid (PBSA) was measured in serial plasma specimens from 62 healthy subjects, 48 patients with colorectal polyps, and 30 patients with colorectal adenocarcinomas. The mean plasma PBSA concentration in healthy smokers was significantly greater than that in healthy nonsmokers and healthy ex-smokers (P less than 0.0001). Villoglandular polyps were associated with higher plasma PBSA values than were the most benign hyperplastic polyps (P less than 0.025). Patients with the most neoplastic villoglandular and villous polyps had significantly greater (P less than 0.010-0.050) plasma PBSA values than healthy subjects. Polypectomy decreased the mean PBSA value significantly to the mean value for healthy subjects only for patients with villoglandular (P less than 0.010) or villous (P less than 0.050) polyps. Colorectal cancer patients had mean plasma PBSA concentrations significantly greater than those for the healthy subjects (P much less than 0.001) and the polyp patients (P much less than 0.001). Surgery significantly reduced (P less than 0.025) the mean PBSA value for the cancer patients to the mean PBSA value observed for the healthy subjects.

Adenocarcinoma↗
PubMed1991

Carcinoembryonic antigen in serum of patients with colorectal polyps: correlation with histology and smoking status.

To measure the concentration of carcinoembryonic antigen (CEA) in serial serum specimens of 47 healthy subjects and in serial sera of 59 patients with colorectal polyps of confirmed histology, obtained before or after (sometimes both) polypectomy, we used the Roche EIA and the Hybritech Tandem-E double monoclonal immunoenzymometric assays. Both methods gave comparable results for the healthy subjects but discordant values for some polyp patients. The Tandem-E test gave increased CEA results more frequently for two groups of polyp patients, the group of ex-smokers with neoplastic polyps (n = 14) and the group of smokers (n = 20). Smokers had significantly greater (P less than 0.025) mean concentrations of serum CEA than did nonsmokers, irrespective of whether they were healthy or had colorectal polyps. Smokers with recurrent polyps demonstrated significantly greater (P less than 0.050) mean concentrations of serum CEA than did smokers with a first occurrence of polyps. Polypectomy was followed by statistically significant decreases (P less than 0.050) of mean concentrations of serum CEA, primarily in polyp patients who were smokers. However, although CEA increases occurred frequently in polyp patients who smoked, these abnormalities did not fully correlate with polyp histology.

Adult↗