Biomedical subjects

J Gralow

Publications and source records attributed to J Gralow.

9 recordsLinked to original sources

PubMed2001

Cancer symptom control: feasibility of a tailored, interactive computerized program for patients.

This study evaluated the feasibility of an innovative computerized symptom assessment tool, SymptomReport, and a computerized, tailored education tool, SymptomConsult, in a sample of 41 outpatients with cancer. After patients completed the computerized programs, an audiotaped telephone interview was conducted to assess patients' impressions. The study found that patients required less than 40 minutes on average to complete SymptomReport. The mean acceptability score was high 11 +/- 2. The 12 patients who completed SymptomConsult did so in an average of 20 minutes. The majority of participants indicated that the computer programs were easy, enjoyable, and informative tools. Initial formative research supports further study of these feasible computerized programs.

Adult↗

PubMed1999

Participation in breast cancer risk counseling among women with a family history.

Recent scientific breakthroughs in the genetics of breast cancer may have had effects on women's perceptions of risk and subsequent worry about breast cancer. Here, we present the rates of interest in counseling among women identified from diverse sources, their levels of cancer worry and perceived risk, and predictors of their agreement to participate in breast cancer risk counseling. Women were identified through breast cancer cases and through media offers. They completed a telephone survey and were ultimately either entered or not entered into a counseling trial. Overall, almost half (46%) of cases who were approached responded to the contact letter asking for information about potentially interested relatives. A total of 588 women responded to the brief media solicitations over a 15-week period. Participants recruited from media contacts reported slightly but significantly higher levels of worry about getting cancer, compared to case-recruited participants. Cancer worry negatively and significantly predicted entry into the counseling project. The results presented here may have implications for recruiting women in the general population with a family history of breast cancer for counseling about their risk for the disease.

Adolescent↗

PubMed1998

Gene therapy for breast and ovarian cancer with BRCA1.

As an initial step toward gene therapy for ovarian cancer, we conducted a Phase 1 trial to assess the pharmacokinetics and toxicity of intraperitoneal BRCA1sv retroviral vector therapy. Gene transfer and expression were documented by PCR, southern blot, RT-PCR and nuclease protection assays. Pharmacokinetics were assessed by PCR and southern blots detecting vector DNA, and toxicity was evaluated by clinical exam and fluid analysis. Three of twelve patients developed an acute sterile peritonitis which spontaneously resolved within 48 hours. Plasma and peritoneal antibodies to the retroviral envelope protein were detected only in patients treated with the highest dose levels but not in others, despite repeat dosing for an interval of up to four months. Eight patients showed stable disease for 4 to 16 weeks. Three patients showed tumor reduction with diminished miliary tumor implants at reoperation (two patients) and radiographic shrinkage of measurable disease (one patient). Ovarian cancer may provide an imporant model for retroviral gene therapy studies due to vector stability, minimal antibody response, and access to tumor by intraperitoneal therapy.

Journal Article↗

PubMed1998

Anthropometric and hormone effects of an eight-week exercise-diet intervention in breast cancer patients: results of a pilot study.

To assess the feasibility of an exercise-diet intervention in sedentary, overweight breast cancer patients, we conducted a pilot 8-week intervention. Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast cancer patients, ages 25-75 years, who were identified through two Seattle breast surgery practices and the University of Washington Breast Clinic. Ten patients were eligible and interested and were enrolled in the intervention, which consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20% of calories from fat) diet. Nine patients completed the program; all adhered well to the intervention and data collection protocol. The patients, ages 40-74 years, lost, on average, 2.6 pounds of body weight, 3.4 cm in waist circumference, 4.6 cm in hip circumference, 2.3% body fat, 3.3 systolic blood pressure points, 0.67 diastolic blood pressure points, and 4.0 pulse beats/min, and they gained an average of 2.3% lean mass. Slight, nonsignificant decreases were observed in serum concentration of total and free estradiol, estrone sulfate, total testosterone, androstenedione, and dehydroepiandrosterone. These pilot data indicate that breast cancer patients are highly motivated to join and adhere to an intense exercise-diet intervention and can experience significant measurable changes in anthropometric and fat mass measures.

Adult↗

PubMed1987

Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses.

Monoclonal anti-idiotype antibodies can be made which are exquisitely specific for B lymphocytic malignancies. We have conducted a clinical trial in which some patients' tumors regressed after infusion of such antibodies. Here, we evaluated characteristics of the antibodies, the tumors, and the patients to determine which features best correlated with the clinical response. Neither the isotype of the murine antibodies, nor their avidity were predictive of clinical outcome. The specific epitope to which the antibodies bound was characterized by immunochemical techniques. Reactivity with a heavy-light chain combinatorial determinant correlated somewhat with clinical effect. Variations in the characteristics of the individual tumors such as antigen sites per cell and ability to modulate the surface immunoglobulin were not predictive of response. In one patient with prolymphocytic leukemia the anti-idiotype antibody had a direct antiproliferative effect on tumor cells in vitro. This patient's tumor response was explainable by such a direct mechanism. In the other patients, who had lymphomas, therapeutic outcome correlated with the number of host nontumor cells infiltrating the tumor. The vast majority of these nontumor cells were mature T lymphocytes of the Leu 4, Leu 3 (T3, T4) phenotype. Thus, a preexistent host-tumor interaction seems to be important in the in vivo effect of anti-idiotype antibodies in B cell tumors.

Antibodies, Anti-Idiotypic↗

PubMed1987

In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias.

The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti-idiotype antibodies.

Antibodies, Anti-Idiotypic↗

PubMed1984

Biclonal B-cell lymphoma.

The cells of most tumors are considered to be genetically homogeneous because they are assumed to represent a single clone descended from one abnormal cell. We have discovered three cases of B-cell lymphoma for which this generalization is not true. In each case, the tumor was composed of two subpopulations of cells, each expressing a different immunoglobulin molecule. Antibodies directed against these immunoglobulins were used to separate the two cell subpopulations of each tumor on a fluorescence-activated cell sorter. DNA extracted from the original tumor and the two fractionated subpopulations was analyzed to determine the configuration of immunoglobulin genes. Differences were found in the arrangement of DNA in at least one immunoglobulin gene for each of the two subpopulations. Thus, biclonality of these tumors was revealed by examination of both protein markers (cell-surface immunoglobulin) and DNA markers (immunoglobulin-gene rearrangements). Our results indicate that the incidence of biclonal B-cell lymphoma may be higher than previously recognized, possibly as high as 10 per cent of all B-cell lymphomas. Furthermore, our findings may have important implications for the diagnosis and therapy of lymphoid cancers.

Adult↗

PubMed1984

The induction of Leu-1 antigen expression in human malignant and normal B cells by phorbol myristic acetate (PMA).

Malignant cells from five patients with B cell leukemia or lymphoma were cultured with phorbol myristic acetate (PMA). PMA was found to induce cell surface expression of the Leu-1 antigen in cells from three of the five patients. Using one- and two-color immunofluorescence staining and flow cytometry, we have shown simultaneous expression of the Leu-1 antigen with other B cell markers. Induction of Leu-1 antigen expression was not related to histologic subtype, in vitro secretion of immunoglobulin, or other clinical features. Biosynthetic labeling experiments showed that synthesis of Leu-1 antigen occurred and preceded expression of the antigen on the cell surface. PMA also induced the appearance of Leu-1 antigen-positive B cells in cultures of normal peripheral blood mononuclear cells. We propose that the Leu-1 antigen is expressed transiently during the differentiation of some B cells.

Antigens, Differentiation, B-Lymphocyte↗

PubMed1984

Strategies for production of monoclonal anti-idiotype antibodies against human B cell lymphomas.

Murine monoclonal antibodies (MAB) against the idiotype (Id) of B lymphocyte malignancies are powerful reagents for the study of these diseases, and are potentially useful for treatment. Different strategies for the production of these anti-Id MAB have been compared. Initially, the Id Ig from nonsecreting B cell tumors was "rescued" by human X mouse or human X human hybridization. These somatic cell hybridizations resulted in the secretion of human Ig in 10 and 100% of the fusions, respectively. In a second step, anti-Id MAB were produced by using the "rescued" Id Ig as immunogen. A more streamlined approach is based on a one-step procedure in which the tumor cell suspension is used as immunogen. This method of immunization, coupled with a four-layer ELISA, results in the detection of anti-Id MAB in a frequency of approximately 1% of the total hybrids. By using a pool of 10 different anti-Id MAB, each reactive with the tumor of one patient, we searched for idiotypic relatedness among a panel of 50 additional tumors. No cross-reactions were found, indicating that our current strategy results in the identification of unique idiotypic determinants among human B cell tumors. Idiotypic Ig can be found in the serum of patients with B cell tumors. Among groups of patients, there is a wide spectrum of serum Id levels, ranging from less than 0.01 microgram/ml to greater than 500 micrograms/ml.

Animals↗