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Biomedical subjects

C Ingvar

Publications and source records attributed to C Ingvar.

79 records · Page 5Linked to original sources

Phase II study of high dose toremifene in advanced breast cancer progressing during tamoxifene treatment.

Thirty-five (34 evaluable) consecutive postmenopausal women with estrogen receptor positive (greater than or equal to 10 fmol/mg) or unknown advanced breast cancer were treated with high dose toremifene in a phase II study. All patients had progressed during prior adjuvant or palliativ antiestrogen treatment. The dose of toremifene was 240 mg per day. No complete or partial responders were registered. Nine patients (26%) were considered to have stable disease (NC). The time to progression for these patients was 5-27+ months with a mean time of twelve months and median time of eight months. Two patients are still on treatment after twelve and 24 months respectively. There seems to be a relationship with receptor value; however, there are two few patients for a safe statistical analysis. The side effects were insignificant. The conclusion is that the efficiency of toremifene as second line hormonal treatment is restricted, although it may be one additional choice.

Antineoplastic Agents↗

Tumour antigen heterogeneity within melanoma metastases--an evaluation by immunohistochemistry.

Fifty-eight metastases of malignant melanoma in 27 consecutive patients were evaluated by immunohistochemistry using monoclonal antibodies (MAb) 96.5, 48.7 and 4.2, all with a high specificity for melanoma tumour associated antigens. MAb OKT3 directed to human T-lymphocytes was used as control and normal mouse serum as background. Different degrees and patterns of staining were recorded using a scale of 0 to 4. 85% of the metastases were positive (score greater than +2) to 96.5 or 48.7 and 78% to antibody 4.2. All metastases were positive for at least one of the three antibodies, 93% for two, and 59% for all three antibodies. No substantial heterogeneity (more than +1 difference) was found in two sections approximately 5 mm apart within the same metastasis (one out of 39 metastases). In 15 patients in whom more than one tumour was examined, heterogeneity between individual metastases was found in one patient for antibody 96.5, three for 48.7 and none for 4.2. The existence of immunological heterogeneity in melanoma metastases must be taken into account when designing techniques for radioimmunoimaging and radioimmunotherapy.

Antibodies, Monoclonal↗

Estrogen receptor and binding site for estramustine in metastatic malignant melanoma.

Enzyme immuno assay (EIA) of estrogen receptor (ER) has confirmed the results of earlier investigations using steroid binding techniques, namely that ER is present at very low concentrations in samples from metastatic melanoma. Thirty-four of 61 samples (56%) were ER positive with EIA. The corresponding figures using isoelectric focusing (IF) for the steroid binding assay were 16 of these 61 samples (26%). The difference between the methods may be due to difficulties in the interpretation of analytical results for IF at low ER concentration levels or to interference from other 3H-estradiol binding components. Estramustine binding site (EMBS) has been found in samples from 15 of 77 patients (20%) with IF in polyacrylamide gels. Estramustine is, together with estramustine, the cytotoxic metabolite of estramustine phosphate (Estracyt). In analogy to the previously suggested therapeutic significance of estramustine binding protein in the treatment of prostatic cancer, the clinical importance of estramustine phosphate should also be studied in metastatic malignant melanoma in correlation with EMBS status.

Adolescent↗

Estrogen and progesterone receptors in melanoma metastases with special reference to analytical methods and prognosis.

Fifty-one tumor biopsies from 33 patients with metastatic melanoma were assessed for estrogen receptor (ER) content, and 46 of these for progesterone receptor (PgR) content in the cytoplasm. ER posivity (above 0.2 fmol/mg protein), as measured with isoelectric focusing on polyacrylamide gels, was found in 23 (70%) of the patients (range 0.2 - 14 fmol/mg protein). With a reference limit of 2 fmol ER/mg protein, 12 patients were positive (36%). PgR was analysed with the dextran coated charcoal technique and no sample demonstrated any positivity with certainty. The ER content was related to clinical prognostic factors without any significant correlation independent of reference limit used. A correlation to survival can not be excluded with ER values above 2 fmol/mg. Pertinent data are given regarding the technique used in comparison with others.

Charcoal↗

Heterogeneous distribution of radiolabelled monoclonal antibody. Autoradiographic evaluation in the nude rat model.

Iodinated monoclonal antibody 96.5 was injected intravenously in the nude rat model transplanted with human melanoma. The activity distribution was evaluated by: 1) direct application of dissected tissue on autoradiographic film, 2) autoradiography of whole-body sections, and 3) beta-camera imaging of fresh frozen tissue. Method (1) is non-quantitative and has a poor resolution. It can only be recommended for simple screening. The whole-body method (2), although complicated, gives more accurate digital information of tissue uptake in individual pixels, or in larger regions of interest (ROIs). The beta camera technique (3) is a rapid method but its accuracy is less than the whole-body method. All three methods showed that the activity distribution in the tumours was more heterogenous than in other tissues. An overlap of activity uptake in tumours and other tissues was often seen. Mean uptake ratios in the whole body autoradiograms correlated well with in vivo uptake ratios from measurements in dissected tissues. At present, whole body autoradiography appears to be the method of choice for imaging the uptake of radiolabelled monoclonal antibodies in experimental animals.

Animals↗

Endometrial thickness and ovarian cysts as measured by ultrasound in asymptomatic postmenopausal breast cancer patients on various adjuvant treatments including tamoxifen.

Endometrial thickness as measured by ultrasound during tamoxifen treatment has previously been reported. However, there has not been any study investigating endometrial thickness before treatment and following it at regular intervals during treatment. 90 patients with breast cancer without any gynecological symptoms were followed (aged more than 50 years at the operation of their breast cancer). They were investigated by vaginal ultrasound and a common clinical investigation at our out-care patient department. Adjuvant breast cancer therapy consisted of tamoxifen, tamoxifen after radiotherapy and/or in a few cases cytostatics, cytostatics with or without the addition of radiotherapy, radiotherapy or no further therapy. Patients with receptor positive tumours were given tamoxifen. Their endometrium was already thicker before the start of adjuvant treatment as measured by ultrasound. After 3 months and 12 months we found the endometrium to be significantly thicker in those treated with tamoxifen compared to other treatment groups. After 12 months of tamoxifen treatment 22/32 women had an endometrial thickness of 5 mm or more. The frequency of ovarian cysts also seemed to be affected by therapy. In patients treated with tamoxifen alone or in combination, the frequency of cysts was 5/35 before treatment, 6/37 after 3 months, and 0/32 after one year. The corresponding frequencies for those not treated with tamoxifen were 2/20, 3/11 and 3/23 respectively.

Antineoplastic Agents, Hormonal↗

Histopathologic findings in thickened endometria, as measured by ultrasound in asymptomatic, postmenopausal breast cancer patients on various adjuvant treatment including tamoxifen.

Pallents with breast cancer exhibit an increased risk of developing cancer from other organs, a risk that might increase due to tamoxifen treatment. This drug has been found to cause activation of oestrogen receptors, leading to oestrogenic effects on the postmenopausal endometrium. We report follow-up of 94 patients with breast cancer without initial symptoms aged more than 50 years at the time of operation. They were followed-up with vaginal ultrasound at regular intervals and endometrial sampling was performed according to treatment after surgery: tamoxifen, tamoxifen in combination with other regimes and without tamoxifen treatment. A large proportion were investigated prior to treatment. We identified endometrial carcinoma, metastasis of breast carcinoma and histopathological changes in 17/67 (25%) of the patients treated with tamoxifen compared to 1/32 in those not treated with tamoxifen.

Breast Neoplasms↗