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Biomedical subjects

G Reiner

Publications and source records attributed to G Reiner.

At least 55 records · Page 3Linked to original sources

Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer.

An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.

Adult↗

[Breast cancer in the male. A long-term follow-up study of 55 patients].

Between 1964 and 1988, 55 male patients were treated for breast cancer. Fifty-one patients were treated by radical mastectomy; only four patients underwent a simple mastectomy. Nineteen cases received postoperative radiotherapy, eleven cases chemotherapy, six cases adjuvant hormonal therapy, and one patient was submitted to orchiectomy. The five-year survival rate for tumors with nodal metastases was 37%, as compared with 57% for patients with negative nodes.

Adult↗

HER-2 oncogene amplification and overall survival of breast carcinoma patients.

DNA was extracted from tumour samples of 77 patients with primary breast carcinoma and HER-2 proto-oncogene amplification was assessed. Prognostic indices such as number of positive lymph nodes, tumour size and histological grading were strongly associated with overall survival. No statistically significant correlation between amplification of HER-2 and overall survival was observed. In addition, prognostic indices, HER-2 amplification and disease-free interval was not correlated. Analysis of HER-2 amplification alone is not a useful guide in the management of patients with mammary carcinoma.

Breast Neoplasms↗

Expression and characterization of human CD4:immunoglobulin fusion proteins.

Different chimeric antibody-like molecules consisting of the four human CD4 extracellular domains (amino acids 1-369) fused to different parts of human IgG1 and IgM heavy-chain constant regions have been created and expressed in mammalian cells. For both IgG1 and IgM fusion proteins, the best expression in COS cells was observed for molecules lacking the CH1 domain of the heavy-chain constant region. The chimeric molecules are potent inhibitors of human immunodeficiency virus (HIV) infection and HIV-mediated cytotoxicity. A CD4:IgG1 hinge fusion protein, which was analyzed in more detail, binds efficiently to HIV gp160 and human Fc receptors and shows complement-assisted inhibition of viral propagation in culture. Half-life studies after intravenous application of the latter human fusion protein into mice and monkeys showed significant prolongation of serum survival compared to soluble CD4. An IgG2b murine homolog of the human CD4:IgG1 hinge fusion protein was prepared and evaluated in mice, where it was found to be nontoxic and to have no detectable effect on the humoral response to soluble antigen.

Amino Acid Sequence↗

[Interstitial radiotherapy of breast cancer. Preliminary report of a prospective study of 165 cases subjected to breast-conserving treatment].

UNLABELLED: The results of a prospective study on breast conserving therapy in early stage breast cancer are presented. From January 1983 to June 1987 165 patients were treated by a standardized therapy-protocol. The criteria for entering the trial were stage T1 to T2 and N0 to N1. Surgical breast conservation was achieved by segmental resection in 148 cases and by tumorectomy in 17 cases. 160 patients underwent axillary lymph node dissection. Obligatory 45 to 50 Gy were delivered percutaneously to the operated breast and optional 50 Gy to the regional lymph nodes (axillary lymph node involvement greater than 3 nodes). In addition, the area of the primary breast lesion itself was boosted interstitially by an Iridium 192 implant (LDR-technique: 15 to 20 Gy, HDR-technique: 10 to 12 Gy). RESULTS: Progression of disease in 10% of the patients (16/165), local recurrence rate in the operated breast: 2% (3/165), axillary recurrence: 0.5% (1/165). 5% of the patients (8/165) died from metastatic disease, two patients died free of recurrence for reasons unrelated to cancer, two other patients died on unknown reasons. Because of the low number of local recurrences and the observation period of 32 months, no statistically contribution on high risk factors for local failure could be found.

Adult↗

Antithrombin III substitution affects survival rate in a murine malaria model.

The effect of AT III substitution on survival time was studied in P. vinkei infected mice. One hundred mice were infected, randomly selected and allocated to two groups of 40 animals each on day 13 after infection. One group was placebo treated, the other group received 3 IU AT III daily on days 13 to 19. Comparison of the survival time in the log rank test showed a prolongation of the median survival time (5 versus 9 days, P less than 0.01). It is concluded that AT III might be beneficial in the treatment of severe malaria cases.

Animals↗

Reactivity of IgE in human Schistosoma mansoni sera to S. mansoni antigens.

Sera from Schistosoma mansoni-infected human patients were tested for total IgE levels and specific IgE and IgG antibodies to S. mansoni adult worm, cercaria, and egg antigen by ELISA. Of 50 sera, 28 were investigated by enzyme-linked crossed immunoelectrophoresis (ELCIE) to detect IgE reactivity to individual adult worm extract components. All sera showed increased total IgE levels. Specific IgE antibody levels to the different antigens varied; they were significantly correlated with each other but independent from total IgE. No correlation was found between specific IgG and any of the IgE antibody levels. Testing of the 28 individual sera by ELCIE revealed heterogeneous patterns. Seven sera were found to be nonreactive: three reacted with one precipitate, and the others reacted with between two and nine precipitates. However, in no case were identical patterns recognized, although four antigens reacted with about 80% of the sera. The number of bands detected by the individual sera depended neither on the levels of total IgE nor on those of specific IgE.

Animals↗

Preclinical investigations of the safety, immunogenicity and efficacy of a purified, inactivated tick-borne encephalitis vaccine.

A new tick-borne encephalitis (TBE) vaccine for human use has been developed. TBE virus (TBEV) was propagated in primary chick embryo cells, inactivated by formalin and purified by continuous-flow density gradient centrifugation. The TBE vaccine was tested for innocuity, immunogenicity and protective capacity in a series of laboratory tests. The results indicated that the vaccine is outstandingly well tolerated, highly immunogenic in various laboratory animals, and induces protective immunity in mice. These data suggest that this new vaccine should be studied in clinical trials.

Animals↗

Erythrocyte osmotic fragility in porcine malignant hyperthermia and effects of halothane.

Malignant Hyperthermia (MH) has been shown to be due to an inherited disorder in cellular membrane systems, which also seem to be affected by halothane. With the erythrocyte osmotic fragility test we tried to find out if the erythrocyte membrane can serve as a diagnostic tool in malignant hyperthermia and as a model for halothane effects on membranes. We obtained MH susceptible and MH resistant pigs and their crossbreeds. The MH susceptible pigs showed the greatest degree of haemolysis in the erythrocyte osmotic fragility test. Furthermore, halothane increased haemolysis more in the erythrocytes of MH susceptible pigs. The MH resistant pigs were only slightly affected in both and the crossbreeds showed intermediate results. The variance occurring within one halothane group could be used to add a further distinguishing characteristic apart from the discrete halothane challenge test and so enable selection within a pure halothane group.

Animals↗

Ki-67 immunoreactivity in breast carcinomas in relation to transferrin receptor expression, estrogen receptor status and morphological criteria. An immunohistochemical study.

The number of proliferating cells was determined by Ki-67 antibody in 107 primary breast carcinomas. These results were compared with transferrin receptor (TrfR) expression, estrogen receptor (ER) status, histologic type, tumor grade, size and axillary lymph node status. The percentage of Ki-67-positive cells ranged from 0.9 to 26.4%. The proportion of Ki-67-positive cells was highest in medullary carcinomas. Immunoreactivity of Ki-67 in relation to TrfR expression showed significant correlation (p = 0.0001). An inverse relationship between ER status and Ki-67 positivity existed (p = 0.0001). 88 cases were subjected to histologic grading. There was a significant relationship showing an increase of Ki-67 immunoreactivity with decrease of tumor differentiation (p = 0.0001). The distribution of Ki-67 reactivity in relation to tumor size and nodal status of the axilla revealed positive correlations (p = 0.02; p less than 0.05). In conclusion, the use of Ki-67 monoclonal antibody as a marker for cell proliferation represents a method to get kinetic data inhering prognostic value.

Antibodies, Monoclonal↗

HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer.

Amplification of HER-2 oncogene was analysed in DNAs obtained from 291 primary human mammary carcinomas. 52/291 (18%) were found to contain amplified HER-2 oncogene. Moderate amplification (2- to 5-fold) was noted in 36/291 (12%). Thirteen tumors (4.5%) had a copy number of 5 to 10. A 10- to 20-fold and greater than 20-fold amplification was observed in 2 and 1 patient, respectively. Sample sizes allowed the determination of estrogen receptor (ER) and progesterone receptor (PgR) levels in 253/291 primary breast cancers. HER-2 gene amplification was noted in 14% of ER+ patients and in 28% of ER- patients, respectively (P = 0.02). Similarly a significantly greater number of PgR- primary mammary carcinoma exhibited an amplification of the HER-2 gene compared to PgR+ cases (22% vs. 16%, P = 0.01). Although statistically not significant, tumors with HER-2 gene amplification were found to have lower levels of ER and PgR. No association of HER-2 amplification with the androgen receptor and EGF receptor was observed. Present data combine to suggest that tumor progression is more stringently controlled by the oncogene upon loss of hormone dependency. Differences found in HER-2 amplification between steroid receptor positive and negative tumors could be helpful to define a specific subset of women to whom adjuvant therapy should be directed.

Breast Neoplasms↗

[Androgen receptors in primary breast carcinoma. Relation to prognostic factors in comparison with estrogen and progesterone receptors].

Androgen receptor content was correlated with various prognostic factors in 274 patients with breast cancer. Receptor content was determined by the dextran-coated charcoal method (DCC). No direct relationship was found between androgen receptor content and age of patient, menstruation status, TN status and number of affected lymph nodes. But in 232 patients in whom tumour differentiation could be determined, there was a highly significant relationship between it and androgen receptor content (P less than 0.01). Similar correlations were found also between these prognostic factors and oestrogen or progesterone receptors. The percentage distribution of tumours of different degrees of differentiation was independent of the kind of demonstrable steroid-hormone receptor. However, the frequency of highly differentiated tumours rose with the number of different receptors that were determined. Thus steroid-hormone receptors can be considered as markers for differentiation. It seems possible that the additional determination of androgen receptors allows for a more exact selection of patients who should receive hormonal treatment.

Adult↗

Histopathologic characterization of human breast cancer in correlation with estrogen receptor status. A comparison of immunocytochemical and biochemical analysis.

A detailed histopathologic analysis of 399 primary breast carcinomas was performed, and several morphologic features were correlated with the estrogen receptor (ER) status. In all cases ER status was determined immunocytochemically by estrogen receptor immunocytochemical assay (ER-ICA). In 359 carcinomas ER status was also biochemically determined. Invasive lobular, mucoid, and tubular carcinomas rather than ductal carcinomas were ER-positive more frequently in ER-ICA. Medullary and papillary carcinomas had corresponding lower or higher ER positivity, respectively, by both methods. The correlation of histologic grade and its single factors with ER status was statistically significant by both methods. Lymphocytic reaction to tumor showed a significant inverse relationship to ER status by both methods. A statistically significant higher number of ER-positive carcinomas in ER-ICA and dextran-coated charcoal assay (DCC) occurred when elastic tissue was present. Different associations were found between stromal content, tumor diameter, and ER status in DCC and ER-ICA, respectively.

Adenocarcinoma↗

Ultrastructural and immunohistochemical characteristics of lipid-rich carcinoma of the breast.

Five cases of lipid-rich carcinomas of the breast were investigated ultrastructurally and immunohistochemically for alpha-lactalbumin (ALA), lactoferrin (Lfr) and human milk fat globule membrane antigen (HMFG-2). Staining for ALA and Lfr showed intensive reaction on nearly all of the tumour cells whereas immunoreaction for HMFG-2 revealed positivity in single cells. All tumours were negative for steroid receptor content. Ultrastructurally the tumour cells showed numerous intracytoplasmic non-membrane bound lipid droplets which were often found within autophagocytic vacuoles. Neither rough endoplasmic reticulum nor Golgi complexes showed any sign of lipid synthesis. Extrusion of lipid droplets and extracellular lipid deposition was not observed. In conclusion, our findings do not justify the consideration of lipid-rich carcinoma of the breast as a clearly defined group of tumours with specific secretory activity. Therefore, the term lipid-rich carcinoma should be used in preference to lipid-secreting, unless there is evidence of active lipid secretion.

Aged↗

Prognostic significance of immunohistochemical parameters in breast carcinomas.

136 breast carcinomas were investigated immunohistochemically for alpha-lactalbumin (ALA), lactoferrin (Lfr), human milk fat globule membrane antigen (HMFG-2), transferrin receptor (TrfR), Ki-67 and epidermal growth factor receptor (EGFR). The relationships of pathologic features and steroid receptor status previously shown to be of prognostic significance and the immunohistochemical parameters were examined. It was found that estrogen receptor (ER) was inverse related to TrfR, Ki-67 and EGFR whereas progesterone receptor (PgR) was inverse correlated to Ki-67 solely. Tumor grading revealed significant correlations between TrfR, Ki-67 and HMFG-2 (inverse correlation). Tumor diameter showed correlation between Ki-67 solely. Moreover there were significant relationships between lymphoid infiltration and TrfR, Ki-67 and HMFG-2 (inverse correlation). The comparison of the immunohistochemical parameters showed correlations between Ki-67 and TrfR, Ki-67 and HMFG-2 (inverse correlation) as well as HMFG-2 and ALA. Therefore it is suggested that functional and tumor kinetic properties determined by HMFG-2, Ki-67 and TrfR may be an additional indicator with prognostic significance. On the other hand immunoreactivities of ALA in conjunction with HMFG-2 possibly indicates a subpopulation of breast carcinomas that may have to be investigated further. Moreover these results showed that lymphoid infiltration was correlated with Ki-67 reactivity as well as TrfR expression.

Adenocarcinoma, Mucinous↗