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Biomedical subjects

A Schauer

Publications and source records attributed to A Schauer.

At least 55 records · Page 3Linked to original sources

Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients.

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.

Biomarkers, Tumor↗

[Septic shock with acute abdomen in idiopathic hemochromatosis].

The case of a patient with abdominal crisis and shock without any discernible origin who died 36 hours after hospital admission despite maximal therapy is described. Gram-negative sepsis, peritonitis and haemochromatosis with hepatic siderosis was the post-mortem diagnosis. We consider spontaneous peritonitis arising from translocation of normal intestinal flora (E. coli) through the intact wall of the gut combined with the impaired ability of the reticulo-endothelial system to remove endotoxin to be the causative factors. It is unknown whether the adrenal insufficiency due to siderophilic adrenal hypophysis and adrenal glands contributed to the fulminant course of the disease. Undiagnosed liver cirrhosis and especially haemochromatosis should therefore be included in the differential diagnostic considerations in patients presenting with these symptoms, and in whom no obvious cause for a septic focus can be found.

Abdomen, Acute↗

Quality control review for radiotherapy of small breast cancer: analysis of 708 patients in the GBSG I trial. German Breast Study Group (GBSG).

Within six years between November 1983 and December 1989 the German Breast Cancer Study Group (GBSG) conducted a prospective multicenter trial on the treatment of pT1 pN0 M0 breast carcinoma. Out of 1036 eligible patients from 69 hospitals, a total of 733 underwent breast preservation surgery and postoperative radiotherapy. A detailed quality control (QC) screening of 708 available radiotherapy records was performed by the radiotherapy reference center. The following quality control scoring system was used for all radiotherapy variables: Radiotherapy treatment "completely according to study protocol" (QC score = 0); "acceptable protocol deviations" (QC score = 1); "unacceptable protocol violations" (QC score = 2); the "overall QC score" was the worst judgement for any single quality control criterion, while the "total QC score" was the summation of all single quality control scores (range: 0 to 14). 292 (41.2%) patients were treated per protocol; 290 (41.0%) had acceptable protocol deviations; and 126 (17.8%) had unacceptable protocol violations. 107 (84.9%) single violations, 15 (11.9%) combinations of two, three (2.4%) combinations of three, and one (0.8%) combination of four unacceptable violations were observed. 564 (79.4%) patients achieved a total QC score of < or = 2, 124 (17.5%) of 3 to 5, and 20 (2.8%) of > or = 6. The criterion "radiotherapy treatment duration" had the highest rate of protocol violations, 67/708 (9.5%); other quality control criteria with protocol violations were "radiotherapy reference dose" (27 = 3.8%), "radiotherapy treatment initiation" (15 = 2.1%) and "other protocol violations" (33 = 4.7%). No protocol violations were observed for the criterion "target volume coverage". The protocol compliance improved slightly during the conduct of the study. Institutional differences in protocol compliance were observed depending upon the accrual rate, the institutional treatment preference and between academic and non-academic hospitals. After a short median follow-up of 48 months, differences in protocol compliance, i.e. protocol violations, have not resulted in a reduced disease-free survival; however, the final prognostic evaluation of the quality control review may require longer follow-up and eventually different treatment endpoints to be analyzed.

Breast Neoplasms↗

Correlation between the occurrence of Ki-67 antigen and clinical parameters in human breast carcinoma.

Cryostat sections of ductal breast carcinomas obtained during surgery from 48 patients were subjected to an indirect immunostaining with an antibody against Ki-67 antigen (Dako). The primary reaction was visualized by the APAAP technique with new fuchsin as chromogen. The percentage of positively stained nuclei was correlated with tumor size, number of metastatic lymph nodes, presence or absence of metastases in distant organs as well as with patient's age. The best correlations were achieved when the data were considered separately within the groups with low, medium and high Ki-67 values. A possible significance of Ki-67 evaluation for the prognosis and therapy is discussed.

Adult↗

[Diagnostic and therapeutic problems in Lamblia infections].

A 28-year-old woman complained of chronic diarrhoea of about one year's duration, made worse by taking food. As a lactose tolerance test showed evidence of severe intolerance she was given a lactose-free diet, but this brought no improvement. Duodenal biopsy showed villous atrophy, and in the duodenal juice there were numerous flagellated lamblia. After a single oral dose of 2 g tinidazole the diarrhoea stopped, the lamblia disappeared, and the lactose intolerance and villous atrophy cleared up. Lamblia were also detected in the duodenal juice of a 50-year-old woman, but her infection was much more difficult to treat. Tinidazole (single dose of 2 g), metronidazole (800 mg twice daily for 6 days), ornidazole orally 500 mg twice daily for 10 days and ornidazole intravenously 500 mg twice daily for four days all proved ineffective. However, after a 5-day course of epsilon-9-aminacridine (100 mg three times daily by mouth) the diarrhoea ceased and both vegetative forms and lamblia cysts disappeared. These cases emphasize that lambliasis should be considered as a possible cause of severe chronic diarrhoea even when there is no history of travel abroad and when the symptoms are atypical. Conventional chemotherapeutic agents may be ineffective.

Adult↗

Alterations of the c-erbB2 gene in human breast cancer.

DNA amplification, RNA overexpression and p185 protein expression of the c-erbB2 oncogene were investigated in 109 cases of breast cancer with the aim of evaluating any correlation between the different methods. A correlation between Southern blotting and immunohistochemical analysis of paraffin-embedded material was found. Thus, amplification of the c-erbB2 oncogene leads to overexpression of the p185 protein. By contrast, no statistical correlation could be shown between RNA overexpression, measured by Northern blotting, and immunohistochemical p185 membrane stainings. It is of special interest that most of the cases that are positive for Northern blotting and negative for immunochemistry are negative for Southern blotting as well. Contradictory findings between RNA overexpression and lack of immunohistochemical staining of p185 give rise to the assumption that a defective protein is encoded, which cannot be incorporated into the substructures of the tumour cell membrane. When screening for point mutations in the transmembrane domain of the c-erbB2 oncogene, no point mutation could be detected, either by using the endonuclease FokI, which cuts at position 2012 (the point mutation in the neu gene of the rat), or by direct sequencing.

Base Sequence↗

Therapy of small breast cancer: a prospective study on 1036 patients with special emphasis on prognostic factors.

In 1983, The German Breast Cancer Study Group, sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer pT1 pN0 M0. Treatment consisted of initial tumorectomy with microscopically free margins and lower axillary dissection. After conformation of a pT1 pN0-stage, additional treatment was either mastectomy or adjuvant radiotherapy (50 Gy in 25 fractions to the entire breast plus 12 Gy electron boost). In medially located tumors, the parasternal and supraclavicular area was also irradiated with 50 Gy. A randomization between both treatment modalities was initially planned but was not feasible and abandoned. Nearly all patients were treated according to their own choice. From November 1983 through December 1989, 1119 patients were recruited. Eighty-three were excluded from the protocol. Out of the remaining 1036 patients, 733 (71%) underwent breast preservation and 303 (29%) mastectomy. A detailed pathohistological examination of all tumorectomy specimens was performed in a pathologic reference center. Oncogen overexpression was evaluated by immunohistological detection of the transmembrane protein p-185 (corresponding to c-erb-B2) in 425 cases. After a median follow-up of 48 months, the frequency of local recurrences (4.7%), regional recurrences (1%), and distant metastases (5.4%) was the same in the breast preservation group and the mastectomy group. The 3-year disease-free survival was 90% after breast preservation and 88% after mastectomy (p = 0.21). In the breast preserving group, 24 patients with microscopically involved margins had a poorer disease-free survival than the study group (75% vs 90% after 3 years). The width of the margins had no impact on prognosis. Other prognostic factors in an univariate and multivariate analysis were tumor size and tumor grade. Age, menopausal status, hormone receptor status, histological tumor type, and treatment (mastectomy vs breast preservation) were not significant. P-185-expression was dependent on tumor grade and was the strongest prognostic factor in an univariate and multivariate analysis (p less than 0.001). The results emphasize the central role of tumor grade for prognosis and suggest the independent prognostic significance of the c-erb-B2 oncogen (corresponding to p-185) in pN0-patients.

Adenocarcinoma↗

Heterogeneity of tumour necrosis factor production in renal cell carcinoma.

Endogenous tumour necrosis factor (TNF) production was investigated by in situ hybridisation and immunohistochemistry in 8 renal cell carcinoma (RCC) patients at different stages of disease. Analysis of frozen sections of tumour biopsy specimens revealed variable degrees of macrophage infiltration and great heterogeneity in TNF gene expression. Two metastatic tumours investigated showed abundant TNF protein production and marked macrophage infiltration. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Two years after nephrectomy the individual survival time was recorded; however, the small numbers did not yet allow any correlation of TNF production to the clinical course of disease. Further studies will be required to eventually reveal the role of TNF in renal cell carcinoma development.

Aged↗

[Overexpression of c-erbB-2 oncogene in primary ovarian cancers: incidence and prognostic significance in 243 patients].

In ovarian cancers, no valuable prognostic factors are available so far for predicting biological behaviour and clinical outcome. During the last years, overexpression of c-erbB-2-oncogene has been reported to be a prognostic factor in various human carcinomas. Its prognostic value in ovarian cancer is still a matter of controversy. The records and histological specimens of 243 patients with primary ovarian cancer were reviewed. Overexpression of c-erbB-2-oncogene encoded transmembrane protein p185 was determined immunohistochemically using polyclonal and monoclonal antibodies. Of 243 investigated tumours, 45 (19%) were positive. We examined the relationship between p185 and clinical stage, histological type, grading and prognosis. p185 overexpression differs within the histological subtypes of tumours. No correlation was found between p185 overexpression and stage or histological grade. The follow-up data demonstrate that patients with positive staining for p185 have a significantly worse prognosis (p = 0.001) than those with negative staining. These results suggest that overexpression of c-erbB-2 oncogene is associated with higher biological aggressiveness and unfavourable course of disease.

Adenocarcinoma↗

Budd-Chiari syndrome as the primary manifestation of a fibrolamellar hepatocellular carcinoma.

An 18-year-old female patient was admitted with ascites, right upper abdominal tenderness and peripheral edema. Angiography showed complete occlusion of the vena cava inferior up to the level of the right atrium. By open heart surgery, masses of thrombotic material were pulled out of the v. cava inferior/vv. iliacae which histologically contained tumor cell populations consistent with a hepatocellular carcinoma. Celiacography showed a highly vascularized tumor in the right hepatic lobe. Histologically, it proved to be fibrolamellar subtype hepatocellular carcinoma.

Adolescent↗

[Breast carcinoma in pregnancy. Clinical, histological and immunohistochemical findings].

The hormonally induced changes in the breast during pregnancy make the diagnosis of breast cancer difficult. Furthermore, examinations during pregnancy tend to concentrate only on the pregnancy itself. In this report the clinical, pathological and immunohistochemical results from 7 patients with breast cancer during pregnancy are presented. All women first noticed the tumor by self-examination. The time periods between discovery of the tumor and medical treatment were between 4 and 22 weeks. An overexpression of c-erbB-2-oncogene coded transmembrane protein p185 could be demonstrated in 4 cases. Of the seven patients, 5 have already passed away. Three of the deceased had p185-positive tumors, and died 4, 8 and 21 months after diagnosis. The two p185-negative patients lived 34 and 65 months post diagnosis. Despite the small amount of cases presented, a trend can be seen that p185 may be an additional prognostic factor for breast cancer in pregnancy.

Adult↗

Breast preservation versus mastectomy in early breast cancer--1991 update of the GBSG 1--protocol and prognostic factors. The German Breast Cancer Study Group.

In 1983, the German Breast Cancer Study Group (GBSG), sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer (pT1 pN0 M0). This was preceded by a three-year reviewing period because of some novelties of medical, juristical and ethical problems in the FRG. University and, in the majority, community hospitals participated, combining all together 69 different institutions. From 11/1983 to 12/1989, 1112 patients were recruited. From 1036 patients, 733 underwent breast preservation (71%) and 303 mastectomy (29%). The randomization rate was only 6%. In 268 patients (26%) the tumor size was less than or equal to 10 mm, in 765 patients (74%) 11 to 22 mm. In 129 cases, we subdivided the tumor grading II[3] into IIa and IIb. Moreover, the immunohistochemical detection of the transmembrane proteins EGFR, p-185 and p-148 by oncogene overexpression and c-myc oncogene were undertaken in 425 breast cancers. After tumorectomy (or wide excision) and a lower axillary dissection (at least eight lymph nodes) the breast was irradiated up to 50 Gy in 25 fractions. A boost of 12 Gy was given to the tumor bed. The medial located lymph nodes were also irradiated in case of medially or centrally tumors. Quality control was performed by pathological, radiotherapeutic and methodical reference centers. Significant correlations could be demonstrated between receptor status and tumor grading, patient age and grading, and tumor size and grading. The results emphasize the central role of tumor grading among the prognostic factors. Especially the differentiation of the Bloom and Richardson score II into IIa and IIb seems to play an important role. After a median follow-up of 41 months, the frequency of local recurrences (4.4%), regional recurrences (1%) and distant metastases (4.6%) was exactly the same in both treatment groups. In multivariate analysis, only tumor size and tumor grading had a significant impact on disease-free survival. 23 patients with tumor-involved margins had a higher recurrence rate (DFS 62% versus 85% after five years). Without any impact on DFS were the other conventionally evaluated prognostic factors: age, menopausal status, hormone receptor status, histological tumor type, tumor localisation, degree of differentiation, pleomorphism, mitotic index and degree of dissociation. Among the transmembrane proteins EGFR, p-185, p-148 and c-myc, only the impact of p-185 and EGRF positivity on DSF is significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast↗

[Initial results of the Project of the German Breast Cancer Study Group on "Breast saving therapy of the small breast cancer"].

In the German Breast Cancer Study Group (GBSG) multicenter trial "Breast preservation in small breast cancer" 1119 patients were accrued over a period of six years. The study was originally designed as a randomized trial which had to be changed into a prospective observation study. A high therapeutic standard was guaranteed by quality control. The univariate analysis of prognostic variables was the first step to a valid treatment comparison. Those factors determined as being significant were combined with the treatment effects in a multivariate analysis. The published results were obtained after a median observation time of four years.

Breast Neoplasms↗

Genomic alterations of the c-myc protooncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomas.

Genomic alterations of c-myc (amplification, rearrangements and hypomethylation) were investigated in 30 breast carcinomas and 20 cervix carcinomas. In breast carcinomas c-myc alterations were compared with overexpression of the c-erbB2 protooncogene and the proliferation marker Ki-67. Alterations of c-myc were found in 50% of the breast carcinomas and in 25% of the cervix carcinomas. In 23% of the breast carcinomas c-erbB2 overexpression was associated with c-myc alterations. In 17% of the cases there was overexpression of c-erbB2 without detectable alterations of c-myc. Hence, in 67% of breast cancers alterations of c-myc and/or c-erbB2 have been found, while in 81% of the samples Ki-67 expression was increased. The results suggest that the study of c-myc alterations provides an important complement to that of other prognostic indicators of breast cancer such as c-erbB2 expression.

Adult↗

Localization of endogenous beta-galactoside-specific lectins by neoglycoproteins, lectin-binding tissue glycoproteins and antibodies and of accessible lectin-specific ligands by mammalian lectin in human breast carcinomas.

Protein-carbohydrate interactions constitute a system of molecular interaction with relevance to pathologic conditions. Carrier-immobilized carbohydrate structures enable the histochemical investigation of the protein part of this recognitive system. However, thorough systematic studies are inevitably required for standardized application of this relatively novel class of markers. Consequently, serial sections of 21 cases of malignant breast lesion were comparatively analyzed with three different types of probe, specific for beta-galactoside-binding lectins. In addition to the chemically lactosylated neoglycoprotein, human lectin-binding glycoproteins, purified by affinity chromatography on resins with an immobilized beta-galactoside-specific lectin, and a lectin-specific antibody were employed to answer the question whether differences occur in their capacity for lectin localization. The patterns of staining were qualitatively similar, the lectin-binding glycoproteins yielding the most intense reaction. Having assured the reliable applicability of the neoglycoprotein, structural alterations of the subterminal carbohydrate residue on the labelled carrier addressed the issue, whether selectivity of binding can be inferred histochemically, allowing rational synthetic tailoring. An N-acetylglucosamine residue in beta-1,3-linkage proved to be a less favorable extension than this type of sugar in beta-1,4-linkage or an N-acetylgalactosamine moiety in beta-1,3-linkage. Binding was clearly reduced in cells of normal breast tissue with this probe. In order to gain evidence on the expression of potential carbohydrate ligands for the glyco- and immunohistochemically localized binding activity, a labelled mammalian beta-galactoside-specific lectin was similarly used as histochemical tool. It effectively bound to accessible sites in the sections. The binding pattern was different to that of plant lectins with specificity to beta-galactosides. This result underscores that caution is necessary in the functional interpretation of results of studies with plant, not mammalian lectins.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗