Search Results - (Author, Cooperation:H. Moch)

2018-07-06

The American Society for Pharmacology and Experimental Therapeutics (ASPET)

0090-9556

1521-009X

Chemistry and Pharmacology

Medicine

2014-10-04

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Base Sequence ; Binding Sites/genetics ; Carcinogenesis/genetics/metabolism/pathology ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Chromosomal Proteins, Non-Histone/metabolism ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Neoplasm Invasiveness ; Nuclear Proteins/*genetics/metabolism ; Oncogene Proteins/metabolism ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Proteasome Endopeptidase Complex/metabolism ; Repressor Proteins/*genetics/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination/*genetics

2015-04-17

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Breast Neoplasms/*classification/*genetics ; Female ; Humans ; Mutation/*genetics ; Translocation, Genetic/*genetics

0165-4608

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Medicine

Electronic Resource

1432-2307

Bladder neoplasm ; p53 ; erbB-2 ; Metastasis

Springer Online Journal Archives 1860-2000

Medicine

Abstract Overexpression of p53 anderbB-2 was studied by immunohistochemistry in formalin-fixed tissue samples of 179 patients with transitional cell carcinoma of the urinary bladder. p53 immunostaining was strongly correlated with tumour stage (P〈0.0001). This was driven by a marked difference in p53 expression between pTa (37% positive) and pT1 (71%) tumours, while there was no difference between pT1 and pT2-4 tumours. Similarly, a strong overall association between p53 expression and grade (P〈0.0001) was driven by a marked difference between grade 1 (28%) and grade 2 tumours (71%), and there was no significant difference between grade 2 and grade 3 tumours. Surprisingly, the frequency oferbB-2 overexpression was higher in pT1 tumours (74%) than in either pTa (49%;P=0.0265) or pT2-T4 (56%;P=0.0645) tumours. Both p53 anderbB-2 expression was also associated with metastasis. Metastases were found in 77% of patients with p53 positive primary tumours, but in only 50% of the patients with p53 negative primary tumours (P=0.022). Metastases were found in 66% of patients witherbB-2 positive primaries, but in only 37% of theerbB-2 negative primaries (P=0.020). Of 32 patients with positivity for both p53 anderbB-2, 84% developed metastases, as compared to 49% of patients with positivity for either one or neither positive (P=0.002). We conclude that both p53 anderbB-2 over-expression are associated with early invasion in bladder cancer. Furthermore, p53 anderbB-2 may be important predictors for metastasis.

Electronic Resource

1432-2307

Malignant mesothelioma ; Lung adenocarcinoma ; Immunohistochemistry ; Expert system ; Discriminant analysis

Springer Online Journal Archives 1860-2000

Medicine

Abstract A panel of 14 antibodies (panepithelial antibody Lu-5, anti-keratin-18, anti-keratin-7, Ber-EP4, anti-Leu-M1, HEA-125, anti-carcinoembryonic antigen, anti-blood group-related antigens A, B, H, B72.3, antiplacental alkaline phosphatase, anti-vimentin and BMA-120), which have been evaluated for use in differentiating mesothelioma from lung adenocarcinoma, was applied to a group of 24 suspected mesotheliomas. Using the established qualitative, descriptive criteria derived from monovariate statistical analysis of the tumour control groups (definite mesotheliomas, adenocarcinomas), a definitive allocation was possible in only 25% of suspected cases. We therefore constructed two “expert systems”, based on multivariate discriminant analysis with either the ALLOC 80 program for ordinal data or a newly developed analysis program for binomial data. With these two systems diagnostic allocation of suspected mesotheliomas was improved to 75% and 79%. The use of binomial data (“positive” versus “negative”) in conjunction with the probability-based test system is of particular interest because the primary data are easy to record and the test results have a higher statistical probability.

Electronic Resource

1432-2307

Malignant mesothelioma ; Lung adenocarcinoma ; Ber-EP4 ; BMA-120 ; Blood-group-isoantigen

Springer Online Journal Archives 1860-2000

Medicine

Abstract Specimens of 27 histologically definite mesotheliomas and 34 proven adenocarcinomas were examined with a panel of 14 antibodies: pan-epithelial antibody Lu-5, anti-keratin-18, anti-keratin-7, Ber-EP4, anti-Leu-M1, HEA-125, anti-carcino-embryonic antigen (CEA), anti-blood group-related antigens (anti-BGR A, B, H), B 72.3, anti-placental alkaline phosphatase (PLAP), anti-vimentin and BMA-120 used to determine their value in the differentiation between pleural mesothelioma and lung adenocarcinoma. Lu-5, anti-cytokeratin-7 and -18, B 72.3 and PLAP reacted in a high percentage of cases with both mesothelioma and adenocarcinoma. Anti-CEA and anti-Leu-Ml did not react with any of the 27 mesotheliomas tested but showed a reaction in 75% (anti-CEA) and 66% (anti-Leu-M1) of the lung adenocarcinomas. Seventeen percent of the adenocarcinomas and 96% of the mesotheliomas showed a positive reaction with anti-vimentin. Ber-EP4 was demonstrated in all lung adenocarcinomas, but only in 2 mesotheliomas in a focal manner (7%). HEA-125 and anti-BGR A, B, H reacted with 83% (HEA-125) and 75% (anti-BGR A, B, H) of the lung adenocarcinomas. The statistical parameters, sensitivity and efficiency were estimated and a normogram for judging the diagnostic power of a single antibody for the differential diagnosis of mesothelioma versus adenocarcinoma was developed. According to this, Ber-EP4, HEA-125, anti-BGR A, B, H and anti-CEA were, in descending order, the most powerful discriminatory antibodies.

Electronic Resource

1434-0879

Renal cell carcinoma ; Prognosis ; p53 ; mdm-2 ; Survival ; Proliferation

Springer Online Journal Archives 1860-2000

Medicine

Abstract The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (1172). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry. p53 positivity was detected in 16% of tumors. mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P=0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P=0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P=0.04) and p53 overexpression were associated with poor prognosis (P=0.0021), whereas mdm-2 overexpression was not related to patient outcome (P=0.73). A Cox regression analysis revealed tumor stage (P〈0.001) and p53 overexpression (P〈0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.

Electronic Resource

1434-0879

Bladder neoplasms ; Flow cytometry ; Fluorescence in situ hybridization ; Chromosome Y ; Chromosome X ; Chromosome 1 ; Chromosome 7 ; Chromosome 9 ; Chromosome 17 ; Aneuploidy

Springer Online Journal Archives 1860-2000

Medicine

Abstract Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%;P〈0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as “superficial bladder cancer.” The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for ≥4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.

Electronic Resource

1432-1963

Schlüsselwörter: Karyomegalie – Niere – Chronische interstitielle Nephritis ; Key words: Karyomegaly – Kidney – Interstitial nephritis

Springer Online Journal Archives 1860-2000

Medicine

Abstract. Systemic karyomegaly associated with interstitial nephritis was first described in 1978 by Mihatsch. Seven cases have been reported to date. We give an account of an autopsy case of systemic karyomegaly in a 30-year-old Italian man. Bizarre enlargement of nuclei was found in renal tubular epithelial cells, Schwann cells and in smooth muscle cells of vessels and bowel and, less obviously, in endothelial and adventitial cells of vessels, in alveolar epithelial cells and in astrocytes of the brain. These findings were associated with chronic interstitial nephritis, nonspecific hepatopathy, adenocarcinoma of the rectum and multiple slerosis. The clinical course was marked by chronic renal failure, chronic haemodialysis and renal transplantation. The patient died 8 years after diagnosis in septic-toxic shock. The aetiology and pathogenesis of the disease are discussed.

Zusammenfassung. Die Karyomegalie der Niere ist ein seltenes Krankheitsbild, von dem bislang nur 7 Fälle beschrieben wurden. Anhand der Autopsie eines 30 Jahre alten Italieners berichten wir über Morphologie und mögliche Ursachen dieser Krankheit. Typische bizarre Vergrößerungen von Zellkernen kommen in Tubulusepithelien der Niere, in Schwannzellen, in glatten Muskelzellen von Gefäßen und Darm und in geringerem Ausmaß in Endothelzellen und Adventitiazellen der Blutgefäße, in Alveolarepithelzellen und in Astrozyten des Gehirns vor. Diese Befunde waren assoziiert mit einer chronischen interstitiellen Nephritis, einer unspezifischen Hepatopathie, einem Adenokarzinom des Rektums und einer multiplen Sklerose. Der klinische Verlauf war charakterisiert durch ein chronisches Nierenversagen, gefolgt von Hämodialyse und konsekutiver Nierentransplantation. Der Patient starb 8 Jahre nach der Diagnose des Krankheitsbildes in einem septisch-toxischen Schock.

Electronic Resource

1432-1963

Schlüsselwörter Epitheloidzellen ; Riesenzellen ; HMB-45 ; Immunhistologie ; Flow-Zytometrie ; Key words Epithelioid cells ; Giant cells ; Immunohistochemistry ; Flow-cytometry

Springer Online Journal Archives 1860-2000

Medicine

Summary Epitheloid angiomyolipoma is a recently recognized tumor entity, of which 9 tumors are documented in the literature. We report a case that occurred in a 19 years old patient. The tumor consisted of epithelioid cells ranging from medium sized and polygonal to giant cells with prominent nucleoli. Remarkably, there were many multinucleated giant cells. Hemorrhage, necrosis, and clusters of foamy macrophages were also present. Obvious elements of typical angiomyolipoma, especially fatty tissue was not found. Flow cytometry revealed diploid tumor cells with a high S-phase fraction of 9.7%. Melanoma-associated antigen HMB-45 and CD 68 was detected in the epithelioid and spindle cells. The multinucleated giant cells stained for desmin and KP1, and to a lesser extent for HMB-45 and vimentin. There was no expression of cytokeratin or epithelial membrane antigen. Epithelioid angiomyolipoma often pose problems in diagnosis, particularly with regard to distinction from renal cell carcinoma. Previous reports in the literature suggest that epithelioid angiomyolipoma may have malignant potential.

Zusammenfassung Das epitheloide Angiomyolipom ist eine neu beschriebene Tumorentität. Bisher wurden 9 Fälle publiziert. Wir berichten über einen weiteren Tumor bei einem 19jährigen Patienten. Der Tumor hatte große, teils epitheloide, teils spindelförmige Zellen mit eosinophilem Zytoplasma, pleomorphen Zellkernen mit prominenten Nukeolen und zahlreiche Schaumzellen. Einige Zellen wiesen eine ganglienzellartige Morphologie auf. Auffallend waren zahlreiche mehrkernige Riesenzellen. Blutungen, Nekrosen und Mitosen wurden ebenfalls angetroffen, jedoch konnte kein Fettgewebe nachgewiesen werden. Die Tumorzellen waren bei der flow-zytometrischen Messung diploid, hatten aber eine hohe S-Phase-Fraktion von 9,7%. Immunhistologisch exprimierten die epitheloiden Tumorzellen das Melanom-assoziierte Antigen HMB-45 und den Makrophagenmarker KP-1. Von den mehrkernigen Riesenzellen wurde Desmin und KP-1 exprimiert, in geringerem Ausmaß auch Vimentin und HMB-45. Es ließ sich keine Zytokeratinexpression und keine Expression von epithelialem Membranantigen (EMA) nachweisen. Anhand dieses Tumors wird dargestellt, daß das epitheloide Angiomyolipom von den verschiedenen Nierenzellkarzinomvarianten abgegrenzt werden kann. Die immunhistologische Untersuchung ist der Schlüssel zur richtigen Diagnose. Aufgrund der bisher publizierten Fallberichte verhalten sich einige epitheloide Angiomyolipome maligne.

Electronic Resource

1432-1963

Key words Onkozytomatose der Nieren ; Multiple renale Onkozytome ; Multiple Tumoren ; Key words Renal oncocytomatosis ; Multiple renal oncocytomas ; Multiple tumors

Springer Online Journal Archives 1860-2000

Medicine

Summary Multiple and bilateral oncocytomas are rare. There are only ten cases that have been previously described. Three of these displayed multiple and bilateral oncocytomas and microoncocytomas, a so-called oncocytomatosis. This report describes a case of renal oncocytomatosis found at autopsy. In addition, we found an adrenal adenoma, a pheochromocytoma and thoracic cicatrices 4 years after curatively resected large cell carcinoma of the lung. In the distal renal tubules we found oncocytic epithelial cells, with partial transition into microoncocytomas. Immunhistochemically, these and the main oncocytomas were CD 10 negative. These findings support the origin of oncocytoma from oncocytically transformed distal tubular epithelium. CGH analysis of the different tumors revealed no common cytogenetic changes. Coexistence of renal oncocytoma with other tumors is rare. Hitherto, coexistence of a renal oncocytomatosis with multiple tumors has not been described.

Zusammenfassung Multiple, bilaterale Onkozytome sind selten. In der Literatur sind bisher 10 Fälle beschrieben. Bei drei dieser Patienten bestanden beidseitig zahlreiche, das Nierenrestparenchym verdrängende Onkozytome mit Mikroherden, eine sog. Onkozytomatose. Wir berichten über einen Autopsiefall mit Onkozytomatose der Nieren. Zusätzlich waren ein Nebennierenrindenadenom, ein Phäochromozytom und ein Status nach Lungenresektion wegen großzelligem Karzinom vorhanden. Die distalen Nierentubuli zeigten herdförmig onkozytär transformierte Epithelzellen, z.T. mit Übergang in Mikroonkozytome. Diese und die eigentlichen Onkozytome waren immunhistochemisch CD 10-negativ. Dies spricht für eine Entstehung der Onkozytome aus onkozytär transformierten distalen Nierentubuli. Die CGH-Untersuchung ergab als Screening-Methode keine Hinweise für eine den verschiedenen Tumoren gemeinsame zytogenetische Veränderungen. Eine Koexistenz renaler Onkozytome mit anderen Tumoren ist selten. Ein Zusammentreffen einer Onkozytomatose der Nieren mit multiplen Tumoren wurde bisher nie beschrieben.

Electronic Resource

1432-1963

Schlüsselwörter Prostatakarzinom ; Zytogenetik ; Gen-Amplifikation ; Polysomie ; Key words Prostate cancer ; Cytogenetics ; Gene amplification ; Polysomy

Springer Online Journal Archives 1860-2000

Medicine

Summary Development and progression of tumors is driven by a malfunction of specific genes. Although prostate cancer is one of the most frequent tumors, little is known about the genes involved. Cytogenetic and molecular examinations have shown that chromosomal deletions most frequently involve 7q, 8p, 10q, 13q, 16q, 17p and the Y chromosome. These loci may carry tumor suppressor genes with relevance for prostate cancer. DNA sequence copy number gains were most frequently observed at chromosomes 7, 8q, and 11q. These regions may carry currently un-known oncogenes. There is increasing evidence for a clinical relevance of genetic alterations. Polysomies of several chromosomes were shown to be associated with poor prog-nosis of prostate cancer patients. Androgen receptor amplification can be found in hormone-refractory carcinomas which may re-spond to total androgen blockage. For the future it is hoped that the identification of the genes involved in prostate cancer and the determination of their function could allow for significant improvements of treatment strategies for prostate cancer patients.

Zusammenfassung Entstehung und Progression von Tumoren werden durch Funktionsstörungen von spezifischen Genen gesteuert. Obwohl das Prostatakarzinom zu den häufigsten Tumoren gehört, ist über die bei diesem Tumor involvierten Gene wenig bekannt. Zytogenetische und molekulare Untersuchungen haben gezeigt, daß chromosomale Deletionen besonders häufig das Y-Chromosom, 7q, 8p, 10q, 13q, 16q und 17p betreffen. Diese Loci dürften für das Prostatakarzinom relevante Tumorsuppressorgene enthalten. Häufige DNS-Sequenzvermehrungen von Chromosom 7, 8q und 11q deuten auf die Lokalisation von möglichen Onkogenen hin. Bereits heute bestehen Anhaltspunkte für eine Prognoserelevanz genetischer Veränderungen. Der Nachweis von Polysomien in Primärtumoren deuten auf eine ungünstige Prognose hin. Eine Amplifikation des Androgenrezeptors spricht für einen Hormontherapie-resistenten Tumor, welcher möglicherweise besonders gut auf eine totale Androgenblockade ansprechen wird. Die Identifikation der alterierten Gene und die Entschlüsselung ihrer Funktion könnte in Zukunft zu deutlich verbesserten Behandlungsstretegien für Patienten mit Prostatakarzinom führten.

Electronic Resource

1432-1963

Schlüsselwörter Samenblase ; Lokalisierte Amyloidose ; Systemische senile Amyloidose ; Lactoferrin ; Autopsie ; Key words Localized amyloidosis ; Seminal vesicle ; Systemic senile amyloidosis ; Autopsy

Springer Online Journal Archives 1860-2000

Medicine

Summary Localized depositions of amyloid in the seminal vesicles may occur in elderly men. Ear-lier immunohistochemical studies have failed to identify immunoreactivity of known amyloid material. In this autopsy study, all seminal vesicles of males older than 50 years were histologically examined to determine incidence and phenotype of seminal vesicle amyloidosis. Seven out of 50 patients (14%) showed depositions of amyloid in the seminal vesicles. These amyloid depositions as well as one additional case were characterized histochemically, immunohistochemically and electronmicroscopically. All but two of these patients (75%) showed simultaneously amyloid depositions in the heart. Lactoferrin immunoreactivity was found in 6 patients (75%). Lactoferrin is an ironbinding, bacteriostatic glycoprotein, which is produced in the seminal vesicles. Four patients with lactoferrin positive amyloid in seminal vesicle showed different amyloid depositions in the heart (immunoglobulin light chain amyloid AL-lambda). Two cases (25%) showed the same amyloid type in heart and seminal vesicles (prealbumin-transthyretin type amyloid). Our study shows that most amyloidoses of the seminal vesicles are organ-limited depositions of lactoferrin. These forms of localized amyloidosis have to be separated from senile systemic amyloidosis with seminal vesicle involvement.

Zusammenfassung Organlimitierte Amyloidablagerungen in den Samenblasen können im höheren Lebensalter auftreten. Die Samenblasenamyloidose konnte bislang keinem bekannten Amyloidtyp zugeordnet werden. In der vorliegenden Studie wurden bei 50 konsekutiven Autopsiefällen von Männern über 50 Jahren die Samenblasen histologisch untersucht, um die Inzidenz und den Phänotyp der Samenblasenamyloidose besser zu charakterisieren. Bei 7 Patienten (14%) wurde eine Samenblasenamyloidose gefunden. Das Amyloid wurde bei diesen Patienten sowie von einem zusätzlichen Fall histochemisch, immunhistologisch und elektronenmikroskopisch charakterisiert. Die Samenblasenamyloidosen waren bei 6 Patienten (75%) mit geringen Amyloidablagerungen im Herzen kombiniert. Die Samenblasenamyloidosen von 6 Patienten (75%) zeigten eine positive Reaktion mit einem Antikörper gegen Lactoferrin, einem in den Samenblasen produzierten Glykoprotein. Bei 4 dieser Patienten bestanden gleichzeitig Amyloidablagerungen im Herzen. Bei diesen Ablagerungen handelte es sich jedoch um einen anderen Amyloidtyp (Immunglobulin Leichtkettenamyloid AL-lambda-Typ). In 2 Fällen (25%) wurde in Herz und Samenblasen der gleiche Amyloidtyp (Präalbumin-Transthyretin-Typ) identifiziert, so daß bei diesen Patienten die Samenblasenamyloidose im Rahmen einer generalisierten Amyloidose aufgetreten ist. Unsere Untersuchungen zeigen, daß die meisten Amyloidablagerungen der Samenblasen organlimitierte Formen sind, die durch Ablagerung von Lactoferrin verursacht werden. Diese Samenblasenamyloidosen sind von einem Begleitbefall im Rahmen einer systemischen senilen Amyloidose abzugrenzen.

Electronic Resource