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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 15 (1994), S. 321-330 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Lunge ; Tumorsuppressorgene ; Onkogene ; Krebsentstehung ; Key words Lung ; Tumor suppressor gene ; Oncogene ; Cancerogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The recent results obtained from investigations based on molecular biological techniques have led to a better understanding of recurrent genetic causes important for the pathogenesis of tumors. Several genes have been identified as being involved in the development of cancer. In many cases, the activation of oncogenes or the inactivation of tumor-suppressor genes is the predominant reason for cancerogenic cell transformation. Functional dysregulation is frequently the consequence of mutations, resulting in an alteration of the primary structure of the DNA. As our understanding of the nature, function, and interaction of these genes evolves, new opportunities for early diagnosis, classification, prevention, and treatment of malignant tumors will arise. The present report summarizes the current molecular biological aspects of several oncogenes (erbB, ras, myc, raf, fos, jun, bcl, mdm 2, myb, kit CSF1R, met) and tumor suppressor genes (p 53, rb, mts) involved in lung-cancer development with respect to the pathology of lung tumors, including the importance of these genes as far as the clinical course of the disease is concerned.
    Notes: Zusammenfassung Die Fortschritte der letzten Jahre, insbesondere auf dem Gebiet der molekularen Genetik, haben wesentlich zum besseren Verständnis der Genese und Progression von Tumoren beigetragen. Nach dem heutigen Erkenntnisstand besitzen morphologisch als tumorös charakterisierte Zellen unterschiedliche genetische Alterationen. Im Verlauf der Tumorprogression kann es zusätzlich zur Akkumulation weiterer genetischer Alterationen kommen. Nach den heute vorherrschenden Arbeitshypothesen sind für eine bösartige Entartung von Zellen 3–10, in der Regel unabhängige genetische Alterationen Voraussetzung. Die Veränderungen in der Erbsubstanz betreffen überwiegend solche Gene, die direkt oder indirekt das Wachstum, die Proliferation oder die Differenzierung der Zelle regulieren. Die für die Entstehung von Tumoren verantwortlichen Gene werden dabei in die Klassen der Onkogene und der Tumor Suppressor Gene oder Anti-Onkogene eingeteilt. Bei Onkogenen führt definitionsgemäß erst eine (Über-) Aktivierung des betreffenden (Proto-) Onkogens zu einer Entartung der Zelle – bei Tumor-Suppressor-Genen ist eine (Teil-) Inaktivierung des Gens Voraussetzung für eine Transformation der Zelle. Neben chromosomalen Abnormalitäten, die in der Regel größere Genomabschnitte betreffen und zum Teil bereits auf lichtmikroskopischer Ebene diagnostiziert werden, spielen bei der Genese und Progression von Lungentumoren gerade genetische Alterationen in Onko- oder Tumor-Suppressor-Genen eine zentrale Rolle. Die vorliegende Übersicht faßt Erkenntnisse über die Gene zusammen, die heute als Faktoren bei der Kanzerogenese von Lungentumoren Bedeutung erlangt haben.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 16 (1995), S. 217-222 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Kleinzelliges Bronchialkarzinom ; Neoadjuvante Chemotherapie ; Therapieinduzierte Tumorregression ; Spontanregression ; Regressionsgrading ; Key words Small cell lung cancer ; Neoadjuvant chemotherapy ; Therapy induced tumor regression ; Spontaneous tumor regression ; Regression grading
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Resection specimens of 14 patients with small cell bronchial carcinoma after neoadjuvant chemotherapy were processed histologically and graded according to a three-step regression grading system: grade I, no or only slight tumor regression; grade II, incomplete tumor regression; grade III, complete tumor regression without vital tumor tissue. In five patients with either no vital tumor tissue or only small tumor remnants in the resection samples, a typical sequence of central fresh tumor necrosis, foam cell rim, vascular granulation tissue and peripheral scar formation was seen. This morphological finding may be interpreted as a characteristic, but unspecific parameter of good response to preoperative chemotherapy. The presence of vital tumor rims surrounding the capillary bed with intermingled necrotic foci, however, argues in favor of spontaneous tumor regression, which is commonly observed in small cell lung cancer.
    Notes: Zusammenfassung Resektionspräparate von 14 Patienten mit kleinzelligen Bronchialkarzinomen nach neoadjuvanter Chemotherapie wurden histologisch aufgearbeitet und nach einem 3 stufigen Regressionsgrading klassifiziert. Regressionsgrad I: keine oder nur geringe Tumorregression, Regressionsgrad II: unvollständige Tumorregression und Regressionsgrad III: vollständige Tumorregression ohne Nachweis vitalen Tumorgewebes. Bei 5 Patienten, deren Resektate kein vitales Tumorgewebe oder nur kleine Tumorreste aufwiesen, konnte eine typische Abfolge von zentraler frischer Tumornekrose, Schaumzellsaum, gefäßreichem Granulationsgewebe und peripherer Vernarbung nachgewiesen werden. Dieser Befund kann als charakteristischer, aber letztlich unspezifischer Ausdruck eines guten Ansprechens auf die präoperative Chemotherapie angesehen werden. Dagegen spricht der Nachweis von kapillarbezogenen vitalen Tumorsäumen mit dazwischen liegenden, schmalen Nekrosen für die beim kleinzelligen Bronchialkarzinom häufig auftretende spontane Tumorregression.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 21 (2000), S. 404-423 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Lunge ; Lungentumoren ; Onkogene ; Tumorsuppressorgene ; Molekularpathologie ; Gentherapie ; Metastasierung ; Keywords Lung ; Lung cancer ; Oncogenes ; Tumor suppressor genes ; Molecular pathology ; Gene therapy ; Metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Therapy and prognosis of lung cancer depend crucially on tumor size, tumor stage, and the histomorphological tumor type at the time of primary diagnosis. A tumor weighing only 1 g and barely detectable by clinical examination consists of about 1×109 tumor cells. The primary histological diagnosis is generally based on small biopsies 1–2 mm in diameter, which allow the assessment of only a few up to some hundred tumor cells in a section of 4 μm. Until 20 years ago light microscopic and histochemical investigations were the basis for sophisticated morphological tumor diagnosis. In recent years electron microscopy, immunohistochemistry, cytometry, and molecular biology have extended our knowledge of the complex tumor biology, with the range of phenotypes and genotypes indicating enormous tumor heterogeneity. The value, expressiveness, and prognostic importance of these laborious and expensive techniques must be examined in studies, keeping in mind new aspects of tumor classification. Histological and cytological findings are still the decisive basis for the primary diagnosis of the pathologist in any given case.
    Notes: Zusammenfassung Therapie und Prognose bösartiger Tumoren der Lungen hängen entscheidend von Tumorgröße, Tumorstadium und der histopathologischen Charakterisierung zum Zeitpunkt der Diagnosestellung ab. Ein klinisch bedingt nachweisbarer Tumor von ca. 1 g Gewicht besteht bereits aus ca. 1 Mrd. Tumorzellen. Die histologische Primärdiagnose basiert im Regelfall auf 1–2 mm im Durchmesser großen Biopsiepräparaten, die in 4 μm dicken Schnitten die Bewertung von einzelnen bis maximal einigen 100 Tumorzellen erlauben. Bis vor 20 Jahren bildeten lichtmikroskopische und histochemische Untersuchungsverfahren die Basis für eine differenzierte morphologische Tumordiagnostik. Die Verfahren der Elektronenmikroskopie, Immunhistochemie, Zytometrie und Molekularbiologie haben unsere Kenntnisse zur komplexen Tumorbiologie mit variablen Bildern als Zeichen einer großen Tumorheterogenität in den letzten Jahren wesentlich erweitert. Wert, Aussagekraft und prognostische Bedeutung dieser aufwendigen und kostspieligen Zusatzuntersuchungen müssen aber unter Studienbedingungen vor dem Hintergrund neuer Gesichtspunkte zur Tumorklassifikation kritisch geprüft werden. Entscheidende Basis für die aktuelle pathologisch-anatomische Primärdiagnostik des Einzelfalles bleiben aber auch heute noch histologische und zytologische Untersuchungsbefunde.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 17 (1996), S. 301-304 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Lunge ; Rundherde ; Lymphomatoide Granulomatose ; Differentialdiagnose ; Key words Pulmonary nodules ; Lymphomatoid granulomatosis ; Differential diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In addition to metastasis, the differential diagnosis of multiple pulmonary nodules also includes tuberculosis, sarcoidosis, and silicosis. Rarer diseases such as amyloid tumors, rheumatic nodules and plasma-cell granulomas can be the cause of this finding. This depends on the clinical manifestation. Based on clinical findings of lymphomatoid granulomatosis, the problems in diagnostics using bronchoscopy, mediastinoscopy and thoracoscopy are outlined. Etiology, morphology and differential diagnosis of lymphomatoid granulomatosis versus necrotizing inflammatory or neoplastic lesions are discussed. Treatment and prognosis are described.
    Notes: Zusammenfassung Die Differentialdiagnose multipler pulmonaler Rundherde umfaßt neben Metastasen auch die Tuberkulose, Sarkoidose und Silikose. Seltenere Erkrankungen wie Amyloidtumoren, Rheumaknoten und Plasmazellgranulome können sich – je nach klinischer Situation – hinter diesem Befund verbergen. Am Beispiel des Krankheitsbildes der lymphomatoiden Granulomatose wird die Problematik der klinisch-pathologischen Diagnosefindung unter Einsatz radiologischer, bronchoskopischer, mediastinoskopischer und thorakoskopischer Untersuchungsverfahren dargestellt. Ätiologie und Morphologie einschließlich differentialdiagnostischer Abgrenzungen zu nekrotisierenden entzündlichen und neoplastischen Erkrankungen sowie therapeutische Ansätze werden behandelt.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 469-477 
    ISSN: 1432-1335
    Keywords: Non-small-cell lung cancer ; Neoadjuvant therapy ; Regression grading ; Therapy-induced tumour regression ; Spontaneous tumour regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a threestep regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression (“responders”) the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression (“non-responders”) with a median survival period of 13.7 months (log-rank test,P=0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 469-477 
    ISSN: 1432-1335
    Keywords: Key words Non-small-cell lung cancer ; Neoadjuvant therapy ; Regression grading ; Therapy-induced tumour regression ; Spontaneous tumour regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a three-step regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression (“responders”) the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression (“non-responders”) with a median survival period of 13.7 months (log-rank test, P=0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.
    Type of Medium: Electronic Resource
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