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K Junker

Publications and source records attributed to K Junker.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Changes in differentiation of small cell lung cancer after chemotherapy].

We reexamined biopsy and resection specimens from seven patients with histologically established primary diagnosis of small-cell lung cancer (SCLC) which showed previously undetected adenocarcinomatous differentiation after chemotherapy. Adenocarcinoma was diagnosed in the same part of the lung as was SCLC before treatment in five cases and in contralateral location in two. Two tumors showed heterogeneous differentiation with small-cell and adenocarcinomatous components, and five had only adenocarcinoma. The interval between histological evidence of SCLC and adenocarcinoma was 3 months-5 years. From the specific findings in the respective patients we can offer two possible explanations for changing differentiation in SCLC after chemotherapy: (a) a primarily heterogeneously differentiated tumor with selection of adenocarcinomatous component under chemotherapy, and (b) an independently developed adenocarcinoma after successful chemotherapy of SCLC, as patients with treated SCLC are known to have an increased risk of non-SCLC. However, therapy-induced alteration of differentiation seems much more unlikely. These findings should be considered in diagnosis and therapy of SCLC to allow early and appropriate reaction to non-SCLC components.

Adenocarcinoma↗
PubMed2000

[Pathology and molecular biology of lung cancer].

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 x 10(9) 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 microns. 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.

Biopsy↗
PubMed2000

p53 tumour-suppressor gene in non-small-cell lung cancer with neoadjuvant therapy.

In a phase II study for optimizing therapeutic management of locally advanced non-small-cell lung cancer the prognostic and therapeutic relevance of the p53 status was investigated. Biopsy or mediastinoscopy samples, collected prior to neoadjuvant chemoradiotherapy and corresponding resection specimens, were analysed immunohistochemically (CM1 antiserum) for p53 accumulation and molecular biologically (polymerase chain reaction/single-strand conformation polymorphism) for p53 mutations. The results were correlated to the response to therapy (regression grade) and to the survival times. p53 accumulation was found in 41.7% (prior to neoadjuvant therapy) and in 40.0% (after surgery) of the tumours. p53 mutation was demonstrated in 45.4% (prior to neoadjuvant therapy) and in 46.4% (after surgery) of the investigated tumours. Neither before nor after therapy was any correlation to the survival times or to the response to therapy seen in the collective analysed. Thus, such investigations are not suitable for identifying patients with locally advanced non-small-cell lung cancer who might benefit, to different extents, from neoadjuvant therapy.

Adult↗
PubMed2000

Leiperia cincinnalis Sambon, 1922 (Pentastomida) from Nile crocodiles Crocodylus niloticus in the Kruger National Park, South Africa, with a description of the male.

A single male and several adult females of the pentastomid Leiperia cincinnalis were recovered from the trachea of five of six Nile crocodiles examined in 1995 and 1998. Infective larvae, pre-adult males and females, as well as mature males, occurred in clusters in the pulmonary artery but infective larvae and pre-adult females were also occasionally taken from the lungs. Irrespective of the developmental stage, the intensity of infection was 3, 6, 48, 72 and 79. Sixty-four percent of eggs recovered from the posterior part of the uterus of a patent L. cincinnalis female contained fully-developed primary larvae and these were used to infect 24 Mozambique bream Oreochromis mossambicus. Within a week of infection all the fish died and hatched primary larvae were recovered from the stomach and anterior part of the intestine. Eggs that had not hatched were found to be unsegmented. The total primary larval count in seven fish was 18, 12, 1, 25, 16, >40 and >50. Descriptions with detailed measurements are given of the females, the males, the eggs, the primary larvae and the infective larvae of L. cincinnalis.

Alligators and Crocodiles↗
PubMed2000

Localization of human serum amyloid P component and heparan sulfate proteoglycan in in vitro-formed Abeta fibrils.

Ultrastructural studies of the localization of serum amyloid P component (SAP) in amyloid fibrils have given divergent results. We here report for the first time that electron microscopy of SAP coincubated with Abeta1-42 peptides or with mature Abeta1-42 fibrils, revealed SAP molecules coating the surface of the mature fibrils and that protofibrils of Abeta1-42 did not bind SAP. Also when incubated with extracted amyloid light chain (AL)-fibrils the SAP molecules aligned on the fibril surface. Heparan sulfate proteoglycan bound to the surface of the Abeta fibrils with a spacing of about 50 nm. We conclude that SAP does not bind to protofibrils but to the surface of mature Abeta fibrils and that it may stabilize and protect the fibrils.

Amyloid beta-Peptides↗
PubMed2000

Fibrocartilaginous embolism of the spinal cord (FCE) in juvenile Irish Wolfhounds.

This study describes the occurrence of fibrocartilaginous embolism of the spinal cord (FCE) in eight juvenile Irish Wolfhounds that were presented within a period of 16 months (1996-1997). The dogs, seven males and one female between eight and 13 weeks of age, were presented because of an acute onset of abnormal locomotion. Five dogs were euthanized and FCE was diagnosed by the histomorphological presence of focal myelomalacia and Alcian blue-positive-nucleus-pulposus material in the spinal cord vasculature. Three dogs, which were thought to have FCE because of their clinical symptoms, improved with partial or almost complete return to normal locomotion. Although the observed high incidence may be a coincidence, oral information from breeders and lay reports of similar cases in journals for dog breeders from various countries suggest that FCE is a common disorder in young Irish Wolfhounds.

Animals↗
PubMed2000

Where are the limits of elective nephron- sparing surgery in renal cell carcinoma?

OBJECTIVES: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is still controversial. The presented study was performed to determine limitations for NSS regarding to multifocality and to characterize the biological importance of these small tumor lesions. METHODS: In 372 patients who underwent radical nephrectomy for RCC consecutively, nephrectomy specimens were investigated by using 3-mm parenchyma sections regarding to local tumor spread and multifocality. To characterize multifocal tumors, we performed cytogenetic and molecular genetic investigations. RESULTS: Serial sections of 372 nephrectomy specimens revealed a total of 92 multifocal tumors in 61 specimens (16.4%). The correlation between tumor size and multifocality is shown as follows: tumor diameter 1-20 mm: 12.5%; 21-30 mm: 23.4%; 31-40 mm: 10.2%; >40 mm: 16.7%. The mean diameter of the multifocal tumors was 8.8x9.1x6.1 mm and the mean distance to the primary tumor was 26.4 mm (5-84 mm). Using cytogenetic and molecular genetic analysis, in nearly one third of all cases a concordance of chromosomal aberrations in primary and secondary tumors was found. CONCLUSIONS: Multifocality of renal cell carcinoma occurs independently from primary tumor size. The evidence of structural and/or numeric aberrations, found in additional tumor foci, obviously is an argument for their malignant potential. This findings have to be considered in preparation of nephron-sparing surgery for patients with renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2000

Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer.

The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.

Adenocarcinoma↗
PubMed2000

Tissue-specific microdissection coupled with ProteinChip array technologies: applications in cancer research.

Analysis of whole genomes to monitor specific changes in gene activation or changes in gene copy number due to perturbation has recently become possible using DNA chip technologies. It is now becoming apparent, however, that knowing the genetic sequence encoding a protein is not sufficient to predict the size or biological nature of a protein. This can be particularly important in cancer research where posttranslational modifications of a protein can specifically lead to the disease. To address this area, several proteomic tools have been developed. Currently the most widely used proteomics tool is two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), which can display protein expression patterns to a high degree of resolution. However, 2D-PAGE can be time consuming; the analysis is complicated and, compared with DNA techniques, is not very sensitive. Although some of these problems can be alleviated by using high-quality homogeneous samples, such as those generated using microdissection techniques, the quantity of sample is often limited and may take several days to generate sufficient material for a single 2D-PAGE analysis. As an alternative to 2D-PAGE, a preliminary study using a new technique was used to generate protein expression patterns from either whole tissue extracts or microdissected material. Surface-enhanced laser desorption and ionization allows the retention of proteins on a solid-phase chromatographic surface or ProteinChip Array with direct detection of retained proteins by time-of-flight mass spectrometry. Using this system, we analyzed tumor and normal tissue from head and neck cancer and microdissected melanoma to determine differentially expressed proteins. In particular, comparisons of the protein expression patterns from microdissected normal and tumor tissues indicated several differences, highlighting the importance of extremely defined tissue lysates for protein profiling.

Biosensing Techniques↗
PubMed2000

Genetic alterations in metastatic renal cell carcinoma detected by comparative genomic hybridization: correlation with clinical and histological data.

In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disease. We analyzed 46 renal tumors along with their metastases, and 15 non-metastatic renal tumors. Tumors were classified pathologically according to the Heidelberg classification of RCC, and staged according to the TNM-system. Standard CGH was performed using microdissected archival tissues and DOP-PCR. The average numbers of chromosomal aberrations per tumor were 3.0, 2.1 and 3.9 in patients without metastasis, in patients who developed metastases after a two-year latency period (late onset of metastatic disease) and in patients who developed metastases within two years after therapy of the primary tumor (early onset of metastatic disease). CGH revealed chromosomal aberrations in 91% of primary metastatic tumors. Deletions or losses of chromosomes 9 (26% vs 6%), 10 (21% vs 6%) and 18 (23% vs 0) and 17 (28% vs 7%) occurred more often in metastatic tumors than in non-metastatic tumors. Furthermore, these aberrations were more common in patients with early metastases. CGH analysis of 40 pairs of primary RCCs and their corresponding metastasis revealed similar aberrations in 70% of cases. In 30%, however, metastases showed additional chromosomal aberrations not detected in the corresponding primary tumors. In conclusion, we identified genetic alterations associated with metastatic disease in RCC which could be useful for predicting prognosis. Genetic changes leading to metastases occurred early in tumorigenesis of metastatic tumors.

Carcinoma, Renal Cell↗
PubMed1999

Novel mutations of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene. These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase. The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that noninherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma.

3T3 Cells↗
PubMed1999

[Limits for organ-preserving surgery in renal cell carcinoma].

The indication for elective organ-preserving surgery in renal cell carcinoma is under discussion. The statements about the maximum tumor size, which could be considered for this surgical procedure, differ in the literature. In a series of 281 consecutive radical tumor nephrectomies we compared the results of preoperative ultrasound and computerized tomography regarding to tumor size and multifocality with the results of the postoperative systematically section of the removed kidneys. Further we analysed the results of 14.793 autopsies regarding to tumor size and multifocality. Serial section of the 281 nephrectomy specimens revealed a total of 64 multifocal tumors in 48 kidneys ( = 17,1 %). The correlation between tumor size and multifocality showed only in tumors up to 20 mm no additional lesions, whereas in the higher tumor categories the incidence was up to 23 %. These clinical investigations were confirmed by the results of the autopsies. In summery of the results we conclude, that the elective organ-preserving surgery of renal cell carcinoma is only indicated in tumors with a maximum diameter of 20 mm.

Carcinoma, Renal Cell↗
PubMed1999

Telomerase activity and telomere lengths: alterations in renal cell carcinomas.

Detection of telomerase activity in renal cell carcinomas may be a key to understanding the loss of growth control in tumor cells. This enzyme forms the end of most chromosomal DNAs (that is, telomeres) found in renal tumors. When activated, the telomeres shorten with every cell cycle and then there is a compensatory lengthening of the cells, which then proliferate and eventually become immortal and metastasize. This complex multigenetic process may prove to be a useful marker of tumor progression and patient outcome.

Carcinoma, Renal Cell↗
PubMed1999

Determination of telomerase activity for differential analysis of multifocal renal cell carcinomas.

Secondary tumors are found in approximately 12 to 22% of all renal cell carcinoma, and their origin is currently unknown. To determine their potential for malignancy, we examined the telomerase activity of primary tumors and secondary lesions, and found that 86% of the lesions had an identical telomerase status as the related primary tumors, and thus probably share their malignancy potential.

Adenocarcinoma, Clear Cell↗
PubMed1999

Genetic characterization of multifocal tumor growth in renal cell carcinoma.

The primary cancer found in the kidney is renal cell carcinoma (RCC), which does not as yet have a delineation of the types of lesions that progress to tumor malignancy. We studied tissues from primary tumors and secondary lesions, and compared it with the surrounding normal kidney tissue using comparative genomic hybridization to determine their potential for malignancy. Although our sample size was small, we found that small multifocal tumors have the same potential as primary carcinoma to lead to RCC malignancy. Further genetic studies in a larger sample of patients is necessary before the risk of different lesions to remain benign or progress to RCC can be defined absolutely.

Carcinoma, Renal Cell↗
PubMed1999

Trimodality therapy in stage III non-small cell lung cancer: prediction of recurrence by assessment of p185neu.

In a trimodality treatment approach for stage III non-small cell lung cancer the prognostic impact of pretherapeutic p185neu assessment was evaluated. Fifty-four patients were admitted to chemotherapy followed by twice-daily radiation with concomittant low-dose chemotherapy and subsequent surgery. Immunohistochemical assessment of p185neu expression was performed in paraffin-embedded mediastinal lymph node metastases, by mediastinoscopy biopsy prior to therapy. Paraffin-embedded biopsies of mediastinal lymph node metastases were available in 33 cases. Seven out of eight patients with positive p185neu staining developed distant metastases, in contrast to seven out of 25 negative cases. Expression of p185neu in mediastinal lymph node metastases was a significant predictor for progression-free survival (p=0.047) and resulted mainly from significant differences in metastases-free survival (p185neu-positive versus p185neu-negative: median, 11 versus 19 months; 2- and 3-yr rates, 13% and 0% versus 40% and 32%; p=0.04). On the basis of these preliminary results it was concluded that further evaluation of p185neu expression in trials on neoadjuvant and adjuvant therapy is warranted. When the prognostic impact of p185neu in such trials with larger patient numbers is confirmed, this may contribute to the identification of stratification variables for future treatment approaches of non-small cell lung cancer.

Adult↗