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K Junker

Publications and source records attributed to K Junker.

At least 19 recordsLinked to original sources

Genomic aberrations are rare in urothelial neoplasms of patients 19 years or younger.

Urothelial neoplasms in patients 19 years of age or younger are rare, and the data regarding clinical outcome are conflicting. Molecular data are not available. Urothelial tumours from 14 patients aged 4 to 19 years were analysed, including FGFR3 and TP53 mutation screening, comparative genomic hybridization (CGH), UroVysion FISH analysis, polymerase chain reaction for human papillomavirus (HPV), microsatellite analysis using the NIH consensus panel for detection of microsatellite instability (MSI) and six markers for loss of heterozygosity on chromosome arms 9p, 9q, and 17p and immunohistochemistry for TP53, Ki-67, CK20 and the mismatch repair proteins (MRPs) hMSH2, hMLH1, and hMSH6. Based on the 2004 WHO classification, one urothelial papilloma, seven papillary urothelial neoplasms of low malignant potential (PUNLMPs), five low-grade, and one high-grade papillary urothelial carcinoma were included. No multifocal tumours were found and recurrence was seen in only one patient with a urothelial papilloma. All patients were alive with no evidence of disease at a median follow-up of 3.0 years. We found no mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss, or HPV positivity in any of the patients. Three cases showed chromosome alterations in CGH analyses, urothelial dedifferentiation with CK20 overexpression, or aneuploidy, and one TP53 mutation with TP53 overexpression was found. Urothelial neoplasms in people younger than 20 years are predominantly low grade and are associated with a favourable clinical outcome. Genetic alterations frequently seen in older adults are extremely rare in young patients. Urothelial neoplasms in children and young adults appear to be biologically distinct and lack genetic instability in most cases.

Adolescent↗

[Identification of biomarkers and therapeutic targets for renal cell cancer using ProteinChip technology].

In order to understand tumour biology in its complexity, it is necessary to investigate the proteomics in addition to the DNA and RNA level. SELDI-TOF-MS represents a new technology allowing a highly sensitive high-throughput analysis to detect specific protein profiles. In renal cancer, it was possible to define specific protein patterns in serum. Several proteins have been identified, i.e. serum amyloid alpha (SAA). Analysis of tumour tissues leads to a better understanding of tumour biology and provides the basis for differential classification and evaluation of prognosis. Investigation of the proteome concerning therapy results opens up the possibility of assessing downstream effects on the one hand and identifying biomarkers for selection of patients and therapy monitoring on the other hand. This review presents the first results for renal cancer.

Carcinoma, Renal Cell↗

[Current morphological diagnosis of malignant lung tumors].

The histological classification of lung tumors is based upon the 2004 WHO classification. Small cell lung cancer (SCLC) is primarily treated by means of anti-neoplastic chemotherapy, independently of the tumor stage. In resectable stages of non-small cell lung cancer (NSCLC, UICC-stages I and II), complete tumor resection is the aim. Therefore, the distinction between SCLC and NSCLC is still of particular importance. Currently, great interest is focused on the identification of specific therapeutic targets, especially on the inhibition of the epidermal growth factor ruptur (EGFR). Today, malignant lung tumors can also be classified by means of molecular pathology. Subgroups with different prognoses can be identified by gene expression profiling. The expression levels of several genes are associated with sensitivity against certain anti-cancer agents.

Carcinoma, Non-Small-Cell Lung↗

Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for the detection of bladder cancer.

Bladder cancer is the fifth most common cancer in adults. Because of the high recurrence rate (up to 70%) new tumor markers for urine are necessary for monitoring patients. In this study, we investigated the value of M-FISH on cells from urine for the detection of bladder cancer. Urine samples from 141 patients suspicious of bladder cancer were analyzed in this study. Cells were isolated from urine before surgical therapy. For FISH analysis, a commercial kit (UroVysion) containing hybridization probes for chromosomes 3, 7, 9p21 and 17, was used. Twenty-five cells were analyzed in each case by two observers. A FISH result was obtained in 121 cases. Overall, sensitivity was 60% and specificity reached 82.6%. Sensitivity and specificity by cytology were 24.1% and 90.5%, respectively. Analyzing results concerning T-category, sensitivity of FISH and cytology was 36.1% and 15% in pTa, 65.2 and 25.7% in pT1, 100% and 66.7% in pT2-3 tumors, respectively. Concerning tumor grade, similar results were obtained: sensitivity was 37% and 14% in G1, 65.4% and 40% in G2, 91.7% and 50% in G3 tumors, for FISH and cytology, respectively. In conclusion, FISH on cells from urine has been shown in all studies to be highly sensitive and specific for detection of bladder cancer. Sensitivity of FISH is higher than conventional cytology and can be used in routine diagnosis additionally to conventional cytology especially in doubtful or negative cases. FISH can detect recurrence earlier than other methods like cytology, cystoscopy or biopsy histological examination.

Cell Nucleus↗

Check-list of the pentastomid parasites crocodilians and freshwater chelonians.

Based on published records and own data a summary is given of the geographical distribution of the currently known species of pentastomid parasites infecting crocodiles and alligators, as well as freshwater chelonians. A brief generic diagnosis is provided for each genus. Fourteen out of the currently 23 living crocodilian species have been recorded as being host to one or more pentastomes. Out of the 32 pentastome species six are considered species inquirendae. Presently, six genera of crocodilian pentastomes, Agema, Alofia, Leiperia, Sebekia, Selfia and Subtriquetra are recognized. African crocodiles harbour eight pentastome species, six of which have been recorded from the Nile crocodile, Crocodylus niloticus. Three species belong to the genus Sebekia, Alofia being represented by two and Leiperia by only one species. Two species, Alofia parva and Agema silvae-palustris, occur in the dwarf crocodile, Osteolaemus tetraspis, and the slender-snouted crocodile, Crocodylus cataphractus, exclusively, but a single Sebekia species is shared with the Nile crocodile. The genus Agema is endemic to the African region. Infective stages of the pentastome Subtriquetra rileyi, thought to utilize Nile crocodiles as final hosts, have been recovered only from fishes. The largest number of pentastome species is found in the Australasian region. Of these, the Indo-Pacific crocodile, Crocodylus porosus, harbours seven, representing the genera Alofia, Sebekia, Leiperia and Selfia. Selfia is exclusive to the latter host. The genus Subtriquetra has been reported from "Indian crocodiles", a term possibly referring to either Crocodylus palustris, Crocodylus porosus or Gavialis gangeticus. Ten species of pentastomes parasitizing the crocodilian genera Alligator, Caiman, Crocodylus and Melanosuchus have been recorded from the Neotropical region including the southern states of the North American continent. The two most wide-spread pentastome genera, Alofia and Sebekia, have been recorded together with representatives of the genus Subtriquetra and immature and larval forms of Leiperia. To date the two monospecific genera, Pelonia, from two terrapin species, Pelusios sinuatus and Pelomedusa subrufa, in South Africa, and Diesingia from Hydraspis geoffroyana and Hydromedusa tectifera in South America, are the only chelonian pentastomes recovered world-wide. A possible exception is the crocodilian pentastome Sebekia mississippiensis which can reach maturity in experimentally infected terrapins.

Africa↗

Gastric nematodes of nile crocodiles, Crocodylus niloticus Laurenti, 1768, in the Okavango River, Botswana.

The ascaridoid nematodes Dujardinascaris madagascariensis Chabaud & Caballero, 1966, Dujardinascaris dujardini (Travassos, 1920), Gedoelstascaris vandenbrandeni (Baylis, 1929) Sprent, 1978 and Multicaecum agile (Wedl, 1861) Baylis, 1923 were recovered from the stomach contents of Crocodylus niloticus Laurenti, 1768 from the Okavango River, Botswana, together with Eustrongylides sp., a dioctophymatoid nematode usually parasitizing piscivorous birds. Dujardinascaris madagascariensis was present in most of the infected hosts, while the remaining species were mostly represented in single collections in one to three hosts. All four ascaridoid nematodes represent new geographic records.

Alligators and Crocodiles↗

ProteinChip technology reveals distinctive protein expression profiles in the urine of bladder cancer patients.

OBJECTIVE: Since accurate biomarkers for the early diagnosis or individual prognosis of the bladder carcinoma are still not available, we used the ProteinChip technology, to search for discriminating protein expressions associated with this cancer and its subtypes. METHODS: A training set consisting of 30 archival urine samples from bladder carcinoma patients and 30 urinary samples from healthy volunteers, was analyzed via ProteinChip technology and computer based data mining. Mass clusters of differentially expressed proteins were verified by a second set (test set) comprising 21 bladder carcinoma urine samples and 21 non-tumor urinary samples. Expression differences between carcinoma subtype sample groups of the initial training set were assessed by a trend test. RESULTS: Bladder carcinoma was segregated from control with a sensitivity and specificity of 80% and 90 to 97% in the trainings set, as well as 52 to 57% and 57 to 62% in the test set, respectively. Segregation of pooled tumor stages pT2-pT3 from stages pT1 and pTa was possible at the 53.3 kDa cluster of the CM10-chip array data derived rule base. CONCLUSION: ProteinChip technology together with adapted computer based data mining tools are useful for the rapid establishment of potential protein biomarkers.

Biomarkers, Tumor↗

[Correlation of histologic results with PET findings for tumor regression and survival in locally advanced non-small cell lung cancer after neoadjuvant treatment].

UNLABELLED: CT cannot provide useful information in a timely manner after neoadjuvant treatment. To evaluate the role of (18)F FDG PET after neoadjuvant chemoradiation for early therapy response and its effect on survival as compared to histopathologic tumor response, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD). INCLUSION CRITERIA: histologically confirmed NSCLC stage IIIA/IIIB. Neoadjuvant treatment: 2-3 cycles with paclitaxel/carboplatin and a block of chemoradiation followed by surgery. Pretherapeutic staging: PET scan in addition to a spiral CT and/or MRI. Second PET scan after completion of neoadjuvant therapy prior to surgery. Documentation of lymph node involvement. Assessment of SUV and the metabolic tumor index for primary tumor and metastatic lymph nodes. Image fusion of PET with CT data followed by molecular radiation treatment planning. Evaluation of histologic regression grade and correlation with PET for primary tumor and each lymph node location. All patients (10/32) with complete response in lymph node metastases detected by PET prior to surgery, had no vital tumor cells (i.e. histologic regression grade/RG III, sensitivity 100%). In primary tumors showing complete response, the RG was IIb or III, in one patient IIa (false negative in PET). False positive findings in PET are due to inflammation (5 patients, histologically confirmed). Univariate analyses: actuarial tumor-specific survival for complete metabolic remission vs. incomplete remission after 24 months: 76 vs. 20% (p=0,0079); for RG III/IIb vs. RG IIa/I after 24 months: 63 vs. 36% (p=0,0123).(18)F FDG PET precedes CT in measuring the tumor response and may predict (long term) therapeutic outcome in stage III NSCLC. Histologic regression grade correlates well with metabolic remission as detected by PET.

Antineoplastic Combined Chemotherapy Protocols↗

[Cellular changes in non-small cell lung cancer after neoadjuvant therapy].

Microscopic analysis of resection specimens of non-small cell lung cancer after neoadjuvant therapy evokes the subjective impression of cytologic changes, especially enlargement of the individual tumor cells and their nuclei. Therefore, objectivization of these changes was tested morphometrically. Corresponding investigations could be carried out in 24 patients who had each received identical neoadjuvant therapy. The diameters and areas of the tumor cells and their nuclei as well as the nucleocytoplasmic ratio were assessed. The adenocarcinomas investigated revealed a significant cellular enlargement after treatment. Moreover, in 18 resection specimens (75%), cytomorphological changes could be shown in comparison to untreated tumor tissue. The cellular and nuclear parameters analysed as well as the cytomorphological changes assessed showed no significant correlation to the grade of therapy-induced tumor regression and thus do not allow an assessment of therapy success. Based on these results, grading of non-small cell lung cancer is not recommended after neoadjuvant therapy and the diagnosis of "large cell anaplastic" carcinoma should be made with reservation.

Adenocarcinoma↗

[Therapy-induced morphological changes in lung cancer].

Especially patients with locally advanced non-small cell lung cancer, but also patients with small cell lung cancer without distant metastases are increasingly treated by means of neoadjuvant multimodality therapy. In corresponding resection specimens of primary tumours and lymph nodes, the extent of therapy-induced tumour regression represents an independent prognostic factor. After neoadjuvant therapy, different-sized target-like foci with central necrosis, adjoining narrow foam cell rim, peripheral vascular granulation tissue and transition into a marked scarry fibrosis can be established in the former tumour area. Morphological changes indicating therapy-induced tumour regression can be graded according to the "Bochum regression grading" system. Cytomorphological changes do not allow reliable conclusions to be drawn about the success of the applied neoadjuvant therapy. In resection specimens, they should not form the basis of a cytopathologic grading or lead to the diagnosis of "large cell anaplastic carcinoma".

Carcinoma, Non-Small-Cell Lung↗

Histopathologic evaluation of mediastinal lymph nodes in lung cancer.

Regional lymph nodes represent the most frequent metastatic site in lung cancer. During histopathologic assessment of lymph-node involvement, in the presence of gross tumour, one or several HEtE-stained sections will suffice to demonstrate the tumour and its possible extranodal extension. In the absence of macroscopically detectable metastatic tumour growth, the entire node should be submitted for microscopic examination and be cut into 3- to 4-mm slices in the longitudinal or transverse plane. If the node is sliced, care should be taken to process different surfaces for microscopic examination. After neoadjuvant therapy, the percentage of therapy-induced necrosis and the still vital tumour tissue in the dissected lymph nodes should be estimated microscopically. EUS-guided fine-needle aspiration with subsequent cytologic examination represents a complementary method in the evaluation of mediastinal lymph-node lesions. The proposed way of histopathologic evaluation of mediastinal lymph nodes tries to reach a high diagnostic yield, and to offer a compromise between theoretical demands and practical feasibility.

Biopsy, Needle↗

[Collision tumor of a hypopharyngeal adenoidcystic carcinoma and a laryngeal squamous cell carcinoma].

INTRODUCTION: Malignancies in head and neck cancer are mainly squamous cell carcinomas. Adenoid cystic carcinomas are rare lesions of this site. Laryngeal adenoid cystic carcinoma is estimated to occur in 0.1 - 0.7 % of all laryngeal carcinomas. Adenoid cystic carcinomas are rarely located in the hypopharynx. To our knowledge there is no case report of adenoid cystic carcinoma of the hypopharynx as part of a collision tumor of the larynx. CASE REPORT: A 47-year-old male patient was diagnosed with an adenoid cystic carcinoma of the hypopharynx and a squamous cell carcinoma of the larynx. Because of local extension of both tumors laryngectomy and partial pharyngotomy with bilateral neck dissection was performed followed by radiation therapy. Clinical aspects as well as histomorphological and immunohistochemical criteria of both tumor entities are discussed. DISCUSSION AND CONCLUSIONS: Immunohistochemical characteristics showed two different carcinoma entities in the larynx and hypopharynx. Only by complete histological investigation of a carcinoma those rare cases of a collision tumor can be detected. Both tumor entities need to be considered for therapy strategy and oncological follow-up planning.

Carcinoma, Adenoid Cystic↗

[Molecular diagnostics of renal diseases with underlying genetic predisposition].

The genetic basis for dysplasia and tumors of the kidney has increasingly become the subject of cytogenetic and molecular genetic investigations over the last decade. For that reason, it is now possible to define the risk of disease recurrence more precisely in families with kidney diseases caused by genetic alterations. The relevant genes and the mutations have been identified for most of these diseases and genetic diagnostics are possible. However, it is necessary to evaluate in each individual case whether genetic diagnostics are reasonable. This will be discussed for polycystic renal diseases, agenesis and dysplasia of the kidney, and hereditary kidney tumors.

DNA Mutational Analysis↗

[Apoptosis and tumor regression in locally advanced non-small cell lung cancer with neoadjuvant therapy].

Dysregulation of apoptosis is closely associated with malignant cell transformation. On the other hand, apoptosis is induced by chemotherapy or irradiation. Therefore, in 54 patients with locally advanced non-small cell lung cancer (NSCLC, 36 squamous cell carcinomas, 18 adenocarcinomas, stage IIIA/IIIB), apoptotic indices were comparatively analysed before onset and after termination of neoadjuvant therapy. The results were compared with the response to neoadjuvant therapy (extent of therapy-induced tumour regression) as well as the survival times. A statistically significant difference could not be established between pre-therapeutically and post-surgically established apoptotic indices (mean values: 0.93% vs. 1.1%). Neither before therapy nor after surgery did the apoptotic indices show a significant predictive value concerning different overall survival times. These results suggest that neoadjuvant therapy does not modify the extent of apoptosis in lung cancer in the long term. Only a few weeks after the completion of the neoadjuvant chemoradiotherapy this contributes to a net proliferation of the residual tumour tissue which is largely equivalent to that of the untreated tumour.

Adenocarcinoma↗

Frequent genetic alterations in flat urothelial hyperplasias and concomitant papillary bladder cancer as detected by CGH, LOH, and FISH analyses.

Flat urothelial hyperplasia, defined as markedly thickened urothelium without cytological atypia, is regarded in the new WHO classification as a urothelial lesion without malignant potential. Frequent deletions of chromosome 9 detected by fluorescence in situ hybridization (FISH) have been previously reported in flat urothelial hyperplasias found in patients with papillary bladder cancer. Using comparative genomic hybridization (CGH) and microsatellite analysis, these hyperplasias and concomitant papillary tumours of the same patients were screened for other genetic alterations to validate and extend the previous findings. Eleven flat hyperplasias detected by 5-ALA-induced fluorescence endoscopy and ten papillary urothelial carcinomas (pTaG1-G2) from ten patients were investigated. After microdissection, the DNA of the lesions was pre-amplified using whole genome amplification (I-PEP-PCR). Loss of heterozygosity (LOH) analyses were performed with five microsatellite markers at chromosomes 9p, 9q, and 17p. CGH was performed using standard protocols. In 6 of 11 hyperplasias and 7 of 10 papillary tumours, deletions at chromosome 9 were simultaneously shown by FISH, LOH, and CGH analyses. There was a good correlation between FISH, LOH, and CGH analyses, with identical results in 6 of 10 patients. In addition to deletions at chromosome 9, further genetic alterations were detected by CGH in 9 of 10 investigated hyperplasias, including changes frequently found in invasive papillary bladder cancer (loss of chromosomes 2q, 4, 8p, and 11p; gain of chromosome 17; and amplification at 11q12q13). There was considerable genetic heterogeneity between hyperplasias and papillary tumours, but a clonal relationship was suggested by LOH and/or CGH analyses in 5 of 10 cases. These data support the hypothesis that flat urothelial hyperplasias can display many genetic alterations commonly found in bladder cancer and could therefore be an early neoplastic lesion in the multistep development of invasive urothelial carcinoma.

Aged↗

[Neoadjuvant therapy in non-small cell lung cancer. Prognostic impact of "mediastinal downstaging"].

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy. Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens. Therapy-induced tumor regression was classified according to a three-step tumor regression grading system. In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% ( n=11) pretherapeutic lymph node status was maintained. Of 26 patients with post-therapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III). Patients with post-therapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02). Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.

Adenocarcinoma↗

Evaluation of the toxicity of concentrated barley beta-glucan in a 28-day feeding study in Wistar rats.

Beta-glucans are water-soluble cell-wall polysaccharides consisting of (1-->3,1-->4)-linked beta-D-glucopyranosyl monomers that comprise a considerable proportion of soluble fiber from certain grains including oats and barley. Consumption of foods containing beta-glucan or beta-glucan-enriched fractions prepared from these grains lower serum cholesterol concentrations in humans and in animal models of hypercholesterolemia. The present study was conducted to evaluate the toxicity of beta-glucan-enriched soluble fiber from barley in Wistar rats on dietary administration at concentrations of 0.7, 3.5 and 7% beta-glucan for 28 days. There were no adverse effects on general condition and behavior, growth, feed and water consumption, feed conversion efficiency, red blood cell and clotting potential parameters, clinical chemistry values, and organ weights. Necropsy and histopathology findings revealed no treatment-related changes in any organ evaluated. A dose-dependent increase in full and empty cecum weight was observed. This is a common physiological response of rodents to high amounts of poorly digestible, fermentable carbohydrates, and was of no toxicological concern. The only finding of possible biological relevance was an increase in the number of circulating lymphocytes observed in males. However, the increase was not dose-dependent and was not observed in females. Results of this study demonstrated that consumption of concentrated barley beta-glucan was not associated with any obvious signs of toxicity in Wistar rats even following consumption of large quantities.

Animal Feed↗