PubMed Health⌕ Search

Biomedical subjects

J Trojan

Publications and source records attributed to J Trojan.

At least 19 recordsLinked to original sources
PubMed2007

Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial.

BACKGROUND: A standard second-line chemotherapy regimen has yet to be defined for patients with gemcitabine (Gem)-refractory advanced pancreatic cancer (PC). PATIENTS AND METHODS: In this multicenter phase II trial, patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen received pemetrexed 500 mg/m(2) as a 10-min infusion every 3 weeks until disease progression or occurrence of unacceptable toxicity. The primary end point was the 3-month survival rate. RESULTS: A total of 192 treatment cycles were given to 52 patients. The overall response rate was 3.8% (two partial responses); 10 patients (19.2%) experienced stable disease, nine of them for >12 weeks. At least one CA 19-9 reduction > or =50% occurred in 12 patients (23.1%). The 3-month survival rate was 75% (95% confidence interval 63.2% to 86.8%), the median time to tumor progression was 7 weeks (range 1-62 weeks) and the median overall survival time was 20 weeks (range 1-84 weeks). Grade 3/4 hematological toxic effects included (percent of patients): neutropenia (17.3%), thrombocytopenia (5.8%) and anemia (3.8%). The most frequent non-hematological toxic effects were diarrhea, nausea and stomatitis/pharyngitis (23.1% each). CONCLUSION: Pemetrexed is a safe treatment option with moderate activity in patients with advanced PC after failure of Gem.

Adult↗
PubMed2005

Characterization of the nuclear import of human MutLalpha.

DNA mismatch repair (MMR) is essential for the maintenance of replication fidelity. Its major task is to recognize mismatches as well as insertion/deletion loops of newly synthesized DNA strands. Although different players of human MMR have been identified, the regulation of essential steps of MMR is poorly understood. Because MMR is initiated in the nucleus, nuclear import might be a mechanism to regulate MMR. Nuclear targeting is accomplished by conserved signal sequences called nuclear localization signals (NLS), which represent clusters of positively charged amino acids (aa). hMLH1 contains two clusters of positively charged amino acids, which are candidate NLS sequences (aa 469-472 and 496-499), while hPMS2 contains one (aa 574-580). To study the effect of these clusters on nuclear import, NLS mutants of hMLH1 and hPMS2 were generated and expressed in 293T cells. The subcellular localization of the mutant constructs was monitored by confocal laser microscopy. We demonstrated that missense mutations of two signal sequences, one in hMLH1 and one in hPMS2, lead to impaired nuclear import, which was especially prominent for mutants of the hMLH1 residues K471 and R472; and hPMS2 residues K577 and R578.

Amino Acid Sequence↗
PubMed2005

Frequency of colorectal polyps in patients with sporadic adenomas or adenocarcinomas of the papilla of vater--an age-matched, controlled study.

BACKGROUND: Epithelial tumors of the papilla of Vater are rare neoplasms of the gastrointestinal tract. The carcinogenesis of these tumors seems to be fairly analogous to the genetic mechanisms which have been described for colorectal carcinoma. Patients with familial adenomatous polyposis bear a particularly increased risk for periampullary tumors. Data on whether the prevalence of colorectal tumors is increased in patients with sporadic ampullary neoplasms are scarce. METHODS: 26 consecutive patients (16 women, 10 men; median age 59 years) with sporadic adenomas (n = 19) or adenocarcinomas (n = 7) of the ampulla of Vater were retrospectively evaluated. The study patients were compared with 104 age-matched asymptomatic controls. All patients had undergone total colonoscopy. RESULTS: Neoplastic colorectal polyps were present in a similar proportion (23%) of patients of the study group compared with 26% in the control group (p > 0.05). Overall, 16 polyps were found among patients with ampullary tumors and 40 in asymptomatic controls (p > 0.05). Colonoscopy detected rectal carcinoma in 2 patients (8%) of the study group. Patients with and without colorectal polyps differed neither significantly by age nor by ampullary histological findings. 50% of the colonic polyps in patients with ampullary neoplasms were located in the ascending colon. CONCLUSIONS: The frequency of colorectal polyps in patients with ampullary tumors did not exceed the risk in the control group. However, the finding of 2 rectal carcinomas among patients with ampullary neoplasms supports the place of screening colonoscopy for the diagnostic work-up of ampullary tumors. Prospective multicenter studies should address this issue to provide a broad basis for future recommendations.

Adenocarcinoma↗
PubMed2005

An infected esophageal duplication cyst in a patient with non-Hodgkin's lymphoma mimicking persistent disease.

Differentiation of mediastinal cysts appearing as soft-tissue attenuation masses on computed tomography (CT) scans from malignant mediastinal masses is difficult. We report a patient with non-Hodgkin's lymphoma, who was considered to have persistent disease in the posterior mediastinum based on CT scans. However, endoscopic ultrasound (EUS) demonstrated a paraesophageal, fluid-filled cyst with echodens inclusions and no evidence of any solid component. EUS-guided fine-needle aspiration (FNA) revealed mucous, epithelial and inflammatory cells, and additionally candida albicans was cultured. Based on these findings and constant size during follow-up, the diagnosis of an infected esophageal duplication cyst was made. Thus, this report further demonstrated the impact of EUS and EUS-FNA for management of posterior mediastinal cystic lesions in selected cases.

Adult↗
PubMed2005

Differentiation of focal nodular hyperplasia and hepatocellular adenoma by contrast-enhanced ultrasound.

Non-invasive differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is difficult. The aim of this study was to assess the accuracy of contrast-enhanced phase inversion ultrasound to differentiate between histologically proven FNH and HCA, analysing the arterial and (early) portal venous phase. 32 patients with histological proven FNH (n=24) or HCA (n=8) have been included in this prospective study. Examination technique: Siemens Elegra, phase inversion harmonic imaging (PIHI) with low mechanical index (MI)<0.2-0.3 using SonoVue (BR 1). The contrast enhancing tumour characteristics were evaluated during the hepatic arterial (starting 8-22 s) and early portal venous phase (starting 12-30 s). The image analysis was performed by three examiners. In 23 of 24 patients with FNH the contrast pattern revealed pronounced arterial and (early) portal venous enhancement. Homogeneous enhancement was detected during the hepatic arterial phase in all eight patients with HCA. In contrast to patients with FNH, no enhancement was seen during the portal venous phase. In conclusion, contrast-enhanced phase inversion ultrasound demonstrated pronounced arterial and portal venous enhancement in patients with focal nodular hyperplasia. In contrast, after homogeneous enhancement during hepatic arterial phase, no enhancement during hepatic portal venous phase was detected in patients with hepatocellular adenoma. Therefore, this technique might improve the functional characterization of benign hypervascular focal liver lesions.

Adenoma, Liver Cell↗
PubMed2004

The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study.

BACKGROUND: Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. AIM: To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. METHODS: We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. RESULTS: Receiver-operator curve analysis revealed <0.7 microg/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). CONCLUSION: The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice.

Adult↗
PubMed2004

Improved characterisation of histologically proven liver tumours by contrast enhanced ultrasonography during the portal venous and specific late phase of SHU 508A.

PURPOSE: Ultrasound is reported to be relatively unreliable in the characterisation of liver tumours. The purpose of this study was to assess the ability of contrast enhanced phase inversion ultrasound (PIUS), a new highly sensitive contrast specific technique, performed during the liver specific phase of Levovist, to differentiate between benign and malignant lesions of the liver. PATIENTS AND METHODS: A total of 174 patients with histologically proven liver tumours were prospectively examined with conventional B mode ultrasound and two minutes after intravenous bolus injection of SHU 508A (Levovist). The examination technique comprised: Siemens Sonoline Elegra, phase inversion harmonic imaging (ECI); high mechanical index (1.2-1.7) using a delayed two minute post contrast scanning technique. RESULTS: In all patients with malignant disease, hypoechoic contrast enhancement was seen during the portal venous phase, and convincing but variably less demarcated in 13 patients with hepatocellular carcinoma compared with all patients with liver metastases. The liver tumours proved to be histologically benign in 95 patients and malignant in 79 patients. Homogenous contrast enhancement with a mainly isoechogenic appearance in the portal venous and liver specific late phase was seen in almost all patients with benign liver lesions with the exception of one patient with an inflammatory pseudotumour of the liver and five patients with abscesses. These six exceptions all demonstrated a hypoechoic appearance in the portal venous and liver specific late phase. DISCUSSION: The ability of unenhanced ultrasonography to characterise liver disease is known to be limited. PIUS performed during the portal venous and liver specific late phase of Levovist may differentiate between benign and malignant liver tumours in most cases, with the exception of, for example, abscesses, scars, necrosis, cysts, and calcifications, which need to be excluded clinically and by conventional B mode ultrasonography.

Adolescent↗
PubMed2004

Evaluation of angiogenesis, p-53 tissue protein expression and serum VEGF in patients with endometrial cancer.

Endometrial carcinoma occurs mostly in post-menopausal women. Classical methods of prognostication, as FIGO stage and histopathologic grade, could be improved by applying additional techniques, utilizing molecular biology and immunochemistry. p-53 tumor suppressor gene, the most commonly mutated gene in human cancers has been shown to play an important role in the biology of gynecologic carcinomas. Angiogenesis, a process of formation of new vessels, being connected to tumors progression and metastatic potential was shown to be linked with tumor suppressor genes expression. The aim of the study was to evaluate relationships between intensity of tumor angiogenesis, serum levels of Vascular Endothelial Growth Factor (VEGF) and tissue p-53 protein expression in endometrial adenocarcinoma. Angiogenic Point's Density (APD) was calculated in hot spots areas using the morphometric appliance. For detection of p53 protein in tumor samples, LSAB + Kit Alkaline Phosphatase (DAKO) was used. VEGF levels were assessed in patient's blood sampled before the operation. Overexpression of p53 protein was found in tumor tissue in 35.2% of cases and mean angiogenic points density was greater in p53 positive cases. Serum levels of VEGF were above the cut off level in 54.5% of patients, in those cases angiogenesis was also elevated. In cases of p53 overexpression, VEGF levels tended to be greater as compared with p53 negative cases. In conclusion, our study demonstrated that angiogenesis was more intensive in p53 positive cases, confirming the hypothesis of tumor suppressor-gene regulation of the process of neovascularization. Serum levels of VEGF were borderline-significantly higher in cases of p53 overexpression, they were also correlated to the angiogenesis. Joint assessment of angiogenesis and tumor suppressor genes expression may contribute to reliable evaluation of the biology of endometrial carcinoma.

Adenocarcinoma↗
PubMed2004

Presence of MHC-I in rat glioma cells expressing antisense IGF-I-receptor RNA.

The supposed immunogenic character of glioma cells transfected with antisense IGF-I-Receptor (IGF-I-R) expression vector was tested for the presence of MHC-I currently present in cells of IGF-I antisense type. C6 rat glioma cell line was comparatively transfected in vitro with IGF I antisense (pMT-Anti-IGF I) or IGF I Receptor antisense (pMT-Anti-IGF I R) expression vectors. The wild and transfected cells were examined for the presence of IGF-I and MHC-I molecules. Using RT PCR technique, the transfected "antisens" cells showed total inhibition of IGF-I. The both transfected cultures of IGF-I and of IGF-I-R type were positively stained for MHC-I. Moreover "antisense IGF-I-R" cells as compared to "IGF-I antisense" cells showed slightly higher expression of MHC-I. The transfected cells showed also the feature of apoptosis in 60% of cells. The immunogenicity of IGF-I-R antisense glioma cells is related to MHC-I presence; therefore both approaches of antisense IGF-I and of antisense IGF-I-R could be use in paralel for cellular therapy of glioblastoma.

Animals↗
PubMed2003

IGF-I triple helix gene therapy of rat and human gliomas.

PURPOSE: IGF-I anti-gene technology was applied in treatment of rat and human gliomas using IGF-I triple helix approach. MATERIAL AND METHODS: CNS-1 rat glioma cell and primary human glioblastoma cell lines established from surgically removed glioblastomas multiforme were transfected in vitro with IGF-I antisense (pMT-Anti-IGF-I) or IGF-I triple helix (pMT-AG-TH) expression vectors. The transfected cells were examined for immunogenicity (immunocytochemistry and flow cytometry analysis) and apoptosis phenomena (electron microscopy). 3 x 10(6) transfected cells were inoculated subcutaneously either into transgenic Lewis rats or in patients with glioblastoma. The peripheral blood lymphocytes (PBL) derived from "vaccinated" patients were immunophenotyped for the set of CD antigens (CD4, CD8 etc). RESULTS: Using immunocytochemistry and Northern blot techniques, the transfected "antisense" and "triple-helix" cells showed total inhibition of IGF. Transfected cultures were positively stained either for both MHC-I and B7 antigens--60% of cloned lines, or for MHC-I only--40% of cloned lines. Moreover "triple helix" cells as compared to "antisense" cells showed slightly higher expression of MHC-I or B7. Transfected cells also showed the feature of apoptosis in 60%-70% of cells. In in vivo experiments with rats bearing tumors, the injection of "triple helix" cells expressing both MHC-I and B7 interrupted tumor growth in 80% of cases. In contrast, transfected cells expressing only MHC-I stopped development in 30% of tumors. In five patients with surgically resected glioblastoma who were inoculated with "triple helix" cells, PBL showed an increased percentage of CD4 + CD25+ and CD8 + CD11b-cells, following two vaccinations. CONCLUSIONS: The anti-tumor effectiveness of IGF-I anti-gene technology may be related to both MHC-I and B7 expression in cells used for therapy. The IGF-I antigene therapy of human glioblastoma multiforme increases immune response of treated patients.

Animals↗
PubMed2003

Growth hormone treatment in pituitary insufficiency: selected cases of children with craniopharyngioma and medulloblastoma.

PURPOSE: The work concerns the substitution treatment with growth hormone (GH) in hypopituitary children, including cases that occurred in the course of tumor disease, craniopharyngioma (CP) and medulloblastoma (MB). MATERIAL AND METHODS: The studied population concerned 117 children who presented either somatotropic or polyhormonal pituitary insufficiency (the average age was 12.6 years for girls and 13.6 years for boys). The diagnosis of somatotropic pituitary insufficiency (SPI) was based on insulin and clonidin stimulation tests evaluating GH reserve of hypophysis. The computer tomography (CT) and nuclear magnetic resonance (NMR) examinations were carried out before GH substitution in all children. The tumors (four CP cases and one case of MB) were all found in boys and they were treated with surgery and/or radiotherapy. All studied children, including CP and MB operated patients were treated with human GH (hGH)--Genotropin 16 IU, administered in subcutaneous injections. The daily dose was calculated as 0.5 IU/kg/week. RESULTS: The annual increase of children height before GH therapy was about 3.2 cm. In the first year of GH therapy the difference in children growth between the CP/MB group as compared with the rest of patients was less than 1.0 cm: 9.4 and 10.2 cm/year, resp. During the second year of hormone substitution the growth became slower: average values were 8.2 cm and 7.4 cm/year, resp. In CP and MB patients the height increase calculated as SDS values was significant (2.7 and 1.0 resp.). Control NMR examination performed in CP/MB patients treated with surgery with subsequent hGH therapy did not demonstrate any recurrence of tumor. CONCLUSIONS: After two years of hGH therapy the final height of hypopituitary children, including CP patients, nearly reached the values observed in healthy children. GH therapy did not induce a recurrence of neoplasm in CP and MB patients.

Adolescent↗
PubMed2002

Role of ultrasonography in the detection of small adrenal masses.

AIM: Computed tomography (CT) scanning is commonly used for evaluation of adrenal masses in adults. In this prospective study we evaluated whether adrenal gland masses of less or equal than 20 mm in diameter could be detected by modern abdominal ultrasonography (US). METHOD: Between July 1999 and June 2000, 44 consecutive patients with 50 adrenal masses documented by contrast-enhanced CT (left adrenal gland, n = 31; right adrenal gland, n = 19; bilateral, n = 6; median size, 15 [5 +/- 80] mm) and, additionally, 50 patients without CT findings of an adrenal mass were prospectively evaluated by high-resolution US performed by physicians. Based upon CT measurement, 34 adrenal masses were </= 20 mm and 16 were > 20 mm in diameter. RESULTS: The overall sensitivity of US for the detection of adrenal masses was 96 % (48/50) (94 % [29/31] for left and 100 % [19/19] for right adrenal masses, respectively). The overall specificity of US for the detection of adrenal masses was 92 % (92/100) (90 % [45/50] for left and 94 % [47/50] for right adrenal masses, respectively). Thus, the diagnostic accuracy of US for the detection of adrenal masses is 93 % (140/150). Sensitivity and specificity of US for the detection of adrenal masses </= 20 mm (n = 34) did not differ significantly from those > 20 mm (n = 16). CONCLUSION: US is effective for detecting small adrenal masses. In rare cases small masses of the left adrenal gland might be missed and nodular adrenal hyperplasia or retroperitoneal lymph nodes might be misinterpreted as adrenal masses.

Adrenal Gland Neoplasms↗
PubMed2002

Frequency of the Amsterdam criteria in a regional German cohort of patients with colorectal cancer.

Estimates of the colon cancer burden associated with hereditary nonpolyposis colorectal cancer (HNPCC) vary from less than 1 % to more than 5 %. Amsterdam criteria fulfilled within a kindred (classic Amsterdam and Amsterdam II criteria) are widely used to identify patients prone to HNPCC. The present study was initiated to assess the frequency of the Amsterdam criteria within a regional German cohort of 207 patients with a history of colorectal cancer (CRC). Data on individual and family cancer histories were available in 154 patients (73 women, 81 men; mean age at diagnosis 62.4 +/- 13.3 years). A total of 843 first degree relatives have been identified within the kindreds of whom 121 had verified cancers. In 28 of 154 families (18 %), at least one first degree relative of the index patient had CRC. With respect to a typical family history, five kindreds (3.2 %) were likely to suffer from HNPCC on a clinical basis (4 kindreds met the classic Amsterdam criteria and one kindred the Amsterdam II criteria). Testing for microsatellite instability could additionally be performed in 4 of 5 patients who met the Amsterdam criteria and revealed DNA instability in 3 cases. Moreover, a missense mutation of MSH2 (Gly965Asp) was detected in one patient with microsatellite instability. Based on the classic Amsterdam and Amsterdam II criteria approximately 3 % of a regional German cohort of patients with CRC are likely to suffer from HNPCC. However, the final diagnosis of HNPCC can only be established by detection of pathogenic germline mutations within the DNA mismatch repair genes.

Adult↗
PubMed2002

A new immunological test strip device for the rapid, qualitative detection of faecal occult blood.

OBJECTIVE: Guaiac tests for faecal occult blood are still the most commonly performed screening procedure for colorectal cancer. Because both sensitivity and specificity of faecal occult blood testing are critical to cost-effective colorectal cancer screening programs, we investigated a rapid immunological test strip device for bedside detection of faecal occult blood. METHODS: Stool specimen from 100 patients were chosen for this study based on the presence (n = 50) or absence (n = 50) of faecal occult blood as measured with a human haemoglobin ELISA (cut-off level </= 10 micro g Hb/g stool). All specimens were analysed for faecal occult blood by a guaiac test (Hemocare) and an immunological test strip device (Prevent ID CC). RESULTS: Sensitivity and specificity of the immunological faecal occult blood test strip device were 76 % and 92 %, compared to 30 % and 90 % for the guaiac test. Increasing the cut-off level of the haemoglobin ELISA to </= 20 micro g Hb/g stool, the corresponding sensitivity and specificity were 86 % and 83 % for the immunological test strip device and 42 % and 92 % for the guaiac faecal occult blood test, respectively. The highest positive predictive value was achieved with the immunological test strip device. CONCLUSIONS: The new immunological test strip device is more sensitive than a guaiac test for the detection of faecal occult blood, whereas the specificity of both tests was comparable. However, the clinical validity of this new immunological faecal occult blood test strip device for colorectal cancer screening has to be established, yet.

Colorectal Neoplasms↗
PubMed2002

Transient mismatch repair gene transfection for functional analysis of genetic hMLH1 and hMSH2 variants.

BACKGROUND: Germline mutations in the mismatch repair (MMR) genes hMLH1 and hMSH2 can cause hereditary non-polyposis colorectal cancer (HNPCC). However, the functional in vitro analysis of hMLH1 and hMSH2 mutations remains difficult. AIMS: To establish an in vitro method for the functional characterisation of hMLH1 and hMSH2 mutations. METHODS: hMLH1 and hMSH2 wild type (wt) genes and several mutated subclones were transiently transfected in mismatch repair deficient cell lines (HCT-116 and LOVO). Apoptosis, proliferation, and regulation of mRNA expression and protein expression of interacting proteins were analysed by Hoechst staining, AlamarBlue staining, real time polymerase chain reaction, and western blotting, respectively. RESULTS: The protein expression of hMLH1 and hMSH2 mutants was significantly decreased after transfection compared with wild type transfections. The hMLH1 and hMSH2 interacting proteins hPMS2 and hMSH6 became detectable only after transfection of the respective wild type genes. In parallel, hMSH6 mRNA levels were increased in hMSH2 wt transfected cells. However, hPMS2 mRNA levels were independent of the mutation status of its interacting partner hMLH1, indicating a post-transcriptional regulating pathway. In the hMLH1 deficient HCT-116 cell line apoptosis was not affected by transfection of any mismatch repair gene, whereas complementation of hMSH2 deficiency in LOVO cells increased apoptosis. Conversely, proliferative activity of HCT-116 was decreased by complementation with hMLH1wt and unaffected in hMSH2 deficient LOVO cells. CONCLUSION: These data show that the cellular role of the MMR genes and its mutations are assessable in a simple transient transfection system and show the influence of MMR gene regulation on major cell growth regulating mechanisms. This method is applicable for the functional definition of mutations in hMLH1 and hMSH2 genes observed in patients with suspected HNPCC.

Adaptor Proteins, Signal Transducing↗