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  • 1
    Keywords: CELLS ; EXPRESSION ; proliferation ; Germany ; human ; DISEASE ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; PATIENT ; MECHANISM ; prognosis ; ANTIGEN ; mechanisms ; FLOW ; treatment ; ALPHA ; PHENOTYPES ; PROGRESSION ; MALIGNANCIES ; gene expression ; resistance ; ARRAYS ; leukemia ; PHENOTYPE ; BEHAVIOR ; POOR-PROGNOSIS ; CD34(+) CELLS ; CHRONIC MYELOGENOUS LEUKEMIA ; HEMATOPOIETIC STEM-CELLS ; gene expression profiling ; expression profiling ; OLIGONUCLEOTIDE ARRAYS ; CYTOKINE ; MALIGNANCY ; data analysis ; IMATINIB MESYLATE ; PHASE ; REMISSION ; DISEASE PROGRESSION ; CML ; RESISTANT ; molecular signature ; EXPANSION ; blast crisis ; CAMPATH-1 ANTIGEN ; CD52
    Abstract: Despite recent success in the treatment of early-stage disease, blastic phase (BP) of chronic myeloid leukemia (CML) that is characterized by rapid expansion of therapy-refractory and differentiation-arrested blasts, remains a therapeutic challenge. The development of resistance upon continuous administration of imatinib mesylate is associated with poor prognosis pointing to the need for alternative therapeutic strategies and a better understanding of the molecular mechanisms underlying disease progression. To identify transcriptional signatures that may explain pathological characteristics and aggressive behavior of BP blasts, we performed comparative gene expression profiling on CD34+ Ph+ cells purified from patients with untreated newly diagnosed chronic phase CML (CP, n=11) and from patients in BP (n=9) using Affymetrix oligonucleotide arrays. Supervised microarray data analysis revealed 114 differentially expressed genes (P 〈 10(-4)), 34 genes displaying more than two-fold transcriptional changes when comparing CP and BP groups. While 24 of these genes were down-regulated, 10 genes, especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52), and four human leukocyte antigen-related genes were strongly overexpressed in BP. Expression of selected genes was validated by real-time-polymerase chain reaction and flow cytometry. Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy
    Type of Publication: Journal article published
    PubMed ID: 16617318
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  • 2
    ISSN: 1435-2451
    Keywords: Key words Rectal cancer ; Local relapse ; Multimodal therapy ; Adjuvant radiotherapy ; Adjuvant radiochemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. Method/Patients: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. Results: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II–III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11–18%, and survival rates significantly improved by 10–14%. Severe acute toxicities occurred in 50–61% of the patients, compromising compatibility, and caused death in 0–1%. Small-bowel obstruction leading to surgery was noted in 2–6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. Conclusion: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-2451
    Keywords: Key words Pancreatic cancer ; Adjuvant therapy ; Neoadjuvant therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. The controversies among those being pro and contra adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. Patients/Methods: The literature regarding the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. The biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities was focussed on, to characterise the disease for an optimally targeted treatment in conjunction with surgical removal of the tumour. The results of systemic and regional chemotherapy and radiotherapy, either alone or in combination, before, during and after surgery were critically analysed with respect to the oncological possibilities and pitfalls of each treatment method. Results: In two randomised trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy, the adjuvant treatment achieved a significant prolongation of the median survival time. The 5-year and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy , the survival times were improved compared with surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalising margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. Conclusions: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being indecisive or against adjuvant therapy, the participation in trials, e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested against surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-2451
    Keywords: Key words Colorectal liver metastasis ; Surgery ; Regional chemotherapy ; Hepatic artery infusion ; Review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Background: Cure is possible by resecting colorectal isolated liver metastases. In non-resectable isolated colorectal liver metastases (CRLM), regional chemotherapy has been advocated to optimize the disease control in the liver in order to improve the results of the alternative, systemic chemotherapy. The drugs are delivered by means of hepatic artery infusion (HAI) via ports or pumps; pharmacological modifications of the hepatic arterial blood-flow-like HAI with starch microspheres or stop-flow and perfusion techniques were applied to improve HAI. Methods: We reviewed the literature and report our progress, up to May 1999, in analyzing the validity of HAI for CRLM therapy. Results: In the majority of phase-II and -III trials, the response rates to HAI were significantly higher than those from systemic chemotherapy, and local disease control could be achieved even when HAI was used second line to systemic chemotherapy. The meta-analysis of randomized trials comparing HAI with either systemic chemotherapy (five trials) or, optionally, either 5-fluorouracil (FU) or symptomatic treatment (two trials) showed a significant advantage of HAI in response (41% vs 14%, P〈10–10) and median survival time (15 months vs 11 months, P〈0.0009). The active anabolite of 5-FU, 5-fluordeoxyuridine (5-FUDR), the drug of choice for HAI in those trials, may cause severe hepatotoxicity. To avoid this toxicity, we developed a HAI protocol using mitoxantrone, 5-FU plus folinic acid (FA) and mitomycin C (MFFM). The response rates of HAI with 5-FU plus FA or MFFM were 45% and 66%, the interim median survival times 19.8 months and 27.4 months. 5-Year survivors were observed in all our protocols. Since no severe hepatotoxicity occurred, 9 of 74 patients were resected after response to HAI with 5-FU plus FA or MFFM, without surgical mortality and with survival times from 2+ months to 58+ months. Conclusion: The high response rates, the long survival times, the possibility of achieving 5-year-survival either by HAI alone or by resection after down staging with HAI all sum up to the evidence that HAI could be the primary choice of treatment for CRLM. Phase-III trials are conducted to compare the protocols with optimal regional versus systemic chemotherapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: theophylline ; pregnancy ; pharmacokinetics ; lactation ; methylxanthines ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61±0.63 l/h and 2.85±1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05±0.49 l/h). Post-partum clearance values (2.16±2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p=0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound=29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00±2.31 h vs 9.53±3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 200 (1963), S. 161-163 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In the KellyNutting model2, the rapid increase in martensite strength (beyond that attributed to solution hardening) and incidence of twinning with increasing carbon content are considered to arise from the effect of carbon in depressing M8 from above to below a critical temperature range for ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Ultramicroscopy 32 (1990), S. 255-264 
    ISSN: 0304-3991
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Ultramicroscopy 45 (1992), S. 15-22 
    ISSN: 0304-3991
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Ultramicroscopy 46 (1992), S. 307-316 
    ISSN: 0304-3991
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0460
    Keywords: Fiberoptics ; Endoscope ; Aspiration ; Pharynx ; Swallowing, pharyngeal stage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new procedure for assessing the pharyngeal stage of swallowing in patients with dysphagia is described. Called the fiberoptic endoscopic examination of swallowing safety (FEESS), it is being used to detect aspiration and to determine the safety of oral feeding in patients for whom the traditional videofluoroscopic evaluation may be difficult or impossible to perform. Patients for whom the FEESS procedure is indicated are identified and information obtainable via endoscopy is outlined.
    Type of Medium: Electronic Resource
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