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  • Springer  (221)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (47)
  • American Physical Society (APS)  (29)
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  • 1
    Electronic Resource
    Electronic Resource
    Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma (1999)
    Springer
    Annals of oncology 10 (1999), S. 235-237 
    Details
    ISSN: 1569-8041
    Keywords: carboplatin ; metastatic nasopharyngeal carcinoma ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients. Patients and methods: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naïve patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible. Results: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3–4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive. Conclusions: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390929826
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  • 2
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    Wnt-induced Phosphorylation Sites in Dvl2 Regulate Signaling [Cell Biology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-03-30
    Description: Dishevelled (Dvl) proteins are intracellular effectors of Wnt signaling that have essential roles in both canonical and noncanonical Wnt pathways. It has long been known that Wnts stimulate Dvl phosphorylation, but relatively little is known about its functional significance. We have previously reported that both Wnt3a and Wnt5a induce Dvl2 phosphorylation that is associated with an electrophoretic mobility shift and loss of recognition by monoclonal antibody 10B5. In the present study, we mapped the 10B5 epitope to a 16-amino acid segment of human Dvl2 (residues 594–609) that contains four Ser/Thr residues. Alanine substitution of these residues (P4m) eliminated the mobility shift induced by either Wnt3a or Wnt5a. The Dvl2 P4m mutant showed a modest increase in canonical Wnt/β-catenin signaling activity relative to wild type. Consistent with this finding, Dvl2 4Pm preferentially localized to cytoplasmic puncta. In contrast to wild-type Dvl2, however, the P4m mutant was unable to rescue Wnt3a-dependent neurite outgrowth in TC-32 cells following suppression of endogenous Dvl2/3. Earlier work has implicated casein kinase 1δ/ϵ as responsible for the Dvl mobility shift, and a CK1δ in vitro kinase assay confirmed that Ser594, Thr595, and Ser597 of Dvl2 are CK1 targets. Alanine substitution of these three residues was sufficient to abrogate the Wnt-dependent mobility shift. Thus, we have identified a cluster of Ser/Thr residues in the C-terminal domain of Dvl2 that are Wnt-induced phosphorylation (WIP) sites. Our results indicate that phosphorylation at the WIP sites reduces Dvl accumulation in puncta and attenuates β-catenin signaling, whereas it enables noncanonical signaling that is required for neurite outgrowth.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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    PAPER CURRENT
  • 3
    Electronic Resource
    Electronic Resource
    Six-Year Follow-Up of Patients With Microinvasive, T1a, and T1b Breast Carcinoma (1999)
    Springer
    Annals of surgical oncology 6 (1999), S. 591-598 
    Details
    ISSN: 1534-4681
    Keywords: Early breast cancer ; Minimal breast cancer ; Microinvasive breast cancer ; Axillary lymph node metastases ; Axillary dissection ; Regional metastases ; Prognosis disease-free survival ; Sentinel node biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Management of patients with breast cancers ≤1 cm remains controversial. Reports of infrequent nodal metastases in tumors ≤5 mm has led to suggestions that axillary dissection should be selective, and that tumor characteristics should guide adjuvant therapy. Methods: A retrospective review of 290 patients with breast cancer 1 cm in size or smaller from 1989 to 1991 was done. Distant disease-free survival (DDFS) was the primary outcome measure. Results: There were 95 T1a (≤5 mm) and 196 T1b (6–10 mm) cancers. Nodal metastases were found in 8 T1a and 26 T1b tumors. Larger size, poorer differentiation, and lymphovascular invasion (LVI) were associated with more nodal metastases, but none of these trends reached statistical significance. The 6-year DDFS was 93% for node-negative and 87% for node-positive patients (P = .02). Overall, breast cancers with poorer differentiation and LVI trended toward a poorer outcome. For patients with node-negative tumors, LVI was associated with a poorer outcome (P = .03). The size of the primary tumor was not predictive of outcome. There were no nodal metastases or recurrences in the 18 patients with microinvasive breast cancer. Conclusions: Lymph node status is the major determinant of outcome in breast cancers 1 cm in size or smaller. Accurate axillary assessment remains crucial in management of small breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s10434-999-0591-5
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  • 4
    Electronic Resource
    Electronic Resource
    Is Routine Intraoperative Frozen-Section Examination of Sentinel Lymph Nodes in Breast Cancer Worthwhile? (2000)
    Springer
    Annals of surgical oncology 7 (2000), S. 651-655 
    Details
    ISSN: 1534-4681
    Keywords: Sentinel lymph nodes ; Frozen section ; Macrometastases ; Micrometastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Routine intraoperative frozen section (FS) of sentinel lymph nodes (SLN) can detect metastatic disease, allowing immediate axillary dissection and avoiding the need for reoperation. Routine FS is also costly, increases operative time, and is subject to false-negative results. We examined the benefit of routine intraoperative FS among the first 1000 patients at Memorial Sloan Kettering Cancer Center who had SLN biopsy for breast cancer. Methods: We performed SLN biopsy with intraoperative FS in 890 consecutive breast cancer patients, none of whom had a back-up axillary dissection planned in advance. Serial sections and immunohistochemical staining for cytokeratins were performed on all SLN that proved negative on FS. The sensitivity of FS was determined as a function of (1) tumor size and (2) volume of metastatic disease in the SLN, and the benefit of FS was defined as the avoidance of a reoperative axillary dissection. Results: The sensitivity of FS ranged from 40% for patients with T1a to 76% for patients with T2 cancers. The volume of SLN metastasis was highly correlated with tumor size, and FS was far more effective in detecting macrometastatic disease (sensitivity 92%) than micrometastases (sensitivity 17%). The benefit of FS in avoiding reoperative axillary dissection ranged from 4% for T1a (6 of 143) to 38% for T2 (45 of 119) cancers. Conclusions: In breast cancer patients having SLN biopsy, the failure of routine intraoperative FS is largely the failure to detect micrometastatic disease. The benefit of routine intraoperative FS increases with tumor size. Routine FS may not be indicated in patients with the smallest invasive cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s10434-000-0651-3
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  • 5
    Electronic Resource
    Electronic Resource
    Sentinel Lymph Node Biopsy: Is It Indicated in Patients With High-Risk Ductal Carcinoma-In-Situ and Ductal Carcinoma-In-Situ With Microinvasion? (2000)
    Springer
    Annals of surgical oncology 7 (2000), S. 636-642 
    Details
    ISSN: 1534-4681
    Keywords: Breast carcinoma ; Ductal carcinoma-in-situ ; Microinvasion ; Sentinel lymph node biopsy ; Intraductal carcinoma ; Micrometastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM). Methods: From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry. Results: Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes; 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis. Conclusions: This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s10434-000-0636-2
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  • 6
    Electronic Resource
    Electronic Resource
    Absence of p16 gene (CDKN2) deletions in microdissected primary breast carcinoma specimens (1997)
    Springer
    Annals of surgical oncology 4 (1997), S. 416-420 
    Details
    ISSN: 1534-4681
    Keywords: p16 ; (CDKN2) ; MTS1 ; Breast carcinoma ; Microdissection ; Genetic alterations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The p16 gene (CDKN2), a tumor suppressor gene located on chromosome 9p21, has been demonstrated to be mutated or deleted with high frequency in a variety of tumor cell lines, including breast. While previous studies have not demonstratedCDKN2 mutations in primary breast carcinomas, it is possible that gene deletion in neoplastic DNA was masked by the presence of contaminating normal stromal DNA in breast carcinoma specimens. Methods: We investigated the incidence of homozygous deletion ofCDKN2 by analyzing 20 microdissected pure populations of primary breast carcinoma cells. Using polymerase chain reaction (PCR) techniques, the entire coding region and intervening introns ofCDKN2 were amplified. The PCR products were resolved by agarose gel electrophoresis and single-strand conformation polymorphism (SSCP) analysis. Results: We detected no deletions or mutations of the p16 gene. Conclusions: CDKN2 is not deleted with high frequency in primary breast carcinomas, and the p16 gene does not play a role in breast carcinogenesis via this mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02305555
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  • 7
    Electronic Resource
    Electronic Resource
    Incidence of axillary lymph node metastases in T1a and T1b breast carcinoma (1998)
    Springer
    Annals of surgical oncology 5 (1998), S. 23-27 
    Details
    ISSN: 1534-4681
    Keywords: Early breast cancer ; Axillary lymph node metastases ; Axillary dissection ; Regional metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We investigated the incidence of axillary lymph node metastases in patients with T1a (⩽0.5 cm) and T1b (〉0.5 cm and ⩽1.0 cm) breast cancers. Methods: The charts of 2000 patients who underwent axillary lymph node dissection for breast cancer at our institution from 1989 to 1991 were reviewed. Of these, 81 patients had T1a and 166 had T1b primary breast cancers. Results: Among the 247 patients with T1a and T1b breast cancers, nodal metastases were present in 30 (12.1%), with a 7.4% positivity rate for patients with T1a and 14.5% positivity rate for T1b tumors. Of the 212 patients who had ⩾10 nodes dissected, 29 (13.7%) had positive nodes. Of those, 6 of 60 (10.0%) patients with T1a and 23 of 152 (15.1%) with T1b tumors had positive nodes. The presence of lymphovascular invasion (LVI) predicted a significantly higher nodal positivity rate (27.8% vs. 10.9%,p=0.05). Conclusions: Of patients with adequately evaluated axillae, 10% with T1a and 15% with T1b cancers were found to have nodal metastases. Although LVI was significantly associated with a higher risk of lymph node metastases, we could not characterize any subgroup at acceptably low risk of nodal positivity. Until a more useful prognostic indicator is discovered, axillary dissection should continue to be part of the mainstay of management for small breast cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02303759
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  • 8
    Electronic Resource
    Electronic Resource
    Toluene degradation pathway from Pseudomonas putida F1: substrate specificity and gene induction by 1-substituted benzenes (2000)
    Springer
    Journal of industrial microbiology and biotechnology 25 (2000), S. 163-170 
    Details
    ISSN: 1476-5535
    Keywords: Keywords: tod pathway; monoalkylbenzenes; toluene dioxygenase; cometabolism; Pseudomonas putida F1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The metabolism of n-alkylbenzenes (C3–C7), biphenyl, styrene and cumene by the tod pathway from Pseudomonas putida F1 was examined in terms of catabolism by the pathway enzymes and the inducibility of the tod operon. F1 cells grown on toluene exhibited oxygen consumption in the presence of the compounds examined. Toluene dioxygenase (TDO) catalyzed the formation of monol, cis-dihydrodiol and triol metabolites from the n-alkylbenzenes tested and the triol formed from n-propylbenzene was metabolized to the derivative, 2-hydroxy-6-oxohexa-2,4-dienoate (HOHD), by subsequent enzymes in the tod pathway. Biotransformation of the tested compounds with toluene-grown F1 cells resulted in the accumulation of ring cleavage HOHD derivatives; the metabolites were inefficiently metabolized by cell extracts of toluene-grown F1 cells, indicating that 6-methyl-HOHD hydrolase encoded by todF might be a determinant for the further degradation of the selected 1-substituted benzenes. The results obtained from enzyme activity assays and reverse transcription polymerase chain reaction (RT-PCR) showed that not only growth-supporting substrates, but also n-propylbenzene, styrene and cumene act as inducers of the tod operon. Journal of Industrial Microbiology & Biotechnology (2000) 25, 163–170.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/sj.jim.7000048
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  • 9
    Electronic Resource
    Electronic Resource
    Multiscale adaptive estimation of the conductivity field from head and tracer data (1993)
    Springer
    Stochastic environmental research and risk assessment 7 (1993), S. 66-82 
    Details
    ISSN: 1436-3259
    Keywords: Parameter identification ; multiscale ; transport ; adaptive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying , Energy, Environment Protection, Nuclear Power Engineering , Geography , Geosciences
    Notes: Abstract Large scale fluctuations in the conductivity field are regionalized and estimated via a maximum likelihood, adjoint-state methodology. Small-scale fluctuations within each region are estimated adaptively via a Kalman-like stochastic filter. The variance and integral scale within each region are assumed to control the small-scale fluctuations. A Monte Carlo technique is used to examine the distribution of large-scale conductivity estimates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01581567
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  • 10
    Electronic Resource
    Electronic Resource
    73. Erfahrungen bei der orthotopen Xenotransplantation der Hundeleber auf das Schwein (1971)
    Springer
    Langenbeck's archives of surgery 329 (1971), S. 222-223 
    Details
    ISSN: 1435-2451
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurde bei 11 Schweinen eine orthotope Xenotransplantation der Hundeleber durchgeführt. Die Überlebensdauer war durchschnittlich 4,3 ± 1,5 Std. Die Todesursachen waren generalisierte Blutungen. Um die hyperakute Abstoßungsreaktion zu bremsen, wurden vor der Verpflanzung der Hundeleber bei 5 Fällen Hundeniere und Hundemilz je 20 min und bei 5 anderen Fällen eine zweite Hundeleber am Femoralkreislauf eingeschaltet. Wegen der stark aufgetretenen Kreislaufreaktion (Tachykardie und Hypotonie) war die Überlebensdauer noch kürzer. Aus gleichen Gründen wurden hohe Dosen Prednisolon intraund postoperativ bei 5 Fällen verabreicht. Die Überlebensdauer von 4 Schweinen war 9,0 :L 2,2 Std. Ein Schwein überlebte 5 Tage. Bei diesem Schwein wurde Hundeproteinsynthese beobachtet.
    Notes: Summary Orthotopic xeno-transplantations of dog livers into 11 pigs were carried out. The survival time was on average 4.3 ± 1.5 h. The cause of death was generalized haemorrhage. To inhibit the hyperacute rejection, before trans-planting the dog liver we connected dog kidneys and dog spleens in 5 cases and in another 5 cases a second dog liver to the femoral circulation, 20 min, before the transplant, in each case. In view of the very strong circulatory reaction (tachycardia and hypotension) the survival time was even shorter. For the same reason high doses of prednisolone were administered intra- and postoperatively in 5 cases. The survival time of 4 pigs was 9.0 ± 2.2 h. One pig survived for 5 days, and in this animal we were able to observe dog-protein synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01770490
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