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  • 1
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cryostat sections of 73 invasive breast carcinomas were immunostained with a rabbit polyclonal antibody to phosphoinositide-specific phospholipase C-γ (PLC-γ), an enzyme that mediates signal transduction in tyrosine kinase growth-factor pathways. Degree of immunoreactivity was then correlated with clinicopathologic data (stage, ER status, recurrence) and immunostaining for tyrosine kinase growth-factor receptors (EGFR, ERBB-2) as well as selected “invasion-associated” proteases (cathepsin D, urokinase plasminogen activator, matrix metalloproteinases 2 and 9 [MMP-2, MMP-9]). Neoplastic epithelial populations were PLC-γ immunoreactive in 95% of tumors although staining was focally distributed (in 〈50% of cells) in 51% of positive cases. Forty-four percent also exhibited immunostaining of peritumoral, spindle-shaped cells (i.e., fibroblasts, endothelium, inflammatory cells). The degree of PLC-γ immunoreactivity in neoplastic epithelium was not significantly correlated with clinicopathologic features, growth factor receptor overexpression, or protease immunostaining. Stromal cell PLC-γ staining, however, was significantly associated with stromal cell immunoreactivity for cathepsin D (p = 0.03), urokinase plasminogen activator (p = 0.01), and MMP-2 (p = 0.04). Disease recurrences were also more frequent in tumors with stroma/spindle cell PLC-γ immunoreactivity (66% vs. 41%, p = 0.04). We conclude that PLC-γ immunostaining, compatible with increased tyrosine kinase pathway signaling activity, is observed not only in a high proportion of neoplastic breast epithelial populations but also in accompanying stromal cell populations in a significant number of cases. Concordance with protease immunoreactivity among peritumoral stromal cells suggests that tyrosine kinase signaling may participate in protease elaboration in vivo, possibly conferring aggressive clinical behavior.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: breast carcinoma ; EGF receptor ; immunoperoxidase ; oncogenes ; tumor suppressor genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative - 59% none positive, 29% one positive, 12% two or more positive, vs. node positive - 37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positve for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1436-0691
    Keywords: Key words: pancreatic cancer ; survival ; adjuvant therapy ; chemotherapy ; radiation ; gene therapy ; K-ras ; p53 ; p21WAF-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Multiple genetic alterations, several of which may be important prognostic markers, characterize the development of cancer in pancreas. We review our findings from previously published studies with regard to molecular alterations associated with survival differences in patients treated with conventional radiation and chemotherapies used as adjuvant or palliative therapy. K-ras-negative patients with pancreas cancer show improved survival with radiation therapy compared to K-ras-positive patients with pancreas cancer. p53 expression is associated with shorter survival when compared to no p53 expression in pancreas cancer patients treated with radiation therapy or chemotherapy. Pancreas cancer patients whose tumors express p21 show significant survival advantages when treated with chemotherapy or radiation therapy. An inverse relationship is observed with respect to p21 and p53 expression and clinical stage. Although stage and surgical resectability remain the most important variables with respect to pancreas cancer survival, these findings suggest promising opportunities for gene therapies designed to enhance p21 expression or restore wild-type K-ras or p53 function in pancreatic tumors.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7217
    Keywords: breast cancer ; galectin-3 ; Line 1 retrotransposon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Galectin-3 is a galactoside binding protein found at elevated levels in a wide variety of neoplastic cells and thought to be involved in cognitive cellular interactions during transformation and metastasis. Previously, we have shown that introduction of human galectin-3 (Mr 31,000) cDNA into the human breast cancer cells BT-549 which are galectin-3 null and non-tumorigenic in nude mice resulted in the establishment of four galectin-3 expressing clones. Three of them acquired tumorigenicity when inoculated in the mammary fat pad of nude mice. Here, we questioned what is the molecular difference between the nude mouse tumorigenic and non-tumorigenic galectin-3 expressing BT-549 cell clones. Differential display analysis and Northern blotting revealed that, unlike the tumorigenic clones, neither the parental cells nor the non-tumorigenic clone expressed a 6.5 Kb transcript. A 607 bp PCR (polymerase chain reaction) product from the differentially displayed mRNA revealed a 93% sequence homology with the human L1 retrotransposon previously suggested to play a role in the pathobiology of some breast cancers. In addition, we show that the two gene products, i.e., galectin-3 and L1, are co-expressed in breast carcinoma specimens and in other nude mouse tumorigenic cell lines.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of muscle research and cell motility 17 (1996), S. 313-334 
    ISSN: 1573-2657
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The myofibrils of adult rat cardiac muscle cells in long-term culture initially break down and later reassemble into mature myofibrils. The objective of this study is to examine the disorganization process of myofibrils and to determine how disorganized myofibrillar proteins, myosin, titin, actin, and α-actinin are reorganized into mature myofibrils in adult cells. Atter dismantlement of myofibrils during initial culture period (24–72 h), myofibrillar proteins became disorganized into amorphous form. These proteins later were observed in vesicular, amorphous, and nonstriated fibrillar forms. Some vesicular structures, containing mainly myosin, titin, α-actin, and α-actinin were observed on the outer surfaces of the cell and outside the cell body. Such vesicles containing F-actin were rare. Punctate structures of α-actinin emerged from the pre-existing amorphous α-actinin along with the appearance of mostly titin periodicities. The periodicities of α-actinin later became prevalent, followed by the appearance of periodicities of actin. α-actinin provided an initiation point on which titin and actin became associated, forming titin-associated I-Z-I structures. Titin traversed the I-bands on either side of the Z-line. The phalloidin-stained I-Z-I structures bound to antibodies to muscle specific sarcomeric proteins (titin, α-actin, α-actinin). The differentiation of myosin periodicities lagged behind those of titin, α-actinin, and actin although presarcomeric structures of immunolabelled titin and myosin were very closely linked in their distributions in the formative myofibrils. Variations in the temporal sequence of emergence of periodicities of α-actinin and myosin were observed among certain myocytes. Also observed was the variation of the temporal sequence of emergence of titin and actin periodicities among different myocytes and within a single myocyte. Even in the late stage of culture (30 days), when the cell body was packed with myofibrils, the myocytes contained remnants of amorphous myofibrillar proteins.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 192-198 
    ISSN: 0730-2312
    Keywords: Proliferation ; differentiation ; oncogene ; growth factors ; upper aerodigestive tract ; biomarkers ; premalignant ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The normal distribution of cell division in squamous mucosa is in the basal or adjacent suprabasal cell layers. Migration of cells toward the epithelial surface results in cell differentiation, most often expressed by high molecular weight keratin intermediate filaments and components of the cornified envelope, including “involucrin.” These latter expressions of terminal differentiation are common in keratinizing dysplasia and invasive squamous cell carcinomas. However, they are less common in the non-keratinizing dysplasias, which fail to express evidence of epithelial maturation. Cell proliferation occurs in or near the basal layer in normal or reactive/reversible hyperplasias. In dysplasia (both keratinizing and non-keratinizing), cell proliferation is observed at all levels of the epithelium. Concomitant with these abnormalities in proliferation and differentiation are nuclear changes characterized by large hyperchromatic nuclei. The enlarged nuclei reflect increased DNA content, as documented by flow cytometry and image analysis techniques. DNA aneuploidy represents a spectrum of genomic alterations reflecting steps toward the progression to invasive carcinoma, which for the most part, have not yet been identified.
    Type of Medium: Electronic Resource
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