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  • 1
    ISSN: 1432-1335
    Keywords: Pseudomonas exotoxin ; TGFα ; Rat bladder carcinoma ; Human bladder carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A protein formed by fusion of transforming growth factor α withPseudomonas exotoxin (TGFα-PE40) has been shown to have the ability to kill or inhibit the growth of several carcinoma cell lines. This study was designed to evaluate thein vitro cytotoxic effects of TGFα-PE40 on rat and human bladder carcinoma cell lines with different biological potential, and normal rat urothelial cells. The rat cell lines used were D44c, LMC19, and MYU3L, which were established in our laboratory. Human cell lines used were RT4, T24, and 253J. As a normal control, we used the first-passage culture of normal rat bladder urothelium (RU-P1). We examined the number and affinity of epidermal growth factor receptors (EGFR) in these cells, the ability of TGFα-PE40 to bind EGFR, and the cytotoxic effect of TGFα-PE40 and PE40. Rat cell lines, D44c, LMC19, and MYU3L (EGFR=4.9×103–11.4×103/cell) had ED50 values (the concentration of TGFα-PE40 needed to reduce the viable cell population by 50%) of 180 pM, 540 pM and 6000 pM respectively; forc 1 (the concentration required to achieve complete inhibition of growth under continuous serum stimulation) TGFα-PE40 concentrations of 104 pM, 104 pM and higher than 104 pM respectively were required. Human cell lines, RT4, T24, and 253J (EGFR=32×103–126×103/cell) had ED50 values of 20 pM, 66 pM, and 330 pM respectively and T24 showedc 1 values of 103 pM. RU-P1 (EGFR =92.6×103/cell) had the highest ED50 value of 8000 pM. These data indicate that the susceptibility to TGFα-PE40 does not always depend on the number of EGFR, that cells having a relatively small number of EGFR respond well to TGFα-PE40, and that normal urothelial cells are more resistant to TGFα-PE40 than are cancer cells. The differential effect of TGFα-PE40 on normal and neoplastic cells provides a rational basis for its use in vivo to control tumor growth.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The three major salivary glands of normal male and female Fischer 344 rats of different ages were examined for the localization of epidermal growth factor (EGF) and transforming growth factor α (TGFα) by immunohistochemical staining. EGF was demonstrated only in the granulated convoluted tubule (GCT) cells of the submandibular gland, the results confirming the previous reports, and most abundantly in adult males and pregnant females. TGFα stain was localized in all three glands and was found throughout the entire duct system, excluding acinar cells. The myoepithelial cells of the sublingual gland were also reactive with the TGFα antibody. The specificity of the staining was confirmed by negative staining reaction with the absorbed antibody and by radio-immunoassay and Western blot methods. This is the first report describing the presence of TGFα in the rat salivary glands.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2021-01-15
    Description: SummaryA retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients treated at the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine. OSCC patients with major risk (n = 88) in the follow-up period were divided into groups with no postsurgical treatment (NP group), with standard postsurgical treatment (SP group), and with postsurgical treatment including cetuximab (CP group), and prognosis were compared among those groups. The 5-year overall survival rate was significantly higher in patients who received postsurgical treatment with cetuximab (CP) compared to that in the other two groups ((CP vs. NP, p = 0.028; CP vs. SP, p = 0.042). Furthermore, we performed multivariate analysis to evaluate the effects of the main components of the treatment. Among CDDP, radiotherapy, and cetuximab, only cetuximab significantly contributed to improved survival by univariate analysis (crude HR:0.228, 95%CI:0.05–0.968, p = 0.045). cetuximab also showed the same tendency in multivariate analysis, although p value did not reach significant level (Adjusted HR: 0.233, 95%CI: 0.053–1.028, p = 0.054). The results suggest that the postsurgical treatment with cetuximab as a preemptive postsurgical therapy after complete surgical resection of a visible tumor is considerably effective for OSCC patients with major risk, in other words, invisible dormant metastasis.
    Print ISSN: 0167-6997
    Electronic ISSN: 1573-0646
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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