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  • 1990-1994  (6)
  • 1950-1954
  • 1945-1949
  • Insulin-like growth factor-1  (3)
  • Melanoma  (3)
  • 1
    ISSN: 1432-0851
    Keywords: TIL ; Melanoma ; Histopathology ; Imaging ; Lymphocytic infiltrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor-infiltrating lymphocytes (TIL) from a wide range of human and murine tumors can be expanded in vitro using interleukin-2 (IL-2). These TIL are cytolytic T lymphocytes with in vivo and in vitro antitumor activity in mice and in humans. TIL from human melanoma can recognize autologous tumor in an MHC-restricted fashion, localize in vivo after111In labeling, and mediate regression of large metastatic deposits. Although studied extensively in vitro, less is known in vivo about TIL activity associated with tumor regression. This study was undertaken, in association with a study of TIL localization, to investigate mechanisms of TIL action by evaluating histopathological changes that occur at the tumor site during TIL administration. A total of 106 pre- and post-treatment pathological specimens from 25 patients enrolled in phase II TIL treatment and111In-TIL imaging protocols were examined blindly by a single pathologist. Histological subtype, lymphocytic infiltration, melanin content, vascularity, and necrosis were documented for each tumor specimen. Average baseline and post-treatment parameters were compared. Any significant changes were evaluated for correlation with clinical response and111In-TIL localization to tumor. Melanin content and vascularity of the tumor did not change as a result of therapy or correlate with either response or TIL localization. However, both increased lymphocytic infiltration and tumor necrosis were present after TIL administration (P=0.044 and 0.032 respectively). Furthermore, increases in lymphocytic infiltration correlated with tumor imaging using111In-TIL, and with the percentage of111In-labeled injectate present per gram of tumor specimen (P=0.036 and 0.0041 respectively). This suggests that TIL either account for the increased lymphocytes directly, or localize to tumor and recruit endogenous lymphocytes. We were unable to demonstrate any pretreatment histopathological predictors of response or variables that significantly correlated with subsequent clinical response, although peak and average values of necrosis were higher in responding patients compared to non-responding patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0851
    Keywords: Melanoma ; Neural crest ; Ewing's sarcoma ; Tumor-infiltrating lymphocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Melanomas from different patients have been shown to express shared tumor antigens, which can be recognized in the context of the appropriate MHC class 1 molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens are expressed on other tumors of neuroectodermal origin, four melanoma-specific cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes (TIL) were tested for lysis of a panel of 23 HLA-A2+ neuroectodermal tumor cell lines of various histologies, including retinoblastoma (1), neuroblastoma (8), neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5). Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23 neuroectodermal tumor lines, and could be enhanced by treatment with interferon γ (IFNγ). Following IFNγ treatment, three Ewing's sarcoma lines were lysed by at least one melanoma TIL culture, and levels of lysis were comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal antibodies directed against MHC class I molecules and against CD3, indicating specific immune recognition of tumor-associated antigens. None of the other neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non-MHC-restricted lymphokine-activated killer cells. This demonstration of immunological cross-reactivity between melanomas and Ewing's sarcomas, two tumors of distinct histological types with a common embryonic origin, has implications for the developmental nature of these CTL-defined tumor antigens. It also raises the possibility that specific antitumor immunotherapies, such as vaccines, may be reactive against more than one form of cancer.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0851
    Keywords: Melanoma ; MAGE-1 ; Tumor-infiltrating lymphocytes ; Immunotherapy ; Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a patient with melanoma. We have produced a MAGE-1-specific CTL line derived from the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1-restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277. A TIL line grew in long-term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen-specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-1+ cell lines. Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY was superior to that of cells pulsed with the immunodominant nonapeptide. Single amino-acid or even side-chain substitutions in the immunodominant nonamer abrogated cytolysis. 1277. A TIL specifically secreted tumor necrosis factor α after co-incubation with HLA-A1-expressing MAGE-1+ cell lines or fresh tumor. These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown from TIL in the presence of synthetic epitope peptides and expanded for adoptive immunotherapy in melanoma patients.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 6 (1992), S. 394-398 
    ISSN: 1432-198X
    Keywords: Growth hormone ; Insulin-like growth factor-1 ; Glomerular filtration rate ; Renal plasma flow ; Renal hypertrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Growth hormone (GH) affects renal function and kidney growth. Pituitary-derived or recombinant human GH (rhGH), acting via insulin-like growth factor-1 (IGF-1), increases glomerular filtration rate (GFR) and renal plasma flow (RPF) in GH-deficient as well as in normal adults. Furthermore, GFR and RPF are low in hypopituitarism and elevated in acromegaly. These effects of GH on GFR and RPF have not been demonstrated in moderate renal insufficiency. IGF-1 is implicated in compensatory renal hypertrophy. Markedly elevated levels of serum GH accelerate glomerular sclerosis in rodents, although the significance of these findings for GH treatment in humans is uncertain. rhGH therapy offers great promise to children with short stature from various aetiologies. Preliminary report on the use of rhGH in children with renal disease and after renal transplantation have not shown any consistent change in kidney function, although follow-up times are short. The long-term impact of rhGH therapy on kidney function in short children needs further evaluation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 6 (1992), S. 483-489 
    ISSN: 1432-198X
    Keywords: Growth hormone ; Insulin-like growth factor-1 ; Calcium homeostasis ; Body composition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Growth hormone (GH), either directly or through insulin-like growth factor-1 (IGF-1), has a wide spectrum of physiological and renal effects. This review concentrates on the effects of GH (derived from either pituitary or recombinant technology) and IGF-1 in three main areas: (1) sodium and water homeostasis; (2) calcium and phosphate balance, bone density and interactions with mineral regulating hormones; (3) fat and lean body mass. Observations of physiological changes in states of GH deficiency and excess in humans and animal models are presented. The lack of long-term toxicological data indicates that GH treatment for short stature in non-GH deficient children, with or without renal disease, should proceed with caution.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-198X
    Keywords: Insulin-like growth factor-1 ; Insulin-like growth factor-binding protein-3 ; Chronic renal failure ; Growth retardation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-like growth factor-binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) levels were measured by specific radioimmunoassays in children with all degrees of chronic renal failure (CRF). Study group 1 comprised 29 children (10 on dialysis) who had been studied one to four times over 2 years to determine whether IGF-1 and IGFBP-3 levels differed from those in age-matched healthy children and to examine the relationship between these levels and heights. IGF-1 and IGFBP-3 levels did not differ from those in normal children. IGF-1 and IGFBP-3 were significantly correlated, increased with pubertal stage in all children and with age in non-dialysis patients. IGF-1, but not IGFBP-3, correlated with age in dialysis patients. There was no correlation between IGF-1 or IGFBP-3 levels (corrected for age) and height standard deviation score (SDS) in either non-dialysis or dialysis patients. Study group 2 comprised 19 children (7 on dialysis) who were studied prospectively for 1–2 years to examine the relationship between IGF-1 and IGFBP-3 levels, growth rates and nutritional parameters. Mean values of IGF-1 and IGFBP-3 (corrected for age) did not change over 1-year periods, while height SDS fell by −0.38 ±0.21 SD/year in dialysis patients and by −0.11 ±0.29 SD/year in non-dialysis patients. No significant correlations were found between IGF-1 or IGFBP-3 levels and growth rates or nutritional parameters. Thus growth retardation in children with CRF is not related to circulating levels of IGF-1 or IGFBP-3.
    Type of Medium: Electronic Resource
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