Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new radioreceptor assay for insulin-like growth factor-II (IGF-II), using receptors on ovine placental membranes, is described. Half-maximal displacement of specifically bound radioiodinated human IGF-II tracer was seen at 1.0 ng/tube of unlabelled IGF-II. The cross-reactivity of IGF-I was 1%, and insulin was entirely without effect. Measured on serum samples from 100 healthy adults, the mean IGF-II concentration (+/- SD) was 576 +/- 160 ng/ml. Identical mean values were seen for all adult age groups up to 65 years. The mean value for 10 acromegalic adults was 583 +/- 155 ng/ml, and for 9 GH-deficient subjects, 161 +/- 26 ng/ml (P less than 0.001 compared to normals). Of eight patients with chronic renal failure, none had an IGF-II level less than 2SD above the normal mean. No significant effect of renal dialysis was seen. In groups of patients with gastric, breast, lung, testicular, oat cell, ovarian, colonic and prostatic carcinoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, sarcoma and teratoma (5-12 patients per group), mean IGF-II levels were in the lower part of the normal range. Thus this study does not provide evidence supporting a role for excessive IGF-II production in the growth of any of these tumour types.
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PMID:Measurement of insulin-like growth factor-II by radioreceptor assay using ovine placental membranes. 301 20

To examine whether the concomitant administration of a gonadotrophin-releasing hormone agonist (GnRHa) during combination chemotherapy to young women with lymphoma may facilitate preservation of gonadal function, a prospective clinical protocol was undertaken in 18 cycling women with lymphoma, aged 15-40 years. Thirteen patients suffered from Hodgkin disease (HD) and 5 from non-Hodgkin lymphoma. After informed consent a monthly injection of depot D-TRP6-GnRHa was administered for a maximum of 6 months starting prior to chemotherapy. Most of these patients (15/18) were treated with the MOPP/ABV(D) combination chemotherapy followed by mantle field irradiation in 10 patients. Hormonal profile [luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol, testosterone, progesterone, insulin-like growth factor (IGF)-1, prolactin] was taken before the GnRHa/chemotherapy co-treatment, and monthly thereafter until resuming spontaneous ovulation and menses. This group of prospectively treated lymphoma patients was compared to a matched control group of 18 women (aged 17-40 years) who have been treated with chemotherapy, mostly MOPP/ABV (14/18), with (11) or without (7) mantle field radiotherapy. Fourteen had Hodgkin's and four non-Hodgkin's lymphoma. Gonadal function was determined clinically, hormonally (LH, FSH, oestradiol, progesterone), and sonographically. Two of the patients in each group died from refractory disease. Of the remaining 16 patients, 15 (93.7%) resumed spontaneous ovulation and menses within 3-8 months of termination of the combined chemotherapy/GnRHa co-treatment. In contrast, only seven (39%) of the 18 similarly treated patients in the control group (chemotherapy without GnRHa) resumed ovarian cyclic activity (regular menses). The other 11 experienced premature ovarian failure (POF) (61%). Out preliminary data suggest a possible significant protective effect of GnRHa co-treatment with chemotherapy from irreversible ovarian damage (POF).
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PMID:Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. 892 Nov 4

The effects of growth hormone are mediated in part by stimulating the production of insulin-like growth factor-1. Insulin-like growth factor-1 has significant effects on cell proliferation and differentiation, it is a potent mitogen, and it is a powerful inhibitor of programmed cell death (apoptosis). Insulin-like growth factor-1 also has a well-established role in the transformation of normal cells to malignant cells. Case reports on a possible association between elevated growth hormone and cancer risk in a variety of patient groups have been published. Here, we describe clinical and laboratory findings for a patient with acromegaly who first developed thyroid cancer, and then, in the follow up period, probably due to poorly controlled insulin-like growth factor-1 levels, developed a large cell non-Hodgkin's lymphoma. A search revealed that a case with these peculiarities had not previously been reported.
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PMID:Insulin-like growth factor-1 is essential to the increased mortality caused by excess growth hormone: a case of thyroid cancer and non-Hodgkin's lymphoma in a patient with pituitary acromegaly. 1866 12

ALK (anaplastic lymphoma kinase) is an RTK (receptor tyrosine kinase) of the IRK (insulin receptor kinase) superfamily, which share an YXXXYY autophosphorylation motif within their A-loops (activation loops). A common activation and regulatory mechanism is believed to exist for members of this superfamily typified by IRK and IGF1RK (insulin-like growth factor receptor kinase-1). Chromosomal translocations involving ALK were first identified in anaplastic large-cell lymphoma, a subtype of non-Hodgkin's lymphoma, where aberrant fusion of the ALK kinase domain with the NPM (nucleophosmin) dimerization domain results in autophosphosphorylation and ligand-independent activation. Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, which play a major role in neuroblastoma, were recently identified. To provide a structural framework for understanding these mutations and to guide structure-assisted drug discovery efforts, the X-ray crystal structure of the unphosphorylated ALK catalytic domain was determined in the apo, ADP- and staurosporine-bound forms. The structures reveal a partially inactive protein kinase conformation distinct from, and lacking, many of the negative regulatory features observed in inactive IGF1RK/IRK structures in their unphosphorylated forms. The A-loop adopts an inhibitory pose where a short proximal A-loop helix (alphaAL) packs against the alphaC helix and a novel N-terminal beta-turn motif, whereas the distal portion obstructs part of the predicted peptide-binding region. The structure helps explain the reported unique peptide substrate specificity and the importance of phosphorylation of the first A-loop Tyr1278 for kinase activity and NPM-ALK transforming potential. A single amino acid difference in the ALK substrate peptide binding P-1 site (where the P-site is the phosphoacceptor site) was identified that, in conjunction with A-loop sequence variation including the RAS (Arg-Ala-Ser)-motif, rationalizes the difference in the A-loop tyrosine autophosphorylation preference between ALK and IGF1RK/IRK. Enzymatic analysis of recombinant R1275Q and F1174L ALK mutant catalytic domains confirms the enhanced activity and transforming potential of these mutants. The transforming ability of the full-length ALK mutants in soft agar colony growth assays corroborates these findings. The availability of a three-dimensional structure for ALK will facilitate future structure-function and rational drug design efforts targeting this receptor tyrosine kinase.
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PMID:Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain. 2063 93