Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergoline (5a), have been prepared. In addition, nitroso (7) and chloroethylcarbamyl (8) derivatives of elymoclavine (6) are reported. Compounds 5a and 5c have activity against L1210 leukemia in mice but only moderate prolactin-inhibiting activity. The chloroethylcarbamyl derivative 8 of elymoclavine is a potent prolacting inhibitor.
 ...
PMID:Ergot alkaloids. Synthesis of nitrosourea derivatives of ergolines as potential anticancer agents. 42 80

Hypophysectomy of rats bearing 7,12-dimethylbenzanthracene-induced leukemia has been reported to result in a prompt and persistent regression of the leukemia. The purpose of this study was to determine whether or not marked alterations in prolactin secretion would influence this neoplastic process. To determine this, immature male and female Long-Evans rats were divided into three groups: Group 1, controls; Group 2, pituitary grafted (hyperprolactinemia); and Group 3, 2-bromo-alpha-ergocryptine-treated (hypoprolactinemia). Two weeks after the initial treatment and at 2-week intervals thereafter (6 total), each rat was given a single intragastric intubation of 7,12-dimethylbenzanthracene (10 mg/rat). Two months after the initial carcinogen treatment and at 2- to 3-week intervals thereafter, all rats had liver biopsies for the identification of leukemia. Results clearly show that despite nearly 10-fold difference in mean serum prolactin levels in the three groups of female rats and nearly a 20-fold difference in the level of this hormone in male rats, no significant differences in the magnitude of this leukemogenic process could be detected. Thus, striking changes in prolactin secretion do not appear to influence significantly this leukemogenic process.
 ...
PMID:Influence of prolactin on carcinogen-induced leukemogenesis in Long-Evans rats. 81 55

The prolactin receptor (Prlr) and growth hormone receptor (Ghr) genes and the Moloney murine leukemia virus integration-2 (Mlvi-2) locus were mapped to mouse chromosome 15 and human chromosome 5 bands p12-p14. To examine the potential relationship between Mlvi-2 and the genes encoding the growth hormone receptor and the prolactin receptor, we determined the chromosomal location of all three loci in the rat, using a panel of rat-mouse somatic cell hybrids, and in the mouse, using a panel of (C57BL/6J x Mus spretus)F1 x C57BL/6J interspecific backcross mice. These analyses revealed that Ghr, Prlr, and Mlvi-2 map to chromosome 2 in the rat and to chromosome 15 in the mouse, in close proximity with each other. Pulsed-field gel electrophoresis of rat genomic DNA showed no overlaps between the gene encoding the prolactin receptor and the remaining loci. Moreover, expression of the prolactin receptor was not affected by provirus insertion in Mlvi-2. During these studies, however, we detected one T-cell lymphoma line (2779) in which the prolactin receptor gene was activated by provirus integration. Sequence analysis of polymerase chain reaction-derived cDNA clones showed that the prolactin receptor RNA message initiates at the 5' long terminal repeat and utilizes the splice donor site 5' of the gag gene to splice the viral sequences onto exon 1 of the prolactin receptor. This message is predicted to encode the intact prolactin receptor protein product. Exposure of the T-cell lymphoma line 2779 to prolactin promoted cellular proliferation.
 ...
PMID:Activation of the prolactin receptor gene by promoter insertion in a Moloney murine leukemia virus-induced rat thymoma. 140 14

The binding of haemopoietic growth factors and cytokines to specific receptors triggers a cascade of intracellular events which results in cell proliferation and differentiation. The knowledge of ligand-receptor-signal pathways is not only important in understanding the pathophysiology of malignant disease but also essential for devising future therapeutic strategies. The advent of recombinant technology has made it possible to test the efficacy of selective differentiation therapy, and haemopoietic growth factors are undergoing clinical trials for a number of indications. In addition, increasingly the receptors for haemopoietic growth factors and cytokines have come under scientific scrutiny. Recently receptors for IL-2 alpha, IL-2 beta, IL-3, IL-4, IL-5, IL-6, IL-7, erythropoietin, G-CSF and GM-CSF have been isolated and cloned. It has become apparent that they have structural homology that is shared by receptors for growth hormone and prolactin, and this receptor group makes up the new cytokine receptor superfamily. The finding of sequence homology within these receptors suggests their evolutionary relationship. These receptors are transmembrane proteins 257-856 amino acids and their extracellular ligand-binding domain contains four conserved cysteine residues and a Trp-Ser-X-Trp-Ser motif. The secondary structure of the extracellular domain is made up of alpha-helices. High and low affinity binding forms exist for all these receptors. Binding affinity may depend on the formation of receptor heterodimers or multimers, association with other membrane proteins or differential glycosylation. Soluble receptor forms have been described for IL-2 alpha, IL-4, IL-5, IL-6 and IL-7. It is not known whether they are actively secreted or represent the degradation products of cell turnover. Their function may be to mop up excess cytokines and thereby confine the cytokine response. There is no sequence homology of the intracytoplasmic domains although several are rich in proline and serine residues, which may be important in mechanisms of signal transduction. No receptor in this superfamily functions as a receptor tyrosine kinase or has intrinsic protein tyrosine kinase activity. Detailed study of individual receptors holds clues to the regulation of receptor expression, ligand-receptor interactions and mechanisms involved in signal transduction. Such knowledge might explain the pleotropic effects cytokines may have on different cell types and their overlap in biological functions. Elevated levels of soluble IL-2 alpha receptor (Tac) are detected in hairy cell leukaemia, lymphomas and adult T-cell leukaemia (TL), and levels reflect tumour burden.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The cytokine receptor superfamily. 166 10

Progeny from one intra- and two inter-specific backcrosses between divergent strains of mice were typed to map multiple markers in relation to two pigment mutations on mouse chromosome 13, beige (bg) and pearl (pe). Both recessive mutants on a C57BL/6J background were crossed separately with laboratory strain PAC (M. domesticus) and the partially inbred M. musculus stock PWK. The intra- and inter-specific F1 hybrids were backcrossed to the C57BL/6J parental strain and DNA was prepared from progeny. Restriction fragment length polymorphisms were used to follow the segregation of alleles in the backcross offspring at loci identified with molecular probes. The linkage analysis defines the association between the bg and pe loci and the loci for the T-cell receptor gamma-chain gene (Tcrg), the spermatocyte specific histone gene (Hist1), the prolactin gene (Prl), the Friend murine leukaemia virus integration site 1 (Fim-1), the murine Hanukuh Factor gene (Muhf/Ctla-3) and the dihydrofolate reductase gene (Dhfr). This data confirms results of prior chromosomal mapping studies utilizing bg as an anchor locus, and provides previously unreported information defining the localization of the prolactin gene on mouse chromosome 13. The relationship of multiple loci in relation to pe is similarly defined. These results may help facilitate localization of the genes responsible for two human syndromes homologous with bg and pe, Chediak-Higashi syndrome and Hermansky-Pudlak syndrome.
 ...
PMID:Linkage of loci associated with two pigment mutations on mouse chromosome 13. 168 16

To assess effects of chemo- and radiotherapy on the endocrine system 31 children with acute leukaemia and NHL (3 AML, 24 ALL, 4 NHL) were investigated. Children were treated according to modified BFM protocols. 25 patients were before, 5 during and one after puberty (2 to 16 y.). Before treatment, during induction therapy, during cranial irradiation, 4-6 weeks later and during maintenance therapy the following hormone values were estimated: TSH and prolactin basal and 30 min. after TRH (5 micrograms/kg i.v.), LH and FSH basal. Final investigations included total T4 and T3. In conclusion, chemo- und radiotherapy lead to transient elevations of TSH and prolactin in a few patients, but without proof for permanent disorders. Due to the fact all 3 patients with hyperprolactinaemia showed high prolactin levels (700 to 770 mU/l) already before treatment it is unlikely therapy was the main cause of these observed alterations. Although basal LH and FSH values were in normal ranges for age the increasing values after cranial irradiation in prepubertal children may reflect a possible initiation of early maturation, reported by others. Furthermore a retrospective growth study was performed in children treated with 2 different protocols. Protocol LSA2L2 used in the past before 1981 resulted in a permanent reduction of the height. In contrast, the mean SDS for height in children treated with protocol VII declined only during the intensive period of treatment. A catch-up growth occured already during maintenance therapy. Prophylactic cranial irradiation with 18 Gy in our patients under protocol LSA2L2 did not affect growth during the first 5 years after diagnosis.
 ...
PMID:Prospective study on the influence of radiochemotherapy on pituitary function in children with acute leukaemia and NHL. 171 81

Testicular size has been studied in 66 adult men who survived leukemia (n = 14) or cancer (n = 52) in childhood. Mean follow-up time was 14.5 years. The testicular size was measured as the length and breadth in mm; testicular volume index was calculated. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and prolactin were measured. A sperm sample was obtained from 46 men. The patients had smaller testicles than healthy medical students; 51 had small testicles. The size was the smallest in patients who survived leukemia. Multivariate analysis showed that the variables with independent effects on testicular size were cranial and testicular irradiation and therapy with cyclophosphamide. Sperm production was dependent on testicular size. We conclude that determination of serum FSH combined with testicular size may offer a practical approach for predicting the subsequent testicular damage in boys with malignancies.
 ...
PMID:Small testicles with impaired production of sperm in adult male survivors of childhood malignancies. 210 85

In an attempt to elucidate the role of viruses in certain neuroendocrine disorders, we have demonstrated that infection of endocrine cells (GH-3 and Y-1) in vitro by moloney murine leukemia virus (M-MuLV) resulted in diminution of cell-specific secretory function, hormone secretion into culture. In GH-3 (rat anterior pituitary gland) active (initial) and persistent infection by M-MuLV resulted in approximately 80% reduction in prolactin and growth hormone secretion. The adrenal cortex tumor cell line (Y-1), when actively infected with the same virus, showed a transient increase in fluorogenic steroid secretion; however, on subsequent passages of infected cell cultures, steroid secretion was markedly reduced to about 10% of the uninfected Y-1 cells. The virus yield from M-MuLV-infected cultures of Y-1 and GH-3 cells produced a significantly lower amount of virus than the control NIH-3T3-infected cell cultures.
 ...
PMID:Modulation of hormone secretion in vitro by murine retrovirus. 227 77

Here we report that the slow-transforming helper component of Friend murine leukaemia virus (Fr-MLV), which produces lymphoid leukaemias in normal mice, induces erythroleukaemia in mice given syngeneic pituitary grafts (SPG). Newborn mice were infected with Fr-MLV and, at one month of age, were transplanted with two pituitary glands under the kidney capsule. Sham-operated infected mice and uninfected transplanted mice served as controls. SPG selectively reduced the mean survival times of infected mice. Histopathology showed that, while most infected non-transplanted mice developed lymphoid leukaemias, virtually all Fr-MLF-infected mice given SPG developed erythroleukaemias. Experiments in vitro showed that Fr-MLV infection markedly depressed concanavalin A induced DNA synthesis in cells from spleen, thymus and lymph nodes. Addition of prolactin or growth hormone further suppressed lectin-induced mitogenesis of lymphoid cells from infected mice, but failed to influence the response of uninfected controls. These experiments indicate that, in mice, pituitary hormones modulate the development and the histological features of Fr-MLV induced leukaemias, and suggest that endocrine-immunological interactions play a role in retrovirus induced tumorigenesis.
 ...
PMID:Fr-MLV infection induces erythroleukaemia instead of lymphoid leukaemia in mice given pituitary grafts. 237 85

Six girls and three boys, asymptomatic after treatment for acute lymphoblastic leukemia (ALL) or endodermal sinus tumor (EST), were investigated for endocrine status and growth. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), testosterone binding capacity (TeBC), 17 alpha-hydroxyprogesterone (17-OHP), progesterone (P), thyroxine (T4), thyroid stimulating hormone (TSH), and cortisol were measured, and pubertal stage and bone age were determined. Growth was evaluated according to accepted curves for height and weight. Four of the girls had normal pubertal development, with serum FSH, LH, and E2 levels correlating to the phase of the menstrual cycle. Only one of the girls had ovulatory cycles (increase in P level). The girl treated for EST by abdominal irradiation had gonadal failure, with postmenopausal serum levels of FSH, LH, and E2. Her karyotype was normal. One of the girls was still prepubertal. None of them was hyperandrogenemic. One boy who was treated with bone marrow transplantation and total body irradiation had gonadal failure. One boy was still prepubertal, and the third boy showed normal pubertal maturation and normal serum FSH, LH, and T levels. All the patients except the boy treated with bone marrow transplantation and irradiation were normoprolactinemic; in addition, all had normal thyroid and adrenal function. Height and weight curves were normal in seven of the patients after the cancer therapy. The girl with EST had finished her growth before the irradiation therapy began. The boy treated with bone marrow transplantation and irradiation failed to exhibit further growth after beginning leukemia therapy at the age of 9.3 years.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Endocrine status and growth after malignancy treated in childhood or adolescence. 290 44


1 2 3 4 5 Next >>