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

In 22 children who were in complete remission after acute lymphoblastic leukaemia endocrinological investigations were performed 5-12 weeks after cessation of therapy. The children had received central nervous system irradiation (tele-Co60, 850-1800 rad), and long term, aggressive cytostatic drug therapy during 21 to 36 months. Growth hormone, TSH, thyroxine, LH, FSH, cortisol secretion, and urinary concentrating capacity were found to be normal, with a few exceptions where borderline results were obtained.
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PMID:Endocrine function after antineoplastic therapy in 22 children with acute lymphoblastic leukaemia. 26 43

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.
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PMID:Prospective study on the influence of radiochemotherapy on pituitary function in children with acute leukaemia and NHL. 171 81

To study long-term testicular function following the treatment of acute lymphoblastic leukaemia (ALL) in childhood, 37 young adult males were assessed at two separate time points. The initial assessment was made by a wedge testicular biopsy after completion of treatment (median 9.7 years; range 4.1-16.3 years) and the subsequent assessment (median 18.6 years; range 15.4-26.8 years) consisted of the clinical examination of pubertal stage, measurement of serum gonadotrophins and testosterone and, in 19 patients, semen analysis. All 37 men completed pubertal development normally and had a testosterone concentration within the normal adult range. Six men showed evidence of severe damage to the seminiferous epithelium, five were azoospermic and one, who did not provide semen for analysis, had a reduced mean testicular volume (11 mls; normal greater than or equal to 15 mls) and a raised basal FSH level (13 UI 1-1; normal less than or equal to 6 IU 1-1). All six men with germ-cell damage had received either cyclophosphamide or both cyclophosphamide and cytosine arabinoside as part of their chemotherapy regimen. Approximately 10.7 years earlier all 37 men had undergone a testicular biopsy after completion of their chemotherapy. Morphological damage to the seminiferous epithelium had been calculated by estimating the tubular fertility index (TFI), which is the percentage of seminiferous tubules containing identifiable spermatogonia (age-matched normal = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Male fertility in long-term survivors of childhood acute lymphoblastic leukaemia. 179 16

Eleven girls treated during childhood for acute leukaemia were followed up during their pubertal development. At each examination weight, height, pubertal stage, FSH, LH, oestradiol, testosterone, androstenedione and dehydroepiandrosterone sulphate levels were evaluated. Clinical and endocrinological studies were performed according to age and pubertal stage and compared to those of healthy girls matched for age and pubertal stage. Results showed that pubertal maturation and gonadal function were not affected by oncotherapy; however menarche was attained earlier. Early menarche was explained by the overweight of treated girls during early puberty. No evidence of early hypothalamic activation was found, but endocrine patterns showed a faster hypothalamopituitary-ovarian axis maturation in patients than controls. Cranial irradiation showed no correlation with pubertal onset and age at which menarche was attained. Adolescent menstrual and endocrine patterns were normal.
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PMID:Pubertal maturation in girls treated for childhood acute leukaemia. 191 14

Chemotherapy for malignant disease can cause gonadal dysfunction. However, little is known about the reversibility and severity of these effects in girls treated during childhood or puberty. For this reason we investigated clinical data and endocrine parameters (FSH, LH, PRL, E2, progesterone) of 51 adolescent females. Our clinical data showed that intermittent pulse chemotherapy as administered to most patients with solid tumours leads to a more pronounced growth retardation than continuous low dose chemotherapy as given to patients with leukemia and lymphomas. Girls treated prior to menarche failed to start menstruation while on chemotherapy, but all had their menarche shortly after cessation of the treatment. Most of the girls treated post menarche developed amenorrhoea, whereas some had irregular cycles unless they were on a very mild drug regimen. From the endocrinous data we concluded that primary ovarian failure was rare and occurred in adolescent girls only after a combination of chemotherapy and radiotherapy. In girls with regular menstrual cycles after treatment a high incidence of anovulation or an inadequate luteal phase could be observed. The latter symptoms may be signs of hypothalamic ovarian failure as caused by stress, anxiety and emotions associated with a malignant disease.
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PMID:[Puberty and ovarian function following cytostatic therapy in childhood]. 308 79

Cranial irradiation is known to affect the neuroendocrine control of GH secretion. The aim of the present study was to clarify the effect of leukaemia treatment on neuroendocrine control of PRL secretion in long-term survivors of acute lymphoblastic leukaemia (ALL). Pituitary LH, FSH and PRL responses to GnRH and to the dopamine receptor antagonist metoclopramide were evaluated in 18 boys 1.6-9 years after discontinuation of medication for ALL. All the boys had been subjected to prophylactic cranial irradiation and 8 to testicular irradiation. Eight of the boys had supranormal gonadotropin levels either basally or after GnRH. All had normal basal PRL levels, but in 14 of the 18 boys the metoclopramide-releasable PRL levels were subnormal. The decreased PRL responses cannot be explained by the hypergonadotropism, since exaggerated rather than decreased responses are frequently found in patients with primary gonadal failure. We conclude that abnormal regulation of PRL secretion is a frequent consequence of treatment of ALL, probably being due to decreased pituitary lactotrop mass.
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PMID:Impaired prolactin responsiveness to a dopamine antagonist in long-term survivors of acute lymphoblastic leukaemia. 311 97

Recombinant activin A was radioiodinated to a high specific activity with maintenance of bioactivity using the Bolton-Hunter method. The human leukemia cell line K562, known to differentiate in response to activin A, was found to possess high affinity [125I]BH-activin A receptors (Kd approximately 0.13 nM) with a low number of receptors per cell (approximately 600 per cell). This receptor was found to be specific as FSH, LH, GnRH, and TGF-beta 1 do not compete for binding. This is the first description of binding sites for this protein hormone on K562 cells.
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PMID:Characterization of activin A binding sites on the human leukemia cell line K562. 320 79

Menopause, conventionally defined as the permanent cessation of menstruation as a result of loss of ovarian follicular activity, is biologically expressed by the collapse of plasma estradiol levels and increased plasma levels of the gonadotrophins FSH (follicle stimulating hormone) and LH (luteinizing hormone). At present, estimation of the ovarian follicle reserve is based on endocrine capacity tests of the ovaries, with increased FSH representing the first sign of exocrine ovarian failure. We report the case of one of our amenorrhoeic patients after chemotherapy, total body radiation and allogenic bone marrow transplantation for acute immunoblastic leukaemia. This patient was included in an in vitro fertilization with oocyte donation (IVF-OD) programme for iatrogenic premature ovarian failure with increased FSH levels. Instead of high levels of gonadotrophins, this young woman recovered spontaneous follicular development, benefited from standard IVF with her own oocytes and brought a twin pregnancy to term. This observation shows that a high FSH level is not a definitive prediction of ovarian exocrine capacity. In young women of child-bearing age such as these wanting a child and showing signs of endogenous estrogen impregnation, evaluation of the existence and quality of follicular development is an important factor.
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PMID:[Recovery of ovarian function after radiation-induced menopause. Does follicle-stimulating hormone (FSH) have a definitive prognostic value?]. 897 71

The majority of ovarian follicles undergo atresia mediated by apoptosis. Bcl-2-related proteins act as regulators of apoptosis via the formation of dimers with proteins inside and outside the Bcl-2 family. Previous studies have identified BAD as a proapoptotic Bcl-2 family member expressed in the ovary. It is known that BAD phosphorylation induced by survival factors leads to its preferential binding to 14-3-3 and suppression of the death-inducing function of BAD. To identify ovarian binding partners for hypophosphorylated BAD, we performed a yeast two-hybrid screening of a rat ovary complementary DNA library using as bait a mutant BAD incapable of binding to 14-3-3. Screening of yeast transformants yielded positive clones encoding the rat ortholog of Mcl-1 (myeloid cell leukemia-1), an antiapoptotic Bcl-2 protein. Amino acid sequence analysis revealed that rat and human Mcl-1 showed a complete conservation of the Bcl-2 homology domains BH1, BH2, and BH3. In the yeast two-hybrid system, Mcl-1 binds to the hypophosphorylated mutant of BAD and interacts preferentially with different proapoptotic (Bax, Bak, Bok, Bik, and BOD) compared with antiapoptotic Bcl-2 family members (Bcl-2, Bcl-xL, Bcl-w, Bfl-1, CED-9, and BHRF-1). Northern blot hybridization demonstrated expression of Mcl-1 transcripts of 2.3 and 3.7 kb in the ovary and diverse other rat tissues. In immature rats, PMSG treatment led to a transient increase in the 2.3-kb Mcl-1 transcript, peaking at 6 h after injection and returning to baseline levels after 24 h. Moreover, the same transcript was induced in the PMSG-primed preovulatory rat ovary 6 h after the administration of ovulatory doses of either hCG or FSH. In situ hybridization studies revealed that the gonadotropin stimulation of ovarian Mcl-1 message occurs in both granulosa and thecal cells. In conclusion, rat Mcl-1 was identified as an ovarian BAD-interacting protein and the message for the antiapoptotic Mcl-1 protein was induced after treatment with gonadotropins in granulosa and thecal cells of growing follicles.
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PMID:Characterization of the antiapoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) and the stimulation of its message by gonadotropins in the rat ovary. 1057 8

Cranial irradiation in prepubertal children with leukemia or brain tumors can lead to precocious or in high doses to late puberty. To unravel the underlying mechanisms, we developed a rat model with selective cranial Co60-irradiation technique. Infantile (12-16 d old) or juvenile (21-23 d old) female Sprague-Dawley rats received a single dose of 4, 5, 6, 9 or 2 x 9 Gy (at days 21 and 23). Each group consisted of 7-20 animals. High radiation doses (9 Gy and more) caused retardation of sexual development, whereas low radiation doses (5 or 6 Gy) led to accelerated onset of puberty in 20% of infantile irradiated rats animals as determined by vaginal opening. Interestingly, at peripubertal age (postnatal day 32-34), 5 or 6 Gy infantile irradiated rats had significantly higher serum LH levels stimulated by GnRH and estradiol levels (p < 0.05). 2 x 9 Gy irradiated rats had at the age of 3 mo a marked growth retardation and significantly lower GH levels than the controls (p < 0.05) whereas prolactin, FSH, TSH, T4, and corticosterone levels were comparable with controls. These studies demonstrate that the GnRH-pulse generator is very radiosensitive as precocious activation occurred after low dose irradiation (5 or 6 Gy) of infantile rats without any other endocrine disorder. High radiation doses (9 or 2 x 9 Gy) induced retardation of sexual maturation and later on growth hormone deficiency. Moreover this model of cranial irradiation seems to be suitable to study the molecular mechanisms of radiation induced pubertal changes.
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PMID:Cranial irradiation of female rats causes dose-dependent and age-dependent activation or inhibition of pubertal development. 1081 81


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