Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperprolactinaemia frequently causes secondary hypogonadism through central suppression of gonadotropin secretion. Macroprolactinomas (> 1 cm diameter) are more common in males and may additionally cause more generalised hypopituitarism. Recovery of the thyrotropic and/or corticotropic axes is well described following selective adenomectomy, but remains poorly defined in relation to medical (dopamine-agonist) therapy of macroprolactinomas. We therefore performed a retrospective examination of case records of male patients who had received medical therapy alone for macroprolactinoma between 1980-2001 (n = 35) and in whom tumor shrinkage was documented by interval pituitary imaging (reported throughout by a single neuroradiologist). Mean prolactin level at baseline was 59,932 mU/L (median 31,400; range 3,215-332,000); mean period of follow up was 4.2 years (median 2.6; range: 1.0-15). Defects of the following axes were evident at diagnosis: LH/FSH-testosterone (n = 27; 77%), TSH-T4 (n = 14; 41%-not including one case with pre-existing 1 degress hypothyroidism), ACTH-cortisol (n = 8; 23%). Overall, 14 men (40%) were deficient in 1 axis, seven (20%) in 2 axes and seven (20%) in 3 axes. Growth hormone secretory status was not systematically evaluated. In all but 6 patients, prolactin levels fell to normal or near-normal levels (mean 764 mU/L; median 260; range: < 10-4,833). Of the patients in whom adequate reassessment had been performed, thyrotroph function recovered in 4/9, corticotroph function in 4/6 and gonadotroph function in 16/26 cases. In four cases (11%) previously described, development of visual impairment as a result of the chiasmal traction syndrome necessitated a dose reduction in medical therapy to allow a degree of controlled tumor re-expansion. The prevalence at diagnosis of TSH and ACTH deficiency in men with macroprolactinomas was 41% and 23%, respectively. Among eight patients with insufficiency of TSH and/or ACTH secretion who underwent complete interval reassessment over several years of treatment, recovery of at least one axis occurred in six cases (75%). This study highlights the importance of screening ACTH- and/or TSH-deficient men during dopamine agonist therapy in order to identify cases where hypopituitarism has resolved.
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PMID:Medical therapy of macroprolactinomas in males: I. Prevalence of hypopituitarism at diagnosis. II. Proportion of cases exhibiting recovery of pituitary function. 1455 72

Growth hormone (GH) protects the intestines from antitumoral therapy, but it is not known whether or not the tumor is also protected in vivo. The aim of the present work was to determine whether GH administration modifies the response by a colonic adenocarcinoma to radiation in vitro and in vivo. BDIX rats were implanted with a colonic adenocarcinoma and two weeks later GH treatment was started. Animals were then irradiated, and four days later samples from the intestines and tumor were taken for analysis. In vitro assays were performed in parallel to confirm the effects observed in vivo. GH reduced radiation-induced intestinal injury by improving proliferation and reducing apoptosis and p53 expression. However, tumor proliferation was reduced by GH while apoptosis and p53 expression remained unchanged. A similar response was observed in vitro. Thus, GH administration before radiotherapy protects the intestines but not the implanted adenocarcinoma in the rat.
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PMID:Differential action of growth hormone in irradiated tumoral and nontumoral intestinal tissue. 1470 22

Growth hormone (GH) is a powerful metabolic hormone that regulates fuel homeostasis through its protein anabolic and lipolytic actions. The introduction of recombinant human GH has expanded the narrow indication of treating children with severe GH deficiency (GHD) to include a broader target population of children with growth retardation and short stature and adults with hypopituitarism and severe GHD. Furthermore, because children continue to receive GH replacement therapy into adult life, the duration of treatment exposure has increased and the safety of long-term GH treatment has become increasingly important. This is of particular concern given that GH-deficient children and adults may be more vulnerable to the mitogenic stimuli of GH and insulin-like growth factor-1, both because of the underlying cause of GHD and also because of previous treatment such as radiotherapy and chemotherapy. This review focuses on the safety of treating adults with severe GHD, with specific emphasis on dose regimens, carbohydrate metabolism, neoplasia, and morbidity and mortality. Available experience from long-term replacement therapy, studies using supraphysiological doses of GH in adults and lessons learned from patients with acromegaly who have high endogenous GH levels over many years, is considered.
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PMID:Safety of growth hormone replacement therapy in adults. 1526 48

Growth hormone releasing hormone (GHRH) is known to have multiple anabolic effects and immune-stimulatory effects. Previous studies suggest that treatment with anabolic hormones also has the potential to mitigate the deleterious effects of cancer cachexia in animals. We studied the effects of plasmid-mediated GHRH supplementation on tumor growth and the role of antitumor immune cells with two different human tumor cell lines, NCI-H358 human bronchioalveolar carcinoma and MDA-MB-468 human breast adenocarcinoma, subcutaneously implanted in nude mice. GHRH supplementation by delivery of human GHRH from a muscle-specific GHRH expression plasmid did not increase tumor progression in tumor-bearing nude mice. Male animals implanted with the NCI-H358 tumor cell line and treated with the GHRH-expressing plasmid exhibited a 40% decrease in the size of the tumors (P<.02), a 48% increase in white blood cells (P<.025) and a 300% increase in monocyte count (P<.0001), as well as an increase in the frequency of activated CD3+ and CD4+ cells in the tumors, compared to tumors of control animals. No adverse effects were observed in animals that received the GHRH-plasmid treatment. The present study shows that physiological stimulation of the GHRH-GH-IGF-I axis in mice with cancer does not promote tumor growth and may provide a viable treatment for cancer cachexia in humans.
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PMID:Growth hormone releasing hormone plasmid supplementation, a potential treatment for cancer cachexia, does not increase tumor growth in nude mice. 1537 78

Acromegaly is a rare disease that, in the majority of cases, is due to the presence of a benign growth hormone (GH)-producing tumor of the pituitary. Growth hormone has profound effects on linear bone growth, bone metabolism, and bone mass. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD). Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. The Autors describe a case of patient affected by acromegaly without hypogonadism with serious osteoporosis and biological signs of osteomalacia.
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PMID:[The strange case of a patient affected by acromegaly with osteoporomalacia without hypogonadism]. 1638 Jul 58

Growth hormone (GH)-cell adenomas are benign pituitary tumors which present with chronic high GH output. Hereditary GH-cell adenomas are rare and include MEN I, McCune Albright Syndrome, Carney complex and familial acromegaly. Most of the tumors causing acromegaly are sporadic. Acromegaly is a disfiguring and disabling disease and, if untreated, life expectancy is reduced by a decade. Elevated GH levels, hypertension and heart disease are major negative survival determinants in these patients. Current treatments for acromegaly attempt to control the disease by reducing growth hormone secretion from the tumor either by surgery, radiotherapy or medical therapy. The choice of therapy depends on age, general health, the severity and complications of the disease and dangers associated with each treatment. Assessment of disease activity in patients with acromegaly following treatment is a problem because no sensitive clinical parameters are available and there is no well-defined clinical endpoint that defines cure. Cure in acromegaly has been defined therefore as normalization of biochemical parameters. A consensus publication recommended biochemical cure be considered as nadir GH of less than 1 microm g/L after OGTT and a normal circulating IGF-I. In optimizing the control of acromegaly new therapeutic strategies are evolving (growth hormone receptor antagonist - pegvisomant, potent dopamine agonists, universal somatostatin receptor ligands, chimeric molecules). The aim of the evolving therapeutic strategies is to produce a normal life expectancy in patients with acromegaly.
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PMID:Acromegaly - evolving strategies. 1644 81

Classical clinical calcium endocrinology was built on measurements of serum Ca, P and alkaline phosphatase as well as urinary Ca. Serum Ca, the most strictly maintained biological constant, occupies the central role among them, controlling PTH secretion and bone metabolism. Ca is strongly bound to proteins especially albumin, so that total serum Ca values are sometimes misleading, necessitating the use of corrected or ionized Ca. Serum Pi rises early in renal insufficiency, playing an important role in vascular calcification. Growth hormone and thyroid hormone functions are also reflected on serum P. Serum alkaline phosphatase especially the bone-specific type is also important for the evaluation of bone dynamics such as growth and tumor metastasis. These classical datasets should be reevaluated in the light of actions of new compounds such as calcimimetics, P-binders, bisphosphonates, vitamin D derivatives, cytokines, etc.
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PMID:[Bone and bone related biochemical examinations. Significance of measurement of serum calcium, phosphorus, alkaline phosphatase, corrected calcium and urine calcium]. 1675 83

A pituitary acidophil adenoma in a domestic shorthaired cat with diabetes mellitus and elevated serum somatomedin C level is described. Growth hormone production by the neoplasm was confirmed by an appropriate reaction using an immunoperoxidase technic.
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PMID:Growth Hormone-producing Pituitary Adenoma, Elevated Serum Somatomedin C Concentration and Diabetes Mellitus in a Cat. 1742 32

Growth hormone release and IGF-I synthesis decrease with increasing age. The regulation of the GH/IGF-I system is dependent on the integrity of the hypothalamus, pituitary and liver. During aging there are several changes which contribute to the decline in GH/IGF-I including changes in signal to the somatotrophs from growth hormone releasing hormone, somatostatin and other factors such as body composition, exercise, diet and sleep. All of these factors are discussed in detail within this review. The phenotypic similarities between aging and adult growth hormone deficiency syndrome combined with this decrease in GH/IGF-I with aging have prompted the question whether aging is a GH deficient state. The advent of recombinant growth hormone has led to a number of studies treating elderly patients with GH alone or in combination with sex steroids or exercise. The results of these studies would not back up the use of GH in elderly non-hypopituitary patients as they did not show efficacy, showed high rates of adverse events and there is also some evidence associating GH/IGF-I and risk of neoplasia. If GH therapy is to be used in this cohort of patients further long term efficacy and safety studies are required.
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PMID:Aging and the growth hormone/insulin like growth factor-I axis. 1749 9

Vascular tumours are common lesions of the skin and subcutaneous tissue, but also occur in many other tissues and internal organs. The well-differentiated tumours consist of irregular anastomosing, blood-filled vascular channels that are lined by variably atypical endothelial cells. The less differentiated tumours may show solid strands and sheets, resembling carcinoma or lymphoma. Several growth factors, including basic fibroblast growth factor, transforming growth factors and vascular endothelial growth factor, play a role in tumour angiogenesis. Growth hormone (GH) is mitogenic for a variety of vascular tissue cells, including smooth muscle cells, fibroblasts and endothelial cells and exerts its regulatory functions in controlling metabolism, balanced growth and differentiated cell expression by acting on specific membrane-bound receptors, which trigger a phosphorylation cascade resulting in the modulation of numerous signalling pathways and of gene expression. Essential to the initiation of a cellular response to GH, the presence of receptors for this hormone may predict the adaptation of tumour cells resulting from GH exposure. To address the site/mode of action through which GH exerts its effects, a well characterized monoclonal antibody, obtained by hybridoma technology from Balb/c mice immunized with purified rabbit and rat liver GH-receptor (GHR) and directed against the hormone binding site of the receptor, was applied, using the ABC technique to determine GHR expression in a panel of vascular tumours. The GHR was cloned from a rabbit liver cDNA library with the aid of an oligonucleotide probe based on a 19 residue tryptic peptide sequence derived from 5900 fold purified rabbit liver receptor. A total of 64 benign and malignant vascular tumours were obtained from different human organ sites, including the chest wall, skin, axillary contents, duodenum, female breast, abdomen, stomach, colon, lymph node, bladder, body flank and neck regions. The tumours were of the following pathological entities: Haemangioma (n = 12); haemangioendothelioma (n = 10); Castleman's disease (n = 3), haemangiopericytoma (n = 4); angiosarcoma, (n = 11), Kaposi's sarcoma with focal infiltration by lymphoma, HIV +ve (n = 7), Kaposi's sarcoma (n = 17). The endothelial cell marker CD-31 was used to establish endothelial cell characteristics and microvascular density. To delineate tumour cell growth, immunohistochemical analysis of cycling nuclear protein and of proliferating cell nuclear antigen, using Ki-67 and PCNA polyclonal antibodies respectively, was used to demonstrate proliferative indexes. Results show that, compared to their normal tissue counterparts, nuclear and cytoplasmic expression of GHR consistently result in strong receptor immunoreactivity in the highly malignant angiosarcomas and Kaposi's sarcomas and was localized in the cell membranes and cytoplasm, but strong nuclear immunoreactivity was also identified. The presence of intracellular GHR is the result of endoplasmic reticulum and Golgi localization. Nuclear localization is due to identical nuclear GHR-binding protein. Furthermore, there was a positive correlation of GHR immunoreactivity with neoplastic cellular proliferation and cycling, as measured by Ki-67 and PCNA. In conclusion, this study shows that GHR expression in vascular tumours is a function of malignancy and cancer progression. Malignant cells, which are highly expressive of the receptor, have a greater proliferation rate and thereby also higher survival rate compared to tumours expressing lower or minimal receptor level. The presence of GHR in endothelial cells of vascular neoplasm indicates that they are target cells and GH is of importance in the proliferation of vascular tumour angiogenesis. GH is necessary not only for differentiation of progenitor cells, but also for their subsequent clonal expansion and maintenance. The results support the hypothesis that GH is involved in the paracrine-autocrine mechanism, acting locally in regulating vascular tumour growth and will be useful for site-specific studies of the evolution of vascular cancers. The use of anti-GHR antibodies to block tumour progression is an intriguing possibility.
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PMID:Growth hormone in vascular pathology: neovascularization and expression of receptors is associated with cellular proliferation. 1822 92


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