Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumors in rats of the Nb strain, arising either spontaneously or after prolonged treatment with s.c. pellets of estrogen, were transplanted to establish whether hormone conditioning was required for their growth. Whereas all spontaneous tumors arising in males and many of those in females were autonomous on transplant, most of those arising in estrogenized rats continued to require hormones for growth after transplantation. The latter included carcinomas of the adrenal cortex, breast, pituitary ectopic tissue, ovary (thecomas), Leydig cells of testis, thymus, pancreas,salivary glands, oribital gland (fibroadenoma), liposarcoma, and lymphoma. Many of the tissues of origin of the tumors have not been considered to be under theinfluence of estrogens. A type of hormone-responsive tumor that was inhibited by estrogen and that grew only in normal rats is described. Ali estrogens tested, including estriol , were interchangeable in action. The incidence of the more common tumors of the adrenal, breast, and pituitary was very low in normal rats, but higher in females. All tumors were more common after estrogenization in both sexes, particularyly in older animals. The secretion of steroids and pitiutary hormones by many tumors led to obvious biological effects. Pituitary secretion led to severe lesions frequently associated with diseases in humans, but the signs of such diseases in the rat apparently were hormone dependent and disappeared if the tumor was removed. The overall results raised the possiblity that estrogens were not carcinogenic per se but stimulated the growth of previously altered cells and that, following their transplantation, this hormone requirement was retained. Irrespective of the mechanism of carcinogenesis, hormone-dependent tumor growth was not irreversible but was controlled in an unexpectedly wide spectrum of organs by exogenous estrogen. Host factors may play a major role in controlling the growth of many tumors and the ultimate course of the disease.
 ...
PMID:Spontaneous and estrogen-produced tumors in Nb rats and their behavior after transplantation. 116 9

Pituitary tumors secreting growth hormone are clonal neoplasms that may arise following a somatic mutation within the somatotroph cell. Promotion of tumor growth also appears to be regulated by hypothalamic growth hormone-releasing hormone, which exerts a trophic action on the pituitary cell. Unraveling the mechanisms of pituitary tumorigenesis will facilitate the application of novel therapeutic techniques, genetic screening, and follow-up of tumor responses.
 ...
PMID:Etiology of pituitary acromegaly. 152 11

Pituitary adenomas may produce local endocrine and neurological effects, as well as systemic metabolic complications due to hormonal hypersecretion. Medical therapy with pharmacological agents has been developed and is based on the neurotransmitter regulation of normal pituitary hormonal secretion. 189 patients with secretory pituitary adenomas underwent medical therapy for the hypersecretory state. 156 of these were prolactin-secreting adenomas, 16 of which were in males. The response of bromocriptine was almost universal with lowering of serum prolactin and reversal of the clinical symptoms, as well as tumor shrinkage of most large adenomas with suprasellar extension. 23 patients with acromegaly were treated with bromocriptine, with 11 noting clinical improvement, and decreased tumor size in two. Five patients with Cushing's disease were treated with cyproheptadine, with only one showing a biochemical and clinical improvement. Two patients with Nelson's syndrome each had progressive tumor growth stabilized with cyproheptadine and bromocriptine in one, and sodium valproate in the other. There appears to be a role for medical therapy in the majority of prolactin-secreting pituitary tumors, some growth hormone secreting pituitary tumors, and selected adrenocorticotropin secreting-pituitary tumors.
 ...
PMID:The medical treatment of the hypersecreting pituitary gland. 299 35

In all stereotactic irradiation procedures, a high dose is delivered to a relatively small target volume. Whether fractionated stereotactic radiotherapy is preferable (based on a therapeutic ratio) or a radiosurgical method (aiming at the precise and complete destruction of a tissue volume) depends on the definition and composition of the target. The methodologies can be grouped in closed-skull external focussed beam stereotactic radiosurgery/radiotherapy and in stereotactic implantation/injection of radiation sources. Although originally developed to treat functional disorders of the brain, stereotactic radiosurgery has been used most successfully for over 4 decades to treat cerebral arteriovenous malformations. Complete obliteration ranges from 30 to 50% after 1 year are reported. At 2 years the results range from 72 to 90%. Clearly the outcome is influenced by patient selection. In the treatment of acoustic neurinomas follow-up data of larger series of radiosurgery show that the treatment performed under local anesthesia on an outpatient basis becomes comparable with the best microsurgery data. Using multiple isocenters and MR localization tumor growth control is achieved in more than 90% of cases, with hearing preservation of approximately 50%. Pituitary tumors with Cushing's syndrome, acromegaly, Nelson's syndrome, prolactinomas and nonsecreting adenomas have been treated with various stereotactic irradiation methods. Further refinement of both localization techniques, dose distribution and beam manipulation will make radiosurgery an attractive modality because of its noninvasive character and low morbidity. Only a small subgroup of patients with low-grade gliomas are candidates for stereotactic localized irradiation treatment, namely those with circumscribed tumors with only limited spread of tumor cells into the periphery. For this subgroup, which usually comprises not more than 25% of all low-grade gliomas, the results from interstitial radiosurgery compete with surgical resection. Apart from the possibility to define the borders of the treatment volume with serial stereotactic biopsies, there are dosimetric advantages of interstitial radiosurgery. Local single high-dose treatment remains controversial for highly malignant infiltrative tumors, and significant treatment benefit remains to be documented. Radiosurgery can be used to effectively treat solitary brain metastases with less invasiveness and dissection of normal tissue, and with lower morbidity and less expense than open surgery.
 ...
PMID:Stereotactic radiation therapy and radiosurgery. 762 37

Radiosurgery aims at the precise destruction of small, defined volumes of tissue by employing ionizing radiation energy. Its methodologies may be subdivided into closed-skull, external focussed beam radiosurgery, and interstitial radiosurgery (brachytherapy). Focussed beam stereotactic radiosurgery has been used successfully for over two decades to treat cerebral arteriovenous malformations. Complete obliteration ranges from 30% to 50% after one year. After two years, obliteration is observed in up to 90% of patients. Outcome, however, is influenced by patient selection. In the treatment of acoustic neurinomas, follow-up data of larger series show that radiosurgery performed under local anesthesia on an out-patient basis is competitive with microsurgery data. Using multiple isocenters and magnetic resonance localization, tumor growth control is achieved in more than 90% of patients with preservation of hearing in approximately 50%. Pituitary tumors with Cushing's syndrome, acromegaly, Nelson's syndrome, prolactinomas and non-secreting adenomas have been treated. Only a small subgroup of patients with low-grade gliomas are candidates for interstitial radiosurgery, namely those with circumscribed tumors with limited spread of tumor cells into the periphery. For this subgroup, which usually comprises not more than 25% of all low-grade gliomas, interstitial radiosurgery competes with surgical resection. Local, single high-dose treatment remains controversial for highly malignant infiltrative tumors, and a significant treatment benefit remains to be demonstrated. Radiosurgery can be used to effectively treat solitary brain metastases (< or = 3 cm diameters) with less invasiveness, and dissection of normal tissue; it may be performed with lower morbidity and with less expense in comparison with open surgery.
 ...
PMID:[Stereotaxic radiosurgery]. 780 64

Studies were undertaken to examine the effects of an estradiol-chemical delivery system (E2-CDS) or castration (CAST) on plasma testosterone (T) and growth of the Segaloff 11095 carcinoma. Fischer 344 rats were implanted subcutaneously with the Segaloff 11095 tumor and tumor growth was monitored thereafter. After optimal tumor growth, when the average tumor size was approximately 25 x 15 mm (length x width; 4-5 g wet weight), rats were randomized into (1) testis-intact controls; (2) CAST; (3) intact+E2-CDS groups (rats received weekly injection of the E2-CDS at 0.5 mg/kg). Animals were killed 7 or 14 days after the initiation of treatments. Blood and tissue samples were collected for subsequent analysis. Plasma T levels were suppressed by 98% and 97% through 14 days after CAST or E2-CDS treatment. CAST increased plasma gonadotropin (LH) concentrations, while E2-CDS reduced LH compared to intact control levels. E2-CDS treatment increased plasma E2 levels to 24 (one injection) or 75 pg/ml (two injections) at 7 or 14 days, respectively. E2-CDS, given once a week for 2 consecutive weeks, resulted in a decreased growth of the prostate tumor by 61%, while CAST reduced the weights of these tumors by only 20%. In response to E2-CDS (one or two injections), weights of the in situ ventral prostate and seminal vesicles were significantly reduced by 70% and 50%, respectively, in tumor-bearing rats. Similarly, CAST reduced the weights of these tissues by 80% (prostate) or 52% (seminal vesicle) at 7 or 14 days after treatment. Pituitary weight increased, while testes weight decreased by 20% with two injections of E2-CDS, compared with intact control rats. Collectively, these data indicate that E2-CDS is effective in reducing the growth rate of prostatic tumors in the rat.
 ...
PMID:Suppression of plasma testosterone and prostate carcinoma size by a redox-based, brain-targeted estrogen delivery system in the rat. 833 87

Pituitary cells appear to be programmed to proliferate in response to cyclic adenosine monophosphate (cAMP), leading to tumorigenesis. Stimulatory neurohormones and inhibitory inputs normally act in opposition to control cAMP levels, but receptor/postreceptor alterations may affect their relative effects. Most growth hormone (GH), corticotropin (ACTH)-, prolactin (PRL)-, and gonadotropin-secreting adenomas and nonfunctioning pituitary adenomas (NFPA) possess specific thyrotropin-releasing hormone (TRH) receptors, normally coupled with cytosolic [Ca2+]i increase and diacyl glycerol production. These cells are also sensitive to other peptides such as vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP), which activate adenylyl cyclase in many hormone-secreting adenomas and in all NFPA. The two main inhibitory agents controlling pituitary function are somatostatin (SS) and dopamine (DA), which have been reported to reduce hormone hypersecretion and tumor growth in a variable percentage of patients. Inhibition of adenylyl cyclase activity and cytosolic [Ca2-]i levels is involved in the transduction of DA signals in normal and tumoral mammotrophs, but in GH-secreting adenomas DA receptors are exclusively and defectively coupled only with [Ca2+]i reduction. The abnormal expression of these receptors can amplify stimulatory signals with both secretory and proliferative potential. The availability of specific G proteins may qualify the cell response to inhibitory agents. For example, in a subset of NFPA, SS alone or DA alone causes an abnormal increase in [Ca2+]i levels due to Ca2+ mobilization from intracellular stores.
 ...
PMID:Cellular abnormalities in pituitary tumors. 876 79

Pituitary adenylate cyclase activating peptide (PACAP) may play a role in neurogenesis, nerve injury, and neural tumor growth. A PACAP ligand receptor system functionally coupled to cAMP production was found to be expressed in the embryonic mouse neural tube at the onset of neurogenesis. PACAP was found to inhibit DNA synthesis and antagonize sonic hedgehog signaling in cells isolated from the neural tube, suggesting that PACAP interacts with patterning factors to regulate neurogenesis and phenotypic specification in the developing CNS. PACAP and PACAP receptor (PAC1) mRNA levels were strongly increased and decreased, respectively, in motor neurons in adult rats after facial nerve axotomy, indicating that PACAP may also act in nerve regeneration. Experiments using a neuroblastoma tumor cell line model indicate that PACAP may execute growth-related functions by activating MAP kinase in addition to cAMP-dependent protein kinase A.
 ...
PMID:PACAP action in nervous system development, regeneration, and neuroblastoma cell proliferation. 1119 16

Pituitary hyperplasia and lactotroph replication are induced by estrogen. The product of the pituitary tumor transforming gene (PTTG) exhibits in vitro and in vivo transforming activity and induces basic bFGF secretion, thereby modulating pituitary angiogenesis and tumor formation. We demonstrated previously that pituitary pttg is induced by estrogen and bFGF, the latter being expressed in a concordant fashion with pttg in experimental and human pituitary adenomas. We now elucidate the role of estrogen in paracrine regulation of pituitary tumorigenesis by PTTG. Coincident with the circulating rat estradiol surge and maximal pituitary proliferation, pituitary pttg mRNA, bFGF, and VEGF expression increased approximately threefold during proestrus and estrus. Osmotic mini-pump coinfusion of estrogen and antiestrogen abrogated estrogen-induced pituitary pttg expression in vivo, suppressed serum PRL concentrations by 88%, and attenuated prolactin-secreting pituitary tumor growth by 41% in rats. Antiestrogen treatment of primary human pituitary tumor cultures reduced PTTG expression approximately 65%. Pituitary pttg, bFGF, and VEGF are cyclically expressed during the rat estrus cycle, concordantly with estrogen levels. Because anti-estrogens reduced PTTG expression in human pituitary tumors in vitro and suppressed experimental tumor growth in vivo, concomitantly with reduced PRL secretion, these results indicate a role for selective antiestrogens in treating pituitary tumors.
 ...
PMID:Functional role of estrogen in pituitary tumor pathogenesis. 1180 40

Pituitary hyperplasia and tumor growth are regulated by various hormones and growth factors. Estrogen (E(2)) stimulates pituitary cell proliferation and prolactin (PRL) production. Estrogen also regulates transforming growth factor-B (TGF-B) effects in the pituitary. IGF-B in turn regulates various cell cycle proteins including p15 and p27(Kip1) (p27). To better understand the regulatory role of growth factors and hormones in the cell cycle we analyzed cyclin D(1), cyclin E, and p27 expression in normal and neoplastic rat pituitary cells. An in vitro analysis using cultured normal pituitary cells and GH(3) tumor cells and an in vivo analysis of estrogen-treated normal pituitary and implanted GH(3) cells were performed. Semiquantitative RT-PCR was used to analyze mRNA expression for cyclin D(1) cyclin E, and p27 in cultured pituitary cells and E(2)-treated pituitaries in vivo, Cyclin D(1) and p27 were localized in the nuclei of normal pituitary cells by immunocytochemistry (ICC). Very weak or absent immunostaining for cyclin D(1) and p27 was present in GH(3) cells. Both normal pituitary and GH(3) cells had strong nuclear staining for cyclin E. Normal pituitary had a 20-fold greater amount of cyclin D mRNA and a 3-fold greater amount of p27 mRNA compared to GH cells, whereas GH cells had slightly (1.5-fold) more cyclin E than normal pituitary cells. Treatment in vivo stimulated cell proliferation and decreased cyclin D(1) mRNA levels in normal pituitary. GH(3) tumor cells, implanted subcutaneously in the same animal, showed increased proliferation after E(2) treatment, but there was no change in cyclin B(1) mRNA in GH(3) cells. Cyclin E and p27 mRNA levels did not change significantly in normal pituitary or in GH(3) cells after E(2) treatment in vivo. Treatment of normal pituitary cells with 10(-9)M TGF-B1 for 3 d in vitro led to significant decreases in cyclin B(1) and p27 mRNAs (p < 0.05 ), whereas cyclin E levels were unchanged. These results indicate that cyclin B(1) and p27 mRNAs are present at significantly higher levels in normal pituitary compared to GH(3) cells, and that both E(2) and TGF-B1 can down-regulate cyclin B(1) mRNA levels in normal pituitary cells, suggesting that these factors regulate G1 to S phase transition in pituitary cells. The lower levels of specific cell cycle regulators in GH cells may explain the decreased regulatory control by E(2) in GH(3) tumor cells.
 ...
PMID:TGF-B and Estrogen Regulate P27(Kip1) and Cyclin D(1) in Normal and Neoplastic Rat Pituitary Cells. 1211 29


1 2 3 4 5 6 7 Next >>