Hypothalamic Hormones and Cancer

Schally, Andrew V.; Comaru‐Schally, Ana Maria; Nagy, Attila; Kovács, Magdolna; Szepesházi, Karoly; Płonowski, Artur; Varga, József; Halmos, Gábor

doi:10.1006/frne.2001.0217

Cited by 265 publications

(508 citation statements)

References 112 publications

Supporting

Mentioning

472

Contrasting

Unclassified

Order By: Relevance

“…In recent years several series of antagonistic analogs of growth hormone-releasing hormone (GHRH) were synthesized in an endeavour to develop a new class of antineoplastic agents [8][9][10][11]. GHRH antagonists inhibit the growth of various experimental human cancers [12], but their effects on triple-negative breast cancers have not been studied.…”

Section: Introductionmentioning

confidence: 99%

“…The indirect, endocrine mechanism operates through the suppression of the GH release from the pituitary, and the resulting inhibition of the hepatic production of IGF-I [8,9]. In addition, it was observed that GHRH antagonists can inhibit the proliferation of diverse cancer lines by direct action in vitro, under conditions in which the contribution of the hypothalamic GHRH/pituitary GH/hepatic IGF-I axis is clearly excluded [8,[13][14][15][16][17][18][19][20][21][22][23][24][25]. These studies led to the conclusion that the main mechanism responsible for tumor inhibition could be a direct effect of the antagonists on the tumor tissue [8,11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Köster

Engel

Schally

et al. 2008

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Köster

Engel

Schally

et al. 2008

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

“…Luteinising hormone-releasing hormone (LHRH) receptors have increased expression in many cancers compared to normal cells (Emons et al, 1998;Schally et al, 2001;Straub et al, 2001), with increased expression in benign prostate hyperplasia (BPH) as well (Straub et al, 2003). The presence of these receptors enables LHRH analogues to affect directly prostate tumour cells (Qayum et al, 1990;Halmos et al, 2000) in addition to the indirect central androgen suppression.…”

mentioning

confidence: 99%

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

2005

View full text Add to dashboard Cite

Cetrorelix, a luteinising hormone-releasing hormone (LHRH) analogue, has been shown to limit growth of the human androgenindependent prostate cell line DU-145, although other inhibitory actions may also be affected. Both growth and invasion of DU-145 cells are linked to autocrine epidermal growth factor receptor (EGFR) signalling. Invasiveness requires not only cells to migrate to conduits, but also reduced adhesiveness between tumour cells to enable separation from the tumour mass. Thus, we investigated whether Cetrorelix alters the DU-145 cell -cell adhesion and if this occurs via altered EGFR signalling. Pharmacologic levels of Cetrorelix limited the invasiveness of a highly invasive DU-145 subline overexpressing full-length EGFR (DU-145 WT). Extended exposure of the cells to Cetrorelix resulted in increased levels of the cell -cell adhesion complex molecules E-cadherin, a-and bcatenin, and p120. Puromycin blocked the increases in E-cadherin and b-catenin levels, suggesting that de novo protein synthesis is required. The Cetrorelix effect appears to occur via transmodulation of EGFR by a protein kinase C (PKC)-dependent mechanism, as there were no changes in DU-145 cells expressing EGFR engineered to negate the PKC transattenuation site (DU-145 A654); downregulation of EGFR signalling produced a similar upregulation in adhesion complex proteins, further suggesting a role for autocrine signalling. Cetrorelix increased the cell -cell adhesiveness of DU-145 WT cells to an extent similar to that seen when autocrine EGFR signalling is blocked; as expected, DU-145 A654 cell -cell adhesion also was unaffected by Cetrorelix. The increased adhesiveness is expected as the adhesion complex molecules moved to the cells' periphery. These data offer direct insight into the possible crosstalk pathways between the LHRH and EGFR receptor signalling. The ability of Cetrorelix to downregulate EGFR signalling and subsequently reverse the antiadhesiveness found in metastatic prostate cancer highlights a novel potential target for therapeutic strategies.

show abstract

“…To sustain this positive and growing trend, further and newer treatment methods must be perceived and instituted. Recent relevant advances encompass the development of three types of analogs of luteinizing hormone releasing hormone (LHRH) and the discovery of expression of receptors for the hypothalamic releasing hormones, including those for LHRH (LHRH-R), in cancer cells [6][7][8][9]. In various studies, analogs of other neurohormones (e.g.…”

Section: Introductionmentioning

confidence: 99%

LHRH receptor expression in sarcomas of bone and soft tissue

Deivaraju¹,

Temple²,

Block³

et al. 2016

Hormone Molecular Biology and Clinical Investigation

Self Cite

View full text Add to dashboard Cite

Aim: Luteinizing hormone releasing hormone (LHRH) is a neurohormone, secreted by the hypothalamus, which regulates the secretion of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. LHRH acts by binding to receptors located in the pituitary gland. These receptors (LHRH receptors) have also been found in the cytoplasm of many tumor cells that involve both the reproductive and non-reproductive organs. These receptors have been demonstrated in prostate and breast cancers, endometrial carcinomas, renal cell carcinoma, lymphoma, carcinoma of liver, pancreas and skin. So far, the expression of LHRH receptors on sarcomas (i.e. malignant tumors of mesenchymal origin) has not been studied, except for endometrial sarcomas. It has also been demonstrated that both LHRH agonists and antagonists can down-regulate these receptors and thus inhibit these tumor cells. Another major therapeutic implication is that these receptors can be targeted specifically by peptides conjugated to anti-cancer drugs. The purpose of this study was to determine if LHRH receptors are expressed in primary and/or metastatic sarcomas of human origin. Methods: We looked at LHRH receptor expression in 38 consecutive sarcoma specimens, using immunohistochemistry. The specimens were either from office biopsy or from resected tumor; these were confirmed as sarcomas by histopathological examination. The receptor staining characteristics and the staining intensity were also documented. The pattern of staining was classified either as "focal or diffuse staining of the cytoplasm" and the intensity of staining was graded on a scale from 1+ to 4+. Results: Positive receptor staining was seen in 25 of the 38 (66%) specimens. Twelve of the specimens stained diffusely and 13 had focally positive staining. Three tumors had 1+ staining, 10 had 2+ staining, six had 3+ staining, and six tumors had 4+ staining. The tumors included undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, myofibroblastic sarcoma, myxofibrosarcoma, liposarcoma, dermatofibrosarcoma protuberans, metastatic chondrosarcoma and chordoma. Conclusion: Sarcomas express LHRH receptors with a varying incidence and degree. Our study suggests that those sarcomas that are LHRH receptor positive could potentially be treated with targeted chemotherapy.

show abstract

Hypothalamic Hormones and Cancer

Cited by 265 publications

References 112 publications

Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

LHRH receptor expression in sarcomas of bone and soft tissue

Contact Info

Product

Resources

About