scholarly journals Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells

2017 ◽  
Vol Volume 10 ◽  
pp. 4329-4338 ◽  
Author(s):  
Yuko Asari ◽  
Kazunori Kageyama ◽  
Yuki Nakada ◽  
Mizuki Tasso ◽  
Shinobu Takayasu ◽  
...  
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Inhibitory Effects ◽  
Hormone Production ◽  
Jak2 Inhibitor

scholarly journals Inhibitory effects of trichostatin A on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT-20 cells

2015 ◽  
Vol 62 (12) ◽  
pp. 1083-1090 ◽  
Author(s):  
Yuki Nakada ◽  
Kazunori Kageyama ◽  
Aya Sugiyama ◽  
Rie Desaki ◽  
Shinobu Takayasu ◽  
...  
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Trichostatin A ◽  
Inhibitory Effects ◽  
Hormone Production

Adrenocorticotropin Production by a Mammary Carcinoma

1977 ◽  
Vol 35 ◽  
pp. 462-463
Author(s):  
K.S. McCarty ◽  
N.R. Wallace ◽  
W. Litaker ◽  
S. Wells ◽  
G. Eisenbarth
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Small Cell ◽  
Hormone Production ◽  
Carcinoma Of The Breast ◽  
Ectopic Acth ◽  
Ultrastructural Studies ◽  
Subcutaneous Metastases ◽  
Ectopic Acth Production ◽  
The Right ◽  
Pituitary Carcinomas

The production of adrenocorticotropic hormone by non-pituitary carcinomas has been documented in several tumors, most frequently small cell carcinoma of the lung, islet cell carcinomas of the pancreas, thymomas and carcinoids. Electron microscopy of these tumors reveals typical membrane-limited "neurosecretory" granules. Confirmation of the granules as adrenocorticotropin (ACTH) requires the use of OsO4 as a primary fixative to give the characteristic cored granule appearance in conjunction with immunohistochemical demonstration of the hormone peptide. Because of the rarity of ectopic ACTH production by mammary carcinomas and the absence of appropriate ultrastructural studies in the two examples of such ectopic hormone production in the literature of which we are aware (1,2), we present biochemical and ultrastructural data from a carcinoma of the breast with apparent ACTH production.The patient had her primary tumor in the right breast in 1969. The tumor recurred as visceral and subcutaneous metastases in 1976 and again in 1977.

scholarly journals ACTH-PRODUCING PERIPHERAL PULMONARY CARCINOID

2018 ◽  
Vol 99 (4) ◽  
pp. 211-215
Author(s):  
I. Z. Korobkova ◽  
D. A. Dremin ◽  
S. M. Kacalov ◽  
I. V. Kirsan ◽  
A. A. Ugrimov ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Adrenocorticotropic Hormone ◽  
Imaging Techniques ◽  
Diagnostic Algorithm ◽  
Integrated Approach ◽  
Hormone Production ◽  
Pulmonary Carcinoid ◽  
Topical Diagnosis ◽  
Acth Secreting ◽  
Rule Out

The paper describes a clinical example of the topical diagnosis of adrenocorticotropic hormone (ACTH)-producing typical peripheral pulmonary carcinoid. The first stage in its diagnosis was to rule out the production of ACTH by the pituitary gland. The paper presents information on the most common localization of functioning neuroendocrine tumors, as well as a diagnostic algorithm to search for an ectopic focus of the ACTH-secreting tumor that causes hypercorticism. Taking into account that bronchopulmonary neuroendocrine tumors with ectopic hormone production occur rarely (5%), a clinical example is given to demonstrate the capabilities of imaging techniques and standards for their implementation using an integrated approach.

scholarly journals Synchronous aldosterone- and cortisol-producing adrenocortical adenomas diagnosed using CYP11B immunohistochemistry

2019 ◽  
Vol 7 ◽  
pp. 2050313X1988377
Author(s):  
Adam Stenman ◽  
Ivan Shabo ◽  
Annica Ramström ◽  
Jan Zedenius ◽  
Carl Christofer Juhlin
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Histopathological Diagnosis ◽  
Hormone Production ◽  
Postoperative Evaluation ◽  
Clinical Routine ◽  
Adrenocortical Adenomas ◽  
Adrenocortical Hyperplasia ◽  
Clinical Consequences ◽  
Autonomous Cortisol Secretion

Immunohistochemistry with antibodies targeting enzymes responsible for the final conversion steps of cortisol (CYP11B1) and aldosterone (CYP11B2) is gaining ground as an adjunct tool in the postoperative evaluation of adrenocortical nodules. The method allows the pathologist to visualize hormone production for each lesion, thereby permitting a more exact assessment regarding the distinction between adrenocortical adenomas and adrenocortical hyperplasia, with implications for patient follow-up. We describe how immunohistochemistry facilitated the histopathological diagnosis of twin adenoma (one cortisol- and one aldosterone-producing) from suspected hyperplasia in a patient with hypertension, mild autonomous cortisol secretion and concurrent adrenocorticotropic hormone–producing adrenomedullary hyperplasia. As the nodules were similar in size and displayed rather analogous histology, CYP11B1 and B2 immunohistochemistry was needed to exclude adrenocortical hyperplasia, allowing us to discharge the patient from further surveillance. We conclude that the application of functional immunohistochemistry has direct clinical consequences and advocates the prompt introduction of these markers in clinical routine.

The Novel JAK2 Inhibitor NVP-BSK805 Has Cytotoxic Activity on Malignant Plasma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2993-2993
Author(s):  
Renate Burger ◽  
Franziska Rademacher ◽  
Matthias Staudinger ◽  
Matthias Peipp ◽  
Andreas Güunther ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Plasma Cell ◽  
Stromal Cells ◽  
Plasma Cells ◽  
Myeloma Cell ◽  
Synergistic Activity ◽  
Jak Inhibitors ◽  
Inhibitory Effects ◽  
Jak2 Inhibitor

Abstract Abstract 2993 In multiple myeloma (MM) and plasma cell leukemia, activation of the JAK/STAT pathway is induced by interleukin (IL)-6, which is produced and secreted into the tumor microenvironment primarily by stromal cells. Upon binding of IL-6 to its specific alpha-chain receptor, dimerization of the gp130 signaling subunits leads to activation of associated JAK kinases and STAT transcription factors. In particular, STAT3 has been shown to be essential for myeloma cell growth and survival. NVP-BSK805 (Novartis) is a novel substituted quinoxaline JAK2 inhibitor tool compound which displays more than 20-fold selectivity for JAK2 over the other JAK family members and more than 100-fold selectivity over a panel of additional kinases (Baffert et al., Mol Cancer Ther 9:1945, 2010). The study presented here aims at growth inhibitory effects of NVP-BSK805 in malignant plasma cells. NVP-BSK805 inhibited the growth of six human myeloma cell lines displaying dose-dependent activity with IC50 concentrations between 2.6 μ mol/L and 6.8 μ mol/L. Among the cell lines, IL-6 dependent INA-6 cells were most sensitive to the inhibitory effects of the compound: both IL-6 and bone marrow stromal cell induced proliferation as measured by [3H]-thymidine uptake was completely inhibited at 4 μ mol/L and IC50 concentrations were less than 1 μ mol/L. Viability of the stromal cells was not significantly affected. NVP-BSK805 concentrations as low as 0.5 μ mol/L were sufficient to yield a marked reduction of IL-6 induced STAT3 phosphorylation and complete abrogation at 2 μ mol/L, thereby blocking essential survival signals. Accordingly, treatment of INA-6 cells with NVP-BSK805 for 48 hours led to significant apoptosis starting at 2 μ mol/L with a 30% increase in annexin V-positive cell numbers compared to DMSO controls. Importantly, NVP-BSK805 showed potent cytotoxic activity on plasma cell-enriched primary tumor samples from patients with extramedullary plasma cell disease that are highly responsive to IL-6: in 3 out of 4 tumor samples the IC50 concentrations were between 0.5 μ mol/L and 0.6 μ mol/L. These studies are extended to combinations of NVP-BSK805 with PI3K, mToR, MAPK, HDAC, and IGF-1R inhibitors in order to optimize targeted therapy strategies facing different pathway alterations in individual myeloma patients. In INA-6 cells, synergistic activity was found combining NVP-BSK805 with rapamycin and the MEK1 inhibitor U0126. Preclinical in vivo studies are ongoing. Our results with NVP-BSK805 substantiate the use of JAK inhibitors as a therapeutic strategy for patients with MM. Since results from studies with pan-JAK inhibitors such as pyridone 6 indicate involvement of additional JAK kinases, the choice of the optimal compound will depend on its JAK family selectivity and the biology of JAK signaling in MM. Disclosures: No relevant conflicts of interest to declare.

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