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Sample records for adrenal cancer cell

  1. Adrenal Insufficiency Associated with Small Cell Lung Cancer: A Case Report and Literature Review.

    PubMed

    Noguchi, Shingo; Torii, Ryo; Shimabukuro, Ikuko; Yamasaki, Kei; Kido, Takashi; Yoshii, Chiharu; Mukae, Hiroshi; Yatera, Kazuhiro

    2016-06-01

    A 78-year-old Japanese man with fatigue, appetite loss, skin hyperpigmentation, hypotension and hypoglycemia, visited our hospital to evaluate an abnormal chest X-ray and adrenal gland swelling in echography in February 2015. Chest computed tomography showed a mass lesion in the right lower lobe and bilateral adrenal swellings, and small cell lung cancer (SCLC) with bilateral adrenal metastasis was diagnosed after bronchoscopy. According to low levels of serum cortisol, elevated adrenocorticotropic hormone (ACTH) and rapid ACTH test, the diagnosis of adrenal insufficiency associated with SCLC was made. Treatment with hydrocortisone (20 mg/day) was started in addition to systemic chemotherapy with carboplatin and etoposide. The patient's symptoms were slightly improved, however, systemic chemotherapy was discontinued according to the patient's request after 1 course of chemotherapy. Thereafter, he received only supportive care, and his general condition gradually worsened and he ultimately died in August 2015. Adrenal insufficiency associated with SCLC, which is caused by tissue destruction more than 90% of the adrenal glands, is rare although adrenal metastasis is not rare in patients with lung cancer. The findings such as general fatigue, appetite loss, hypotension, and hyponatremia are often got follow up as findings of advanced cancer, but appropriate therapy for adrenal insufficiency, supplement of the adrenal corticosteroid hormone, may lead to a significant improvement in the symptoms and quality of life in clinical practice of lung cancer. Therefore, physicians must consider potential adrenal insufficiency in lung cancer patients with bilateral adrenal metastasis. PMID:27302729

  2. Adrenal Gland Cancer

    MedlinePlus

    ... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

  3. What Is Adrenal Cortical Cancer?

    MedlinePlus

    ... include pheochromocytomas (which are most often benign) and neuroblastomas . This document is about tumors and cancers of ... does not discuss tumors of the adrenal medulla. Neuroblastoma s are covered in a separate document . Adrenal cortex ...

  4. Amitosis in human adrenal cells.

    PubMed

    Magalhães, M C; Pignatelli, D; Magalhães, M M

    1991-04-01

    Adrenal pieces obtained from 3 female and 2 male patients showed morphological figures of amitosis in adrenal zona reticularis cells. Such aspects were observed in both normal and hyperactive adrenals. Nuclei appeared constricted, heavily stained, with coarse chromatin, sometimes scattered among cytoplasmic organelles, but never marginating in crescentic caps. Cleavage of the cells originated two halves with a nucleolus in each pole. Binucleated cells were also seen in zona reticularis. The meaning of amitosis in human adrenal is discussed. PMID:1802124

  5. What Should You Ask Your Doctor about Adrenal Cortical Cancer?

    MedlinePlus

    ... after treatment for adrenal cancer? What should you ask your doctor about adrenal cancer? As you deal ... frank, open discussions with your cancer care team. Ask any questions, no matter how trivial they might ...

  6. Diagnosis and Management of Hereditary Adrenal Cancer.

    PubMed

    Angelousi, Anna; Zilbermint, Mihail; Berthon, Annabel; Espiard, Stéphanie; Stratakis, Constantine A

    2016-01-01

    Benign adrenocortical tumours (ACT) are relatively frequent lesions; on the contrary, adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with unfavourable prognosis. Recent advances in the molecular understanding of adrenal cancer offer promise for better therapies in the future. Many of these advances stem from the molecular elucidation of genetic conditions predisposing to the development of ACC. Six main clinical syndromes have been described to be associated with hereditary adrenal cancer. In these conditions, genetic counselling plays an important role for the early detection and follow-up of the patients and the affected family members. PMID:27075352

  7. Adrenal metastases in lung cancer: clinical implications of a mathematical model.

    PubMed

    Bazhenova, Lyudmila; Newton, Paul; Mason, Jeremy; Bethel, Kelly; Nieva, Jorge; Kuhn, Peter

    2014-04-01

    Adrenal gland metastases are common in lung cancer. It is well recognized that aggressive treatment of solitary adrenal metastases leads to improved outcomes but the exact nature of adrenal deposits is not well understood. Controversy exists as to the routing of cancer cells to the adrenal gland with some believing that this transmission is lymphatic, in contrast to the more generally accepted theory of hematogenous spread. Recently published mathematical modeling of cancer progression strongly supports the lymphatic theory. With that in mind, we performed a literature review to look for biological plausibility of simulation results and believe that evidence supports the contention that metastases to the adrenal gland can be routed by means of lymphatic channels. This could explain improved survival for patients in whom solitary adrenal metastases are managed aggressively with surgical or radiation modalities. We are calling for clinical trials prospectively testing this hypothesis. PMID:24736064

  8. Endocytosis of connexin protein in adrenal cells.

    PubMed

    Murray, Sandra A; Nickel, B M; Gay, V L

    2004-11-01

    The ability of adrenocorticotropin (ACTH) to affect gap junctions was examined in adrenal cells in vivo and in vitro. Treatment with ACTH increased the size and number of gap junction plaques on the cell membranes in hypophysectomized animals and in adrenal culture. Intracellular (cytoplasmic) annular gap junctions were observed in cells of the inner adrenal cortical zones and in adrenal cell cultures. To investigate the relationship of annular gap junctions to surface junctions, adrenal cells in culture were transfected with cDNA encoding a green fluorescent protein tagged connexin 43 construct (Cx43-GFP), and subsequently studied by time-lapse video microscopy, immunocytochemistry, and transmission electron microscopy (TEM). Internalization of part or all of a surface gap junction plaque resulted in annular gap junction formation. These studies support the hypothesis that cytoplasmic vesicles, initially described with TEM methods, can result from removal of gap junction plaques from the cell surface. It is suggested that hormones can play a regulatory role in cell-cell communication by influencing the availability of gap junction protein at the cell surface and that hormonally-sensitive processes might serve as a means of altering intercellular communication. PMID:15666807

  9. [Adrenalitis].

    PubMed

    Saeger, W

    2016-05-01

    Inflammation of the adrenal glands is caused by autoimmunopathies or infections and can induce adrenal insufficiency. Autoimmune lymphocytic adrenalitis is often combined with other autoimmune diseases and the most frequent cause of Addison's disease; however, it only becomes clinically apparent when more than 90 % of the adrenal cortex has been destroyed. Histological features are characterized by lymphoplasmacytic inflammation leading to an increased destruction of adrenocortical tissue but less severe courses can also occur. The second most frequent form of adrenalitis is adrenal tuberculosis, showing typical granulomatous findings that are nearly always caused by spreading from a tuberculous pulmonary focus. Other bacterial as well as viral infections, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and others, generally affect the adrenal glands only in patients with immunodeficiency disorders. In these infections, the adrenal cortex and medulla are frequently involved to roughly the same extent. Although surgical specimens from inflammatory adrenal lesions are extremely rare, the various forms of adrenalitis play an important role in the post-mortem examination of the adrenal glands for clarification of unclear causes of death (e.g. death during an Addisonian crisis). PMID:27099224

  10. Preoperative CT evaluation of adrenal glands in non-small cell bronchogenic carcinoma

    SciTech Connect

    Nielsen, M.E. Jr.; Heaston, D.K.; Dunnick, N.R.; Korobkin, M.

    1982-08-01

    Preoperative chest computed tomographic (CT) scans in 84 patients with biopsy-proven non-small cell bronchogenic carcinoma were reviewed. At least one adrenal gland was visualized in 70 of these. Evidence of a solid adrenal mass was present in 18 (14.5%) glands in 15 (21.4%) patients. Percutaneous needle aspiration under CT guidance confirmed metastatic malignancy in the four patients who were biopsied. Because the documented presence of adrenal metastases in non-small cell lung cancer makes surgical resection or local irradiation inappropriate, it is recommended that both adrenal glands in their entirety be specifically included whenever a staging chest CT examination is performed in patients with such tumors. Percutaneous needle biopsy for pathologic confirmation of the nature of solid adrenal masses discovered in this process is also useful.

  11. Acute Abdominal Pain after Intercourse: Adrenal Hemorrhage as the First Sign of Metastatic Lung Cancer

    PubMed Central

    Packer, Clifford D.

    2014-01-01

    Although the adrenal glands are a common site of cancer metastases, they are often asymptomatic and discovered incidentally on CT scan or autopsy. Spontaneous adrenal hemorrhage associated with metastatic lung cancer is an exceedingly rare phenomenon, and diagnosis can be difficult due to its nonspecific symptoms and ability to mimic other intra-abdominal pathologies. We report a case of a 65-year-old man with a history of right upper lobectomy seven months earlier for stage IB non-small cell lung cancer who presented with acute abdominal pain after intercourse. CT scan revealed a new right adrenal mass with surrounding hemorrhage, and subsequent FDG-PET scan confirmed new metabolic adrenal metastases. The patient's presentation of abdominal pain and adrenal hemorrhage immediately after sexual intercourse suggests that exertion, straining, or increased intra-abdominal pressure might be risk factors for precipitation of hemorrhage in patients with adrenal metastases. Management includes pain control and supportive treatment in mild cases, with arterial embolization or adrenalectomy being reserved for cases of severe hemorrhage. PMID:25126096

  12. Transplantation of Adrenal Cortical Progenitor Cells Enriched by Nile Red

    PubMed Central

    Dunn, James C.Y.; Chu, Yinting; Qin, Harry H.; Zupekan, Tatiana

    2009-01-01

    Background The adrenal cortex may contain progenitor cells useful for tissue regeneration. Currently there are no established methods to isolate these cells. Material and Methods Murine adrenal cells were sorted into a Nile-Red-bright (NRbright) and a Nile-Red-dim (NRdim) population of cells according to their degree of cholesterol content revealed by Nile Red fluorescence. The cells were transplanted under the renal capsule to determine their ability for regeneration. Results The NRbright cells contained an abundance of lipid droplets, whereas the NRdim cells contained little. The NRbright cells expressed Sf1 and the more differentiated adrenal cortical genes including Cyp11a1, Cyp11b1, and Cyp11b2, whereas the NRdim cells expressed Sf1 but not the more differentiated adrenal cortical genes. After 56 days of implantation in unilateral adrenalectomized mice, the NRdim cells expressed Sf1 and the more differentiated adrenal cortical genes, whereas the NRbright cells ceased to express Sf1 as well as the more differentiated adrenal cortical genes. NRdim cells also proliferated in the presence of basic fibroblast growth factor. Conclusions The population of NRdim cells contained adrenal cortical progenitor cells that can proliferate and give rise to differentiated daughter cells. These cells may be useful for adrenal cortical regeneration. PMID:19592014

  13. Intrinsic GABAergic system of adrenal chromaffin cells.

    PubMed Central

    Kataoka, Y; Gutman, Y; Guidotti, A; Panula, P; Wroblewski, J; Cosenza-Murphy, D; Wu, J Y; Costa, E

    1984-01-01

    Histochemical and biochemical studies demonstrate that gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (EC 4.1.1.15), and GABA aminotransferase (EC 2.6.1.19) are present in bovine adrenal chromaffin cells. Moreover, [3H]GABA can be taken up and stored by primary cultures of adrenal chromaffin cells. Nicotinic receptor stimulation or KCl depolarization releases the [3H]GABA taken up by these cell cultures. GABA and benzodiazepine recognition sites located in chromaffin cells interact with each other with modalities similar to those described for GABA and benzodiazepine recognition sites located in synaptic membranes prepared from brain tissue. Bicuculline facilitates the release of catecholamine from chromaffin cells induced by nicotinic receptor stimulation but it fails to influence the release of catecholamine evoked by K+ depolarization. Since the GABA-benzodiazepine receptor system appears to modulate nicotinic receptor function, it is suggested that GABA transmission might participate in modulating responsiveness of chromaffin cells to incoming cholinergic stimuli. Images PMID:6328506

  14. [Mantle cell lymphoma markedly infiltrated into adrenal glands with adrenal insufficiency].

    PubMed

    Hashimoto, Ryo; Iwakiri, Rika; Tsutsumi, Hisashi; Ohta, Masatsugu; Mori, Mayumi

    2004-07-01

    A 66-year-old male was admitted to our hospital complaining of bilateral hypochondrial pain, back pain and loss of weight in May, 2002. Superficial lymph nodes were not palpable on admission. The leukocyte count was 3430/microl, hemoglobin concentration, 13.0g/dl, and platelet count, 174000/microl. LDH, soluble IL-2 receptor, ACTH and cortisol values were out of the normal range (LDH 1368IU/l, sIL-2R 2630U/ml, ACTH 132pg/ml, cortisol 7.4microg/dl). Abdominal CT scan showed bilateral adrenal masses, and abnormal uptake of Ga-scintigraphy was seen correspondent with the bilateral adrenal masses. The histological diagnosis of bilateral adrenal masses cannot be performed because of the bleeding tendency, but atypical cells were observed in the patient's bone marrow aspirate. Surface marker analysis of atypical cells showed CD5+, cyclin D1+, CD19+, CD20+ and HLA-DR+. From these results we diagnosed this case as a mantle cell lymphoma (stage IV B) markedly infiltrated into the adrenal glands with adrenal insufficiency. The bilateral adrenal masses dramatically reduced in size after CHOP chemotherapy with hydrocortisone supplementation. We report on the present case and summarize the reports of adrenal grand-infiltrating lymphomas. PMID:15359915

  15. Lymphangiogenesis may explain adrenal selectivity in lung cancer metastases.

    PubMed

    Onuigbo, Wilson I B

    2010-08-01

    The 'seed and soil' hypothesis of organ selectivity in cancer metastasis dated back to the 1870s. A century later, a review of significant selectivity data revealed that the adrenals featured in 11 of 12 classes of it, thus promoting these two organs for research. Fortunately, two discoveries have also occurred, namely, (a) that cancer stimulates lymph vessel formation, i.e., lymphangiogenesis, and (b) that lymph and blood vessels are differentially stainable. Accordingly, these interesting ideas should be exploited with a hypothesis. Therefore, it is proposed that, at autopsy in lung cancer cases, the tissues between the primary lung tumor and the adrenal secondary should be meticulously serially sectioned and disjunctively stained because they must reveal what naturally occurs in this zone during life. It is predicted that this maneuver will identify lymphangiogenesis as the phenomenon responsible for the age-old puzzle of adrenal selectivity. Indeed, it may explain other puzzles such as intracranial lymphatic connectivity. PMID:20303219

  16. Extensive esterification of adrenal C19-delta 5-sex steroids to long-chain fatty acids in the ZR-75-1 human breast cancer cell line

    SciTech Connect

    Poulin, R.; Poirier, D.; Merand, Y.; Theriault, C.; Belanger, A.; Labrie, F.

    1989-06-05

    Estrogen-sensitive human breast cancer cells (ZR-75-1) were incubated with the 3H-labeled adrenal C19-delta 5-steroids dehydroepiandrosterone (DHEA) and its fully estrogenic derivative, androst-5-ene-3 beta,17 beta-diol (delta 5-diol) for various time intervals. When fractionated by solvent partition, Sephadex LH-20 column chromatography and silica gel TLC, the labeled cell components were largely present (40-75%) in three highly nonpolar, lipoidal fractions. Mild alkaline hydrolysis of these lipoidal derivatives yielded either free 3H-labeled DHEA or delta 5-diol. The three lipoidal fractions cochromatographed with the synthetic DHEA 3 beta-esters, delta 5-diol 3 beta (or 17 beta)-monoesters and delta 5-diol 3 beta,17 beta-diesters of long-chain fatty acids. DHEA and delta 5-diol were mainly esterified to saturated and mono-unsaturated fatty acids. For delta 5-diol, the preferred site of esterification of the fatty acids is the 3 beta-position while some esterification also takes place at the 17 beta-position. Time course studies show that ZR-75-1 cells accumulate delta 5-diol mostly (greater than 95%) as fatty acid mono- and diesters while DHEA is converted to delta 5-diol essentially as the esterified form. Furthermore, while free C19-delta 5-steroids rapidly diffuse out of the cells after removal of the precursor (3H)delta 5-diol, the fatty acid ester derivatives are progressively hydrolyzed, and DHEA and delta 5-diol thus formed are then sulfurylated prior to their release into the culture medium. The latter process however is rate-limited, since new steady-state levels of free steroids and fatty acid esters are rapidly reached and maintained for extended periods of time after removal of precursor, thus maintaining minimal concentrations of intracellular steroids.

  17. Principles and management of adrenal cancer

    SciTech Connect

    Javadpour, N.

    1987-01-01

    This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imaging techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.

  18. Isolated adrenal masses in nonsmall-cell bronchogenic carcinoma

    SciTech Connect

    Oliver, T.W. Jr.; Bernardino, M.E.; Miller, J.I.; Mansour, K.; Greene, D.; Davis, W.A.

    1984-10-01

    Computed tomography has become an important diagnostic modality in the preoperative staging of patients with bronchogenic carcinoma. The adrenal glands represent one of the most frequent sites of metastasis. Therefore, an isolated adrenal mass discovered on preoperative thoracoabdominal CT poses a diagnostic problem. Three hundred thirty patients with histologically proved nonsmall-cell bronchogenic carcinoma were evaluated. Thirty-two had adrenal masses without further evidence of disease in the abdomen, Eight of these 32 masses were metastases, 17 were proved adenomas, and 7 did not undergo biopsy. Thus an isolated adrenal mass is more likely benign than metastatic, and biopsy is advocated prior to withholding potentially curative surgery.

  19. Giant adrenal pseudocyst harbouring adrenocortical cancer

    PubMed Central

    Wilkinson, Michael; Fanning, Deirdre Mary; Moloney, James; Flood, Hugh

    2011-01-01

    The authors report a very rare case of adreno-cortical carcinoma arising in a giant adrenal pseudocyst. A 64-year-old woman presented to the emergency department with a 6 week history of progressively worsening severe left abdominal pain, anorexia, anergia and constipation. On examination, she was cachectic with tenderness over the left abdomen and flank. Medical history was significant for gastritis and anaemia. During her investigation, a well-defined para-renal 12×6 centimetre multi-loculated cyst, of uncertain origin was identified on CT. Ultrasound-guided biopsy was not diagnostic. MRI showed the cyst to be likely adrenal in origin. Serum and urinary catecholamines were unremarkable. At laparotomy an unresectable large, tense, fixed, cystic mass was seen to occupy the left side of the abdomen. The cyst was de-roofed. Pathology showed a high-grade poorly differentiated adreno-cortical carcinoma with a pseudo-capsule. She died 2 months postoperatively. PMID:22679267

  20. Adrenal metastasis of breast cancer with involvement of the inferior vena cava.

    PubMed

    Fernández Sarabia, Maria Trinidad; Rodríguez García, Jose Manuel; Cardenal Escarcena, Antonio; Serrano Vicente, Justo; García Bernardo, Lucia

    2008-11-01

    Tumour thrombosis of the inferior cava vein is usually associated with primary renal cell cancer. To our knowledge, this is the first case reported of adrenal metastasis of breast cancer extending into the inferior vena cava. There are few references in the literature documenting this extension with positron emission tomography (PET) and enhanced computed tomography (CT). The authors focus on the role of combined PET-CT imaging in the accurate detection of malignant thrombus. PMID:19015074

  1. Incidentally Solitary, Synchronous, Metastatic Left Adrenal Mass From Colon Cancer

    PubMed Central

    Alvandipour, Mina; Khalvati, Mehdi; Khodabakhsh, Hamed

    2016-01-01

    The authors report the case of a 63-year-old man who underwent an open adrenalectomy for a synchronous, malignant, metastatic left adrenal tumor and a total colectomy for T3N0M1 (stage 4) primary, malignant colon cancer. Two polypoid lesions, one measuring 40 mm × 30 mm × 30 mm and the other measuring 20 mm × 10 mm × 10 mm, were found in the ascending colon and rectosigmoid (RS) junction, respectively, and a synchronous, malignant, left adrenal gland lesion measuring 70 mm × 50 mm × 30 mm was incidentally found on abdominal computed tomography scan. Histological examination revealed a metastatic, necrotic adenocarcinoma of the left adrenal mass, an adenocarcinoma of the cecal mass, and an adenomatous polyp (tubulovillous type) of the smallest polypoid lesion in RS junction that had invaded deeply into the submucosal layer. The patient recovered uneventfully, and his condition is now stable, with no evidence of local recurrence or metastatic disease, 2 years after the surgery. To the best of our knowledge, only 25 cases of an adrenalectomy for treating metastatic adrenal gland tumors have been reported to date; physicians should be aware of the possibility of this event. PMID:27218099

  2. Vesicle Pools: Lessons from Adrenal Chromaffin Cells

    PubMed Central

    Stevens, David R.; Schirra, Claudia; Becherer, Ute; Rettig, Jens

    2011-01-01

    The adrenal chromaffin cell serves as a model system to study fast Ca2+-dependent exocytosis. Membrane capacitance measurements in combination with Ca2+ uncaging offers a temporal resolution in the millisecond range and reveals that catecholamine release occurs in three distinct phases. Release of a readily releasable (RRP) and a slowly releasable (SRP) pool are followed by sustained release, due to maturation, and release of vesicles which were not release-ready at the start of the stimulus. Trains of depolarizations, a more physiological stimulus, induce release from a small immediately releasable pool of vesicles residing adjacent to calcium channels, as well as from the RRP. The SRP is poorly activated by depolarization. A sequential model, in which non-releasable docked vesicles are primed to a slowly releasable state, and then further mature to the readily releasable state, has been proposed. The docked state, dependent on membrane proximity, requires SNAP-25, synaptotagmin, and syntaxin. The ablation or modification of SNAP-25 and syntaxin, components of the SNARE complex, as well as of synaptotagmin, the calcium sensor, and modulators such complexins and Snapin alter the properties and/or magnitudes of different phases of release, and in particular can ablate the RRP. These results indicate that the composition of the SNARE complex and its interaction with modulatory molecules drives priming and provides a molecular basis for different pools of releasable vesicles. PMID:21423410

  3. Immunohistochemical distinction of metastases of renal cell carcinoma to the adrenal from primary adrenal nodules, including oncocytic tumor.

    PubMed

    Li, Hongmei; Hes, Ondrej; MacLennan, Gregory T; Eastwood, Daniel C; Iczkowski, Kenneth A

    2015-05-01

    Metastases of clear cell renal cell carcinoma to the adrenal can mimic primary adrenal cortical neoplasms or normal adrenal, especially in biopsy material. We compared 34 cases of clear cell renal cell carcinoma metastasis to the adrenal with 49 primary adrenal lesions (16 carcinoma, 22 adenoma, 9 oncocytic tumor, and 2 hyperplasia). Normal adrenal was available in 59 cases. Each entity was represented on tissue microarrays by duplicate-triplicate evaluable spots taken from spatially separate areas. Two pathologists evaluated all reactivity from 0 to 3+. A panel of 12 immunohistochemical stains was performed, including the first diagnostic uses of steroid receptor coactivator (SRC1) and equilibrative nucleoside transporter 1 (ENT1). The most sensitive and specific renal cell carcinoma markers were membranous reactivity for carbonic anhydrase IX (CAIX) and RCC marker and nuclear reactivity for PAX8. For adrenal cortical carcinomas, best markers were synaptophysin, SRC1, and MelanA; and for adrenal oncocytic tumor, synaptophysin and ENT1. Optimal markers for adrenal cortical adenoma and normal adrenal were ENT1 (more specific) and either MelanA or SRC1 (more sensitive). Calretinin, cytokeratin 34βE12 and CAM5.2, inhibin, and steroidogenic factor 1 (SF1) proved less valuable to the panel. Nonspecific cytoplasmic biotin reactivity was frequent for CAIX and PAX8. Tumors with high-grade cytology should be worked up with 2 of the 3 stains: CAIX, PAX8, or RCC marker; and either SRC1 or MelanA. Adrenal adenoma, or normal adrenal, versus low-grade renal cell carcinoma are distinguished by a panel of: CAIX, PAX8, or RCC Marker; ENT1 and either SRC1 or MelanA. PMID:25690138

  4. The effects of stress on brain and adrenal stem cells.

    PubMed

    de Celis, M F R; Bornstein, S R; Androutsellis-Theotokis, A; Andoniadou, C L; Licinio, J; Wong, M-L; Ehrhart-Bornstein, M

    2016-05-01

    The brain and adrenal are critical control centers that maintain body homeostasis under basal and stress conditions, and orchestrate the body's response to stress. It is noteworthy that patients with stress-related disorders exhibit increased vulnerability to mental illness, even years after the stress experience, which is able to generate long-term changes in the brain's architecture and function. High levels of glucocorticoids produced by the adrenal cortex of the stressed subject reduce neurogenesis, which contributes to the development of depression. In support of the brain-adrenal connection in stress, many (but not all) depressed patients have alterations in the components of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis, with enlarged adrenal cortex and increased glucocorticoid levels. Other psychiatric disorders, such as post-traumatic stress disorder, bipolar disorder and depression, are also associated with abnormalities in hippocampal volume and hippocampal function. In addition, hippocampal lesions impair the regulation of the LHPA axis in stress response. Our knowledge of the functional connection between stress, brain function and adrenal has been further expanded by two recent, independent papers that elucidate the effects of stress on brain and adrenal stem cells, showing similarities in the way that the progenitor populations of these organs behave under stress, and shedding more light into the potential cellular and molecular mechanisms involved in the adaptation of tissues to stress. PMID:26809844

  5. Acute adrenal insufficiency secondary to bilateral adrenal B-cell lymphoma: a case report and review of the literature

    PubMed Central

    De Miguel Sánchez, Carlos; Ruiz, Luis; González, Jose Luis; Hernández, Jose Luis

    2016-01-01

    Primary adrenal lymphoma is an extremely rare entity which constitutes less than 1% of extranodal lymphomas. Most cases present with bilateral adrenal masses and without extraadrenal involvement, which can lead to symptoms of adrenal insufficiency. The prognosis is usually poor and chemotherapy is the first-line treatment option. We report here on a 78-year-old man admitted to our Internal Medicine Department because of constitutional symptoms and high fever spikes. He was diagnosed with adrenal insufficiency and a CT-scan revealed bilateral adrenal masses of about 6 cm in diameter. A percutaneous biopsy was performed and the histological exam was consistent with diffuse large B cell lymphoma. A review of the literature of this unusual entity was also carried out. PMID:27170834

  6. GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens.

    PubMed

    Lymperopoulos, Anastasios; Brill, Ava; McCrink, Katie A

    2016-08-01

    The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as "presynaptic autoreceptors" in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the α2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and β-arrestins in these processes and particular points of focus for future research will be highlighted, as well. PMID:26851510

  7. [Primary bilateral adrenal T-cell lymphoma. A case report rarer than B-cell lymphoma].

    PubMed

    Sfaxi, M; Bouzouita, A; Bouasker, I; Kourda, N; Ben Slama, M R; Ben Jilani Baltaji, S; Chebil, M

    2008-06-01

    Primary adrenal lymphoma is a rare condition. Only 70 cases were described in the literature. Adrenal lymphoma is often bilateral and in most of the cases of B-cell type. T-cell lymphoma is exceptional. The prognosis is bad and patient can die early because of acute adrenal insufficiency. We report a case of a 70-year-old man who was admitted for acute adrenal insufficiency due to primary bilateral adrenal T-cell lymphoma. He had corticotherapy and surgical exploration for intra-abdominal sepsis. He died because of multivisceral deficiency. Clinical features and imaging are not specific. (18)F-FDG PET Scan is an excellent mean to detect malignant tumor of adrenal gland. Percutaneous needle biopsy is useful to determine histology. The standard treatment is chemotherapy. PMID:18455145

  8. Recurrence of renal cell carcinoma diagnosed using contralateral adrenal biopsy with endoscopic ultrasound-guided fine-needle aspiration

    PubMed Central

    TANIMOTO, AZUSA; TAKEUCHI, SHINJI; YAEGASHI, HIROSHI; KOTANI, HIROSHI; KITAI, HIDENORI; NANJO, SHIGEKI; EBI, HIROMICHI; YAMASHITA, KANAME; MOURI, HISATSUGU; OHTSUBO, KOUSHIRO; IKEDA, HIROKO; YANO, SEIJI

    2016-01-01

    A 76-year-old female in whom a renal cell carcinoma (RCC) lesion was resected 19 years previously presented to our hospital with cognitive dysfunction. Magnetic resonance imaging and computed tomography revealed nodules in the brain, lung, adrenal gland and a pelvic osteolytic lesion. To identify the primary cancer site, the present study performed endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the left adrenal lesion. Consequently, the pathological findings of the tissue obtained by EUS-FNA were similar to those of the previous nephrectomy specimen, revealing that the adrenal lesion was the recurrence of RCC. The majority of the metastatic lesions in the patient were reduced in size by the multiple kinase inhibitor, pazopanib. Contralateral adrenal metastasis of RCC is rare and the use of EUS-FNA in the diagnosis of adrenal lesions remains to be elucidated. This is a rare case of adrenal lesion, diagnosed by EUS-FNA. Therefore, EUS-FNA is considered to be a useful diagnostic modality of adrenal metastases from unidentified primary tumor types. PMID:27073657

  9. Adrenal Gland Tumor

    MedlinePlus

    ... here Home > Types of Cancer > Adrenal Gland Tumor Adrenal Gland Tumor This is Cancer.Net’s Guide to Adrenal Gland Tumor. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Adrenal Gland Tumor Introduction Statistics Risk Factors Symptoms and ...

  10. Effects of cannabinoids on adrenaline release from adrenal medullary cells

    PubMed Central

    Niederhoffer, Nathalie; Hansen, Henrik H; Fernandez-Ruiz, Javier J; Szabo, Bela

    2001-01-01

    The objective of the present study was to analyse the peripheral effects of cannabinoids on adrenaline release from adrenal chromaffin cells. In pithed rabbits with electrically stimulated sympathetic outflow, intravenous injection of the cannabinoid receptor agonists WIN55212-2 and CP55940 (5, 50 and 500 μg kg−1) markedly lowered the plasma adrenaline concentration. The effect of WIN55212-2 was attenuated by the selective CB1 cannabinoid receptor antagonist SR141716A (500 μg kg−1). WIN55212-3 (same doses as WIN55212-2), the enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect on the plasma adrenaline concentration. In rabbit isolated adrenal glands, the release of adrenaline elicited by electrical stimulation was measured by fast cyclic voltammetry. Electrically-evoked adrenaline release was inhibited by WIN55212-2 (0.3, 1, 3 and 10 μM) and this effect was antagonized by SR141716A (1 μM). The non-cholinergic component of adrenaline release observed after blockade of nicotinic (by hexamethonium 100 μM) and muscarinic (by atropine 0.5 μM) acetylcholine receptors was not depressed by WIN55212-2. WIN55212-3 (10 μM) had no effect on adrenaline release. No detectable specific CB1 receptor binding and mRNA expression were found in rabbit adrenal glands with autoradiography and in situ hybridization. The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB1 receptor-mediated inhibition of acetylcholine release from preganglionic sympathetic neurons. The inhibition of adrenaline secretion in adrenal glands most probably accounts for the decrease in the plasma adrenaline concentration observed after cannabinoid administration in pithed rabbits. PMID:11704653

  11. Resistant arterial hypertension: association with syncronous kidney cancer and adrenal adenoma.

    PubMed

    Pittavini, Loretta; De Gaetano, Andrea; Solano, Giuseppe; Losito, Attilio

    2010-01-01

    The coexistence of renal cancer and adrenal adenoma is rare. We report the case of a 60-year-old patient with synchronous hypernephroma and adrenal adenoma. The patient presented with resistant hypertension, high plasma renin activity and aldosterone and target organ damage. Removal of the affected kidney cured the hypertension and normalized the plasma renin activity (PRA) and circulating aldosterone. This suggests that the coexistence of kidney cancer and adrenal adenoma may be a curable cause of resistant hypertension. The potential mechanisms accounting for the lack of suppression of PRA are discussed. PMID:20383873

  12. Diagnostic accuracy of computed tomography in detecting adrenal metastasis from primary lung cancer

    SciTech Connect

    Allard, P.

    1988-01-01

    The main study objective was to estimate the diagnostic accuracy of computed tomography (CT) for detection of adrenal metastases from primary lung cancer. A secondary study objective was to measure intra-reader and inter-reader agreement in interpretation of adrenal CT. Results were compared of CT film review and the autopsy findings of the adrenal glands. A five-level CT reading scale was used to assess the effect of various positivity criteria. The diagnostic accuracy of CT for detection of adrenal metastases was characterized by a tradeoff between specificity and sensitivity. At various positivity criteria, high specificity is traded against low sensitivity. The CT inability to detect many metastatic adrenals was related to frequent metastatic spread without morphologic changes of the gland.

  13. GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Fujihara, Hiroaki; Ueta, Yoichi; Yanagawa, Yuchio; Inoue, Masumi

    2016-01-01

    Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABAA receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABAA receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABAA receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. PMID:27147972

  14. GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells.

    PubMed

    Harada, Keita; Matsuoka, Hidetada; Fujihara, Hiroaki; Ueta, Yoichi; Yanagawa, Yuchio; Inoue, Masumi

    2016-01-01

    Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABAA receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABAA receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABAA receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. PMID:27147972

  15. Cholinergic regulation of protein phosphorylation in bovine adrenal chromaffin cells

    SciTech Connect

    Haycock, J.W.; Browning, M.D.; Greengard, P.

    1988-03-01

    Chromaffin cells were isolated from bovine adrenal medullae and maintained in primary culture. After prelabeling with /sup 32/PO/sub 4/, exposure of the chromaffin cells to acetylcholine increased the phosphorylation of a M/sub r/ approx. = 100,000 protein and a M/sub r/ approx. = 60,000 protein (tyrosine hydroxylase), visualized after separation of total cellular proteins in NaDodSO/sub 4//polyacrylamide gels. Immunoprecipitation with antibodies to three known phosphoproteins (100-kDa, 87-kDa, and protein III) revealed an acetylcholine-dependent phosphorylation of these proteins. These three proteins were also shown to be present in bovine adrenal chromaffin cells by immunolabeling techniques. 100-kDa is a M/sub r/ approx. = 100,000 protein selectively phosphorylated by calcium/calmodulin-dependent protein kinase III, 87-kDa is a M/sub r/ approx. = 87,000 protein selectively phosphorylated by protein kinase C, and protein III is a phosphoprotein doublet of M/sub r/ approx. = 74,000 (IIIa) and M/sub r/ approx. = 55,000 (IIIb) phosphorylated by cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase I. The data demonstrate that cholinergic activation of chromaffin cells increases the phosphorylation of several proteins and that several protein kinase systems may be involved in these effects.

  16. Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: antiproliferative effects of peptide analogues.

    PubMed

    Ziegler, C G; Brown, J W; Schally, A V; Erler, A; Gebauer, L; Treszl, A; Young, L; Fishman, L M; Engel, J B; Willenberg, H S; Petersenn, S; Eisenhofer, G; Ehrhart-Bornstein, M; Bornstein, S R

    2009-09-15

    Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4-71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors. PMID:19717419

  17. Normal adrenal glands in small cell lung carcinoma: CT-guided biopsy

    SciTech Connect

    Pagani, J.J.

    1983-05-01

    Twenty-four small cell lung carcinoma patients with morphologically normal adrenal glands by computed tomographic (CT) criteria underwent percutaneous thin-needle biopsy of their adrenal glands. Of 43 glands biopsied, 29 had adequate cellular material for interpretation. Five (17%) of the 29 glands were positive for metastases; the rest had negative biopsies. This series indicates an approximate 17% false-negative diagnosis rate by CT when staging the adrenal glands in patients with small cell lung carcinoma. It also demonstrates the utility of percutaneous needle biopsy as an investigational tool to further evaluate normal-sized adrenal glands in the oncologic patient.

  18. Adrenalectomy for solitary adrenal metastasis from colorectal cancer: A case report

    PubMed Central

    Kosmidis, Christopher; Efthimiadis, Christopher; Anthimidis, George; Levva, Sofia; Ioannidou, Georgia; Zaramboukas, Thomas; Emmanouilides, Christos; Baka, Sofia; Kosmidou, Maria; Basdanis, Georgios; Fachantidis, Epaminondas

    2008-01-01

    Background Patients with adrenal metastasis from various primary tumours are regarded as cases of diffuse systemic spread and considered unsuitable for surgical resection. We herein report an operable case of heterochronic adrenal metastasis from colorectal carcinoma in a 63-year-old woman. Case presentation Sixteen months after low anterior resection for the primary tumour, left lower pneumonectomy was performed for a solitary lung metastasis. Four months later a right adrenal metastasis was detected by magnetic resonance imaging (MRI), as sole evidence of metastatic disease. A right adrenalectomy was performed. The histopathological examination revealed adenocarcinoma compatible with the colorectal carcinoma resected 19 months earlier. The patient received adjuvant chemotherapy after each operation and is alive and free of disease 21 months after the adrenalectomy. Conclusion The possibility of adrenal metastasis should be considered in the follow-up of patients after primary surgery for colorectal cancer, even though other sites are the main metastatic sites. Although the prognosis of adrenal metastasis from colorectal cancer is poor, we suggest that patients with solitary adrenal metastasis may benefit from complete removal of it. PMID:18638404

  19. A case of primary adrenal diffuse large B-cell lymphoma in HIV.

    PubMed

    Malik, Seema; Chapman, Cordelia B-P; Drew, Olivia

    2016-07-01

    Primary adrenal diffuse large B-cell lymphoma in HIV is a very rare, highly aggressive extra-nodal lymphoma. There is only one previous case reported in the literature. Our patient presented with isolated bilateral adrenal masses with no lymphadenopathy or visceral involvement, which made the diagnosis challenging. PMID:26113518

  20. 12. Patterns of Adrenal Gland Involvement from Lung Cancer Shown by 18F-Fluorodeoxyglucose Positron Emission Tomography Compared to Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Zubeldia; Abou-Zied; Nabi

    2000-07-01

    Purpose: The frequency of adrenal metastases from non-small cell lung cancer (NSCLC) varies between 4 to 25%. Adrenal metastases are frequently missed (78%) by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The purpose of this study was to characterize the patterns of adrenal gland involvement from lung cancer by 18-F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET).Methods: Retrospective review of patients evaluated for known or suspected lung carcinoma. Results of 18FDG-PET, CT, MRI, and scans were compared.Results: From February 1996 to May 2000, 91 patients with known (85 patients) or suspected (6 patients) lung cancer were evaluated with 18FDG-PET scan. Twenty-two patients (mean age 63, range 38-88 years) had abnormal adrenal glands by either 18FDG-PET (16 patients), CT (12 patients) or MRI (1 patient). In 13 cases 18FDG-PET scan was ordered to clarify CT or MRI findings. Only 7 patients showed adrenal gland involvement: 5 patients (5.5%) with unilateral disease and 2 patients (2.2%) with bilateral disease. PET depicted unsuspected findings in 9 patients: 8 patients (8.8%) with unilateral disease and 1 patient (1.1%) with bilateral disease.(18)FDG-PET upstaged 9 patients from limited (N1M0) to widespread disease (M1), thus obviating surgical intervention.Conclusion: This study demonstrates the potential of 18FDG-PET scanning in revealing unsuspected adrenal metastases in patients with early stages of NSCLC as well as characterizing CT or MRI equivocal adrenal masses. PMID:11150769

  1. Fetal adrenal capsular cells serve as progenitor cells for steroidogenic and stromal adrenocortical cell lineages in M. musculus

    PubMed Central

    Wood, Michelle A.; Acharya, Asha; Finco, Isabella; Swonger, Jessica M.; Elston, Marlee J.; Tallquist, Michelle D.; Hammer, Gary D.

    2013-01-01

    The lineage relationships of fetal adrenal cells and adrenal capsular cells to the differentiated adrenal cortex are not fully understood. Existing data support a role for each cell type as a progenitor for cells of the adult cortex. This report reveals that subsets of capsular cells are descendants of fetal adrenocortical cells that once expressed Nr5a1. These fetal adrenocortical cell descendants within the adrenal capsule express Gli1, a known marker of progenitors of steroidogenic adrenal cells. The capsule is also populated by cells that express Tcf21, a known inhibitor of Nr5a1 gene expression. We demonstrate that Tcf21-expressing cells give rise to Nr5a1-expressing cells but only before capsular formation. After the capsule has formed, capsular Tcf21-expressing cells give rise only to non-steroidogenic stromal adrenocortical cells, which also express collagen 1a1, desmin and platelet-derived growth factor (alpha polypeptide) but not Nr5a1. These observations integrate prior observations that define two separate origins of adult adrenocortical steroidogenic cells (fetal adrenal cortex and/or the adrenal capsule). Thus, these observations predict a unique temporal and/or spatial role of adult cortical cells that arise directly from either fetal cortical cells or from fetal cortex-derived capsular cells. Last, the data uncover the mechanism by which two populations of fetal cells (fetal cortex derived Gli1-expressing cells and mesenchymal Tcf21-expressing mesenchymal cells) participate in the establishment of the homeostatic capsular progenitor cell niche of the adult cortex. PMID:24131628

  2. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells

    PubMed Central

    Saito, Ryuta; Terasaki, Natsuko; Yamazaki, Makoto; Masutomi, Naoya; Tsutsui, Naohisa; Okamoto, Masahiro

    2016-01-01

    Adrenal toxicity is one of the major concerns in drug development. To quantitatively understand the effect of endocrine-active compounds on adrenal steroidogenesis and to assess the human adrenal toxicity of novel pharmaceutical drugs, we developed a mathematical model of steroidogenesis in human adrenocortical carcinoma NCI-H295R cells. The model includes cellular proliferation, intracellular cholesterol translocation, diffusional transport of steroids, and metabolic pathways of adrenal steroidogenesis, which serially involve steroidogenic proteins and enzymes such as StAR, CYP11A1, CYP17A1, HSD3B2, CYP21A2, CYP11B1, CYP11B2, HSD17B3, and CYP19A1. It was reconstructed in an experimental dynamics of cholesterol and 14 steroids from an in vitro steroidogenesis assay using NCI-H295R cells. Results of dynamic sensitivity analysis suggested that HSD3B2 plays the most important role in the metabolic balance of adrenal steroidogenesis. Based on differential metabolic profiling of 12 steroid hormones and 11 adrenal toxic compounds, we could estimate which steroidogenic enzymes were affected in this mathematical model. In terms of adrenal steroidogenic inhibitors, the predicted action sites were approximately matched to reported target enzymes. Thus, our computer-aided system based on systems biological approach may be useful to understand the mechanism of action of endocrine-active compounds and to assess the human adrenal toxicity of novel pharmaceutical drugs. PMID:27057163

  3. Cell-To-Cell Communication in Bilateral Macronodular Adrenal Hyperplasia Causing Hypercortisolism

    PubMed Central

    Lefebvre, Hervé; Duparc, Céline; Prévost, Gaëtan; Bertherat, Jérôme; Louiset, Estelle

    2015-01-01

    It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes, and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia (BMAH), a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events, which cause the disease, favor abnormal adrenal differentiation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms, which are likely to play a role in the pathophysiology of BMAH-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept. PMID:25941513

  4. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

    PubMed Central

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  5. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

    PubMed

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  6. Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line

    PubMed Central

    Kitaoka, Kazuyoshi; Kawata, Shiyori; Yoshida, Tomohiro; Kadoriku, Fumiya; Kitamura, Mitsuo

    2016-01-01

    Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression is considered to involve adrenal steroidogenesis, which is triggered by ELF-MF exposure. However, how ELF-MFs stimulate adrenal steroidogenesis is controversial. In the current study, we investigated the effect of ELF-MF exposure on the mouse adrenal cortex-derived Y-1 cell line and the human adrenal cortex-derived H295R cell line to clarify whether the ELF-MF stimulates adrenal steroidogenesis directly. ELF-MF exposure was found to significantly stimulate adrenal steroidogenesis (p < 0.01–0.05) and the expression of adrenal steroid synthetic enzymes (p < 0.05) in Y-1 cells, but the effect was weak in H295R cells. Y-1 cells exposed to an ELF-MF showed significant decreases in phosphodiesterase activity (p < 0.05) and intracellular Ca2+ concentration (p < 0.01) and significant increases in intracellular cyclic adenosine monophosphate (cAMP) concentration (p < 0.001–0.05) and cAMP response element-binding protein phosphorylation (p < 0.05). The increase in cAMP was not inhibited by treatment with NF449, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study. PMID:27100201

  7. Adrenal myelolipoma.

    PubMed

    Cyran, K M; Kenney, P J; Memel, D S; Yacoub, I

    1996-02-01

    In 1905, Gierke [1] first described the occurrence of a tumor in the adrenal composed of mature fat and mixed myeloid and erythroid cells, subsequently termed "formations myelolipomatoses" by Oberling [2] in 1929. PMID:8553954

  8. Angiotensin II binding to cultured bovine adrenal chromaffin cells: identification of angiotensin II receptors

    SciTech Connect

    Boyd, V.L.; Printz, M.P.

    1986-03-05

    Physiological experiments have provided evidence that angiotensin II stimulates catecholamine secretion from the adrenal gland. Their laboratory and others have now shown by receptor autoradiography the presence of angiotensin II receptors (AIIR) in bovine and rat adrenal medulla. In order to extend these studies they have undertaken to define AIIR on cultured bovine adrenal chromaffin cells. Cells were isolated using the method of Levitt including cell enrichment with Percoll gradient centrifugation. Primary cultures of bovine adrenal medullary cells were maintained in DME/F12 medium containing 10% FCS. Cells were characterized by immunocytochemistry for Met- and Leu-enkephalin, PNMT, DBH and Chromagranin A. Cultured cells bind with high affinity and specificity (/sup 125/I)-ANG II yielding a K/sub D/ of 0.74 nM and B/sub max/ of 24,350 sites/cell. After Percoll treatment values of .77 nm and 34,500 sites/cell are obtained. K/sub D/ values are in close agreement with that obtained in adrenal slices by Healy. Competition studies identify a rank order of binding by this receptor similar to that of other tissues. They conclude that cultured chromaffin cells provide a suitable model system for the investigation and characterization of the ANG II receptor and for cellular studies of its functional significance.

  9. Generation of Murine Sympathoadrenergic Progenitor-Like Cells from Embryonic Stem Cells and Postnatal Adrenal Glands

    PubMed Central

    Saxena, Shobhit; Wahl, Joachim; Huber-Lang, Markus S.; Stadel, Dominic; Braubach, Peter; Debatin, Klaus-Michael; Beltinger, Christian

    2013-01-01

    Sympathoadrenergic progenitor cells (SAPs) of the peripheral nervous system (PNS) are important for normal development of the sympathetic PNS and for the genesis of neuroblastoma, the most common and often lethal extracranial solid tumor in childhood. However, it remains difficult to isolate sufficient numbers of SAPs for investigations. We therefore set out to improve generation of SAPs by using two complementary approaches, differentiation from murine embryonic stem cells (ESCs) and isolation from postnatal murine adrenal glands. We provide evidence that selecting for GD2 expression enriches for ESC-derived SAP-like cells and that proliferating SAP-like cells can be isolated from postnatal adrenal glands of mice. These advances may facilitate investigations about the development and malignant transformation of the sympathetic PNS. PMID:23675538

  10. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  11. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  12. A Rare Case of Renal Cell Carcinoma With Leiomyomatous Stroma and Concomitant Ruptured Adrenal Aneurysm.

    PubMed

    Lu, Chuanyong; Nicastri, Anthony; Shao, Charles

    2016-09-01

    Here we report a rare case of coexisting renal cell carcinoma (RCC) with leiomyomatous stroma and a ruptured adrenal aneurysm. The patient was a 75-year-old woman with acute abdominal pain. Imaging studies showed a left peri-renal hematoma and a mass in the left kidney. Left nephrectomy and adrenalectomy were performed. Pathological examination showed a ruptured aneurysm in the left adrenal gland. The renal mass was composed of tubules and acini of epithelial cells and a prominent leiomyomatous stroma. The tumor cells were positive for carbonic anhydrase IX, cytokeratin 7, and negative for AMACR, consistent with clear cell (tubulo) papillary RCC. PMID:27516974

  13. Temporal and spatial distribution of mast cells and steroidogenic enzymes in the human fetal adrenal.

    PubMed

    Naccache, Alexandre; Louiset, Estelle; Duparc, Céline; Laquerrière, Annie; Patrier, Sophie; Renouf, Sylvie; Gomez-Sanchez, Celso E; Mukai, Kuniaki; Lefebvre, Hervé; Castanet, Mireille

    2016-10-15

    Mast cells are present in the human adult adrenal with a potential role in the regulation of aldosterone secretion in both normal cortex and adrenocortical adenomas. We have investigated the human developing adrenal gland for the presence of mast cells in parallel with steroidogenic enzymes profile and serotonin signaling pathway. RT-QPCR and immunohistochemical studies were performed on adrenals at 16-41 weeks of gestation (WG). Tryptase-immunopositive mast cells were found from 18 WG in the adrenal subcapsular layer, close to 3βHSD- and CYP11B2-immunoreactive cells, firstly detected at 18 and 24 WG, respectively. Tryptophan hydroxylase and serotonin receptor type 4 expression increased at 30 WG before the CYP11B2 expression surge. In addition, HDL and LDL cholesterol receptors were expressed in the subcapsular zone from 24 WG. Altogether, our findings suggest the implication of mast cells and serotonin in the establishment of the mineralocorticoid synthesizing pathway during fetal adrenal development. PMID:27302892

  14. Adrenalectomy for metastatic adrenal tumors.

    PubMed

    Kita, Masafumi; Tamaki, Gaku; Okuyama, Mitsuhiko; Saga, Yuji; Kakizaki, Hidehiro

    2007-11-01

    The indications for adrenalectomy in cases of metastatic adrenal tumor remain controversial. To clarify indications and outcomes of adrenalectomy for adrenal metastasis, we performed a retrospective review of all 8 patients who underwent adrenalectomy for adrenal metastasis between 1990 and 2006 in Asahikawa Medical College Hospital. The Primary tumor was renal cell carcinoma in 2 cases, and eccrine poro carcinoma, rectal cancer, lung cancer, melanoma, bladder cancer and cancer of unknown origin in 1 case each. Open adrenalectomy was performed in all cases, including 1 case that was converted from laparoscopic adrenalectomy. Of the 4 patients with solitary adrenal metastasis, 3 were considered tumor-free after adrenalectomy, while the remaining patient was not due to unresectable primary tumor. Of the 3 patients with complete resection, one remained alive as of 88 months after adrenalectomy but was then lost to follow-up, and the other 2 patients remain alive 12 and 7 months after adrenalectomy. Of the 2 patients with other resectable metastasis who were tumor-free after removal of all metastases, one was alive 31 months postoperatively and the other died 23 months after operation. The remaining 2 cases with other unresectable metastasis died within 6 months after adrenalectomy. At least in cases of solitary adrenal metastasis, adrenalectomy can be effective if other valid methods are unavailable. PMID:18051798

  15. Cell cycle-dependent regulation of extra-adrenal glucocorticoid synthesis in murine intestinal epithelial cells.

    PubMed

    Atanasov, Atanas G; Leiser, Dominic; Roesselet, Corinne; Noti, Mario; Corazza, Nadia; Schoonjans, Kristina; Brunner, Thomas

    2008-12-01

    Glucocorticoids are anti-inflammatory steroids with important applications in the treatment of inflammatory diseases. Endogenous glucocorticoids are mainly produced by the adrenal glands, although there is increasing evidence for extra-adrenal sources. Recent findings show that intestinal crypt cells produce glucocorticoids, which contribute to the maintenance of intestinal immune homeostasis. Intestinal glucocorticoid synthesis is critically regulated by the transcription factor liver receptor homologue-1 (LRH-1). As expression of steroidogenic enzymes and LRH-1 is restricted to the proliferating cells of the crypts, we aimed to investigate the role of the cell cycle in the regulation of LRH-1 activity and intestinal glucocorticoid synthesis. We here show that either pharmacological or molecular modulation of cell cycle progression significantly inhibited expression of steroidogenic enzymes and synthesis of glucocorticoids in intestinal epithelial cells. Synchronization of intestinal epithelial cells in the cell cycle revealed that expression of steroidogenic enzymes is preferentially induced at the G(1)/S stage. Differentiation of immature intestinal epithelial cells to mature nonproliferating cells also resulted in reduced expression of steroidogenic enzymes. This cell cycle-related effect on intestinal steroidogenesis was found to be mediated through the regulation of LRH-1 transcriptional activity. This mechanism may restrict intestinal glucocorticoid synthesis to the proliferating cells of the crypts. PMID:18711026

  16. The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.

    PubMed

    Vidal, Valerie; Sacco, Sonia; Rocha, Ana Sofia; da Silva, Fabio; Panzolini, Clara; Dumontet, Typhanie; Doan, Thi Mai Phuong; Shan, Jingdong; Rak-Raszewska, Aleksandra; Bird, Tom; Vainio, Seppo; Martinez, Antoine; Schedl, Andreas

    2016-06-15

    Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life. PMID:27313319

  17. Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis

    PubMed Central

    Leal, Letícia F.; Bueno, Ana Carolina; Gomes, Débora C.; Abduch, Rafael; de Castro, Margaret; Antonini, Sonir R.

    2015-01-01

    Background To date, there is no effective therapy for patients with advanced/metastatic adrenocortical cancer (ACC). The activation of the Wnt/beta-catenin signaling is frequent in ACC and this pathway is a promising therapeutic target. Aim To investigate the effects of the inhibition of the Wnt/beta-catenin in ACC cells. Methods Adrenal (NCI-H295 and Y1) and non-adrenal (HeLa) cell lines were treated with PNU-74654 (5–200 μM) for 24–96 h to assess cell viability (MTS-based assay), apoptosis (Annexin V), expression/localization of beta-catenin (qPCR, immunofluorescence, immunocytochemistry and western blot), expression of beta-catenin target genes (qPCR and western blot), and adrenal steroidogenesis (radioimmunoassay, qPCR and western blot). Results In NCI-H295 cells, PNU-74654 significantly decreased cell proliferation 96 h after treatment, increased early and late apoptosis, decreased nuclear beta-catenin accumulation, impaired CTNNB1/beta-catenin expression and increased beta-catenin target genes 48 h after treatment. No effects were observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreased cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreased SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impaired corticosterone secretion 24 h after treatment but did not decrease cell viability. Conclusions Blocking the Tcf/beta-catenin complex inhibits the Wnt/beta-catenin signaling in adrenocortical tumor cells triggering increased apoptosis, decreased cell viability and impairment of adrenal steroidogenesis. These promising findings pave the way for further experiments inhibiting the Wnt/beta-catenin pathway in pre-clinical models of ACC. The inhibition of this pathway may become a promising adjuvant therapy for patients with ACC. PMID:26515592

  18. Adrenal Insufficiency

    MedlinePlus

    ... What is adrenal insufficiency? Did you know? The adrenal glands, located on top of the kidneys, make hormones ... body functions. The outer layer (cortex) of the adrenal glands makes three types of steroid hormones. In adrenal ...

  19. Differentiation of mesenchymal stem cells into gonad and adrenal steroidogenic cells

    PubMed Central

    Yazawa, Takashi; Imamichi, Yoshitaka; Miyamoto, Kaoru; Umezawa, Akihiro; Taniguchi, Takanobu

    2014-01-01

    Hormone replacement therapy is necessary for patients with adrenal and gonadal failure. Steroid hormone treatment is also employed in aging people for sex hormone deficiency. These patients undergo such therapies, which have associated risks, for their entire life. Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems. Among various stem cell types, mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro. In particular, they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins (steroidogenic factor-1 and liver receptor homolog-1) with the aid of cAMP. This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies. It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases. PMID:24772247

  20. Endothelial cells from bovine adrenal medulla develop capillary-like growth patterns in culture.

    PubMed Central

    Banerjee, D K; Ornberg, R L; Youdim, M B; Heldman, E; Pollard, H B

    1985-01-01

    The endocrine barrier between chromaffin cells and the blood stream in the adrenal medulla is made of capillary endothelial cells. We have now succeeded in isolating endothelial cells from adrenal medullary tissue, which are probably derived from this barrier. These cells grow on plastic surfaces in the absence of special growth factors or collagen overlays and differentiate into organized structures quite similar to true capillaries. The cells contain factor VIII:R, a marker for endothelial cells, and form intercellular junctions characteristic of capillary endothelial cells. They also synthesize and secrete basal lamina structures and engage in transcytosis, a characteristic ultrastructural and functional combination of exocytosis and endocytosis across the thin endothelial cell processes. These endothelial cells can take up and deaminate catecholamines by A-type monoamine oxidase, an enzyme functionally distinct from the B-type monoamine oxidase found in chromaffin cells. These data indicate that the chromaffin cell and its endothelial cell neighbor may constitute the functional unit of catecholamine metabolism in the adrenal medulla. Images PMID:3927288

  1. PC12 Cells Differentiate into Chromaffin Cell-Like Phenotype in Coculture with Adrenal Medullary Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Mizrachi, Yaffa; Naranjo, Jose R.; Levi, Ben-Zion; Pollard, Harvey B.; Lelkes, Peter I.

    1990-08-01

    Previously we described specific in vitro interactions between PC12 cells, a cloned, catecholamine-secreting pheochromocytoma cell line derived from the rat adrenal medulla, and bovine adrenal medullary endothelial cells. We now demonstrate that these interactions induce the PC12 cells to acquire physical and biochemical characteristics reminiscent of chromaffin cells. Under coculture conditions involving direct cell-cell contact, the endothelial cells and the PC12 cells reduced their rates of proliferation; upon prolonged coculture PC12 cells clustered into nests of cells similar to the organization of chromaffin cells seen in vivo. Within 3 days in coculture with endothelial cells, but not with unrelated control cells, PC12 cells synthesized increased levels of [Met]enkephalin. In addition, PC12 cells, growing on confluent endothelial monolayers, failed to extend neurites in response to nerve growth factor. Neither medium conditioned by endothelial cells nor fixed endothelial cells could by themselves induce all of these different phenomena in the PC12 cells. These results suggest that under coculture conditions PC12 cells change their state of differentiation toward a chromaffin cell-like phenotype. The rapid, transient increase in the expression of the protooncogene c-fos suggests that the mechanism(s) inducing the change in the state of differentiation in PC12 cells in coculture with the endothelial cells may be distinct from that described for the differentiation of PC12 cells--e.g., by glucocorticoids. We propose that similar interactions between endothelial cells and chromaffin cell precursors may occur during embryonic development and that these interactions might be instrumental for the organ-specific differentiation of the adrenal medulla in vivo.

  2. MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans

    PubMed Central

    Hughes, Claire R.; Guasti, Leonardo; Meimaridou, Eirini; Chuang, Chen-Hua; Schimenti, John C.; King, Peter J.; Costigan, Colm; Clark, Adrian J.L.; Metherell, Louise A.

    2012-01-01

    An interesting variant of familial glucocorticoid deficiency (FGD), an autosomal recessive form of adrenal failure, exists in a genetically isolated Irish population. In addition to hypocortisolemia, affected children show signs of growth failure, increased chromosomal breakage, and NK cell deficiency. Targeted exome sequencing in 8 patients identified a variant (c.71-1insG) in minichromosome maintenance–deficient 4 (MCM4) that was predicted to result in a severely truncated protein (p.Pro24ArgfsX4). Western blotting of patient samples revealed that the major 96-kDa isoform present in unaffected human controls was absent, while the presence of the minor 85-kDa isoform was preserved. Interestingly, histological studies with Mcm4-depleted mice showed grossly abnormal adrenal morphology that was characterized by non-steroidogenic GATA4- and Gli1-positive cells within the steroidogenic cortex, which reduced the number of steroidogenic cells in the zona fasciculata of the adrenal cortex. Since MCM4 is one part of a MCM2-7 complex recently confirmed as the replicative helicase essential for normal DNA replication and genome stability in all eukaryotes, it is possible that our patients may have an increased risk of neoplastic change. In summary, we have identified what we believe to be the first human mutation in MCM4 and have shown that it is associated with adrenal insufficiency, short stature, and NK cell deficiency. PMID:22354170

  3. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    SciTech Connect

    Chartier, L.; Schiffrin, E.L.

    1987-04-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC/sub 50/) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC/sub 50/. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated /sup 45/Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.

  4. Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells

    SciTech Connect

    Reyland, M.E.; Forgez, P.; Prack, M.M.; Williams, D.L. ); Gwynne, J.T. )

    1991-03-15

    The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, the authors have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to {gt}100-fold relative to Y1 parent cells. Addition of 5-cholesten-3{beta},25-idol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl ({sup 14}C)oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl ({sup 14}C)oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells.

  5. Left adrenal gland metastasis of breast invasive ductal carcinoma: A case report

    PubMed Central

    HE, TAO; LIU, JIAJU; LI, YIFAN; JIN, LU; SUN, SHUOLEI; NI, LIANGCHAO; MAO, XIANGMING; YANG, SHANGQI; LAI, YONGQING

    2016-01-01

    The majority of the metastatic lesions of the adrenal gland normally originate from lung cancer, colon malignant tumor, renal cell carcinoma and melanoma. However, adrenal gland metastasis that metastasize from breast invasive ductal carcinoma are extremely rare. The present study reported a rare case of left adrenal gland metastasis in a 35-year-old female who was diagnosed as breast carcinoma 5 years ago with a mass located on the left adrenal gland, which was detected during a routine examination. The patient was asymptomatic and adrenal gland computed tomography revealed a mass in the left adrenal gland. Definitive preoperative diagnosis failed to be established. Left adrenal gland laparoscopic adrenalectomy was performed and the diagnosis of adrenal gland metastasis of breast invasive ductal carcinoma was confirmed by pathological and immunohistochemical examination. The patient remained in good condition by the time of writing. PMID:27123296

  6. Synthesis of hydroxyeicosatetraenoic acids (HETE's) by adrenal glomerulosa cells and incorporation into cellular lipids

    SciTech Connect

    Campbell, W.B.; Richards, C.F.; Brady, M.T.; Falck, J.R.

    1986-03-05

    The role of lipoxygenase metabolites of arachidonic acid (AA) in the regulation of aldosterone secretion was studied in isolated rat adrenal glomerulosa cells. Cells were incubated with /sup 14/C-AA in the presence of angiotensin (AII). The media was extracted, metabolites isolated by HPLC, and structures of the metabolites determined by UV absorbance and mass spectrometry. The major products were 12- and 15-HETE with lesser amounts of 11- and 5-HETE. When adrenal cells were incubated with 15-, 12- or 5-HPETE or their respective HETE's (0.03-300nM), there was no significant change in basal or AII-stimulated aldosterone release. Cells were incubated with (/sup 3/H)-AA, -5-HETE, -15-HETE, -12-HETE or -LTB. The cellular lipids were extracted and analyzed by TLC. AA was incorporated into phospholipids (22%), cholesterol esters (50%) and triglycerides (21%). Neither the HETE's or LTB/sub 4/ were incorporated into phospholipids. 5-HETE was taken up into di- and mono-glycerides. The rates of incorporation of AA and 5-HETE were similar (+ 1/2 = 10 min). The incorporation of 5-HETE into glycerol esters did not modify the release of aldosterone by the cells. Thus, while adrenal cells synthesize HETE's, these eicosanoids do not appear to alter the synthesis of aldosterone.

  7. Asthma Pregnancy Alters Postnatal Development of Chromaffin Cells in the Rat Adrenal Medulla

    PubMed Central

    Li, Xiao-Zhao; Zou, Ye-Qiang; Zou, Jun-Tao; Li, Yuan-Yuan; Feng, Jun-Tao

    2011-01-01

    Background Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown. Methodology/Principal Findings This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3) to postnatal day 60 (P60). Asthmatic pregnant rats (AP), nerve growth factor (NGF)-treated pregnant rats (NP) and NGF antibody-treated pregnant rats (ANP) were sensitized and challenged with ovalbumin (OVA); NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP), offspring from AP (OAP), offspring from NP (ONP), and offspring from ANP (OANP). The expressions of phenylethanolamine N-methyltransferase (PNMT) protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI), corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC) were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP. Conclusion/Significance Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation. PMID:21647384

  8. Effect of angiotensin II, ATP, and ionophore A23187 on potassium efflux in adrenal glomerulosa cells

    SciTech Connect

    Lobo, M.V.; Marusic, E.T.

    1986-02-01

    Angiotensin II stimulus on perifused bovine adrenal glomerulosa cells elicited an increase in 86Rb efflux from cells previously equilibrated with the radioisotope. When 45Ca fluxes were measured under similar conditions, it was observed that Ca and Rb effluxes occurred within the first 30 s of the addition of the hormone and were independent of the presence of external Ca. The 86Rb efflux due to angiotensin II was inhibited by quinine and apamin. The hypothesis that the angiotensin II response is a consequence of an increase in the K permeability of the glomerulosa cell membrane triggered by an increase in cytosolic Ca is supported by the finding that the divalent cation ionophore A23187 also initiated 86Rb or K loss (as measured by an external K electrode). This increased K conductance was also seen with 10(-4) M ATP. Quinine and apamin greatly reduced the effect of ATP or A23187 on 86Rb or K release in adrenal glomerulosa cells. The results suggest that Ca-dependent K channels or carriers are present in the membranes of bovine adrenal glomerulosa cells and are sensitive to hormonal stimulus.

  9. Tetrodotoxin-insensitive Na+ channel activator palytoxin inhibits tyrosine uptake into cultured bovine adrenal chromaffin cells

    SciTech Connect

    Morita, K.; Teraoka, K.; Azuma, M.; Oka, M.; Hamano, S. )

    1991-07-01

    The effects of the tetrodotoxin-insensitive Na+ channel activator palytoxin on both the secretion of endogenous catecholamines and the formation of 14C-catecholamines from (14C)tyrosine were examined using cultured bovine adrenal chromaffin cells. Palytoxin was shown to cause the stimulation of catecholamine secretion in a concentration-dependent manner. However, this toxin caused the reduction rather than the stimulation of 14C-catecholamine formation at the same concentrations. Palytoxin failed to cause any alteration in the activity of tyrosine hydroxylase prepared from bovine adrenal medulla. Furthermore, the uptake of (14C)tyrosine into the cells was shown to be inhibited by this toxin under the conditions in which the suppression of 14C-catecholamine formation was observed, and this inhibitory action on tyrosine uptake was closely correlated with that on catecholamine formation. The inhibitory action of palytoxin on tyrosine uptake into the cells was observed to be noncompetitive, and this effect was not altered by the removal of Na+ from the incubation mixture. These results suggest that palytoxin may be able to inhibit the uptake of (14C)tyrosine into the cells, resulting in the suppression of 14C-catecholamine formation, probably through its direct action on the plasma membranes of bovine adrenal chromaffin cells.

  10. Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency

    PubMed Central

    Gineau, Laure; Cognet, Céline; Kara, Nihan; Lach, Francis Peter; Dunne, Jean; Veturi, Uma; Picard, Capucine; Trouillet, Céline; Eidenschenk, Céline; Aoufouchi, Said; Alcaïs, Alexandre; Smith, Owen; Geissmann, Frédéric; Feighery, Conleth; Abel, Laurent; Smogorzewska, Agata; Stillman, Bruce; Vivier, Eric; Casanova, Jean-Laurent; Jouanguy, Emmanuelle

    2012-01-01

    Natural killer (NK) cells are circulating cytotoxic lymphocytes that exert potent and nonredundant antiviral activity and antitumoral activity in the mouse; however, their function in host defense in humans remains unclear. Here, we investigated 6 related patients with autosomal recessive growth retardation, adrenal insufficiency, and a selective NK cell deficiency characterized by a lack of the CD56dim NK subset. Using linkage analysis and fine mapping, we identified the disease-causing gene, MCM4, which encodes a component of the MCM2-7 helicase complex required for DNA replication. A splice-site mutation in the patients produced a frameshift, but the mutation was hypomorphic due to the creation of two new translation initiation methionine codons downstream of the premature termination codon. The patients’ fibroblasts exhibited genomic instability, which was rescued by expression of WT MCM4. These data indicate that the patients’ growth retardation and adrenal insufficiency likely reflect the ubiquitous but heterogeneous impact of the MCM4 mutation in various tissues. In addition, the specific loss of the NK CD56dim subset in patients was associated with a lower rate of NK CD56bright cell proliferation, and the maturation of NK CD56bright cells toward an NK CD56dim phenotype was tightly dependent on MCM4-dependent cell division. Thus, partial MCM4 deficiency results in a genetic syndrome of growth retardation with adrenal insufficiency and selective NK deficiency. PMID:22354167

  11. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC ...

  12. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  13. Characterization of insulin-like growth factor I and insulin receptors on cultured bovine adrenal fasciculata cells. Role of these peptides on adrenal cell function

    SciTech Connect

    Penhoat, A.; Chatelain, P.G.; Jaillard, C.; Saez, J.M.

    1988-06-01

    We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 +/- (SE) 0.3 x 10(-9) M and 19,200 +/- 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked (/sup 125/I)iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (Kd) of 10(-9) M. Under reduction conditions (/sup 125/I)iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 micrograms/ml) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED50 approximately equal to 10(-9) M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less.

  14. Pannexin 1 channels: new actors in the regulation of catecholamine release from adrenal chromaffin cells

    PubMed Central

    Momboisse, Fanny; Olivares, María José; Báez-Matus, Ximena; Guerra, María José; Flores-Muñoz, Carolina; Sáez, Juan C.; Martínez, Agustín D.; Cárdenas, Ana M.

    2014-01-01

    Chromaffin cells of the adrenal gland medulla synthesize and store hormones and peptides, which are released into the blood circulation in response to stress. Among them, adrenaline is critical for the fight-or-flight response. This neurosecretory process is highly regulated and depends on cytosolic [Ca2+]. By forming channels at the plasma membrane, pannexin-1 (Panx1) is a protein involved in many physiological and pathological processes amplifying ATP release and/or Ca2+ signals. Here, we show that Panx1 is expressed in the adrenal gland where it plays a role by regulating the release of catecholamines. In fact, inhibitors of Panx1 channels, such as carbenoxolone (Cbx) and probenecid, reduced the secretory activity induced with the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP, 50 μM) in whole adrenal glands. A similar inhibitory effect was observed in single chromaffin cells using Cbx or 10Panx1 peptide, another Panx1 channel inhibitors. Given that the secretory response depends on cytosolic [Ca2+] and Panx1 channels are permeable to Ca2+, we studied the possible implication of Panx1 channels in the Ca2+ signaling occurring during the secretory process. In support of this possibility, Panx1 channel inhibitors significantly reduced the Ca2+ signals evoked by DMPP in single chromaffin cells. However, the Ca2+ signals induced by caffeine in the absence of extracellular Ca2+ was not affected by Panx1 channel inhibitors, suggesting that this mechanism does not involve Ca2+ release from the endoplasmic reticulum. Conversely, Panx1 inhibitors significantly blocked the DMPP-induce dye uptake, supporting the idea that Panx1 forms functional channels at the plasma membrane. These findings indicate that Panx1 channels participate in the control the Ca2+ signal that triggers the secretory response of adrenal chromaffin cells. This mechanism could have physiological implications during the response to stress. PMID:25237296

  15. The innervation of the adrenal gland. IV. Innervation of the rat adrenal medulla from birth to old age. A descriptive and quantitative morphometric and biochemical study of the innervation of chromaffin cells and adrenal medullary neurons in Wistar rats.

    PubMed Central

    Tomlinson, A; Coupland, R E

    1990-01-01

    The innervation of the adrenal medulla has been investigated in normal Wistar rats from birth to old age and ultrastructural findings compared with biochemical markers of the cholinergic innervation of the adrenal gland and catecholamine storage. Morphological evidence of the immaturity of the innervation during the first postnatal week is provided and using quantitative morphometry the innervation of chromaffin cells is shown to reach a mean total of 5.4 synapses per chromaffin cell during the period 26 days to 12 weeks of age. The variation in contents of synaptic profiles is discussed in the light of recent work that demonstrates a major sensory as well as visceral efferent innervation of the gland. Adrenal medullary neurons usually occur in closely packed groups, intimately associated with Schwann cells. Axodendritic and axosomatic synapses on these neurons are described and the likely origin of axonal processes innervating the neurons discussed. In old age the density of innervation remains the same as in young adult animals even though the medulla shows evidence of hyperplasia and hypertrophy of individual chromaffin cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23 Fig. 24 Fig. 25 PMID:2384334

  16. Quantitative and qualitative evaluation of CART-containing cells in adrenal glands of male rats with hypertension.

    PubMed

    Kasacka, I; Piotrowska, Ż; Knaś, M; Lewandowska, A

    2014-10-01

    Adrenal activity is stimulated and secretion of stress hormones is increased during advanced stages of renovascular hypertension. The literature suggests that the neuropeptide, cocaine and amphetamine regulated transcript (CART), might regulate adrenal secretory function and thus could influence its activity. We assessed potential quantitative and qualitative changes in the cells that contained CART in the adrenal glands of rats with renovascular hypertension. The renal arteries of ten rats were subjected to a clipping procedure, i.e., two-kidney one-clip (2K1C) model of arterial hypertension, and after 6 weeks each rat developed stable hypertension. CART was localized using immunohistochemistry. CART was detected in a large population of cells in the medulla, sparse nerve fibers in the cortex and the capsule of the adrenal gland. The population of CART-positive cells in adrenal glands of two kidney-one clip (2K1C) treated rats was greater and their immunoreactivity was increased compared to controls. Similarly, the length, width, area and diameter of CART-immunoreactive cells were significantly greater in the hypertensive rats than in controls. We demonstrated that renovascular hypertension alters the number and immunoreactivity of CART-containing cells in adrenal glands. PMID:25151991

  17. Stimulatory actions of bioflavenoids on tyrosine uptake into cultured bovine adrenal chromaffin cells

    SciTech Connect

    Morita, K.; Hamano, S.; Oka, M.; Teraoka, K. )

    1990-09-28

    The effects of flavenoids on L-({sup 14}C)tyrosine uptake into cultured adrenal chromaffin cells were examined. Flavone markedly stimulated tyrosine uptake into these cells in a manner dependent on its concentration. Apigenin also caused a moderate stimulatory action, but quercetin had no significant effect on the uptake. Flavone also stimulated the uptake of histidine, but did not affect the uptake of serine, lysine, or glutamic acid. These results are considered to propose the possibility that flavonoids may be able to stimulate the precursor uptake into the cells, resulting in an enhancement of the biogenic amine production.

  18. Squamous cell skin cancer

    MedlinePlus

    ... cell; NMSC - squamous cell; Squamous cell skin cancer; Squamous cell carcinoma of the skin ... squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type does not spread to ...

  19. Stress sensitivity in metastatic breast cancer: analysis of hypothalamic-pituitary-adrenal axis function.

    PubMed

    Spiegel, David; Giese-Davis, Janine; Taylor, C Barr; Kraemer, Helena

    2006-11-01

    The normal diurnal cortisol cycle has a peak in the morning, decreasing rapidly over the day, with low levels during the night, then rising rapidly again to the morning peak. A pattern of flatter daytime slopes has been associated with more rapid cancer progression in both animals and humans. We studied the relationship between the daytime slopes and other daytime cortisol responses to both pharmacological and psychosocial challenges of hypothalamic-pituitary-adrenal (HPA) axis function as well as DHEA in a sample of 99 women with metastatic breast cancer, in hopes of elucidating the dysregulatory process. We found that the different components of HPA regulation: the daytime cortisol slope, the rise in cortisol from waking to 30 min later, and cortisol response to various challenges, including dexamethasone (DEX) suppression, corticotrophin releasing factor (CRF) activation, and the Trier Social Stress Task, were at best modestly associated. Escape from suppression stimulated by 1mg of DEX administered the night before was moderately but significantly associated with flatter daytime cortisol slopes (r=0.28 to .30 at different times of the post DEX administration day, all p<.01). Daytime cortisol slopes were also moderately but significant associated with the rise in cortisol from waking to 30 min after awakening (r=.29, p=.004, N=96), but not with waking cortisol level (r=-0.13, p=.19). However, we could not detect any association between daytime cortisol slope and activation of cortisol secretion by either CRF infusion or the Trier Social Stress Task. The CRF activation test (following 1.5mg of DEX to assure that the effect was due to exogenous CRF) produced ACTH levels that were correlated (r=0.66, p<.0001, N=74) with serum cortisol levels, indicating adrenal responsiveness to ACTH stimulation. Daytime cortisol slopes were significantly correlated with the slope of DHEA (r=.21, p=.04, N=95). Our general findings suggest that flatter daytime cortisol slopes among

  20. Synthetic High-Density Lipoprotein (sHDL) Inhibits Steroid Production in HAC15 Adrenal Cells.

    PubMed

    Taylor, Matthew J; Sanjanwala, Aalok R; Morin, Emily E; Rowland-Fisher, Elizabeth; Anderson, Kyle; Schwendeman, Anna; Rainey, William E

    2016-08-01

    High density lipoprotein (HDL) transported cholesterol represents one of the sources of substrate for adrenal steroid production. Synthetic HDL (sHDL) particles represent a new therapeutic option to reduce atherosclerotic plaque burden by increasing cholesterol efflux from macrophage cells. The effects of the sHDL particles on steroidogenic cells have not been explored. sHDL, specifically ETC-642, was studied in HAC15 adrenocortical cells. Cells were treated with sHDL, forskolin, 22R-hydroxycholesterol, or pregnenolone. Experiments included time and concentration response curves, followed by steroid assay. Quantitative real-time RT-PCR was used to study mRNA of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, lanosterol 14-α-methylase, cholesterol side-chain cleavage enzyme, and steroid acute regulatory protein. Cholesterol assay was performed using cell culture media and cell lipid extracts from a dose response experiment. sHDL significantly inhibited production of cortisol. Inhibition occurred in a concentration- and time-dependent manner and in a concentration range of 3μM-50μM. Forskolin (10μM) stimulated cortisol production was also inhibited. Incubation with 22R-hydroxycholesterol (10μM) and pregnenolone (10μM) increased cortisol production, which was unaffected by sHDL treatment. sHDL increased transcript levels for the rate-limiting cholesterol biosynthetic enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Extracellular cholesterol assayed in culture media showed a positive correlation with increasing concentration of sHDL, whereas intracellular cholesterol decreased after treatment with sHDL. The current study suggests that sHDL inhibits HAC15 adrenal cell steroid production by efflux of cholesterol, leading to an overall decrease in steroid production and an adaptive rise in adrenal cholesterol biosynthesis. PMID:27253994

  1. Interaction of urokinase with specific receptors stimulates mobilization of bovine adrenal capillary endothelial cells

    SciTech Connect

    Fibbi, G.; Ziche, M.; Morbidelli, L. ); Magnelli, L.; Del Rosso, M. )

    1988-12-01

    On the basis of {sup 125}I-labeled plasminogen activator binding analysis the authors have found that bovine adrenal capillary endothelial cells have specific receptors for human urinary-type plasminogen activator on the cell membrane. Each cell exposes about 37,000 free receptors with a K{sub d} of 0.8958{times}10{sup {minus}12} M. A monoclonal antibody against the 17,500 proteolytic fragment of the A chain of the plasminogen activator, not containing the catalytic site of the enzyme, impaired the specific binding, thus suggesting the involvement of a sequence present on the A chain in the interaction with the receptor, as previously shown in other cell model systems. Both the native molecule and the A chain are able to stimulate endothelial cell motility in the Boyden chamber, when used at nanomolar concentrations. The use of the same monoclonal antibody that can inhibit ligand-receptor interaction can impair the plasminogen activator and A-chain-induced endothelial cell motility, suggesting that under the conditions used in this in vitro model system, the motility of bovine adrenal capillary endothelial cells depends on the specific interaction of the ligand with free receptors on the surface of endothelial cells.

  2. Mobile and immobile calcium buffers in bovine adrenal chromaffin cells.

    PubMed Central

    Zhou, Z; Neher, E

    1993-01-01

    1. The calcium binding capacity (kappa S) of bovine chromaffin cells preloaded with fura-2 was measured during nystatin-perforated-patch recordings. 2. Subsequently, the perforated patch was ruptured to obtain a whole-cell recording situation, and the time course of kappa S was monitored during periods of up to one hour. 3. No rapid change (within 10-20 s) of kappa S was observed upon transition to whole-cell recording, as would be expected, if highly mobile organic anions contributed significantly to calcium buffering. However, approximately half of the cells investigated displayed a drop in kappa S within 2-5 min, indicative of the loss of soluble Ca2+ binding proteins in the range of 7-20 kDa. 4. The average Ca2+ binding capacity (differential ratio of bound calcium over free calcium) was 9 +/- 7 (mean +/- S.E.M.) for the poorly mobile component and 31 +/- 10 for the fixed component. It was concluded that a contribution of 7 from highly mobile buffer would have been detected, if present. Thus, this value can be considered as an upper bound to highly mobile Ca2+ buffer. 5. Both mobile and fixed calcium binding capacity appeared to have relatively low Ca2+ affinity, since kappa S did not change in the range of Ca2+ concentrations between 0.1 and 3 microM. 6. It was found that cellular autofluorescence and contributions to fluorescence of non-hydrolysed or compartmentalized dye contribute a serious error in estimation of kappa S. 'Balanced loading', a degree of fura-2 loading such that the calcium binding capacity of fura-2 equals cellular calcium binding capacity, minimizes these errors. Also, changes in kappa S at the transition from perforated-patch to whole-cell recording can be most faithfully recorded for similar degrees of loading in both situations. 7. Nystatin was found unable to make pores from inside of the plasma membrane of chromaffin cells. With careful preparation and storage the diluted nystatin solution maintained its high activity of membrane

  3. Identification, characterization, and regulation of a nicotinic acetylcholine receptor on bovine adrenal chromaffin cells in culture

    SciTech Connect

    Higgins, L.S.

    1988-01-01

    Synaptic input to bovine adrenal chromaffin cells is mediated by nicotinic acetylcholine receptors (AChRs) and results in secretion of catecholamines. Three probes previously shown to recognize AChRs on neurons were used to identify the AChR on bovine adrenal chromaffin cells in culture: monoclonal antibody mAb 35, a toxin that blocks receptor function, and the agonist nicotine. Competition for {sup 3}H-nicotine binding was used to measure the affinity of cholinergic ligands, and revealed the pharmacological profile expected for a neuronal-type AChR. At steady state the rate both of receptor insertion into and loss from the plasma membrane is about 3%/hour, resulting in a half-life in the surface of about 24 hours. Exposure to the anti-AChR antibody results in a loss of AChRs from the surface of the cells through a process that has the characteristics of antigenic modulation. The number of AChRs on the surface of the chromaffin cells can also be modulated by agonists and hormones, including glucocotricoids. Catecholamines, three peptides that may be secreted by chromaffin cells, and K{sup +}-induced secretion reduce agonist-induced catecholamine release by decreasing the number of AChRs, providing a mechanism for autoregulation.

  4. Enucleation-induced rat adrenal gland regeneration: expression profile of selected genes involved in control of adrenocortical cell proliferation.

    PubMed

    Tyczewska, Marianna; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Trejter, Marcin; Hochol-Molenda, Anna; Nowak, Krzysztof W; Malendowicz, Ludwik K

    2014-01-01

    Enucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes. Factors encoded by these genes obscure possible priming effects of various cytokines on initiation of regeneration. In regenerating adrenals we identified over 100 up- or downregulated genes involved in adrenocortical cell proliferation. The changes were most significant at days 2-3 after enucleation and their number decreased during regeneration. For example, expression analysis revealed a notable upregulation of the growth arrest gene, Gadd45, only 24 hours after surgery while expression of cyclin B1 and Cdk1 genes was notably elevated between days 1-8 of regeneration. These changes were accompanied by changes in expression levels of numerous growth factors and immediate-early transcription factors genes. Despite notable differences in mechanisms of adrenal and liver regeneration, in regenerating adrenals we identified genes, the expression of which is well recognized in regenerating liver. Thus, it seems legitimate to suggest that, in the rat, the general model of liver and adrenal regeneration demonstrate some degree of similarity. PMID:25431590

  5. Enucleation-Induced Rat Adrenal Gland Regeneration: Expression Profile of Selected Genes Involved in Control of Adrenocortical Cell Proliferation

    PubMed Central

    Tyczewska, Marianna; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Trejter, Marcin; Hochol-Molenda, Anna; Nowak, Krzysztof W.; Malendowicz, Ludwik K.

    2014-01-01

    Enucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes. Factors encoded by these genes obscure possible priming effects of various cytokines on initiation of regeneration. In regenerating adrenals we identified over 100 up- or downregulated genes involved in adrenocortical cell proliferation. The changes were most significant at days 2-3 after enucleation and their number decreased during regeneration. For example, expression analysis revealed a notable upregulation of the growth arrest gene, Gadd45, only 24 hours after surgery while expression of cyclin B1 and Cdk1 genes was notably elevated between days 1–8 of regeneration. These changes were accompanied by changes in expression levels of numerous growth factors and immediate-early transcription factors genes. Despite notable differences in mechanisms of adrenal and liver regeneration, in regenerating adrenals we identified genes, the expression of which is well recognized in regenerating liver. Thus, it seems legitimate to suggest that, in the rat, the general model of liver and adrenal regeneration demonstrate some degree of similarity. PMID:25431590

  6. Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

    SciTech Connect

    Sanborn, B.B.; Schneider, A.S. )

    1990-01-01

    Inositol trisphosphate (IP{sub 3}), a product of the phosphoinositide cycle, mobilizes intracellular Ca{sup 2+} in many cell types. New evidence suggests that inositol tetrakisphosphate (IP{sub 4}), an IP{sub 3} derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP{sub 4} are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP{sub 4} in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine stimulated an increase in ({sup 3}H)IP{sub 4} and ({sup 3}H)IP{sub 3} accumulation in chromaffin cells and this effect was completely blocked by atropine. ({sup 3}H)IP{sub 4} accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP{sub 3} and IP{sub 4} hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP{sub 4} and calcium homeostasis.

  7. Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells.

    PubMed

    Hao, Zhenhua; Wei, Lisi; Feng, Yaqin; Chen, Xiaowei; Du, Wen; Ma, Jing; Zhou, Zhuan; Chen, Liangyi; Li, Wei

    2015-04-01

    The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky-Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs. PMID:25673877

  8. Woman with virilizing congenital adrenal hyperplasia and Leydig cell tumor of the ovary.

    PubMed

    Fernández-García Salazar, Rosario; Muñoz-Darias, Carmen; Haro-Mora, Juan Jesús; Almaraz, M Cruz; Audí, Laura; Martínez-Tudela, Juana; Yahyaoui, Raquel; Esteva, Isabel

    2014-08-01

    We report the case of a 36-year-old woman with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and corticosteroid replacement therapy since birth. She manifested persistent virilization and high testosterone levels that were attributed to nonadherence to medical treatment. The patient was referred to our gender unit for genitoplastic surgery. We recommended the patient for left oophorectomy after detecting an ovarian mass. Pathologic findings confirmed an ovarian hilus cell tumor. Testosterone levels fell back to normal and masculinization disappeared but ACTH remained elevated. This case represents a very rare type of primary ovarian tumor that must be considered in persistent virilizing symptoms in women with CAH. PMID:24702195

  9. Identification and characterization of an angiotensin II receptor on cultured bovine adrenal chromaffin cells

    SciTech Connect

    Boyd, V.L.

    1987-01-01

    The presence of an angiotensin II receptor on cultured bovine adrenal chromaffin cells was demonstrated by radioligand binding. A single class of finding sites with a K/sub D/ of 0.7 nM was characterized. The use of radioligands also allows the localization of receptors by autoradiography. Autoradiography demonstrated that approximately 50% of the isolated cells bound angiotensin II. It was of interest to see if angiotensin II bound to a cell that possessed a certain phenotype. In order to evaluate this possibility a technique was developed that combined autoradiography and immunocytochemistry. Results indicated that angiotensin II binding sites were not localized preferentially to either norepinephrine or epinephrine cells. Binding of angiotensin II was associated with the release of intracellular catecholamine stores. Cells were pre-loaded with /sup 3/H-norepinephrine and secretion was monitored by following radioactivity released into the supernatant. Alternatively, release of endogenous catecholamines was determined by fluorometric assay.

  10. Adrenal glands

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002219.htm Adrenal glands To use the sharing features on this page, please enable JavaScript. The adrenal glands are two triangle-shaped glands. One gland is ...

  11. Combined steroidogenic characters of fetal adrenal and Leydig cells in childhood adrenocortical carcinoma.

    PubMed

    Fujisawa, Yasuko; Sakaguchi, Kimiyoshi; Ono, Hiroyuki; Yamaguchi, Rie; Kato, Fumiko; Kagami, Masayo; Fukami, Maki; Ogata, Tsutomu

    2016-05-01

    Although childhood adrenocortical carcinomas (c-ACCs) with a TP53 mutation are known to produce androgens, detailed steroidogenic characters have not been clarified. Here, we examined steroid metabolite profiles and expression patterns of steroidogenic genes in a c-ACC removed from the left adrenal position of a 2-year-old Brazilian boy with precocious puberty, using an atrophic left adrenal gland removed at the time of tumorectomy as a control. The c-ACC produced not only abundant dehydroepiandrosterone-sulfate but also a large amount of testosterone via the Δ5 pathway with Δ5-androstenediol rather than Δ4-androstenedione as the primary intermediate metabolite. Furthermore, the c-ACC was associated with elevated expressions of CYP11A1, CYP17A1, POR, HSD17B3, and SULT2A1, a low but similar expression of CYB5A, and reduced expressions of AKR1C3 (HSD17B5) and HSD3B2. Notably, a Leydig cell marker INSL3 was expressed at a low but detectable level in the c-ACC. Furthermore, molecular studies revealed a maternally inherited heterozygous germline TP53 mutation, and several post-zygotic genetic aberrations in the c-ACC including loss of paternally derived chromosome 17 with a wildtype TP53 and loss of maternally inherited chromosome 11 and resultant marked hyperexpression of paternally expressed growth promoting gene IGF2 and drastic hypoexpression of maternally expressed growth suppressing gene CDKN1C. These results imply the presence of combined steroidogenic properties of fetal adrenal and Leydig cells in this patient's c-ACC with a germline TP53 mutation and several postzygotic carcinogenic events. PMID:26940356

  12. Primary extra-renal clear cell renal cell carcinoma masquerading as an adrenal mass: A diagnostic challenge

    PubMed Central

    Hasan, Roumina; Kumar, Sandeep; Monappa, Vidya; Ayachit, Anurag

    2015-01-01

    We present the first case of a nonmetastasizing renal cell carcinoma (RCC) masquerading as an adrenal mass, in the presence of normal bilateral native kidneys, in a young adult. The possibility of this mass developing in a supernumerary kidney was ruled out, since no identifiable renal tissue, pelvis or ureters was seen within the mass, nor was any separate systemic arterial supply to the mass seen. The diagnosis of extra-renal clear cell RCC was based on cyto-morphological features, further confirmed by immunohistochemistry findings. The origin of this extra-renal clear cell renal cell is proposed to be from the mesodermal embryonic rests. PMID:26692677

  13. Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans.

    PubMed

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2015-01-01

    Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:26417403

  14. Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans

    PubMed Central

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2015-01-01

    Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women’s Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:26417403

  15. Stimulation of secretion from bovine adrenal chromaffin cells by microsecond bursts of therapeutic levels of ultrasound.

    PubMed Central

    Robinson, I M; Kinnick, R R; Greenleaf, J F; Fernandez, J M

    1996-01-01

    1. In this study the secretory response of individual bovine adrenal chromaffin cells was monitored using amperometric carbon-fibre microelectrodes. Cells were stimulated to secrete by exposure to 20-100 microseconds long tonebursts of ultrasound (2-4 x 10(5) Pa; peak pressure at 1 MHz). 2. Three types of secretory responses were observed: an almost instantaneous response, a delayed release of catecholamines, or a series of 'burst-like' secretory bouts. 3. Fura-2 measurements of intracellular Ca2+ concentrations showed that the release of catecholamines was accompanied by an increase in the intracellular Ca2+ concentration. In the absence of extracellular Ca2+, secretory responses were not evoked showing that Ca2+ entry was necessary to elicit catecholamine release. Images Figure 1 PMID:8730600

  16. Selective accumulation of meso-tetra(hydroxyphenyl)chlorin in steroid-synthesizing cells of the rat adrenal gland

    NASA Astrophysics Data System (ADS)

    Colombo-Benkmann, Mario; Muhm, Markus; Gahlen, Johannes; Vry, Magnus-Sebastian; Deubzer, Hedwig; Holloschi, Andreas; Haffner, Matthias; Heym, Christine; Senninger, Norbert

    1998-04-01

    Rat adrenal glands fluoresce intensely after systemic application of meso-tetra(hydroxyphenyl)chlorin (mTHPC). We investigated which parts of the adrenal gland accumulate mTHPC. Furthermore we examined the time course of adrenal mTHPC-accumulation. Ten male Wistar rats each were given 0.5 or 0.7 mg mTHPC kg-1 iv. Each two animals were perfused with normal saline and Zamboni fixative 6, 12, 24, 48 and 72 hours after photosensitization. Untreated animals served as controls. Fluorescence was quantified on 20 micrometer frozen sections with CCD-camera and appropriate software. Immunohistochemistry identified specific cell types with antibodies to steroid-synthesizing enzymes. The cortex exhibited an intense fluorescence, with weaker fluorescence of corticocytes in the zona glomerulosa compared to the other zones. Besides intensely fluorescing singly lying scattered cells, the medulla showed a faint mTHPC-induced fluorescence. Immunohistochemistry revealed that intramedullary cells with intense fluorescence were corticocytes, showing a positive reaction to the 21-(beta) -hydroxylase antibody. Peak accumulation of mTHPC was always observed after 24 hours. Our results indicate for the first time that only steroid synthesizing cells of the adrenal gland exhibit an intense photosensitizer-induced fluorescence. Thus mTHPC-application is an uncomplicated method to identify steroid-synthesizing cells, possibly also in other organs.

  17. Secretion of Catecholamines from Adrenal Gland by a Single Electrical Shock: Electrotonic Depolarization of Medullary Cell Membrane

    NASA Astrophysics Data System (ADS)

    Wakade, Arun R.; Wakade, Taruna D.

    1982-05-01

    Transmural stimulation of the isolated adrenal gland of the rat and guinea pig results in secretion of catecholamines. The secretion is due to activation of cholinergic receptors of the adrenal medulla by acetylcholine released from splanchnic nerve terminals after transmural stimulation. Our aim was to see whether the same experimental technique could be used to directly excite the adrenal medullary cell membrane by electrical stimulation and whether such stimulation would result in secretion of catecholamines. We demonstrate here that a single electrical shock to the perfused adrenal gland of the rat results in massive secretion of epinephrine and norepinephrine. The secretion is directly related to the strength and duration of the applied stimulus over a wide range. Catecholamine secretion is unaffected by tetrodotoxin or hexamethonium/atropine but is abolished by Ca2+ lack or 3 mM Mn2+. We suggest that the adrenal medullary membrane undergoes nonpropagated electrotonic depolarization on electrical stimulation and thereby voltage-dependent Ca2+ channels are opened to initiate secretion.

  18. YPEL4 modulates HAC15 adrenal cell proliferation and is associated with tumor diameter.

    PubMed

    Oki, Kenji; Plonczynski, Maria W; Gomez-Sanchez, Elise P; Gomez-Sanchez, Celso E

    2016-10-15

    Yippee-like (YPEL) proteins are thought to be related to cell proliferation because of their structure and location in the cell. The aim of this study was to clarify the effects of YPEL4 on aldosterone production and cell proliferation in the human adrenocortical cell line (HAC15) and aldosterone producing adenoma (APA). Basal aldosterone levels in HAC15 cells over-expressing YPEL4 was higher than those of control HAC15 cells. The positive effects of YPEL4 on cell proliferation were detected by XTT assay and crystal violet staining. YPEL4 levels in 39 human APA were 2.4-fold higher compared to those in 12 non-functional adrenocortical adenomas, and there was a positive relationship between YPEL4 levels and APA diameter (r = 0.316, P < 0.05). In summary, we have demonstrated that YPEL4 stimulates human adrenal cortical cell proliferation, increasing aldosterone production as a consequence. These results in human adrenocortical cells are consistent with the clinical observations with APA in humans. PMID:27333825

  19. CD44 expression in normal adrenal tissue and adrenal tumours.

    PubMed Central

    Barshack, I; Goldberg, I; Nass, D; Olchovsky, D; Kopolovic, J

    1998-01-01

    BACKGROUND: CD44 is a cell surface glycoprotein found on many normal cells, mainly lymphoid and epithelial. Normal cells usually express standard CD44 (CD44-S), whereas malignant tumours may express CD44 variant isoforms (CD44-V). CD44 expression has been described for neural crest derivatives. Characterisation of differences in CD44 expression may help in the diagnosis and differentiation of distinct adrenal tumours. AIMS: To examine CD44 expression in different layers of cortical cortex, in adrenal medulla, and in adrenal tumours. METHODS: CD44-S and CD44-V6 expression were studied in 12 cases of adrenal cortical adenoma, 3 of adrenal cortical carcinoma, 10 of pheochromocytoma, and 4 normal adrenal glands. RESULTS: CD44-V6 staining showed cytoplasmic expression in normal adrenal cortex and in cortical adenomas and carcinomas. Pheochromocytomas also showed CD44-V6 expression but in 5 of the 10 cases it was sparse, focal, and sometimes perinuclear. Strong membranous staining for CD44-S was observed in normal adrenal medulla. Analysis of CD44-S expression revealed differences between cortical adrenal tumours and pheochromocytomas. Ten of 12 cortical adenomas and 2 of 3 cortical carcinoma cells showed weak to moderate cytoplasmic staining, but all cases of pheochromocytoma had strong membranous staining. CONCLUSIONS: Membranous CD44-S staining may help to distinguish pheochromocytoma from adrenal cortical adenoma. Images PMID:9577373

  20. Calcitriol-mediated hypercalcemia in a patient with bilateral adrenal non-Hodgkin's B-cell lymphoma case report

    PubMed Central

    Abaroa-Salvatierra, Ana; Shaikh, Bilal; Deshmukh, Mrunalini; Alweis, Richard; Patel, Arti

    2016-01-01

    Calcitriol-mediated hypercalcemia is a frequent manifestation of hematological malignancies. However, there are a few reports of cases presenting with increased angiotensin-converting enzyme (ACE) level, which suggests a possible mechanism similar to that of granulomatous diseases. We present a patient with hypercalcemia, normal parathyroid hormone, and parathyroid hormone-related protein levels but high calcitriol and ACE levels that, after further investigation, was diagnosed with bilateral adrenal non-Hodgkin's B-cell lymphoma. Primary adrenal lymphoma represents only 1% of all non-Hodgkin's lymphomas and is usually asymptomatic but should be considered by clinicians among the malignancies that cause calcitriol-mediated hypercalcemia. PMID:27124160

  1. L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion.

    PubMed

    Marcantoni, A; Baldelli, P; Hernandez-Guijo, J M; Comunanza, V; Carabelli, V; Carbone, E

    2007-01-01

    Voltage-gated L-type (Cav1.2 and Cav1.3) channels are widely expressed in cardiovascular tissues and represent the critical drug-target for the treatment of several cardiovascular diseases. The two isoforms are also abundantly expressed in neuronal and neuroendocrine tissues. In the brain, Cav1.2 and Cav1.3 channels control synaptic plasticity, somatic activity, neuronal differentiation and brain aging. In neuroendocrine cells, they are involved in the genesis of action potential generation, bursting activity and hormone secretion. Recent studies have shown that Cav1.2 and Cav1.3 are also expressed in chromaffin cells but their functional role has not yet been identified despite that L-type channels possess interesting characteristics, which confer them an important role in the control of catecholamine secretion during action potentials stimulation. In intact rat adrenal glands L-type channels are responsible for adrenaline and noradrenaline release following splanchnic nerve stimulation or nicotinic receptor activation. L-type channels can be either up- or down-modulated by membrane autoreceptors following distinct second messenger pathways. L-type channels are tightly coupled to BK channels and activate at relatively low-voltages. In this way they contribute to the action potential hyperpolarization and to the pace-maker current controlling action potential firings. L-type channels are shown also to regulate the fast secretion of the immediate readily releasable pool of vesicles with the same Ca(2+)-efficiency of other voltage-gated Ca(2+) channels. In mouse adrenal slices, repeated action potential-like stimulations drive L-type channels to a state of enhanced stimulus-secretion efficiency regulated by beta-adrenergic receptors. Here we will review all these novel findings and discuss the possible implication for a specific role of L-type channels in the control of chromaffin cells activity. PMID:17561252

  2. Detection of angiotensin II binding to single adrenal zona glomerulosa cells by confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    McCoy, Michael J.; Habermann, Timothy J.; Hanke, Craig J.; Adar, Fran; Campbell, William B.; Nithipatikom, Kasem

    1999-04-01

    We developed a confocal Raman microspectroscopic technique to study ligand-receptor bindings in single cells using Raman-labeled ligands and surface-enhanced Raman scattering (SERS). The adrenal zona glomerulosa (ZG) cells were used as a model in this study. ZG cells have a high density of angiotensin II (AII) receptors on the cellular membrane. There are two identified subtypes of AII receptors,namely AT1 and AT2 receptors. AII is a peptidic hormone, which upon binding to its receptors, stimulates the release of aldosterone from ZG cells. The cellular localization of these receptors subtypes was detected in single ZG cells by using immunocomplexation of receptors with specific antibodies and confocal Raman microspectroscopy. In the binding study, we used biotin-labeled AII to bind to its receptors in ZG cells. Then, avidin and Raman-labeled AII. The binding was measure directly on the single ZG cells. The results showed that the binding was displaced with unlabeled AII and specific AII antagonists. This is a rapid and sensitive technique for detection of cellular ligand bindings as well as antagonists screening in drug discovery.

  3. POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells

    PubMed Central

    França, M. M.; Abreu, N. P.; Vrechi, T. A. M.; Lotfi, C. F.

    2015-01-01

    During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G) and fasciculata/reticularis (F/R) cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells. PMID:26421867

  4. Cell phones and cancer

    MedlinePlus

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of exposure ...

  5. Cell phones and cancer

    MedlinePlus

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of ...

  6. Congenital Adrenal Hyperplasia

    MedlinePlus

    MENU Return to Web version Congenital Adrenal Hyperplasia Overview What is congenital adrenal hyperplasia? Congenital adrenal hyperplasia, or CAH, is a disorder that affects the adrenal glands. The adrenal ...

  7. Simultaneous amperometric measurement of ascorbate and catecholamine secretion from individual bovine adrenal medullary cells.

    PubMed

    Cahill, P S; Wightman, R M

    1995-08-01

    Secretion of ascorbate and catecholamines from single bovine adrenal medullary cells has been detected with amperometry at carbon-fiber microelectrodes. Two carbon-fiber electrodes were employed. One was beveled, and voltammograms at this electrode showed overlap of the responses for ascorbate and the catecholamines. The other was beveled and electrochemically oxidized to shift the ascorbate oxidation wave to potentials more negative than that of the catecholamines. Thus, at an applied potential of 0.05 V vs SSCE, ascorbate was selectively oxidized at the treated electrode and both catecholamines and ascorbate were oxidized at an applied potential of 0.65 V at the untreated electrode. Exocytotic release from the cell was stimulated with K+, nicotine, and digitonin. Nicotine and K+ depolarize the cell membrane and elicit vesicular release. Digitonin is a detergent that reacts with cholesterol in the plasma membrane and causes the formation of pores. Ascorbate efflux from individual cells could be induced by digitonin but not by K+ or nicotine and was observed as a single peak with a full width at half-maximum of 4 s. In contrast, catecholamine release was observed as many rapid, sequential current spikes when the cell was exposed to either digitonin, K+, or nicotine. The two different types of release show that ascorbate and catecholamines are being released from two different cellular compartments. The calcium independence of the digitonin-induced ascorbate release provides additional evidence that ascorbate is released by a nonexocytotic process. PMID:8849026

  8. Gallium-68 PSMA uptake in adrenal adenoma.

    PubMed

    Law, W Phillip; Fiumara, Frank; Fong, William; Miles, Kenneth A

    2016-08-01

    Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenomas should be one with which reporting clinicians are familiar. PMID:26394552

  9. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome

    PubMed Central

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika PMID:27212842

  10. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome.

    PubMed

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika. PMID:27212842

  11. Expression of the beacon gene in the rat adrenal gland: direct inhibitory effect of beacon[47-73] on aldosterone secretion from dispersed adrenal zona glomerulosa cells.

    PubMed

    Ziolkowska, Agnieszka; Rucinski, Marcin; Neri, Giuliano; Di Liddo, Rosa; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2004-02-01

    Beacon gene was recently identified in the rat hypothalamus, and there is evidence that beacon may be involved in the functional regulation of neuroendocrine axes. Reverse transcription-polymerase chain reaction and immunocytochemistry showed the expression of beacon mRNA and protein in the rat adrenal gland, especially in the cortex. Beacon[47-73], at a concentration over 10(-7) M decreased basal aldosterone secretion from dispersed rat zona glomerulosa (ZG) cells, without affecting the ACTH-stimulated one. Basal and agonist-stimulated corticosterone secretion from dispersed zona fasciculata-reticularis cells and catecholamine release from adrenomedullary slices were unaffected by beacon[47-73]. The suppressive effect of beacon[47-73] on aldosterone secretion from ZG cells was abolished by either H-89 or calphostin-C, which are inhibitors of protein kinase A and C signaling cascades. Taken together, these findings allow us to suggest that beacon can be included in the group of regulatory peptides involved in the fine tuning of ZG secretory activity. PMID:14719126

  12. Expression of the spexin gene in the rat adrenal gland and evidences suggesting that spexin inhibits adrenocortical cell proliferation.

    PubMed

    Rucinski, Marcin; Porzionato, Andrea; Ziolkowska, Agnieszka; Szyszka, Marta; Macchi, Veronica; De Caro, Raffaele; Malendowicz, Ludwik K

    2010-04-01

    Spexin (SPX, also called NPQ) is a recently identified, highly conserved peptide which is processed and secreted. We analysed the SPX gene and its protein product in the rat adrenal gland to ascertain whether SPX is involved in the regulation of corticosteroid secretion of and growth of adrenocortical cells. In adult rat adrenal glands the highest levels of SPX mRNA were present in the glomerulosa (ZG) and fasciculate/reticularis (ZF/R) zones. High SPX gene expression levels were found in freshly isolated adult rat ZG and ZF/R cells. In cultured adrenocortical cells the levels of SPX mRNA were lower than in freshly isolated cells. SPX mRNA expression levels were found to be 2-3 times higher during days 90-540 of postnatal development than found during days 2-45. Prolonged ACTH administration lowered and dexamethasone increased adrenal SPX mRNA levels in vivo. Adrenal enucleation produced a significant linear increase in SPX mRNA levels, with the highest value occurring at day 8 after surgery, with control values taken on day 30 after enucleation. Immunohistochemistry revealed SPX-like immunoreactivity in the entire cortex of the adult male rat and in enucleation-induced regenerating cortex. A concentration of 10-6M SPX peptide stimulated basal aldosterone secretion by freshly isolated ZG. In prolonged exposure of adrenocortical cell primary cultures to SPX (10-6M) resulted in a small increase in corticosterone secretion and a notable decrease in BrdU incorporation. The results suggest the direct involvement of SPX in the regulation of adrenocortical cell proliferation; however, the mechanism of action remains unknown. PMID:20045034

  13. Catecholamines-evoked cytosolic Ca2+ rise in endothelial cells from bovine adrenal medulla.

    PubMed

    Vinet, R; Rojas, F; Luxoro, M; Vargas, F; Cortés, M

    2000-01-01

    The effects of catecholamines on intracellular Ca2+ concentrations ([Ca2+]i) in single acutely dissociated bovine adrenal medulla endothelial cells (BAMECs) were measured using the intracellular fluorescent probe Fluo-3 AM. 100 microm epinephrine or norepinephrine induced a biphasic [Ca2+]i rise with an initial peak followed by a delayed phase. 10 microm phenylephrine (alpha1-adrenergic agonist) caused a [Ca2+]i rise similar to that evoked by catecholamines. The increase in [Ca2+]i induced by 10 microm phenylephrine was reverted by 10 microm phenoxybenzamine (alpha-adrenergic antagonist). Neither isoproterenol (beta-adrenergic agonist) nor clonidine (alpha2-adrenergic agonist) induced [Ca2+]i rise. The initial peak was insensitive to zero external Ca2+ and it was abolished after Ca2+ internal storages were emptied by 10 mM caffeine. The delayed phase was reduced to near zero by external Ca2+ removal. These results indicate that BAMECs possess alpha1-adrenergic receptors associated to both the release of caffeine-sensitive intracellular Ca2+ stores and the entry of extracellular Ca2+. We suggest that chromaffin cell secretion may activate BAMECs in vivo through an increase in [Ca2+]i which could induce the secretion of vasoactive factors allowing a rapid entry of hormones into the circulation. PMID:10724332

  14. Diabetic ketoacidosis with concurrent pancreatitis, pancreatic β islet cell tumor, and adrenal disease in an obese ferret (Mustela putorius furo).

    PubMed

    Phair, Kristen A; Carpenter, James W; Schermerhorn, Thomas; Ganta, Chanran K; DeBey, Brad M

    2011-07-01

    A 5.5-y-old spayed female ferret (Mustela putorius furo) with a history of adrenal disease, respiratory disease, and chronic obesity was evaluated for progressive lethargy and ataxia, diminished appetite, and possible polyuria and polydipsia. Physical examination revealed obesity, lethargy, tachypnea, dyspnea, a pendulous abdomen, significant weakness and ataxia of the hindlimbs, prolonged skin tenting, and mild tail-tip alopecia. Clinicopathologic analysis revealed severe hyperglycemia, azotemia, an increased anion gap, glucosuria, ketonuria, proteinuria, and hematuria. Abdominal ultrasonography showed hyperechoic hepatomegaly, bilateral adrenomegaly, splenic nodules, mild peritoneal effusion, and thickened and mildly hypoechoic limbs of the pancreas with surrounding hyperechoic mesentery. Fine-needle aspirates of the liver were highly suggestive of hepatic lipidosis. In light of a diagnosis of concurrent diabetic ketoacidosis and pancreatitis, the ferret was treated with fluid therapy, regular and long-acting insulin administration, and pain medication. However, electrolyte derangements, metabolic acidosis, dyspnea, and the clinical appearance of the ferret progressively worsened despite treatment, and euthanasia was elected. Necropsy revealed severe hepatic lipidosis, severe suppurative pancreatitis and vacuolar degeneration of pancreatic islet cells, a pancreatic β islet cell tumor, bilateral adrenal cortical adenomas, and myocardial fibrosis. To our knowledge, this case represents the first report of concurrent diabetes mellitus, pancreatitis, pancreatic β islet cell tumor (insulinoma), and adrenal disease in a domestic ferret. The simultaneous existence of 3 endocrine diseases, pancreatitis, and their associated complications is a unique and clinically challenging situation. PMID:21838985

  15. Diabetic Ketoacidosis with Concurrent Pancreatitis, Pancreatic β Islet Cell Tumor, and Adrenal Disease in an Obese Ferret (Mustela putorius furo)

    PubMed Central

    Phair, Kristen A; Carpenter, James W; Schermerhorn, Thomas; Ganta, Chanran K; DeBey, Brad M

    2011-01-01

    A 5.5-y-old spayed female ferret (Mustela putorius furo) with a history of adrenal disease, respiratory disease, and chronic obesity was evaluated for progressive lethargy and ataxia, diminished appetite, and possible polyuria and polydipsia. Physical examination revealed obesity, lethargy, tachypnea, dyspnea, a pendulous abdomen, significant weakness and ataxia of the hindlimbs, prolonged skin tenting, and mild tail-tip alopecia. Clinicopathologic analysis revealed severe hyperglycemia, azotemia, an increased anion gap, glucosuria, ketonuria, proteinuria, and hematuria. Abdominal ultrasonography showed hyperechoic hepatomegaly, bilateral adrenomegaly, splenic nodules, mild peritoneal effusion, and thickened and mildly hypoechoic limbs of the pancreas with surrounding hyperechoic mesentery. Fine-needle aspirates of the liver were highly suggestive of hepatic lipidosis. In light of a diagnosis of concurrent diabetic ketoacidosis and pancreatitis, the ferret was treated with fluid therapy, regular and long-acting insulin administration, and pain medication. However, electrolyte derangements, metabolic acidosis, dyspnea, and the clinical appearance of the ferret progressively worsened despite treatment, and euthanasia was elected. Necropsy revealed severe hepatic lipidosis, severe suppurative pancreatitis and vacuolar degeneration of pancreatic islet cells, a pancreatic β islet cell tumor, bilateral adrenal cortical adenomas, and myocardial fibrosis. To our knowledge, this case represents the first report of concurrent diabetes mellitus, pancreatitis, pancreatic β islet cell tumor (insulinoma), and adrenal disease in a domestic ferret. The simultaneous existence of 3 endocrine diseases, pancreatitis, and their associated complications is a unique and clinically challenging situation. PMID:21838985

  16. Conditional Mutagenesis of Gata6 in SF1-Positive Cells Causes Gonadal-Like Differentiation in the Adrenal Cortex of Mice

    PubMed Central

    Pihlajoki, Marjut; Gretzinger, Elisabeth; Cochran, Rebecca; Kyrönlahti, Antti; Schrade, Anja; Hiller, Theresa; Sullivan, Laura; Shoykhet, Michael; Schoeller, Erica L.; Brooks, Michael D.; Heikinheimo, Markku

    2013-01-01

    Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of transcription factor GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex. Cytomegalic changes were evident in fetal and adult cKO adrenal glands, and chromaffin cells were ectopically located at the periphery of the glands. Corticosterone secretion in response to exogenous ACTH was blunted in cKO mice. Spindle-shaped cells expressing Gata4, a marker of gonadal stroma, accumulated in the adrenal subcapsule of Gata6 cKO mice. RNA analysis demonstrated the concomitant upregulation of other gonadal-like markers, including Amhr2, in the cKO adrenal glands, suggesting that GATA6 inhibits the spontaneous differentiation of adrenocortical stem/progenitor cells into gonadal-like cells. Lhcgr and Cyp17 were overexpressed in the adrenal glands of gonadectomized cKO vs control mice, implying that GATA6 also limits sex steroidogenic cell differentiation in response to the hormonal changes that accompany gonadectomy. Nulliparous female and orchiectomized male Gata6 cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of these mice. Our findings offer genetic proof that GATA6 regulates the differentiation of steroidogenic progenitors into adrenocortical cells. PMID:23471215

  17. Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells.

    PubMed

    Gomes, Andreia; Correia, Gustavo; Coelho, Marisa; Araújo, João Ricardo; Pinho, Maria João; Teixeira, Ana Luisa; Medeiros, Rui; Ribeiro, Laura

    2015-05-01

    Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo. PMID:25727966

  18. Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C

    PubMed Central

    Wesche, B; Jaeckel, E; Trautwein, C; Wedemeyer, H; Falorni, A; Frank, H; von zur Muhlen, A; Manns, M; Brabant, G

    2001-01-01

    BACKGROUND/AIMS—Interferon alpha (IFN-α) therapy for chronic hepatitis C may trigger induction of autoimmunity against several organs. Immune reactions against distinct adrenocortical protein antigens involved in adrenal autoimmune disease have not been reported to date. Therefore, we investigated the development of highly sensitive and specific adrenal autoantibodies in patients with chronic hepatitis C in response to IFN-α treatment. In addition, we studied induction of pancreatic islet and thyroid autoantibodies.
PATIENTS/METHODS—Sera of 75 patients (42 males, 33 females; mean age 47 (13) years) were analysed before, during, and after IFN-α therapy (9-18×106 IE/week; mean duration 8.3 (3.5) months). Autoantibodies (Abs) to adrenal 21-hydroxylase (21OH-Abs), and to islet glutamic acid decarboxylase (GAD65-Abs) and protein tyrosine phosphatase (IA2-Abs) were determined by a radiobinding assay using 35S labelled protein generated by an in vitro translation system. Thyroid antibodies were measured by a commercially available ELISA.
RESULTS—Thirteen of 75 patients were initially positive for some of the autoantibodies. During or after IFN-α therapy, 3/62 initially negative patients (4.8%) developed 21OH-Abs. GAD65-Abs or IA2-Abs appeared in 5/62 and 1/62 patients, respectively (9.7% in total). In 12/62 patients (19.4%), thyroid specific antibodies appeared. In none of the 21OH-Ab positive subjects was adrenal dysfunction observed, and no patient with islet autoantibodies developed diabetes mellitus or impaired glucose tolerance.
CONCLUSIONS—IFN-α induces 21OH-Abs in some cases, while islet and thyroid specific autoantibodies are more frequently found. However, our results indicate for the first time that the adrenal cortex also has to be considered as a potential target of IFN-α related autoimmunity.


Keywords: hepatitis C; interferon alpha; autoantibodies; adrenal cortex; pancreatic islet cells PMID:11171829

  19. Synchronous renal cell carcinoma metastasis to the contralateral adrenal gland and pancreas: A case report with 7-year follow-up subsequent to surgical therapy

    PubMed Central

    WU, CUNZAO; ZHOU, ZHENXU; YE, XUETING; HU, WEILIE

    2016-01-01

    Metastatic renal cell carcinoma (RCC) disseminates to a number of organ sites and few patients demonstrate long-term survival following surgery. However, synchronous metastasis of RCC to the contralateral adrenal gland and pancreas is rare. In the present report, a case of synchronous RCC metastasis to the contralateral adrenal gland and pancreas in a 55-year-old patient, with an 116×92×61 mm right renal tumor and a 96×79×57 mm left adrenal lesion, is described. In April 2007, right nephrectomy was performed to treat the RCC, left adrenalectomy was performed to treat the adrenal tumor and the pancreatic metastases were resected. The patient remained alive at the 7-year follow-up appointment. PMID:27313756

  20. In vivo evidence for the crucial role of SF1 in steroid-producing cells of the testis, ovary and adrenal gland

    PubMed Central

    Buaas, F. William; Gardiner, Jennifer R.; Clayton, Sally; Val, Pierre; Swain, Amanda

    2012-01-01

    Adrenal and gonadal steroids are essential for life and reproduction. The orphan nuclear receptor SF1 (NR5A1) has been shown to regulate the expression of enzymes involved in steroid production in vitro. However, the in vivo role of this transcription factor in steroidogenesis has not been elucidated. In this study, we have generated steroidogenic-specific Cre-expressing mice to lineage mark and delete Sf1 in differentiated steroid-producing cells of the testis, the ovary and the adrenal gland. Our data show that SF1 is a regulator of the expression of steroidogenic genes in all three organs. In addition, Sf1 deletion leads to a radical change in cell morphology and loss of identity. Surprisingly, sexual development and reproduction in mutant animals were not compromised owing, in part, to the presence of a small proportion of SF1-positive cells. In contrast to the testis and ovary, the mutant adult adrenal gland showed a lack of Sf1-deleted cells and our studies suggest that steroidogenic adrenal cells during foetal stages require Sf1 to give rise to the adult adrenal population. This study is the first to show the in vivo requirements of SF1 in steroidogenesis and provides novel data on the cellular consequences of the loss of this protein specifically within steroid-producing cells. PMID:23136395

  1. Enhanced BDNF signalling following chronic hypoxia potentiates catecholamine release from cultured rat adrenal chromaffin cells

    PubMed Central

    Scott, Angela L; Zhang, Min; Nurse, Colin A

    2015-01-01

    Environmental stressors, including chronic hypoxia, enhance the ability of adrenomedullary chromaffin cells (AMCs) to secrete catecholamines; however, the underlying molecular mechanisms remain unclear. Here, we investigated the role of brain-derived neurotrophic factor (BDNF) signalling in rat AMCs exposed to chronic hypoxia. In rat adrenal glands, BDNF and its tropomyosin-related kinase B (TrkB) receptor are highly expressed in the cortex and medulla, respectively. Exposure of AMCs to chronic hypoxia (2% O2; 48 h) in vitro caused a significant increase to TrkB mRNA expression. A similar increase was observed in an immortalized chromaffin cell line (MAH cells); however, it was absent in MAH cells deficient in the transcription factor HIF-2α. A specific TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), stimulated quantal catecholamine secretion from chronically hypoxic (CHox; 2% O2) AMCs to a greater extent than normoxic (Nox; 21% O2) controls. Activation of TrkB by BDNF or 7,8-DHF increased intracellular Ca2+ ([Ca2+]i), an effect that was significantly larger in CHox cells. The 7,8-DHF-induced [Ca2+]i rise was sensitive to the tyrosine kinase inhibitor K252a and nickel (2 mm), but not the Ca2+ store-depleting agent cyclopiazonic acid. Blockade of T-type calcium channels with TTA-P2 (1 μm) or voltage-gated Na+ channels with TTX inhibited BDNF-induced [Ca2+]i increases. BDNF also induced a dose-dependent enhancement of action potential firing in CHox cells. These data demonstrate that during chronic hypoxia, enhancement of BDNF-TrkB signalling increases voltage-dependent Ca2+ influx and catecholamine secretion in chromaffin cells, and that T-type Ca2+ channels play a key role in the signalling pathway. Key points We investigated the role of the neurotrophin BDNF signalling via the TrkB receptor in rat adrenomedullary chromaffin cells (AMCs) exposed to normoxia (Nox; 21% O2) and chronic hypoxia (CHox; 2% O2) in vitro for ∼48 h. TrkB receptor expression was

  2. Photosensitizer-induced fluorescence of the rat adrenal gland and rat pheochromocytoma cells (PC 12) by meso-tetra(hydroxyphenyl)chlorin (mTHPC)

    NASA Astrophysics Data System (ADS)

    Colombo-Benkmann, Mario; Muhm, Markus; Gahlen, Johannes; Heym, Christine; Senninger, Norbert

    1997-12-01

    Rat adrenal glands exhibit an intense mTHPC-induced fluorescence. The objective of our study was the identification of adrenal cells exhibiting mTHPC-induced fluorescence under normal conditions and under stimulation of adrenal proliferation by reserpine. Furthermore mTHPC-uptake of rat pheochromocytoma (PC 12) cells was investigated. Four male Wistar rats received 0.5 mg mTHPC/kg iv 48 hours before perfusion. Furthermore four rats received reserpine (2 mg/kg im od), bromo-deoxy-uridine (BrdU; 50 mg/kg ip od) each for one week and mTHPC (0.5 mg/kg) 48 hours before perfusion. BrdU was detected immunohistochemically. PC 12-cells were incubated with 0.5 mg mTHPC/l culture medium for 24 or 48 hours. Cells and tissues were examined by fluorescence microscopy. The adrenal cortex exhibited an intense mTHPC-induced fluorescence. The adrenal medulla fluoresced faintly. Reserpine increased fluorescence of intramedullary cells, not coinciding with adrenal proliferation. Cortical fluorescence remained unchanged. PC 12-cells lying singly or in small groups and differentiating cells showed a more intense mTHPC- induced fluorescence than confluent cells. Differences of cortical and medullary uptake of mTHPC are independent of proliferation and may be explained by lipophilia of mTHPC, since adrenocytes have an uptake mechanism for cholesterol. The difference of mTHPC-uptake between PC 12-cells and chromaffin cells implicate the possibility of photodynamic applications for medullary neoplasia.

  3. Fragmentation of cancer cells

    NASA Astrophysics Data System (ADS)

    Vanapalli, Siva; Kamyabi, Nabiollah

    Tumor cells have to travel through blood capillaries to be able to metastasize and colonize in distant organs. Among the numerous cells that are shed by the primary tumor, very few survive in circulation. In vivo studies have shown that tumor cells can undergo breakup at microcapillary junctions affecting their survival. It is currently unclear what hydrodynamic and biomechanical factors contribute to fragmentation and moreover how different are the breakup dynamics of highly and weakly metastatic cells. In this study, we use microfluidics to investigate flow-induced breakup of prostate and breast cancer cells. We observe several different modes of breakup of cancer cells, which have striking similarities with breakup of viscous drops. We quantify the breakup time and find that highly metastatic cancer cells take longer to breakup than lowly metastatic cells suggesting that tumor cells may dynamically modify their deformability to avoid fragmentation. We also identify the role that cytoskeleton and membrane plays in the breakup process. Our study highlights the important role that tumor cell fragmentation plays in cancer metastasis. Cancer Prevention and Research Institute of Texas.

  4. Basal cell cancer (image)

    MedlinePlus

    ... is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure rate of more than 95%, but regular examination ...

  5. Direct visualization of secretion from single bovine adrenal chromaffin cells by laser-induced native fluorescence imaging microscopy

    SciTech Connect

    Tong, W.; Yeung, E.S.

    1998-03-01

    Direct visualization of the secretion process of individual bovine adrenal chromaffin cells was achieved with laser-induced native fluorescence imaging microscopy. By monitoring the native fluorescence of catecholamines excited by the 275 nm laser line with an intensified charge-coupled-device (CCD) camera, we obtained good temporal and spatial resolution simultaneously without using additional fluorescent probes. Large variations were found among individual cells in terms of the amounts of catecholamines secreted and the rates of secretion. Different regions of a cell also behave differently during the secretion process. However, the degree of this local heterogeneity is smaller than in neurons and neuralgia. The influence of deep-ultraviolet (UV) laser excitation on cells is also discussed. This quantitative imaging technique provides a useful noninvasive approach for the study of dynamic cellular changes and the understanding of the molecular mechanisms of secretory processes. {copyright} {ital 1998} {ital Society for Applied Spectroscopy}

  6. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  7. Cancer Stem Cells in Pancreatic Cancer

    PubMed Central

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  8. Bilateral adrenal haemorrhage leading to adrenal crisis

    PubMed Central

    McGowan-Smyth, Sam

    2014-01-01

    A 77-year-old man presented with an acute worsening of chronic back pain. CT showed dense bilateral adrenal glands suggestive of adrenal haemorrhage which was confirmed by MRI. Despite appropriate glucocorticoid replacement for adrenal insufficiency, 7 days after admission this patient suffered an adrenal crisis. Owing to the timely diagnosis, appropriate treatment was given and the patient survived. Large bilateral adrenal haemorrhage however, can lead to cardiovascular collapse and death if not appropriately diagnosed and managed promptly. Despite its rarity, bilateral adrenal haemorrhage should always be considered as a differential for back pain in the setting of an acute illness due to its potentially fatal consequences. PMID:24969071

  9. Radionuclide therapy of adrenal tumors.

    PubMed

    Carrasquillo, Jorge A; Pandit-Taskar, Neeta; Chen, Clara C

    2012-10-01

    Adrenal tumors arising from chromaffin cells will often accumulate radiolabeled metaiodobenzylguanidine (MIBG) and thus are amenable to therapy with I-131 MIBG. More recently, therapy studies have targeted the somatostatin receptors using Lu-177 or Y-90 radiolabeled somatostatin analogs. Because pheochromocytoma (PHEO)/paraganglioma (PGL) and neuroblastoma (NB), which often arise from the adrenals, express these receptors, clinical trials have been performed with these reagents. We will review the experience using radionuclide therapy for targeting PHEO/PGL and NBs. PMID:22718415

  10. Gap junction-mediated cell-to-cell communication in bovine and human adrenal cells. A process whereby cells increase their responsiveness to physiological corticotropin concentrations.

    PubMed Central

    Munari-Silem, Y; Lebrethon, M C; Morand, I; Rousset, B; Saez, J M

    1995-01-01

    We have studied the role of gap junction-mediated intercellular communication on the steroidogenic response of bovine (BAC) and human (HAC) adrenal fasciculo-reticularis cells in culture to corticotropin (ACTH). Indirect immunofluorescence analyses showed that intact human and bovine adreno-cortical tissue as well as HAC and BAC in culture expressed the gap junction protein connexin43 (also termed alpha 1 connexin). Both HAC and BAC were functionally coupled through gap junctions as demonstrated by microinjection of a low molecular mass fluorescent probe, Lucifer yellow. The cell-to-cell transfer of the probe was blocked by 18 alpha-glycyrrhetinic acid (GA), an inhibitor of gap junction-mediated intercellular communication. GA markedly decreased the steroidogenic response (cortisol production) of both HAC and BAC to low (10 pM) but not to high (5 nM) concentrations of ACTH. GA had no inhibitory effect on the steroidogenic response to 8 Br-cAMP (at either low or high concentrations) and did neither modify the binding of 125I-ACTH to its receptor nor the ACTH-induced cAMP production. BAC cultured at high or low cell densities (2.4 x 10(5) vs. 0.24 x 10(5) cells/cm2) exhibited distinct levels of intercellular communication and were differently responsive to sub-maximal ACTH concentrations. The ACTH ED50 values for cortisol production were 8.5 +/- 1.3 and 45 +/- 14 pM (P < 0.02) for BAC cultured at high and low density, respectively. In the presence of GA, there was a shift of the ACTH concentration-response curves in the two culture conditions. The ACTH ED50 of high density and low density cultured BAC increased 25- and 5-fold, respectively, and became similar (220 +/- 90 and 250 +/- 120 pM). These results demonstrate that gap junction-mediated communication between hormone-responsive and nonresponsive cells is one mechanism by which adrenal cells increase their responsiveness to low ACTH concentrations. Images PMID:7706446

  11. Rodent and primate adrenal medullary cells in vitro: phenotypic plasticity in response to coculture with C6 glioma cells or NGF.

    PubMed

    Notter, M F; Hansen, J T; Okawara, S; Gash, D M

    1989-01-01

    In order to maintain a chronic supply of growth factor for medulla cells in vitro, chromaffin cells from rat, African green monkeys and man were co-cultured with C6 glioma cells, which secrete growth factors that sustain sympathetic neurons in vitro. The response of chromaffin cells to coculture was compared to treatment of medullary cells with nerve growth factor (NGF) alone. Dispersed chromaffin cell preparations were obtained by a trypsin-collagenase procedure, and subjected to differential plating on collagen-coated surfaces. With both human and monkey tissue, non-chromaffin cells did attach to the culture plates and an enriched chromaffin cell population could be replated. Rat adrenal medulla cells survived very poorly in vitro and were not enriched in this procedure. Cultured human and monkey chromaffin cells survived as epithelial cells (50%) and showed neuritic outgrowth on 55 to 66% of the cells after eight days when treated with nerve growth factor (NGF). These cells showed strong catecholamine histofluorescence, tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) immunoreactivity. In contrast, only ten percent of adult rat chromaffin cells survived in culture, although NGF treatment rescued an additional 20% of the cells and induced neuritic outgrowth after one week in vitro. C6 glioma cells were treated with mitomycin C bromodeoxyuridine to inhibit mitosis and were plated with the various medulla cells in a one to one ratio. Both human and monkey chromaffin cells expressed extensive and enhanced neuritic arborization within eight days of co-culture, (64-82% respectively) and exhibited intimate contact with the glioma cells as seen at the ultrastructural level. Importantly, survival of adult rat adrenal medulla cells was enhanced to 50% or more with 40% of the cells extending neurites when co-cultured with glioma cells for seven days. Chromaffin cells from all three species reacted for TH, DBH and PNMT in co-culture and were histo

  12. Low white blood cell count and cancer

    MedlinePlus

    Neutropenia and cancer; Absolute neutrophil count and cancer; ANC and cancer ... A person with cancer can get a low white blood cell count from the cancer or from treatment for the cancer. Cancer may ...

  13. Halothane inhibits the cholinergic-receptor-mediated influx of calcium in primary culture of bovine adrenal medulla cells

    SciTech Connect

    Yashima, N.; Wada, A.; Izumi, F.

    1986-04-01

    Adrenal medulla cells are cholinoceptive cells. Stimulation of the acetylcholine receptor causes the influx of Ca to the cells, and Ca acts as the coupler of the stimulus-secretion coupling. In this study, the authors investigated the effects of halothane on the receptor-mediated influx of /sup 45/Ca using cultured bovine adrenal medulla cells. Halothane at clinical concentrations (0.5-2%) inhibited the influx of /sup 45/Ca caused by carbachol, with simultaneous inhibition of catecholamine secretion. The influx of /sup 45/Ca and the secretion of catecholamines caused by K depolarization were inhibited by a large concentration of Mg, which competes with Ca at Ca channels, but not inhibited by halothane. Inhibition of the /sup 45/Ca influx by halothane was not overcome by increase in the carbachol concentration. Inhibition of the /sup 45/Ca influx by halothane was examined in comparison with that caused by a large concentration of Mg by the application of Scatchard analysis as the function of the external Ca concentration. Halothane decreased the maximal influx of /sup 45/Ca without altering the apparent kinetic constant of Ca to Ca channels. On the contrary, a large concentration of Mg increased the apparent kinetic constant without altering the maximal influx of /sup 45/Ca. Based on these findings, the authors suggest that inhibition of the /sup 45/Ca influx by halothane was not due to the direct competitive inhibition of Ca channels, nor to the competitive antagonism of agonist-receptor interaction. As a possibility, halothane seems to inhibit the receptor-mediated activation of Ca channels through the interference of coupling between the receptor and Ca channels.

  14. Extragonadal Germ Cell Cancer (EGC)

    MedlinePlus

    ... Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell ... seen in young adults. Patients with mediastinal nonseminomatous EGC are typically classed as poor risk patients because ...

  15. Membrane in cancer cells

    SciTech Connect

    Galeotti, T.; Cittadini, A.; Neri, G.; Scarpa, A.

    1988-01-01

    This book contains papers presented at a conference on membranes in cancer cells. Topics covered include Oncogenies, hormones, and free-radical processes in malignant transformation in vitro and Superoxide onion may trigger DNA strand breaks in human granulorytes by acting as a membrane target.

  16. Pancreatic small cell cancer.

    PubMed

    El Rassy, Elie; Tabchi, Samer; Kourie, Hampig Raphael; Assi, Tarek; Chebib, Ralph; Farhat, Fadi; Kattan, Joseph

    2016-06-01

    Small cell carcinoma (SCC) is most commonly associated with lung cancer. Extra-pulmonary SCC can originate in virtually any organ system, with the gastrointestinal tract being the most common site of involvement. We review the clinical presentation, pathogenesis, histology, imaging modalities and optimal therapeutic management of PSCC in light of available evidence. PMID:26566245

  17. Nonsmall cell lung cancer.

    PubMed

    Sculier, Jean-Paul

    2013-03-01

    The objective of this review is to report the Clinical Year in Review proceedings in the field of nonsmall cell lung cancer that were presented at the 2012 European Respiratory Society Congress in Vienna, Austria. Various topics were reviewed, including epidemiology, screening, diagnosis, treatment, prognosis, and palliative and end of life care. PMID:23457162

  18. VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production.

    PubMed

    Tsai, Ying-Ying; Rainey, William E; Johnson, Maribeth H; Bollag, Wendy B

    2016-09-15

    Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone production are still unclear. Here we demonstrate in human adrenocortical carcinoma (HAC15) cells that submaximal concentrations of angiotensin II and VLDL stimulate aldosterone production in an additive fashion, suggesting the possibility of common mechanisms of action. We show using inhibitors that VLDL-induced aldosterone production is mediated by the PLC/IP3/PKC signaling pathway. Our results suggest that PKC is upstream of the extracellular signal-regulated kinase (ERK) activation previously observed with VLDL. An understanding of the mechanisms mediating VLDL-induced aldosterone production may provide insights into therapies to treat obesity-associated hypertension. PMID:27222295

  19. Cushing syndrome due to adrenal tumor

    MedlinePlus

    ... levels Dexamethasone suppression test Blood cortisol levels Blood DHEA level Saliva cortisol level Tests to determine cause ... not possible, such as in cases of adrenal cancer, medicines can be used to stop the release ...

  20. Laparoscopic Resection of Adrenal Teratoma

    PubMed Central

    Vitagliano, Gonzalo; Villeta, Matias; Arellano, Leonardo; Santis, Oscar

    2006-01-01

    Background: Teratoma is a germ-cell tumor that commonly affects the gonads. Its components originate in the ectoderm, endoderm, and mesoderm. Extragonadal occurrence is rare. Teratomas confined to the adrenal gland are exceptional; only 3 cases have been reported in the English-language literature. We report 2 cases of mature teratomas of the adrenal gland that were laparoscopically excised. Methods: Two patients (ages 8 and 61 years) were diagnosed with adrenal teratoma at our institution. Radiological examination showed a solid 8-cm adrenal lesion in both cases. Hormonal assessment was normal. Both patients underwent laparoscopic transperitoneal adrenalectomy. Results: Surgical time was 120 minutes and 50 minutes, respectively. One patient was discharged on postoperative day 2, and the other remained hospitalized until day 10. The latter patient required percutaneous drainage of a retroperitoneal collection. Both tumors were identified as mature cystic teratomas. No evidence was present of recurring disease in either patient. Conclusions: Adrenal teratoma is rare. Laparoscopic transperitoneal adrenalectomy is a feasible, effective technique that enables excellent oncologic results. To our knowledge, this is the first report of laparoscopic adrenalectomy for pure adrenal teratoma. PMID:17575773

  1. Small Cell Lung Cancer

    PubMed Central

    Kalemkerian, Gregory P.; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura QM; Downey, Robert J.; Gandhi, Leena; Ganti, Apar Kishor P.; Govindan, Ramaswamy; Grecula, John C.; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W.; Merritt, Robert E.; Moran, Cesar A.; Niell, Harvey B.; O’Malley, Janis; Patel, Jyoti D.; Ready, Neal; Rudin, Charles M.; Williams, Charles C.; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted. PMID:23307984

  2. Intraventricular encapsulated calf adrenal chromaffin cells: viable for at least 500 days in vivo without detectable adverse effects on behavioral/cognitive function or host immune sensitization in rats.

    PubMed

    Lindner, M D; Plone, M A; Frydel, B; Kaplan, F A; Krueger, P M; Bell, W J; Blaney, T J; Winn, S R; Sherman, S S; Doherty, E J; Emerich, D F

    1997-01-01

    Numerous studies have reported that adrenal chromaffin cell transplants, including encapsulated xenogeneic adrenal chromaffin cells, have analgesic effects. However, in addition to efficacy, the clinical utility of encapsulated xenogeneic adrenal chromaffin cells for treatment of chronic pain is dependent on the duration of cell viability in vivo, and their relative safety. The objectives of the present study in rats were to: (1) examine encapsulated calf adrenal chromaffin (CAC) cells for evidence of viable cells and continued release of analgesic agents after an extended period in vivo; (2) determine if intraventricular encapsulated CAC cells produce detectable adverse effects on behavioral/cognitive function; and (3) test for evidence of host immune sensitization after an extended period of exposure to encapsulated xenogeneic adrenal chromaffin cells. Results of the present study suggest that some encapsulated CAC cells remain viable for nearly 1.5 years in vivo and continue to produce catecholamines and met-enkephalin. Post-explant device norepinephrine output was equivalent to amounts previously shown to produce analgesic effects with intrathecal implants. Encapsulated adrenal chromaffin cells also appeared relatively safe, even when implanted in the cerebral ventricals, with a lower side-effect profile than systemic morphine (4 mg/kg). There was no evidence that encapsulated CAC-cells implanted in the ventricles affected body weight, spontaneous activity levels, or performance in the delayed matching to position operant task which is sensitive to deficits in learning, memory, attention, motivation, and motor function. Finally, encapsulated CAC cells produced no detectable evidence of host immune sensitization after 16.7 months in vivo, although unencapsulated CAC cells produced a robust immune response even in aged rats. The results of the present study suggest that adrenal chromaffin cells remain viable in vivo for long periods of time, and that long

  3. Radiographic Characteristics of Adrenal Masses in Oncologic Patients

    PubMed Central

    Lee, Ji Hyun; Kim, Eun Ky; Hong, A Ram; Roh, Eun; Bae, Jae Hyun; Kim, Jung Hee; Shin, Chan Soo; Kim, Seong Yeon

    2016-01-01

    Background We aimed to assess the usefulness of pre-contrast Hounsfield unit (HU) and mass size on computed tomography to differentiate adrenal mass found incidentally in oncologic patients. Methods From 2000 to 2012, 131 oncologic patients with adrenal incidentaloma were reviewed retrospectively. Receiver operating characteristic (ROC) curves were applied to determine the optimal cut-off value of the mean HU and size for detecting adrenal metastasis. Results The median age was 18 years, and 80 patients were male. The initial mass size was 18 mm, and 71 (54.2%) of these were on the left side. A bilateral adrenal mass was found in 11 patients (8.4%). Biochemically functional masses were observed in 9.2% of patients. Thirty-six out of 119 patients with nonfunctional masses underwent adrenalectomy, which revealed metastasis in 13. The primary cancers were lung cancer (n=4), renal cell carcinoma (n=2), lymphoma (n=2), hepatocellular carcinoma (n=2), breast cancer (n=1), and others (n=2). The area under the curve for the size and HU for clinically suspicious metastasis were 0.839 (95% confidence interval [CI], 0.761 to 0.900; P<0.001) and 0.959 (95% CI, 0.898 to 0.988; P<0.001), respectively. The cut-off value to distinguish between metastasis and benign masses were 22 mm for size and 20 for HU. Conclusion ROC curve results suggest that pre-contrast HU >20 can be used as a diagnostic reference to suggest metastasis in oncologic patients with adrenal masses. PMID:26676336

  4. Increased Catecholamine Secretion from Single Adrenal Chromaffin Cells in DOCA-Salt Hypertension Is Associated with Potassium Channel Dysfunction

    PubMed Central

    2013-01-01

    The mechanism of catecholamine release from single adrenal chromaffin cells isolated from normotensive and DOCA-salt hypertensive rats was investigated. These cells were used as a model for sympathetic nerves to better understand how exocytotic release of catecholamines is altered in this model of hypertension. Catecholamine secretion was evoked by local application of acetylcholine (1 mM) or high K+ (70 mM), and continuous amperometry was used to monitor catecholamine secretion as an oxidative current. The total number of catecholamine molecules secreted from a vesicle, the total number of vesicles fusing and secreting, and the duration of secretion in response to a stimulus were all significantly greater for chromaffin cells from hypertensive rats as compared to normotensive controls. The greater catecholamine secretion from DOCA-salt cells results, at least in part, from functionally impaired large conductance, Ca2+-activated (BK) and ATP-sensitive K+ channels. This work reveals that there is altered vesicular release of catecholamines from these cells (and possibly from perivascular sympathetic nerves) and this may contribute to increased vasomotor tone in DOCA-salt hypertension. PMID:23937098

  5. Ectopically expressed pro-group X secretory phospholipase A2 is proteolytically activated in mouse adrenal cells by furin-like proprotein convertases: implications for the regulation of adrenal steroidogenesis.

    PubMed

    Layne, Joseph D; Shridas, Preetha; Webb, Nancy R

    2015-03-20

    Group X secretory phospholipase A2 (GX sPLA2) hydrolyzes mammalian cell membranes, liberating free fatty acids and lysophospholipids. GX sPLA2 is produced as a pro-enzyme (pro-GX sPLA2) that contains an N-terminal 11-amino acid propeptide ending in a dibasic motif, suggesting cleavage by a furin-like proprotein convertase (PC). Although propeptide cleavage is clearly required for enzymatic activity, the protease(s) responsible for pro-GX sPLA2 activation have not been identified. We previously reported that GX sPLA2 negatively regulates adrenal glucocorticoid production, likely by suppressing liver X receptor-mediated activation of steroidogenic acute regulatory protein expression. In this study, using a FLAG epitope-tagged pro-GX sPLA2 expression construct (FLAG-pro-GX sPLA2), we determined that adrenocorticotropic hormone (ACTH) enhanced FLAG-pro-GX sPLA2 processing and phospholipase activity secreted by Y1 adrenal cells. ACTH increased the expression of furin and PCSK6, but not other members of the PC family, in Y1 cells. Overexpression of furin and PCSK6 in HEK 293 cells significantly enhanced FLAG-pro-GX sPLA2 processing, whereas siRNA-mediated knockdown of both PCs almost completely abolished FLAG-pro-GX sPLA2 processing in Y1 cells. Expression of either furin or PCSK6 enhanced the ability of GX sPLA2 to suppress liver X receptor reporter activity. The PC inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone significantly suppressed FLAG-pro-GX sPLA2 processing and sPLA2 activity in Y1 cells, and it significantly attenuated GX sPLA2-dependent inhibition of steroidogenic acute regulatory protein expression and progesterone production. These findings provide strong evidence that pro-GX sPLA2 is a substrate for furin and PCSK6 proteolytic processing and define a novel mechanism for regulating corticosteroid production in adrenal cells. PMID:25623068

  6. CaV1.3 as pacemaker channels in adrenal chromaffin cells: specific role on exo- and endocytosis?

    PubMed

    Comunanza, Valentina; Marcantoni, Andrea; Vandael, David H; Mahapatra, Satyajit; Gavello, Daniela; Carabelli, Valentina; Carbone, Emilio

    2010-01-01

    Voltage-gated L-type calcium channels (LTCCs) are expressed in adrenal chromaffin cells. Besides shaping the action potential (AP), LTCCs are involved in the excitation-secretion coupling controlling catecholamine release and in Ca (2+) -dependent vesicle retrieval. Of the two LTCCs expressed in chromaffin cells (CaV1.2 and CaV1.3), CaV1.3 possesses the prerequisites for pacemaking spontaneously firing cells: low-threshold, steep voltage-dependence of activation and slow inactivation. By using CaV1 .3 (-/-) KO mice and the AP-clamp it has been possible to resolve the time course of CaV1.3 pacemaker currents, which is similar to that regulating substantia nigra dopaminergic neurons. In mouse chromaffin cells CaV1.3 is coupled to fast-inactivating BK channels within membrane nanodomains and controls AP repolarization. The ability to carry subthreshold Ca (2+) currents and activate BK channels confers to CaV1.3 the unique feature of driving Ca (2+) loading during long interspike intervals and, possibly, to control the Ca (2+) -dependent exocytosis and endocytosis processes that regulate catecholamine secretion and vesicle recycling. PMID:21084859

  7. Stochastic elimination of cancer cells.

    PubMed Central

    Michor, Franziska; Nowak, Martin A; Frank, Steven A; Iwasa, Yoh

    2003-01-01

    Tissues of multicellular organisms consist of stem cells and differentiated cells. Stem cells divide to produce new stem cells or differentiated cells. Differentiated cells divide to produce new differentiated cells. We show that such a tissue design can reduce the rate of fixation of mutations that increase the net proliferation rate of cells. It has, however, no consequence for the rate of fixation of neutral mutations. We calculate the optimum relative abundance of stem cells that minimizes the rate of generating cancer cells. There is a critical fraction of stem cell divisions that is required for a stochastic elimination ('wash out') of cancer cells. PMID:14561289

  8. Imaging of adrenal and renal hemorrhage.

    PubMed

    Hammond, Nancy A; Lostumbo, Antonella; Adam, Sharon Z; Remer, Erick M; Nikolaidis, Paul; Yaghmai, Vahid; Berggruen, Senta M; Miller, Frank H

    2015-10-01

    Hemorrhage of the kidneys and adrenal glands has many etiologies. In the adrenal glands, trauma, anticoagulation, stress, sepsis, surgery, and neoplasms are common causes of hemorrhage. In the kidneys, reasons for hemorrhage include trauma, bleeding diathesis, vascular diseases, infection, infarction, hemorrhagic cyst rupture, the Antopol-Goldman lesion, and neoplasms. Angiomyolipoma and renal cell carcinoma are the neoplasms most commonly associated with hemorrhage in the kidneys and adrenal cortical carcinoma, metastases, and pheochromocytoma are associated with hemorrhage in the adrenal glands. Understanding the computed tomography and magnetic resonance imaging features, and causes of hemorrhage in the kidneys and adrenal glands is critical. It is also important to keep in mind that mimickers of hemorrhage exist, including lymphoma in both the kidneys and adrenal glands, and melanoma metastases in the adrenal glands. Appropriate imaging follow-up of renal and adrenal hemorrhage should occur to exclude an underlying malignancy as the cause. If there is suspicion for malignancy that cannot be definitively diagnosed on imaging, surgery or biopsy may be warranted. Angiography may be indicated when there is a suspected underlying vascular disease. Unnecessary intervention, such as nephrectomy, may be avoided in patients with benign causes or no underlying disease. Appropriate management is dependent on accurate diagnosis of the cause of renal or adrenal hemorrhage and it is incumbent upon the radiologist to determine the etiology. PMID:26036792

  9. Voltage-dependent currents and modulation of calcium channel expression in zona fasciculata cells from rat adrenal gland.

    PubMed Central

    Barbara, J G; Takeda, K

    1995-01-01

    1. Whole-cell voltage-activated currents from single zona fasciculata (ZF) cells from rat adrenal glands were studied. T- and L-type Ca2+ currents and a slowly inactivating A-type K+ current were the three major currents observed. 2. In freshly isolated cells, the A-type K+ current and the T-type Ca2+ current were predominant. The A-type current was activated at -50 mV and inhibited by 4-amino-pyridine with a half-maximal block (IC50) at 130 microM while the T-type current was activated at -70 mV and blocked by Cd2+, Ni2+ and amiloride with IC50 values of 24.1, 132.4 and 518.9 microM, respectively. 3. Under current clamp, depolarizing current pulses produced a single Ca2+ action potential with Cs+ in the pipette internal solution. Upon replacement of Cs+ by K+, the half-amplitude width of the action potential was shortened and membrane potential oscillations were seen after the spike. 4. In freshly isolated cells and during the first 24 h after plating, the T-type current was observed in all cells, with L-type current being observed in < 2% of cells, even in the presence of (+)SDZ 202,791, a dihydropyridine Ca2+ channel agonist. With time in culture, the T-type current disappeared, and a high-voltage-activated L-type current became increasingly apparent. In cells tested after > 2 days in culture, (+)SDZ 202,791 potentiated L-type current by 407 +/- 12% and the antagonist (-)SDZ 202,791 blocked this increase. The L-type current was activated between -30 and -20 mV and was sensitive to nitrendipine and omega-conotoxin GVIA. 5. Pre-incubation of cultured ZF cells with adrenocorticotrophic hormone (ACTH) or vasoactive intestinal peptide (VIP) for 3 days resulted in a high, sustained level of expression of T-type current, with a mean amplitude of 34.2 +/- 5.5 pA pF-1 for ACTH-treated cells compared with 3.4 +/- 1.8 pA pF-1 for untreated cells. Cycloheximide strongly inhibited this effect. Neither treatment affected L-type current expression. 6. The expression of both Ca

  10. How Is Adrenal Surgery Performed?

    MedlinePlus

    HOME ADRENAL GLANDS Background Where are the adrenal glands? What do the adrenal glands do? Is this adrenal tumor a genetic problem? Primary hyperaldosteronism (aldosterone-producing tumor) What is primary hyperaldosteronism? Signs ...

  11. Adrenal steroidogenesis and congenital adrenal hyperplasia.

    PubMed

    Turcu, Adina F; Auchus, Richard J

    2015-06-01

    Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids (primarily aldosterone), glucocorticoids (primarily cortisol), and adrenal androgens (primarily dehydroepiandrosterone and its sulfate) occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal-recessive enzymatic defects in cortisol biosynthesis. 21-Hydroxylase (21OHD) deficiency accounts for more than 90% of CAH cases and, when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. PMID:26038201

  12. Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

    PubMed Central

    Turcu, Adina F.; Auchus, Richard J.

    2015-01-01

    Synopsis Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids, glucocorticoids and adrenal androgens occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive enzymatic defects in cortisol biosynthesis. 21-hydroxylase (21OHD) deficiency accounts for over 90% of CAH cases and when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. This review discusses in detail the epidemiology, genetics, diagnostic, clinical aspects and management of 21OHD. PMID:26038201

  13. Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Miyata, Hironori; Matsui, Minoru; Inoue, Masumi

    2015-01-01

    Background and Purpose Activation of muscarinic receptors results in catecholamine secretion in adrenal chromaffin cells in many mammals, and muscarinic receptors partly mediate synaptic transmission from the splanchnic nerve, at least in guinea pigs. To elucidate the physiological functions of muscarinic receptors in chromaffin cells, it is necessary to identify the muscarinic receptor subtypes involved in excitation. Experimental Approach To identify muscarinic receptors, pharmacological tools and strains of mice where one or several muscarinic receptor subtypes were genetically deleted were used. Cellular responses to muscarinic stimulation in isolated chromaffin cells were studied with the patch clamp technique and amperometry. Key Results Muscarinic M1, M4 and M5 receptors were immunologically detected in mouse chromaffin cells, and these receptors disappeared after the appropriate gene deletion. Mouse cells secreted catecholamines in response to muscarinic agonists, angiotensin II and a decrease in external pH. Genetic deletion of M1, but not M3, M4 or M5, receptors in mice abolished secretion in response to muscarine, but not to other stimuli. The muscarine-induced secretion was suppressed by MT7, a snake peptide toxin specific for M1 receptors. Similarly, muscarine failed to induce an inward current in the presence of MT7 in mouse and rat chromaffin cells. The binding affinity of VU0255035 for the inhibition of muscarine-induced currents agreed with that for the M1 receptor. Conclusions and Implications Based upon the effects of genetic deletion of muscarinic receptors and MT7, it is concluded that the M1 receptor alone is responsible for muscarine-induced catecholamine secretion. PMID:25393049

  14. Targeting Breast Cancer Stem Cells

    PubMed Central

    Liu, Suling; Wicha, Max S.

    2010-01-01

    There is increasing evidence that many cancers, including breast cancer, contain populations of cells that display stem-cell properties. These breast cancer stem cells, by virtue of their relative resistance to radiation and cytotoxic chemotherapy, may contribute to treatment resistance and relapse. The elucidation of pathways that regulate these cells has led to the identification of potential therapeutic targets. A number of agents capable of targeting breast cancer stem cells in preclinical models are currently entering clinical trials. Assessment of the efficacy of the agents will require development of innovative clinical trial designs with appropriate biologic and clinical end points. The effective targeting of breast cancer stem cells has the potential to significantly improve outcome for women with both early-stage and advanced breast cancer. PMID:20498387

  15. Formation of inositol 1,3,4,6-tetrakisphosphate during angiotensin II action in bovine adrenal glomerulosa cells

    SciTech Connect

    Balla, T.; Guillemette, G.; Baukal, A.J.; Catt, K.J.

    1987-10-14

    Angiotensin II stimulates the formation of several inositol polyphosphates in cultured bovine adrenal glomerulosa cells prelabelled with (/sup 3/H) inositol. Analysis by high performance anion exchange chromatography of the inositol-phosphate compounds revealed the existence of two additional inositol tetrakisphosphate (InsP4) isomers in proximity to Ins-1,3,4,5-P4, the known phosphorylation product of Ins-1,4,5-trisphosphate and precursor of Ins-1,3,4-trisphosphate. Both of these new compounds showed a slow increase after stimulation with angiotensin II. The structure of one of these new InsP4 isomers, which is a phosphorylation product of Ins-1,3,4-P3, was deduced by its resistance to periodate oxidation to be Ins-1,3,4,6-P4. The existence of multiple cycles of phosphorylation-dephosphorylation reactions for the processing of Ins-1,4,5-P4 may represent a new aspect of the inositol-lipid related signalling mechanism in agonist-activated target cells.

  16. Adrenal Gland Disorders

    MedlinePlus

    The adrenal glands are small glands located on top of each kidney. They produce hormones that you can't live ... stress and has many other important functions. With adrenal gland disorders, your glands make too much or not ...

  17. Laparoscopic Adrenal Gland Removal

    MedlinePlus

    ... adrenal tumors that appear malignant. What are the Advantages of Laparoscopic Adrenal Gland Removal? In the past, ... of procedure and the patients overall condition. Common advantages are: Less postoperative pain Shorter hospital stay Quicker ...

  18. [Combined modality therapy for a patient with primary adrenal lymphoma].

    PubMed

    Matsuno, Teppei; Kuroda, Hiroyuki; Jomen, Wataru; Yoshida, Masahiro; Yamada, Michiko; Sato, Masanori; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Nojiri, Shuichi; Arihara, Yohei; Kato, Junji

    2014-04-01

    A 71-year-old man with malaise, anorexia, and weight loss was referred to our hospital from a clinic. Abdominal computed tomography(CT)revealed bilateral adrenal masses. An ultrasound-guided percutaneous needle biopsy of the adrenal grand indicated diffuse large B-cell lymphoma. A rapid adrenocorticotropic hormone(ACTH)test revealed primary adrenal failure. Rituximab-cyclophosphamide/doxorubicin/vincristine/prednisolone(common name, R-CHOP)therapy accompanied by intrathecal treatment was initiated along with steroid replacement therapy. After the fourth courses, a CT scan showed a reduction of the adrenal masses, and there was no[18F]-fluorodeoxyglucose(FDG)uptake in the adrenal masses. The patient has remained in metabolic complete remission. Subsequently, both adrenal lymphomas were irradiated. The patient has been disease-free for 6 months after the diagnosis of primary adrenal lymphoma. The combined modality of chemoradiation therapy plus intrathecal treatment could be effective for primary adrenal lymphoma with a poor prognosis. PMID:24743371

  19. Treatment Option Overview (Small Cell Lung Cancer)

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points ...

  20. Stages of Small Cell Lung Cancer

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points ...

  1. Adrenal imaging (Part 2): Medullary and secondary adrenal lesions

    PubMed Central

    Dhamija, Ekta; Panda, Ananya; Das, Chandan J.; Gupta, A. K.

    2015-01-01

    Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations. PMID:25593821

  2. Comparison between adrenal, gonadal, and pituitary hormones on the behavior of rhesus monkey kidney cells in culture.

    PubMed

    Hull, S; Benghuzzi, H; Tucci, M; Hughes, J

    1999-01-01

    Recently, several studies have indicated that the use of Rhesus Monkey Kidney epithelial cells (RMKEC) in culture could provide significant knowledge regarding the alteration or dysfunction of kidney tissues that often resulted into kidney failure. The interrelationship between various steroid hormones, as well as, growth-promoting hormones such as growth hormone (GH) and RMKEC has not been fully investigated. The specific objective of this study was to investigate the effects of cortisol (C), testosterone (T), dehydroepiandrosterone (DHEA), estradiol (E), and GH on the proliferation and viability of RMKEC in culture. The cell line was adapted to grow in Morgan, Morton, and Parker's medium 199 (with 1.68 g/L sodium bicarbonate) supplemented with 1% horse serum. A total of 30 tubes were plated with RMKEC and divided into six equal groups. In-groups 1-5, each well (n = 5) were treated with a physiological dose of C, T, DHEA, E, and GH, respectively. At 24, 48, and 96 hours the cells and supernatants were collected and stored for further analysis. The biochemical markers were assessed using lactate dehydrogenase (LDH), catalase, and malinodialdehyde (MDA). Data obtained suggest that: (I) treatment of RMKEC with C and DHEA resulted in an increase in MDA levels compared to the control and other experimental groups, (II) no significant increase was observed in LDH levels in all treated tubes compared to the control group, (III) higher proliferation rate was observed in cells treated with T compared to the control group. However, treatment with C showed suppression to the proliferation rate and no significant difference was observed between DHEA, GH and the control groups. In conclusion this study suggests that steroid hormones regardless of the source of secretion (gonads or adrenals) can influence the functional capacity of RMKEC in culture. PMID:11143395

  3. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  4. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  5. Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells.

    PubMed Central

    Nadler, J L; Natarajan, R; Stern, N

    1987-01-01

    Angiotensin II (AII) in adrenal glomerulosa cells activates phospholipase C resulting in the formation of inositol phosphates and diacylglycerol rich in arachidonic acid (AA). Although glomerulosa cells can metabolize AA via cyclooxygenase (CO), this pathway plays little role in aldosterone synthesis. Recent evidence suggests that the lipoxygenase (LO) pathway may be important for hormonal secretion in endocrine tissues such as the islet of Langerhans. However, the capacity of the glomerulosa cell to synthesize LO products and their role in aldosterone secretion is not known. To study this, the effect of nonselective and selective LO inhibitors on AII, ACTH, and potassium-induced aldosterone secretion and LO product formation was evaluated in isolated rat glomerulosa cells. BW755c, a nonselective LO inhibitor dose dependently reduced the AII-stimulated level of aldosterone without altering AII binding (91 +/- 6 to 36 +/- 4 ng/10(6) cells/h 10(-4) M, P less than 0.001). The same effect was observed with another nonselective LO blocker, phenidone, and a more selective 12-LO inhibitor, Baicalein. In contrast U-60257, a selective 5-LO inhibitor did not change the AII-stimulated levels of aldosterone (208 +/- 11% control, AII 10(-9) M vs. 222 +/- 38%, AII + U-60257). The LO blockers action was specific for AII since neither BW755c nor phenidone altered ACTH or K+-induced aldosterone secretion. AII stimulated the formation of the 12-LO product 12-hydroxyeicosatetraenoic acid (12-HETE) as measured by ultraviolet detection and HPLC in AA loaded cells and by a specific RIA in unlabeled cells (501 +/- 50 to 990 +/- 10 pg/10(5) cells, P less than 0.02). BW755c prevented the AII-mediated rise in 12-HETE formation. In contrast, neither ACTH nor K+ increased 12-HETE levels. The addition of 12-HETE or its unstable precursor 12-HPETE (10(-9) or 10(-8) M) completely restored AII action during LO blockade. AII also produced an increase in 15-HETE formation, but the 15-LO products

  6. Control of adrenal androgen production.

    PubMed

    Odell, W D; Parker, L N

    The major adrenal androgens are dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and androstenedione (delta 4). Studies by Cutler et al in 1978 demonstrated that these androgens are detectable in blood of all domestic and laboratory animals studied, but that only 4 species show increase in one or more with sexual maturation: rabbit, dog, chimpanzee and man. Studies by Grover and Odell in 1975 show these androgens do not bind to the androgen receptor obtained from rat prostate and thus probably are androgens only by conversion to an active androgen in vivo. Thomas and Oake in 1974 showed human skin converted DHEA to testosterone. The control of adrenal androgen secretion is in part modulated by ACTH. However, other factors or hormones must exist also, for a variety of clinical observations show dissociation in adrenal androgen versus cortisol secretion. Other substances that have been said to be controllers of adrenal androgen secretion include estrogens, prolactin, growth hormone, gonadotropins and lipotropin. None of these appear to be the usual physiological modulator, although under some circumstances each may increase androgen production. Studies from our laboratory using in vivo experiments in the castrate dog and published in 1979 indicated that crude extracts of bovine pituitary contained a substance that either modified ACTH stimulation of adrenal androgen secretion, or stimulated secretion itself - Cortisol Androgen Stimulating Hormone. Parker et al in 1983 showed a 60,000 MW glycoprotein was extractable from human pituitaries, which stimulated DHA secretion by dispersed canine adrenal cells in vitro, but did not stimulate cortisol secretion. This material contained no ACTH by radioimmunoassay. In 1982 Brubaker et al reported a substance was also present in human fetal pituitaries, which stimulated DHA secretion, but did not effect cortisol. PMID:6100259

  7. Microelectrode Arrays of Diamond-Insulated Graphitic Channels for Real-Time Detection of Exocytotic Events from Cultured Chromaffin Cells and Slices of Adrenal Glands.

    PubMed

    Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Marcantoni, Andrea; Pasquarelli, Alberto; Carbone, Emilio; Olivero, Paolo; Carabelli, Valentina

    2016-08-01

    A microstructured graphitic 4 × 4 multielectrode array was embedded in a single-crystal diamond substrate (4 × 4 μG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time-effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20 × 3.5 μm(2)) separated by 200 μm gaps. Taking advantage of the array geometry we addressed the following specific issues: (i) detect both the spontaneous and KCl-evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, (ii) resolve the waveform of different subsets of exocytotic events, and (iii) monitoring quantal secretory events from thin slices of the adrenal gland. The frequency of spontaneous release was low (0.12 and 0.3 Hz, respectively, for adrenal slices and cultured cells) and increased up to 0.9 Hz after stimulation with 30 mM KCl in cultured cells. The spike amplitude as well as rise and decay time were comparable with those measured by carbon fiber microelectrodes and allowed to identify three different subsets of secretory events associated with "full fusion" events, "kiss-and-run" and "kiss-and-stay" exocytosis, confirming that the device has adequate sensitivity and time resolution for real-time recordings. The device offers the significant advantage of shortening the time to collect data by allowing simultaneous recordings from cell populations either in primary cell cultures or in intact tissues. PMID:27376596

  8. Human adrenal tumor cell line SW-13 contains a natriuretic peptide receptor system that responds preferentially to ANP among various natriuretic peptides

    SciTech Connect

    Mizuno, T.; Katafuchi, T.; Hagiwara, H.; Ito, T.; Kangawa, K.; Matsuo, H.; Hirose, S. )

    1990-12-31

    A new type of ANP receptor system which clearly distinguishes natriuretic peptides A and B (ANP and BNP) has been identified in the human adrenal tumor cell line SW-13 and characterized. SW-13 cells responded to nanomolar concentrations of ANP with large increases in cGMP levels but in the case of BNP, much higher concentrations were required to produce the same extent of response. This property is unique since the 140-kDa ANP receptors so far characterized do not discriminate between ANP and BNP. For comparison, various natriuretic peptide receptors were also re-characterized using the recently identified CNP.

  9. Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells

    SciTech Connect

    Reinhard, J.F. Jr.; Diliberto, E.J. Jr.; Viveros, O.H.; Daniels, A.J.

    1987-11-01

    Cultures of bovine adrenomedullary chromaffin cells accumulated 1-methyl-4-phenylpyridinium (MPP/sup +/) in a time- and concentration-dependent manner by a process that was prevented by desmethylimipramine. The subcellular localization of the incorporated (methyl-/sup 3/H)MPP/sup +/ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. When chromaffin cell membranes were made permeable with the detergent digitonin the absence of calcium, there was no increase in the release of (/sup 3/H)MPP/sup +/, indicating that there is negligible accumulation of the neurotoxin in the cytosol. Simultaneous exposure to digitonin and calcium induced cosecretion of MPP/sup +/ and catecholamines. Stimulation of the cells with nicotine released both catecholamines and MPP/sup +/ at identical rates and percentages of cellular content in a calcium-dependent manner. Last, when cells were incubated with MPP/sup +/ in the presence of tetrabenazine (an inhibitor of vesicular uptake), the chromaffin cell toxicity of MPP/sup +/ was potentiated. The authors submit that the ability of the chromaffin cells to take up and store MPP/sup +/ in the chromaffin vesicle prevents the toxin's interaction with other structures and, thus, prevents cell damage. As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP/sup +/ in the storage vesicle.

  10. Autophagy, cell death, and cancer

    PubMed Central

    Lin, Lin; Baehrecke, Eric H

    2015-01-01

    Autophagy is an evolutionarily conserved intracellular catabolic process that is used by all cells to degrade dysfunctional or unnecessary cytoplasmic components through delivery to the lysosome. Increasing evidence reveals that autophagic dysfunction is associated with human diseases, such as cancer. Paradoxically, although autophagy is well recognized as a cell survival process that promotes tumor development, it can also participate in a caspase-independent form of programmed cell death. Induction of autophagic cell death by some anticancer agents highlights the potential of this process as a cancer treatment modality. Here, we review our current understanding of the molecular mechanism of autophagy and the potential roles of autophagy in cell death, cancer development, and cancer treatment. PMID:27308466

  11. Role of [Na+]i and [Ca2+]i in nicotine-induced norepinephrine release from bovine adrenal chromaffin cells.

    PubMed

    Gerber, S H; Haunstetter, A; Krüger, C; Kaufmann, A; Nobiling, R; Haass, M

    1995-09-01

    Intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) concentrations were determined by sodium-binding benzofuran isophthalate (SBFI) and fura 2 microfluorimetry, respectively, in bovine adrenal chromaffin cells (BCC). Validation of SBFI microfluorimetry by in vitro and in vivo calibration revealed a reliable assessment of [Na+]i within a range of 1-30 mM in single BCC. Nicotine (0.1-10 microM) induced concentration-dependent increases of both [Na+]i (from 3.3 +/- 0.1 to 25.6 +/- 0.4 mM, n = 76, P < 0.001) and [Ca2+]i (from 64 +/- 1 to 467 +/- 16 nM, n = 87, P < 0.001), which were accompanied by an increase in [3H]norepinephrine (NE) release. Consistent with an exocytotic release mechanism, nicotine-induced increments of [Ca2+]i and [3H]NE release were reduced under calcium-free conditions and by gadolinium chloride (40 microM), whereas [Na+]i was not affected. In contrast, a parallel attenuation of nicotine-evoked changes in [Na+]i, [Ca2+]i, and [3H]NE release was observed during reduction of the extracellular sodium concentration. The nicotine-evoked responses were neutralized by the nicotinic receptor antagonist hexamethonium (100 microM) but not by blockade of voltage-dependent sodium channels (1 microM tetrodotoxin). In conclusion, the nicotine-induced exocytotic release of [3H]NE is triggered by an increase in [Ca2+]i, which is facilitated by sodium influx through the nicotinic receptor ionophore. PMID:7573386

  12. Clonality as Expression of Distinctive Cell Kinetics Patterns in Nodular Hyperplasias and Adenomas of the Adrenal Cortex

    PubMed Central

    Díaz-Cano, Salvador J.; de Miguel, Manuel; Blanes, Alfredo; Tashjian, Robert; Galera, Hugo; Wolfe, Hubert J.

    2000-01-01

    Although histopathologic criteria for adrenal cortical nodular hyperplasias (ACNHs) and adenomas (ACAs) have been developed, their kinetics and clonality are virtually unknown. We studied 20 ACNHs and 25 ACAs (based on World Health Organization criteria) from 45 females. Representative samples were histologically evaluated, and the methylation pattern of the androgen receptor alleles was analyzed on microdissected samples. Consecutive sections were selected for slide cytometry, flow cytometry, and in situ end labeling (ISEL). Apoptosis was studied by flow cytometry (nuclear area/DNA content plotter analysis) and by ISEL. Appropriate tissue controls were run in every case. Polyclonal gel patterns were revealed in 14/18 informative ACNHs and in 3/22 informative ACAs, whereas monoclonal gel patterns were observed in 4/18 ACNHs and 19/22 ACAs. Overlapping proliferation rates (PRs) were observed in both clonal groups, and apoptosis was detected only in G0/G1 cells, especially in monoclonal ACNHs (3/4; 75%) and in polyclonal ACAs (2/3; 67%). Significantly higher PRs were observed in ACNHs with polyclonal patterns and G0/G1 apoptosis and in ACAs regardless of clonality pattern and presence of G0/G1 apoptosis. All except one ACNH (19/20; 95%) and 15/25 ACAs (60%) showed diploid DNA content, whereas the remaining cases were hyperdiploid. A direct correlation between PR and ISEL was observed in polyclonal lesions (PR = 29.32 ISEL − 1.93), whereas the correlation was inverse for monoclonal lesions (PR = −9.13 ISEL + 21.57). We concluded that only simultaneous down-regulated apoptosis and high proliferation result in selective kinetic advantage, dominant clone expansion, and unbalanced methylation patterns of androgen receptor alleles in ACNHs and ACAs. PMID:10623680

  13. Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex.

    PubMed

    Díaz-Cano, S J; de Miguel, M; Blanes, A; Tashjian, R; Galera, H; Wolfe, H J

    2000-01-01

    Although histopathologic criteria for adrenal cortical nodular hyperplasias (ACNHs) and adenomas (ACAs) have been developed, their kinetics and clonality are virtually unknown. We studied 20 ACNHs and 25 ACAs (based on World Health Organization criteria) from 45 females. Representative samples were histologically evaluated, and the methylation pattern of the androgen receptor alleles was analyzed on microdissected samples. Consecutive sections were selected for slide cytometry, flow cytometry, and in situ end labeling (ISEL). Apoptosis was studied by flow cytometry (nuclear area/DNA content plotter analysis) and by ISEL. Appropriate tissue controls were run in every case. Polyclonal gel patterns were revealed in 14/18 informative ACNHs and in 3/22 informative ACAs, whereas monoclonal gel patterns were observed in 4/18 ACNHs and 19/22 ACAs. Overlapping proliferation rates (PRs) were observed in both clonal groups, and apoptosis was detected only in G(0)/G(1) cells, especially in monoclonal ACNHs (3/4; 75%) and in polyclonal ACAs (2/3; 67%). Significantly higher PRs were observed in ACNHs with polyclonal patterns and G(0)/G(1) apoptosis and in ACAs regardless of clonality pattern and presence of G(0)/G(1) apoptosis. All except one ACNH (19/20; 95%) and 15/25 ACAs (60%) showed diploid DNA content, whereas the remaining cases were hyperdiploid. A direct correlation between PR and ISEL was observed in polyclonal lesions (PR = 29.32 ISEL - 1.93), whereas the correlation was inverse for monoclonal lesions (PR = -9.13 ISEL + 21.57). We concluded that only simultaneous down-regulated apoptosis and high proliferation result in selective kinetic advantage, dominant clone expansion, and unbalanced methylation patterns of androgen receptor alleles in ACNHs and ACAs. PMID:10623680

  14. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  15. Colocalization of calcium entry and exocytotic release sites in adrenal chromaffin cells.

    PubMed Central

    Robinson, I M; Finnegan, J M; Monck, J R; Wightman, R M; Fernandez, J M

    1995-01-01

    "Snapshot" images of localized Ca2+ influx into patch-clamped chromaffin cells were captured by using a recently developed pulsed-laser imaging system. Transient opening of voltage-sensitive Ca2+ channels gave rise to localized elevations of Ca2+ that had the appearance of either "hotspots" or partial rings found immediately beneath the plasma membrane. When the Ca2+ imaging technique was employed in conjunction with flame-etched carbon-fiber electrodes to spatially map the release sites of catecholamines, it was observed that the sites of Ca2+ entry and catecholamine release were colocalized. These results provide functional support for the idea that secretion occurs from "active zone"-like structures in neuroendocrine cells. Images Fig. 2 PMID:7708668

  16. Invasive cancer cells and metastasis

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  17. Internalization and lysosomal association of (/sup 125/I)angiotensin II in norepinephrine-containing cells of the rat adrenal medulla

    SciTech Connect

    Bianchi, C.; Gutkowska, J.; Charbonneau, C.; Ballak, M.; Anand-Srivastava, M.B.; De Lean, A.; Genest, J.; Cantin, M.

    1986-10-01

    The morphological localization of (/sup 125/I)angiotensin II (AII) in the rat adrenal medulla (AM) was studied by light- and electron-microscopic radioautography in vivo. With light microscopy the presence of binding sites for AII in both norepinephrine-containing (NE) and epinephrine-containing (E) cells was confirmed. With electron microscopy, it was found that AII binds to the cell surface of NE cells, is progressively internalized, and is associated with lysosomes and Golgi complex within 20 min, whereas in E cells AII seems to be internalized earlier and recycled back to the cell surface within 5 min without any appreciable association with intracellular organelles. These results suggest different intracellular pathways for AII in NE and E cells of the rat AM.

  18. Congenital Adrenal Hyperplasia

    PubMed Central

    Speiser, Phyllis W.

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management. PMID:26339484

  19. Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors.

    PubMed

    Pivonello, Rosario; Ferone, Diego; de Herder, Wouter W; de Krijger, Ronald R; Waaijers, Marlijn; Mooij, Diana M; van Koetsveld, Peter M; Barreca, Antonina; De Caro, Maria Laura del Basso; Lombardi, Gaetano; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2004-09-01

    Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D(2)), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D(2) localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D(2) isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D(2) analog (125)I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia. At RT-PCR, both D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D(2), D(4), and D(5) were expressed in pheochromocytomas. In all D(2

  20. Nitric oxide sets off an antioxidant response in adrenal cells: involvement of sGC and Nrf2 in HO-1 induction.

    PubMed

    Astort, F; Mercau, M; Giordanino, E; Degese, M S; Caldareri, L; Coso, O; Cymeryng, C B

    2014-02-15

    Induction of microsomal heme oxygenase 1 (HO-1) activity is considered a cytoprotective mechanism in different cell types. In adrenal cells, HO-1 induction by ACTH exerts a modulatory effect on steroid production as well. As nitric oxide (NO) has been also regarded as an autocrine/paracrine modulator of adrenal steroidogenesis we sought to study the effects of NO on the induction of HO-1 and the mechanism involved. We hereby analyzed the time and dose-dependent effect of a NO-donor (DETA/NO) on HO-1 induction in a murine adrenocortical cell line. We showed that this effect is mainly exerted at a transcriptional level as it is inhibited by actinomycin D and HO-1 mRNA degradation rates were not affected by DETA/NO treatment. HO-1 induction by NO does not appear to involve the generation of oxidative stress as it was not affected by antioxidant treatment. We also demonstrated that NO-treatment results in the nuclear translocation of the nuclear factor-erythroid 2-related factor (Nrf2), an effect that is attenuated by transfecting the cells with a dominant negative isoform of Nrf2. We finally show that the effects of the NO-donor are reproduced by a permeable analog of cGMP and that a soluble guanylate cyclase specific inhibitor blocked both the induction of HO-1 by NO and the nuclear translocation of Nrf2. PMID:24361900

  1. Primary Bilateral Non-Hodgkin's Lymphoma of the Adrenal Gland Presenting as Incidental Adrenal Masses

    PubMed Central

    Rizzo, Christopher; Camilleri, David James; Gatt, Andre'

    2015-01-01

    Although lymphoma may occasionally involve the adrenal glands as part of a generalized disease process, primary adrenal lymphoma (PAL) is a rare disease. We present a case of a 62-year-old woman with a history of mild/moderate hereditary spherocytosis with a well-compensated baseline haemoglobin, who presented with rapidly progressive symptomatic anaemia. During the diagnostic workup, imaging revealed bilateral large adrenal masses and she was later diagnosed with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), with the adrenal glands being the dominant site of the disease. The patient was started on systemic chemotherapy, but her disease progressed with neurological involvement which responded to second-line therapy. Her adrenal disease however was refractory to further therapy. PMID:26681947

  2. α-Conotoxins Identify the α3β4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells.

    PubMed

    Hone, Arik J; McIntosh, J Michael; Azam, Layla; Lindstrom, Jon; Lucero, Linda; Whiteaker, Paul; Passas, Juan; Blázquez, Jesús; Albillos, Almudena

    2015-11-01

    Ligands that selectively inhibit human α3β2 and α6β2 nicotinic acetylcholine receptor (nAChRs) and not the closely related α3β4 and α6β4 subtypes are lacking. Current α-conotoxins (α-Ctxs) that discriminate among these nAChR subtypes in rat fail to discriminate among the human receptor homologs. In this study, we describe the development of α-Ctx LvIA(N9R,V10A) that is 3000-fold more potent on oocyte-expressed human α3β2 than α3β4 and 165-fold more potent on human α6/α3β2β3 than α6/α3β4 nAChRs. This analog was used in conjuction with three other α-Ctx analogs and patch-clamp electrophysiology to characterize the nAChR subtypes expressed by human adrenal chromaffin cells. LvIA(N9R,V10A) showed little effect on the acetylcholine-evoked currents in these cells at concentrations expected to inhibit nAChRs with β2 ligand-binding sites. In contrast, the β4-selective α-Ctx BuIA(T5A,P6O) inhibited >98% of the acetylcholine-evoked current, indicating that most of the heteromeric receptors contained β4 ligand-binding sites. Additional studies using the α6-selective α-Ctx PeIA(A7V,S9H,V10A,N11R,E14A) indicated that the predominant heteromeric nAChR expressed by human adrenal chromaffin cells is the α3β4* subtype (asterisk indicates the possible presence of additional subunits). This conclusion was supported by polymerase chain reaction experiments of human adrenal medulla gland and of cultured human adrenal chromaffin cells that demonstrated prominent expression of RNAs for α3, α5, α7, β2, and β4 subunits and a low abundance of RNAs for α2, α4, α6, and α10 subunits. PMID:26330550

  3. Salivary Gland Cancer Stem Cells

    PubMed Central

    Adams, April; Warner, Kristy; Nör, Jacques E.

    2013-01-01

    Emerging evidence suggests the existence of a tumorigenic population of cancer cells that demonstrate stem cell-like properties such as self-renewal and multipotency. These cells, termed cancer stem cells (CSC), are able to both initiate and maintain tumor formation and progression. Studies have shown that CSC are resistant to traditional chemotherapy treatments preventing complete eradication of the tumor cell population. Following treatment, CSC are able to re-initiate tumor growth leading to patient relapse. Salivary gland cancers are relatively rare but constitute a highly significant public health issue due to the lack of effective treatments. In particular, patients with mucoepidermoid carcinoma or adenoid cystic carcinoma, the two most common salivary malignancies, have low long-term survival rates due to the lack of response to current therapies. Considering the role of CSC in resistance to therapy in other tumor types, it is possible that this unique sub-population of cells is involved in resistance of salivary gland tumors to treatment. Characterization of CSC can lead to better understanding of the pathobiology of salivary gland malignancies as well as to the development of more effective therapies. Here, we make a brief overview of the state-of-the-science in salivary gland cancer, and discuss possible implications of the cancer stem cell hypothesis to the treatment of salivary gland malignancies. PMID:23810400

  4. Basal cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. This type of skin ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  5. Squamous cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. The earliest form of ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  6. Schwann cells induce cancer cell dispersion and invasion

    PubMed Central

    Deborde, Sylvie; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William F.; Chernichenko, Natalya; Lee, Sei-Young; Barajas, Fernando; Chen, Chun-Hao; Bakst, Richard L.; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J.

    2016-01-01

    Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression. PMID:26999607

  7. Innate Lymphoid Cells in Cancer.

    PubMed

    Vallentin, Blandine; Barlogis, Vincent; Piperoglou, Christelle; Cypowyj, Sophie; Zucchini, Nicolas; Chéné, Matthieu; Navarro, Florent; Farnarier, Catherine; Vivier, Eric; Vély, Frédéric

    2015-10-01

    The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFNγ. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples. PMID:26438443

  8. Inhibition of /sup 22/Na influx by tricyclic and tetracyclic antidepressants and binding of (/sup 3/H)imipramine in bovine adrenal medullary cells

    SciTech Connect

    Arita, M.; Wada, A.; Takara, H.; Izumi, F.

    1987-10-01

    In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. (/sup 3/H)Imipramine bound specifically to adrenal medullary cells. Binding was saturable, reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of (/sup 3/H)imipramine at the same concentrations as they inhibited /sup 22/Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of (/sup 3/H)imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.

  9. Cancer stem cell signaling pathways.

    PubMed

    Matsui, William H

    2016-09-01

    Tissue development and homeostasis are governed by the actions of stem cells. Multipotent cells are capable of self-renewal during the course of one's lifetime. The accurate and appropriate regulation of stem cell functions is absolutely critical for normal biological activity. Several key developmental or signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the Janus-activated kinase/signal transducer and activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3-kinase/phosphatase and tensin homolog, and nuclear factor-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Unsurprisingly, many of these crucial signaling pathways are dysregulated in cancer. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells capable of self-renewal, differentiation, and generation of serially transplantable heterogeneous tumors of several types of cancer. PMID:27611937

  10. Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: in vivo studies on the regenerating rat adrenal cortex.

    PubMed

    Rucinski, Marcin; Tortorella, Cinzia; Ziolkowska, Agnieszka; Nowak, Magdalena; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2008-05-01

    Previous studies have shown that proteasome inhibitors promote the accumulation of steroidogenic acute regulatory protein (StAR) in cultured rat adrenocortical cells. Unexpectedly, this response was associated with a moderate lowering in the corticosterone secretion and proliferation rate of cultured cells. Hence, we studied the effects of proteasome inhibitors MG115 and MG132 on the secretion and proliferative activity of the regenerating adrenal cortex in rats 5 days after surgery. Animals were given two subcutaneous injections of 0.15 or 1.5 nmol/100 g of inhibitors 24 and 12 h before decapitation. Real-time PCR and Western blotting showed that StAR expression, both mRNA and protein, was markedly lower in regenerating adrenals than in the intact gland of sham-operated rats. Neither MG115 nor MG132 affected StAR expression in regenerating gland. Inhibitors induced a slight decrease in the plasma concentrations of aldosterone and corticosterone, but did not significantly alter metaphase index of the regenerating adrenal cortex. Our findings provide the first evidence that down-regulation of StAR occurs during the early stages of adrenal regeneration. Moreover, this suggests that the steroidogenic pathway is more sensitive to proteasome inhibitors than that regulating proliferative activity of regenerating adrenal cortex in the rat. PMID:18425351

  11. Nanomechanical analysis of cells from cancer patients

    NASA Astrophysics Data System (ADS)

    Cross, Sarah E.; Jin, Yu-Sheng; Rao, Jianyu; Gimzewski, James K.

    2007-12-01

    Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread. Despite several studies on architectural changes in cultured cell lines, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

  12. Regulation of cytochrome b5 gene transcription by Sp3, GATA-6, and steroidogenic factor 1 in human adrenal NCI-H295A cells.

    PubMed

    Huang, Ningwu; Dardis, Andrea; Miller, Walter L

    2005-08-01

    Sex steroid synthesis requires the 17,20 lyase activity of P450c17, which is enhanced by cytochrome b5, acting as an allosteric factor to promote association of P450c17 with its electron donor, P450 oxidoreductase. Cytochrome b5 is preferentially expressed in the fetal adrenal and postadrenarchal adrenal zona reticularis; the basis of this tissue-specific, developmentally regulated transcription of the b5 gene is unknown. We found b5 expression in all cell lines tested, including human adrenal NCI-H295A cells, where its mRNA is reduced by cAMP and phorbol ester. Multiple sites, between -83 and -122 bp upstream from the first ATG, initiate transcription. Deletional mutagenesis localized all detectable promoter activity within -327/+15, and deoxyribonuclease I footprinting identified protein binding at -72/-107 and -157/-197. DNA segments -65/-40, -114/-70 and -270/-245 fused to TK32/Luc yielded significant activity, and mutations in their Sp sites abolished that activity; electrophoretic mobility shift assay (EMSA) showed that Sp3, but not Sp1, binds to these Sp sites. Nuclear factor 1 (NF-1) and GATA-6, but not GATA-4 bind to the NF-1 and GATA sites in -157/-197. In Drosophila S2 cells, Sp3 increased -327/Luc activity 58-fold, but Sp1 and NF-1 isoforms were inactive. Mutating the three Sp sites ablated activity without or with cotransfection of Sp1/Sp3. In NCI-H295A cells, mutating the three Sp sites reduced activity to 39%; mutating the Sp, GATA, and NF-1 sites abolished activity. In JEG-3 cells, GATA-4 was inactive, GATA-6 augmented -327/Luc activity to 231% over the control, and steroidogenic factor 1 augmented activity to 655% over the control; these activities required the Sp and NF-1 sites. Transcription of cytochrome b5 shares many features with the regulation of P450c17, whose activity it enhances. PMID:15831526

  13. Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1980-01-01

    The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

  14. High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.

    PubMed

    Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

    2016-02-01

    Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. PMID:26802905

  15. General Information about Small Cell Lung Cancer

    MedlinePlus

    ... Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  16. General Information about Renal Cell Cancer

    MedlinePlus

    ... Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  17. Acute adrenal crisis

    MedlinePlus

    ... cortisol and adrenaline are released in response to stress . Cortisol production is regulated by the pituitary gland. This ... adrenal crisis include: Dehydration Infection and other physical ... medicines such as prednisone or hydrocortisone Surgery Trauma

  18. Invasive cancer cells and metastasis

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  19. Role of adrenal imaging in surgical management

    SciTech Connect

    Lamki, L.M.; Haynie, T.P. )

    1990-03-01

    Adrenal imaging using radiopharmaceuticals is a functional test that can contribute significantly to surgical management and follow-up of patients with either benign or malignant conditions of the adrenal cortex and medulla. Imaging of the cortex is achieved by iodine-131-labeled iodomethyl nor-cholesterol (NP-59), while adrenal medulla imaging can be successfully accomplished by 131I-metaiodobenzylguanidine (MIBG), which localizes in the adrenergic nerve terminal with norepinephrine. Both tests carry high sensitivity and specificity for functional tumors and hyperplasia, and often better than CT scanning. This article reviews the current status and clinical utility of nuclear imaging of the adrenal cortex in congenital hyperplasia, low renin hypertension and aldosteronism, and Cushing's syndrome. Adrenal medulla imaging is reviewed in light of our experience at the University of Texas M.D. Anderson Cancer Center in pheochromocytoma, neuroblastoma, and other neuroectodermal tumors. Investigation of {sup 131}I-MIBG therapy of metastatic tumors of neuroectodermal origin potentially offers a means of at least controlling symptoms of hormonal secretion in these patients. 40 references.

  20. Activation of spinal MrgC-Gi-NR2B-nNOS signaling pathway by Mas oncogene-related gene C receptor agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice

    PubMed Central

    Sun, Yu’e; Zhang, Juan; Lei, Yishan; Lu, Cui’e; Hou, Bailing; Ma, Zhengliang; Gu, Xiaoping

    2016-01-01

    Objectives: In the present study, we investigate the effects of Mas oncogene-related gene (Mrg) C receptors (MrgC) on the expression and activation of spinal Gi protein, N-methyl-D-aspartate receptor subunit 2B (NR2B), and neuronal nitric oxide synthase (nNOS) in mouse model of bone cancer pain. Methods: The number of spontaneous foot lift (NSF) and paw withdrawal mechanical threshold (PWMT) were measured after inoculation of tumor cells and intrathecal injection of MrgC agonist bovine adrenal medulla 8-22 (BAM8-22) or MrgC antagonist anti-MrgC for 14 days after operation. Expression of spinal MrgC, Gi protein, NR2B and nNOS and their phosphorylated forms after inoculation was examined by immunohistochemistry and Western blotting. Double labeling was used to identify the co-localization of NR2B or nNOS with MrgC in spinal cord dorsal horn (SCDH) neurons. The effects of intrathecal injection of BAM8-22 or anti-MrgC on nociceptive behaviors and the corresponding expression of spinal MrgC, Gi protein, NR2B and nNOS were also investigated. Results: The expression of spinal MrgC, Gi protein, NR2B, and nNOS was higher in tumor-bearing mice in comparison to sham mice or normal mice. Intrathecal injection of MrgC agonist BAM8-22 significantly alleviated bone cancer pain, up-regulated MrgC and Gi protein expression, and down-regulated the expression of spinal p-NR2B, t-nNOS and p-nNOS in SCDH on day 14 after operation, whereas administration of anti-MrgC produced the opposite effect. Meanwhile, MrgC-like immunoreactivity (IR) co-localizes with NR2B-IR or nNOS-IR in SCDH neurons. Conclusions: The present study demonstrates that MrgC-activated spinal Gi-NR2B-nNOS signaling pathway plays important roles in the development of bone cancer pain. These findings may provide a novel strategy for the treatment of bone cancer pain. PMID:27158400

  1. Targeting the Checkpoint to Kill Cancer Cells

    PubMed Central

    Benada, Jan; Macurek, Libor

    2015-01-01

    Cancer treatments such as radiotherapy and most of the chemotherapies act by damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell cycle checkpoints, which provides them time for DNA repair. Inhibiting the checkpoint allows entry to mitosis despite the presence of DNA damage and can lead to cell death. Importantly, as cancer cells exhibit increased levels of endogenous DNA damage due to an excessive replication stress, inhibiting the checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we review the current status of inhibitors targeted towards the checkpoint effectors and discuss mechanisms of their actions in killing of cancer cells. PMID:26295265

  2. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  3. On the Stem Cell Origin of Cancer

    PubMed Central

    Sell, Stewart

    2010-01-01

    In each major theory of the origin of cancer—field theory, chemical carcinogenesis, infection, mutation, or epigenetic change—the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth. PMID:20431026

  4. Cancer stem cells and exosome signaling.

    PubMed

    Hannafon, Bethany N; Ding, Wei-Qun

    2015-01-01

    Exosomes have been recognized as mediators of intercellular communication among different cell populations in various biological model systems. By transfer of signaling molecules such as proteins, lipids, and RNAs between different cell types, exosomes are implicated in both physiological and pathological processes. The tumor microenvironment consists of multiple types of cells including adult stem cells, cancer stem cells, and stromal cells. These cells are known to intercommunicate with each other thereby modulating tumor progression. Recent studies have provided evidence demonstrating that exosomes mediate the interactions among different types of cells within the tumor microenvironment, providing new insight into how these cells interact with each other through exosome signaling. This review is focused on recent studies that have examined exosome-mediated intercommunication among cancer stem cells, adult stem cells, cancer cells, and stromal cells within the tumor microenvironment. Based on the current literature, it seems clear that adult stem cells and cancer stem cells secret exosomes that can be transferred to their surrounding cells thereby modulating cancer progression. Likewise, cancer cells and stromal cells also release exosomes that can be taken up by cancer stem cells or adult stem cells, leading to alterations to their phenotype. The molecular mechanisms and biological consequences of the exosome-mediated interactions of these cells remain to be further elucidated. A better understanding of how exosomes mediate intercellular communication in the tumor microenvironment and the specific biological consequences of these interactions will likely offer new opportunities in the development of diagnostic or therapeutic strategies against cancer. PMID:27358879

  5. Cancer stem cells and exosome signaling

    PubMed Central

    Hannafon, Bethany N.

    2015-01-01

    Exosomes have been recognized as mediators of intercellular communication among different cell populations in various biological model systems. By transfer of signaling molecules such as proteins, lipids, and RNAs between different cell types, exosomes are implicated in both physiological and pathological processes. The tumor microenvironment consists of multiple types of cells including adult stem cells, cancer stem cells, and stromal cells. These cells are known to intercommunicate with each other thereby modulating tumor progression. Recent studies have provided evidence demonstrating that exosomes mediate the interactions among different types of cells within the tumor microenvironment, providing new insight into how these cells interact with each other through exosome signaling. This review is focused on recent studies that have examined exosome-mediated intercommunication among cancer stem cells, adult stem cells, cancer cells, and stromal cells within the tumor microenvironment. Based on the current literature, it seems clear that adult stem cells and cancer stem cells secret exosomes that can be transferred to their surrounding cells thereby modulating cancer progression. Likewise, cancer cells and stromal cells also release exosomes that can be taken up by cancer stem cells or adult stem cells, leading to alterations to their phenotype. The molecular mechanisms and biological consequences of the exosome-mediated interactions of these cells remain to be further elucidated. A better understanding of how exosomes mediate intercellular communication in the tumor microenvironment and the specific biological consequences of these interactions will likely offer new opportunities in the development of diagnostic or therapeutic strategies against cancer.

  6. [Addison's disease : Primary adrenal insufficiency].

    PubMed

    Pulzer, A; Burger-Stritt, S; Hahner, S

    2016-05-01

    Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them. PMID:27129928

  7. Basal cell skin cancer

    MedlinePlus

    ... occur in younger people who have had extensive sun exposure. You are more likely to get basal cell ... severe sunburns early in life Long-term daily sun exposure (such as the sun exposure received by people ...

  8. [Dendritic cells in cancer immunotherapy].

    PubMed

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities. PMID:26486534

  9. Telomerase reverse transcriptase promoter mutations in tumors originating from the adrenal gland and extra-adrenal paraganglia.

    PubMed

    Papathomas, Thomas G; Oudijk, Lindsey; Zwarthoff, Ellen C; Post, Edward; Duijkers, Floor A; van Noesel, Max M; Hofland, Leo J; Pollard, Patrick J; Maher, Eamonn R; Restuccia, David F; Feelders, Richard A; Franssen, Gaston J H; Timmers, Henri J; Sleijfer, Stefan; de Herder, Wouter W; de Krijger, Ronald R; Dinjens, Winand N M; Korpershoek, Esther

    2014-08-01

    Hotspot mutations in the promoter of the telomerase reverse transcriptase (TERT) gene have been recently reported in human cancers and proposed as a novel mechanism of telomerase activation. To explore TERT promoter mutations in tumors originating from the adrenal gland and extra-adrenal paraganglia, a set of 253 tumors (38 adrenocortical carcinomas (ACCs), 127 pheochromocytomas (PCCs), 18 extra-adrenal paragangliomas (ea PGLs), 37 head and neck PGLs (HN PGLs), and 33 peripheral neuroblastic tumors) was selected along with 16 human neuroblastoma (NBL) and two ACC cell lines to assess TERT promoter mutations by the Sanger sequencing method. All mutations detected were confirmed by a SNaPshot assay. Additionally, 36 gastrointestinal stromal tumors (GISTs) were added to explore an association between TERT promoter mutations and SDH deficiency. TERT promoter mutations were found in seven out of 289 tumors and in three out of 18 human cell lines; four C228T mutations in 38 ACCs (10.5%), two C228T mutations in 18 ea PGLs (11.1%), one C250T mutation in 36 GISTs (2.8%), and three C228T mutations in 16 human NBL cell lines (18.75%). No mutation was detected in PCCs, HN PGLs, neuroblastic tumors as well as ACC cell lines. TERT promoter mutations preferentially occurred in a SDH-deficient setting (P=0.01) being present in three out of 47 (6.4%) SDH-deficient tumors vs zero out of 171 (0%) SDH-intact tumors. We conclude that TERT promoter mutations occur in ACCs and ea PGLs. In addition, preliminary evidence indicates a potential association with the acquisition of TERT promoter mutations in SDH-deficient tumors. PMID:24951106

  10. Catecholamines of the adrenal medula and their morphological changes during adaptation to repeated immobilization stress

    NASA Technical Reports Server (NTRS)

    Kvetnansky, R.; Mitro, A.; Mikulaj, L.; Hocman, G.

    1980-01-01

    Changes of the adrenal medulla of rats were studied in the course of adaptation to repeated immobilization stress. An increase in the number of cells in the adrenal medulla was found in the adapted animals; this increase was confirmed by weight indices of the medulla and by cell counts per surface unit. Simultaneous karyometric measurements of the nuclei of adrenal medulla cells and an analysis of the catecholamine contents in the adrenals explain the increased activity of the adrenal medulla in the course of adaptation.

  11. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  12. Adrenal Schwannomas: Rare Tumor of the Retroperitoneum.

    PubMed

    Grasso, Emanuele; Simone, Michele

    2015-01-01

    Schwannoma is a benign neurogenic tumor originating from Schwann cells. These produce the myelin sheath that covers peripheral nerves that are often affected. This latter localization is extremely rare, and only a few case reports can be found in the medical literature. Studies have shown that approximately 0.5% to 5% of schwannomas are retroperitoneal, constituting 0.2% of adrenal incidental tumors. These usually present as incidental findings, nonsecreting adrenal masses in asymptomatic patients. Diagnosis of a schwannoma is based on detection of spindle cells with Antoni A and Antoni B regions in histological sections and positive staining for S-100 protein by immunohistochemical analysis. We report a case of an incidentally identified during an abdominal ultrasound examination with schwannoma localized in the left adrenal gland. PMID:26101687

  13. ATR-101, a Selective and Potent Inhibitor of Acyl-CoA Acyltransferase 1, Induces Apoptosis in H295R Adrenocortical Cells and in the Adrenal Cortex of Dogs.

    PubMed

    LaPensee, Christopher R; Mann, Jacqueline E; Rainey, William E; Crudo, Valentina; Hunt, Stephen W; Hammer, Gary D

    2016-05-01

    ATR-101 is a novel, oral drug candidate currently in development for the treatment of adrenocortical cancer. ATR-101 is a selective and potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase 1 (ACAT1), an enzyme located in the endoplasmic reticulum (ER) membrane that catalyzes esterification of intracellular free cholesterol (FC). We aimed to identify mechanisms by which ATR-101 induces adrenocortical cell death. In H295R human adrenocortical carcinoma cells, ATR-101 decreases the formation of cholesteryl esters and increases FC levels, demonstrating potent inhibition of ACAT1 activity. Caspase-3/7 levels and terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeled-positive cells are increased by ATR-101 treatment, indicating activation of apoptosis. Exogenous cholesterol markedly potentiates the activity of ATR-101, suggesting that excess FC that cannot be adequately esterified increases caspase-3/7 activation and subsequent cell death. Inhibition of calcium release from the ER or the subsequent uptake of calcium by mitochondria reverses apoptosis induced by ATR-101. ATR-101 also activates multiple components of the unfolded protein response, an indicator of ER stress. Targeted knockdown of ACAT1 in an adrenocortical cell line mimicked the effects of ATR-101, suggesting that ACAT1 mediates the cytotoxic effects of ATR-101. Finally, in vivo treatment of dogs with ATR-101 decreased adrenocortical steroid production and induced cellular apoptosis that was restricted to the adrenal cortex. Together, these studies demonstrate that inhibition of ACAT1 by ATR-101 increases FC, resulting in dysregulation of ER calcium stores that result in ER stress, the unfolded protein response, and ultimately apoptosis. PMID:26986192

  14. A boundary for histone acetylation allows distinct expression patterns of the Ad4BP/SF-1 and GCNF loci in adrenal cortex cells

    SciTech Connect

    Ishihara, Satoru L.; Morohashi, Ken-ichirou . E-mail: moro@nibb.ac.jp

    2005-04-08

    Ad4BP/SF-1 is a nuclear receptor whose expression is restricted to tissues involved in steroid hormone synthesis such as the adrenal cortex and gonads. Recent sequence data analysis has shown that the Ad4BP/SF-1 gene is located only 13 kb downstream of the last exon of the neighboring GCNF gene that is expressed in some neurons and gonadal germ cells. Despite the close proximity of the two genes, regulatory elements from one do not interfere with the transcription of the neighboring gene, resulting in distinct expression patterns of Ad4BP/SF-1 and GCNF. This observation has led to the prediction that an insulator element must exist between the two loci to establish independent transcription units. We performed DNase I hypersensitivity assays on the adrenal cortex cell line, Y-1, to test for the existence of an insulator. Three hypersensitive sites were identified in the region spanning 2.1 kb between the last exon of GCNF and the first exon of Ad4BP/SF-1. The most upstream site contains a binding site for CTCF, a known insulator protein, while the other sites are predicted to associate with the nuclear matrix. Chromatin immunoprecipitation analysis using anti-acetylated histone H3 and H4 antibodies showed a discontinuous pattern of histone H3 and H4 acetylation upstream of these sites. Our data suggest that the chromatin architecture specialized by CTCF and the nuclear matrix contribute to the distinct pattern of transcriptional regulation of these genes.

  15. A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1

    PubMed Central

    Huang, Chen-Che Jeff; Kraft, Cary; Moy, Nicole; Ng, Lily

    2015-01-01

    The development of the adrenal cortex involves the formation and then subsequent regression of immature or fetal inner cell layers as the mature steroidogenic outer layers expand. However, controls over this remodeling, especially in the immature inner layer, are incompletely understood. Here we identify an inner cortical cell population that expresses thyroid hormone receptor-β1 (TRβ1), one of two receptor isoforms encoded by the Thrb gene. Using mice with a Thrbb1 reporter allele that expresses lacZ instead of TRβ1, β-galactosidase was detected in the inner cortex from early stages. Expression peaked at juvenile ages in an inner zone that included cells expressing 20-α-hydroxysteroid dehydrogenase, a marker of the transient, so-called X-zone in mice. The β-galactosidase-positive zone displayed sexually dimorphic regression in males after approximately 4 weeks of age but persisted in females into adulthood in either nulliparous or parous states. T3 treatment promoted hypertrophy of inner cortical cells, induced some markers of mature cortical cells, and, in males, delayed the regression of the TRβ1-positive zone, suggesting that TRβ1 could partly divert the differentiation fate and counteract male-specific regression of inner zone cells. TRβ1-deficient mice were resistant to these actions of T3, supporting a functional role for TRβ1 in the inner cortex. PMID:25774556

  16. Percutaneous Ablation of Adrenal Tumors

    PubMed Central

    Venkatesan, Aradhana M.; Locklin, Julia; Dupuy, Damian E.; Wood, Bradford J.

    2010-01-01

    Adrenal tumors comprise a broad spectrum of benign and malignant neoplasms, and include functional adrenal adenomas, pheochromocytomas, primary adrenocortical carcinoma and adrenal metastases. Percutaneous ablative approaches that have been described and used in the treatment of adrenal tumors include percutaneous radiofrequency ablation (RFA), cryoablation, microwave ablation and chemical ablation. Local tumor ablation in the adrenal gland presents unique challenges, secondary to the adrenal gland’s unique anatomic and physiologic features. The results of clinical series employing percutaneous ablative techniques in the treatment of adrenal tumors are reviewed in this article. Clinical and technical considerations unique to ablation in the adrenal gland are presented, including approaches commonly used in our practices, and risks and potential complications are discussed. PMID:20540918

  17. REGULATION OF ADRENAL CHROMAFFIN CELL DEVELOPMENT BY THE CENTRAL MONOAMINERGIC SYSTEM: DIFFERENTIAL CONTROL OF NOREPINEPHRINE AND EPINEPHRINE LEVELS AND SECRETORY RESPONSES (JOURNAL VERSION)

    EPA Science Inventory

    In the mature rat, reflex sympathetic stimulation by insulin-induced hypoglycemia resulted in profound depletion of adrenal epinephrine, and to a lesser extent, Norepinephrine. In the developing rat, insulin evoked little or no secretory response from the adrenals prior to 1 week...

  18. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research. PMID:21044008

  19. Cancer stem cells in small cell lung cancer

    PubMed Central

    Verlicchi, Alberto; Rosell, Rafael

    2016-01-01

    Small cell lung cancer (SCLC) is one of the most aggressive lung tumors, with poor survival rates. Although patients may initially respond to treatment, this is followed by rapid development of drug resistance and disease progression. SCLC patients often present with metastasis at time of diagnosis, ruling out surgery as a treatment option. Currently, treatment options for this disease remain limited and platinum-based chemotherapy is the treatment of choice. A better understanding of the biology of SCLC could allow us to identify new therapeutic targets. Cancer stem cell (CSC) theory is currently crucial in cancer research and could provide a viable explanation for the heterogeneity, drug resistance, recurrence and metastasis of several types of tumors. Some characteristics of SCLC, such as aggressiveness, suggest that this kind of tumor could be enriched in CSCs, and drug resistance in SCLC could be attributable to the existence of a CSC subpopulation in SCLC. Herein we summarize current understanding of CSC in SCLC, including the evidence for CSC markers and signaling pathways involved in stemness. We also discuss potential ongoing strategies and areas of active research in SCLC, such as immunotherapy, that focus on inhibition of signaling pathways and targeting molecules driving stemness. Understanding of signaling pathways and the discovery of new therapeutic markers specific to CSCs will lead to new advances in therapy and improvements in prognosis of SCLC patients. Therefore, evaluation of these CSC-specific molecules and pathways may become a routine part of SCLC diagnosis and therapy. PMID:26958490

  20. [Giant adrenal myelolipoma].

    PubMed

    El Mejjad, Amine; Fekak, Hamid; Dakir, Mohamed; Sarf, Ismail; Manni, Ahmed; Meziane, Fethi

    2004-02-01

    Adrenal myelolipoma is a rare, benign, non-secreting tumour composed of adipose and haematopoietic tissue. The authors report a rare case of giant adrenal myelolipoma in a 53-year-old patient presenting with low back pain and a palpable flank mass on examination. CT scan suggested the diagnosis and surgical resection was indicated in view of the size and symptomatic nature of this mass. Histological examination confirmed the diagnosis. The outcome was favourable without recurrence after a follow-up of one year. The diagnosis of adrenal myelolipoma is based on radiology. Conservative management is generally sufficient for small asymptomatic tumours, but resection is required for large (> 5 cm) and/or symptomatic tumours. PMID:15098761

  1. Frequency of varicella zoster virus DNA in human adrenal glands.

    PubMed

    Badani, Hussain; White, Teresa; Schulick, Nicole; Raeburn, Christopher D; Topkaya, Ibrahim; Gilden, Don; Nagel, Maria A

    2016-06-01

    Varicella zoster virus (VZV) becomes latent in ganglionic neurons derived from neural crest cells. Because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for VZV and herpes simplex virus type 1 (HSV-1). We found VZV, but not HSV-1, DNA in 4/63 (6 %) normal adrenal glands. No VZV transcripts or antigens were detected in the 4 VZV DNA-positive samples. No VZV or HSV-1 DNA was found in 21 pheochromocytomas. PMID:26843382

  2. Multiple Myeloma Cancer Stem Cells

    PubMed Central

    Huff, Carol Ann; Matsui, William

    2008-01-01

    Multiple myeloma is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic bone disease. The disease is highly responsive to a wide variety of anticancer treatments including conventional cytotoxic chemotherapy, corticosteroids, radiation therapy, and a growing number of agents with novel mechanisms of action. However, few if any patients are cured with these modalities and relapse remains a critical issue. A better understanding of clonogenic multiple myleoma cells is essential to ultimately improving long-term outcomes, but the nature of the cells responsible for myeloma regrowth and disease relapse is unclear. We review evidence that functional heterogeneity exists in multiple myeloma and discuss potential strategies and clinical implications of the stem-cell model of cancer in this disease. PMID:18539970

  3. Noncholinergic control of adrenal catecholamine secretion.

    PubMed Central

    Livett, B G; Marley, P D

    1993-01-01

    It has been known for over 70 years that adrenal catecholamine secretion can be modulated or elicited by noncholinergic neurotransmitters and hormones. However, our understanding of the cellular mechanisms by which these agents produce their effects and the physiological conditions under which they act are not well characterised. Here we briefly review the mechanisms by which one such agent (the neuropeptide substance P) modulates the cholinergic secretory response of adrenal chromaffin cells, and another agent (angiotensin II) elicits catecholamine secretion independently of the cholinergic innervation. PMID:7507911

  4. Head and Neck Cancer Stem Cells

    PubMed Central

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the “drivers” of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  5. Head and neck cancer stem cells.

    PubMed

    Krishnamurthy, S; Nör, J E

    2012-04-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  6. Myxoid adrenal adenoma with focal pseudoglandular pattern.

    PubMed

    De Padua, Michelle; Rajagopal, V

    2008-05-01

    Adrenal cortical tumors with myxoid change are rare tumors. To our knowledge, only 22 cases have been described so far in literature, which include 13 carcinomas and 9 adenomas. A pseudoglandular pattern has been described in 9 of these tumors. We report a case of a myxoid adenoma of the left adrenal gland in a 67-year-old woman, with a focal pseudoglandular pattern involving about 20% of the studied tumor. Rest of the tumor was composed of anastomosing cords of tumor cells. Abundant myxoid stroma was present, which stained positively with alcian blue and was weakly focally positive with periodic acid Schiff. Immunophenotype was consistent with an adrenal tumor, i.e., positive for vimentin, inhibin, and melan A. Cytokeratin AE1/AE3 and chromogranin were negative. MIB-1 index was < 0.1%. PMID:18579979

  7. Role of phospholipases in adrenal steroidogenesis.

    PubMed

    Bollag, Wendy B

    2016-04-01

    Phospholipases are lipid-metabolizing enzymes that hydrolyze phospholipids. In some cases, their activity results in remodeling of lipids and/or allows the synthesis of other lipids. In other cases, however, and of interest to the topic of adrenal steroidogenesis, phospholipases produce second messengers that modify the function of a cell. In this review, the enzymatic reactions, products, and effectors of three phospholipases, phospholipase C, phospholipase D, and phospholipase A2, are discussed. Although much data have been obtained concerning the role of phospholipases C and D in regulating adrenal steroid hormone production, there are still many gaps in our knowledge. Furthermore, little is known about the involvement of phospholipase A2, perhaps, in part, because this enzyme comprises a large family of related enzymes that are differentially regulated and with different functions. This review presents the evidence supporting the role of each of these phospholipases in steroidogenesis in the adrenal cortex. PMID:26878860

  8. Nonclassic Congenital Adrenal Hyperplasia

    PubMed Central

    Witchel, Selma Feldman; Azziz, Ricardo

    2010-01-01

    Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase deficiency) is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH. PMID:20671993

  9. How cell death shapes cancer

    PubMed Central

    Labi, V; Erlacher, M

    2015-01-01

    Apoptosis has been established as a mechanism of anti-cancer defense. Members of the BCL-2 family are critical mediators of apoptotic cell death in health and disease, often found to be deregulated in cancer and believed to lead to the survival of malignant clones. However, over the years, a number of studies pointed out that a model in which cell death resistance unambiguously acts as a barrier against malignant disease might be too simple. This is based on paradoxical observations made in tumor patients as well as mouse models indicating that apoptosis can indeed drive tumor formation, at least under certain circumstances. One possible explanation for this phenomenon is that apoptosis can promote proliferation critically needed to compensate for cell loss, for example, upon therapy, and to restore tissue homeostasis. However, this, at the same time, can promote tumor development by allowing expansion of selected clones. Usually, tissue resident stem/progenitor cells are a major source for repopulation, some of them potentially carrying (age-, injury- or therapy-induced) genetic aberrations deleterious for the host. Thereby, apoptosis might drive genomic instability by facilitating the emergence of pathologic clones during phases of proliferation and subsequent replication stress-associated DNA damage. Tumorigenesis initiated by repeated cell attrition and repopulation, as confirmed in different genetic models, has parallels in human cancers, exemplified in therapy-induced secondary malignancies and myelodysplastic syndromes in patients with congenital bone marrow failure syndromes. Here, we aim to review evidence in support of the oncogenic role of stress-induced apoptosis. PMID:25741600

  10. Extinction models for cancer stem cell therapy

    PubMed Central

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  11. Adrenal venous sampling in a patient with adrenal Cushing syndrome

    PubMed Central

    Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

  12. Colon Cancer Cell Separation by Dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Yang, Fang; Yang, Xiaoming; Jiang, H.; Wood, P.; Hrushesky, W.; Wang, Guiren

    2009-11-01

    Separation of cancer cells from the other biological cells can be useful for clinical cancer diagnosis and cancer treatment. In this presentation, conventional dielectrophoresis (c-DEP) is used in a microfluidic chip to manipulate and collect colorectal cancer HCT116 cell, which is doped with Human Embryonic Kidney 293 cells (HEK 293). It is noticed that, the HCT116 cell are deflected to a side channel from a main channel clearly by apply electric field at particular AC frequency band. This motion caused by negative DEP can be used to separate the cancer cell from others. In this manuscript, chip design, flow condition, the DEP spectrum of the cancer cell are reported respectively, and the separation and collection efficiency are investigated as well. The sorter is microfabricated using plastic laminate technology. -/abstract- This work has been financially supported by the NSF RII funding (EP

  13. Mitochondria, cholesterol and cancer cell metabolism.

    PubMed

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  14. Cancer stem cells and differentiation therapy.

    PubMed

    Sell, Stewart

    2006-01-01

    Cancers arise from stem cells in adult tissues and the cells that make up a cancer reflect the same stem cell --> progeny --> differentiation progression observed in normal tissues. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells); the number of new cells produced in normal tissue lineages roughly equals the number of old cells that die. Cancers result from maturation arrest of this process, resulting in continued proliferation of cells and a failure to differentiate and die. The biological behavior, morphological appearance, and clinical course of a cancer depend on the stage of maturation at which the genetic lesion is activated. This review makes a comparison of cancer cells to embryonic stem cells and to adult tis sue stem cells while addressing two basic questions: (1) Where do cancers come from?, and (2) How do cancers grow? The answers to these questions are critical to the development of approaches to the detection, prevention, and treatment of cancer. PMID:16557043

  15. Mast cells, angiogenesis and cancer.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2011-01-01

    Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis. MCs have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, the question as to the possible contribution of MCs to tumor development has progressively been emerging. In this chapter, the specific involvement of MCs in tumor biology and tumor fate will be considered, with particular emphasis on the capacity of these cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Data from experimental carcinogenesis and from different tumor settings in human pathology will be summarized. Information to be presented will suggest that MCs may serve as a novel therapeutic target for cancer treatment. PMID:21713661

  16. Ouabain enhances lung cancer cell detachment.

    PubMed

    Ruanghirun, Thidarat; Pongrakhananon, Varisa; Chanvorachote, Pithi

    2014-05-01

    A human steroid hormone, ouabain, has been shown to play a role in several types of cancer cell behavior; however, its effects on cancer metastasis are largely unknown. Herein, we demonstrate that sub-toxic concentrations of ouabain facilitate cancer cell detachment from the extracellular matrix in human lung cancer cells. Ouabain at concentrations of 0-10 pM significantly enhanced cell detachment in dose- and time- dependent manners, while having minimal effect on cell viability. The detachment-inducing effect of ouabain was found to be mediated through focal-adhesion kinase and ATP-dependent tyrosine kinase pathways. Alpha-5 and beta-1 integrins were found to be down-regulated in response to ouabain treatment. Since detachment of cancer cells is a prerequisite process for metastasis to begin, these insights benefit our understanding over the molecular basis of cancer biology. PMID:24778025

  17. Endothelial cell metabolism: parallels and divergences with cancer cell metabolism

    PubMed Central

    2014-01-01

    The stromal vasculature in tumors is a vital conduit of nutrients and oxygen for cancer cells. To date, the vast majority of studies have focused on unraveling the genetic basis of vessel sprouting (also termed angiogenesis). In contrast to the widely studied changes in cancer cell metabolism, insight in the metabolic regulation of angiogenesis is only just emerging. These studies show that metabolic pathways in endothelial cells (ECs) importantly regulate angiogenesis in conjunction with genetic signals. In this review, we will highlight these emerging insights in EC metabolism and discuss them in perspective of cancer cell metabolism. While it is generally assumed that cancer cells have unique metabolic adaptations, not shared by healthy non-transformed cells, we will discuss parallels and highlight differences between endothelial and cancer cell metabolism and consider possible novel therapeutic opportunities arising from targeting both cancer and endothelial cells. PMID:25250177

  18. The biology of cancer stem cells.

    PubMed

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. PMID:17645413

  19. Restoration of normal phenotype in cancer cells

    DOEpatents

    Bissell, Mina J.; Weaver, Valerie M.

    1998-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  20. Restoration of normal phenotype in cancer cells

    DOEpatents

    Bissell, M.J.; Weaver, V.M.

    1998-12-08

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying {beta}{sub 1} integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive. 14 figs.

  1. Congenital adrenal hyperplasia

    MedlinePlus

    ... or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to 18,000 ... penis but normal testes Well-developed muscles Both boys and girls will be tall as children, but much shorter ...

  2. Cancer

    MedlinePlus

    ... body. Cancerous cells are also called malignant cells. Causes Cancer grows out of cells in the body. Normal ... of many cancers remains unknown. The most common cause of cancer-related death is lung cancer. In the U.S., ...

  3. Deregulation of Cell Signaling in Cancer

    PubMed Central

    Giancotti, Filippo G.

    2014-01-01

    Summary Oncogenic mutations disrupt the regulatory circuits that govern cell function, enabling tumor cells to undergo de-regulated mitogenesis, to resist to proapoptotic insults, and to invade through tissue boundaries. Cancer cell biology has played a crucial role in elucidating the signaling mechanisms by which oncogenic mutations sustain these malignant behaviors and thereby in identifying rational targets for cancer drugs. The efficacy of such targeted therapies illustrate the power of a reductionist approach to the study of cancer. PMID:24561200

  4. Targeting Aldehyde Dehydrogenase Cancer Stem Cells in Ovarian Cancer

    PubMed Central

    Landen, Charles N.; Goodman, Blake; Katre, Ashwini A.; Steg, Adam D.; Nick, Alpa M.; Stone, Rebecca L.; Miller, Lance D.; Mejia, Pablo Vivas; Jennings, Nicolas B.; Gershenson, David M.; Bast, Robert C.; Coleman, Robert L.; Lopez-Berestein, Gabriel; Sood, Anil K.

    2010-01-01

    Aldehyde dehydrogenase-1A1 (ALDH1A1) expression characterizes a subpopulation of cells with tumor initiating or cancer stem cell properties in several malignancies. Our goal was to characterize the phenotype of ALDH1A1-positive ovarian cancer cells and examine the biological effects of ALDH1A1 gene silencing. In our analysis of multiple ovarian cancer cell lines, we found that ALDH1A1 expression and activity was significantly higher in taxane and platinum-resistant cell lines. In patient samples, 72.9% of ovarian cancers had ALDH1A1 expression, in whom the percent of ALDH1A1-positive cells correlated negatively with progression-free survival (6.05 v 13.81 months, p<0.035). Subpopulations of A2780cp20 cells with ALDH1A1 activity were isolated for orthotopic tumor initiating studies, where tumorigenicity was approximately 50-fold higher with ALDH1A1-positive cells. Interestingly, tumors derived from ALDH1A1-positive cells gave rise to both ALDH1A1-positive and ALDH1A1-negative populations, but ALDH1A1-negative cells could not generate ALDH1A1-positive cells. In an in vivo orthotopic mouse model of ovarian cancer, ALDH1A1 silencing using nanoliposomal siRNA sensitized both taxane- and platinum-resistant cell lines to chemotherapy, significantly reducing tumor growth in mice compared to chemotherapy alone (a 74–90% reduction, p<0.015). These data demonstrate that the ALDH1A1 subpopulation is associated with chemoresistance and outcome in ovarian cancer patients, and targeting ALDH1A1 sensitizes resistant cells to chemotherapy. ALDH1A1-positive cells have enhanced, but not absolute, tumorigenicity, but do have differentiation capacity lacking in ALDH1A1-negative cells. This enzyme may be important for identification and targeting of chemoresistant cell populations in ovarian cancer. PMID:20889728

  5. Role of stem cells in cancer therapy and cancer stem cells: a review

    PubMed Central

    Sagar, Jayesh; Chaib, Boussad; Sales, Kevin; Winslet, Marc; Seifalian, Alexander

    2007-01-01

    For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research field and possible potential future treatment modalities for the cancer. Aim of this review is primarily focus on the recent developments in the use of the stem cells in the cancer treatments, then to discuss the cancer stem cells, now considered as backbone in the development of the cancer; and their role in carcinogenesis and their implications in the development of possible new cancer treatment options in future. PMID:17547749

  6. Treatment Options by Stage (Small Cell Lung Cancer)

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points ...

  7. Regulation of NANOG in cancer cells.

    PubMed

    Gong, Shuai; Li, Qiuhui; Jeter, Collene R; Fan, Qingxia; Tang, Dean G; Liu, Bigang

    2015-09-01

    As one of the key pluripotency transcription factors, NANOG plays a critical role in maintaining the self-renewal and pluripotency in normal embryonic stem cells. Recent data indicate that NANOG is expressed in a variety of cancers and its expression correlates with poor survival in cancer patients. Of interest, many studies suggest that NANOG enhances the defined characteristics of cancer stem cells and may thus function as an oncogene to promote carcinogenesis. Therefore, NANOG expression determines the cell fate not only in pluripotent cells but also in cancer cells. Although the regulation of NANOG in normal embryonic stem cells is reasonably well understood, the regulation of NANOG in cancer cells has only emerged recently. The current review provides a most updated summary on how NANOG expression is regulated during tumor development and progression. PMID:26013997

  8. Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature.

    PubMed

    Liu, Yu-Yi; Chen, Zhi-Hui; Zhai, Er-Tao; Yang, Jie; Xu, Jian-Bo; Cai, Shi-Rong; Song, Wu

    2016-04-14

    Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients' follow up for colorectal cancer with or without subsequent adrenal metastasis. PMID:27076775

  9. Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature

    PubMed Central

    Liu, Yu-Yi; Chen, Zhi-Hui; Zhai, Er-Tao; Yang, Jie; Xu, Jian-Bo; Cai, Shi-Rong; Song, Wu

    2016-01-01

    Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients’ follow up for colorectal cancer with or without subsequent adrenal metastasis. PMID:27076775

  10. Confocal Raman imaging for cancer cell classification

    NASA Astrophysics Data System (ADS)

    Mathieu, Evelien; Van Dorpe, Pol; Stakenborg, Tim; Liu, Chengxun; Lagae, Liesbet

    2014-05-01

    We propose confocal Raman imaging as a label-free single cell characterization method that can be used as an alternative for conventional cell identification techniques that typically require labels, long incubation times and complex sample preparation. In this study it is investigated whether cancer and blood cells can be distinguished based on their Raman spectra. 2D Raman scans are recorded of 114 single cells, i.e. 60 breast (MCF-7), 5 cervix (HeLa) and 39 prostate (LNCaP) cancer cells and 10 monocytes (from healthy donors). For each cell an average spectrum is calculated and principal component analysis is performed on all average cell spectra. The main features of these principal components indicate that the information for cell identification based on Raman spectra mainly comes from the fatty acid composition in the cell. Based on the second and third principal component, blood cells could be distinguished from cancer cells; and prostate cancer cells could be distinguished from breast and cervix cancer cells. However, it was not possible to distinguish breast and cervix cancer cells. The results obtained in this study, demonstrate the potential of confocal Raman imaging for cell type classification and identification purposes.

  11. Dendritic cell-based cancer therapeutic vaccines

    PubMed Central

    Palucka, Karolina; Banchereau, Jacques

    2013-01-01

    The past decade has seen tremendous developments in novel cancer therapies, through targeting of tumor cell-intrinsic pathways whose activity is linked to genetic alterations, as well as the targeting of tumor cell-extrinsic factors such as growth factors. Furthermore, immunotherapies are entering the clinic at an unprecedented speed following the demonstration that T cells can efficiently reject tumors and that their anti-tumor activity can be enhanced with antibodies against immune regulatory molecules (checkpoints blockade). Current immunotherapy strategies include monoclonal antibodies against tumor cells or immune regulatory molecules, cell-based therapies such as adoptive transfer of ex vivo activated T cells and natural killer (NK) cells, and cancer vaccines. Herein, we discuss the immunological basis for therapeutic cancer vaccines and how the current understanding of dendritic cell (DC) and T cell biology might enable development of next-generation curative therapies for patients with cancer. PMID:23890062

  12. "Parallel array" of tubules with pipe-like structure in the mitochondria of glomerulosa cells of adrenal cortex. Ultrastructural and freeze-fracture replica studies.

    PubMed

    Kawai, K; Shigematsu, K; Irie, J; Tsuchiyama, H

    1989-01-01

    We found "parallel array" of tubules with a pipe-like structure in the mitochondria of glomerulosa cells of the adrenal cortex of the rats treated with atrial natriuretic factor (ANF) that inhibits aldosterone production. This structure was characterized by the regular parallel arrays of tubules running straight along the mitochondrial long axis, representing a pipe-like structure. The cross section exhibited the round shape with an electron lucent core measuring about 40 nm and dual thick membranes measuring 10 nm in thickness. Some of these tubules were connected with the mitochondrial inner membrane. Freeze fracture replica represented round particles distributed on the surface membrane of these tubules, indicating protein particles. This particular structure was considered to be one of the changes occurring in the mitochondrial inner membrane on which structural proteins were localized. These tubules probably appeared in connection with the impaired mitochondrial protein synthesis in the process of the biosynthesis of mineralcorticoid, because this structure was found only in the glomerulosa cells under the decreased and increased aldosterone production. PMID:2527759

  13. Epigenetic targeting of ovarian cancer stem cells.

    PubMed

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  14. Radiofrequency treatment alters cancer cell phenotype

    NASA Astrophysics Data System (ADS)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  15. Radiofrequency treatment alters cancer cell phenotype

    PubMed Central

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-01-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment. PMID:26165830

  16. Breast cancer cell lines: friend or foe?

    PubMed Central

    Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

    2003-01-01

    The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research. PMID:12631387

  17. Congenital Adrenal Hyperplasia: Unresolved Issues.

    PubMed

    Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

    2016-01-01

    Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. PMID:27211889

  18. Turning Cancer Cells into Cancer Killers.

    PubMed

    2016-01-01

    Researchers have changed leukemia cells into natural killer cells by adding a specific antibody to bone marrow cells from patients with acute myeloblastic leukemia. The induced natural killer cells killed leukemia cells in culture. The antibody does not trigger the same conversion in bone marrow from healthy patients. PMID:26621762

  19. Cancer stem cell targeted therapy: progress amid controversies

    PubMed Central

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  20. Primary adrenal lymphoma: a systematic review.

    PubMed

    Rashidi, Armin; Fisher, Stephen I

    2013-12-01

    Fewer than 200 cases of primary adrenal lymphoma (PAL) have been reported. We have systematically reviewed all 187 cases of PAL reported in the English literature until June 2013, from which we drew the following conclusions: PAL is typically a highly symptomatic and aggressive, metabolically hyperactive, hypovascular, hypoechoic (and heterogeneous on ultrasound), hypodense (with slight to moderate enhancement on computed tomography), high-grade lymphoma, primarily affecting elderly males and presenting with large bilateral adrenal masses. Most cases have adrenal insufficiency, B-symptoms, and elevated lactate dehydrogenase. Hepatosplenomegaly, lymphadenopathy, concurrent or prior immune dysregulation, and bone marrow involvement are uncommon. Epstein-Barr virus positivity is observed in more than half of cases and the disease is disseminated at presentation in 18 % of cases. The two most common WHO 2008-defined PAL subtypes are diffuse large B cell lymphoma (78 %) and peripheral T cell lymphoma (7 %). The prognosis of PAL has improved with the advent of rituximab-containing chemotherapeutic regimens. According to our results, administration of chemotherapy and adrenal insufficiency are significant independent predictors of prognosis. PMID:23771429

  1. Cancer stem cells in glioblastoma

    PubMed Central

    Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.; Valentim, Claudia L.L.; Rich, Jeremy N.

    2015-01-01

    Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial. PMID:26109046

  2. How Is Adrenal Cancer Diagnosed?

    MedlinePlus

    ... levels before symptoms occur. Tests for high cortisol levels The levels of cortisol are measured in the ... cause high cortisol levels. Tests for high aldosterone levels The level of aldosterone will be measured and ...

  3. How Is Adrenal Cancer Found?

    MedlinePlus

    ... Excess growth of facial, pubic, and underarm hair Enlargement of the penis (boys) Enlargement of the clitoris (girls) A different set of ... make estrogen may have slight breast tenderness and enlargement. They may also notice less sex drive and ...

  4. Interfacial geometry dictates cancer cell tumorigenicity

    NASA Astrophysics Data System (ADS)

    Lee, Junmin; Abdeen, Amr A.; Wycislo, Kathryn L.; Fan, Timothy M.; Kilian, Kristopher A.

    2016-08-01

    Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.

  5. Interfacial geometry dictates cancer cell tumorigenicity.

    PubMed

    Lee, Junmin; Abdeen, Amr A; Wycislo, Kathryn L; Fan, Timothy M; Kilian, Kristopher A

    2016-08-01

    Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis. PMID:27043781

  6. CT demonstration of bilateral adrenal hemorrhage

    SciTech Connect

    Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.

    1983-08-01

    Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.

  7. Organ Preference of Cancer Metastasis and Metastasis-Related Cell Adhesion Molecules Including Carbohydrates.

    PubMed

    Kawaguchi, Takanori

    2016-01-01

    This review starts on one of our special interests, the organ preference of metastasis. We examined data on 1,117 autopsy cases and found that the organ distribution of metastasis of cancers of the lung, pancreas, stomach, colon, rectum, uterine cervix, liver, bile duct, and esophagus involved the lung, liver, adrenal gland, bone/bone marrow, lymph node, and pleura/peritoneum. Cancers of the kidney, thyroid, ovary, choriocarcinoma, and breast, however, manifested different metastatic patterns. The distribution of leukemia and lymphoma metastases was quite different from that of epithelial cancers. On the basis of experimental studies, we believe that the anatomical-mechanical hypothesis should be replaced by the microinjury hypothesis, which suggests that tissue microinjury induced by temporal tumor cell embolization is crucial for successful metastasis. This hypothesis may actually reflect the so-called inflammatory oncotaxis concept. To clarify the mechanisms underlying metastasis, we developed an experimental model system of a rat hepatoma AH7974 that embraced substrate adhesiveness. This model did not prove a relationship between substrate-adhesion potential and metastatic lung-colonizing potential of tumor cells, but metastatic potential was correlated with the expression of the laminin carbohydrate that was recognized by Griffonia (Bandeiraea) simplicifolia isolectin G4. Therefore, we investigated the relationship between carbohydrate expression profiles and metastasis and prognosis. We indeed found an intimate relationship between the carbohydrate expression of cancer cells and the progression of malignant tumors, organ preference of metastasis, metastatic potential of tumor cells, and prognosis of patients. PMID:26521885

  8. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors

    PubMed Central

    Minn, Andy J.; Kang, Yibin; Serganova, Inna; Gupta, Gaorav P.; Giri, Dilip D.; Doubrovin, Mikhail; Ponomarev, Vladimir; Gerald, William L.; Blasberg, Ronald; Massagué, Joan

    2005-01-01

    We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual cells from a population established in culture from the pleural effusion of a breast cancer patient showed distinct patterns of organ-specific metastasis. Single-cell progenies derived from this population exhibited markedly different abilities to metastasize to the bone, lung, or adrenal medulla, which suggests that metastases to different organs have different requirements. Transcriptomic profiling revealed that these different single-cell progenies similarly express a previously described “poor-prognosis” gene expression signature. Unsupervised classification using the transcriptomic data set supported the hypothesis that organ-specific metastasis by breast cancer cells is controlled by metastasis-specific genes that are separate from a general poor-prognosis gene expression signature. Furthermore, by using a gene expression signature associated with the ability of these cells to metastasize to bone, we were able to distinguish primary breast carcinomas that preferentially metastasized to bone from those that preferentially metastasized elsewhere. These results suggest that the bone-specific metastatic phenotypes and gene expression signature identified in a mouse model may be clinically relevant. PMID:15630443

  9. Cancer: The Transforming Power of Cell Competition.

    PubMed

    Gil, Jesus; Rodriguez, Tristan

    2016-02-22

    The tumour-host microenvironment plays key roles in cancer, but the mechanisms involved are not fully understood. Two new studies provide insight into this problem by showing that through cell competition, a fitness-sensing process that usually eliminates defective cells, pre-cancerous lesions signal the death of surrounding tissue that in turn promotes their neoplastic transformation. PMID:26906487

  10. Learning about Cancer by Studying Stem Cells

    MedlinePlus

    ... About Cancer by Studying Stem Cells Inside Life Science View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem ... Once Upon a Stem Cell This Inside Life Science article also appears on LiveScience . Learn about related ...

  11. New Directions for the Treatment of Adrenal Insufficiency

    PubMed Central

    Ruiz-Babot, Gerard; Hadjidemetriou, Irene; King, Peter James; Guasti, Leonardo

    2015-01-01

    Adrenal disease, whether primary, caused by defects in the hypothalamic–pituitary–adrenal (HPA) axis, or secondary, caused by defects outside the HPA axis, usually results in adrenal insufficiency, which requires lifelong daily replacement of corticosteroids. However, this kind of therapy is far from ideal as physiological demand for steroids varies considerably throughout the day and increases during periods of stress. The development of alternative curative strategies is therefore needed. In this review, we describe the latest technologies aimed at either isolating or generating de novo cells that could be used for novel, regenerative medicine application in the adrenocortical field. PMID:25999916

  12. Radioguided Adrenal Surgery

    PubMed Central

    Deus, Javier; Millera, Alfonso; Andrés, Alejandro; Prats, Enrique; Gil, Ismael; Suarez, Manuel; Salcini, José L.; Lahoz, Manuel

    2015-01-01

    Abstract The laparoscopic adrenalectomy is considered as the procedure of choice for the treatment of adrenal hyperplasia and tumor lesions. However, some special situations may limit the use of this method due to the difficulty to locate the gland and perform the lesion excision. We analyze 2 patients of a left adrenal tumor, explaining how they have overcome the difficulties in both situations. The first case was a patient with a history of intra-abdominal surgery and the other patient suffered from severe obesity. We performed with the use of the gamma probe, and the 2 cases, was of great help to access and glandular localization. The help of gamma probe test was achieved in the surgical bed, that removal was complete. The use of the portable gamma probe facilitated the access to the left adrenal gland as well as conducting the glandular excision without delay, despite the difficulties due to the intra abdominal surgery caused by the previous surgery, and in the case of severe obesity. PMID:26426608

  13. Folliculo-stellate cells - potential mediators of the inflammaging-induced hyperactivity of the hypothalamic-pituitary-adrenal axis in healthy elderly individuals.

    PubMed

    Jovanović, Ivan; Ugrenović, Slađana; Ljubomirović, Miljana; Vasović, Ljiljana; Cukuranović, Rade; Stefanović, Vladisav

    2014-10-01

    Some evidence has suggested that, with age, the hypothalamic-pituitary-adrenal (HPA) axis becomes less resilient, leading to higher glucocorticoids nocturnal levels and a flattening of the circadian profiles. Such age-related changes in the activity of the HPA axis has overexposed the brain and peripheral organs to the effects of the glucocorticoids, increasing the morbidity and mortality rates of the elderly. Debate among scientists regarding the contributions of HPA axis age-related changes of impaired feedback regulation vs. direct overactivation persists. Supporters of impaired feedback regulation assumed that this effect might be the consequence of the hippocampal age-related neuronal loss and the reduction of the number of mineralocorticoid and glucocorticoid receptors. On the other hand, healthy elderly individuals are characterized by an increase of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, and the development of a chronic low-grade inflammatory state, known as inflammaging. Cytokines central to inflammaging send signals to the brain, activate HPA axis, and, by increased cortisol secretion, down-regulate inflammaging in a process known as anti-inflammaging. Even as these cytokines act at the level of the hypothalamic paraventricular nucleus, they are hampered by the intact blood-brain barrier. Further, the corticotropes in the anterior pituitary do not express cytokine receptors, and the density of folliculo-stellate cells generally increases with age. Therefore, we assumed that folliculo-stellate cells were the target structures through which the elevated levels of cytokines, as a part of the inflammaging phenomenon, would cause the overactivation of the HPA axis in healthy elderly individuals. Folliculo-stellate cells are non-endocrine cells that were originally considered to act as supporting cells for the endocrine cells. Despite the fact that FS cells do not produce any of the established hormones of the anterior pituitary, they

  14. Response of Breast Cancer Cells and Cancer Stem Cells to Metformin and Hyperthermia Alone or Combined

    PubMed Central

    Lee, Hyemi; Park, Heon Joo; Park, Chang-Shin; Oh, Eun-Taex; Choi, Bo-Hwa; Williams, Brent; Lee, Chung K.; Song, Chang W.

    2014-01-01

    Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5–10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44high/CD24low cells of MCF-7 cells and, CD44high/CD24high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs) of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia. PMID:24505341

  15. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    PubMed Central

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

    2014-01-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  16. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland.

    PubMed

    Slominski, Andrzej T; Kim, Tae-Kang; Shehabi, Haleem Z; Tang, Edith K Y; Benson, Heather A E; Semak, Igor; Lin, Zongtao; Yates, Charles R; Wang, Jin; Li, Wei; Tuckey, Robert C

    2014-03-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)₂D2, 1,20(OH)₂D2, 25(OH)D2 and 1,25(OH)₂D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)₂D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)₂D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  17. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  18. Breast cancer stem cells and radiation

    NASA Astrophysics Data System (ADS)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1

  19. Dendritic cell-based cancer immunotherapy for colorectal cancer

    PubMed Central

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  20. The Role of gsp Mutations on the Development of Adrenocortical Tumors and Adrenal Hyperplasia

    PubMed Central

    Villares Fragoso, Maria Candida Barisson; Wanichi, Ingrid Quevedo; Cavalcante, Isadora Pontes; Mariani, Beatriz Marinho de Paula

    2016-01-01

    Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune–Albright syndrome (MAS) and have also been described in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma, thyroid cancer, ovarian and testicular Leydig cell tumors, and primary macronodular adrenocortical hyperplasia (PMAH) (1–3). The involvement of gsp mutations in adrenal tumors was first described by Lyons et al. Since then, several studies have detected the presence of gsp mutations in adrenal tumors, but none of them could explain its presence along or the mechanism that leads to tumor formation and hormone hypersecretion. As a result, the molecular pathogenesis of the majority of sporadic adrenocortical tumors remains unclear (3). PMAH has also been reported with gsp somatic mutations in a few cases. Fragoso et al. identified two distinct gsp somatic mutations affecting arginine residues on codon 201 of GNAS in a few patients with PMAH who lacked any features or manifestations of MAS. Followed by this discovery, other studies have continued looking for gsp mutations based on strong prior evidence demonstrating that increased cAMP signaling is sufficient for cell proliferation and cortisol production (2, 4). With consideration for the previously reported findings, we conjecture that although somatic activating mutations in GNAS are a rare molecular event, these mutations could probably be sufficient to induce the development of macronodule hyperplasia and variable cortisol secretion. In this manuscript, we revised the presence of gsp mutations associated with adrenal cortical tumors and hyperplasia. PMID:27512387

  1. Wnt and the Cancer Niche: Paracrine Interactions with Gastrointestinal Cancer Cells Undergoing Asymmetric Cell Division

    PubMed Central

    Xin, Hong-Wu; Ambe, Chenwi M.; Ray, Satyajit; Kim, Bo-Kyu; Koizumi, Tomotake; Wiegand, Gordon W.; Hari, Danielle; Mullinax, John E.; Jaiswal, Kshama R.; Garfield, Susan H.; Stojadinovic, Alexander; Rudloff, Udo; Thorgeirsson, Snorri S.; Avital, Itzhak

    2013-01-01

    Objective: Stem-like cancer cells contribute to cancer initiation and maintenance. Stem cells can self-renew by asymmetric cell division (ACD). ACD with non-random chromosomal cosegregation (ACD-NRCC) is one possible self-renewal mechanism. There is a paucity of evidence supporting ACD-NRCC in human cancer. Our aim was to investigate ACD-NRCC and its potential interactions with the cancer niche (microenvironment) in gastrointestinal cancers. Design: We used DNA double and single labeling approaches with FACS to isolate live cells undergoing ACD-NRCC. Results: Gastrointestinal cancers contain rare subpopulations of cells capable of ACD-NRCC. ACD-NRCC was detected preferentially in subpopulations of cells previously suggested to be stem-like/tumor-initiating cancer cells. ACD-NRCC was independent of cell-to-cell contact, and was regulated by the cancer niche in a heat-sensitive paracrine fashion. Wnt pathway genes and proteins are differentially expressed in cells undergoing ACD-NRCC vs. symmetric cell division. Blocking the Wnt pathway with IWP2 (WNT antagonist) or siRNA-TCF4 resulted in suppression of ACD-NRCC. However, using a Wnt-agonist did not increase the relative proportion of cells undergoing ACD-NRCC. Conclusion: Gastrointestinal cancers contain subpopulations of cells capable of ACD-NRCC. Here we show for the first time that ACD-NRCC can be regulated by the Wnt pathway, and by the cancer niche in a paracrine fashion. However, whether ACD-NRCC is exclusively associated with stem-like cancer cells remains to be determined. Further study of these findings might generate novel insights into stem cell and cancer biology. Targeting the mechanism of ACD-NRCC might engender novel approaches for cancer therapy. PMID:23901343

  2. Adrenal Metastasis from Uterine Papillary Serous Carcinoma

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara

    2016-01-01

    Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  3. Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

    SciTech Connect

    Lohr, E.; Leder, L.D.

    1987-01-01

    Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgical Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.

  4. Outcome and Prognostic Factors After Adrenalectomy for Patients with Distant Adrenal Metastasis

    PubMed Central

    Howell, Gina M.; Carty, Sally E.; Armstrong, Michaele J.; Stang, Michael T.; McCoy, Kelly L.; Bartlett, David L.; Yip, Linwah

    2016-01-01

    Purpose To describe a single institution experience with adrenal metastasectomy, and to elucidate factors that may bear prognostic significance. Methods Single center, retrospective review of patients with adrenal metastasis who underwent adrenalectomy performed with curative intent between 2000–2012. Kaplan-Meier method was utilized to evaluate overall survival from time of adrenalectomy to death or last follow-up. Primary endpoint was death from any cause. Clinical variables were examined for association with survival. Results Study included 62 patients with mean age of 60 (± 12) years. 55% (34/62) were male, 85% (53/62) presented with isolated adrenal metastasis, and 82% (51/62) had metachronous disease with median DFI of 22 months (range 6–217). Non-small cell lung cancer (NSCLC) was the most common primary comprising 50% of cases. Median survival for the study population was 30 months (range 1–145) and 5-year survival was 31%. Patients with NSCLC had significantly shortened survival compared to non-NSCLC with median and 5-yr survival of 17 vs. 47 months and 27% vs. 38%, respectively (p=0.033). Synchronous metastasis (p=0.028) and DFI <12 months (p=0.038) were also associated with worse survival outcome, though male gender (p=0.69) and oligometastatic disease (p=0.62) were not. Conclusion Adrenal metastasectomy resulted in median survival of 30 months and 5-year survival of 31%. Shorter survival was associated with lung primary, short disease-free interval, and synchronous metastasis, but not with the presence of oligometastatic disease provided that the primary cancer and additional metastatic lesions were adequately controlled and amenable to resection. PMID:23793361

  5. Adrenal imaging with technetium-99m-labelled low density lipoproteins

    SciTech Connect

    Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Strauss, H.W.; Barlai-Kovach, M.; Moore, T.J.

    1986-04-01

    Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of /sup 99m/Tc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of /sup 99m/Tc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with /sup 99m/Tc, can be used to evaluate adrenal cortical function by external imaging.

  6. Non-Functional Adrenal Gland Ganglioneuroma Masquerading as Chronic Calculus Cholecystitis.

    PubMed

    Patel, Rashmi D; Vanikar, Aruna V; Trivedi, H L

    2015-09-01

    Adrenal ganglioneuromas in young adults are rare and ill-understood. We report an incidentally detected adrenal gland tumor diagnosed as ganglioneuroma (mature type) in 33 years old man who presented with vomiting and epigastric pain for 2 months. Histopathology examination revealed a well-encapsulated benign tumor of mature ganglion cells and Schwann-like cells arranged in fascicles, staining strongly with NSE and s-100 proteins, with adjacent unremarkable adrenal cortex and medulla. PMID:27608876

  7. Cancer Stem Cells in the Thyroid

    PubMed Central

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  8. Therapeutic strategies targeting cancer stem cells

    PubMed Central

    Ning, Xiaoyan; Shu, Jianchang; Du, Yiqi; Ben, Qiwen; Li, Zhaoshen

    2013-01-01

    Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy. PMID:23358473

  9. Cell Fate Decisions During Breast Cancer Development

    PubMed Central

    Gross, Kayla; Wronski, Ania; Skibinski, Adam; Phillips, Sarah; Kuperwasser, Charlotte

    2016-01-01

    During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we review how initial genetic or epigenetic alterations within mammary epithelial cells (MECs) can alter cell fate decisions and put pre-malignant cells on a path towards cancer development with specific phenotypes. Understanding the early stages of breast cancer initiation and progression and how normal developmental processes are hijacked during transformation has significant implications for improving early detection and prevention of breast cancer. In addition, insights gleaned from this understanding may also be important for developing subtype-specific treatment options. PMID:27110512

  10. Therapeutic strategies targeting cancer stem cells.

    PubMed

    Ning, Xiaoyan; Shu, Jianchang; Du, Yiqi; Ben, Qiwen; Li, Zhaoshen

    2013-04-01

    Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy. PMID:23358473

  11. Cancer Stem Cells in the Thyroid.

    PubMed

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  12. Ultrasound Effect on Cancerous versus Non-Cancerous Cells.

    PubMed

    Azagury, Aharon; Amar-Lewis, Eliz; Yudilevitch, Yana; Isaacson, Carol; Laster, Brenda; Kost, Joseph

    2016-07-01

    Previous studies have found that cancer cells whose metastatic potential is low are more vulnerable to mechanical stress-induced trauma to their cytoskeleton compared with benign cells. Because ultrasound induces mechanical stresses on cells and tissues, it is postulated that there may be a way to apply ultrasound to tumors to reduce their ability to metastasize. The difference between low-malignant-potential cancer cells and benign cells could be a result of their different responses to the mechanical stress insonation induced. This hypothesis was tested in vitro and in vivo. Low-malignant-potential cells were found to be more sensitive to insonation, resulting in a significantly higher mortality rate compared with that of benign cells, 89% versus 21%, respectively. This effect can be controlled by varying ultrasound parameters: intensity, duration, and duty cycle. Thus, the results presented in this study suggest the application of ultrasound to discriminate between benign and malignant cells. PMID:27067417

  13. Cancer stem cells in multiple myeloma.

    PubMed

    Ghosh, Nilanjan; Matsui, William

    2009-05-01

    Several key observations providing evidence for the cancer stem cell hypothesis and insights into the unique biology of these cells have come from the study of multiple myeloma. These include evidence that cancer cells may be functionally heterogeneous in spite of their genetic homogeneity and that malignant progenitors share many biological features with normal adult stem cells including drug resistance and regulatory processes governing self-renewal. We review studies that have examined clonogenic cells in multiple myeloma, highlight controversies regarding the cell of origin in multiple myeloma, and discuss potential targeting strategies. PMID:18809245

  14. Hallmarks of cancer stem cell metabolism

    PubMed Central

    Sancho, Patricia; Barneda, David; Heeschen, Christopher

    2016-01-01

    Cancer cells adapt cellular metabolism to cope with their high proliferation rate. Instead of primarily using oxidative phosphorylation (OXPHOS), cancer cells use less efficient glycolysis for the production of ATP and building blocks (Warburg effect). However, tumours are not uniform, but rather functionally heterogeneous and harbour a subset of cancer cells with stemness features. Such cancer cells have the ability to repopulate the entire tumour and thus have been termed cancer stem cells (CSCs) or tumour-initiating cells (TICs). As opposed to differentiated bulk tumour cells relying on glycolysis, CSCs show a distinct metabolic phenotype that, depending on the cancer type, can be highly glycolytic or OXPHOS dependent. In either case, mitochondrial function is critical and takes centre stage in CSC functionality. Remaining controversies in this young and emerging research field may be related to CSC isolation techniques and/or the use of less suitable model systems. Still, the apparent dependence of CSCs on mitochondrial function, regardless of their primary metabolic phenotype, represents a previously unrecognised Achilles heel amendable for therapeutic intervention. Elimination of highly chemoresistant CSCs as the root of many cancers via inhibition of mitochondrial function bears the potential to prevent relapse from disease and thus improve patients' long-term outcome. PMID:27219018

  15. Hallmarks of cancer stem cell metabolism.

    PubMed

    Sancho, Patricia; Barneda, David; Heeschen, Christopher

    2016-06-14

    Cancer cells adapt cellular metabolism to cope with their high proliferation rate. Instead of primarily using oxidative phosphorylation (OXPHOS), cancer cells use less efficient glycolysis for the production of ATP and building blocks (Warburg effect). However, tumours are not uniform, but rather functionally heterogeneous and harbour a subset of cancer cells with stemness features. Such cancer cells have the ability to repopulate the entire tumour and thus have been termed cancer stem cells (CSCs) or tumour-initiating cells (TICs). As opposed to differentiated bulk tumour cells relying on glycolysis, CSCs show a distinct metabolic phenotype that, depending on the cancer type, can be highly glycolytic or OXPHOS dependent. In either case, mitochondrial function is critical and takes centre stage in CSC functionality. Remaining controversies in this young and emerging research field may be related to CSC isolation techniques and/or the use of less suitable model systems. Still, the apparent dependence of CSCs on mitochondrial function, regardless of their primary metabolic phenotype, represents a previously unrecognised Achilles heel amendable for therapeutic intervention. Elimination of highly chemoresistant CSCs as the root of many cancers via inhibition of mitochondrial function bears the potential to prevent relapse from disease and thus improve patients' long-term outcome. PMID:27219018

  16. Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-12-16

    Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  17. Cancer stem cells in head and neck cancer.

    PubMed

    Allegra, Eugenia; Trapasso, Serena

    2012-01-01

    Cancer stem cells (CSCs), also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal), giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division). A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on the presence of specific surface markers for selective cytotoxic agent vehicles. Finally, some research groups are trying to induce these cells to

  18. Ca2+ and K+ channels of normal human adrenal zona fasciculata cells: properties and modulation by ACTH and AngII.

    PubMed

    Enyeart, John J; Enyeart, Judith A

    2013-08-01

    In whole cell patch clamp recordings, we found that normal human adrenal zona fasciculata (AZF) cells express voltage-gated, rapidly inactivating Ca(2+) and K(+) currents and a noninactivating, leak-type K(+) current. Characterization of these currents with respect to voltage-dependent gating and kinetic properties, pharmacology, and modulation by the peptide hormones adrenocorticotropic hormone (ACTH) and AngII, in conjunction with Northern blot analysis, identified these channels as Cav3.2 (encoded by CACNA1H), Kv1.4 (KCNA4), and TREK-1 (KCNK2). In particular, the low voltage-activated, rapidly inactivating and slowly deactivating Ca(2+) current (Cav3.2) was potently blocked by Ni(2+) with an IC50 of 3 µM. The voltage-gated, rapidly inactivating K(+) current (Kv1.4) was robustly expressed in nearly every cell, with a current density of 95.0 ± 7.2 pA/pF (n = 64). The noninactivating, outwardly rectifying K(+) current (TREK-1) grew to a stable maximum over a period of minutes when recording at a holding potential of -80 mV. This noninactivating K(+) current was markedly activated by cinnamyl 1-3,4-dihydroxy-α-cyanocinnamate (CDC) and arachidonic acid (AA) and inhibited almost completely by forskolin, properties which are specific to TREK-1 among the K2P family of K(+) channels. The activation of TREK-1 by AA and inhibition by forskolin were closely linked to membrane hyperpolarization and depolarization, respectively. ACTH and AngII selectively inhibited the noninactivating K(+) current in human AZF cells at concentrations that stimulated cortisol secretion. Accordingly, mibefradil and CDC at concentrations that, respectively, blocked Cav3.2 and activated TREK-1, each inhibited both ACTH- and AngII-stimulated cortisol secretion. These results characterize the major Ca(2+) and K(+) channels expressed by normal human AZF cells and identify TREK-1 as the primary leak-type channel involved in establishing the membrane potential. These findings also suggest a model

  19. Cell Senescence: Aging and Cancer

    ScienceCinema

    Campisi, Judith

    2013-05-29

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  20. Cell Senescence: Aging and Cancer

    SciTech Connect

    Campisi, Judith

    2008-01-01

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  1. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    NASA Astrophysics Data System (ADS)

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-08-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and supporting experiments suggest that there exist non-linear growth kinetics of CSCs and negative feedback mechanisms to control the balance between the population of CSCs and that of non-stem cancer cells. The model predictions can help us explain a few long-standing questions in the field of cancer stem cell research, and can be potentially used to predict the efficicacy of anti-cancer therapy.

  2. Understanding cellular architecture in cancer cells

    NASA Astrophysics Data System (ADS)

    Bianco, Simone; Tang, Chao

    2011-03-01

    Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies.

  3. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  4. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia T.

    2015-10-01

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  5. Adrenal myelolipoma, cholelithiasis and calcified spleen: retrospective diagnosis of sickle cell anemia using a novel triad of abdominal imaging findings.

    PubMed

    Jakhere, Sandeep G; Kumbhar, Raju S; Dhongade, Harshal V

    2014-04-01

    Sickle cell anemia is an inherited abnormality of the globin chain with very high prevalence in the Indian subcontinent. A significant proportion of these patients present late in life and are at a risk of complications like acute chest syndrome and painful episodes till a definitive diagnosis is reached and appropriate treatment is started . We report a novel triad of abdominal imaging findings which is not reported in literature until now and which may suggest a diagnosis of sickle cell anemia in retrospect. Patients with this triad of abdominal findings should be suspected to have an underlying hemoglobinopathy and should be referred for further hematological workup. Although in our case the patient was diagnosed to have sickle cell anemia depending on the abnormal morphology of red cells and hemoglobin electrophoresis, it should be remembered that this triad of findings may be seen in other hemoglobinopathies which induce a state of chronic anemia. PMID:25053687

  6. Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high-density diamond ultra-microelectrode arrays

    PubMed Central

    Gosso, Sara; Turturici, Marco; Franchino, Claudio; Colombo, Elisabetta; Pasquarelli, Alberto; Carbone, Emilio; Carabelli, Valentina

    2014-01-01

    Here we describe the ability of a high-density diamond microelectrode array targeted to resolve multi-site detection of fast exocytotic events from single cells. The array consists of nine boron-doped nanocrystalline diamond ultra-microelectrodes (9-Ch NCD-UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose–response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl-enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9-Ch NCD-UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12–27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The ‘non-active’ (‘silent’) zones covered 24% of the total and persisted for 6–8 min, indicating stable location. The 9-Ch NCD-UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution. PMID:24879870

  7. Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high-density diamond ultra-microelectrode arrays.

    PubMed

    Gosso, Sara; Turturici, Marco; Franchino, Claudio; Colombo, Elisabetta; Pasquarelli, Alberto; Carbone, Emilio; Carabelli, Valentina

    2014-08-01

    Here we describe the ability of a high-density diamond microelectrode array targeted to resolve multi-site detection of fast exocytotic events from single cells. The array consists of nine boron-doped nanocrystalline diamond ultra-microelectrodes (9-Ch NCD-UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose-response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl-enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9-Ch NCD-UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12-27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The 'non-active' ('silent') zones covered 24% of the total and persisted for 6-8 min, indicating stable location. The 9-Ch NCD-UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution. PMID:24879870

  8. Stem cells and cancer: an overview.

    PubMed

    Sales, Kevin M; Winslet, Marc C; Seifalian, Alexander M

    2007-12-01

    Definite evidence of the importance of cancer stem cells in the progression of cancer has now come to light. Key markers of these cells have been identified in many solid tumours as well as leukaemias. Specific studies modelling the tumour induction of specific cells isolated by surface antigens such as CD44 have demonstrated that these cells are not only present in tumours but that they are the key units in their tumourgenecity. These findings provide useful insight for disease progression, treatment and metastasis. The wide variety of proposed markers, and their similarity to endothelial progenitor cells found in angiogenesis, complicates these studies. Definite proof falls only in the induction of tumours in vivo. Here we review the developments in cancer stem cells and the markers that have been found for these cells. PMID:17955391

  9. Cell Polarity Proteins in Breast Cancer Progression.

    PubMed

    Rejon, Carlis; Al-Masri, Maia; McCaffrey, Luke

    2016-10-01

    Breast cancer, one of the leading causes of cancer related death in women worldwide, is a heterogeneous disease with diverse subtypes that have different properties and prognoses. The developing mammary gland is a highly proliferative and invasive tissue, and some of the developmental programs may be aberrantly activated to promote breast cancer progression. In the breast, luminal epithelial cells exhibit apical-basal polarity, and the failure to maintain this organizational structure, due to disruption of polarity complexes, is implicated in promoting hyperplasia and tumors. Therefore, understanding the mechanisms underlying loss of polarity will contribute to our knowledge of the early stages leading to the pathogenesis of the disease. In this review, we will discuss recent findings that support the idea that loss of apical-basal cell polarity is a crucial step in the acquisition of the malignant phenotype. Oncogene induced loss of tissue organization shares a conserved cellular mechanism with developmental process, we will further describe the role of the individual polarity complexes, the Par, Crumbs, and Scribble, to couple cell division orientation and cell growth. We will examine symmetric or asymmetric cell divisions in mammary stem cell and their contribution to the development of breast cancer subtypes and cancer stem cells. Finally, we will highlight some of the recent advances in our understanding of the molecular mechanisms by which changes in epithelial polarity programs promote invasion and metastasis through single cell and collective cell modes. J. Cell. Biochem. 117: 2215-2223, 2016. © 2016 Wiley Periodicals, Inc. PMID:27362918

  10. Identifying cancer origin using circulating tumor cells

    PubMed Central

    Lu, Si-Hong; Tsai, Wen-Sy; Chang, Ying-Hsu; Chou, Teh-Ying; Pang, See-Tong; Lin, Po-Hung; Tsai, Chun-Ming; Chang, Ying-Chih

    2016-01-01

    ABSTRACT Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK+ and CK18+ CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7+ or TTF-1+, (CK20/ CDX2)+, or (PSA/ PSMA)+ corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID:26828696

  11. Identifying cancer origin using circulating tumor cells.

    PubMed

    Lu, Si-Hong; Tsai, Wen-Sy; Chang, Ying-Hsu; Chou, Teh-Ying; Pang, See-Tong; Lin, Po-Hung; Tsai, Chun-Ming; Chang, Ying-Chih

    2016-04-01

    Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK(+) and CK18(+) CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7(+) or TTF-1(+), (CK20/ CDX2)(+), or (PSA/ PSMA)(+) corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID:26828696

  12. Adrenal hemangioma: a case report.

    PubMed

    Auh, Y H; Anand, J; Zirinsky, K; Kazam, E

    1986-01-01

    Adrenal hemangioma is a very rare tumor. Presented is the 18th case proved by autopsy or surgery reported in world literature. The tumor was incidentally discovered at autopsy. Unless this tumor has characteristic calcifications, phlebolith or phlebolithlike, its computed tomography appearance is nonspecific. Therefore, by computed tomography this tumor cannot be differentiated from other primary or secondary adrenal tumors. PMID:3943357

  13. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    SciTech Connect

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  14. Signaling in colon cancer stem cells.

    PubMed

    Roy, Sanchita; Majumdar, Adhip Pn

    2012-01-01

    : Colorectal cancer is the fourth most common form of cancer worldwide and ranks third among the cancer-related deaths in the US and other Western countries. It occurs with equal frequency in men and women, constituting 10% of new cancer cases in men and 11% in women. Despite recent advancement in therapeutics, the survival rates from metastatic are less than 5%. Growing evidence supports the contention that epithelial cancers including colorectal cancer, the incidence of which increases with aging, are diseases driven by the pluripotent, self-renewing cancer stem cells (CSCs). Dysregulation of Wnt, Notch, Hedgehog and/or TGF-β signaling pathways that are involved in proliferation and maintenance of CSCs leads to the development of CRC. This review focuses on the signaling pathways relevant for CRC to understand the mechanisms leading to tumor progression and therapy resistance, which may help in the development of therapeutic strategies for CRC. PMID:22866952

  15. Targeting natural killer cells in cancer immunotherapy.

    PubMed

    Guillerey, Camille; Huntington, Nicholas D; Smyth, Mark J

    2016-08-19

    Alteration in the expression of cell-surface proteins is a common consequence of malignant transformation. Natural killer (NK) cells use an array of germline-encoded activating and inhibitory receptors that scan for altered protein-expression patterns, but tumor evasion of detection by the immune system is now recognized as one of the hallmarks of cancer. NK cells display rapid and potent immunity to metastasis or hematological cancers, and major efforts are now being undertaken to fully exploit NK cell anti-tumor properties in the clinic. Diverse approaches encompass the development of large-scale NK cell-expansion protocols for adoptive transfer, the establishment of a microenvironment favorable to NK cell activity, the redirection of NK cell activity against tumor cells and the release of inhibitory signals that limit NK cell function. In this Review we detail recent advances in NK cell-based immunotherapies and discuss the advantages and limitations of these strategies. PMID:27540992

  16. ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells

    SciTech Connect

    Colonna, Cecilia . E-mail: ccolonna@fmed.uba.ar; Podesta, Ernesto J.

    2005-04-01

    Y1 adrenocortical cells respond to ACTH with a characteristic rounding-up that facilitates cAMP signaling, critical for transport of cholesterol to the mitochondria and increase in steroid secretion. We here demonstrate that caveolin-1 participates in coupling activation of protein kinase A (PKA) to the control of cell shape. ACTH/8-Br-cAMP induced reorganization of caveolin-1-positive structures in correlation with the cellular rounding-up. Concomitant with this change, there was an increase in the phosphorylation of caveolin-1 (Tyr-14) localized at focal adhesions (FA) with reorganization of FA to rounded, ringlike structures. Colocalization with phalloidin showed that phosphocaveolin is present at the edge of actin filaments and that after ACTH stimulation F-actin dots at the cell periphery become surrounded by phosphocaveolin-1. These observations along with electron microscopy studies revealed these structures as podosomes. Podosome assembly was dependent on both PKA and tyrosine kinase activities because their formation was impaired after treatment with specific inhibitors [myristoylated PKI (mPKI) or PP2, respectively] previous to ACTH/8-Br-cAMP stimulation. These results show for the first time that ACTH induces caveolin-1 phosphorylation and podosome assembly in Y1 cells and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are related to cytoskeleton dynamics.

  17. Gene sensitizes cancer cells to chemotherapy drugs

    Cancer.gov

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  18. Measuring the metastatic potential of cancer cells

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.; Gratzner, Howard; Atassi, M. Z.

    1993-01-01

    Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

  19. Endothelial metabolism of angiotensin II to angiotensin III, not angiotensin (1-7), augments the vasorelaxation response in adrenal cortical arteries.

    PubMed

    Kopf, Phillip G; Campbell, William B

    2013-12-01

    Hyperaldosteronism is linked to the development and progression of several different cardiovascular diseases. Angiotensin (Ang) II increases aldosterone secretion and adrenal blood flow. Ang II peptide fragments are produced by various peptidases, and these Angs have diverse and vital physiologic roles. Due to the uncharacteristic vasorelaxation of adrenal arteries by Ang II, we tested the hypothesis that Ang II metabolism contributes to its relaxant activity in adrenal arteries. Metabolism of Angs by bovine adrenal cortical arteries and isolated bovine adrenal vascular cells was measured by liquid chromatography-mass spectrometry. The primary Ang metabolites of adrenal arteries are Ang III and Ang (1-7), with Ang IV produced to a lesser extent. Bovine microvascular endothelial cells produced a similar metabolic profile to adrenal arteries, whereas bovine adrenal artery smooth muscle cells exhibited less metabolism. In preconstricted adrenal arteries, Ang II caused relaxation in picomolar concentrations and constrictions at 10nM. Ang-converting enzyme 2 inhibition augmented this relaxation response, whereas aminopeptidase inhibition did not. Ang III was equipotent to Ang II in relaxing adrenal arteries. Ang IV did not cause relaxation. Nitric oxide synthase inhibition enhanced Ang II-induced constriction of adrenal arteries. Aminopeptidase inhibition increased the concentration range for Ang II-induced constriction of adrenal arteries. Ang III and Ang IV did not change the basal tone but caused constriction of adrenal arteries with nitric oxide synthase inhibition. These data indicate that Ang II metabolism modulates the vascular effects of Ang II in the adrenal vasculature. PMID:24092640

  20. Enhanced Ca(2+)-induced Ca(2+) release from intracellular stores contributes to catecholamine hypersecretion in adrenal chromaffin cells from spontaneously hypertensive rats.

    PubMed

    Segura-Chama, Pedro; López-Bistrain, Patricia; Pérez-Armendáriz, Elia Martha; Jiménez-Pérez, Nicolás; Millán-Aldaco, Diana; Hernández-Cruz, Arturo

    2015-11-01

    Adrenal chromaffin cells (CCs) from spontaneously hypertensive rats (SHRs) secrete more catecholamine (CA) upon stimulation than CCs from normotensive Wistar Kyoto rats (WKY). Unitary CA exocytosis events, both spontaneous and stimulated, were amperometrically recorded from cultured WKY and SHR CCs. Both strains display spontaneous amperometric spikes but SHR CCs produce more spikes and of higher mean amplitude. After a brief stimulation with high K(+) or caffeine which produces voltage-gated Ca(2+) influx or intracellular Ca(2+) release, respectively, more spikes and of greater mean amplitude and unitary charge were recorded in SHR CCs. Consequently, peak cumulative charge was ~2-fold higher in SHR CCs. Ryanodine (10 μM), a specific blocker of the ryanodine receptors reduced depolarization-induced peak cumulative charge by ~10 % in WKY and ~77 % in SHR CCs, suggesting, a larger contribution of Ca(2+)-induced Ca(2+) release to CA exocytosis in SHR CCs. Accordingly, Ca(2+) imaging showed larger [Ca(2+)]i signals induced both by depolarization and caffeine in SHR CCs. Distribution amplitude histograms showed that small amperometric spikes (0-50 pA) are more frequent in WKY than in SHR CCs. Conversely, medium (50-190 pA) and large (190-290 pA) spikes are more numerous in SHR than in WKY CCs. This study reveals that the enhanced CA secretion in SHR CCs results from a combination of (1) larger depolarization-induced Ca(2+) transients, due to a greater Ca(2+)-induced intracellular Ca(2+) release, (2) more exocytosis events per time unit, and (3) a greater proportion of medium and large amperometric spikes probably due to a higher mean CA content per granule. Enhanced CA release by excessive amplification by Ca(2+) induced Ca(2+) release and larger granule catecholamine content contributes to the increased CA plasma levels and vasomotor tone in SHRs. PMID:25791627

  1. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  2. FOXA1 defines cancer cell specificity

    PubMed Central

    Zhang, Gaihua; Zhao, Yongbing; Liu, Yi; Kao, Li-Pin; Wang, Xiao; Skerry, Benjamin; Li, Zhaoyu

    2016-01-01

    A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a “flower-blooming” hypothesis for cell-specific transcriptional regulation based on these observations. PMID:27034986

  3. Cancer stem cells: progress and challenges in lung cancer

    PubMed Central

    Templeton, Amanda K.; Miyamoto, Shinya; Babu, Anish; Munshi, Anupama

    2014-01-01

    The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called “cancer stem cells” (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs.

  4. Printing Cancer Cells into Intact Microvascular Networks: A Model for Investigating Cancer Cell Dynamics during Angiogenesis

    PubMed Central

    Phamduy, Theresa B.; Sweat, Richard S.; Azimi, Mohammad S.; Burow, Matthew E.; Murfee, Walter L.; Chrisey, Douglas B.

    2016-01-01

    While cancer cell invasion and metastasis is dependent on cancer cell-stroma, cancer cell-blood vessel, and cancer cell-lymphatic vessel interactions, our understanding of these interactions remain largely unknown. A need exists for physiologically-relevant models that more closely mimic the complexity of cancer cell dynamics in a real tissue environment. The objective of this study was to combine laser-based cell printing and tissue culture methods to create a novel ex vivo model in which cancer cell dynamics can be tracked during angiogenesis in an intact microvascular network. Laser direct-write (LDW) was utilized to reproducibly deposit breast cancer cells (MDA-MB-231 and MCF-7) and fibroblasts into spatially-defined patterns on cultured rat mesenteric tissues. In addition, heterogeneous patterns containing co-printed MDA-MB-231/fibroblasts or MDA-MB-231/MCF-7 cells were generated for fibroblast-directed and collective cell invasion models. Printed cells remained viable and the cells retained the ability to proliferate in serum-rich media conditions. Over a culture period of five days, time-lapse imaging confirmed fibroblast and MDA-MB-231 cell migration within the microvascular networks. Confocal microscopy indicated that printed MDA-MB-231 cells infiltrated the tissue thickness and were capable of interacting with endothelial cells. Angiogenic network growth in tissue areas containing printed cancer cells was characterized by significantly increased capillary sprouting compared to control tissue areas containing no printed cells. Our results establish an innovative ex vivo experimental platform that enables time-lapse evaluation of cancer cell dynamics during angiogenesis within a real microvascular network scenario. PMID:26190039

  5. Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors

    PubMed Central

    Pilon, Catia; Rebellato, Andrea; Urbanet, Riccardo; Guzzardo, Vincenza; Cappellesso, Rocco; Sasano, Hironobu; Fassina, Ambrogio

    2015-01-01

    We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis. PMID:26843863

  6. A Case Report of Adrenocortical Adenoma Mimicking Congenital Adrenal Hyperplasia in a Young Girl.

    PubMed

    Sheng, Qingfeng; Lv, Zhibao; Xu, Weijue; Liu, Jiangbin; Wu, Yibo; Xi, Zhengjun

    2015-06-01

    Adrenal cortical tumors are rare in children. Secondary tumors associated with untreated congenital adrenal hyperplasia (CAH) have also been reported in pediatric population. It is difficult for pediatricians to differentiate these 2 lesions.We described a 4.5-year-old girl who presented with symptoms and signs of virilization. Bone age was 9.5 years. Genetic analysis of CYP21A2 and CYP11B1 revealed a heterozygous mutation of CYP11B1 at c.1157C>T (A386V). No germline p53 gene mutation including R337H was detected.The patient was first misdiagnosed as CAH and treated with hydrocortisone for 3 months. Diagnosis of an adrenal cortical tumor was confirmed by laboratory data and abdominal computed tomography. After resection of the tumor, serum steroids normalized and clinical signs receded. The child received no additional treatment and remains disease free after 12 months of close observation. Histological examination showed neoplasia cells with predominantly eosinophilic cytoplasm and few atypical mitotic figures. The proliferation-associated Ki-67 index was <1% detected by immunohistochemistry.Neoplasm is a rare but significant cause of precocious puberty (PP). The possibility of neoplasms should always be considered early to avoid delayed cancer diagnosis and treatment in cases of PP. PMID:26107677

  7. Adrenal function testing.

    PubMed

    Dluhy, R G

    1978-12-01

    Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis. PMID:216524

  8. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    PubMed Central

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM’s cancer biology. PMID:27148537

  9. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme.

    PubMed

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T; Peng, Lifeng; Davis, Paul F; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM's cancer biology. PMID:27148537

  10. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  11. Follicular cell-derived thyroid cancer.

    PubMed

    Dralle, Henning; Machens, Andreas; Basa, Johanna; Fatourechi, Vahab; Franceschi, Silvia; Hay, Ian D; Nikiforov, Yuri E; Pacini, Furio; Pasieka, Janice L; Sherman, Steven I

    2015-01-01

    Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health-related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies. PMID:27188261

  12. Diagnostic dilemmas in enlarged and diffusely hemorrhagic adrenal glands.

    PubMed

    Diolombi, Mairo L; Khani, Francesca; Epstein, Jonathan I

    2016-07-01

    We have noted an increasing number of cases of enlarged adrenal glands where the underlying diagnosis was masked by a diffusely hemorrhagic process. We identified from our database 59 cases (32 consults, 27 routine) of adrenal glands with diffuse (>25%) hemorrhage received between 2000 and 2014. Fifty-three adrenalectomies and 6 biopsies were identified. The diagnoses after central review were 41 adrenocortical adenomas, 1 nodular adrenocortical hyperplasia with associated myelolipoma, 1 benign adrenocortical cyst, and 10 nonneoplastic adrenal glands with hemorrhage. A definitive diagnosis for the 6 biopsies was precluded by the sample size. The adrenocortical adenomas (size, 1-13 cm; 25%-95% hemorrhage) showed clear cell change in the neoplastic area (10%-80% of the tumor), 19 showed focal calcification (1 with ossification), 11 showed areas of papillary endothelial hyperplasia, 10 showed scattered lymphoplasmacytic inflammation, 6 showed benign cortical tissue extending beyond the adrenal capsule into soft tissue, 1 showed necrosis in the form of ghost cells, 2 showed lipomatous change, and 6 were associated with incidental benign lesions (1 cortical cyst, 1 schwannoma, and 4 myelolipomas). Twenty-four of the adrenocortical adenomas were consults where the referring pathologist had trouble classifying the lesion. Of the 10 nonneoplastic adrenals (4.5-22 cm; 40%-80% hemorrhage), 2 were consults. In summary, pathologists have difficulties recognizing adrenocortical adenomas in the setting of a massively enlarged and hemorrhagic adrenal gland. Although there is a correlation between adrenocortical malignancy and size, hemorrhage into nonmalignant adrenal glands can result in markedly enlarged adrenals. PMID:27001431

  13. Natural flavonoids targeting deregulated cell cycle progression in cancer cells.

    PubMed

    Singh, Rana Pratap; Agarwal, Rajesh

    2006-03-01

    The prolonged duration requiring alteration of multi-genetic and epigenetic molecular events for cancer development provides a strong rationale for cancer prevention, which is developing as a potential strategy to arrest or reverse carcinogenic changes before the appearance of the malignant disease. Cell cycle progression is an important biological event having controlled regulation in normal cells, which almost universally becomes aberrant or deregulated in transformed and neoplastic cells. In this regard, targeting deregulated cell cycle progression and its modulation by various natural and synthetic agents are gaining widespread attention in recent years to control the unchecked growth and proliferation in cancer cells. In fact, a vast number of experimental studies convincingly show that many phytochemicals halt uncontrolled cell cycle progression in cancer cells. Among these phytochemicals, natural flavonoids have been identified as a one of the major classes of natural anticancer agents exerting antineoplastic activity via cell cycle arrest as a major mechanism in various types of cancer cells. This review is focused at the modulatory effects of natural flavonoids on cell cycle regulators including cyclin-dependent kinases and their inhibitors, cyclins, p53, retinoblastoma family of proteins, E2Fs, check-point kinases, ATM/ATR and survivin controlling G1/S and G2/M check-point transitions in cell cycle progression, and discusses how these molecular changes could contribute to the antineoplastic effects of natural flavonoids. PMID:16515531

  14. Angiotensin II promotes endometrial cancer cell survival.

    PubMed

    Nowakowska, Magdalena; Matysiak-Burzyńska, Zuzanna; Kowalska, Karolina; Płuciennik, Elżbieta; Domińska, Kamila; Piastowska-Ciesielska, Agnieszka W

    2016-08-01

    Endometrial cancer (EC) is one of the most common female cancers. One of the key processes involved in EC development is uncontrolled proliferation stimulated by local factors such as angiotensin. The aim of the present study was to evaluate the influence of angiotensin II (Ang II) on human EC cells. Biological assays and gene expression analysis were performed on three cell lines: ISH, MFE-296 and MFE-280. Our results indicated that at the beginning of cancerogenesis Ang II induced abnormal proliferation at lower doses. We also showed that dose-dependent induction of proliferation was connected with changes in the expression of MKI67, CCND1 and CCNE1 genes in well- and poorly differentiated cancer cells. After Ang II treatment, poorly differentiated endometrial cancer cell line acquired a mesenchymal phenotype, which was characterized by induced expression of EMT-related genes (VIM, CD44, SNAI1, ZEB1 and ZEB2). Our study revealed that Ang II influences EC cells in terms of cancer-related processes, and is responsible for increased proliferation, reduction in apoptosis, increased mobility and modulation of adhesion potential. Its effect and effectiveness appear to be highly connected with the differentiation status of the cancerous cells, as Ang II appears to play a crucial role in the early and late stages of malignant transformation. PMID:27349856

  15. Metastatic cancer stem cells: new molecular targets for cancer therapy.

    PubMed

    Leirós, G J; Balañá, M E

    2011-11-01

    The cancer stem cell (CSC) hypothesis, predicts that a small subpopulation of cancer cells that possess "stem-like" characteristics, are responsible for initiating and maintaining cancer growth. According to the CSC model the many cell populations found in a tumour might represent diverse stages of differentiation. From the cellular point of view metastasis is considered a highly inefficient process and only a subset of tumour cells is capable of successfully traversing the entire metastatic cascade and eventually re-initiates tumour growth at distant sites. Some similar features of both normal and malignant stem cells suggest that CSCs are not only responsible for tumorigenesis, but also for metastases. The CSC theory proposes that the ability of a tumour to metastasize is an inherent property of a subset of CSCs. The similar biological characteristics shared by normal stem cells (NSCs) and CSCs mainly implicate self-renewal and differentiation potential, survival ability, niche-specific microenvironment requirements and specific homing to metastatic sites and may have important implications in terms of new approaches to cancer therapy in the metastatic setting. There are several agents targeting many of these CSC features that have shown to be effective both in vitro and in vivo. Although clinical trials results are still preliminary and continue under investigation, these new therapies are very promising. The identification of new therapeutic targets and drugs based on CSC model constitutes a great challenge. PMID:21470128

  16. Cancer Stem Cells: A Stride Towards Cancer Cure?

    PubMed Central

    SENGUPTA, AMITAVA; CANCELAS, JOSE A.

    2014-01-01

    Despite major refinements in cancer therapy drugs, our progress at increasing the cure rates of most cancers has been hampered by high relapse rates. A possible biological explanation of the high frequency of relapse and resistance to currently available drugs has been provided by the cancer stem cell (CSC) proposition. Basically, the CSC theory hypothesizes the presence of a hierarchically organized, relatively rare population of cells that is responsible for tumor initiation, self-renewal and maintenance, mutation accumulation and therapy resistance. Since first postulated by John Dick, multiple reports have provided support for this hypothesis by isolating (more or less) rare cell populations, where the ability to initiate tumors in vivo has been demonstrated. Most progress and stronger data supporting this theory are found predominantly in myelogenous leukemias, whose study has benefited from over half-a-century progress in our understanding of the normal hierarchical organization of hematopoiesis. This review, however, also analyzes the advancement in the quantitative and functional analysis of solid tumor stem cells and in the analysis of the tumor microenvironment as specialized, nurturing niches for CSCs. Overall, this review intends to briefly summarize most of the evidences that support the CSC theory and the apparent contradictions, if not skepticism from the scientific community, about its validity for all forms of cancer, or alternatively on just a few cancers initiated by a limited number of somatic or germinal mutations. PMID:20458736

  17. Transbronchial Dissemination of Squamous Cell Lung Cancer

    PubMed Central

    Tadokoro, Akira; Kanaji, Nobuhiro; Ishii, Tomoya; Watanabe, Naoki; Inoue, Takuya; Kadowaki, Norimitsu; Bandoh, Shuji

    2015-01-01

    We report a case of squamous cell lung cancer with transbronchial dissemination in a 73-year-old man. Bronchoscopic examination revealed multiple bronchial mucosal nodules that existed independently of one another. We reviewed 16 previous cases of endobronchial metastasis in lung cancer. All patients were men. Among the reports that described the smoking history, most patients were smokers (6/7), and the most frequent histological type of cancer was squamous cell carcinoma (11/17). Although hematogenous and lymphogenous routes have been reported as metastatic mechanisms, no previous cases involving transbronchial dissemination have been described. Transbronchial dissemination may be an alternative pathway of endobronchial metastasis. PMID:26672760

  18. Adrenal glands of Spix's yellow-toothed cavy (Galea spixii, Wagler, 1831): morphological and morphometric aspects.

    PubMed

    Santos, A C; Viana, D C; Bertassoli, B M; Vasconcelos, B G; Oliveira, D M; Rici, R E G; Oliveira, M F; Miglino, M A; Assis-Neto, A C

    2016-05-01

    Considering the physiological importance and need of greater morphophysiological knowledge of adrenal glands, the aims of present study were compare the morphometric data between left and right adrenal of male and female; perform a histological, scanning and transmission electron microscopy study showing tissue constitution of glands; finally, in order to define the presence and correct site of the cytochrome P450c17 expression in adrenal glands, immunohistochemical study of this enzyme was performed in 18 adrenal glands (right n=9 and left n=9) of nine adult Galea spixii (four males and five females). Right adrenal was more cranially positioned than left adrenal; dimensions (weight, length and width) of right adrenal was larger than left adrenal; no differences between male and female body and adrenal measurements were found; the morphology of cells and different amounts of lipid droplets may be related to the different demands of steroid hormones production, related to each zone of the adrenal cortex; and, the cytochrome P450c17 immunolocalization in fasciculate and reticular zone may be related with synthesis of 17-hydroxy-pregnenolone, 17-hydroxy-progesterone, dehydroepiandrosterone or androstenedione. PMID:27143060

  19. Dendritic cell defects in the colorectal cancer

    PubMed Central

    Legitimo, Annalisa; Consolini, Rita; Failli, Alessandra; Orsini, Giulia; Spisni, Roberto

    2014-01-01

    Colorectal cancer (CRC) results from the accumulation of both genetic and epigenetic alterations of the genome. However, also the formation of an inflammatory milieu plays a pivotal role in tumor development and progression. Dendritic cells (DCs) play a relevant role in tumor by exerting differential pro-tumorigenic and anti-tumorigenic functions, depending on the local milieu. Quantitative and functional impairments of DCs have been widely observed in several types of cancer, including CRC, representing a tumor-escape mechanism employed by cancer cells to elude host immunosurveillance. Understanding the interactions between DCs and tumors is important for comprehending the mechanisms of tumor immune surveillance and escape, and provides novel approaches to therapy of cancer. This review summarizes updated information on the role of the DCs in colon cancer development and/or progression. PMID:25483675

  20. Mitochondrial structure in the rat adrenal cortex.

    PubMed Central

    Merry, B J

    1975-01-01

    Two distinct classes of mitochondria are described in the normal adrenal cortex of the Sprague Dawley CFY rat. Polyaminar mitochondria were frequently observed in the zona fasciculata and zona reticularis, particularly after ACTH stimulation of the cortex resulting from cold-stress exposure. It is uncertain whether such organelles are degenerating forms, or whether they have a specific functional role related to steroidogenesis in the normal cortical cell. In both normal and stressed adrenal cortices, protrusions of the outer membrane of mitochondria were evident, and were often seen penetrating lipid droplets. It is suggested that these protrusions may have some significance in the transport of cholesterol from the lipid droplet to the inner mitochondrial memrane 'desmolase complex', thus facilitating side-chain cleavage of cholesterol to pregnenolone. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:166969

  1. Genetics of primary macronodular adrenal hyperplasia.

    PubMed

    Fragoso, Maria Candida Barisson Villares; Alencar, Guilherme Asmar; Lerario, Antonio Marcondes; Bourdeau, Isabelle; Almeida, Madson Queiroz; Mendonca, Berenice Bilharinho; Lacroix, André

    2015-01-01

    ACTH-independent macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome (CS), accounting for <2% of all endogenous CS cases; however it is more frequently identified incidentally with sub-clinical cortisol secretion. Recently, cortisol secretion has been shown to be regulated by ectopic corticotropin, which is in turn produced by clusters of steroidogenic cells of the hyperplastic adrenal nodules. Hence, the term 'ACTH-independent' is not entirely appropriate for this disorder. Accordingly, the disease is designated primary macronodular adrenal hyperplasia (PMAH) in this review article. The means by which cortisol production is regulated in PMAH despite the suppressed levels of ACTH of pituitary origin is exceedingly complex. Several molecular events have been proposed to explain the enhanced cortisol secretion, increased cell proliferation, and nodule formation in PMAH. Nonetheless, the precise sequence of events and the molecular mechanisms underlying this condition remain unclear. The purpose of this review is therefore to present new insights on the molecular and genetic profile of PMAH pathophysiology, and to discuss the implications for disease progression. PMID:25472909

  2. Nicotinic receptor Alpha7 expression during mouse adrenal gland development.

    PubMed

    Gahring, Lorise C; Myers, Elizabeth; Palumbos, Sierra; Rogers, Scott W

    2014-01-01

    The nicotinic acetylcholine receptor alpha 7 (α7) is a ligand-activated ion channel that contributes to a diversity of cellular processes involved in development, neurotransmission and inflammation. In this report the expression of α7 was examined in the mouse developing and adult adrenal gland that expresses a green fluorescent protein (GFP) reporter as a bi-cistronic extension of the endogenous α7 transcript (α7(G)). At embryonic day 12.5 (E12.5) α7(G) expression was associated with the suprarenal ganglion and precursor cells of the adrenal gland. The α7(G) cells are catecholaminergic chromaffin cells as reflected by their progressive increase in the co-expression of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) that is complete by E18.5. In the adult, α7(G) expression is limited to a subset of chromaffin cells in the adrenal medulla that cluster near the border with the adrenal cortex. These chromaffin cells co-express α7(G), TH and DBH, but they lack phenylethanolamine N-methyltransferase (PNMT) consistent with only norepinephrine (NE) synthesis. These cell groups appear to be preferentially innervated by pre-ganglionic afferents identified by the neurotrophin receptor p75. No afferents identified by beta-III tubulin, neurofilament proteins or p75 co-expressed α7(G). Occasional α7(G) cells in the pre-E14.5 embryos express neuronal markers consistent with intrinsic ganglion cells and in the adult some α7(G) cells co-express glutamic acid decarboxylase. The transient expression of α7 during adrenal gland development and its prominent co-expression by a subset of NE chromaffin cells in the adult suggests that the α7 receptor contributes to multiple aspects of adrenal gland development and function that persist into adulthood. PMID:25093893

  3. Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-06-04

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  4. Cancer stem cells: the lessons from pre-cancerous stem cells

    PubMed Central

    Gao, Jian-Xin

    2008-01-01

    Abstract How a cancer is initiated and established remains elusive despite all the advances in decades of cancer research. Recently the cancer stem cell (CSC) hypothesis has been revived, challenging the long-standing model of ‘clonal evolution’ for cancer development and implicating the dawning of a potential cure for cancer [1]. The recent identification of pre-cancerous stem cells (pCSCs) in cancer, an early stage of CSC development, however, implicates that the clonal evolution is not contradictory to the CSC hypothesis but is rather an aspect of the process of CSC development [2]. The discovery of pCSC has revealed and will continue to reveal the volatile properties of CSC with respect to their phenotype, differentiation and tumourigenic capacity during initiation and progression. Both pCSC and CSC might also serve as precursors of tumour stromal components such as tumour vasculogenic stem/progenitor cells (TVPCs). Thus, the CSC hypothesis covers the developing process of tumour-initiating cells (TIC) → pCSC → CSC → cancer, a cellular process that should parallel the histological process of hyperplasia/metaplasia (TIC) → pre-cancerous lesions (pCSC) → malignant lesions (CSC → cancer). The embryonic stem (ES) cell and germ line stem (GS) cell genes are subverted in pCSCs. Especially the GS cell protein piwil2 may play an important role during the development of TIC → pCSC → CSC, and this protein may be used as a common biomarker for early detection, prevention, and treatment of cancer. As cancer stem cell research is yet in its infancy, definitive conclusions regarding the role of pCSC cannot be made at this time. However, this review will discuss what we have learned from pCSC and how this has led to innovative ideas that may eventually have major impacts on the understanding and treatment of cancer. PMID:18053092

  5. Iron, inflammation and invasion of cancer cells

    PubMed Central

    FISCHER-FODOR, EVA; MIKLASOVA, NATALIA; BERINDAN-NEAGOE, IOANA; SAHA, BHASKAR

    2015-01-01

    Chronic inflammation is associated with the metastasis of tumor cells evolving from a benign tumor to disseminating cancer. Such a metastatic progression is fostered by the angiogenesis propelled by various mediators interacting at the site of tumor growth. Angiogenesis causes two major changes that are assisted by altered glycosylation and neo-antigen presentation by the cancer cells. The angiogenesis-promoted pathological changes include enhanced inflammation and degradation of tissue matrices releasing tumor cells from the site of its origin. The degraded tumor cells release the neo-antigens resulting from altered glycosylation. Presentation of neo-antigens to T cells escalates metastasis and inflammation. Inflammasome activation and inflammation in several infections are regulated by iron. Based on the discrete reports, we propose a link between iron, inflammation, angiogenesis and tumor growth. Knowing the link better may help us formulate a novel strategy for cancer immunotherapy. PMID:26609256

  6. Overcoming Multidrug Resistance in Cancer Stem Cells

    PubMed Central

    Moitra, Karobi

    2015-01-01

    The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC) transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed. PMID:26649310

  7. Biomechanical investigation of colorectal cancer cells

    NASA Astrophysics Data System (ADS)

    Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro

    2014-09-01

    The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.

  8. Ubiquitin ligase CHIP suppresses cancer stem cell properties in a population of breast cancer cells.

    PubMed

    Tsuchiya, Mai; Nakajima, Yuka; Hirata, Naoya; Morishita, Tamaki; Kishimoto, Hiroyuki; Kanda, Yasunari; Kimura, Keiji

    2014-10-01

    Cancer stem cells (CSCs) have several distinctive characteristics, including high metastatic potential, tumor-initiating potential, and properties that resemble normal stem cells such as self-renewal, differentiation, and drug efflux. Because of these characteristics, CSC is regarded to be responsible for cancer progression and patient prognosis. In our previous study, we showed that a ubiquitin E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) suppressed breast cancer malignancy. Moreover, a recent clinical study reported that CHIP expression levels were associated with favorable prognostic parameters of patients with breast cancer. Here we show that CHIP suppresses CSC properties in a population of breast cancer cells. CHIP depletion resulted in an increased proportion of CSCs among breast cancers when using several assays to assess CSC properties. From our results, we propose that inhibition of CSC properties may be one of the functions of CHIP as a suppressor of cancer progression. PMID:25234599

  9. Adrenal involvement in non-Hodgkin lymphoma

    SciTech Connect

    Paling, M.R.; Williamson, B.R.J.

    1983-08-01

    Adrenal masses are described in seven cases of non-Hodgkin lymphoma in a series of 173 patients. In all seven patients the lymphoma was diffuse rather than nodular. Three patients had adrenal masses at the time of presentation, whereas in four cases the adrenal gland was a site of tumor recurrence after therapy. Three patients had simultaneous bilateral adrenal involvement by tumor. No characteristic features were recognized that might have distinguished these tumors from other adrenal masses. Appropriate therapy successfully resolved the adrenal masses in all but one case. The latter patient was the only one with evidence of adrenal insufficiency.

  10. Cancer stem cells: a metastasizing menace!

    PubMed

    Bandhavkar, Saurabh

    2016-04-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. PMID:26773710

  11. DNA From Dead Cancer Cells Induces TLR9-Mediated Invasion and Inflammation In Living Cancer Cells

    PubMed Central

    Tuomela, Johanna; Sandholm, Jouko; Kaakinen, Mika; Patel, Ankita; Kauppila, Joonas H.; Ilvesaro, Joanna; Chen, Dongquan; Harris, Kevin W.; Graves, David; Selander, Katri S.

    2014-01-01

    TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID:24212717

  12. Perspectives on cancer stem cells in osteosarcoma.

    PubMed

    Basu-Roy, Upal; Basilico, Claudio; Mansukhani, Alka

    2013-09-10

    Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. These mesenchymal tumors are derived from progenitor cells in the osteoblast lineage that have accumulated mutations to escape cell cycle checkpoints leading to excessive proliferation and defects in their ability to differentiate appropriately into mature bone-forming osteoblasts. Like other malignant tumors, osteosarcoma is often heterogeneous, consisting of phenotypically distinct cells with features of different stages of differentiation. The cancer stem cell hypothesis posits that tumors are maintained by stem cells and it is the incomplete eradication of a refractory population of tumor-initiating stem cells that accounts for drug resistance and tumor relapse. In this review we present our current knowledge about the biology of osteosarcoma stem cells from mouse and human tumors, highlighting new insights and unresolved issues in the identification of this elusive population. We focus on factors and pathways that are implicated in maintaining such cells, and differences from paradigms of epithelial cancers. Targeting of the cancer stem cells in osteosarcoma is a promising avenue to explore to develop new therapies for this devastating childhood cancer. PMID:22659734

  13. Natural T cell immunity against cancer.

    PubMed

    Nagorsen, Dirk; Scheibenbogen, Carmen; Marincola, Francesco M; Letsch, Anne; Keilholz, Ulrich

    2003-10-01

    It has long been a matter of debate whether tumors are spontaneously immunogenic in patients. With the availability of sensitive methods, naturally occurring T cells directed against tumor-associated antigens (TAAs) can be frequently detected in cancer patients. In this review, we summarize the current data on T cell responses to TAAs in various malignancies, including melanoma, colorectal cancer, leukemia, and breast cancer. T cell responses against various antigens, including melanoma differentiation antigens, carcinoembryonic antigen, epithelial cell adhesion molecule, her-2/neu, Wilms' tumor protein, proteinase 3, NY-ESO-1, and surviving, have been reported in a substantial number of patients. In contrast, other TAAs, including most antigens of the MAGE family, do not usually elicit spontaneous T cell responses. A distinction between direct ex vivo T cell responses and in vitro-generated T cell responses is provided because in vitro stimulation results in quantitative and functional changes of T cell responses. The possible role of TAA-specific T cells in immunosurveillance and tumor escape and the implications for immunological treatment strategies are discussed. Naturally occurring T cells against TAAs are a common phenomenon in tumor patients. Understanding the mechanisms and behavior of natural TAA-specific T cells could provide crucial information for rational development of more efficient T cell-directed immunotherapy. PMID:14555498

  14. Congenital adrenal hyperplasia

    PubMed Central

    Dessinioti, Cleo; Katsambas, Andreas

    2009-01-01

    Congenital adrenal hyperplasia consists of a heterogenous group of inherited disorders due to enzymatic defects in the biosynthetic pathway of cortisol and/or aldosterone. This results in glucocorticoid deficiency, mineralocorticoid deficiency, and androgen excess. 95% of CAH cases are due to 21-hydroxylase deficiency. Clinical forms range from the severe, classical CAH associated with complete loss of enzyme function, to milder, non-classical forms (NCAH). Androgen excess affects the pilosebaceous unit, causing cutaneous manifestations such as acne, androgenetic alopecia and hirsutism. Clinical differential diagnosis between NCAH and polycystic ovary syndrome may be difficult. In this review, the evaluation of patients with suspected CAH, the clinical presentation of CAH forms, with emphasis on the cutaneous manifestations of the disease, and available treatment options, will be discussed. PMID:22523607

  15. Dual effect of digitalis glycosides on norepinephrine release from human atrial tissue and bovine adrenal chromaffin cells: differential dependence on [Na+]i and [Ca2+]i.

    PubMed

    Haass, M; Serf, C; Gerber, S H; Krüger, C; Haunstetter, A; Vahl, C F; Nobiling, R; Kübler, W

    1997-06-01

    It was the aim of the present study (1) to characterize the influence of Na+/K(+)-ATPase inhibition by the digitalis glycoside ouabain on both spontaneous and nicotine-evoked norepinephrine release from the human heart; and (2) to further investigate the role of glycoside-induced changes in [Na+]i and [Ca2+]i (determined by microfluorimetry) for catecholamine release. The latter experiments were performed in bovine adrenal medullary chromaffin cells (BCC), an established cell culture model for sympathetic nerves. Ouabain (1-1000 mumol/l) exerted a dual effect on norepinephrine release (determined by HPLC) from incubated human atrial tissue: (I) Ouabain induced a concentration-dependent increase in norepinephrine release, that was calcium-independent and almost completely prevented by blockade of the uptake1-carrier by desipramine (1 mumol/l). The characteristics of this release process are consistent with a non-exocytotic mechanism. (II) In addition, ouabain augmented the nicotine-evoked (1-100 mumol/l) calcium-dependent norepinephrine release, which can be considered to be exocytotic. Na+/K(+)-ATPase inhibition also reduced the threshold concentration of nicotine from 10 to 1 mumol/l and it delayed the rapid tachyphylaxis of its norepinephrine releasing effect in human atrial tissue. In BCC, ouabain increased [Na+]i, [Ca2+]i and [3H]-norepinephrine release in parallel. Under calcium-free conditions, not only the ouabain-induced increase in [Na+]i, but also [3H]-norepinephrine release were enhanced. The ouabain-induced [3H]-norepinephrine release was always closely related to changes in [Na+]i, indicating a key role of [Na+]i for this calcium-independent non-exocytotic norepinephrine release. In addition, pretreatment with ouabain (1 mmol/l) augmented the nicotine-evoked (0.1-10 mumol/l) increments in [Na+]i, [Ca2+]i and [3H]-norepinephrine release. As nicotine-induced norepinephrine release depends on an increase in both [Na+]i and [Ca2+]i, these findings are

  16. A case of androgen-secreting adrenal carcinoma with non-classical congenital adrenal hyperplasia.

    PubMed

    Varma, Tarun; Panchani, Roopal; Goyal, Ashutosh; Maskey, Robin

    2013-10-01

    Androgen excess is one of the most common and disturbing endocrine disorder of reproductive-aged women, affecting approximately 7% of this population Androgen excess results in the development of androgenic features in the women affected, with the development of hirsutism, androgenic alopecia, ovulatory dysfunction, and, if extreme, even virilization and masculinization. Adrenocortical carcinoma (ACC) is a rare malignancy accounting for 0.02% of all annual cancers reported. About 60% are functional tumors secreting hormones, with its consequent clinical manifestations, the Cushing's syndrome due to cortisone, virilization due to androgens, feminization due to estrogens, or hypertension due to aldosterone. Adrenal tumors that secrete androgens exclusively are extremely rare. Here, we present a rare case of androgen-secreting adrenocortical carcinoma with non-classical congenital adrenal hyperplasia. PMID:24251173

  17. Dietary intake of sodium chloride in the rat influences [3H]nitrendipine binding to adrenal glomerulosa cell membranes but does not alter binding to vascular smooth muscle membranes.

    PubMed Central

    Schiebinger, R J

    1985-01-01

    Angiotensin II-stimulated secretion by adrenal glomerulosa cells and contraction by vascular smooth muscle (VSM) are dependent on calcium influx through membrane calcium channels. We have examined the hypothesis that the altered responsiveness of adrenal glomerulosa cells and VSM to angiotensin II during NaCl restriction may be associated with a change in membrane calcium channel number. To test this hypothesis, female rats were placed on a high or low NaCl diet. On the 14th day, membranes were prepared from the zona glomerulosa, aorta, mesenteric artery, and uterus. [3H]Nitrendipine binding was used to monitor calcium channel number. The [3H]nitrendipine binding capacity was observed to be higher in the zona glomerulosa during NaCl restriction than during high NaCl intake (83 +/- 18 vs. 49 +/- 9 fmol/mg protein, P less than 0.025, n = 6 paired experiments). The binding capacities of [3H]nitrendipine on the low and high NaCl diet were similar in the mesenteric artery (10 +/- 1 vs. 9 +/- 1 fmol/mg protein, n = 8), aorta (33 +/- 5 vs. 35 +/- 8 fmol/mg protein, n = 5), or uterus (87 +/- 15 vs. 85 +/- 16 fmol/mg protein, n = 4), respectively. The dissociation constants of [3H]nitrendipine binding did not differ on a low or high NaCl intake in the zona glomerulosa (0.84 +/- .12 vs. 0.79 +/- .10 nM), mesenteric artery (0.82 +/- .06 vs. 83 +/- .05 nM), aorta (0.90 +/- .11 vs. 0.92 +/- .12 nM), or uterus (0.55 +/- .12 vs. 0.56 +/- .10 nM), respectively. We conclude that the blunted response of VSM to angiotensin II during NaCl restriction is best explained by the previously reported lower number of angiotensin II receptors since calcium channel number does not change. In the adrenal glomerulosa cell, NaCl restriction is associated with a higher number of membrane calcium channels and angiotensin II receptors. The increase in calcium channel number may reflect the influence of an unknown factor(s) believed to be necessary for the full expression of the adrenal glomerulosa

  18. Abdomen: Retroperitoneum, peritoneum, gastrointestinal tract, kidney, and adrenal gland

    SciTech Connect

    Suen, K.C.

    1987-01-01

    In this book the author explores aspiration biopsy as it can be applied to lesions of the retroperitoneum, gastrointestinal tract, kidney, peritoneum, and adrenal gland. With experience from two different institutions - one an acute general care hospital, the other a cancer referral center - Dr. Suen has achieved in creating a text that reflects a wide range of experience. Throughout the work, Dr. Suen stresses pattern recognition of cytologic material. And a chapter on unusual and interesting lesions is included. Contents: Introduction and General Considerations; Abdomen Imaging Techniques; Clinical Relevance; Indentification of Normal ABC; retroperitoneum; Gastrointestinal Tract; Kidney; Adrenal Gland; Unusual Lesions; Immunocytochemistry and Electron Microscopy; Index.

  19. Adrenal lymphangioma: clinicopathologic and immunohistochemical characteristics of a rare lesion.

    PubMed

    Ellis, Carla L; Banerjee, Priya; Carney, Erin; Sharma, Rajni; Netto, George J

    2011-07-01

    flattened, bland, simple lining. The cystic channels/spaces occasionally contained proteinaceous material and lacked red blood cell content. On immunohistochemical stains, D2-40 cytoplasmic staining was positive in all 9 examined lesions, whereas AE1/AE3 was negative, thus, confirming their lymphatic nature. D2-40 staining was diffuse in 2 and focal in the 7 remaining lesions. Adrenal lymphangiomas are very rare, benign lymphatic neoplasms with a female, right-sided predominance in our current series. They may clinically present with abdominal pain or can be incidentally found during adulthood as a mass, necessitating surgical removal to rule out other types of adrenal neoplasms. PMID:21315417

  20. CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells

    PubMed Central

    Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

    2016-01-01

    Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, chemo-resistance property and in vivo tumor formation abilities were detected. A549 CD24- cells formed smaller colonies, slower proliferated in comparison to A549 CD24+ cells. Besides, A549 CD24- exhibited stronger resistance to chemotherapy drug. However, A549 CD24- didn’t exert any stronger tumor formation ability in vivo, which is the gold standard of CSCs. These results showed that CD24- A549 cells showed some properties of CSCs but not actually CSCs. This study provides evidence that CD24 cannot be considered as lung CSCs marker. PMID:27073722

  1. Biomechanics and biophysics of cancer cells

    PubMed Central

    Suresh, Subra

    2010-01-01

    The past decade has seen substantial growth in research into how changes in the biomechanical and biophysical properties of cells and subcellular structures influence, and are influenced by, the onset and progression of human diseases. This paper presents an overview of the rapidly expanding, nascent field of research that deals with the biomechanics and biophysics of cancer cells. The review begins with some key observations on the biology of cancer cells and on the role of actin microfilaments, intermediate filaments and microtubule biopolymer cytoskeletal components in influencing cell mechanics, locomotion, differentiation and neoplastic transformation. In order to set the scene for mechanistic discussions of the connections among alterations to subcellular structures, attendant changes in cell deformability, cytoadherence, migration, invasion and tumor metastasis, a survey is presented of the various quantitative mechanical and physical assays to extract the elastic and viscoelastic deformability of cancer cells. Results available in the literature on cell mechanics for different types of cancer are then reviewed. Representative case studies are presented next to illustrate how chemically induced cytoskeletal changes, biomechanical responses and signals from the intracellular regions act in concert with the chemomechanical environment of the extracellular matrix and the molecular tumorigenic signaling pathways to effect malignant transformations. Results are presented to illustrate how changes to cytoskeletal architecture induced by cancer drugs and chemotherapy regimens can significantly influence cell mechanics and disease state. It is reasoned through experimental evidence that greater understanding of the mechanics of cancer cell deformability and its interactions with the extracellular physical, chemical and biological environments offers enormous potential for significant new developments in disease diagnostics, prophylactics, therapeutics and drug

  2. Cancer Cells with Irons in the Fire

    PubMed Central

    Bystrom, Laura M.; Rivella, Stefano

    2014-01-01

    Iron is essential for the growth and proliferation of cells, as well as for many biological processes that are important for the maintenance and survival of the human body. However, excess iron is associated with the development of cancer and other pathological conditions, due in part to the pro-oxidative nature of iron and its damaging effects on DNA. Current studies suggest that iron depletion may be beneficial for patients that have diseases associated with iron overload or other iron metabolism disorders that may increase the risk for cancer. On the other hand, studies suggest that cancer cells are more vulnerable to the effects of iron depletion and oxidative stress in comparison to normal cells. Therefore, cancer patients might benefit from treatments that alter both iron metabolism and oxidative stress. This review highlights the pro-oxidant effects of iron, the relationship between iron and cancer development, the vulnerabilities of iron-dependent cancer phenotype, and how these characteristics may be exploited to prevent or treat cancer. PMID:24835768

  3. Phenotype heterogeneity in cancer cell populations

    NASA Astrophysics Data System (ADS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  4. Computed tomography evaluation of the adrenal gland in the preoperative assessment of bronchogenic carcinoma

    SciTech Connect

    Sandler, M.A.; Pearlberg, J.L.; Madrazo, B.L.; Gitschlag, K.F.; Gross, S.C.

    1982-12-01

    One hundred ten patients with proved bronchogenic carcinoma who were undergoing computed tomography (CT) of the thorax also underwent CT of the adrenals to determine the value of routine preoperative assessement of this gland. Sixteen adrenal masses were found in 11 patients. In five patients the adrenals were the only site of metastasis. CT of the adrenals should be performed routinely when the thorax is examined pre-operatively in patients with non-oat-cell bronchogenic carcinoma to improve patient selection for thoractomy.

  5. High prevalence of side population in human cancer cell lines

    PubMed Central

    Boesch, Maximilian; Zeimet, Alain G.; Fiegl, Heidi; Wolf, Barbara; Huber, Julia; Klocker, Helmut; Gastl, Guenther

    2016-01-01

    Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin. This should be considered when interpreting research involving these model systems. PMID:27226981

  6. Quantifying Collective Cell Migration during Cancer Progression

    NASA Astrophysics Data System (ADS)

    Lee, Rachel; Stuelten, Christina; Nordstrom, Kerstin; Parent, Carole; Losert, Wolfgang

    2014-03-01

    As tumors become more malignant, cells invade the surrounding tissue and migrate throughout the body to form secondary, metastatic tumors. This metastatic process is initiated when cells leave the primary tumor, either individually or as groups of collectively migrating cells. The mechanisms regulating how groups of cells collectively migrate are not well characterized. Here we study the migration dynamics of epithelial sheets composed of many cells using quantitative image analysis techniques. By extracting motion information from time-lapse images of cell lines of varying malignancy, we are able to measure how migration dynamics change during cancer progression. We further investigate the role that cell-cell adhesion plays in these collective dynamics by analyzing the migration of cell lines with varying levels of E-cadherin (a cell-cell adhesion protein) expression.

  7. [Cancer stemness and circulating tumor cells].

    PubMed

    Saito, Tomoko; Mimori, Koshi

    2015-05-01

    The principle concept of cancer stem cells (CSCs) giving rise to the carcinogenesis, relapse or metastasis of malignancy is broadly recognized. On the other hand, circulating tumor cells (CTCs) also plays important roles in relapse or metastasis of malignancy, and there has been much focused on the association between CSCs and CTCs in cancer cases. The technical innovations for detection of CTCs enabled us to unveil the nature of CTCs. We now realize that CTCs isolated by cell surface antibodies, such as DCLK1, LGR5 indicated CSC properties, and CTCs with epitherial-mesenchymal transition(EMT) phenotype showed characteristics of CSCs. PMID:25985635

  8. Immune cell interplay in colorectal cancer prognosis

    PubMed Central

    Norton, Samuel E; Ward-Hartstonge, Kirsten A; Taylor, Edward S; Kemp, Roslyn A

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, particularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship between cancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment. PMID:26483876

  9. Targeting cancer stem cells with oncolytic virus

    PubMed Central

    Tong, Yin

    2014-01-01

    Cancer stem cells (CSCs) represent a distinct subpopulation of cancer cells which are shown to be relatively resistant to conventional anticancer therapies and have been correlated to disease recurrence. Oncolytic viruses utilize methods of cell killing that differ from traditional therapies and thus are able to elude the typical mechanisms that CSCs use to resist current chemotherapies and radiotherapies. Moreover, genetically engineered oncolytic viruses may further augment the oncolytic effects. Here we review the recent data regarding the ability of several oncolytic viruses to eradicate CSCs.

  10. Adrenal Metastasis from Uterine Papillary Serous Carcinoma.

    PubMed

    Singh Lubana, Sandeep; Singh, Navdeep; Tuli, Sandeep S; Seligman, Barbara

    2016-01-01

    BACKGROUND Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. CASE REPORT A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. CONCLUSIONS UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  11. Lipid metabolic reprogramming in cancer cells

    PubMed Central

    Beloribi-Djefaflia, S; Vasseur, S; Guillaumond, F

    2016-01-01

    Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We reviewed the major lipid dysfunctions occurring during tumor development, as determined using systems biology approaches. In it, we provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. Finally, we summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression. PMID:26807644

  12. Adoptive T Cell Immunotherapy for Cancer

    PubMed Central

    Perica, Karlo; Varela, Juan Carlos; Oelke, Mathias; Schneck, Jonathan

    2015-01-01

    Harnessing the immune system to recognize and destroy tumor cells has been the central goal of anti-cancer immunotherapy. In recent years, there has been an increased interest in optimizing this technology in order to make it a clinically feasible treatment. One of the main treatment modalities within cancer immunotherapy has been adoptive T cell therapy (ACT). Using this approach, tumor-specific cytotoxic T cells are infused into cancer patients with the goal of recognizing, targeting, and destroying tumor cells. In the current review, we revisit some of the major successes of ACT, the major hurdles that have been overcome to optimize ACT, the remaining challenges, and future approaches to make ACT widely available. PMID:25717386

  13. Cell Phones and Cancer Risk

    MedlinePlus

    ... Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at NCI (Intramural) ... is heating. The ability of microwave ovens to heat food is one example of this effect of ...

  14. Dielectrophoretic Separation of Cancer Cells from Blood

    PubMed Central

    Gascoyne, Peter R. C.; Wang, Xiao-Bo; Huang, Ying; Becker, Frederick F.

    2009-01-01

    Recent measurements have demonstrated that the dielectric properties of cells depend on their type and physiological status. For example, MDA-231 human breast cancer cells were found to have a mean plasma membrane specific capacitance of 26 mF/m2, more than double the value (11 mF/m2) observed for resting T-lymphocytes. When an inhomogeneous ac electric field is applied to a particle, a dielectrophoretic (DEP) force arises that depends on the particle dielectric properties. Therefore, cells having different dielectric characteristics will experience differential DEP forces when subjected to such a field. In this article, we demonstrate the use of differential DEP forces for the separation of several different cancerous cell types from blood in a dielectric affinity column. These separations were accomplished using thin, flat chambers having microelectrode arrays on the bottom wall. DEP forces generated by the application of ac fields to the electrodes were used to influence the rate of elution of cells from the chamber by hydrodynamic forces within a parabolic fluid flow profile. Electrorotation measurements were first made on the various cell types found within cell mixtures to be separated, and theoretical modeling was used to derive the cell dielectric parameters. Optimum separation conditions were then predicted from the frequency and suspension conductivity dependencies of cell DEP responses defined by these parameters. Cell separations were then undertaken for various ratios of cancerous to normal cells at different concentrations. Eluted cells were characterized in terms of separation efficiency, cell viability, and separation speed. For example, 100% efficiency was achieved for purging MDA-231 cells from blood at the tumor to normal cell ratio 1:1 × 105 or 1:3 × 105, cell viability was not compromised, and separation rates were at least 103 cells/s. Theoretical and experimental criteria for the design and operation of such separators are presented. PMID

  15. Adrenal Gland Disorders: Condition Information

    MedlinePlus

    ... of salt and water Controlling the "fight or flight" response to stress Maintaining pregnancy Initiating and controlling ... overview of the adrenal glands: Beyond fight or flight . Retrieved June 29, 2012 from http://www.endocrineweb. ...

  16. Nano-discs Destroy Cancer Cells

    SciTech Connect

    2010-01-01

    A new technique, designed with the potential to treat brain cancers, is under study at Argonne National Laboratory and the University of Chicago Medical Center. The micron-sized magnetic materials, with vortex-like arrangements of spins, were successfully interfaced with Glioblastoma multiforme (GBM) cancer cells. The microdisks are gold-coated and biofunctionalized with a cancer-targeting antibody. The antibody recognizes unique receptors on the cancer cells and attaches to them (and them alone), leaving surrounding healthy cells unaffected during treatment. Under application of an alternative magnetic field, the magnetic vortices shift, leading to oscillatory motion of the disks and causing the magneto-mechanic stimulus to be transmitted directly to the cancer cell. Probably because of the damage to the cancer cell membrane, this results in cellular signal transduction and amplification, causing initiation of apoptosis (programmed cell death or "cell suicide"). Manifestation of apoptosis is of clinical significance because the malignant cells are known to be almost "immortal" (due to suppressed apoptosis), and, consequently, highly resistant to conventional (chemo- and radio-) therapies. Due to unique properties of the vortex microdisks, an extremely high spin-vortex-induced cytotoxicity effect can be caused by application of unprecedentedly weak magnetic fields. An alternative magnetic field as slow as about 10s Hertz (for comparison, 60 Hertz in a electrical outlet) and as small as less than 90 Oersteds (which is actually less than the field produced by a magnetized razor blade) applied only for 10 minutes was sufficient to cause ~90% cancer cell destruction in vitro. The study has only been conducted in cells in a laboratory; animal trials are being planned. Watch a news clip of the story from ABC-7 News: http://abclocal.go.com/wls/story?section=news/health&id=7245605 More details on this study can be found in the original research paper: Biofunctionalized

  17. Cancer-Associated Myeloid Regulatory Cells.

    PubMed

    De Vlaeminck, Yannick; González-Rascón, Anna; Goyvaerts, Cleo; Breckpot, Karine

    2016-01-01

    Myeloid cells are critically involved in the pathophysiology of cancers. In the tumor microenvironment (TME), they comprise tumor-associated macrophages (TAMs), neutrophils (TANs), dendritic cells, and myeloid-derived suppressor cells, which are further subdivided into a monocytic subset and a granulocytic subset. Some of these myeloid cells, in particular TAMs and TANs, are divided into type 1 or type 2 cells, according to the paradigm of T helper type 1 or type 2 cells. Type 1-activated cells are generally characterized as cells that aid tumor rejection, while all other myeloid cells are shown to favor tumor progression. Moreover, these cells are often at the basis of resistance to various therapies. Much research has been devoted to study the biology of myeloid cells. This endeavor has proven to be challenging, as the markers used to categorize myeloid cells in the TME are not restricted to particular subsets. Also from a functional and metabolic point of view, myeloid cells share many features. Finally, myeloid cells are endowed with a certain level of plasticity, which further complicates studying them outside their environment. In this article, we challenge the exclusive use of cell markers to unambiguously identify myeloid cell subsets in the TME. We further propose to divide myeloid cells into myeloid regulatory or stimulatory cells according to their pro- or antitumor function, because we contend that for therapeutic purposes it is not targeting the cell subsets but rather targeting their protumor traits; hence, myeloid regulatory cells will push antitumor immunotherapy to the next level. PMID:27065074

  18. Cancer-Associated Myeloid Regulatory Cells

    PubMed Central

    De Vlaeminck, Yannick; González-Rascón, Anna; Goyvaerts, Cleo; Breckpot, Karine

    2016-01-01

    Myeloid cells are critically involved in the pathophysiology of cancers. In the tumor microenvironment (TME), they comprise tumor-associated macrophages (TAMs), neutrophils (TANs), dendritic cells, and myeloid-derived suppressor cells, which are further subdivided into a monocytic subset and a granulocytic subset. Some of these myeloid cells, in particular TAMs and TANs, are divided into type 1 or type 2 cells, according to the paradigm of T helper type 1 or type 2 cells. Type 1-activated cells are generally characterized as cells that aid tumor rejection, while all other myeloid cells are shown to favor tumor progression. Moreover, these cells are often at the basis of resistance to various therapies. Much research has been devoted to study the biology of myeloid cells. This endeavor has proven to be challenging, as the markers used to categorize myeloid cells in the TME are not restricted to particular subsets. Also from a functional and metabolic point of view, myeloid cells share many features. Finally, myeloid cells are endowed with a certain level of plasticity, which further complicates studying them outside their environment. In this article, we challenge the exclusive use of cell markers to unambiguously identify myeloid cell subsets in the TME. We further propose to divide myeloid cells into myeloid regulatory or stimulatory cells according to their pro- or antitumor function, because we contend that for therapeutic purposes it is not targeting the cell subsets but rather targeting their protumor traits; hence, myeloid regulatory cells will push antitumor immunotherapy to the next level. PMID:27065074

  19. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  20. Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells

    PubMed Central

    Burnett, Riesa M.; Craven, Kelly E.; Krishnamurthy, Purna; Goswami, Chirayu P.; Badve, Sunil; Crooks, Peter; Mathews, William P.; Bhat-Nakshatri, Poornima; Nakshatri, Harikrishna

    2015-01-01

    Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically. PMID:25926557

  1. Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells.

    PubMed

    Burnett, Riesa M; Craven, Kelly E; Krishnamurthy, Purna; Goswami, Chirayu P; Badve, Sunil; Crooks, Peter; Mathews, William P; Bhat-Nakshatri, Poornima; Nakshatri, Harikrishna

    2015-05-20

    Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically. PMID:25926557

  2. Spermatogonial stem cells, infertility and testicular cancer

    PubMed Central

    Singh, Shree Ram; Burnicka-Turek, Ozanna; Chauhan, Chhavi; Hou, Steven X

    2011-01-01

    Abstract The spermatogonial stem cells (SSCs) are responsible for the transmission of genetic information from an individual to the next generation. SSCs play critical roles in understanding the basic reproductive biology of gametes and treatments of human infertility. SSCs not only maintain normal spermatogenesis, but also sustain fertility by critically balancing both SSC self-renewal and differentiation. This self-renewal and differentiation in turn is tightly regulated by a combination of intrinsic gene expression within the SSC as well as the extrinsic gene signals from the niche. Increased SSCs self-renewal at the expense of differentiation result in germ cell tumours, on the other hand, higher differentiation at the expense of self-renewal can result in male sterility. Testicular germ cell cancers are the most frequent cancers among young men in industrialized countries. However, understanding the pathogenesis of testis cancer has been difficult because it is formed during foetal development. Recent studies suggest that SSCs can be reprogrammed to become embryonic stem (ES)-like cells to acquire pluripotency. In the present review, we summarize the recent developments in SSCs biology and role of SSC in testicular cancer. We believe that studying the biology of SSCs will not only provide better understanding of stem cell regulation in the testis, but eventually will also be a novel target for male infertility and testicular cancers. PMID:21155977

  3. Neural stem cell therapy for cancer.

    PubMed

    Bagó, Juli Rodriguez; Sheets, Kevin T; Hingtgen, Shawn D

    2016-04-15

    Cancers of the brain remain one of the greatest medical challenges. Traditional surgery and chemo-radiation therapy are unable to eradicate diffuse cancer cells and tumor recurrence is nearly inevitable. In contrast to traditional regenerative medicine applications, engineered neural stem cells (NSCs) are emerging as a promising new therapeutic strategy for cancer therapy. The tumor-homing properties allow NSCs to access both primary and invasive tumor foci, creating a novel delivery platform. NSCs engineered with a wide array of cytotoxic agents have been found to significantly reduce tumor volumes and markedly extend survival in preclinical models. With the recent launch of new clinical trials, the potential to successfully manage cancer in human patients with cytotoxic NSC therapy is moving closer to becoming a reality. PMID:26314280

  4. Nicotine-induced exocytotic norepinephrine release in guinea-pig heart, human atrium and bovine adrenal chromaffin cells: modulation by single components of ischaemia.

    PubMed

    Krüger, C; Haunstetter, A; Gerber, S; Serf, C; Kaufmann, A; Kübler, W; Haass, M

    1995-08-01

    The influence of single components of myocardial ischaemia, such as anoxia, substrate withdrawal, hyperkalemia and extracellular acidosis, on nicotine-induced norepinephrine (NE) release was investigated in the isolated perfused guinea-pig heart, in incubated human atrial tissue and in cultured bovine adrenal chromaffin cells (BCC). In normoxia, nicotine (1-1000 mumol/l) evoked a concentration-dependent release of NE (determined by high pressure liquid chromatography and electrochemical detection) from guinea-pig heart and human atrium. In contrast to selective anoxia (Po2 < 5 mmHg) or glucose withdrawal, respectively, anoxia in combination with glucose withdrawal (5-40 min) markedly potentiated nicotine-induced NE release both in guinea-pig heart and human atrium. The sensitization of cardiac sympathetic nerve endings to nicotine was characterized by a lower threshold concentration and an approximate two-fold increase of maximum NE release, peaking after 10 min of anoxia and glucose withdrawal. Cyanide intoxication (1 mmol/l) combined with glucose withdrawal resulted in a similar increase of nicotine-induced sympathetic transmitter release both in guinea-pig heart and human atrium. In contrast, the nicotine-induced (10 mumol/l) NE overflow was only slightly potentiated by 10 min of global ischaemia in guinea-pig heart. Both hyperkalemia ([K+] 16 mmol/l) and acidosis (pH 6.8-6.0) distinctly attenuated the stimulatory effect of nicotine in guinea-pig heart and human atrium under normoxic conditions. Consistent with an exocytotic release mechanism, NE release was dependent on the presence of extracellular calcium under all conditions tested. Furthermore, NE overflow from guinea-pig heart was accompanied by a release of the exocytosis marker neuropeptide Y (NPY; determined by radioimmunoassay). In BCC, nicotine (1-10 mumol/l) evoked a release of NE and NPY and a transient rise of [Ca2+]i (determined with fura-2) during normoxia which were both dependent on the

  5. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology

    PubMed Central

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A. Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions. PMID:27499746

  6. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.

    PubMed

    Koizumi, Keiichi; Hojo, Shozo; Akashi, Takuya; Yasumoto, Kazuo; Saiki, Ikuo

    2007-11-01

    The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. PMID:17894551

  7. Surgery for small cell lung cancer.

    PubMed

    de Hoyos, Alberto; DeCamp, Malcolm M

    2014-11-01

    Small-cell lung cancer (SCLC) comprises approximately 14% of all lung cancer cases. Most patients present with locally advanced or metastatic disease and are therefore treated nonoperatively with chemotherapy, radiotherapy, or both. A small subset of patients with SCLC present with early-stage disease and will benefit from surgical resection plus chemotherapy. The rationale for radiotherapy in these patients remains controversial. PMID:25441133

  8. Thyroid Hormones as Renal Cell Cancer Regulators

    PubMed Central

    Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

    It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma. PMID:27034829

  9. Cell Membrane Softening in Cancer Cells

    NASA Astrophysics Data System (ADS)

    Schmidt, Sebastian; Händel, Chris; Käs, Josef

    Biomechanical properties are useful characteristics and regulators of the cell's state. Current research connects mechanical properties of the cytoskeleton to many cellular processes but does not investigate the biomechanics of the plasma membrane. We evaluated thermal fluctuations of giant plasma membrane vesicles, directly derived from the plasma membranes of primary breast and cervical cells and observed a lowered rigidity in the plasma membrane of malignant cells compared to non-malignant cells. To investigate the specific role of membrane rigidity changes, we treated two cell lines with the Acetyl-CoA carboxylase inhibitor Soraphen A. It changed the lipidome of cells and drastically increased membrane stiffness by up regulating short chained membrane lipids. These altered cells had a decreased motility in Boyden chamber assays. Our results indicate that the thermal fluctuations of the membrane, which are much smaller than the fluctuations driven by the cytoskeleton, can be modulated by the cell and have an impact on adhesion and motility.

  10. The role of mast cells in cancers

    PubMed Central

    Maciel, Thiago T.; Moura, Ivan C.

    2015-01-01

    Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer. Here we review observations suggesting that mast cells could modulate tumor growth in humans. We also discuss the drawbacks related to observations from mast cell-deficient mouse models, which could have consequences in the determination of a potential causative relationship between mast cells and cancer. We believe that the understanding of the precise role of mast cells in tumor development and progression will be of critical importance for the development of new targeted therapies in human cancers. PMID:25705392

  11. Chemotherapy in heterogeneous cultures of cancer cells with interconversion

    NASA Astrophysics Data System (ADS)

    Dilão, Rui

    2015-02-01

    Recently, the interconversion between differentiated and stem-like cancer cells has been observed. Here, we model the in vitro growth of heterogeneous cell cultures in the presence of interconversion from differentiated cancer cells to cancer stem cells (CSCs), showing that, by targeting only CSC with cytotoxic agents, it is not always possible to eradicate cancer. We have determined the kinetic conditions under which cytotoxic agents in in vitro heterogeneous cultures of cancer cells eradicate cancer. In particular, we have shown that the chemotherapeutic elimination of in vitro cultures of heterogeneous cancer cells is effective only if it targets all cancer cell types, and if the induced death rates for the different subpopulations of cancer cell types are large enough. The quantitative results of the model are compared and validated with experimental data.

  12. The metabolic landscape of cancer stem cells.

    PubMed

    Dando, Ilaria; Dalla Pozza, Elisa; Biondani, Giulia; Cordani, Marco; Palmieri, Marta; Donadelli, Massimo

    2015-09-01

    Cancer stem cells (CSCs) are a sub-population of quiescent cells endowed with self-renewal properties that can sustain the malignant behavior of the tumor mass giving rise to more differentiated cancer cells. For this reason, the specific killing of CSCs represents one of the most important challenges of the modern molecular oncology. However, their particular resistance to traditional chemotherapy and radiotherapy imposes a thorough understanding of their biological and biochemical features. The metabolic peculiarities of CSCs may be a therapeutic and diagnostic opportunity in cancer research. In this review, we summarize the most significant discoveries on the metabolism of CSCs describing and critically analyzing the studies supporting either glycolysis or mitochondrial oxidative phosphorylation as a primary source of energy for CSCs. PMID:26337609

  13. Pathology of the adrenal cortex: a reappraisal of the past 25 years focusing on adrenal cortical tumors.

    PubMed

    Papotti, Mauro; Duregon, Eleonora; Volante, Marco; McNicol, Anne Marie

    2014-03-01

    A reappraisal of the major advances in the diagnostic pathology of adrenal cortical lesions and tumors in the last 25 years is presented, with special reference to the definition of malignancy in primary adrenal cancer and its variants. Slightly more than 25 years ago, Weiss proposed his diagnostic scoring system for adrenal cortical carcinoma. This represented a milestone for adrenal pathologists and the starting point for further modifications of the system, either through minor changes in the scoring procedure itself or concentrating on some particular Weiss criterion such as mitotic index, integrated into alternative scoring schemes or algorithms that are currently under validation. Improvements in diagnostic immunohistochemistry have led to the identification of markers of cortical origin, such as Melan-A, alpha-inhibin, and SF-1 and of prognostic factors in carcinoma, such as the Ki-67 proliferation index and SF-1 itself. With regard to hyperplastic conditions, genetic investigations have allowed the association of the majority of cases of primary pigmented nodular adrenocortical disease (PPNAD) in Carney complex to mutations in the gene encoding the regulatory subunit 1A of protein kinase A (PRKAR1A). Other hereditary conditions are also associated with adrenal cortical tumors, including the Li-Fraumeni, Beckwith-Wiedemann, Gardner, multiple endocrine neoplasia type 1, and neurofibromatosis type 1 syndromes. Moreover, several advances have been made in the knowledge of the molecular background of sporadic tumors, and a number of molecules/genes are of particular interest as potential diagnostic and prognostic biomarkers. PMID:24382573

  14. Interconversion of inositol (1,4,5)-trisphosphate to inositol (1,3,4,5)-tetrakisphosphate and (1,3,4)-trisphosphate in permeabilized adrenal glomerulosa cells is calcium-sensitive and ATP-dependent

    SciTech Connect

    Rossier, M.F.; Dentand, I.A.; Lew, P.D.; Capponi, A.M.; Vallotton, M.B.

    1986-08-29

    The metabolism of (/sub 3/H)inositol (1,4,5)-trisphosphate was followed in permeabilized bovine adrenal glomerulosa cells. At low Ca++ concentration (pCa = 7.2), more than 90% of (/sub 3/H)inositol (1,4,5)-trisphosphate had disappeared within 2 min, while two other metabolites, (/sub 3/H)inositol (1,3,4)-trisphosphate and (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate appeared progressively. At higher Ca++ concentrations (pCa = 5.7 and 4.8), the formation of these two metabolites was markedly increased, but completely abolished if the medium was ATP-depleted. The peak levels for the generation of (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate (1 min) preceded those of (3H)inositol (1,3,4)-trisphosphate and were closely correlated. These results suggest that, in adrenal glomerulosa cells, the isomer inositol (1,3,4)-trisphosphate is generated from inositol (1,4,5)-trisphosphate via a calcium-sensitive and ATP-dependent phosphorylation/dephosphorylation pathway involving the formation of inositol (1,3,4,5)-tetrakisphosphate.

  15. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells

    PubMed Central

    Liu, Su; Uppal, Harpreet; Demaria, Marco; Desprez, Pierre-Yves; Campisi, Judith; Kapahi, Pankaj

    2015-01-01

    Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells, and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance. PMID:26658759

  16. [Cancer cell plasticity and metastatic dissemination].

    PubMed

    Moyret-Lalle, Caroline; Pommier, Roxane; Bouard, Charlotte; Nouri, Ebticem; Richard, Geoffrey; Puisieux, Alain

    Metastatic dissemination consists of a sequence of events resulting in the invasion by cancer cells of tissues located away from the primary tumour. This process is highly inefficient, since each event represents an obstacle that only a limited number of cells can overcome. However, two biological phenomena intrinsically linked with tumour development facilitate the dissemination of cancer cells throughout the body and promote the formation of metastases, namely the genetic diversity of cancer cells within a given tumour, which arises from their genetic instability and from successive clonal expansions, and cellular plasticity conveyed to the cells by micro-environmental signals. Genetic diversity increases the probability of selecting cells that are intrinsically resistant to biological and physical constraints encountered during metastatic dissemination, whereas cellular plasticity provides cells with the capacity to adapt to stressful conditions and to changes in the microenvironment. The epithelial-mesenchymal transition, an embryonic trans-differentiation process frequently reactivated during tumour development, plays an important role in that context by endowing tumor cells with a unique capacity of motility, survival and adaptability to the novel environments and stresses encountered during the invasion-metastasis cascade. PMID:27615180

  17. Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The administration of morphine to hypophysectomized rats potentiated the steroidogenic response of the adrenal cortex to exogenous adrenocorticotrophic hormone (ACTH) in a dose-dependent fashion. Conversely, the opiate antagonist naloxone inhibited the adrenal response to ACTH. Naloxone pretreatment also antagonized the potentiating effect of morphine on ACTH-induced steroidogenesis in a dose-dependent manner. Neither morphine nor naloxone, administered to hypophysectomized rats, had any direct effect on adrenal steroidogenesis. These adrenal actions were stereospecific since neither the (+)-stereoisomer of morphine, nor that or naloxone, had any effect on the adrenal response to ACTH. The administration of human beta-endorphin to hypophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose-dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone-secreting cells of the adrenal cortex.

  18. Stimulation of adrenal DNA synthesis in cadmium-treated male rats

    SciTech Connect

    Nishiyama, S.; Nakamura, K.

    1984-07-01

    Cadmium chloride (CdCl2) at a dose of 1 mg/kg body wt was injected into male rats of the Wistar strain, weighing 250 g on the average, twice a day (12-hr intervals) for 7 consecutive days. DNA and RNA contents and (/sup 3/H)-thymidine and (/sup 3/H)-uridine incorporation into the acid-insoluble fraction significantly increased in the adrenals of rats treated with Cd for 2 and 7 consecutive days. Adrenal protein content and weight also significantly increased. These results indicate that continued treatment with Cd stimulates DNA and RNA synthesis in the adrenal cortex, which in turn results in the increase of the total protein contents of the adrenal gland and subsequently in the enlargement of the gland. Serum adrenocorticotrophin (ACTH) and insulin levels in Cd-treated rats were not higher than control levels, suggesting that the stimulation of DNA synthesis in the adrenals of Cd-treated rats is due to factor(s) other than serum ACTH and insulin. Treatment with Cd inhibited DNA synthesis in cultured adrenocortical cells at concentrations of 10(-4) to 10(-8) M, suggesting that Cd does not directly stimulate DNA synthesis in the adrenal gland in vivo. Although the adrenal gland became enlarged, the total adrenal corticosterone content decreased significantly. The decrease of total adrenal corticosterone content may be due to the fall in serum ACTH level of Cd-treated rats.

  19. Wnt signaling in cancer stem cells and colon cancer metastasis

    PubMed Central

    Ben-Ze'ev, Avri

    2016-01-01

    Overactivation of Wnt signaling is a hallmark of colorectal cancer (CRC). The Wnt pathway is a key regulator of both the early and the later, more invasive, stages of CRC development. In the normal intestine and colon, Wnt signaling controls the homeostasis of intestinal stem cells (ISCs) that fuel, via proliferation, upward movement of progeny cells from the crypt bottom toward the villus and differentiation into all cell types that constitute the intestine. Studies in recent years suggested that cancer stem cells (CSCs), similar to ISCs of the crypts, consist of a small subpopulation of the tumor and are responsible for the initiation and progression of the disease. Although various ISC signature genes were also identified as CRC markers and some of these genes were even demonstrated to have a direct functional role in CRC development, the origin of CSCs and their contribution to cancer progression is still debated. Here, we describe studies supporting a relationship between Wnt-regulated CSCs and the progression of CRC. PMID:27134739

  20. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    SciTech Connect

    Nobiletti, J.B.

    1985-01-01

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, (/sup 3/H) leucine pulse-chase labeling experiments were conducted in two systems - the isolated retrograde perfused cat adrenal gland and cultured bovine adrenal chromaffin cells to compare chromaffin granule soluble dopamine-B-hydroxylase (DBH) turnover (marker for granule soluble content turnover) to that of membrane-bound DBH (marker for granule membrane turnover). Experiments in cat adrenal glands showed that at all chase periods the granule distribution of radiolabeled DBH was in agreement with the DBH activity distribution (73% membrane-bound/27% soluble) - a result consistent with parallel turnover of soluble and membrane-bound DBH. Experiments in cultured bovine cells showed that labeled soluble and membrane-bound DBH had parallel turnover patterns and at all chase period, the distribution of radiolabeled DBH between the soluble contents and membranes was similar to the DBH activity distribution (50% soluble/50% membrane-bound). The above experiments showed that the soluble contents and membranes turnover in parallel and are consistent with nonreutilization of chromaffin granule membranes following exocytosis. Isolated retrograde perfused bovine adrenal glands were subjected to repetitive acetylcholine stimulation to induce exocytosis and then the dense and less-dense chromaffin granule fractions were isolated. Since both approaches gave results consistent with membrane nonreutilization, the authors conclude that once a chromaffin granule is involved in exocytosis, its membrane is not reutilized for the further synthesis, storage, and secretion of catecholamines.

  1. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  2. Foxp3 expression in human cancer cells

    PubMed Central

    Karanikas, Vaios; Speletas, Matthaios; Zamanakou, Maria; Kalala, Fani; Loules, Gedeon; Kerenidi, Theodora; Barda, Angeliki K; Gourgoulianis, Konstantinos I; Germenis, Anastasios E

    2008-01-01

    Objective Transcription factor forkhead box protein 3 (Foxp3) specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs). Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia) were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression. PMID:18430198

  3. Genetics Home Reference: X-linked adrenal hypoplasia congenita

    MedlinePlus

    ... glands on top of each kidney called the adrenal glands . These glands produce a variety of hormones that ... disorder is adrenal insufficiency, which occurs when the adrenal glands do not produce enough hormones. Adrenal insufficiency typically ...

  4. Sulindac suppresses beta-catenin expression in human cancer cells.

    PubMed

    Han, Anjia; Song, Zibo; Tong, Chang; Hu, Dong; Bi, Xiuli; Augenlicht, Leonard H; Yang, Wancai

    2008-03-31

    Sulindac has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells. In this study, we treated human breast cancer cell line MCF-7 and lung cancer cell line A549 as well as colon cancer cell line SW620 with sulindac to observe the effects of sulindac in other tissue sites. In all cell lines, proliferation was significantly inhibited by sulindac after 24 and 72 h of treatment. Apoptosis was induced by sulindac in both lung cancer cells and colon cancer cells but was not induced in breast cancer cells. Western blots showed that p21 protein level were induced by sulindac in lung cancer cells and colon cancer cells, but not in breast cancer cells. However, the suppression of beta-catenin, a key mediator of Wnt signaling pathway, was seen in all three cell lines with sulindac administration. Further studies revealed that transcriptional activities of beta-catenin were significantly inhibited by sulindac and that the inhibition was sulindac dosage-dependent. The transcriptional targets of beta-catenin, c-myc, cyclin D1 and cdk 4 were also dramatically downregulated. In conclusion, our data demonstrated that the efficacy of sulindac in the inhibition of cell proliferation (rather than the induction of apoptosis) might be through the suppression of beta-catenin pathway in human cancer cells. PMID:18291362

  5. Targeting Lung Cancer Stem Cells with Antipsychological Drug Thioridazine

    PubMed Central

    Yue, Haiying; Huang, Dongning; Qin, Li; Zheng, Zhiyong; Hua, Li; Wang, Guodong; Huang, Jian

    2016-01-01

    Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells. PMID:27556038

  6. Cell membrane softening in human breast and cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

  7. Expression of prepro-ghrelin and related receptor genes in the rat adrenal gland and evidences that ghrelin exerts a potent stimulating effect on corticosterone secretion by cultured rat adrenocortical cells.

    PubMed

    Rucinski, Marcin; Ziolkowska, Agnieszka; Tyczewska, Marianna; Malendowicz, Ludwik K

    2009-08-01

    The orexigenic peptide ghrelin (GHREL) and obestatin (OBS) originate from the same peptide precursor, preproghrelin (ppGHREL). Apart from orexigenic effect, GHREL also regulates neuroendocrine function. We investigated GHREL and OBS effects on corticosterone secretion by freshly isolated and cultured rat adrenocortical cells. Classic RT-PCR revealed the presence of ppGHREL, GHS-R1a, GPR39v1 and GPR39v2 and GOAT4 (ghrelin O-acyl transferase) mRNAs in rat adrenals and cultured for 4 days rat adrenocortical cells. Expression of ppGHREL, GHS-R1a, and GOAT genes was notably higher in the cortex than in medulla. High expression level of GOAT gene was found in the zona glomerulosa, while expression level of both GPR39v1 and GPR39v2 genes was similar in adrenal cortical zones and in medulla. In freshly isolated cells neither GHREL nor OBS had an effect on corticosteroid output. Prolonged exposure of cultured cells to GHREL resulted in a potent, comparable to ACTH, stimulating effect of GHREL on corticosterone secretion. Prolonged exposure to OBS was ineffective. Neither GHREL nor OBS had any effect on proliferation of studied cells, while ACTH notably lowered it. GHREL down regulated GHS-R1a gene expression while both ACTH and GHREL stimulated expression level of GPR39v1 gene. Expression of CYP11A1 gene was notably stimulated and that of StAR gene remained unaffected by ACTH or GHREL. Thus, our study is the first to demonstrate direct stimulating effect of GHREL on corticosterone output by cultured rat adrenocortical cells. This stimulating action differs from that evoked by ACTH and is not dependent on the presence of functional ACTH receptor. PMID:19416745

  8. Cancer stem-like cells and thyroid cancer.

    PubMed

    Guo, Zhenying; Hardin, Heather; Lloyd, Ricardo V

    2014-10-01

    Thyroid cancer is one of the most rapidly increasing malignancies. The reasons for this increase is not completely known, but increases in the diagnosis of papillary thyroid microcarcinomas and follicular variant of papillary thyroid carcinomas along with the enhanced detection of well-differentiated thyroid carcinomas are probably all contributing factors. Although most cases of well-differentiated thyroid carcinomas are associated with an excellent prognosis, a small percentage of patients with well-differentiated thyroid carcinomas as well as most patients with poorly differentiated and anaplastic thyroid carcinomas have recurrent and/or metastatic disease that is often fatal. The cancer stem-like cell (CSC) model suggests that a small number of cells within a cancer, known as CSCs, are responsible for resistance to chemotherapy and radiation therapy, as well as for recurrent and metastatic disease. This review discusses current studies about thyroid CSCs, the processes of epithelial-to-mesenchymal transition (EMT), and mesenchymal-to-epithelial transition that provide plasticity to CSC growth, in addition to the role of microRNAs in CSC development and regulation. Understanding the biology of CSCs, EMT and the metastatic cascade should lead to the design of more rational targeted therapies for highly aggressive and fatal thyroid cancers. PMID:24788702

  9. Proteomic analysis of cancer stem cells in human prostate cancer cells

    SciTech Connect

    Lee, Eun-Kyung; Cho, Hyungdon; Kim, Chan-Wha

    2011-08-26

    Highlights: {yields} DU145 prostate cancer cell line was isolated into CD44+ or CD44- cells. {yields} We confirmed CD44+ DU145 cells are more proliferative and tumorigenic than CD44- DU145 cells. {yields} We analyzed and identified proteins that were differentially expressed between CD44+ and CD44- DU145 cells. {yields} Cofilin and Annexin A5 associated with cancer were found to be positively correlated with CD44 expression. -- Abstract: Results from recent studies support the hypothesis that cancer stem cells (CSCs) are responsible for tumor initiation and formation. Here, we applied a proteome profiling approach to investigate the mechanisms of CSCs and to identify potential biomarkers in the prostate cancer cell line DU145. Using MACS, the DU145 prostate cancer cell line was isolated into CD44+ or CD44- cells. In sphere culture, CD44+ cells possessed stem cell characteristics and highly expressed genes known to be important in stem cell maintenance. In addition, they showed strong tumorigenic potential in the clonogenic assay and soft agar colony formation assay. We then analyzed and identified proteins that were differentially expressed between CD44+ and CD44- using two-dimensional gel electrophoresis and LC-MS/MS. Cofilin and Annexin A5, which are associated with proliferation or metastasis in cancer, were found to be positively correlated with CD44 expression. These results provide information that will be important to the development of new cancer diagnostic tools and understanding the mechanisms of CSCs although a more detailed study is necessary to investigate the roles of Cofilin and Annexin A5 in CSCs.

  10. Reactive Oxygen Species in Cancer Stem Cells

    PubMed Central

    Shi, Xiaoke; Zhang, Yan; Zheng, Junheng

    2012-01-01

    Abstract Significance: Reactive oxygen species (ROS), byproducts of aerobic metabolism, are increased in many types of cancer cells. Increased endogenous ROS lead to adaptive changes and may play pivotal roles in tumorigenesis, metastasis, and resistance to radiation and chemotherapy. In contrast, the ROS generated by xenobiotics disturb the redox balance and may selectively kill cancer cells but spare normal cells. Recent Advances: Cancer stem cells (CSCs) are integral parts of pathophysiological mechanisms of tumor progression, metastasis, and chemo/radio resistance. Currently, intracellular ROS in CSCs is an active field of research. Critical Issues: Normal stem cells such as hematopoietic stem cells reside in niches characterized by hypoxia and low ROS, both of which are critical for maintaining the potential for self-renewal and stemness. However, the roles of ROS in CSCs remain poorly understood. Future Directions: Based on the regulation of ROS levels in normal stem cells and CSCs, future research may evaluate the potential therapeutic application of ROS elevation by exogenous xenobiotics to eliminate CSCs. Antioxid. Redox Signal. 16, 1215–1228. PMID:22316005

  11. Stromal influences on breast cancer cell growth.

    PubMed Central

    van Roozendaal, C. E.; van Ooijen, B.; Klijn, J. G.; Claassen, C.; Eggermont, A. M.; Henzen-Logmans, S. C.; Foekens, J. A.

    1992-01-01

    Paracrine influences from fibroblasts derived from different sources of breast tissue on epithelial breast cancer cell growth in vitro were investigated. Medium conditioned (CM) by fibroblasts derived from tumours, adjacent normal breast tissue, and normal breast tissue obtained from reduction mammoplasty or from skin tissue significantly stimulated the growth of the steroid-receptor positive cell lines MCF-7 and ZR 75.1. The proliferation index (PI) on MCF-7 cells with CM from fibroblasts derived from breast tumour tissue was significantly higher than that obtained with fibroblasts derived from adjacent normal breast tissue (2p less than 0.05, n = 8). The PI obtained with CM from normal fibroblast cultures from reduction mammoplasty tissue, like normal tissue adjacent to the tumour, fell in the lower range of values. Skin fibroblast, like tumour tissue derived fibroblast, CM caused a high range PI. MDA-MB-231 and Evsa-T, two steroid-receptor negative cell lines, showed only a minor growth stimulatory responses with some of the fibroblast CM's. Evsa-T was occasionally inhibited by CM's. In conclusion, stromal factors play a role in the growth regulation of human breast cancer cells. The effects on cancer cell growth are, however, varying depending on the source of the stroma and the characteristics of the epithelial tumour cells. PMID:1733444

  12. Lymphatic endothelial cells actively regulate prostate cancer cell invasion.

    PubMed

    Shah, Tariq; Wildes, Flonne; Kakkad, Samata; Artemov, Dmitri; Bhujwalla, Zaver M

    2016-07-01

    Lymphatic vessels serve as the primary route for metastatic spread to lymph nodes. However, it is not clear how interactions between cancer cells and lymphatic endothelial cells (LECs), especially within hypoxic microenvironments, affect the invasion of cancer cells. Here, using an MR compatible cell perfusion assay, we investigated the role of LEC-prostate cancer (PCa) cell interaction in the invasion and degradation of the extracellular matrix (ECM) by two human PCa cell lines, PC-3 and DU-145, under normoxia and hypoxia, and determined the metabolic changes that occurred under these conditions. We observed a significant increase in the invasion of ECM by invasive PC-3 cells, but not poorly invasive DU-145 cells when human dermal lymphatic microvascular endothelial cells (HMVEC-dlys) were present. Enhanced degradation of ECM by PC-3 cells in the presence of HMVEC-dlys identified interactions between HMVEC-dlys and PCa cells influencing cancer cell invasion. The enhanced ECM degradation was partly attributed to increased MMP-9 enzymatic activity in PC-3 cells when HMVEC-dlys were in close proximity. Significantly higher uPAR and MMP-9 expression levels observed in PC-3 cells compared to DU-145 cells may be one mechanism for increased invasion and degradation of matrigel by these cells irrespective of the presence of HMVEC-dlys. Hypoxia significantly decreased invasion by PC-3 cells, but this decrease was significantly attenuated when HMVEC-dlys were present. Significantly higher phosphocholine was observed in invasive PC-3 cells, while higher glycerophosphocholine was observed in DU-145 cells. These metabolites were not altered in the presence of HMVEC-dlys. Significantly increased lipid levels and lipid droplets were observed in PC-3 and DU-145 cells under hypoxia reflecting an adaptive survival response to oxidative stress. These results suggest that in vivo, invasive cells in or near lymphatic endothelial cells are likely to be more invasive and degrade the ECM

  13. Circulating Tumor Cells in Breast Cancer Patients.

    PubMed

    Hall, Carolyn; Valad, Lily; Lucci, Anthony

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer among women, resulting in an estimated 40,000 deaths in 2014.1 Metastasis, a complex, multi-step process, remains the primary cause of death for these patients. Although the mechanisms involved in metastasis have not been fully elucidated, considerable evidence suggests that metastatic spread is mediated by rare cells within the heterogeneous primary tumor that acquire the ability to invade into the bloodstream. In the bloodstream, they can travel to distant sites, sometimes remaining undetected and in a quiescent state for an extended period of time before they establish distant metastases in the bone, lung, liver, or brain. These occult micrometastatic cells (circulating tumor cells, CTCs) are rare, yet their prognostic significance has been demonstrated in both metastatic and non-metastatic breast cancer patients. Because repeated tumor tissue collection is typically not feasible and peripheral blood draws are minimally invasive, serial CTC enumeration might provide "real-time liquid biopsy" snapshots that could be used to identify early-stage breast cancer patients with micrometastatic disease who are at risk for disease progression and monitor treatment response in patients with advanced disease. In addition, characterizing CTCs might aid in the development of novel, personalized therapies aimed at eliminating micrometastases. This review describes current CTC isolation, detection, and characterization strategies in operable breast cancer. PMID:27481009

  14. New insights into pancreatic cancer stem cells

    PubMed Central

    Rao, Chinthalapally V; Mohammed, Altaf

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biological understanding of pancreatic cancer. Even after the emergence of recent new targeted agents and the use of multiple therapeutic combinations, no treatment option is viable in patients with advanced cancer. Developing novel strategies to target progression of PC is of intense interest. A small population of pancreatic cancer stem cells (CSCs) has been found to be resistant to chemotherapy and radiation therapy. CSCs are believed to be responsible for tumor initiation, progression and metastasis. The CSC research has recently achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent. This leads to focus on understanding the role of pancreatic CSCs. The focus on CSCs may offer new targets for prevention and treatment of this deadly cancer. We review the most salient developments in important areas of pancreatic CSCs. Here, we provide a review of current updates and new insights on the role of CSCs in pancreatic tumor progression with special emphasis on DclK1 and Lgr5, signaling pathways altered by CSCs, and the role of CSCs in prevention and treatment of PC. PMID:25914762

  15. Circulating tumor cells in lung cancer.

    PubMed

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. PMID:23207444

  16. Prolonged Drug Selection of Breast Cancer Cells and Enrichment of Cancer Stem Cell Characteristics

    PubMed Central

    Calcagno, Anna Maria; Salcido, Crystal D.; Gillet, Jean-Pierre; Wu, Chung-Pu; Fostel, Jennifer M.; Mumau, Melanie D.; Gottesman, Michael M.; Varticovski, Lyuba

    2010-01-01

    Background Cancer stem cells are presumed to have virtually unlimited proliferative and self-renewal abilities and to be highly resistant to chemotherapy, a feature that is associated with overexpression of ATP-binding cassette transporters. We investigated whether prolonged continuous selection of cells for drug resistance enriches cultures for cancer stem–like cells. Methods Cancer stem cells were defined as CD44+/CD24− cells that could self-renew (ie, generate cells with the tumorigenic CD44+/CD24− phenotype), differentiate, invade, and form tumors in vivo. We used doxorubicin-selected MCF-7/ADR cells, weakly tumorigenic parental MCF-7 cells, and MCF-7/MDR, an MCF-7 subline with forced expression of ABCB1 protein. Cells were examined for cell surface markers and side-population fractions by microarray and flow cytometry, with in vitro invasion assays, and for ability to form mammospheres. Xenograft tumors were generated in mice to examine tumorigenicity (n = 52). The mRNA expression of multidrug resistance genes was examined in putative cancer stem cells and pathway analysis of statistically significantly differentially expressed genes was performed. All statistical tests were two-sided. Results Pathway analysis showed that MCF-7/ADR cells express mRNAs from ABCB1 and other genes also found in breast cancer stem cells (eg, CD44, TGFB1, and SNAI1). MCF-7/ADR cells were highly invasive, formed mammospheres, and were tumorigenic in mice. In contrast to parental MCF-7 cells, more than 30% of MCF-7/ADR cells had a CD44+/CD24− phenotype, could self-renew, and differentiate (ie, produce CD44+/CD24− and CD44+/CD24+ cells) and overexpressed various multidrug resistance–linked genes (including ABCB1, CCNE1, and MMP9). MCF-7/ADR cells were statistically significantly more invasive in Matrigel than parental MCF-7 cells (MCF-7 cells = 0.82 cell per field and MCF-7/ADR = 7.51 cells per field, difference = 6.69 cells per field, 95% confidence interval = 4.82 to 8

  17. Compensatory adrenal growth - A neurally mediated reflex

    NASA Technical Reports Server (NTRS)

    Dallman, M. F.; Engeland, W. C.; Shinsako, J.

    1976-01-01

    The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adrenal at 12 h resulted in an enlarged right adrenal at 12 h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement of 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.

  18. Modeling Selective Elimination of Quiescent Cancer Cells from Bone Marrow

    PubMed Central

    Cavnar, Stephen P.; Rickelmann, Andrew D.; Meguiar, Kaille F.; Xiao, Annie; Dosch, Joseph; Leung, Brendan M.; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2015-01-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. PMID:26408255

  19. A rare-cell detector for cancer

    PubMed Central

    Krivacic, Robert T.; Ladanyi, Andras; Curry, Douglas N.; Hsieh, H. B.; Kuhn, Peter; Bergsrud, Danielle E.; Kepros, Jane F.; Barbera, Todd; Ho, Michael Y.; Chen, Lan Bo; Lerner, Richard A.; Bruce, Richard H.

    2004-01-01

    Although a reliable method for detection of cancer cells in blood would be an important tool for diagnosis and monitoring of solid tumors in early stages, current technologies cannot reliably detect the extremely low concentrations of these rare cells. The preferred method of detection, automated digital microscopy (ADM), is too slow to scan the large substrate areas. Here we report an approach that uses fiber-optic array scanning technology (FAST), which applies laser-printing techniques to the rare-cell detection problem. With FAST cytometry, laser-printing optics are used to excite 300,000 cells per sec, and emission is collected in an extremely wide field of view, enabling a 500-fold speed-up over ADM with comparable sensitivity and superior specificity. The combination of FAST enrichment and ADM imaging has the performance required for reliable detection of early-stage cancer in blood. PMID:15249663

  20. Omental milky spots in screening gastric cancer stem cells.

    PubMed

    Cao, L; Hu, X; Zhang, Y; Sun, X T

    2011-01-01

    The existence of cancer stem and progenitor cells in solid tumors has been widely postulated. However, neither the cancer stem cells nor the cancer progenitor cells have been definitively identified and functionally characterized. Here we propose a new strategy to identify and isolate gastric cancer stem cells -using omental milky spots to screen gastric cancer stem cells in peritoneal metastasis mouse models of gastric cancer. In this study, we used the property that the macrophages in omental milky spots are cytotoxic against tumor cells and so able to screen and collect cancer stem cells. Our findings suggest that macrophages in omental milky spots have not only cytotoxic properties against tumor cells but also provide a microenvironment within milky spots in which cancer stem cells are capable to survive and grow into micrometastasis. Omental milky spot become a cancer stem cell niche in this situation. Further we studied the omental milky spots for screening gastric cancer cells (OMSS-GCCs) and found that omental milky spot enriched the volume of gastric cancer stem cells. Tumors were consistently generated after an injection of 1×103 OMSS-GCCs. OMSS-GCCs high express CD133 and low express CD324. Omental milky spots are a highly efficient "natural filter" for screening gastric cancer stem cells. PMID:21067262

  1. Apoptotic Death of Cancer Stem Cells for Cancer Therapy

    PubMed Central

    He, Ying-Chun; Zhou, Fang-Liang; Shen, Yi; Liao, Duan-Fang; Cao, Deliang

    2014-01-01

    Cancer stem cells (CSCs) play crucial roles in tumor progression, chemo- and radiotherapy resistance, and recurrence. Recent studies on CSCs have advanced understanding of molecular oncology and development of novel therapeutic strategies. This review article updates the hypothesis and paradigm of CSCs with a focus on major signaling pathways and effectors that regulate CSC apoptosis. Selective CSC apoptotic inducers are introduced and their therapeutic potentials are discussed. These include synthetic and natural compounds, antibodies and recombinant proteins, and oligonucleotides. PMID:24823879

  2. EXAFS studies of prostate cancer cell lines

    NASA Astrophysics Data System (ADS)

    Czapla, J.; Kwiatek, W. M.; Lekki, J.; Kisiel, A.; Steininger, R.; Goettlicher, J.

    2013-04-01

    Sulphur plays a vital role in every human organism. It is known, that sulphur-bearing compounds, such as for example cysteine and glutathione, play critical roles in development and progression of many diseases. Any alteration in sulphur's biochemistry could become a precursor of serious pathological conditions. One of such condition is prostate cancer, the most frequently diagnosed malignancy in the western world and the second leading cause of cancer related death in men. The purpose of presented studies was to examine what changes occur in the nearest chemical environment of sulphur in prostate cancer cell lines in comparison to healthy cells. The Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy was used, followed by theoretical calculations. The results of preliminary analysis is presented.

  3. The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines.

    PubMed

    Joseph, Immanual; Tressler, Robert; Bassett, Ekaterina; Harley, Calvin; Buseman, Christen M; Pattamatta, Preeti; Wright, Woodring E; Shay, Jerry W; Go, Ning F

    2010-11-15

    Cancer stem cells (CSC) are rare drug-resistant cancer cell subsets proposed to be responsible for the maintenance and recurrence of cancer and metastasis. Telomerase is constitutively active in both bulk tumor cell and CSC populations but has only limited expression in normal tissues. Thus, inhibition of telomerase has been shown to be a viable approach in controlling cancer growth in nonclinical studies and is currently in phase II clinical trials. In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. Additionally, imetelstat treatment reduced the CSC fractions present in the breast and pancreatic cell lines. In vitro treatment with imetelstat, but not control oligonucleotides, also reduced the proliferation and self-renewal potential of MCF7 mammospheres and resulted in cell death after <4 weeks of treatment. In vitro treatment of PANC1 cells showed reduced tumor engraftment in nude mice, concomitant with a reduction in the CSC levels. Differences between telomerase activity expression levels or telomere length of CSCs and bulk tumor cells in these cell lines did not correlate with the increased sensitivity of CSCs to imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations. Our results suggest that imetelstat-mediated depletion of CSCs may offer an alternative mechanism by which telomerase inhibition may be exploited for cancer therapy. PMID:21062983

  4. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    SciTech Connect

    Felthaus, O.; Ettl, T.; Gosau, M.; Driemel, O.; Brockhoff, G.; Reck, A.; Zeitler, K.; Hautmann, M.; Reichert, T.E.; Schmalz, G.; Morsczeck, C.

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  5. Primary malignant lymphoma combined with clinically "silent" pheochromocytoma in the same adrenal gland.

    PubMed

    Babinska, Anna; Peksa, Rafał; Sworczak, Krzysztof

    2015-01-01

    An increased number of adrenal tumors are now diagnosed due to the increased number of abdominal CT scans being performed. We present the first case of malignant lymphoma combined with clinically "silent" pheochromocytoma in the same adrenal gland. An abdominal CT scan demonstrates unilateral adrenal lesion which suggests pheochromocytoma or adrenal carcinoma. Laboratory examinations revealed a slight increase of 24-h urine vanillylmandelic acid and 24-h urinary methanephrine excretion. Histological examination revealed two intermingled tumor cell proliferations-diffuse B cell lymphoma and pheochromocytoma.Unexpected coexistence of catecholamine-producing tumor with the other adrenal lesion can lead to serious complications of diagnosis and treatment. The adequate preparation for surgery can protect patient from threatening catecholamine crisis. PMID:26419235

  6. Orthotopic Injection of Pancreatic Cancer Cells.

    PubMed

    Aiello, Nicole M; Rhim, Andrew D; Stanger, Ben Z

    2016-01-01

    Pancreatic ductal adenocarcinoma is an aggressive disease with a 5-yr survival rate of only 5%. The location of the pancreas in the abdomen, where it is obscured by other organs, makes it a difficult tissue to study and manipulate. This protocol describes in detail how to orthotopically inject cancer cells into the pancreas in mice. This technique is particularly useful when the cells must be manipulated in ways that cannot be modeled genetically. PMID:26729902

  7. Human Colon Cancer Cells Cultivated in Space

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  8. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    PubMed

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  9. Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism.

    PubMed

    Phiboonchaiyanan, Preeyaporn Plaimee; Kiratipaiboon, Chayanin; Chanvorachote, Pithi

    2016-04-25

    Cancer stem cells (CSCs), a subpopulation of cancer cells with high aggressive behaviors, have been identified in many types of cancer including lung cancer as one of the key mediators driving cancer progression and metastasis. Here, we have reported for the first time that ciprofloxacin (CIP), a widely used anti-microbial drug, has a potentiating effect on CSC-like features in human non-small cell lung cancer (NSCLC) cells. CIP treatment promoted CSC-like phenotypes, including enhanced anchorage-independent growth and spheroid formation. The known lung CSC markers: CD133, CD44, ABCG2 and ALDH1A1 were found to be significantly increased, while the factors involving in epithelial to mesenchymal transition (EMT): Slug and Snail, were depleted. Also, self-renewal transcription factors Oct-4 and Nanog were found to be up-regulated in CIP-treated cells. The treatment of CIP on CSC-rich populations obtained from secondary spheroids resulted in the further increase of CSC markers. In addition, we have proven that the mechanistic insight of the CIP induced stemness is through Caveolin-1 (Cav-1)-dependent mechanism. The specific suppression of Cav-1 by stably transfected Cav-1 shRNA plasmid dramatically reduced the effect of CIP on CSC markers as well as the CIP-induced spheroid formation ability. Cav-1 was shown to activate protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways in CSC-rich population; however, such an effect was rarely found in the main lung cancer cells population. These findings reveal a novel effect of CIP in positively regulating CSCs in lung cancer cells via the activation of Cav-1, Akt and ERK, and may provoke the awareness of appropriate therapeutic strategy in cancer patients. PMID:26947806

  10. Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

    PubMed Central

    Bhummaphan, Narumol; Chanvorachote, Pithi

    2015-01-01

    As cancer stem cells (CSCs) contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt) signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs. PMID:26339272

  11. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-07-06

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  12. Adrenal oncoctyoma of uncertain malignant potential: a rare etiology of adrenal incidentaloma.

    PubMed

    Kedia, Rohit R; Muinov, Lucy; Lele, Subodh M; Shivaswamy, Vijay

    2016-03-01

    A rare cause for rapid adrenal enlargement is adrenal oncocytoma of uncertain malignant potential. A full biochemical evaluation is warranted to screen secreting adrenal adenomas as well as to evaluate adrenal cortical carcinoma. Careful pathologic evaluation is required as the diagnosis of AOC cannot be made by imaging. PMID:27014458

  13. Cushing syndrome due to adrenal tumor

    MedlinePlus

    ... syndrome. It occurs when a tumor of the adrenal gland releases excess amounts of the hormone cortisol. Causes ... hormone cortisol. This hormone is made in the adrenal glands . Too much cortisol can be due to various ...

  14. Giant adrenal cyst displacing the right kidney

    PubMed Central

    Chodisetti, Subbarao; Boddepalli, Yogesh; Kota, Malakondareddy

    2016-01-01

    Adrenal cysts are rare and should be considered in the differential diagnosis of retroperitoneal cysts. We present a case of a huge adrenal cyst displacing the right kidney anteriorly toward the left side in a young female. PMID:26941503

  15. Unusual Adrenal and Brain Metastases From Follicular Thyroid Carcinoma Revealed by 131I SPECT/CT.

    PubMed

    Zhao, Zhen; Shen, Guo-hua; Liu, Bin; Kuang, An-ren

    2016-01-01

    The adrenal metastasis from differentiated thyroid carcinoma is uncommon. Metastatic involvement of both adrenal and brain in the same patient from differentiated thyroid carcinoma is rare. Here, we described an unusual case with iodine-avid lung, bone, adrenal, liver, and brain metastases from follicular thyroid carcinoma confirmed by 131I SPECT/CT. The utilization of SPECT/CT in thyroid cancer patients can detect the presence of metastases and also exclude potential false-positive lesions. Our case demonstrates that SPECT/CT is helpful in localizing and confirming metastatic lesions from differentiated thyroid carcinoma in rare and unusual sites. PMID:26018699

  16. [Stereotactic body radiation radiotherapy for oligometastatic non-small cell lung cancer (NSCLC): A case report].

    PubMed

    Leduc, C; Antoni, D; Quoix, É; Noël, G

    2015-05-01

    Metastatic non-small cell lung cancer is associated with a poor prognosis, and palliative chemotherapy is the mainstay of treatment. However, long-time survival has been observed in oligometastatic patients treated with locally ablative therapies to all sites of metastatic disease. An 80-year-old man was diagnosed with an adenocarcinoma of the lung. The right upper lobe lesion was classified cT2aN0M0 and was treated with stereotactic body radiation therapy at the dose of 60Gy in eight fractions. A few months after, he successively presented with two brain metastases and one left adrenal metastasis, with a complete response on the primary tumor. The three secondary lesions were treated with stereotactic body radiation therapy alone. Thirty months after the diagnosis and 12months after metastases' apparition, primary and brain lesion kept controlled (complete response). Oligometastatic non-small cell lung cancer management is not clear. Locally ablative therapies such as stereotactic body radiation therapy, surgery and radiofrequency are efficient and should be considered. A phase III study should evaluate radical treatment strategies in such patients. PMID:25841992

  17. What Is Kidney Cancer (Renal Cell Carcinoma)?

    MedlinePlus

    ... the key statistics about kidney cancer? What is kidney cancer? Kidney cancer is a cancer that starts ... and spread, see What Is Cancer? About the kidneys To understand more about kidney cancer, it helps ...

  18. Adrenal cortex dysfunction: CT findings

    SciTech Connect

    Huebener, K.H.; Treugut, H.

    1984-01-01

    The computed tomographic appearance of the adrenal gland was studied in 302 patients with possible endocrinologic disease and 107 patients undergoing CT for nonendocrinologic reasons. Measurements of adrenal size were also made in 100 adults with no known adrenal pathology. CT proved to be a sensitive diagnostic tool in combination with clinical studies. When blood hormone levels are increased, CT can differentiate among homogeneous organic hyperplasia, nodular hyperplasia, benign adenoma, and malignant cortical adenoma. When blood hormone levels are decreased, CT can demonstrate hypoplasia or metastatic tumorous destruction. Calcifications can be demonstrated earlier than on plain radiographs. When hormone elimination is increased, the morphologic substrate can be identified; tumorous changes can be localized and infiltration of surrounding organs recognized.

  19. Dendritic Cells in the Cancer Microenvironment

    PubMed Central

    Ma, Yang; Shurin, Galina V.; Peiyuan, Zhu; Shurin, Michael R.

    2013-01-01

    The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs) represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer. PMID:23386903

  20. Angiomyolipoma and Malignant PEComa: Discussion of Two Rare Adrenal Tumors

    PubMed Central

    Kwazneski II, Douglas; Merrill, Megan; Young, Jessica; Sell, Harry

    2016-01-01

    Angiomyolipoma and PEComa are rare tumors descending from perivascular epithelial cells (PECs), with distinctive IHC, morphological, and ultrastructural features. The kidney is the most frequent site of origin, but not the only one; however, adrenal gland angiomyolipomas are extremely rare. We describe two cases being found in the adrenal glands. Given the paucity of literature on the subject, more information on this disease is necessary for diagnosis and treatment. Here, we describe two complete case reports, from presentation to treatment and follow-up, along with imaging and microscopic pathology samples, and provide a comprehensive review as to the history and current literature available regarding these extremely rare tumors. PMID:26998374

  1. Pharmacogenomic agreement between two cancer cell line data sets.

    PubMed

    2015-12-01

    Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases. PMID:26570998

  2. Budesonide-related adrenal insufficiency.

    PubMed

    Arntzenius, Alexander; van Galen, Louise

    2015-01-01

    Iatrogenic adrenal insufficiency is a potential harmful side effect of treatment with corticosteroids. It manifests itself when an insufficient cortisol response to biological stress leads to an Addisonian crisis: a life-threatening situation. We describe a case of a patient who developed an Addisonian crisis after inappropriate discontinuation of budesonide (a topical steroid used in Crohn's disease) treatment. Iatrogenic adrenal insufficiency due to budesonide use has been rarely reported. Prescribers should be aware of the resulting risk for an Addisonian crisis. PMID:26430235

  3. Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.

    PubMed

    Zhang, Wenwen; Cao, Lulu; Sun, Zijia; Xu, Jing; Tang, Lin; Chen, Weiwei; Luo, Jiayan; Yang, Fang; Wang, Yucai; Guan, Xiaoxiang

    2016-05-18

    The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy. PMID:27111245

  4. Ceramide signaling in cancer and stem cells

    PubMed Central

    Bieberich, Erhard

    2008-01-01

    Most of the previous work on the sphingolipid ceramide has been devoted to its function as an apoptosis inducer. Recent studies, however, have shown that in stem cells, ceramide has additional nonapoptotic functions. In this article, ceramide signaling will be reviewed in light of ‘systems interface biology’: as an interconnection of sphingolipid metabolism, membrane biophysics and cell signaling. The focus will be on the metabolic interconversion of ceramide and sphingomyelin or sphingosine-1-phosphate. Lipid rafts and sphingolipid-induced protein scaffolds will be discussed as a membrane interface for lipid-controlled cell signaling. Ceramide/sphingomyelin and ceramide/sphingosine-1-phosphate-interdependent cell-signaling pathways are significant for the regulation of cell polarity, apoptosis and/or proliferation, and as novel pharmacologic targets in cancer and stem cells. PMID:19050750

  5. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    SciTech Connect

    Gonzalez Valverde, F.M. Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-04-15

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture.

  6. Spontaneous bilateral adrenal hemorrhage following cholecystectomy

    PubMed Central

    Dahan, Meryl; Lim, Chetana; Salloum, Chady

    2016-01-01

    Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment. PMID:27275469

  7. Principles of cancer cell culture.

    PubMed

    Cree, Ian A

    2011-01-01

    The basics of cell culture are now relatively common, though it was not always so. The pioneers of cell culture would envy our simple access to manufactured plastics, media and equipment for such studies. The prerequisites for cell culture are a well lit and suitably ventilated laboratory with a laminar flow hood (Class II), CO(2) incubator, benchtop centrifuge, microscope, plasticware (flasks and plates) and a supply of media with or without serum supplements. Not only can all of this be ordered easily over the internet, but large numbers of well-characterised cell lines are available from libraries maintained to a very high standard allowing the researcher to commence experiments rapidly and economically. Attention to safety and disposal is important, and maintenance of equipment remains essential. This chapter should enable researchers with little prior knowledge to set up a suitable laboratory to do basic cell culture, but there is still no substitute for experience within an existing well-run laboratory. PMID:21516394

  8. Lymphocyte Infusion in Treating Patients With Relapsed Cancer After Bone Marrow or Peripheral Stem Cell Transplantation

    ClinicalTrials.gov

    2011-11-28

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  9. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    ClinicalTrials.gov

    2013-03-25

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  10. Hazard function for cancer patients and cancer cell dynamics.

    PubMed

    Horová, Ivana; Pospísil, Zdenek; Zelinka, Jirí

    2009-06-01

    The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data. PMID:18634801

  11. Cancer stem cells: Involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics

    PubMed Central

    Tanase, Cristiana Pistol; Neagu, Ana Iulia; Necula, Laura Georgiana; Mambet, Cristina; Enciu, Ana-Maria; Calenic, Bogdan; Cruceru, Maria Linda; Albulescu, Radu

    2014-01-01

    Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells (CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs. PMID:25152582

  12. Cancer stem cells: involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics.

    PubMed

    Tanase, Cristiana Pistol; Neagu, Ana Iulia; Necula, Laura Georgiana; Mambet, Cristina; Enciu, Ana-Maria; Calenic, Bogdan; Cruceru, Maria Linda; Albulescu, Radu

    2014-08-21

    Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells (CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs. PMID:25152582

  13. Targeting telomerase-expressing cancer cells

    PubMed Central

    Ouellette, Michel M; Wright, Woodring E; Shay, Jerry W

    2011-01-01

    Abstract The role of telomeres and telomerase as a target for cancer therapeutics is an area of continuing interest. This review is intended to provide an update on the field, pointing to areas in which our knowledge remains deficient and exploring the details of the most promising areas being advanced into clinical trials. Topics that will be covered include the role of dysfunctional telomeres in cellular aging and how replicative senescence provides an initial barrier to the emergence of immortalized cells, a hallmark of cancer. As an important translational theme, this review will consider possibilities for selectively targeting telomeres and telomerase to enhance cancer therapy. The role of telomerase as an immunotherapy, as a gene therapy approach using telomerase promoter driven oncolytic viruses and as a small oligonucleotide targeted therapy (Imetelstat) will be discussed. PMID:21332640

  14. Treating Cancer with Genetically Engineered T Cells

    PubMed Central

    Park, Tristen S.; Rosenberg, Steven A.; Morgan, Richard A.

    2011-01-01

    Administration of ex-vivo cultured, naturally occurring tumor-infiltrating lymphocytes (TILs) have been shown to mediate durable regression of melanoma tumors. However, the generation of TIL is not possible in all patients and there has been limited success in generating TIL in other cancers. Advances in genetic engineering have overcome these limitations by introducing tumor-antigen-targeting receptors into human T lymphocytes. Physicians can now genetically engineer lymphocytes to express highly active T-cell receptors (TCRs) or chimeric antigen receptors (CARs) targeting a variety of tumor antigens expressed in cancer patients. In this review we discuss the development of TCR and CAR gene transfer technology and the expansion of these therapies into different cancers with the recent demonstration of the clinical efficacy of these treatments. PMID:21663987

  15. Targeting telomerase-expressing cancer cells.

    PubMed

    Ouellette, Michel M; Wright, Woodring E; Shay, Jerry W

    2011-07-01

    The role of telomeres and telomerase as a target for cancer therapeutics is an area of continuing interest. This review is intended to provide an update on the field, pointing to areas in which our knowledge remains deficient and exploring the details of the most promising areas being advanced into clinical trials. Topics that will be covered include the role of dysfunctional telomeres in cellular aging and how replicative senescence provides an initial barrier to the emergence of immortalized cells, a hallmark of cancer. As an important translational theme, this review will consider possibilities for selectively targeting telomeres and telomerase to enhance cancer therapy. The role of telomerase as an immunotherapy, as a gene therapy approach using telomerase promoter driven oncolytic viruses and as a small oligonucleotide targeted therapy (Imetelstat) will be discussed. PMID:21332640

  16. Hypoxia and metabolic adaptation of cancer cells

    PubMed Central

    Eales, K L; Hollinshead, K E R; Tennant, D A

    2016-01-01

    Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype. PMID:26807645

  17. Xanthogranulomatous Adrenalitis: A Case Report of a Diabetic, 55-Year-Old Male.

    PubMed

    Reed, Caitlyn Trotter; Adams, Kristen; Shenoy, Veena

    2015-09-01

    We report a rare case of xanthogranulomatous adrenalitis in a 55-year-old man. The patient presented to the hospital with fever, nausea, and right flank pain. His medical history was significant for diabetes and an adrenal mass that was detected 6 years prior to presentation during a computed tomography (CT) scan for trauma secondary to a motor vehicle collision. The mass was thought to be a myelolipoma. Magnetic resonance imaging (MRI) revealed a 12-cm right adrenal mass that was considered suspicious for carcinoma, which was surgically excised and cultured intraoperatively. The cultures subsequently grew methicillin-resistant Staphylococcus aureus (MRSA). Grossly, the adrenal mass was an encapsulated, necrotic lesion with surrounding areas of fat necrosis. On histologic examination, the tissue showed sheets of histiocytes, lymphocytes, and plasma cells diffusely involving the adrenal gland along with bright yellow lipofuscin crystals in a background of necrosis and fibrosis. PMID:26044256

  18. Calcifying fibrous pseudotumor of the adrenal gland: A rare case report

    PubMed Central

    Wu, Tao; Zhu, Pingyu; Duan, Xi; Yang, Xuesong; Lu, Dongliang

    2016-01-01

    Calcifying fibrous pseudotumor (CFP) is a rare benign soft tissue lesion. We herein present an extremely rare case of CFP of the adrenal gland. A 32-year-old male patient presented to our hospital with a tumor-like lesion in the area of the left adrenal gland detected by ultrasound during a routine check-up several days prior. Contrast-enhanced magnetic resonance imaging examination revealed a solitary, well-circumscribed mass, in close proximity to the medial arterial branch of the left adrenal gland. Histological examination revealed that the tumor consisted of sheets of varying amount of inflammatory cell infiltration; interstitial fibrosis and psammomatous calcifications were also observed. To the best of our knowledge, this is the third case of CFP occurring in the adrenal gland in the published literature. We herein report the findings of this case and review the two previously reported cases of CFP of the adrenal gland with valuable information.

  19. Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

    PubMed Central

    Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N

    2015-01-01

    Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315

  20. Permanently Blocked Stem Cells Derived from Breast Cancer Cell Lines

    PubMed Central

    Sajithlal, Gangadharan B.; Rothermund, Kristi; Zhang, Fang; Dabbs, David J.; Latimer, Jean J.; Grant, Stephen G.; Prochownik, Edward V.

    2016-01-01

    Cancer stem cells (CSCs) are thought to be resistant to standard chemotherapeutic drugs and the inimical conditions of the tumor microenvironment. Obtaining CSCs in sufficient quantities and maintaining their undifferentiated state have been major hurdles to their further characterization and to the identification of new pharmaceuticals that preferentially target these cells. We describe here the tagging of CSC-like populations from four human breast cancer cell lines with green fluorescent protein (GFP) under the control of the Oct3/4 stem cell-specific promoter. As expected, GFP was expressed by the CSC-enriched populations. An unanticipated result, however, was that these cells remained blocked in a CSC-like state and tended to be resistant to chemotherapeutic drugs as well as acidotic and hypoxic conditions. These CSC-like cells possessed several other in vitro attributes of CSCs and were able to reproducibly generate tumors in immuno-compromised mice from as few as 100 cells. Moreover, the tumors derived from these cells were comprised almost exclusively of pure CSCs. The ability of the Oct3/4 promoter to block CSC differentiation underscores its potential general utility for obtaining highly purified CSC populations, although the mechanism by which it does so remains undefined and subject to further study. Nonetheless, such stable cell lines should be extremely valuable tools for studying basic questions pertaining to CSC biology and for the initial identification of novel CSC-specific chemotherapeutic agents, which can then be verified in primary CSCs. PMID:20506227

  1. Melanoma Cancer Stem Cells: Markers and Functions

    PubMed Central

    Parmiani, Giorgio

    2016-01-01

    The discovery of cancer stem cells (CSCs) in human solid tumors has allowed a better understanding of the biology and neoplastic transformation of normal melanocytes, and the possible mechanisms by which melanoma cells acquire tumorigenicity. In this review I summarize the literature findings on the potential biomarkers of melanoma CSCs, their presence in the melanoma cell populations, the interaction with the immune system (with both T and NK cells) and the role of melanoma CSCs in the clinics. Given the extraordinary progress in the therapy of melanoma caused by immune checkpoint antibodies blockade, I discuss how these antibodies can work by the activation of melanoma infiltrating T cells specifically recognizing neo-antigens expressed even by melanoma CSCs. This is the mechanism that can induce a regression of the metastatic melanomas. PMID:26978405

  2. AFM indentation study of breast cancer cells

    SciTech Connect

    Li, Q.S.; Lee, G.Y.H.; Ong, C.N.; Lim, C.T.

    2008-10-03

    Mechanical properties of individual living cells are known to be closely related to the health and function of the human body. Here, atomic force microscopy (AFM) indentation using a micro-sized spherical probe was carried out to characterize the elasticity of benign (MCF-10A) and cancerous (MCF-7) human breast epithelial cells. AFM imaging and confocal fluorescence imaging were also used to investigate their corresponding sub-membrane cytoskeletal structures. Malignant (MCF-7) breast cells were found to have an apparent Young's modulus significantly lower (1.4-1.8 times) than that of their non-malignant (MCF-10A) counterparts at physiological temperature (37 deg. C), and their apparent Young's modulus increase with loading rate. Both confocal and AFM images showed a significant difference in the organization of their sub-membrane actin structures which directly contribute to their difference in cell elasticity. This change may have facilitated easy migration and invasion of malignant cells during metastasis.

  3. Anesthetic Considerations on Adrenal Gland Surgery

    PubMed Central

    Domi, Rudin; Sula, Hektor; Kaci, Myzafer; Paparisto, Sokol; Bodeci, Artan; Xhemali, Astrit

    2015-01-01

    Adrenal gland surgery needs a multidisciplinary team including endocrinologist, radiologist, anesthesiologist, and surgeon. The indications for adrenal gland surgery include hormonal secreting and non-hormonal secreting tumors. Adrenal hormonal secreting tumors present to the anesthesiologist unique challenges requiring good preoperative evaluation, perioperative hemodynamic control, corrections of all electrolytes and metabolic abnormalities, a detailed and careful anesthetic strategy, overall knowledge about the specific diseases, control and maintaining of postoperative adrenal function, and finally a good collaboration with other involved colleagues. This review will focus on the endocrine issues, as well as on the above-mentioned aspects of anesthetic management during hormone secreting adrenal gland tumor resection. PMID:25368694

  4. AB241. Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P

    PubMed Central

    Huang, Bin; Wang, Dao-Hu; Chen, Jun-Xing; Qiu, Shao-Peng

    2016-01-01

    Background Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Methods We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Results Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells among five cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Conclusions Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.

  5. Adrenal Insufficiency and Addison's Disease

    MedlinePlus

    ... through hormonal blood and urine tests. A health care provider uses these tests first to determine whether cortisol levels are too ... if the diagnosis remains unclear. [ Top ] What other tests might a health care provider perform after diagnosis of adrenal insufficiency? After ...

  6. Endocrinopathies. Thyroid and adrenal disorders.

    PubMed

    Merchant, S R; Taboada, J

    1997-11-01

    This article focuses on common adrenal and thyroid diseases in the geriatric patient consisting of hypothyroidism in the dog, hyperthyroidism in the cat, and hyperadrenocorticism in the dog to include clinical signs, diagnosis, and management. A brief section on hyperadrenocorticism in the cat, thyroid tumors in the dog, and pheochromocytoma in the dog and cat are also included. PMID:9348631

  7. Targeting cancer stem cells using immunologic approaches

    PubMed Central

    Pan, Qin; Li, Qiao; Liu, Shuang; Ning, Ning; Zhang, Xiaolian; Xu, Yingxin; Chang, Alfred E.; Wicha, Max S.

    2015-01-01

    Cancer stem cells (CSCs) represent a small subset of tumor cells which have the ability to self-renew and generate the diverse cells that comprise the tumor bulk. They are responsible for local tumor recurrence and distant metastasis. However, they are resistant to conventional radiotherapy and chemotherapy. Novel immunotherapeutic strategies which specifically target CSCs may improve the efficacy of cancer therapy. To immunologically target CSC phenotypes, innate immune responses to CSCs have been reported using NK cells and γδT cells. To target CSC specifically, in vitro CSC-primed T cells have been successfully generated and shown targeting of CSCs in vivo after adoptive transfer. Recently, CSC-based dendritic cell vaccine has demonstrated significant induction of anti-CSC immunity both in vivo in immunocommpetent hosts and in vitro as evident by CSC reactivity of CSC vaccine-primed antibodies and T cells. In addition, identification of specific antigens or genetic alterations in CSCs may provide more specific targets for immunotherapy. ALDH, CD44, CD133 and HER2 have served as markers to isolate CSCs from a number of tumor types in animal models and human tumors. They might serve as useful targets for CSC immunotherapy. Finally, since CSCs are regulated by interactions with the CSC niche, these interactions may serve as additional targets for CSC immunotherapy. Targeting the tumor microenvironment, such as interrupting the immune cell e.g. myeloid derived suppressor cells, and cytokines e.g. IL-6 and IL-8, as well as the immune checkpoint (PD1/PDL1, et.al) may provide additional novel strategies to enhance the immunological targeting of CSCs. PMID:25873269

  8. Ewing's sarcoma cancer stem cell targeted therapy.

    PubMed

    Todorova, Roumiana

    2014-01-01

    Ewing`s sarcoma (ES) family of tumors (ESFTs) are round cell tumors of bone and soft tissues, afflicting children and young adults. This review summarizes the present findings about ES cancer stem cell (CSC) targeted therapy: prognostic factors, chromosomal translocations, initiation, epigenetic mechanisms, candidate cell of ES origin (Mesenchymal stem cells (MSCs) and Neural crest stem cells (NCSCs)). The ES CSC model, histopathogenesis, histogenesis, pathogenesis, ES mediated Hematopoietic stem progenitor cells (HSPCs) senescence are also discussed. ESFTs therapy is reviewed concerning CSCs, radiotherapy, risk of subsequent neoplasms, stem cell (SC) support, promising therapeutic targets for ES CSCs (CSC markers, immune targeting, RNAi phenotyping screens, proposed new drugs), candidate EWS-FLI1 target genes and further directions (including human embryonic stem cells (hESCs)). Bone marrow-derived human MSCs are permissive for EWS-FLI1 expression with transition to ESFT-like cellular phenotype. ESFTs are genetically related to NCSC, permissive for EWS-FLI1 expression and susceptible to oncogene-induced immortalization. Primitive neuroectodermal features and MSC origin of ESFTs provide a basis of immune targeting. The microRNAs profile of ES CSCs is shared by ESCs and CSCs from divergent tumor types. Successful reprogramming of differentiated human somatic cells into a pluripotent state allows creation of patient- and disease-specific SCs. The functional role of endogenous EWS at stem cell level on both senescence and tumorigenesis is a link between cancer and aging. The regulatory mechanisms of oncogenic activity of EWS fusions could provide new prognostic biomarkers, therapeutic opportunities and tumor-specific anticancer agents against ESFTs. PMID:24294922

  9. Cancer stem cells, metabolism, and therapeutic significance.

    PubMed

    Yang, Mengqi; Liu, Panpan; Huang, Peng

    2016-05-01

    Cancer stem cells (CSCs) have attracted much attention of the research community in the recent years. Due to their highly tumorigenic and drug-resistant properties, CSCs represent important targets for developing novel anticancer agents and therapeutic strategies. CSCs were first described in hematopoietic malignancies and subsequently identified in various types of solid tumors including brain, breast, lung, colon, melanoma, and ovarian cancer. CSCs possess special biological properties including long-term self-renewal capacity, multi-lineage differentiation, and resistance to conventional chemotherapy and radiotherapy. As such, CSCs are considered as a major source of residual disease after therapy leading to disease occurrence. Thus, it is very important to understand the cellular survival mechanisms specific to CSCs and accordingly develop effective therapeutic approaches to eliminate this subpopulation of cancer cells in order to improve the treatment outcome of cancer patients. Possible therapeutic strategies against CSCs include targeting the self-renewal pathways of CSCs, interrupting the interaction between CSCs and their microenvironment, and exploiting the unique metabolic properties of CSCs. In this review article, we will provide an overview of the biological characteristics of CSCs, with a particular focus on their metabolic properties and potential therapeutic strategies to eliminate CSCs. PMID:26864589

  10. Sialylation: an Avenue to Target Cancer Cells.

    PubMed

    Vajaria, Bhairavi N; Patel, Kinjal R; Begum, Rasheedunnisa; Patel, Prabhudas S

    2016-07-01

    Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration. PMID:26685886

  11. Heat induces gene amplification in cancer cells

    SciTech Connect

    Yan, Bin; Ouyang, Ruoyun; Huang, Chenghui; Liu, Franklin; Neill, Daniel; Li, Chuanyuan; Dewhirst, Mark

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and

  12. Cancer cell adaptation to chemotherapy

    PubMed Central

    Di Nicolantonio, Federica; Mercer, Stuart J; Knight, Louise A; Gabriel, Francis G; Whitehouse, Pauline A; Sharma, Sanjay; Fernando, Augusta; Glaysher, Sharon; Di Palma, Silvana; Johnson, Penny; Somers, Shaw S; Toh, Simon; Higgins, Bernie; Lamont, Alan; Gulliford, Tim; Hurren, Jeremy; Yiangou, Constantinos; Cree, Ian A

    2005-01-01

    Background Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Methods Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. Results In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. Conclusion This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of

  13. A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities

    PubMed Central

    Vizeacoumar, Franco J; Arnold, Roland; Vizeacoumar, Frederick S; Chandrashekhar, Megha; Buzina, Alla; Young, Jordan T F; Kwan, Julian H M; Sayad, Azin; Mero, Patricia; Lawo, Steffen; Tanaka, Hiromasa; Brown, Kevin R; Baryshnikova, Anastasia; Mak, Anthony B; Fedyshyn, Yaroslav; Wang, Yadong; Brito, Glauber C; Kasimer, Dahlia; Makhnevych, Taras; Ketela, Troy; Datti, Alessandro; Babu, Mohan; Emili, Andrew; Pelletier, Laurence; Wrana, Jeff; Wainberg, Zev; Kim, Philip M; Rottapel, Robert; O'Brien, Catherine A; Andrews, Brenda; Boone, Charles; Moffat, Jason

    2013-01-01

    Improved efforts are necessary to define the functional product of cancer mutations currently being revealed through large-scale sequencing efforts. Using genome-scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co-culture competition assays to generate a high-confidence genetic interaction network of differentially essential or differential essentiality (DiE) genes. The network uncovered examples of conserved genetic interactions, densely connected functional modules derived from comparative genomics with model systems data, functions for uncharacterized genes in the human genome and targetable vulnerabilities. Finally, we demonstrate a general applicability of DiE gene signatures in determining genetic dependencies of other non-isogenic cancer cell lines. For example, the PTEN−/− DiE genes reveal a signature that can preferentially classify PTEN-dependent genotypes across a series of non-isogenic cell lines derived from the breast, pancreas and ovarian cancers. Our reference network suggests that many cancer vulnerabilities remain to be discovered through systematic derivation of a network of differentially essential genes in an isogenic cancer cell model. PMID:24104479

  14. Clinical significance of T cell metabolic reprogramming in cancer.

    PubMed

    Herbel, Christoph; Patsoukis, Nikolaos; Bardhan, Kankana; Seth, Pankaj; Weaver, Jessica D; Boussiotis, Vassiliki A

    2016-12-01

    Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process. Currently, there is intense interest in understanding the cause and effect relationship between metabolic reprogramming and T cell differentiation. After the recent success of cancer immunotherapy, the crosstalk between immune system and cancer has come to the forefront of clinical and basic research. One of the key goals is to delineate how metabolic alterations of cancer influence metabolism-regulated function and differentiation of tumor resident T cells and how such effects might be altered by immunotherapy. Here, we review the unique metabolic features of cancer, the implications of cancer metabolism on T cell metabolic reprogramming during antigen encounters, and the translational prospective of harnessing metabolism in cancer and T cells for cancer therapy. PMID:27510264

  15. Targeting cancer cell metabolism in pancreatic adenocarcinoma

    PubMed Central

    Cohen, Romain; Neuzillet, Cindy; Tijeras-Raballand, Annemilaï; Faivre, Sandrine; de Gramont, Armand; Raymond, Eric

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided. PMID:26164081

  16. Genomics of Squamous Cell Lung Cancer

    PubMed Central

    Rooney, Melissa; Devarakonda, Siddhartha

    2013-01-01

    Approximately 30% of patients with non-small cell lung cancer have the squamous cell carcinoma (SQCC) histological subtype. Although targeted therapies have improved outcomes in patients with adenocarcinoma, no agents are currently approved specifically for use in SQCC. The Cancer Genome Atlas (TCGA) recently published the results of comprehensive genomic analyses of tumor samples from 178 patients with SQCC of the lung. In this review, we briefly discuss key molecular aberrations reported by TCGA and other investigators and their potential therapeutic implications. Carefully designed preclinical and clinical studies based on these large-scale genomic analyses are critical to improve the outcomes of patients with SQCC of lung in the near future. PMID:23728941

  17. Cancer stem cells in haematological malignancies

    PubMed Central

    Golab, Jakub

    2015-01-01

    At least several types of human haematological malignancies can now be seen as ‘stem-cell diseases’. The best-studied in this context is acute myeloid leukaemia (AML). It has been shown that these diseases are driven by a pool of ‘leukaemia stem cells (LSC)’, which remain in the quiescent state, have the capacity to survive and self-renew, and are responsible for the recurrence of cancer after classical chemotherapy. It has been understood that LSC must be eliminated in order to cure patients suffering from haematological cancers. Recent advances in LSC research have allowed for description of LSC phenotype and identification of potential targets for anti-LSC therapies. This concise review summarises the current view on LSC biology and targeted approaches against LSC. PMID:25691816

  18. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  19. Mutations in ribosomal proteins: Apoptosis, cell competition, and cancer.

    PubMed

    Baker, Nicholas E; Kale, Abhijit

    2016-01-01

    Mutations affecting multiple ribosomal proteins are implicated in cancer. Using genetic mosaics in the fruit fly Drosophila, we describe 3 apoptotic mechanisms that affect Rp/Rp homozygous mutant cells, Rp/+ heterozygous cells, or Rp/+ heterozygous cells in competition with nearby wild type cells, and discuss how apoptosis might be related to cancer predisposition. PMID:27308545

  20. Inhibition of Cancer Cell Migration by Multiwalled Carbon Nanotubes.

    PubMed

    García-Hevia, Lorena; Valiente, Rafael; Fernández-Luna, José L; Flahaut, Emmanuel; Rodríguez-Fernández, Lidia; Villegas, Juan C; González, Jesús; Fanarraga, Mónica L

    2015-08-01

    Inhibiting cancer cell migration and infiltration to other tissues makes the difference between life and death. Multiwalled carbon nanotubes (MWCNTs) display intrinsic biomimetic properties with microtubules, severely interfering with the function of these protein filaments during cell proliferation, triggering cell death. Here it is shown MWCNTs disrupt the centrosomal microtubule cytoskeletal organization triggering potent antimigratory effects in different cancer cells. PMID:26097131

  1. Hepatic cancer stem cells may arise from adult ductal progenitors

    PubMed Central

    Nikolaou, Kostas C; Talianidis, Iannis

    2016-01-01

    Cancer stem cells (CSCs) are defined as cells within tumors that can self-renew and differentiate into heterogeneous lineages of cancerous cells. The origin of CSCs is not well understood. Recent evidence suggests that CSCs in hepatocellular carcinoma could be generated via oncogenic transformation and partial differentiation of adult hepatic ductal progenitor cells.

  2. Mutations in ribosomal proteins: Apoptosis, cell competition, and cancer

    PubMed Central

    Baker, Nicholas E.; Kale, Abhijit

    2016-01-01

    Mutations affecting multiple ribosomal proteins are implicated in cancer. Using genetic mosaics in the fruit fly Drosophila, we describe 3 apoptotic mechanisms that affect Rp/Rp homozygous mutant cells, Rp/+ heterozygous cells, or Rp/+ heterozygous cells in competition with nearby wild type cells, and discuss how apoptosis might be related to cancer predisposition. PMID:27308545

  3. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    PubMed Central

    Hu, Chenxia; Niestroj, Martin; Yuan, Daniel; Chang, Steven; Chen, Jie

    2015-01-01

    Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design

  4. Hypoxia-Inducible Factors in Cancer Stem Cells and Inflammation

    PubMed Central

    Peng, Gong; Liu, Yang

    2015-01-01

    Hypoxia-inducible factors (HIF) mediate metabolic switch in cells in hypoxic environments, including those in both normal and malignant tissues with limited supplies of oxygen. Paradoxically, recent studies have shown that cancer stem cells and activated immune effector cells exhibit high HIF activity in normoxic environments and that HIF activity is critical in maintenance of cancer stem cells as well as differentiation and function of inflammatory cells. Since inflammation and cancer stem cells are two major barriers to effective cancer therapy, targeting HIF may provide a new approach for the ultimate challenges. PMID:25857287

  5. Intraoperative identification of adrenal-renal fusion.

    PubMed

    Boll, Griffin; Rattan, Rishi; Yilmaz, Osman; Tarnoff, Michael E

    2015-01-01

    Adrenal - renal fusion is a rare entity defined as incomplete encapsulation of the adrenal gland and kidney with histologically adjacent functional tissue. This report describes the first published intraoperative identification of this anomaly during laparoscopic adrenalectomy. The patient was a 59-year-old man with chronic hypertension refractory to multiple antihypertensives found to be caused by a right-sided aldosterone-producing adrenal adenoma in the setting of bilateral adrenal hyperplasia. During laparoscopic adrenalectomy, the normal avascular plane between the kidney and adrenal gland was absent. Pathologic evaluation confirmed adrenal - renal fusion without adrenal heterotopia. Identified intraoperatively, this may be misdiagnosed as invasive malignancy, and thus awareness of this anomaly may help prevent unnecessarily morbid resection. PMID:26195881

  6. [Effect of Conditioned Medium from Endothelial Cells on Cancer Stem Cell Phenotype of Hepatoma Cells].

    PubMed

    Feng, Chuan; Yang, Xianjiong; Sun, Jinghui; Luo, Qing; Song, Guanbin

    2015-10-01

    In this study, we aimed to investigate the influences of conditioned medium from human umbilical vein endothelial cells (HUVEC) on cancer stem cell phenotype of human hepatoma cells. HUVEC and human hepatoma cells (MHCC97H) were cultured, respectively, and then the MHCC97H cells were co-cultured with conditioned medium from HUVEC (EC-CM) with Transwell system. Anti-cancer drug sensitivity, colony-formation, migration/invasion ability, expression of cancer stem cell marker and sphere formation were performed to determine the cancer stem cell phenotype in MHCC97H cells. We found that MHCC97H cells co-cultured with EC-CM exhibited significantly higher colony-formation ability and lower sensitivity of anti-cancer drugs 5-FU and Cis. Transwell assay showed that treatment with EC-CM obviously increased migration and invasion of MHCC97H cells. Moreover, increased sphere forming capability and expression of CD133 in MHCC97H cells were observed after co-cultured with EC-CM. These results suggested that EC-CM could promote cancer stem cell phenotype of hepatoma cells. PMID:26964312

  7. Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells

    PubMed Central

    Oh, Jisun; Hlatky, Lynn; Jeong, Yong-Seob; Kim, Dohoon

    2016-01-01

    Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs. PMID:27376325

  8. Targeting the sumoylation pathway in cancer stem cells

    PubMed Central

    Bogachek, Maria V; De Andrade, James P; Weigel, Ronald J

    2014-01-01

    Cancer stem cells (CSCs) represent a subset of tumor cells with tumor-initiating potential. We recently demonstrated that inhibition of the sumoylation pathway cleared the CSC population and repressed the outgrowth of basal breast cancer xenografts. Targeting the sumoylation pathway offers a novel treatment strategy for basal breast cancer. PMID:27308355

  9. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  10. CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer.

    PubMed

    Cui, Fei; Wang, Jian; Chen, Duan; Chen, Yi-Jiang

    2011-03-01

    Lung cancer is the most common cause of cancer-related death worldwide. Current investigations in the field of cancer research have intensively focused on the 'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially considered as a stem cell marker only in the hematopoietic system and the nervous system, the membrane antigen also identifies tumorigenic cells in certain solid tumors. In this study, we investigated the human lung cancer cell lines A549, H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after chemotherapy drug selection and the fluorescence-activated cell sorting analysis showed that CD133 only functioned as a marker in the small cell lung cancer line H446. The sorted CD133+ subset presented stem cell-like features, including self-renewal, differentiation, proliferation and tumorigenic capacity in subsequent assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain stable, which may explain the controversies arising from previous studies. Therefore, the CD133+ subset should provide an enriched source of tumor-initiating cells among H446 cells. Moreover, the antigen could be used as an investigative marker of the tumorigenic process and an effective treatment for small cell lung cancer. PMID:21174061

  11. Reprogramming of human cancer cells to pluripotency for models of cancer progression

    PubMed Central

    Kim, Jungsun; Zaret, Kenneth S

    2015-01-01

    The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. PMID:25712212

  12. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients. PMID:26483336

  13. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma

    PubMed Central

    Banat, G-Andre; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Wilhelm, Jochen; Weigert, Andreas; Olesch, Catherine; Ebel, Katharina; Stiewe, Thorsten; Grimminger, Friedrich; Seeger, Werner; Fink, Ludger; Savai, Rajkumar

    2015-01-01

    Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition. PMID:26413839

  14. Microrheology of keratin networks in cancer cells

    NASA Astrophysics Data System (ADS)

    Paust, T.; Paschke, S.; Beil, M.; Marti, O.

    2013-12-01

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a deceasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior.

  15. Microrheology of keratin networks in cancer cells.

    PubMed

    Paust, T; Paschke, S; Beil, M; Marti, O

    2013-12-01

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a decreasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. PMID:24305115

  16. Wnt/{beta}-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    SciTech Connect

    Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

    2010-02-12

    Wnt/{beta}-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that {beta}-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of {beta}-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of {beta}-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/{beta}-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

  17. Cancer Cell Invasion: Treatment and Monitoring Opportunities in Nanomedicine

    PubMed Central

    Veiseh, Omid; Kievit, Forrest; Ellenbogen, Richard G.; Zhang, Miqin

    2011-01-01

    Cell invasion is an intrinsic cellular pathway whereby cells respond to extracellular stimuli to migrate through and modulate the structure of their extracellular matrix (ECM) in order to develop, repair, and protect the body’s tissues. In cancer cells this process can become aberrantly regulated and lead to cancer metastasis. This cellular pathway contributes to the vast majority of cancer related fatalities, and therefore has been identified as a critical therapeutic target. Researchers have identified numerous potential molecular therapeutic targets of cancer cell invasion, yet delivery of therapies remains a major hurdle. Nanomedicine is a rapidly emerging technology which may offer a potential solution for tackling cancer metastasis by improving the specificity and potency of therapeutics delivered to invasive cancer cells. In this review we examine the biology of cancer cell invasion, its role in cancer progression and metastasis, molecular targets of cell invasion, and therapeutic inhibitors of cell invasion. We then discuss how the field of nanomedicine can be applied to monitor and treat cancer cell invasion. We aim to provide a perspective on how the advances in cancer biology and the field of nanomedicine can be combined to offer new solutions for treating cancer metastasis. PMID:21295093

  18. Biomarkers to Target Heterogeneous Breast Cancer Stem Cells

    PubMed Central

    Hwang-Verslues, Wendy W.; Lee, Wen-Hwa; Lee, Eva Y.-H.P.

    2012-01-01

    Breast cancer is the most common cancer and the second leading cause of death in U.S. women. Due to early detection and advanced treatment, the breast cancer death rate has been declining since 1990. However, disease recurrence is still the major obstacle in moving from therapy to truly curative treatments. Recent evidence has indicated that breast cancer recurrence is often caused by a subpopulation of breast cancer cells. This subset of cancer cells, usually referred to as breast cancer stem cells (BCSCs), exhibits stem cell phenotypes. They can self-renew and asymmetrically divide to more differentiated cancer cells. These cells are also highly resistant to conventional therapeutic reagents. Therefore, identifying and characterizing these BCSC subpopulations within the larger population of breast cancer cells is essential for developing new strategies to treat breast cancer and prevent recurrence. In this review article, we discuss the current proposed model for the origin of tumor heterogeneity, summarize the recent findings of cell surface and cytoplasmic markers for BCSC identification, review the regulatory mechanisms by which BCSCs maintain or non-cancer stem cells acquire BCSC characteristics, describe the proposed strategies to eliminate BCSCs, and highlight the current limitations and challenges to translate basic BCSC research to clinical application including establishment of clinical biomarkers and therapeutic treatments specifically targeting BCSCs. PMID:24977105

  19. Cell-ECM Interactions During Cancer Invasion

    NASA Astrophysics Data System (ADS)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  20. Cloning of human lung cancer cells.

    PubMed Central

    Walls, G. A.; Twentyman, P. R.

    1985-01-01

    We have carried out a comparison of two different methods for cloning human lung cancer cells. The method of Courtenay & Mills (1978) generally gave higher plating efficiencies (PE) than the method of Carney et al. (1980). The number of colonies increased with incubation time in both methods and the weekly medium replenishment in the Courtenay method was advantageous for longer incubation times of several weeks. In the Courtenay method, the use of August rat red blood cells (RBC) and low oxygen tension were both found to be necessary factors for maximum plating efficiency. The usefulness of heavily irradiated feeder cells in improving PE is less certain; each cell type may have its own requirement. PMID:3904799