Management of neoplastic meningitis.

Science.gov (United States)

Roth, Patrick; Weller, Michael

2015-06-01

Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.

Total gastrectomy for non-neoplastic diseases

DEFF Research Database (Denmark)

Bjorn, Niels; Ainsworth, Alan Patrick; Mortensen, Michael Bau

2017-01-01

Background: The aim of this study was to describe patients who had total gastrectomy for non-neoplastic diseases within a well-defined geographical area. Material and Methods: Retrospective study of patients who had gastrectomy for a non-neoplastic disease at the Department of Surgery, Odense...... University Hospital from 1 January 2005 to 31 December 2014. Results: A total of 268 gastrectomies were performed with the 10-year period. Of these, ten (4%) were done for non-neoplastic diseases. Two were men and eight women with a median age of 51 years (range 31 to 96 years). Six had emergency surgery...... of 10 and 2 of 10, respectively. Histology of the resected specimens showed: Oedema, inflammation and/or necrosis (n=6), Menetrier's disease (n=2) and perforation (n=2). Conclusions: Gastrectomy for non-neoplastic diseases accounts for less than 5% of all gastrectomies. The majority of these cases...

The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.

Science.gov (United States)

Tanimoto, Ryuta; Palladino, Chiara; Xu, Shi-Qiong; Buraschi, Simone; Neill, Thomas; Gomella, Leonard G; Peiper, Stephen C; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2017-12-01

Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis. Copyright © 2017. Published by Elsevier B.V.

Early neuroimaging findings of glioblastoma mimicking non-neoplastic cerebral lesion.

Science.gov (United States)

Jung, Tae-Young; Jung, Shin

2007-09-01

A 54-year-old man and a 63-year-old woman presented with glioblastoma manifesting as seizure and headache, respectively. Magnetic resonance imaging of the two patients revealed hypointense area on T(1)-weighted imaging, and hyperintense area on T(2)-weighted and diffusion-weighted imaging, with no enhancement after gadolinium administration. Both patients underwent conservative therapy under diagnoses of non-neoplastic cerebral lesion. Six months later, they suffered aggravated symptoms and new neurological deficits. Follow-up magnetic resonance imaging revealed hypointense area on diffusion-weighted imaging and ring enhancement on T(1)-weighted imaging with gadolinium at the site of the previously detected lesions. The tumors showed growth pattern of superficial origin. The large enhanced masses were totally removed through craniotomy under neuronavigator guidance. The histological diagnoses were glioblastoma. Glioblastoma may mimic non-neoplastic conditions on neuroimaging in the early stages. Close follow up of such patients is essential.

DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats

International Nuclear Information System (INIS)

Christov, K.; Thomas, C.; Sandritter, W.

1975-01-01

Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. In stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated that most chromosomes were diploid; only a few cells were hyperdiploid. In thyroid adenomas and carcinomas scattering of the diploid region and an increased number of hyperdiploid cells were found. Among the various types of thyroid tumors neither a difference in the number of hyperdiploid cells, nor the typical pattern of the distribution of these cells in a histogram was found. The increased number of hyperdiploid cells in hyperplastic and neoplastic thyroids only suggested an increase in the proportion of cells entering the cell cycle and not an appearance of a neoplastic strain. (author)

DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats

Energy Technology Data Exchange (ETDEWEB)

Christov, K [National Center of Oncology, Academy of Medicine, Sofia-56 (Bulgaria); Thomas, C; Sandritter, W [Freiburg Univ. (F.R. Germany). Pathologisches Inst.

1975-01-01

Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. In stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated that most chromosomes were diploid; only a few cells were hyperdiploid. In thyroid adenomas and carcinomas scattering of the diploid region and an increased number of hyperdiploid cells were found. Among the various types of thyroid tumors neither a difference in the number of hyperdiploid cells, nor the typical pattern of the distribution of these cells in a histogram was found. The increased number of hyperdiploid cells in hyperplastic and neoplastic thyroids only suggested an increase in the proportion of cells entering the cell cycle and not an appearance of a neoplastic strain.

Electricity regulation and economic growth

OpenAIRE

Costa, M. Teresa (Maria Teresa), 1951-; Garcia-Quevedo, Jose; Trujillo-Baute, Elisa

2018-01-01

The main objective of this paper is to analyse the effect of electricity regulation on economic growth. Although the relationship between electricity consumption and economic growth has been extensively analysed in the empirical literature, this framework has not been used to estimate the effect of electricity regulation on economic growth. Understanding this effect is essential for the assessment of regulatory policy. Specifically, we assess the effects of two major areas of regulation, rene...

Pten regulates spindle pole movement through Dlg1-mediated recruitment of Eg5 to centrosomes

NARCIS (Netherlands)

Ree, J.H. van; Nam, H.J.; Jeganathan, K.B.; Kanakkanthara, A.; Deursen, J.M.A. van

2016-01-01

Phosphatase and tensin homologue (Pten) suppresses neoplastic growth by negatively regulating PI(3)K signalling through its phosphatase activity. To gain insight into the actions of non-catalytic Pten domains in normal physiological processes and tumorigenesis, we engineered mice lacking the

Morphological spectrum of non‑neoplastic lesions of the uterine ...

African Journals Online (AJOL)

Background: The uterine cervix is a gateway to several non‑neoplastic and neoplastic gynecological lesions. Most of these non‑neoplastic lesions are commonly found in women of reproductive age. These lesions constitute a source of morbidity and mortality in women worldwide hence the need to analyze them to provide ...

Development of a method for the accurate measurement of protein turnover in neoplastic cells grown in culture

International Nuclear Information System (INIS)

Silverman, J.A.

1984-01-01

In this study, it was shown that standard techniques for cell recovery and sample preparation for liquid scintillation counting led to underestimation of the radioactivity present in cell proteins by 20-40%. These techniques involved labeling with 3 He leucine or 14 C leucine, scraping the cells from the dish in a buffer, TCA precipitation of the cell proteins, solubilization in NaOH and counting in a liquid scintillation counter. Hydrolysis of the proteins with HCl or Pronase significantly increased the recovery of the labeled proteins. Also, solubilization in situ with NaOH or hydrolysis in situ with Pronase recovered 5-10% additional labeled proteins. The techniques developed here allow the accurate measurement of radioactivity in cell proteins. In addition, these techniques were used to study protein turnover in rat hepatoma cells grown in culture. These cells regulated their growth rate through changes in the protein synthesis rate as opposed to changes in the protein degradation rate. These data support the hypothesis that neoplastic cells, unlike normal cells, do not regulate proteolysis in growth control; normal cells under similar conditions have been shown to activate lysosomal proteolysis as they reach confluence. The physiologic implications of this observation are discussed

Connective tissue growth factor (CTGF) and cancer progression.

Science.gov (United States)

Chu, Chia-Yu; Chang, Cheng-Chi; Prakash, Ekambaranellore; Kuo, Min-Liang

2008-11-01

Connective tissue growth factor (CTGF) is a member of the CCN family of secreted, matrix-associated proteins encoded by immediate early genes that play various roles in angiogenesis and tumor growth. CCN family proteins share uniform modular structure which mediates various cellular functions such as regulation of cell division, chemotaxis, apoptosis, adhesion, motility, angiogenesis, neoplastic transformation, and ion transport. Recently, CTGF expression has been shown to be associated with tumor development and progression. There is growing body of evidence that CTGF may regulate cancer cell migration, invasion, angiogenesis, and anoikis. In this review, we will highlight the influence of CTGF expression on the biological behavior and progression of various cancer cells, as well as its regulation on various types of protein signals and their mechanisms.

Process for producing vegetative and tuber growth regulator

Science.gov (United States)

Stutte, Gary W. (Inventor); Yorio, Neil C. (Inventor)

1999-01-01

A process of making a vegetative and tuber growth regulator. The vegetative and tuber growth regulator is made by growing potato plants in a recirculating hydroponic system for a sufficient time to produce the growth regulator. Also, the use of the vegetative and growth regulator on solanaceous plants, tuber forming plants and ornamental seedlings by contacting the roots or shoots of the plant with a sufficient amount of the growth regulator to regulate the growth of the plant and one more of canopy size, plant height, stem length, internode number and presence of tubers in fresh mass. Finally, a method for regulating the growth of potato plants using a recirculating hydroponic system is described.

Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

Science.gov (United States)

Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

2011-01-01

Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

Depleted uranium induces neoplastic transformation in human lung epithelial cells.

Science.gov (United States)

Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

2010-02-15

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

Imaging of limbic para-neoplastic encephalitis

International Nuclear Information System (INIS)

Rimmelin, A.; Sellat, F.; Morand, G.; Quoix, E.; Clouet, P.L.; Dietemann, J.L.

1997-01-01

Para-neoplastic limbic encephalitis is a rare syndrome mostly associated with small cell lung cancer. We present the case of a 69-year-old man with selective amnesia suggesting limbic encephalitis. A neuroendocrine cell lung cancer was found, confirming the diagnostics of para-neoplastic limbic encephalitis. Contrast-enhanced cerebral CT was normal whether magnetic resonance imaging showed signal abnormalities of the medial part of temporal lobes and hippocampal regions. Because neurologic improvement may follow treatment of the primary tumor, early diagnosis is important. (authors)

Neoplastic pericardial disease. Analysis of 26 patients

Directory of Open Access Journals (Sweden)

Helena Nogueira Soufen

1999-01-01

Full Text Available PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

Stringency of environmental regulation and aquaculture growth

DEFF Research Database (Denmark)

Gedefaw Abate, Tenaw; Nielsen, Rasmus; Tveterås, Ragnar

2016-01-01

remarkable growth in aquaculture while others have stagnated or even declined have not been determined. In this article, we investigate whether environmental regulations have an impact on aquaculture growth. Using a cross-country regression analysis, we show that stringent environmental regulations......During the last three decades, aquaculture has been the fastest growing animal-food-producing sector in the world, accounting for half of the present seafood supply. However, there is a significant growth disparity among aquaculture-producing countries. The reasons why some countries have achieved...... are negatively related to aquaculture growth, whereas GDP growth has a positive effect. Countries often face a difficult balancing act between growth and environmental considerations when devising regulations. Our empirical results suggest that stricter environmental regulations in developed countries have...

Positive regulation of prostate cancer cell growth by lipid droplet forming and processing enzymes DGAT1 and ABHD5

OpenAIRE

Mitra, Ranjana; Le, Thuc T.; Gorjala, Priyatham; Goodman Jr., Oscar B.

2017-01-01

Background Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prosta...

Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

Directory of Open Access Journals (Sweden)

Spyros Darmanis

2017-10-01

Full Text Available Summary: Glioblastoma (GBM is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor’s genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration. : Darmanis et al. perform single-cell transcriptomic analyses of neoplastic and stromal cells within and proximal to primary glioblastomas. The authors describe a population of neoplastic-infiltrating glioblastoma cells as well as a putative role of tumor-infiltrating immune cells in supporting tumor growth. Keywords: single cell, RNA-seq, glioma, glioblastoma, GBM, brain, heterogeneity, infiltrating, diffuse, checkpoint

Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

Science.gov (United States)

Russo, Francesco; Linsalata, Michele; Orlando, Antonella

2014-10-07

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

Photodynamic therapy and the treatment of neoplastic and non-neoplastic diseases of the larynx

International Nuclear Information System (INIS)

Biel, M.A.

1992-01-01

Approximately 12000 new cases of laryngeal carcinoma are reported yearly in the united States. Early carcinomas of the larynx (Tis, T1 and T2) are presently treated with either radiation therapy or surgery alone. Five year cure rates achieved with this therapy are 75-85%. Radiation therapy has the advantage of preserving physical integrity of the larynx, thereby preserving voice. Radiation therapy, however, has significant disadvantages even when small laryngeal fields of radiation are used. These disadvantages include discomfort and mucositis during and for potential prolonged periods after therapy, permanently altered voice quality, dysphagia, chondroradionecrosis of the larynx and trachea, and the prolonged length of therapy (6-7 weeks). This report presents the results of 10 patients treated with PDT for neo-plastic and non-neoplastic diseases of the larynx and tracheobronchial tree. (author). 12 refs., 1 tab

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

Science.gov (United States)

Findling, James W; Raff, Hershel

2017-05-01

Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

OpenAIRE

Camara, Geni NL; Cerqueira, Daniela M; Oliveira, Ana PG; Silva, Evandro O; Carvalho, Luciano GS; Martins, Cláudia RF

2003-01-01

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using c...

Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

Directory of Open Access Journals (Sweden)

Annika Mohr

Full Text Available Immunohistochemistry (IHC is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1, progesterone receptor (PGR, prolactin receptor (PRLR and growth hormone receptor (GHR gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

KAUST Repository

Li, Yulin; Choi, Peter  S.; Casey, Stephanie  C.; Dill, David  L.; Felsher, Dean  W.

2014-01-01

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

KAUST Repository

Li, Yulin

2014-08-01

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

NEOPLASTIC LESIONS OF THE APPENDIX

Directory of Open Access Journals (Sweden)

Piotr Bryk

2013-11-01

Full Text Available The aim of the research was to present the clinical observations of neoplastic lesions of the appendix (one carcinoid and two mucous cysts and to discuss various manners of treatment and prognosis. Material and methods: The authors of the following paper present a description of three cases of appendix tumours, two patients with a mucous cyst and a patient with carcinoid, against the background of all the appendectomies performed at the Clinical Department of General, Endocrine and Oncological Surgery of the Provincial Polyclinical Hospital in Kielce in the years 2005–2011. Results : Within the 7-year period, a total of 11 719 surgical operations have been performed, where 834 (7.1% were that of appendectomy. Among all of the removed vermiform appendixes, neoplastic lesions occurred in three cases constituting a mere 0.3% of all of the appendectomies performed within that period. In two of the cases there was a suspicion of mucous cysts before the surgical operation. In none of the above-mentioned cases was is possible to ultimately establish the diagnosis before the operation. The patients were subjected to a simple appendectomy. The patients are in good clinical health, with no signs of relapse. Conclusions : The presented cases of patients with appendix tumours illustrate the difficulty of preoperative detection of a neoplastic lesion. This is mainly due to a scantily symptomatic course or symptoms typical of appendicitis. In light of this, histopathological examination of each appendix should be treated as obligatory.

X-ray-induced in vitro neoplastic transformation of human diploid cells

International Nuclear Information System (INIS)

Borek, C.

1980-01-01

Techniques have recently been developed to identify and score quantitatively neoplastic transformation caused by x-rays in cultured cells derived from rodents. The present report describes for the first time the neoplastic transformation in vitro of human diploid cells by x-ray irradiation into cells which can progress in vitro into advanced stages of neoplastic development, namely, to form colonies in agar and give rise to tumors when injected into nude mice

Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: Morphologic and immunohistochemical findings and differential diagnosis

Directory of Open Access Journals (Sweden)

Pei-Wen Huang

2015-01-01

Full Text Available Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms′ tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result.

Genomic Analyses Reveal Global Functional Alterations That Promote Tumor Growth and Novel Tumor Suppressor Genes in Natural Killer-Cell Malignancies

DEFF Research Database (Denmark)

Kucuk, Can; Iqbal, Javeed; J. deLeeuw, Ronald

in cell proliferation, growth and energy metabolic processes important for the neoplastic cells. In deleted regions, genes showing decreased expression included transcription factors or repressors (e.g. SP4, PRDM1, NCOR1 and ZNF10), tumor suppressors or negative regulators of the cell cycle (e.g. CDKN2C...

Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation

Directory of Open Access Journals (Sweden)

Yiannis Drosos

2016-03-01

Full Text Available The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness.

A nine - year retrospective study of avian neoplastic diseases in ...

African Journals Online (AJOL)

Avian neoplastic diseases have been identified as one of the leading causes of mortality and production losses in commercial chickens in Nigeria. Although available reports described the trend of Marek's disease in Zaria, Kaduna state, they did not take cognizance of other neoplastic diseases of poultry hence the need for ...

Dasatinib inhibits the growth and survival of neoplastic human eosinophils (EOL-1) through targeting of FIP1L1-PDGFRalpha.

Science.gov (United States)

Baumgartner, Christian; Gleixner, Karoline V; Peter, Barbara; Ferenc, Veronika; Gruze, Alexander; Remsing Rix, Lily L; Bennett, Keiryn L; Samorapoompichit, Puchit; Lee, Francis Y; Pickl, Winfried F; Esterbauer, Harald; Sillaber, Christian; Superti-Furga, Giulio; Valent, Peter

2008-10-01

Chronic eosinophilic leukemia (CEL) is a myeloproliferative disorder characterized by molecular and/or cytogenetic evidence of clonality of eosinophils, marked eosinophilia, and organ damage. In many patients, the transforming mutation FIP1L1-PDGFRalpha and the related CHIC2 deletion are found. The respective oncoprotein, FIP1L1-PDGFRalpha, is considered to play a major role in malignant cell growth in CEL. The tyrosine kinase (TK) inhibitor imatinib (STI571) has been described to counteract the TK activity of FIP1L1-PDGFRalpha in most patients. However, not all patients with CEL show a response to imatinib. Therefore, several attempts have been made to identify other TK inhibitors that counteract growth of neoplastic eosinophils. We provide evidence that dasatinib, a multi-targeted kinase inhibitor, blocks the growth and survival of EOL-1, an eosinophil leukemia cell line carrying FIP1L1-PDGFRalpha. The effects of dasatinib on proliferation of EOL-1 cells were dose-dependent, with an IC50 of 0.5 to 1 nM, which was found to be in the same range when compared to IC50 values produced with imatinib. Dasatinib was also found to induce apoptosis in EOL-1 cells in a dose-dependent manner (IC50: 1-10 nM). The apoptosis-inducing effects of dasatinib on EOL-1 cells were demonstrable by light microscopy, flow cytometry, and in a TUNEL assay. In Western blot experiments, dasatinib completely blocked the phosphorylation of FIP1L1-PDGFRalpha in EOL-1 cells. Dasatinib inhibits the growth of leukemic eosinophils through targeting of the disease-related oncoprotein FIP1L1-PDGFRalpha. Based on this observation, dasatinib may be considered as a new interesting treatment option for patients with CEL.

Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo.

Directory of Open Access Journals (Sweden)

Jason R Sutherland

Full Text Available Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2, cytokines interleukin (IL -6, and -11 and vascular endothelial growth factor-A (VEGF-A. To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.

Gene regulation by growth factors

International Nuclear Information System (INIS)

Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

1988-01-01

To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies.

Science.gov (United States)

Aragona, Pasquale; Allegra, Alessandro; Postorino, Elisa Imelde; Rania, Laura; Innao, Vanessa; Wylegala, Edward; Nowinska, Anna; Ieni, Antonio; Pisani, Antonina; Musolino, Caterina; Puzzolo, Domenico; Micali, Antonio

2016-05-01

To investigate corneal confocal microscopic changes in nonneoplastic and neoplastic monoclonal gammopathies. Three groups of subjects were considered: group 1, twenty normal subjects; group 2, fifteen patients with monoclonal gammopathy of undetermined significance (MGUS); group 3, eight patients with smoldering multiple myeloma and eight patients with untreated multiple myeloma. After hematologic diagnosis, patients underwent ophthalmologic exam and in vivo confocal microscopic study. The statistical analysis was performed using ANOVA and Student-Newman-Keuls tests and receiver operating characteristic (ROC) curve analysis. Epithelial cells of gammopathic patients showed significantly higher reflectivity than controls, demonstrated by optical density (P < 0.001). Subbasal nerve density, branching, and beading were significantly altered in gammopathic patients (P = 0.01, P = 0.02, P = 0.02, respectively). The number of keratocytes was significantly reduced in neoplastic patients (P < 0.001 versus both normal and MGUS) in the anterior, medium, and posterior stroma. The ROC curve analysis showed good sensitivity and specificity for this parameter. Group 2 and 3 keratocytes showed higher nuclear and cytoplasmatic reflectivity in the medium and posterior stroma. Endothelial cells were not affected. Patients with neoplastic gammopathies showed peculiar alterations of the keratocyte number, which appeared significantly reduced. A follow-up with corneal confocal microscopy of patients with MGUS is suggested as a useful tool to identify peripheral tissue alterations linked to possible neoplastic disease development.

The effects of environmental deuterium on normal and neoplastic cultured cell development

International Nuclear Information System (INIS)

Bild, W.; Schuller, T.; Zhihai, Qin; Blankenstein, T.; Nastasa, V.; Haulica, I.

2000-01-01

The powdered culture media (RPMI - 1640) were reconstituted either with normal distilled water (150 ppm deuterium) either with deuterium - depleted water (DDW) in various concentrations (30, 60, 90 ppm) and sterilized by filtration with 0.2 μm filters. The cell lines used were NIH (normal mouse fibroblasts), RAG (mouse renal carcinoma) and TS/A (mouse mammary adenocarcinoma). In auxiliary tests, BAIBC mouse splenocytes in direct culture were used, stimulated for growth with concanavalin A or LPS (bacterial lipopolysaccharide). The estimation of the growth was made using the MTT assay or direct counting with trypan blue exclusion. The following results were obtained: Deuterium - depleted water had a stimulating effect on cell growth, the most important stimulating action being from the 90 ppm deuterium-water. The growth curves show, in a first phase, a stimulation of the rapid -growing neoplastic cells, followed by a slower growth of the normal cells. Amiloride 100 mM blocking of the Na + /K + membrane pump did not affect the cell growth curves, while the lansoprazole 100 mM blocking of the K + /H + ATP-ase brought the growth curves at the level of those with normal water. This might show an eventual involvement of the K + /H + antiport in the stimulating effects of the DDW. (authors)

X-ray-induced in vitro neoplastic transformation of human diploid cells

International Nuclear Information System (INIS)

Borek, C.

1980-01-01

The neoplastic transformation, in vitro, of human diploid cells by x-ray irradiation into cells which can progress, in vitro, into advanced stages of neoplastic development is described. The cells are shown to form colonies in agar and to give rise to tumours when injected into nude mice. (U.K.)

The spectrum of non- neoplastic skin lesions in Ibadan, Nigeria: a ...

African Journals Online (AJOL)

The other common specific skin lesions were lichen planus/lichenoid dermatitis 27(12.9% of 209 cases), verruca vulgaris 25 (12% of 209 cases). Conclusion: The number of histologically diagnosed non-neoplastic skin lesions is relatively small. There is a very wide spectrum of non-neoplastic skin lesions diagnosed within ...

Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

International Nuclear Information System (INIS)

Kuwert, T.; Morgenroth, C.; Woesler, B.; Matheja, P.; Palkovic, S.; Vollet, B.; Samnick, S.; Maasjosthusmann, U.; Lerch, H.; Gildehaus, F.J.; Wassmann, H.; Schober, O.

1996-01-01

Using single-photon emission tomography (SPET), the radiopharmaceutical L-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating higc-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. (orig.)

Knowledge of nursing students about the care provided to people with neoplastic wounds

Directory of Open Access Journals (Sweden)

Roseane Ferreira Gomes

2017-05-01

Full Text Available Objective: To investigate the knowledge of nursing students about the care provided to patients with neoplastic wound. Method: This is an exploratory research of a qualitative nature, which was attended by 15 students of the Bachelor's Degree in Nursing from the Center of Education and Health of the Federal University of Campina Grande, campus Cuité - PB, in the period from October to November 2015. For data collection, we used a form for an interview. The data were analyzed through the Technique of Thematic Analysis of Minayo. Results: From the analysis of the empirical material emerged the following thematic categories: Category 1 - Defining neoplastic wounds; Category 2 - Knowledge incipient on ‘neoplastic wounds’ for academic and professional practice; Category 3 - Envisioning the theme "neoplastic wound" in the Academy; Category 4 - Knowledge about methods of evaluation of neoplastic wounds and Category 5 - Knowledge of therapeutic modalities of neoplastic wounds. Conclusions: The academics know the evaluative method of a patient with neoplastic wound as integralizadora unit of care process; recognize palliative care as the best therapeutic modality for these customers, especially when they are in completion and indicate the products contraindicated in the treatment of these lesions; however, do not mention the covers and recommended substances for the control of the signs and symptoms of these injuries. In this context, it is believed that the creation of academic projects of extension, with the aim of creating opportunities for integration between theory and practice, is one of the ways to improve the knowledge.   Keywords: Knowledge; Students of Nursing; Skin Neoplasms.

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

Directory of Open Access Journals (Sweden)

Yasushi Hara

unable to activate Akt and also demonstrates that M-COPA is efficacious for growth suppression of neoplastic mast cells.

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

Science.gov (United States)

Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

2017-01-01

activate Akt and also demonstrates that M-COPA is efficacious for growth suppression of neoplastic mast cells.

Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene.

Science.gov (United States)

Preston, G A; Lang, J E; Maronpot, R R; Barrett, J C

1994-08-01

A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup +I) and non-tumor suppressor stage II (sup -II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup +I and sup -II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup +I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G0/G1 phase of the cell cycle. The sup -II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup +I cells, and sup -II cells were injected s.c. into nude mice. At 5 or 21 days after

Simulating tumor growth in confined heterogeneous environments

International Nuclear Information System (INIS)

Gevertz, Jana L; Torquato, Salvatore; Gillies, George T

2008-01-01

The holy grail of computational tumor modeling is to develop a simulation tool that can be utilized in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies. In order to develop such a predictive model, one must account for many of the complex processes involved in tumor growth. One interaction that has not been incorporated into computational models of neoplastic progression is the impact that organ-imposed physical confinement and heterogeneity have on tumor growth. For this reason, we have taken a cellular automaton algorithm that was originally designed to simulate spherically symmetric tumor growth and generalized the algorithm to incorporate the effects of tissue shape and structure. We show that models that do not account for organ/tissue geometry and topology lead to false conclusions about tumor spread, shape and size. The impact that confinement has on tumor growth is more pronounced when a neoplasm is growing close to, versus far from, the confining boundary. Thus, any clinical simulation tool of cancer progression must not only consider the shape and structure of the organ in which a tumor is growing, but must also consider the location of the tumor within the organ if it is to accurately predict neoplastic growth dynamics

Chemical Growth Regulators for Guayule Plants

Science.gov (United States)

Dastoor, M. N.; Schubert, W. W.; Petersen, G. R.

1982-01-01

Test Tubes containing Guayule - tissue cultures were used in experiments to test effects of chemical-growth regulators. The shoots grew in response to addition of 2-(3,4-dichlorophenoxy)-triethylamine (triethylamine (TEA) derivative) to agar medium. Preliminary results indicate that a class of compounds that promotes growth in soil may also promote growth in a culture medium. Further experiments are needed to define the effect of the TEA derivative.

Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing

Directory of Open Access Journals (Sweden)

Lei Wei

2016-10-01

Full Text Available Abstract Background The rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent to the excised neoplasm is often used for this purpose as it is simultaneously collected and generally contains the same tissue type as the neoplasm. Following NGS analysis, we and others have frequently observed low-level somatic mutations in these non-neoplastic tissues, which may impose additional challenges to somatic mutation detection as it complicates germline variant filtering. Methods We hypothesized that the low-level somatic mutation observed in non-neoplastic tissues may be entirely or partially caused by inadvertent contamination by neoplastic cells during the surgical pathology gross assessment or tissue procurement process. To test this hypothesis, we applied a systematic protocol designed to collect multiple grossly non-neoplastic tissues using different methods surrounding each single neoplasm. The procedure was applied in two breast cancer lumpectomy specimens. In each case, all samples were first sequenced by whole-exome sequencing to identify somatic mutations in the neoplasm and determine their presence in the adjacent non-neoplastic tissues. We then generated ultra-deep coverage using targeted sequencing to assess the levels of contamination in non-neoplastic tissue samples collected under different conditions. Results Contamination levels in non-neoplastic tissues ranged up to 3.5 and 20.9 % respectively in the two cases tested, with consistent pattern correlated with the manner of grossing and procurement. By carefully controlling the conditions of various steps during this process, we were able to eliminate any detectable contamination in both patients. Conclusion The results demonstrated that the

Superficial inflammatory and primary neoplastic lymphadenopathy: diagnostic accuracy of power-doppler sonography

International Nuclear Information System (INIS)

Magarelli, N.; Guglielmi, G.; Savastano, M.; Toro, V.; Sborgia, M.; Fioritoni, G.; Mattei, P.A.; Steinbach, L.; Bonomo, L.

2004-01-01

Objective: To evaluate the sensitivity, specificity and diagnostic accuracy of a cut-off of the resistive index of 0.5 for the differentiation between inflammatory and neoplastic primary lymphadenopathies. Subjects and methods: We measured the resistive index of superficial enlarged lymph nodes in a total of 50 patients (29 males and 21 females; age range 12-72 years, mean age 41.6 year) using an ATL 5000 HDI. A resistive index greater than or equal to 0.5 indicated an inflammatory lymph node and a resistive index <0.5 was consistent with neoplastic primary lymphadenopathies. The gold standard was either surgical biopsy or lymph-node reduction seen with ultrasound examination after antibiotic therapy. Results: The sensitivity of the resistive index for distinguishing inflammatory from neoplastic lymphadenopathy was 84.6%, the specificity 100% and the diagnostic accuracy 95.7% (P<0.001, statistically significant). Conclusion: The results of this study indicate that power-Doppler using a resistive index cut-off of 0.5 was a valid technique for distinguising between inflammatory and primary neoplastic lymph nodes in patients with superficial lymphadenopathies

Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention

International Nuclear Information System (INIS)

Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B.

2001-01-01

Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [de

Treatment of non-neoplastic renal hemorrhage with segmental embolization of renal artery

International Nuclear Information System (INIS)

Zhu Bing

2007-01-01

Objective: To explore the value of segmental embolization of renal artery in dealing with non- neoplastic renal hemorrhage. Methods: Four cases of non-neoplastic hemorrhage, including 2 with bleeding after renal acupuncture biopsy, 2 with bleeding after nephrolithotomy and 1 with congenital renal arteriovenous malformation, were treated with superselective segmental embolization of renal artery. 2 were embolized with coil, 1 with alcohol plus coil and 1 with PVA parcels. Results: Hematuria disappeared in 1-3 days. There was no recurrence in 7-45 months follow up and no complications induced by embolization. Conclusion: It is a safe and reliable therapy to treat non-neoplastic renal hemorrhage with segmental embolization of renal artery. (authors)

GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

Science.gov (United States)

Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

2011-01-01

Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

Diffusion tensor imaging in inflammatory and neoplastic intramedullary spinal cord lesions: Focusing on fiber tracking

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyo Jin; Lee, Joon Woo; Lee, Eugene; Kim, Sung Gon; Kang, Yu Suhn; Ahn, Joong Mo; Kang, Heung Sik [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

2017-02-15

Inflammatory and neoplastic intramedullary spinal cord lesions have overlapping clinical features, and it is occasionally difficult to distinguish one from the other on conventional magnetic resonance imaging. We aimed to compare diffusion tensor imaging findings between inflammatory and neoplastic intramedullary spinal cord lesions, with a specific focus on patterns of fiber tracking. Diffusion tensor imaging was performed in patients with either inflammatory or neoplastic intramedullary spinal cord lesions. The fiber tracking patterns (categorized as “intact,” “displaced,” or “interrupted”) were compared between these two groups. Eight patients were included in the study: 5 patients with pathologically or clinically confirmed inflammatory lesions and 3 patients with pathologically or clinically confirmed neoplastic lesions. Among the 5 patients with inflammatory lesions, 2 patients exhibited the displaced pattern and 3 patients exhibited the intact pattern. Among the 3 patients with neoplastic lesions, 1 patient exhibited the intact pattern, 1 patient exhibited the displaced pattern, and 1 patient exhibited the interrupted pattern. In this study, inflammatory and neoplastic intramedullary spinal cord lesions were not clearly differentiated by fiber tracking; both conditions can present with overlapping features such as displaced fibers. The exclusion of inflammatory conditions based on the presence of displaced fibers in fiber tracking images should be avoided.

Effect of growth regulators on growth, flowering and rhizome yield of ...

African Journals Online (AJOL)

Field experiments were conducted in 2001 and 2002, to study the effect of foliar application of growth regulators on growth; flowering and rhizome yield of ginger (Zingiber officinale Rosc.). Treatments consisted of gibberellic acid (GA3) at 0,150 and 300 ppm; ethrel at 0,100 and 200 ppm and cycocel (CCC) at 0,250 ppm ...

Cyp26b1 within the growth plate regulates bone growth in juvenile mice

International Nuclear Information System (INIS)

Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

2014-01-01

Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

DEFF Research Database (Denmark)

Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

2009-01-01

Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

Science.gov (United States)

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Marolla, Ana Paula Cleto [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Waisberg, Jaques [Hospital do Servidor Público Estadual, São Paulo, SP (Brazil); Faculdade de Medicina do ABC, Santo André, SP (Brazil); Saba, Gabriela Tognini [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Waisberg, Daniel Reis [Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva [Faculdade de Medicina do ABC, Santo André, SP (Brazil)

2015-07-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

International Nuclear Information System (INIS)

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues

Warts signaling controls organ and body growth through regulation of ecdysone

DEFF Research Database (Denmark)

Møller, Morten Erik; Nagy, Stanislav; Gerlach, Stephan Uwe

2017-01-01

Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms...... under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin....../insulin-like growth factor (IGF) (insulin) signaling [2, 5]. The interplay between insulin and ecdysone signaling regulates systemic growth and controls organismal size. Here, we show that Warts (Wts; LATS1/2) signaling regulates systemic growth in Drosophila by activating basal ecdysone production, which negatively...

Extracellular matrix in tumours as a source of additional neoplastic lesions - a review

Directory of Open Access Journals (Sweden)

Madej Janusz A.

2014-03-01

Full Text Available The review describes the role of cells of extracellular matrix (ECM as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog. Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST, which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue, which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna, currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading are more important factors than the histogenesis of the tumour.

Business regulation and economic growth in the Western Balkan countries

Directory of Open Access Journals (Sweden)

Engjell PERE

2013-06-01

Full Text Available Actually economic policies in many countries aimed to stimulate their economic growth, particularly after negative impact of the global economic crisis. In this regards, fiscal regulation are an important aspect of those policies, that can promote or obstacle the economic growth in general. In this point of view this paper aims to analyze the system of administration rules in different Western Balkans Countries, (which includes Albania, Bosnia & Herzegovina, Croatia, Kosovo, Macedonia (FYROM, Montenegro and Serbia. Moreover, a special attention is given investigation of the regulation and administrative facilitation aspects of doing business in the above-mentioned countries, whether this system stimulates, or not, the development of private business and economic growth.The paper is divided into three main sections. The first part provides a retrospective of economic growth in the Western Balkan countries and the dependence of this growth on global economic development. The second part proceeds with the investigations of the impact of administrative regulation on economic growth. The third part, based on an econometric model, will analyze the correlation between economic growth and elaborated indicators which present the level of business administrative regulation system. Furthermore, this last section discusses the results and concludes. In this analysis, the paper is based substantially on the data base of "Doing Business 2013" (World Bank.

The effect of plant growth regulators, explants and cultivars on ...

African Journals Online (AJOL)

To achieve the best explants and media for spinach tissue culture, the effects of two different plant growth regulators, two explants and cultivars on adventitious shoot regeneration were tested. The Analysis of Variance (ANOVA) showed that the effects of plant growth regulators on spinach tissue culture were significant; ...

A HISTOPATHOLOGICAL STUDY OF NEOPLASTIC LESIONS OF UTERINE CERVIX OF PERI AND POSTMENOPAUSAL WOMEN

Directory of Open Access Journals (Sweden)

Jogesh Kakati

2017-03-01

Full Text Available BACKGROUND Neoplastic lesions of uterine cervix is one of the most common malignant neoplasms in women. The tremendous success in giving a confirmed diagnosis of the disease by doing histopathological examination is of prime importance in giving the most appropriate treatment and to understand the prognosis. The aim of the study is to study the incidence and age-wise distribution of the neoplastic lesions of the uterine cervix in peri and postmenopausal women by doing histopathological examination of neoplastic lesions and by doing correlation of clinical findings with histopathological examination. MATERIALS AND METHODS The study included 803 cases of total cervical specimens, out of which 180 cases of neoplastic cervical lesions were found, out of which 150 cases were found in the peri and postmenopausal age groups, i.e. above 40 years of age. The study was done in Gauhati Medical College and Hospital, Guwahati, from the period 1 st June, 2013, to 1 st June, 2014. The specimens that were included in the study were punch biopsies, hysterectomies and polypectomies and cervical specimens were studied by doing histopathological examinations. RESULTS Out of the 150 cases of neoplastic lesions in the peri and postmenopausal women, the most common neoplastic lesion was cervical intraepithelial neoplasia, i.e. CIN (8.3% of the cervix, followed by malignant (5.6% and benign (4.7% lesions of the cervix in this study group of patients. CONCLUSION Histopathological examination of the cervix is an effective method of giving a confirmed diagnosis of all the noncancerous, precancerous and cancerous lesions of uterine cervix, which helps in giving the most appropriate treatment and also helps in understanding the prognosis.

Cyp26b1 within the growth plate regulates bone growth in juvenile mice

Energy Technology Data Exchange (ETDEWEB)

Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

2014-11-07

Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

Epigenetic regulation of axon and dendrite growth

Directory of Open Access Journals (Sweden)

Ephraim F Trakhtenberg

2012-03-01

Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

International Nuclear Information System (INIS)

Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

2013-01-01

be part of a pro-survival pathway that helps to evade the toxic effects of endogenous oxidants and contributes to testicular neoplastic growth

Regulation of intestinal mucosal growth by amino acids.

Science.gov (United States)

Ray, Ramesh M; Johnson, Leonard R

2014-03-01

Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as epidermal growth factor and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis, or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1, and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine, and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the

Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer.

Science.gov (United States)

O'Sullivan, Aine G; Mulvaney, Eamon P; Kinsella, B Therese

2017-04-01

The prostanoid thromboxane (TX) A 2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA 2 /TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA 2 -TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA 2 /TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA 2 /TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA 2 /TP signalling axis in PCa, including potentially in CRPC. Copyright © 2017 Elsevier B.V. All rights reserved.

Ihh signaling regulates mandibular symphysis development and growth.

Science.gov (United States)

Sugito, H; Shibukawa, Y; Kinumatsu, T; Yasuda, T; Nagayama, M; Yamada, S; Minugh-Purvis, N; Pacifici, M; Koyama, E

2011-05-01

Symphyseal secondary cartilage is important for mandibular development, but the molecular mechanisms underlying its formation remain largely unknown. Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and growth. By embryonic days 16.5 to 18.5, Sox9-expressing chondrocytes formed within condensed Tgfβ-1/Runx2-expressing mesenchymal cells at the prospective symphyseal joint site, and established a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns. In post-natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differentiated into chondrocytes, and contributed to anterior growth of alveolar bone. In Ihh-null mice, however, symphyseal development was defective, mainly because of enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells. Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal development. Thus, Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth.

Regulation of planar growth by the Arabidopsis AGC protein kinase UNICORN.

Science.gov (United States)

Enugutti, Balaji; Kirchhelle, Charlotte; Oelschner, Maxi; Torres Ruiz, Ramón Angel; Schliebner, Ivo; Leister, Dario; Schneitz, Kay

2012-09-11

The spatial coordination of growth is of central importance for the regulation of plant tissue architecture. Individual layers, such as the epidermis, are clonally propagated and structurally maintained by symmetric cell divisions that are oriented along the plane of the layer. The developmental control of this process is poorly understood. The simple cellular basis and sheet-like structure of Arabidopsis integuments make them an attractive model system to address planar growth. Here we report on the characterization of the Arabidopsis UNICORN (UCN) gene. Analysis of ucn integuments reveals localized distortion of planar growth, eventually resulting in an ectopic multicellular protrusion. In addition, ucn mutants exhibit ectopic growth in filaments and petals, as well as aberrant embryogenesis. We further show that UCN encodes an active AGC VIII kinase. Genetic, biochemical, and cell biological data suggest that UCN suppresses ectopic growth in integuments by directly repressing the KANADI transcription factor ABERRANT TESTA SHAPE. Our findings indicate that UCN represents a unique plant growth regulator that maintains planar growth of integuments by repressing a developmental regulator involved in the control of early integument growth and polarity.

Symbiotic regulation of plant growth, development and reproduction

Science.gov (United States)

Russell J. Rodriguez; D. Carl Freeman; E. Durant McArthur; Yong Ok Kim; Regina S. Redman

2009-01-01

The growth and development of rice (Oryzae sativa) seedlings was shown to be regulated epigenetically by a fungal endophyte. In contrast to un-inoculated (nonsymbiotic) plants, endophyte colonized (symbiotic) plants preferentially allocated resources into root growth until root hairs were well established. During that time symbiotic roots expanded at...

Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

International Nuclear Information System (INIS)

Benson, M.D.; Cohen, A.S.

1979-01-01

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease

Imaging of limbic para-neoplastic encephalitis; Imagerie de l`encephalite limbique paraneoplastique

Energy Technology Data Exchange (ETDEWEB)

Rimmelin, A.; Sellat, F.; Morand, G.; Quoix, E.; Clouet, P.L.; Dietemann, J.L. [Centre Hospitalier Universitaire, 67 - Strasbourg (France)

1997-09-01

Para-neoplastic limbic encephalitis is a rare syndrome mostly associated with small cell lung cancer. We present the case of a 69-year-old man with selective amnesia suggesting limbic encephalitis. A neuroendocrine cell lung cancer was found, confirming the diagnostics of para-neoplastic limbic encephalitis. Contrast-enhanced cerebral CT was normal whether magnetic resonance imaging showed signal abnormalities of the medial part of temporal lobes and hippocampal regions. Because neurologic improvement may follow treatment of the primary tumor, early diagnosis is important. (authors). 10 refs.

Positive regulation of prostate cancer cell growth by lipid droplet forming and processing enzymes DGAT1 and ABHD5.

Science.gov (United States)

Mitra, Ranjana; Le, Thuc T; Gorjala, Priyatham; Goodman, Oscar B

2017-09-06

Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prostate cancer-specific modifications in lipid storage pathways so that these modified gene products can be identified and therapeutically targeted. To identify genes that promote lipid droplet formation and storage, the expression profiles of candidate genes were assessed and compared between peripheral blood mononuclear cells and prostate cancer cells. Subsequently, differentially expressed genes were inhibited and growth assays performed to elucidate their role in the growth of the cancer cells. Cell cycle, apoptosis and autophagy assays were performed to ascertain the mechanism of growth inhibition. Our results indicate that DGAT1, ABHD5, ACAT1 and ATGL are overexpressed in prostate cancer cells compared to PBMCs and of these overexpressed genes, DGAT1 and ABHD5 aid in the growth of the prostate cancer cells. Blocking the expression of both DGAT1 and ABHD5 results in inhibition of growth, cell cycle block and cell death. DGAT1 siRNA treatment inhibits lipid droplet formation and leads to autophagy where as ABHD5 siRNA treatment promotes accumulation of lipid droplets and leads to apoptosis. Both the siRNA treatments reduce AMPK phosphorylation, a key regulator of lipid metabolism. While DGAT1 siRNA reduces phosphorylation of ACC, the rate limiting enzyme in de novo fat synthesis and triggers phosphorylation of raptor and ULK-1 inducing autophagy and cell death, ABHD5 siRNA decreases P70S6 phosphorylation, leading to PARP cleavage, apoptosis and cell death. Interestingly, DGAT-1 is involved

SMAD family proteins: the current knowledge on their expression and potential role in neoplastic diseases

Directory of Open Access Journals (Sweden)

Magdalena Witkowska

2014-03-01

Full Text Available Transforming growth factor beta (TGF-β plays a crucial role and takes part in many processes in the human body both in physiology and pathology. This cytokine is involved in angiogenesis, regulates apoptosis and stimulates divisions of cells, such as hepatocytes, lymphocytes or hematopoietic cells. SMAD proteins family is a unique group of particles responsible for transducting the signal induced by TGF-β into the nucleus. This molecules, after receiving a signal from activated TGF-β, act on transcription factors in the nucleus, leading directly to the expression of the corresponding genes. According to current knowledge, disturbances in the functioning of SMAD proteins are present in a number of diseases. The reduced expression was observed, for example in cardiovascular diseases such as primary pulmonary hypertension or myocardial infarction, autoimmune diseases for instance systemic lupus erythematosus and multiple sclerosis, Alzheimer’s disease or osteoporosis. The latest clinical data showed the presence of mutations in SMAD proteins in cancerogenesis. Mutation of SMAD-4 protein can be detected in half of the patients with pancreatic cancer, 20% of patients with colorectal cancer and 10% of patients with lung cancer. However, mutation in SMAD-2 protein was observed in 7% of both patients with colorectal cancer and lung cancer. On the basis of numerous works, SMAD protein expression would be valuable prognostic factor in some of neoplastic diseases.

Effects of plant growth regulators on callus, shoot and root formation ...

African Journals Online (AJOL)

Root and stem explants of fluted pumpkin were cultured in medium containing different types and concentrations of plant growth regulators (PGRs). The explants were observed for callus, root and shoot formation parameters after four months. Differences among explants, plant growth regulators and their interaction were ...

Targeting the erythropoietin receptor on glioma cells reduces tumour growth

International Nuclear Information System (INIS)

Peres, Elodie A.; Valable, Samuel; Guillamo, Jean-Sebastien; Marteau, Lena; Bernaudin, Jean-Francois; Roussel, Simon; Lechapt-Zalcman, Emmanuele; Bernaudin, Myriam; Petit, Edwige

2011-01-01

Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

Knowledge on neoplastic diseases among young rural inhabitants

Directory of Open Access Journals (Sweden)

Anna Lewandowska

2017-09-01

According to self-assessment, every third respondent stated having a low or average level of knowledge. The most frequently used source of knowledge was the Internet, and much more rarely a doctor or a nurse. Very few of the respondents could enumerate the tests applied in the early detection of neoplastic diseases.

Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study.

Science.gov (United States)

D'Silva, Shaloom; Sumathi, M K; Balaji, N; Shetty, Nisha K N; Pramod, K M; Cheeramelil, Jacob

2013-12-01

Calretinin a 29-kDa calcium binding protein is expressed widely in normal human tissue and tumours including amelobastoma. The objective of this study was to determine calretinin expression in heamatoxylin and eosin diagnosed cases of ameloblastoma and non-neoplastic odontogenic cysts. The lining epithelium in 3 cases of radicular cysts, 5 cases of odontogenic keratocysts, 5 cases of dentigerous cysts and 11 cases of ameloblastomas were examined for expression of calretinin. No positive epithelial staining was observed in radicular and dentigerous cysts. In comparison, however 100% of cases of ameloblastomas and 40% of cases of odontogenic karatocysts showed positive calretinin expression. Calretinin may be a specific immunohistochemical marker for ameloblastoma. If there is any possible relation between calretinin expression and neural origin of the odontogenic epithelium and its neoplastic transformation and if calretinin could be used as an early marker to predict the tendency of neoplastic change of odontogenic epithelium could be answered through further researches. How to cite this article: D'Silva S, Sumathi MK, Balaji N, Shetty NK, Pramod KM, Cheeramelil J. Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study. J Int Oral Health 2013; 5(6):42-8 .

Glycaemic adverse drug reactions from anti-neoplastics used in ...

African Journals Online (AJOL)

235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

Value of the biological data in the sonographic diagnosis of neoplastic biliary obstruction

Energy Technology Data Exchange (ETDEWEB)

Ferrari, F; Fagioli Zucchi, A; Rappuoli, G; Guercia, M; Terrosi Vagnoli, P

1988-01-01

The authors' purpose is to demonstrate the possibility of improving US reliability in the diagnosis of neoplastic obstructions of the bile ducts, basing their study on the hematic alkaline phosphates level (AP), wich is an earlier sign of obstruction than bilirubine values. All 368 patients observed had AP levels above the threshold of 270 IU/l. The 34 patients with neoplastic obstruction (including 13 without jaundice) had more than twice the normal level of AP, and presented with at least one dilated bile duct in the biliary tree. Coronal scans of the main bile duct are fundamental in the diagnosis of the level of obstruction. It seems thus possible to affirm that US diagnosis of the biliary obstruction, together with high AP values (more than twice the normal), provides with reliable information as to the neoplastic nature of the biliary obstruction, even if jaundice is not present.

Value of the biological data in the sonographic diagnosis of neoplastic biliary obstruction

International Nuclear Information System (INIS)

Ferrari, F.; Fagioli Zucchi, A.; Rappuoli, G.; Guercia, M.; Terrosi Vagnoli, P.

1988-01-01

The authors' purpose is to demonstrate the possibility of improving US reliability in the diagnosis of neoplastic obstructions of the bile ducts, basing their study on the hematic alkaline phosphates level (AP), wich is an earlier sign of obstruction than bilirubine values. All 368 patients observed had AP levels above the threshold of 270 IU/l. The 34 patients with neoplastic obstruction (including 13 without jaundice) had more than twice the normal level of AP, and presented with at least one dilated bile duct in the biliary tree. Coronal scans of the main bile duct are fundamental in the diagnosis of the level of obstruction. It seems thus possible to affirm that US diagnosis of the biliary obstruction, together with high AP values (more than twice the normal), provides with reliable information as to the neoplastic nature of the biliary obstruction, even if jaundice is not present

Growth rate regulated genes and their wide involvement in the Lactococcus lactis stress responses

Directory of Open Access Journals (Sweden)

Redon Emma

2008-07-01

Full Text Available Abstract Background The development of transcriptomic tools has allowed exhaustive description of stress responses. These responses always superimpose a general response associated to growth rate decrease and a specific one corresponding to the stress. The exclusive growth rate response can be achieved through chemostat cultivation, enabling all parameters to remain constant except the growth rate. Results We analysed metabolic and transcriptomic responses of Lactococcus lactis in continuous cultures at different growth rates ranging from 0.09 to 0.47 h-1. Growth rate was conditioned by isoleucine supply. Although carbon metabolism was constant and homolactic, a widespread transcriptomic response involving 30% of the genome was observed. The expression of genes encoding physiological functions associated with biogenesis increased with growth rate (transcription, translation, fatty acid and phospholipids metabolism. Many phages, prophages and transposon related genes were down regulated as growth rate increased. The growth rate response was compared to carbon and amino-acid starvation transcriptomic responses, revealing constant and significant involvement of growth rate regulations in these two stressful conditions (overlap 27%. Two regulators potentially involved in the growth rate regulations, llrE and yabB, have been identified. Moreover it was established that genes positively regulated by growth rate are preferentially located in the vicinity of replication origin while those negatively regulated are mainly encountered at the opposite, thus indicating the relationship between genes expression and their location on chromosome. Although stringent response mechanism is considered as the one governing growth deceleration in bacteria, the rigorous comparison of the two transcriptomic responses clearly indicated the mechanisms are distinct. Conclusion This work of integrative biology was performed at the global level using transcriptomic analysis

Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Science.gov (United States)

Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

2016-04-01

The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

Science.gov (United States)

Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

2014-01-01

Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

Directory of Open Access Journals (Sweden)

Patrícia F. Castro

2016-01-01

Full Text Available Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates.

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

Science.gov (United States)

Castro, Patrícia F.; Fantoni, Denise T.; Miranda, Bruna C.; Matera, Julia M.

2016-01-01

Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

Non-neoplastic surgical diseases of the lung and pleura

International Nuclear Information System (INIS)

Walter, P.A.

1987-01-01

Non-neoplastic diseases of the bronchi, pulmonary parenchyma, mediastinum, and pleura that are amenable to surgical management represent a wide range of unrelated etiopathogenic conditions that usually have a focal distribution. The author discusses the presurgical clinical, radiographic, and laboratory assessment and prognoses, and addresses therapeutic recommendations

[Non-neoplastic enlargement of salivary glands: clinico-histologic analysis].

Science.gov (United States)

González Guevara, Martha Beatriz; Torres Tejero, Marco Antonio; Martínez Mata, Guillermo

2005-01-01

We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

Energy Technology Data Exchange (ETDEWEB)

Kay, Steve A. [Univ. of Southern California, Los Angeles, CA (United States)

2017-10-20

Objectives: Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass Brachypodium distachyon also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation. Description: The project is divided in three main parts: 1) Performing time-lapse imaging and growth measurement in B. distachyon and S. bicolor to determine growth rate dynamic during the day/night cycle. Identifying growth-associated genes whose expression patterns follow the observed growth dynamics using deep sequencing technology, 2) identifying regulators of these genes by screening for DNA-binding proteins interacting with the growth-associated gene promoters identified in Aim 1. Screens will be performed using a validated yeast-one hybrid strategy paired with a specifically designed B. distachyon and S. bicolor transcription factor libraries (1000 clones each), and 3) Selecting 50 potential growth regulators from the screen for downstream characterization. The selection will be made by using a sytems biology approach by calculating the connectivity between growth rate, rhythmic gene expression profiles and TF expression profile and determine which TF is likely part of a hub

Effects of growth regulator herbicide on downy brome (Bromus tectorum) seed production

Science.gov (United States)

Previous research showed growth regulator herbicides, such as picloram and aminopyralid, have a sterilizing effect on Japanese brome (Bromus japonicus Thunb.) that can reduce this invasive annual grass’s seed production nearly 100%. This suggests growth regulators might be used to control invasive ...

Enteroclysis of non-neoplastic disorders of the small intestine

International Nuclear Information System (INIS)

Nolan, D.J.

2000-01-01

Enteroclysis is now widely used for examining the jejunum and ileum. The technique is ideal for demonstrating the extent and severity of disorders that cause morphological changes to the small intestine. In this review many non-neoplastic small intestinal disorders as demonstrated by enteroclysis are described and illustrated. (orig.)

Effect of plant growth regulators on production of alpha-linolenic ...

Indian Academy of Sciences (India)

Sujana Kokkiligadda

2017-10-05

Oct 5, 2017 ... MS received 13 October 2016; revised 22 March 2017; accepted 30 May 2017; ... Plant growth regulators; microalgae; Chlorella pyrenoidosa; alpha-linolenic acid. 1. ... the growth period by flocculation method [9] using alum.

Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver

Energy Technology Data Exchange (ETDEWEB)

Kanematsu, M. E-mail: masa-gif@umin.ac.jp; Kondo, H.; Semelka, R.C.; Matsuo, M.; Goshima, S.; Hoshi, H.; Moriyama, N.; Itai, Y

2003-10-01

AIM: To assess the frequency, cause, and significance of early-enhancing, non-neoplastic (EN) lesions on gadolinium-enhanced magnetic resonance imaging (MRI) of the liver performed for the detection of malignant hepatic tumours. MATERIALS AND METHODS: From September 1997 to September 2000, we reviewed the images of 125 patients, suspected of having hepatic tumours, in whom (1) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) imaging in addition to unenhanced T1- and T2-weighted MRI was performed, (2) conventional angiography and combination computed tomography (CT) hepatic arteriography and CT during arterial portography were performed within 2 weeks of the MRI, and (3) definitive surgery within 2 weeks of the MRI or follow-up study by means of intravenously contrast-enhanced CT or MRI in 10 months or more was performed. Angiographic studies were correlated to determine the underlying causes of the EN lesions. RESULTS: We found 78 EN lesions in 36 patients (29%), ranging in size from 4 and 50 mm (mean, 12.2 mm). From the MR reports, our radiologists had prospectively diagnosed EN lesions as probable malignant tumours in eight (10%), possible malignant tumours in 36 (46%), and probable non-neoplastic lesion in 34 (44%). EN lesions were found in 27 of 81 (33%) cirrhotic patients and in nine of 44 (20%) non-cirrhotic patients. Fifty-one EN lesions (65%) were located along the liver edge. The shape was circular in 42 (54%), oval in 14 (18%), irregular in 12 (15%), wedge-shaped in seven (9%), and fan-shaped in three (4%). Twenty EN lesions (26%) appeared slightly hyperintense on T2-weighted images. The causes were non-neoplastic arterio-portal shunting in 48 (62%), cystic venous drainage in four (5%), rib compression in four (5%), aberrant right gastric venous drainage in two (3%), and unknown in 20 (26%). CONCLUSION: Over half the number of EN lesions were caused by non-neoplastic arterio-portal shunting, occasionally showing slight hyperintensity on

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

Science.gov (United States)

Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

Activated Hepatic Stellate Cells Induce Tumor Progression of Neoplastic Hepatocytes in a TGF-β Dependent Fashion

Science.gov (United States)

MIKULA, M.; PROELL, V.; FISCHER, A.N.M.; MIKULITS, W.

2010-01-01

The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells. For both tumorigenesis and hepatic fibrogenesis, transforming growth factor (TGF)-β signaling executes key roles and therefore is considered as a hallmark of these pathological events. By employing cellular transplantation we show that the interaction of neoplastic MIM-R hepatocytes with the tumor microenvironment, containing either activated hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs), induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M-HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear localization of Smad2/3 as well as of β-catenin. Genetic interference with TGF-β signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling are devoid of nuclear β-catenin accumulation, indicating a crosstalk between TGF-β and β-catenin signaling. Together, these data demonstrate that activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF-β dependent fashion by inducing autocrine TGF-β signaling and nuclear β-catenin accumulation in neoplastic hepatocytes. These results indicate that intervention with TGF-β signaling is highly promising in liver cancer therapy. PMID:16883581

Joint approach based on clinical and imaging features to distinguish non-neoplastic from neoplastic pituitary stalk lesions.

Directory of Open Access Journals (Sweden)

Ji Ye Lee

Full Text Available Distinguishing non-neoplastic pituitary stalk lesions (non-NPSLs from neoplastic pituitary stalk lesions (NPSLs is a major concern in guiding treatment for a thickened pituitary stalk. Our study aimed to aid provide preoperative diagnostic assistance by combining clinical and magnetic resonance imaging (MRI findings to distinguish non-NPSLs from NPSLs.We recruited 158 patients with thickened pituitary stalk lesions visible on MRI. Laboratory findings included hypopituitarism, diabetes insipidus (DI, and hyperprolactinemia. MR images were assessed for anterior-posterior thickness (mm, diffuse pituitary stalk thickening, cystic changes, a high T1 signal, and glandular or extrasellar involvement. A diagnostic model was developed using a recursive partitioning logistic regression analysis. The model was validated in an independent dataset comprising 63 patients, and its diagnostic performance was compared with that of the original radiological reports.A univariate analysis found significant associations of DI (P = 0.006, absence of extrasellar involvement (P = 0.002, and lower stalk thickness (P = 0.031 with non-NPSLs. A diagnostic model was created using the following parameters (in order of priority: 1 lack of extrasellar involvement, 2 stalk thickness < 5.3 mm, and 3 presence of DI. The diagnostic performance (area under the curve; AUC of this model in the independent set was 0.813, representing a significant improvement over the original radiological reports (AUC: 0.713, P = 0.029.The joint diagnostic approach based on clinical and imaging-based factors robustly distinguished non-NPSLs from NPSLs. This approach could guide treatment strategies and prevent unnecessary surgery in patients with non-NPSL.

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

Directory of Open Access Journals (Sweden)

Geni NL Camara

2003-10-01

Full Text Available As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061 were less frequent (= or < 2.5% each. The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

Regulation of dendrite growth and maintenance by exocytosis

OpenAIRE

Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

2015-01-01

Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential req...

Endogenous versus exogenous growth factor regulation of articular chondrocytes.

Science.gov (United States)

Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

2014-01-01

Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

Non-neoplastic conditions presenting as soft-tissue tumours

International Nuclear Information System (INIS)

Crundwell, N.; O'Donnell, P.; Saifuddin, A.

2007-01-01

Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed

Non-neoplastic conditions presenting as soft-tissue tumours

Energy Technology Data Exchange (ETDEWEB)

Crundwell, N. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); O' Donnell, P. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); Saifuddin, A. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom)]. E-mail: asif.saifuddin@rnoh.nhs.uk

2007-01-15

Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed.

The influence of theosophy on Mondrian's neoplastic work

OpenAIRE

Bris Marino, Pablo

2014-01-01

(ENG)The influence of Theosophy in the symbolist painting of Mondrian (1908-1911) has been unanimously recognized. There is not, however, the same consensus with respect to the influence of theosophy in his neoplastic period. There is a relationship between Mondrian’s theoretical writing and his practical work, but no proportionality. Mondrian’s theoretical discourse is not limited to painting and touches on other arts and disciplines (architecture,...

Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

Science.gov (United States)

Weisman, Ronit

2016-10-01

All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

Case of a rare type of non-neoplastic mucinous pancreatic cyst – likely new pathological entity?

International Nuclear Information System (INIS)

Hilendarov, A.; Nedeva, M.; Belovejdov, V.; Aleksieva, D.; Sirakov, N.

2013-01-01

Full text:Introduction: The cystic lesions of the pancreas consists of a range of pathologies which may be broadly divided into neoplastic, non- neoplastic and cysts. Recently a new non-neoplastic cystic lesions, called mucinous non-neoplastic cysts, have been described. Materials and Methods: The imaging methods (ultrasound and CT ) were used as well as invasive imaging methods under image control with a view of the histological verification of the diagnosis. A case of pancreatic cystic lesion is described, accidentally detected by ultrasound and CT scan made for different purpose. Results : The finding was a 28/32 mm cyst in the body of the pancreas, apparently communicating with the pancreatic duct . The Endoscopic Retrograde Cholangiopancreatography and laboratory tests of liver function, serum CEA and carbohydrate antigen C19 -9 were within normal limits. After the distal pancreatectomy and splenectomy the lasting histological specimen showed a simple cyst, lined with mucinous epithelium. Conclusion: The presented case guides the imaging diagnosticians and surgeons towards seeking a thorough preoperative clarification of pancreatic cystic lesions. It is recommended that patients diagnosed with 'benign' mucinous neoplasm are closely monitored due to the inability to completely confirm the benign nature of the lesion

The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics

Directory of Open Access Journals (Sweden)

Huang Yung-Cheng

2011-12-01

Full Text Available Abstract Background Brown adipose tissue (BAT has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT in people living in the tropics, where the influence of outdoor temperature was low. Methods 18F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and 18F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature. Results Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043 and a higher TMA (p = 0.028 than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016. Conclusions Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.

78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

Science.gov (United States)

2013-12-17

... include updating the medical terminology in the listings. For example, we would replace the term ``Hodgkin... Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases); Proposed Rule #0;#0...

Focus formation and neoplastic transformation by herpes simplex virus type 2 inactivated intracellularly by 5-bromo-2'-deoxyuridine and near UV light

International Nuclear Information System (INIS)

Manak, M.M.; Aurelian, L.; Ts'o, P.O.

1981-01-01

The induction of focus formation in low serum and of neoplastic transformation of Syrian hamster embryo cells was examined after the expression of herpes simplex virus type 2 functions. Syrian hamster embryo cells infected at a high multiplicity (5 PFU/cell) with 5-bromo-2'-deoxyuridine-labeled herpes simplex virus type 2 (11% substitution of thymidine residues) were exposed to near UV light irradiation at various times postinfection. This procedure specifically inactivated the viral genome, while having little, if any, effect on the unlabeled cellular DNA. Focus formation in 1% serum and neoplastic transformation were observed in cells exposed to virus inactivated before infection, but the frequency was enhanced (15- to 27-fold) in cells in which the virus was inactivated at 4 to 8 h postinfection. Only 2 to 45 independently isolated foci were capable of establishing tumorigenic lines. The established lines exhibited phenotypic alterations characteristic of a transformed state, including reduced serum requirement, anchorage-independent growth, and tumorigenicity. They retained viral DNA sequences and, even at relatively late passage, expressed viral antigens, including ICP 10

Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111In-DTPA ventriculography

International Nuclear Information System (INIS)

Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

1982-01-01

Cerebrospinal fluid flow dynamics were evaluated by 111 In-diethylenetriamine pentaacetic acid ( 111 In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that 111 In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis

Synthesis and application of labelled growth regulators

International Nuclear Information System (INIS)

Shyutte, G.R.

1982-01-01

For the investigation of the metabolism both of phytoeffectors like herbicides and plant growth regulators such compounds are needed in radioactive labelled form. The synthesis of radioactive labelled fluorodifen, nitrofen, ethephon, diphenylic acetic acid, 2,4-dichlorophenoxyisobutyric acid, abscisic acid, hydroxybenzoic acids and different conjugates are described. Some examples of these compounds metabolism in plants are discussed [ru

Nitroxide radicals formed in situ as polymer chain growth regulators

International Nuclear Information System (INIS)

Kolyakina, Elena V; Grishin, Dmitry F

2009-01-01

Published data on controlled synthesis of macromolecules using nitroxide radicals, formed in situ during polymerization, as polymer chain growth regulators are systematized and generalized. The attention is focused on the mechanism of polymer chain growth control during reversibly inhibited radical homopolymerization and the effect of structure of precursors and regulating additives on the polymerization kinetics of monomers of different nature and the molecular-mass characteristics of the polymers thus formed. The key methods for generation of nitroxide radicals directly during polymerization are considered. The prospects for development and practical use of these approaches for the synthesis of new polymeric materials are evaluated.

Regulation of Nutrient Transport in Quiescent, Lactating, and Neoplastic Mammary Epithelia.

Science.gov (United States)

1996-10-01

comp... 96 0.93 emb X80301 NTAXI1G N.tabacum axi 1 gene 95 0.96 emb X12727 AOAMY3 Aspergillus oryzae amy3 gene for alph... 94 0.98 emb X56838 HSGSTMU3...transport properties, nutrient utilization, growth characteristics , and cellular morphology c. use of mammary epithelial cells transplanted into a cleared...the novel protein, but also effects on cellular phenotype, such as altered glucose transport, growth characteristics , or morphology. Expression in

Growth regulating properties of isoprene and isoprenoid-based essential oils.

Science.gov (United States)

Jones, Andrew Maxwell P; Shukla, Mukund R; Sherif, Sherif M; Brown, Paula B; Saxena, Praveen K

2016-01-01

Essential oils have growth regulating properties comparable to the well-documented methyl jasmonate and may be involved in localized and/or airborne plant communication. Aromatic plants employ large amounts of resources to produce essential oils. Some essential oils are known to contain compounds with plant growth regulating activities. However, the potential capacity of essential oils as airborne molecules able to modulate plant growth/development has remained uninvestigated. Here, we demonstrate that essential oils from eight taxonomically diverse plants applied in their airborne state inhibited auxin-induced elongation of Pisum sativum hypocotyls and Avena sativa coleoptiles. This response was also observed using five monoterpenes commonly found in essential oils as well as isoprene, the basic building block of terpenes. Upon transfer to ambient conditions, A. sativa coleoptiles resumed elongation, demonstrating an antagonistic relationship rather than toxicity. Inclusion of essential oils, monoterpenes, or isoprene into the headspace of culture vessels induced abnormal cellular growth along hypocotyls of Arabidopsis thaliana. These responses were also elicited by methyl jasmonate (MeJA); however, where methyl jasmonate inhibited root growth essential oils did not. Gene expression studies in A. thaliana also demonstrated differences between the MeJA and isoprenoid responses. This series of experiments clearly demonstrate that essential oils and their isoprenoid components interact with endogenous plant growth regulators when applied directly or as volatile components in the headspace. The similarities between isoprenoid and MeJA responses suggest that they may act in plant defence signalling. While further studies are needed to determine the ecological and evolutionary significance, the results of this study and the specialized anatomy associated with aromatic plants suggest that essential oils may act as airborne signalling molecules.

The role of growth regulators, embryo age and genotypes on ...

African Journals Online (AJOL)

Administrator

2011-06-06

Jun 6, 2011 ... 0.1 mg/l kinetin, MS + 0.1 mg/l IAA and MS + 0.1 mg/l kinetin + 0.1 mg/l IAA were used as growth regulators. ... factor for a high success in zygotic embryo culture is the ... regulators components have proved to influence the.

Independent regulation of skeletal growth by Ihh and IGF signaling.

Science.gov (United States)

Long, Fanxin; Joeng, Kyu-Sang; Xuan, Shouhong; Efstratiadis, Argiris; McMahon, Andrew P

2006-10-01

The insulin-like growth factors (IGFs) play a major role in regulating the systemic growth of mammals. However, it is unclear to what extent their systemic and/or local functions act in concert with other local growth factors controlling the sizes of individual organs. We have specifically addressed whether growth control of the skeleton by IGFs interacts genetically with that by Indian hedgehog (Ihh), a locally produced growth signal for the endochondral skeleton. Here, we report that disruption of both IGF and Ihh signaling resulted in additive reduction in the size of the embryonic skeleton. Thus, IGF and Ihh signaling appear to control the growth of the skeleton in parallel pathways.

Regulation of dendrite growth and maintenance by exocytosis

Science.gov (United States)

Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

2015-01-01

ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382

Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

International Nuclear Information System (INIS)

Walker, C.; Nettesheim, P.; Barrett, J.C.; Gilmer, T.M.

1987-01-01

Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of ≅ 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

Directory of Open Access Journals (Sweden)

Laghi Luigi

2006-04-01

Full Text Available Abstract Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia, dysplastic (large regenerative, low and high grade dysplastic nodules and neoplastic (hepatocellular adenoma and carcinoma growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis to hepatocellular nodules (p RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly methylated, that this condition takes place as an age-related phenomenon and that the early setting and spreading over time of an epigenetically methylated hepatocyte subpopulation, might be related to liver tumorigenesis.

Callus induction via different growth regulators from cotyledon ...

African Journals Online (AJOL)

Cicer arietinum L.) cultivars KK-1 and Hassan-2K on MS and B5 media containing different combinations and concentrations of growth regulators. Different MS and B5 callusing media containing varying level of 2, 4-D (2 and 4 mg/l), NAA (0.50 ...

Auxin-BR Interaction Regulates Plant Growth and Development

Science.gov (United States)

Tian, Huiyu; Lv, Bingsheng; Ding, Tingting; Bai, Mingyi; Ding, Zhaojun

2018-01-01

Plants develop a high flexibility to alter growth, development, and metabolism to adapt to the ever-changing environments. Multiple signaling pathways are involved in these processes and the molecular pathways to transduce various developmental signals are not linear but are interconnected by a complex network and even feedback mutually to achieve the final outcome. This review will focus on two important plant hormones, auxin and brassinosteroid (BR), based on the most recent progresses about these two hormone regulated plant growth and development in Arabidopsis, and highlight the cross-talks between these two phytohormones. PMID:29403511

Neoplastic and proliferative disorders of the perinephric space

International Nuclear Information System (INIS)

Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

2012-01-01

The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

Exogenous application of plant growth regulators increased the total ...

African Journals Online (AJOL)

PRECIOUS

2009-11-02

Nov 2, 2009 ... the exogenous application of flavonoids reports plant growth regulation ... method used for extraction and quantification of endogenous gibberellins was ... 365 nm) while separation was done on a C18 reverse-phase HPLC.

Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors

Directory of Open Access Journals (Sweden)

Justin D. Schumacher

2016-01-01

Full Text Available Fibroblast growth factors (FGFs are a family of growth factors critically involved in developmental, physiological, and pathological processes, including embryogenesis, angiogenesis, wound healing, and endocrine functions. In the liver, several FGFs are produced basally by hepatocytes and hepatic stellate cells (HSCs. Upon insult to the liver, expression of FGFs in HSCs is greatly upregulated, stimulating hepatocyte regeneration and growth. Various FGF isoforms have also been shown to directly induce HSC proliferation and activation thereby enabling autocrine and paracrine regulation of HSC function. Regulation of HSCs by the endocrine FGFs, namely, FGF15/19 and FGF21, has also recently been identified. With the ability to modulate HSC proliferation and transdifferentiation, targeting FGF signaling pathways constitutes a promising new therapeutic strategy to treat hepatic fibrosis.

Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: mass effect and contrast enhancement

International Nuclear Information System (INIS)

Raininko, R.; Thelin, L.; Eeg-Olofsson, O.

2001-01-01

Abstract Children and young adults with neurofibromatosis type 1 often have small high-signal foci on T2-weighted images of the brain. We describe follow-up of two patients in whom one of the foci had atypical features, commonly regarded as signs of a neoplasm. In the first, one lesion showed temporary contrast enhancement and decreasing mass effect. The second developed an expanding lesion that increased minimally in size over 4.5 year's follow-up. The borderline between neoplastic and non-neoplastic lesions seems to be indistinct. (orig.)

Effects of Plant Growth Regulators and Photoperiod on In

African Journals Online (AJOL)

Shahin

using the combination of two plant growth regulators and same photoperiod. Key words: Tissue culture, ... they can be stored and transplanted directly into the field without an acclimatization ..... SAS user's guide. cary, NC: Statistical Analysis ...

Growth regulators, DNA content and anatomy in vitro -cultivated ...

African Journals Online (AJOL)

Growth regulators, DNA content and anatomy in vitro -cultivated Curcuma longa ... Shoots were inoculated in MS culture medium with the addition of 30 g/L of sucrose ... flow cytometry, utilizing two reference standards, green pea, and tomato.

Interleukin 1 is an autocrine regulator of human endothelial cell growth

International Nuclear Information System (INIS)

Cozzolino, F.; Torcia, M.; Aldinucci, D.; Ziche, M.; Bani, D.; Almerigogna, F.; Stern, D.M.

1990-01-01

Proliferation of endothelial cells is regulated through the autocrine production of growth factors and the expression of cognate surface receptors. In this study, the authors demonstrate that interleukin 1 (IL-1) is an inhibitor of endothelial growth in vitro and in vivo. IL-1 arrested growing, cultured endothelial cells in G 1 phase; inhibition of proliferation was dose dependent and occurred in parallel with occupancy of endothelial surface IL-1 receptors. In an angiogenesis model, IL-1 could inhibit fibroblast growth factor-induced vessel formation. The autocrine nature of the IL-1 effect on endothelial proliferation was demonstrated by the observation that occupancy of cell-surface receptors by endogenous IL-1 depressed cell growth. The potential significance of this finding was emphasized by the detection of IL-1 in the native endothelium of human umbilical veins. A mechanism by which IL-1 may exert its inhibitory effect on endothelial cell growth was suggested by studies showing that IL-1 decreased the expression of high-affinity fibroblast growth factor binding sites on endothelium. These results point to a potentially important role of IL-1 in regulating blood vessel growth the suggest that autocrine production of inhibitory factors may be a mechanism controlling proliferation of normal cells

Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

Directory of Open Access Journals (Sweden)

Breuninger Holger

2012-03-01

Full Text Available Abstract Background Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB, a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation. Results To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved. Conclusions This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.

The effect of cutting origin and organic plant growth regulator on the growth of Daun Ungu (Graptophyllum pictum) through stem cutting method

Science.gov (United States)

Pratama, S. P.; Yunus, A.; Purwanto, E.; Widyastuti, Y.

2018-03-01

Graptophyllum pictum is one of medical plants which has important chemical content to treat diseases. Leaf, bark and flower can be used to facilitate menstruation, treat hemorrhoid, constipation, ulcers, ulcers, swelling, and earache. G. pictum is difficult to propagated by seedling due to the long duration of seed formation, thusvegetative propagation is done by stem cutting. The aims of this study are to obtain optimum combination of cutting origin and organic plant growth regulator in various consentration for the growth of Daun Ungu through stem cutting method. This research was conducted at Research center for Medicinal Plant and Traditional DrugTanjungsari, Tegal Gede, Karanganyar in June to August 2016. Origin of cuttings and organic plant growth regulator were used as treatments factor. A completely randomized design (RAL) is used and data were analyzed by F test (ANOVA) with a confidence level of 95%. Any significant differences among treatment followed with Duncan test at a = 5%. The research indicates that longest root was resulted from the treatment of 0,5 ml/l of organic plant growth regulator. The treatment of 1 ml/l is able to increase the fresh and dry weight of root, treatment of 1,5 ml/l of organic plant growth regulator was able to increase the percentage of growing shoots. Treatment of base part as origin of cuttings increases the length, fresh weight and and dry weight of shoot, increase the number of leaves. Interaction treatment between 1 ml/l consentration of organic plant growth regulator and central part origin of cuttings is capable of increasing the leaf area, whereas treatment without organic plant growth regulator and base part as planting material affects the smallest leaf area.

Transcriptome analysis reveals the regulation of brassinosteroids on petal growth in Gerbera hybrida

Directory of Open Access Journals (Sweden)

Gan Huang

2017-05-01

Full Text Available Gerbera hybrida is a cut-flower crop of global importance, and an understanding of the mechanisms underlying petal development is vital for the continued commercial development of this plant species. Brassinosteroids (BRs, a class of phytohormones, are known to play a major role in cell expansion, but their effect on petal growth in G. hybrida is largely unexplored. In this study, we found that the brassinolide (BL, the most active BR, promotes petal growth by lengthening cells in the middle and basal regions of petals, and that this effect on petal growth was greater than that of gibberellin (GA. The RNA-seq (high-throughput cDNA sequencing technique was employed to investigate the regulatory mechanisms by which BRs control petal growth. A global transcriptome analysis of the response to BRs in petals was conducted and target genes regulated by BR were identified. These differentially expressed genes (DEGs include various transcription factors (TFs that were activated during the early stage (0.5 h of BL treatment, as well as cell wall proteins whose expression was regulated at a late stage (10 h. BR-responsive DEGs are involved in multiple plant hormone signal pathways, hormone biosynthesis and biotic and abiotic stress responses, showing that the regulation of petal growth by BRs is a complex network of processes. Thus, our study provides new insights at the transcriptional level into the molecular mechanisms of BR regulation of petal growth in G. hybrida.

Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

Directory of Open Access Journals (Sweden)

Ana Paula Cleto Marolla

2016-01-01

Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

Stiff mutant genes of Phycomyces target turgor pressure and wall mechanical properties to regulate elongation growth rate

Directory of Open Access Journals (Sweden)

Joseph K. E. Ortega

2012-05-01

Full Text Available Regulation of cell growth is paramount to all living organisms. In plants, algae and fungi, regulation of expansive growth of cells is required for development and morphogenesis. Also, many sensory responses of stage IVb sporangiophores of Phycomyces blakesleeanus are produced by regulating elongation growth rate (growth responses and differential elongation growth rate (tropic responses. Stiff mutant sporangiophores exhibit diminished tropic responses and are found to be defective in at least four genes; madD, madE, madF and madG. Prior experimental research suggests that the defective genes affect growth regulation, but this was not verified. All the growth of the single-celled stalk of the stage IVb sporangiophore occurs in a short region termed the growth zone. Prior experimental and theoretical research indicates that elongation growth rate of the stage IVb sporangiophore can be regulated by controlling the cell wall mechanical properties within the growth zone and the magnitude of the turgor pressure. A quantitative biophysical model for elongation growth rate is required to elucidate the relationship between wall mechanical properties and turgor pressure during growth regulation. In this study, it is hypothesized that the mechanical properties of the wall within the growth zone of stiff mutant sporangiophores are different compared to wild type. A biophysical equation for elongation growth rate is derived for fungal and plant cells with a growth zone. Two strains of stiff mutants are studied, C149 madD120 (- and C216 geo- (-. Experimental results demonstrate that turgor pressure is larger but irreversible deformation rates of the wall within the growth zone and growth zone length are smaller for stiff mutant sporangiophores compared to wild type. These findings explain the diminished tropic responses of the stiff mutant sporangiophores and suggest that the defective genes affect the amount of wall-building material delivered to the inner

Mechanical Properties of Human Cells Change during Neoplastic Processes

Science.gov (United States)

Guthold, Martin; Guo, Xinyi; Bonin, Keith; Scarpinato, Karin

2014-03-01

Using an AFM with a spherical probe of 5.3 μm, we determined mechanical properties of individual human mammary epithelial cells that have progressed through four stages of neoplastic transformation: normal, immortal, tumorigenic, and metastatic. Measurements on cells in all four stages were taken over both the nucleus and the cytoplasm. Moreover, the measurements were made for cells outside of a colony (isolated), on the periphery of a colony, and inside a colony. By fitting the AFM force vs. indentation curves to a Hertz model, we determined the Young's modulus, E. We found a distinct contrast in the influence a cell's colony environment has on its stiffness depending on whether the cells are normal or cancer cells. We also found that cells become softer as they advance to the tumorigenic stage and then stiffen somewhat in the final step to metastatic cells. For cells averaged over all locations the stiffness values of the nuclear region for normal, immortal, tumorigenic, and metastatic cells were (mean +/- sem) 880 +/- 50, 940+/-50, 400 +/- 20, and 600 +/-20 Pa respectively. Cytoplasmic regions followed a similar trend. These results point to a complex picture of the mechanical changes that occur as cells undergo neoplastic transformation. This work is supported by NSF Materials and Surface Engineering grant CMMI-1152781.

Using natural and synthetic growth regulators of plants in industrial mycology and malting

Directory of Open Access Journals (Sweden)

O. V. Kuznetcova

2010-07-01

Full Text Available Data on the expansion of the use the plants growth regulators in different areas are presented. The positive impact of the growth stimulators on the development of the Pleurotus ostreatus mycelium’s on agar nutrient media during surface cultivation is shown. The results for growth regulators stimulating effect on the fungus biosynthetic activity in submerged cultures are obtained. The possibility of using fumar and heteroauxin for malting is considered. The decline of malting time and increase of amylolytic activity of the malt are recorded.

The effect of some growth regulators on enzyme systems in irradiated barley grain using disinfestation doses

International Nuclear Information System (INIS)

Bachman, S.

1973-01-01

Disinfestation doses of 20 to 100 krad may cause changes in the biological systems of barley grain and, therefore, may influence undesirably the technological quality of malted grain. The effect of some growth regulators on irradiated grain has been investigated. The experiments have been carried out on brewery barley var. Visa Breuns. Following growth-regulators were used: gibberellic acid (Polish preparation ''Gibrescol''), kinetin (6-furfurylo-aminopurin), CCC (2-chloroethyl trimethyl ammonium chloride), and betaine hydrochloride. By treating the irradiated barley with solutions of growth regulators it was possible to diminish the loss of enzyme activity. A ''regenerating'' effect of growth substances, mainly gibberellic acid and betain hydrochloride in 10 -4 M solutions, was observed. Amylolytic activity decreased immediately after irradiation but in samples treated with growth regulators it was higher than in those without regulators. The results may have a practical importance since gibberellic acid has just been introduced into the brewery industry. (F.J.)

Productivity growth and price regulation of Slovenian water distribution utilities

Directory of Open Access Journals (Sweden)

Jelena Zorić

2010-06-01

Full Text Available This paper aims to analyse the price regulation method and performance of thewater industry in Slovenia. A stochastic cost frontier model is employed to estimate and decompose the total factor productivity (TFP growth of water distribution utilities in the 1997-2003 period. The main goal is to find out whether the lack of proper incentives to improve performance has resulted in the low TFP growth of Slovenian water distribution utilities. The evidence suggests that cost inefficiencies are present in water utilities, which indicates considerable cost saving potential in the analysed industry. Technical change is found to have positively affected the TFP growth over time, while cost inefficiency levels remained essentially unchanged. Overall, the average annual TFP growth in the analysed period is estimated to be only slightly above zero, which is a relatively poor result. This can largely be contributed to the present institutional and regulatory setting that does not stimulate utilities to improve productivity. Therefore, the introduction of an independent regulatory agency and an incentive-based price regulation scheme should be seriously considered in order to enhance the performance of Slovenian water distribution utilities.

Regulation of Long Bone Growth in Vertebrates; It Is Time to Catch Up.

Science.gov (United States)

Roselló-Díez, Alberto; Joyner, Alexandra L

2015-12-01

The regulation of organ size is essential to human health and has fascinated biologists for centuries. Key to the growth process is the ability of most organs to integrate organ-extrinsic cues (eg, nutritional status, inflammatory processes) with organ-intrinsic information (eg, genetic programs, local signals) into a growth response that adapts to changing environmental conditions and ensures that the size of an organ is coordinated with the rest of the body. Paired organs such as the vertebrate limbs and the long bones within them are excellent models for studying this type of regulation because it is possible to manipulate one member of the pair and leave the other as an internal control. During development, growth plates at the end of each long bone produce a transient cartilage model that is progressively replaced by bone. Here, we review how proliferation and differentiation of cells within each growth plate are tightly controlled mainly by growth plate-intrinsic mechanisms that are additionally modulated by extrinsic signals. We also discuss the involvement of several signaling hubs in the integration and modulation of growth-related signals and how they could confer remarkable plasticity to the growth plate. Indeed, long bones have a significant ability for "catch-up growth" to attain normal size after a transient growth delay. We propose that the characterization of catch-up growth, in light of recent advances in physiology and cell biology, will provide long sought clues into the molecular mechanisms that underlie organ growth regulation. Importantly, catch-up growth early in life is commonly associated with metabolic disorders in adulthood, and this association is not completely understood. Further elucidation of the molecules and cellular interactions that influence organ size coordination should allow development of novel therapies for human growth disorders that are noninvasive and have minimal side effects.

Spatial Regulation of Root Growth: Placing the Plant TOR Pathway in a Developmental Perspective

Science.gov (United States)

Barrada, Adam; Montané, Marie-Hélène; Robaglia, Christophe; Menand, Benoît

2015-01-01

Plant cells contain specialized structures, such as a cell wall and a large vacuole, which play a major role in cell growth. Roots follow an organized pattern of development, making them the organs of choice for studying the spatio-temporal regulation of cell proliferation and growth in plants. During root growth, cells originate from the initials surrounding the quiescent center, proliferate in the division zone of the meristem, and then increase in length in the elongation zone, reaching their final size and differentiation stage in the mature zone. Phytohormones, especially auxins and cytokinins, control the dynamic balance between cell division and differentiation and therefore organ size. Plant growth is also regulated by metabolites and nutrients, such as the sugars produced by photosynthesis or nitrate assimilated from the soil. Recent literature has shown that the conserved eukaryotic TOR (target of rapamycin) kinase pathway plays an important role in orchestrating plant growth. We will summarize how the regulation of cell proliferation and cell expansion by phytohormones are at the heart of root growth and then discuss recent data indicating that the TOR pathway integrates hormonal and nutritive signals to orchestrate root growth. PMID:26295391

Immunogenetical study of the atomic-bombed patients of neoplastic diseases

International Nuclear Information System (INIS)

Hirota, Masaki; Miyazaki, Takashige; Tomonaga, Akimitsu; Hara, Kohei; Hirose, Takeshi

1978-01-01

The immunogenetical backgrounds of 30 patients with neoplastic diseases (group I) and 30 with non-neoplastic diseases (group II) who were exposed to the A-bomb within 30 km of the center of explosion were studied using human leucocyte antigen (HLA), whose gene combines with Ir-gene, as an index. Eighty-four healthy, non-exposed persons (group III) were selected as controls. Regarding phenotype and genotype frequency, type A9 showed Aw24 and type A10 showed A26 in all cases. Except for Bw40, there was no significant difference among the groups (frequency of A9, I>II; that of A10, II< III). Bw40 was frequently observed in group I although it had racial specificity. There were 16 cases of Bw40 in group I (53.3%), 10 cases in group II (33.3%), and 23 cases in group III (27.3%). Further analysis of Bw40 revealed that Bw40.1 and Bw40.2 were more frequent in group I than in the control group. Bw40.3 was not observed in any of the groups. (Tsunoda, M.)

Growth-Rate Dependent Regulation of tRNA Level and Charging in Bacillus licheniformis.

Science.gov (United States)

Ferro, Iolanda; Liebeton, Klaus; Ignatova, Zoya

2017-10-13

Cellular growth crucially depends on protein synthesis and the abundance of translational components. Among them, aminoacyl-tRNAs play a central role in biosynthesis and shape the kinetics of mRNA translation, thus influencing protein production. Here, we used microarray-based approaches to determine the charging levels and tRNA abundance of Bacillus licheniformis. We observed an interesting cross-talk among tRNA expression, charging pattern, and growth rate. For a large subset of tRNAs, we found a co-regulated and augmented expression at high growth rate. Their tRNA aminoacylation level is kept relatively constant through riboswitch-regulated expression of the cognate aminoacyl-tRNA-synthetase (AARS). We show that AARSs with putative riboswitch-controlled expression are those charging tRNAs with amino acids which disfavor cell growth when individually added to the nutrient medium. Our results suggest that the riboswitch-regulated AARS expression in B. licheniformis is a powerful mechanism not only to maintain a constant ratio of aminoacyl-tRNA independent of the growth rate but concomitantly to control the intracellular level of free amino acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

delta-EF1 is a negative regulator of Ihh in the developing growth plate.

Science.gov (United States)

Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko

2009-11-30

Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

Science.gov (United States)

Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

2006-01-15

The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

Response of pine hypocotyl sections to growth regulators and related substances

Directory of Open Access Journals (Sweden)

J. Zakrzewski

2015-01-01

Full Text Available Growth response of Pinus silvestris hypocotyl sections to some synthetic growth regulators and related substances was studied. Elongation of hypocotyl sections was stimulated by naphtaleneacetic acid, indole-3-acetic acid, in-dole-3-propionic acid, indole-3-butyric acid, 2,4-dichlorophenoxyacetic acid, indoleaoetic amide, indoleacetic nitrile and coumarin. Indole-3-acetic acid and naphtaleneacetic acid extended period of growth up to 16 and 24 hours, respectively. Growth was inhibited by kinetin, trans-cinnamic acid and 2,3,5-tri-iodobenzoic acid. No effect of gibberellic acid, tryptophan and biotin was observed.

Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

International Nuclear Information System (INIS)

DiCicco-Bloom, E.; Black, I.B.

1988-01-01

While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [ 3 H]thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of [ 3 H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain

Effect of plant growth regulators, explants type and efficient plantlet ...

African Journals Online (AJOL)

use

2011-12-05

Dec 5, 2011 ... Plant Pathology, Tissue Culture and Biotechnology Laboratory, Department of Botany,. University of ... variability in response to growth regulators. In vitro rooting ..... an adult tree Wrightia tomentosa through enhanced axillary.

Effects of plant growth regulators in heliconia ‘Red Opal’

Directory of Open Access Journals (Sweden)

Ana Cecilia Ribeiro de Castro

2016-12-01

Full Text Available The objective of this study was to evaluate growth regulators with purpose of reducing the size of heliconia ‘Red Opal’ potted plants. The experiment was carried out in randomized block design with five treatments (trinexapac-ethyl and paclobutrazol at rates of 37.5 and 75.0 mg of active ingredient per pot and control without growth regulator and five replicates. The treatments were applied 40 days after planting the rhizomes in pots filled with soil. Thirty and 150 days after the growth regulator application, plant height, number of leaves and shoots, petioles length and leaf area were evaluated. One year after planting the rhizomes in pots the number of inflorescence and leaves (leaves, sheathing leaf bases and inflorescences and rhizomes (rhizomes and roots dry mass were determined. Trinexapac-ethyl had no differences compared to the control in any of the variables evaluated. Paclobutrazol proved effective in reducing plant height, leaf area and petiole length and increase in number of leaves and shoots but the effect was temporary. Also, it did not affect the inflorescences production and leaves and rhizomes dry mass. Paclobutrazol is efficient to promote height reduction and to increase the number of shoots in heliconia ‘Red Opal’ potted plants without affect the inflorescence formation but its effects is temporary.

Toxicity of the insect growth regulator lufenuron on the ...

African Journals Online (AJOL)

Metarhizium anisopliae has been considered a promising alternative with low environmental impacts for the biological control of a variety of insect-pests. Another alternative is the use of biological pesticides such as insect growth regulators, including lufenuron. An assessment of the potential impact of fungicides on M.

Mechanisms of chemical modification of neoplastic cell transformation by ionizing radiation

International Nuclear Information System (INIS)

Yang, T.C.; Tobias, C.A.

1985-01-01

During space travel, astronauts will be continuously exposed to ionizing radiation; therefore, it is necessary to minimize the radiation damage by all possible means. The authors' studies show that DMSO (when present during irradiation) can protect cells from being killed and transformed by X rays and that low concentration of DMSO can reduce the transformation frequency significantly when it is applied to cells, even many days after irradiation. The process of neoplastic cell transformation is a complicated one and includes at least two different stages: induction and expression. DMSO apparently can modify the radiation damage during both stages. There are several possible mechanisms for the DMSO effect: (1) changing the cell membrane structure and properties; (2) inducing cell differentiation by acting on DNA; and (3) scavanging free radicals in the cell. Recent studies with various chemical agents, e.g., 5-azacytidine, dexamethane, rhodamin-123, etc., indicate that the induction of cell differentiation by acting on DNA may be an important mechanism for the suppression of expression of neoplastic cell transformation by DMSO

Role of growth factors in the growth of normal and transformed cells

International Nuclear Information System (INIS)

Lokeshwar, V.B.

1989-01-01

Growth factors play an important role in the growth of normal cells. However, their untimely and/or excess production leads to neoplastic transformation. The role of growth factors in the growth of normal cells was studied by investigating the mechanism of transmodulation of the cell surface EGF receptor number by protamine. Protamine increased the EGF stimulated mitogenic response in Swiss mouse 3T3 cells and A431 cells by increasing the number of functionally active EGF receptors. Protamine also increased EGF receptor number in plasma membranes and solubilized membranes. This was evidenced by an increase in both 125 I-EGF-EGF-receptor complex and EGF stimulated phosphorylation of the EGF receptor. The solubilized EGF receptor was retained on a protamine-agarose gel indicating that protamine might increase EGF receptor number by directly activating cryptic EGF receptors in the plasma membranes. The role of growth factors in neoplastic transformation was studied by investigating the role of the oncogene v-sis in the growth of Simian sarcoma virus (SSV) transformed cells. The product of the oncogene v-sis is 94% homologous to the B chain of PDGF. This study found that (i) v-sis gene product is synthesized as a 32 kDa unglycosylated monomer which is glycosylated, dimerized and proteolytically processed into p36, p72, p68, p58, p44 and p27 mol. wt. species respectively. (ii) p36, p72, p68 and p58 are very likely formed in the endoplasmic reticulum and/or Golgi complex. A fraction of newly synthesized p72, p68 and p58 is degraded intracellularly at a fast rate. (iii) p44 is a secretory product which remains tightly associated with the cell surface. p44 is recaptured by the cells through interaction with cell surface PDGF receptors and degraded into p27. (iv) During long term cultures p44 is extracellularly cleaved into a 27 kDa product

Methods for growth regulation of greenhouse produced ornamental pot- and bedding plants – a current review

Directory of Open Access Journals (Sweden)

Bergstrand Karl-Johan I.

2017-06-01

Full Text Available Chemical plant growth regulators (PGRs are used in the production of ornamental potted and bedding plants. Growth control is needed for maximizing production per unit area, reducing transportation costs and to obtain a desired visual quality. However, the use of PGRs is associated with toxicity risks to humans and the environment. In many countries the availability of PGRs is restricted as few substances are registered for use. A number of alternative methods have been suggested. The methods include genetic methods (breeding and crop cultivation practices such as fertigation, temperature and light management. A lot of research into “alternative” growth regulation was performed during the 1980-1990s, revealing several possible ways of using different climatic factors to optimize plant growth with respect to plant height. In recent years, the interest in climatic growth regulation has been resurrected, not least due to the coming phase-out of the plant growth regulator chlormequat chloride (CCC. Today, authorities in many countries are aiming towards reducing the use of agrochemicals. At the same time, there is a strong demand from consumers for products produced without chemicals. This article provides a broad overview of available methods for non-chemical growth control. It is concluded that a combination of plant breeding and management of temperature, fertigation and light management has the potential of replacing chemical growth regulators in the commercial production of ornamental pot- and bedding plants.

Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

Science.gov (United States)

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-04-01

Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

Metabolic regulation of mycobacterial growth and antibiotic sensitivity.

Directory of Open Access Journals (Sweden)

Seung-Hun Baek

2011-05-01

Full Text Available Treatment of chronic bacterial infections, such as tuberculosis (TB, requires a remarkably long course of therapy, despite the availability of drugs that are rapidly bacteriocidal in vitro. This observation has long been attributed to the presence of bacterial populations in the host that are "drug-tolerant" because of their slow replication and low rate of metabolism. However, both the physiologic state of these hypothetical drug-tolerant populations and the bacterial pathways that regulate growth and metabolism in vivo remain obscure. Here we demonstrate that diverse growth-limiting stresses trigger a common signal transduction pathway in Mycobacterium tuberculosis that leads to the induction of triglyceride synthesis. This pathway plays a causal role in reducing growth and antibiotic efficacy by redirecting cellular carbon fluxes away from the tricarboxylic acid cycle. Mutants in which this metabolic switch is disrupted are unable to arrest their growth in response to stress and remain sensitive to antibiotics during infection. Thus, this regulatory pathway contributes to antibiotic tolerance in vivo, and its modulation may represent a novel strategy for accelerating TB treatment.

Growth Hormone Receptor Signaling Pathways and its Negative Regulation by SOCS2

DEFF Research Database (Denmark)

Fernández Pérez, Leandro; Flores-Morales, Amilcar; Guerra, Borja

2016-01-01

Growth hormone (GH) is a critical regulator of linear body growth during childhood but continues to have important metabolic actions throughout life. The GH receptor (GHR) is ubiquitously expressed, and deficiency of GHR signaling causes a dramatic impact on normal physiology during somatic devel...

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

Science.gov (United States)

Lee, Jeong Sub; Kim, Jung Hoon; Kim, Yong Jae; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Young; Han, Joon Koo

2017-07-01

To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

Adaptive Response Against Spontaneous Neoplastic Transformation In Vitro Induced by Ionizing Radiation

International Nuclear Information System (INIS)

Redpath, J. Leslie

2003-01-01

The goal of this project was to establish a dose response curve for radiation-induced neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro under experimental conditions were an adaptive response, if it were induced, would have an opportunity to be expressed. During the first two years of the grant an exhaustive series of experiments were performed and the resulting data were reported at the 2000 Annual Meeting of the Radiation Research Society and then Subsequently published. The data showed that an adaptive response against spontaneous neoplastic transformation was seen up to doses of 10cGy of Cs-137 gamma rays. At dose of 30, 50 and 100 cGy the transformation frequencies were above background. This indicated that for this system, under the specific experimental conditions used, there was a threshold of somewhere between 10 and 30 cGy. The results also indicated some unexpected, though very interesting, correlations with relative risk estimates made from human epidemiologic studies

Chondroblastoma and chondromyxoid fibroma : disentangling the neoplastic chondrogenesis of two rare cartilaginous tumours

NARCIS (Netherlands)

Romeo, Salvatore

2010-01-01

The scope of this study was to disentangle neoplastic chondrogenesis in two rare cartilaginous tumours: chondroblastoma and chondromyxoid fibroma. It was addressed: 1 The spectrum of phenotypic differentiation in chondroblastoma and chondromyxoid fibroma, 2 The signalling pathways driving

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Energy Technology Data Exchange (ETDEWEB)

Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2017-06-15

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

International Nuclear Information System (INIS)

Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

2017-01-01

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

The effect of postirradiation holding at 22 degrees C on the repair of sublethal, potentially lethal and potentially neoplastic transforming damage in gamma-irradiated HeLa x skin fibroblast human hybrid cells

International Nuclear Information System (INIS)

Redpath, J.L.; Antoniono, R.J.; Mendonca, M.S.; Sun, C.

1994-01-01

The effect of postirradiation holding at 22 degrees C on cell growth, progression of cells through the cell cycle, and the repair of sublethal, potentially lethal and potentially neoplastic transforming damage in γ-irradiated HeLa x skin fibroblast human hybrid cells has been examined. Cell growth and cell cycle progression were essentially stopped at this reduced temperature. Cell survival was dramatically reduced by holding confluent cultures for 6 h at 22 degrees C, as opposed to 37 degrees C, after 7.5 Gy γ radiation delivered at a rate of 2 Gy/min. Return of the cells to 37 degrees C for 6 h after holding at 22 degrees C did not result in increased survival. A similar effect was obtained when the cells were held at 22 degrees C between split-dose irradiation of log-phase cultures where no increase in survival was observed over a split-dose interval of 4 h. In this case a partial increase in survival was observed upon returning the cells to 37 degrees C for 3 h after holding at 22 degrees C for the first 3 h of the split-dose interval. Neoplastic transformation frequency was not enhanced by holding confluent cultures for 6 h at 22 degrees C after 7.5 Gy γ radiation. This is consistent with previous observations that misrepair of potentially neoplastic transforming damage already occurs at 37 degrees C. The overall results are interpreted in terms of the reduced temperature favoring misrepair, rather than inhibition of repair, of sublethal, potentially lethal and potentially transforming radiation damage. 24 refs., 5 figs., 3 tabs

Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

International Nuclear Information System (INIS)

Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

2012-01-01

Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

Effect of plant growth regulators on in vitro germination of coffee ...

African Journals Online (AJOL)

ajl yemi

2011-12-19

Dec 19, 2011 ... Germination times of zygotic embryos cultured in MS medium had a mean of 5.1 days, ... growth regulators used, gibberellic acid at 0.1 mg l-1 proved to be the most efficient in .... process, and the biological role of regulators was invest- ... thiamine, 25 mg l-1 cysteine, and 3% sucrose for MS; and 100 mg l-1.

Degradation of type IV collagen by neoplastic human skin fibroblasts

International Nuclear Information System (INIS)

Sheela, S.; Barrett, J.C.

1985-01-01

An assay for the degradation of type IV (basement membrane) collagen was developed as a biochemical marker for neoplastic cells from chemically transformed human skin fibroblasts. Type IV collagen was isolated from basement membrane of Syrian hamster lung and type I collagen was isolated from rat tails; the collagens were radioactively labelled by reductive alkylation. The abilities of normal (KD) and chemically transformed (Hut-11A) human skin fibroblasts to degrade the collagens were studied. A cell-associated assay was performed by growing either normal or transformed cells in the presence of radioactively labelled type IV collagen and measuring the released soluble peptides in the medium. This assay also demonstrated that KD cells failed to synthesize an activity capable of degrading type IV collagen whereas Hut-11A cells degraded type IV collagen in a linear manner for up to 4 h. Human serum at very low concentrations, EDTA and L-cysteine inhibited the enzyme activity, whereas protease inhibitors like phenylmethyl sulfonyl fluoride, N-ethyl maleimide or soybean trypsin inhibitor did not inhibit the enzyme from Hut-11A cells. These results suggest that the ability to degrade specifically type IV collagen may be an important marker for neoplastic human fibroblasts and supports a role for this collagenase in tumor cell invasion

Growth in Adolescent Self-Regulation and Impact on Sexual Risk-Taking: A Curve-of-Factors Analysis.

Science.gov (United States)

Crandall, AliceAnn; Magnusson, Brianna M; Novilla, M Lelinneth B

2018-04-01

Adolescent self-regulation is increasingly seen as an important predictor of sexual risk-taking behaviors, but little is understood about how changes in self-regulation affect later sexual risk-taking. Family financial stress may affect the development of self-regulation and later engagement in sexual risk-taking. We examined whether family financial stress influences self-regulation in early adolescence (age 13) and growth in self-regulation throughout adolescence (from age 13-17 years). We then assessed the effects of family financial stress, baseline self-regulation, and the development of self-regulation on adolescent sexual risk-taking behaviors at age 18 years. Using a curve-of-factors model, we examined these relationships in a 6-year longitudinal study of 470 adolescents (52% female) and their parents from a large northwestern city in the United States. Results indicated that family financial stress was negatively associated with baseline self-regulation but not with growth in self-regulation throughout adolescence. Both baseline self-regulation and growth in self-regulation were predictive of decreased likelihood of engaging in sexual risk-taking. Family financial stress was not predictive of later sexual risk-taking. Intervening to support the development of self-regulation in adolescence may be especially protective against later sexual risk-taking.

Self-regulating and diameter-selective growth of GaN nanowires

International Nuclear Information System (INIS)

Kuo, C-K; Hsu, C-W; Wu, C-T; Lan, Z-H; Mou, C-Y; Chen, C-C; Yang, Y-J; Chen, L-C; Chen, K-H

2006-01-01

We report diameter-selective growth of GaN nanowires (NWs) by using mono-dispersed Au nanoparticles (NPs) on a ligand-modified Si substrate. The thiol-terminal silane was found to be effective in producing well-dispersed Au NPs in low density on Si substrates so that the agglomeration of Au NPs during growth could be avoided. The resultant GaN NWs exhibited a narrow diameter distribution and their mean diameter was always larger than, while keeping a deterministic relation with, the size of the Au NPs from which they were grown. A self-regulating steady growth model is proposed to account for the size-control process

BMP signaling regulates satellite cell-dependent postnatal muscle growth.

Science.gov (United States)

Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

2017-08-01

Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

International Nuclear Information System (INIS)

Boll, Daniel T.; Lewin, Jonathan S.; Young, Philip; Gilkeson, Robert C.; Siwik, Ernest S.

2005-01-01

The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, nonembolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel centerlines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries. (orig.)

Neoplastic meningitis: a retrospective review of clinical presentations, radiological and cerebrospinal fluid findings.

Science.gov (United States)

Jearanaisilp, Sorrawit; Sangruji, Tumthip; Danchaivijitr, Chotipat; Danchaivijitr, Nasuda

2014-08-01

To review the clinical, radiological, and laboratory presentations of patients with neoplastic meningitis. Patients with neoplastic meningitis were recruited by a retrospective search of cerebrospinal fluid (CSF) cytopathological report database of Siriraj Hospital between 1997 and 2006. Clinical information and CSF result of these patients were extracted from their medical records. Neuroimagings were reviewed by a neuroradiologist. The present study revealed 40 cases of neoplastic meningitis, which comprised of 17 cases with carcinomatous meningitis (CM) and 23 lymphoma/leukemia meningitis (LM) cases. In patients with CM, the majority (70%) had adenocarcinoma of lung or breast. Three of 17 cases with unknown primary tumor had carcinomatous meningitis as an initial presentation. In LM most of the cases (70%) were diagnosed with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The most common symptom among patients with CM and LM was headache follow by cranial nerve palsy. In CM cases, CSF cytology was positive in the first specimen in 15 cases (82.35%) and in 22 from 23 cases (95.7%) in LM cases. Overall CSF showed pleocytosis in 36 cases (90%), most of which were lymphocyte predominant. The most common findings from brain imagings were leptomeningeal enhancement and hydrocephalus. The common primary sites were lung and breast cancer in the CM group and ALL and NHL in the LM group. The common symptoms were headache and cranial nerve palsy. Routine CSF examination was abnormal in virtually all cases. Positive CSF cytology was a gold standard for a diagnosis of leptomeningeal metastasis. High index of suspicious and awareness were required to avoid miss diagnosis.

Nuclear Division Index may Predict Neoplastic Colorectal Lesions.

Science.gov (United States)

Ionescu, Mirela E; Ciocirlan, Mihai; Becheanu, Gabriel; Nicolaie, Tudor; Ditescu, Cristina; Teiusanu, Adriana G; Gologan, Serban I; Arbanas, Tudor; Diculescu, Mircea M

2011-07-01

Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker.

In vitro production of growth regulators and phosphatase activity by ...

African Journals Online (AJOL)

The result showed that the population levels of phosphobacteria were higher in the rhizosphere soil of groundnut plant. Further, all the strains of phosphobacteria were able to produce phytohormones and phosphatase enzyme under in vitro conditions. Keywords: In vitro, phosphobacteria, growth regulators ...

Effects of photoperiod, plant growth regulators and culture media on in vitro growth of seedlings of Cyrtochilum loxense (Lindl. Kraenzl. an endemic and endangered orchid from Ecuador

Directory of Open Access Journals (Sweden)

Yadira González

2014-10-01

Full Text Available Cyrtochilum loxense (Lindl. Kraenzl. is an endemic and seriously endangered orchid species endemic in the Loja Province (Southern Ecuador. The main goals of this research were to analyze how culture media, plant growth regulators and photoperiod affect the growth of C. loxense. Eight month old plants (approximate 1 – 1.5 cm in height obtained by in vitro germination, were cultivated on MS media or Knudson C; MS with three levels of naphthalene acetic acid (NAA and 6-benzylaminopurine (BAP (2/0.5; 1/0.5 y 0.5/ 0.5 mg-1L; and three photoperiodic regimes (24/0, 16/8, 8/16 h on MS with and without plant growth regulators. No significant differences of shoot induction were observed on media with or without plant growth regulators, and all tested photoperiods. The highest growth (1.2 cm was observed in plantlets cultivated on growth regulator-free media with a 16/8 photoperiod. Also the shoot and root formation was better in this species in absence of plant growth regulators. Probably this response is due to the endogenous hormone levels in the tissues or due to the kind and concentrations of PGRs used were too low to induce positive morphogenetic responses.

2-[(aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Coγ-ray irradiation

International Nuclear Information System (INIS)

Hill, C.K.; Nagy, B.; Peraino, C.; Grdina, D.

1986-01-01

The effect of 2[(aminopropyl)amino]ethanethiol (WR1065) has been studied on the induction of neoplastic transformation using 10T1/2 cells and on mutation of the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using Chinese hamster V79 cells. The first observations that treatment of 10T1/2 cells with 1 mM WR1065 for a total of 35 min during irradiation with 60 C γ-rays significantly reduces the incidence of neoplastic transformation while having no effect on cell viability are reported. In a similar experiment with V79 cells in which 4mM WR1065 was used, a significant reduction in mutation frequency at the HGPRT locus and significant protection against cell killing was found. These results suggest that WR1965 acts to modulate both acute damage and sub-lethal processes that lead to mutation and neoplastic transformation. Beyond the purely mechanistic approach of these studies, the potential application of these agents to minimizing the long-term neoplastic effects of radiation or chemotherapeutic agents currently in use for treating potentially curable cancer patients should be further investigated. (author)

Regulation of insulin-like growth factor I receptors on vascular smooth muscle cells by growth factors and phorbol esters.

Science.gov (United States)

Ververis, J J; Ku, L; Delafontaine, P

1993-06-01

Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells. To characterize regulation of vascular IGF I receptors, we performed radioligand displacement experiments using rat aortic smooth muscle cells (RASMs). Serum deprivation for 48 hours caused a 40% decrease in IGF I receptor number. Exposure of quiescent RASMs to platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), or angiotensin II (Ang II) caused a 1.5-2.0-fold increase in IGF I receptors per cell. After FGF exposure, there was a marked increase in the mitogenic response to IGF I. IGF I downregulated its receptors in the presence of platelet-poor plasma. Stimulation of protein kinase C (PKC) by exposure of quiescent RASMs to phorbol 12-myristate 13-acetate caused a biphasic response in IGF I binding; there was a 42% decrease in receptor number at 45 minutes and a 238% increase at 24 hours. To determine the role of PKC in growth factor-induced regulation of IGF I receptors, we downregulated PKC by exposing RASMs to phorbol 12,13-dibutyrate (PDBu) for 48 hours. PDGF- and FGF- but not Ang II-mediated upregulation of IGF I receptors was completely inhibited in PDBu-treated cells. Thus, acute PKC activation by phorbol esters inhibits IGF I binding, whereas chronic PKC activation increases IGF I binding. PDGF and FGF but not Ang II regulate vascular IGF I receptors through a PKC-dependent pathway. These data provide new insights into the regulation of vascular smooth muscle cell IGF I receptors in vitro and are of potential importance in characterizing vascular proliferative responses in vivo.

Up-regulated EMMPRIN/CD147 protein expression might play a role in colorectal carcinogenesis and its subsequent progression without an alteration of its glycosylation and mRNA level.

Science.gov (United States)

Zheng, Hua-chuan; Wang, Wei; Xu, Xiao-yan; Xia, Pu; Yu, Miao; Sugiyama, Toshiro; Takano, Yasuo

2011-04-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of colorectal carcinomas (CRC). EMMPRIN expression was examined on tissue microarray containing colorectal carcinomas, adenoma and non-neoplastic mucosa (NNM) by immunohistochemistry and in situ hybridization (ISH). Colorectal carcinoma cell lines (DLD-1, HCT-15, SW480 and WiDr) and tissues were studied for EMMPRIN expression by Western blot or RT-PCR, followed by sequencing. All carcinoma cell lines showed EMMPRIN expression at both mRNA and protein levels. Two synonymous mutations were found in carcinoma cell lines at codon109 (GCT → GCC: Ala) or 179 (GAT → GAC: Asp). Frozen CRC tissues displayed higher EMMPRIN expression than paired NNM (P EMMPRIN expression was immunohistochemically stronger in colorectal high-grade adenoma, adenocarcinoma and metastatic carcinoma than non-neoplastic superficial epithelium and low-grade adenoma (P 0.05). Immunohistochemically, EMMPRIN expression was positively correlated with tumor size, depth of invasion, vascular or lymphatic invasion, grade of infiltration (INF), ki-67 and VEGF expression of CRCs (P EMMPRIN expression in CRCs (P EMMPRIN protein expression might contribute to colorectal carcinogenesis without the alteration of its glycosylation and mRNA level. Aberrant EMMPRIN protein expression might promote growth or invasion of CRCs possibly through increased ki-67 expression and inducible angiogenesis via up-regulating VEGF expression.

The A-myb transcription factor in neoplastic and normal B cells.

Science.gov (United States)

Golay, J; Facchinetti, V; Ying, G; Introna, M

1997-07-01

The myb family of transcription factors has been strongly implicated in the regulation of cell growth and differentiation in the haematopoietic system. The v-myb oncogene, carried by avian defective retroviruses, causes leukaemias in the chicken and transforms haematopoietic cells in vitro. Its normal cellular equivalent c-myb, has been shown to promote the proliferation and block the differentiation of haematopoietic cells in several experimental models and is required for fetal haematopoiesis. Two other members of the family have been cloned more recently, A-myb and B-myb, which show sequence homology with c-myb in several domains, of which the DNA binding domain as well as other regulatory domains. Both have been shown to be transcription factors. B-myb is also involved in the control of proliferation and differentiation, but, unlike c-myb, it is expressed in many cell types. The third member of the family, A-myb, shows the most restricted pattern of expression, suggesting a very specific role for this transcription factor. A-myb is expressed in a subpopulation of normal B lymphocytes activated in vivo and localised in the germinal center of peripheral lymphoid organs and is not detected at significant levels in all other mature or immature haematopoietic populations studied, including bone marrow cells, T lymphocytes, granulocytes, monocytes, either at rest or after in vitro activation. These studies indicate that A-myb plays a role during a narrow window of normal B cell differentiation. A-myb expression has also been studied in a wide range of neoplastic B cells, representing the whole spectrum of B cell differentiation. A-myb is strongly expressed in Burkitt's lymphomas (BL) and slg+ B-acute lymphoblastic leukaemias (B-ALL) and not in all other leukaemias/lymphomas tested, with the exception of a subset of CLL (about 25% of cases). It is intriguing that the A-myb genome has been localised relatively close to the c-myc gene on chromosome 8, suggesting that

Prioritizing plant defence over growth through WRKY regulation facilitates infestation by non-target herbivores

Science.gov (United States)

Li, Ran; Zhang, Jin; Li, Jiancai; Zhou, Guoxin; Wang, Qi; Bian, Wenbo; Erb, Matthias; Lou, Yonggen

2015-01-01

Plants generally respond to herbivore attack by increasing resistance and decreasing growth. This prioritization is achieved through the regulation of phytohormonal signaling networks. However, it remains unknown how this prioritization affects resistance against non-target herbivores. In this study, we identify WRKY70 as a specific herbivore-induced, mitogen-activated protein kinase-regulated rice transcription factor that physically interacts with W-box motifs and prioritizes defence over growth by positively regulating jasmonic acid (JA) and negatively regulating gibberellin (GA) biosynthesis upon attack by the chewing herbivore Chilo suppressalis. WRKY70-dependent JA biosynthesis is required for proteinase inhibitor activation and resistance against C. suppressalis. In contrast, WRKY70 induction increases plant susceptibility against the rice brown planthopper Nilaparvata lugens. Experiments with GA-deficient rice lines identify WRKY70-dependent GA signaling as the causal factor in N. lugens susceptibility. Our study shows that prioritizing defence over growth leads to a significant resistance trade-off with important implications for the evolution and agricultural exploitation of plant immunity. DOI: http://dx.doi.org/10.7554/eLife.04805.001 PMID:26083713

Para neoplastic syndromes: Usefulness of 18F-fluoro-deoxy-glucose (F.D.G.) positron emission tomography (PET)

International Nuclear Information System (INIS)

Banayan, S.; Janier, M.; Guillerma-Zucchi, N.; Billotey, C.; Ninet, J.; Delmas, P.; Thivolet, C.; Pellet, O.

2008-01-01

Background We evaluated the performance of 18 F-fluorodeoxyglucose ( 18 F.D.G.) positron emission tomography (PET) in the diagnosis of underlying malignancy in cases of suspected para neoplastic syndrome (P.S.). Methods 18 F.D.G.-PET was performed in 31 patients, clinically suspected to have P.S.. The P.S. were 34, among which 12 neurological diseases, eight endocrine, seven rheumatological, one dermatological and six vascular. We compared computed tomography (CT), iodine-enhanced most of the time, and 18 F.D.G.-PET reports to clinicians definitive conclusion at the end of the work-up and a follow-up period of, at least, two months. Results We obtained a histological diagnosis of cancer for ten patients, but could only identify the primary site of malignancy for nine of them. 18 F.D.G.-PET showed six primary sites among which three were not seen on CT. CT disclosed four primary sites, among which one was not seen on 18 F.D.G.-PET. In one case, 18 F.D.G.-PET disclosed regional lymph node metastases whereas these were not identified by CT. Eleven non-neoplastic causes were evidenced, among which 18 F.D.G.-PET played a major role in three cases. Ten causes were still undetermined at the end of the study. Conclusion Whole-body 18 F.D.G.-PET study plays an important role in the identification of underlying malignancy in clinically suspected para neoplastic syndromes; either by identifying the primary tumor or by directing biopsy of metastases. Furthermore, it can identify non-neoplastic causes. (authors)

Neoplastic progression of rat tracheal epithelial cells involves resistance to transforming growth factor beta

International Nuclear Information System (INIS)

Hubbs, A.F.; Hahn, F.F.; Thomassen, D.G.

1988-01-01

Primary, transformed, and tumor-derived rat tracheal epithelial (RTE) cells were grown in serum-free medium containing 0 to 300 pg/mL transforming growth factor beta (TGFβ) markedly inhibited the growth of primary RTE cells with a 50% drop in the efficiency of colony formation seen at TGFβ concentrations between 10 and 30 pg/ mL. The effect of TGFβ on preneoplastic RTE cells was similar to the effect on normal primary RTE cells. Cell lines established from tumors produced by inoculation of transformed RTE cells into nude mice were relatively resistant to -TGFβ-induced growth inhibition. Resistance to TGFβ-induced growth inhibition, therefore, appears to be a late event in the development of neoplasia. (author)

Reduced temperature (22 degrees C) results in enhancement of cell killing and neoplastic transformation in noncycling HeLa x skin fibroblast human hybrid cells irradiated with low-dose-rate gamma radiation

International Nuclear Information System (INIS)

Redpath, J.L.; Antoniono, R.J.

1995-01-01

The effect of reduced temperature (22 degrees C) or serum deprivation during low-dose-rate (0.66 cGy/min) γ irradiation on cell killing and neoplastic transformation has been examined using the HeLa x skin fibroblast human hybrid cell system. The reduced temperature stops progression of these cells through the cell cycle while serum deprivation slows down cell turnover markedly. The data demonstrate an enhancement in both of the end points when cells are held at 22 degrees C compared to parallel experiments done at 37 degrees C. In operational terms, the decreased survival and increased neoplastic transformation are consistent with our earlier hypothesis of a higher probability of misrepair at reduced temperature. The interpretation that this damage enhancement was associated with the reduced temperature, and not the fact that the cells were noncycling, was supported by the results of experiments performed with cells cultured at 37 degrees C in serum-free medium for 35 h prior to and then during the 12.24 h low-dose-rate radiation exposure. Under these conditions, cell cycle progression, as shown by reduction in growth rate and dual-parameter flow cytometric analysis, was considerable inhibited (cell cycle time increased from 20 h to 40 h), and there was no significant enhancement of cell killing or neoplastic transformation. 23 refs., 2 figs., 1 tab

EFFECTS OF SOME PLANT GROWTH REGULATORS ON JASMONIC ACID INDUCED INHIBITION OF SEED GERMINATION AND SEEDLING GROWTH OF BARLEY

Directory of Open Access Journals (Sweden)

Kürşat ÇAVUŞOĞLU

2009-02-01

Full Text Available Abstract: The effects of gibberellic acid, kinetin, benzyladenine, ethylene, 24-epibrassinolide and polyamines (spermine, spermidine, putrescine, cadaverine on jasmonic acid inhibition of seed germination and seedling growth of barley were studied. All of the plant growth regulators studied were determined to have a succesful performance in reversing of the inhibitory effects of jasmonic acid on the seed germination and seedling growth. Moreover, the above mentioned growth regulators overcame the inhibitory effect of JA on the percentages of germination and coleoptile emergence in the same ratio, while GA3 was the most successful hormone on the fresh weight and radicle and coleoptile elongation in comparison with the other growth regulators. Key words: Barley, jasmonic acid, plant growth regulator, seed germination, seedling growth ARPANIN TOHUM ÇİMLENMESİ VE FİDE BÜYÜMESİNİN JASMONİK ASİT TEŞVİKLİ İNHİBİSYONU ÜZERİNE BAZI BİTKİ BÜYÜME DÜZENLEYİCİLERİNİN ETKİLERİ Özet: Arpanın tohum çimlenmesi ve fide büyümesinin jasmonik asit inhibisyonu üzerine gibberellik asit, kinetin, benziladenin, etilen, 24-epibrassinolit ve poliaminlerin (spermin, spermidin, putressin, kadaverin etkileri araştırılmıştır. Çalışılan bitki büyüme düzenleyicilerinin tümünün tohum çimlenmesi ve fide büyümesi üzerinde jasmonik asitin engelleyici etkisini tersine çevirmede başarılı bir performansa sahip oldukları belirlenmiştir. Dahası, yukarıda sözü edilen büyüme düzenleyicileri çimlenme ve koleoptil çıkış yüzdeleri üzerinde aynı oranda etkili olurken, taze ağırlık ve radikula ve koleoptil uzaması üzerinde diğer büyüme düzenleyicileri ile karşılaştırıldığında en başarılı hormon GA3 olmuştur. Anahtar kelimeler: Arpa, jasmonik asit, bitki büyüme düzenleyicisi, tohum çimlenmesi, fide büyümesi

Effect of plant growth regulators on callus induction and plant ...

African Journals Online (AJOL)

The present study was conducted to investigate the effects of different concentrations and combinations of growth regulators on callus induction and plant regeneration of potato (Solanum tuberosum L.) cultivar Diamant. The tuber segments were used as explants and cultured on Murashige and Skoog (MS) medium ...

Overview of OVATE FAMILY PROTEINS, a novel class of plant-specific growth regulators

Directory of Open Access Journals (Sweden)

Shucai eWang

2016-03-01

Full Text Available OVATE FAMILY PROTEINS (OFPs are a class of proteins with a conserved OVATE domain. OVATE protein was first identified in tomato as a key regulator of fruit shape. OFPs are plant-specific proteins that are widely distributed in the plant kingdom including mosses and lycophytes. Transcriptional activity analysis of Arabidopsis OFPs (AtOFPs in protoplasts suggests that they act as transcription repressors. Functional characterization of OFPs from different plant species including Arabidopsis, rice, tomato, pepper and banana suggests that OFPs regulate multiple aspects of plant growth and development, which is likely achieved by interacting with different types of transcription factors including the KNOX and BELL classes, and/or directly regulating the expression of target genes such as Gibberellin 20 oxidase (GA20ox. Here, we examine how OVATE was originally identified, summarize recent progress in elucidation of the roles of OFPs in regulating plant growth and development, and describe possible mechanisms underpinning this regulation. Finally, we review potential new research directions that could shed additional light on the functional biology of OFPs in plants.

Drosophila Big bang regulates the apical cytocortex and wing growth through junctional tension.

Science.gov (United States)

Tsoumpekos, Giorgos; Nemetschke, Linda; Knust, Elisabeth

2018-03-05

Growth of epithelial tissues is regulated by a plethora of components, including signaling and scaffolding proteins, but also by junctional tension, mediated by the actomyosin cytoskeleton. However, how these players are spatially organized and functionally coordinated is not well understood. Here, we identify the Drosophila melanogaster scaffolding protein Big bang as a novel regulator of growth in epithelial cells of the wing disc by ensuring proper junctional tension. Loss of big bang results in the reduction of the regulatory light chain of nonmuscle myosin, Spaghetti squash. This is associated with an increased apical cell surface, decreased junctional tension, and smaller wings. Strikingly, these phenotypic traits of big bang mutant discs can be rescued by expressing constitutively active Spaghetti squash. Big bang colocalizes with Spaghetti squash in the apical cytocortex and is found in the same protein complex. These results suggest that in epithelial cells of developing wings, the scaffolding protein Big bang controls apical cytocortex organization, which is important for regulating cell shape and tissue growth. © 2018 Tsoumpekos et al.

Effectiveness of growth regulators, based on the heterylcarbon acid, on forcing of Tulips (Tulips HD

Directory of Open Access Journals (Sweden)

Derevianko Natalia

2016-03-01

Full Text Available The main factor in growing flowers for forcing is their rate of growth, on account of the fact that in short period of time it is necessary to grow quickly a large number of flowers and to cut them simultaneously. The influence of growth regulators (GR based on heterylcarbon acid on the forcing of tulips in greenhouse conditions (winter period was studied. It was determined that the application of GR1 of the basic within tulip’s forcing period reduces in average to 5 days (from all period of forcing. In case of application GR2 the tulip’s forcing period also reduces to 3 days (from all period of forcing compared with a control group of tulips. The ability of the plant growth regulators under research to accelerate growing properties of flowers is associated with the presence of heterylcarbon acid and potassium ions in their structure of substances. These growth regulators relate to non-toxic compounds and possess antioxidant properties.

GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

Science.gov (United States)

Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

2015-07-29

The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

Fluoxetine regulates cell growth inhibition of interferon-α.

Science.gov (United States)

Lin, Yu-Min; Yu, Bu-Chin; Chiu, Wen-Tai; Sun, Hung-Yu; Chien, Yu-Chieh; Su, Hui-Chen; Yen, Shu-Yang; Lai, Hsin-Wen; Bai, Chyi-Huey; Young, Kung-Chia; Tsao, Chiung-Wen

2016-10-01

Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

International Nuclear Information System (INIS)

Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

2013-01-01

Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

Directory of Open Access Journals (Sweden)

Carlstrom Lucas P

2011-11-01

Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

Linking gene regulation to cell behaviors in the posterior growth zone of sequentially segmenting arthropods.

Science.gov (United States)

Williams, Terri A; Nagy, Lisa M

2017-05-01

Virtually all arthropods all arthropods add their body segments sequentially, one by one in an anterior to posterior progression. That process requires not only segment specification but typically growth and elongation. Here we review the functions of some of the key genes that regulate segmentation: Wnt, caudal, Notch pathway, and pair-rule genes, and discuss what can be inferred about their evolution. We focus on how these regulatory factors are integrated with growth and elongation and discuss the importance and challenges of baseline measures of growth and elongation. We emphasize a perspective that integrates the genetic regulation of segment patterning with the cellular mechanisms of growth and elongation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of plant growth regulators on regeneration of the endangered ...

African Journals Online (AJOL)

Development of an efficient in vitro regeneration protocol of Calligonum comosum is important and that has achieved to protect the endangered multipurpose medicinally important desert plant in the Kingdom of Bahrain. Nodal segments were used as explants source and the effect of various plant growth regulators (PGRs) ...

Emergence of robust growth laws from optimal regulation of ribosome synthesis.

Science.gov (United States)

Scott, Matthew; Klumpp, Stefan; Mateescu, Eduard M; Hwa, Terence

2014-08-22

Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large-scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome-wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply-driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

Energy Technology Data Exchange (ETDEWEB)

Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

2012-07-15

In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

Non-neoplastic cystic and cystic-like lesions of the pancreas: may mimic pancreatic cystic neoplasms.

Science.gov (United States)

Goh, Brian K P; Tan, Yu-Meng; Chung, Yaw-Fui A; Chow, Pierce K H; Ong, Hock-Soo; Lim, Dennis T H; Wong, Wai-Keong; Ooi, London L P J

2006-05-01

Cystic lesions of the pancreas consist of a broad range of pathological entities. With the exception of the pancreatic pseudocyst, these are usually caused by pancreatic cystic neoplasms. Non-neoplastic pancreatic cystic and cystic-like lesions are extremely rare. In the present article, the surgical experience with these unusual entities over a 14-year period is reported. Between 1991 and 2004, all patients who underwent surgical exploration for a cystic lesion of the pancreas were retrospectively reviewed. Patients with a pancreatic pseudocyst were excluded. There were 106 patients of whom 8 (7.5%) had a final pathological diagnosis consistent with a non-neoplastic pancreatic cystic or cystic-like lesion, including 3 patients with a benign epithelial cyst, 2 with a pancreatic abscess (one tuberculous and one foreign body), 2 with mucous retention cysts and 1 with a mucinous non-neoplastic cyst. These eight patients are the focus of this study. There were six female and two male patients with a median age of 61.5 years (range, 41-71 years). All the patients were of Asian origin including seven Chinese and one Indian. Four of the patients were asymptomatic and their pancreatic cysts were discovered incidentally on radiological imaging for other indications. All the patients underwent preoperative radiological investigations, including ultrasonography, computed tomography or magnetic resonance imaging, which showed a cystic lesion of the pancreas. Three patients, all of whom were symptomatic, were diagnosed preoperatively with a malignant cystic neoplasm on the basis of radiological imaging. Two patients were eventually found to have a pancreatic abscess, one tuberculous and the other, secondary to foreign body perforation. The third patient was found on final histology to have chronic pancreatitis with retention cysts. The remaining five patients had a preoperative diagnosis of an indeterminate cyst; on pathological examination, they were found to have a benign

Institutions and Regulation for Economic Growth ? : public interests versus public incentives

NARCIS (Netherlands)

Wubben, E.F.M.

2011-01-01

Realizing institutions and regulations that foster economic growth is an essential asset for contemporary economies. This book investigates practices and options for steering individual and firm behaviour that prevents unacceptable externalities and boosts public interests. These multi-dimensional

Foliar fertilizations with boron and growth regulators on lettuce (Lactuca sativa L.) cv floresta culture

International Nuclear Information System (INIS)

Masunaga, S.I.; Chueire, F.B.; Teixeira, N.T.

1989-01-01

The experiment was realized to verify the possibility of applying Boron as foliar fertilization with growth regulators: indol acetic acid, giberellic acid, ethephon and cycocel. The other objective was to compare the foliar and soil fertilization, with Boron, on the lettuce culture. The results showed that there wasn't difference of production between the treatments. Meanwhile the application of growth regulator modified the Boron grade in the leaves. (author) [pt

The effect of plant growth regulators, explants and cultivars on ...

African Journals Online (AJOL)

ONOS

2010-07-05

Jul 5, 2010 ... The effect of plant growth regulators, explants and cultivars on spinach (Spinacia oleracea L.) tissue culture. Taha Roodbar Shojaei1*, Vahid Salari2, Darioush Ramazan3, Mahdi Ehyaei1, Javad. Gharechahi4 and Roya Motallebi Chaleshtori5. 1Department of Agronomy and Plant Breeding, College of ...

Biological Characteristics of Caspase-14 and Its Expression in Neoplastic Diseases in the View of Translational Medicine

Directory of Open Access Journals (Sweden)

Kang-sheng LIU

2016-06-01

Full Text Available Caspase-14, a member of caspase family, only exists in mammals. As the most divergent member in the family of mammalian caspases, caspase-14 displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. At present, it has been found that caspase-14 is functionally different from the inflammatory reaction group of typical caspase family members. It exerts a certain effect in the promotion of final differentiation of epidermal cells and hydration of stratum corneum so as to maintain the steady state of skin barrier. In recent years, caspase-14 expression has been discovered in neoplastic diseases. Translational medicine integrates experimental research results and clinical guidance into the optimal implementation criteria for promoting the prediction, prevention and treatment of diseases. Via human genomics and molecular biology, translational medicine offers a possibility of screening molecular markers so that it can be used to diagnose the neoplastic diseases. In this article, the biological characteristics and substrates of caspase-14 as well as its expression in embryonic period and neoplastic diseases were reviewed.

Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy.

Directory of Open Access Journals (Sweden)

Michael Anthony Ruiz

Full Text Available Glucose-induced augmented vascular endothelial growth factor (VEGF production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2, has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation and that inhibition of PRC2 increases miR-200b while reducing VEGF. Furthermore, retinal tissue from animal models of diabetes showed increased expression of major PRC2 components, demonstrating in vivo relevance. This research established a repressive relationship between PRC2 and miR-200b, providing evidence of a novel mechanism of miRNA regulation through histone methylation.

Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

Directory of Open Access Journals (Sweden)

A. Silvani

2013-01-01

Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

The Fat-Dachsous signaling pathway regulates growth of horns in Trypoxylus dichotomus, but does not affect horn allometry.

Science.gov (United States)

Hust, James; Lavine, Mark D; Worthington, Amy M; Zinna, Robert; Gotoh, Hiroki; Niimi, T; Lavine, Laura

Males of the Asian rhinoceros beetle, Trypoxylus dichotomus, possess exaggerated head and thoracic horns that scale dramatically out of proportion to body size. While studies of insulin signaling suggest that this pathway regulates nutrition-dependent growth including exaggerated horns, what regulates disproportionate growth has yet to be identified. The Fat signaling pathway is a potential candidate for regulating disproportionate growth of sexually-selected traits, a hypothesis we advanced in a previous paper (Gotoh et al., 2015). To investigate the role of Fat signaling in the growth and scaling of the sexually dimorphic, condition-dependent traits of the in the Asian rhinoceros beetle T. dichotomus, we used RNA interference to knock down expression of fat and its co-receptor dachsous. Knockdown of fat, and to a lesser degree dachsous, caused shortening and widening of appendages, including the head and thoracic horns. However, scaling of horns to body size was not affected. Our results show that Fat signaling regulates horn growth in T. dichotomus as it does in appendage growth in other insects. However, we provide evidence that Fat signaling does not mediate the disproportionate, positive allometric growth of horns in T. dichotomus. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

Science.gov (United States)

Ververis, J; Ku, L; Delafontaine, P

1994-02-01

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

The apical scaffold big bang binds to spectrins and regulates the growth of Drosophila melanogaster wing discs.

Science.gov (United States)

Forest, Elodie; Logeay, Rémi; Géminard, Charles; Kantar, Diala; Frayssinoux, Florence; Heron-Milhavet, Lisa; Djiane, Alexandre

2018-03-05

During development, cell numbers are tightly regulated, ensuring that tissues and organs reach their correct size and shape. Recent evidence has highlighted the intricate connections between the cytoskeleton and the regulation of the key growth control Hippo pathway. Looking for apical scaffolds regulating tissue growth, we describe that Drosophila melanogaster big bang (Bbg), a poorly characterized multi-PDZ scaffold, controls epithelial tissue growth without affecting epithelial polarity and architecture. bbg -mutant tissues are smaller, with fewer cells that are less apically constricted than normal. We show that Bbg binds to and colocalizes tightly with the β-heavy-Spectrin/Kst subunit at the apical cortex and promotes Yki activity, F-actin enrichment, and the phosphorylation of the myosin II regulatory light chain Spaghetti squash. We propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex, where Bbg promotes actomyosin contractility to regulate epithelial tissue growth. © 2018 Forest et al.

The role of growth regulators, embryo age and genotypes on ...

African Journals Online (AJOL)

One of the most important problem of tomato breeders is lengthy seed to seed cycle in a breeding program. In vitro techiques provide a lot of advantages for breeders. The objective of this work was to determine the effect of growth regulators and immature embryo age on embryo germination and rapid generation ...

Arising podosomal structures are associated with neoplastic cell morphological phenotype induced by the microenvironment

Czech Academy of Sciences Publication Activity Database

Veselý, Pavel; Blase, C.; Matoušková, Eva; Bereiter-Hahn, J.

2006-01-01

Roč. 26, - (2006), s. 967-972 ISSN 0250-7005 R&D Projects: GA MZd(CZ) NR8145 Institutional research plan: CEZ:AV0Z50520514 Keywords : podosomes * neoplastic cell morphotype * phenotypic plasticity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.479, year: 2006

Analysis of the Yeast Kinome Reveals a Network of Regulated Protein Localization during Filamentous Growth

OpenAIRE

Bharucha, Nikë; Ma, Jun; Dobry, Craig J.; Lawson, Sarah K.; Yang, Zhifen; Kumar, Anuj

2008-01-01

The subcellular distribution of kinases and other signaling proteins is regulated in response to cellular cues; however, the extent of this regulation has not been investigated for any gene set in any organism. Here, we present a systematic analysis of protein kinases in the budding yeast, screening for differential localization during filamentous growth. Filamentous growth is an important stress response involving mitogen-activated protein kinase and cAMP-dependent protein kinase signaling m...

Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens.

Science.gov (United States)

Lin, Shumao; Li, Hongmei; Mu, Heping; Luo, Wen; Li, Ying; Jia, Xinzheng; Wang, Sibing; Jia, Xiaolu; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

2012-07-10

A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3' untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. There is a critical miRNA, let-7b

Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

Science.gov (United States)

Granger, D L; Lehninger, A L

1982-11-01

Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

DEFF Research Database (Denmark)

Sölétormos, G; Fogh, J M; Sehested-Hansen, B

1997-01-01

A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (hGH...

Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings

International Nuclear Information System (INIS)

Uranga, Carla C.; Beld, Joris; Mrse, Anthony; Córdova-Guerrero, Iván; Burkart, Michael D.; Hernández-Martínez, Rufina

2016-01-01

The Botryosphaeriaceae are a family of trunk disease fungi that cause dieback and death of various plant hosts. This work sought to characterize fatty acid derivatives in a highly virulent member of this family, Lasiodiplodia theobromae. Nuclear magnetic resonance and gas chromatography-mass spectrometry of an isolated compound revealed (Z, Z)-9,12-ethyl octadecadienoate, (trivial name ethyl linoleate), as one of the most abundant fatty acid esters produced by L. theobromae. A variety of naturally produced esters of fatty acids were identified in Botryosphaeriaceae. In comparison, the production of fatty acid esters in the soil-borne tomato pathogen Fusarium oxysporum, and the non-phytopathogenic fungus Trichoderma asperellum was found to be limited. Ethyl linoleate, ethyl hexadecanoate (trivial name ethyl palmitate), and ethyl octadecanoate, (trivial name ethyl stearate), significantly inhibited tobacco seed germination and altered seedling leaf growth patterns and morphology at the highest concentration (0.2 mg/mL) tested, while ethyl linoleate and ethyl stearate significantly enhanced growth at low concentrations, with both still inducing growth at 98 ng/mL. This work provides new insights into the role of naturally esterified fatty acids from L. theobromae as plant growth regulators with similar activity to the well-known plant growth regulator gibberellic acid. - Highlights: • Lasiodiplodia theobromae produces a wide variety of fatty acid esters in natural substrates. • Ethyl stearate and ethyl linoleate inhibit tobacco germination at 0.2 mg/mL. • Ethyl stearate and ethyl linoleate induce tobacco germination at 98 ng/mL. • Tobacco growth increase in ethyl stearate and ethyl linoleate parallels gibberellic acid. • A role as plant growth regulators is proposed for fatty acid esters.

Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings

Energy Technology Data Exchange (ETDEWEB)

Uranga, Carla C., E-mail: curanga@cicese.edu.mx [Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana 3918, Zona Playitas, 22860 Ensenada, B.C. (Mexico); Beld, Joris, E-mail: joris.beld@drexelmed.edu [University of California, San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0358 (United States); Mrse, Anthony, E-mail: amrse@ucsd.edu [University of California, San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0358 (United States); Córdova-Guerrero, Iván, E-mail: icordova@uabc.edu.mx [Universidad Autónoma de Baja California (UABC), Calzada Universidad 14418 Parque Industrial Internacional Tijuana, Tijuana, B.C. 22390 (Mexico); Burkart, Michael D., E-mail: mburkart@ucsd.edu [University of California, San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0358 (United States); Hernández-Martínez, Rufina, E-mail: ruhernan@cicese.mx [Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana 3918, Zona Playitas, 22860 Ensenada, B.C. (Mexico)

2016-04-01

The Botryosphaeriaceae are a family of trunk disease fungi that cause dieback and death of various plant hosts. This work sought to characterize fatty acid derivatives in a highly virulent member of this family, Lasiodiplodia theobromae. Nuclear magnetic resonance and gas chromatography-mass spectrometry of an isolated compound revealed (Z, Z)-9,12-ethyl octadecadienoate, (trivial name ethyl linoleate), as one of the most abundant fatty acid esters produced by L. theobromae. A variety of naturally produced esters of fatty acids were identified in Botryosphaeriaceae. In comparison, the production of fatty acid esters in the soil-borne tomato pathogen Fusarium oxysporum, and the non-phytopathogenic fungus Trichoderma asperellum was found to be limited. Ethyl linoleate, ethyl hexadecanoate (trivial name ethyl palmitate), and ethyl octadecanoate, (trivial name ethyl stearate), significantly inhibited tobacco seed germination and altered seedling leaf growth patterns and morphology at the highest concentration (0.2 mg/mL) tested, while ethyl linoleate and ethyl stearate significantly enhanced growth at low concentrations, with both still inducing growth at 98 ng/mL. This work provides new insights into the role of naturally esterified fatty acids from L. theobromae as plant growth regulators with similar activity to the well-known plant growth regulator gibberellic acid. - Highlights: • Lasiodiplodia theobromae produces a wide variety of fatty acid esters in natural substrates. • Ethyl stearate and ethyl linoleate inhibit tobacco germination at 0.2 mg/mL. • Ethyl stearate and ethyl linoleate induce tobacco germination at 98 ng/mL. • Tobacco growth increase in ethyl stearate and ethyl linoleate parallels gibberellic acid. • A role as plant growth regulators is proposed for fatty acid esters.

miRNA and mRNA Expression Profiles Reveal Insight into Chitosan-Mediated Regulation of Plant Growth.

Science.gov (United States)

Zhang, Xiaoqian; Li, Kecheng; Xing, Ronge; Liu, Song; Chen, Xiaolin; Yang, Haoyue; Li, Pengcheng

2018-04-18

Chitosan has been numerously studied as a plant growth regulator and stress tolerance inducer. To investigate the roles of chitosan as bioregulator on plant and unravel its possible metabolic responses mechanisms, we simultaneously investigated mRNAs and microRNAs (miRNAs) expression profiles of wheat seedlings in response to chitosan heptamer. We found 400 chitosan-responsive differentially expressed genes, including 268 up-regulated and 132 down-regulated mRNAs, many of which were related to photosynthesis, primary carbon and nitrogen metabolism, defense responses, and transcription factors. Moreover, miRNAs also participate in chitosan-mediated regulation on plant growth. We identified 87 known and 21 novel miRNAs, among which 56 miRNAs were induced or repressed by chitosan heptamer, such as miRNA156, miRNA159a, miRNA164, miRNA171a, miRNA319, and miRNA1127. The integrative analysis of miRNA and mRNA expression profiles in this case provides fundamental information for further investigation of regulation mechanisms of chitosan on plant growth and will facilitate its application in agriculture.

Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

International Nuclear Information System (INIS)

Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

1979-01-01

Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

A progesterone-brown fat axis is involved in regulating fetal growth.

NARCIS (Netherlands)

McIlvride, Saraid; Mushtaq, Aleena; Papacleovoulou, Georgia; Hurling, Chloe; Steel, Jennifer; Jansen, Eugène; Abu-Hayyeh, Shadi; Williamson, Catherine

2017-01-01

Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT

Endocrine gland derived-VEGF is down-regulated in human pituitary adenoma.

Science.gov (United States)

Raica, Marius; Coculescu, Mihail; Cimpean, Anca Maria; Ribatti, Domenico

2010-10-01

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic molecule restricted to endocrine glands and, particularly, to steroid-secreting cells. The expression of EG-VEGF and its significance in human adenohypophysis in physiological and pathological conditions is still unknown. In this study, we investigated by immunohistochemistry the expression of EG-VEGF in 2 samples of normal adenohypophysis and 43 bioptic samples of pituitary adenoma. Moreover, the expression of growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and adrenocorticoprophic hormone (ACTH) were also estimated. The results of this study for the first time demonstrate a down-regulation of EG-VEGF expression in human pituitary adenoma as compared to normal adenohypophysis, suggesting an impaired function of the neoplastic cells in terms of hormone release in the blood stream, as a consequence of impaired tumor angiogenesis in the tumor. On the basis of our data showing a marked decrease in the expression of EG-VEGF in pituitary adenoma, with the exception of LH-secreting adenomas, we suggest that LH might be involved in the induction of EG-VEGF secretion.

Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of a long bone?

Science.gov (United States)

Brouwers, J E M; van Donkelaar, C C; Sengers, B G; Huiskes, R

2006-01-01

Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.

LIGHT REGULATION OF GROWTH AND MELANIN FORMATION IN Inonotus оbliquus (Pers. Pilat

Directory of Open Access Journals (Sweden)

N. L. Poyedinok

2013-04-01

Full Text Available The study aims to investigate possibilities of using different sources of low-intensity light for the regulation of mycelium growth and melanin synthesis by medicinal mushroom Inonotus obliquus (Pers. Pilat. Studies of the light’s influence on the linear growth, biomass accumulation and melanin synthesis I. obliquus were performed using experimental installations that provide both lasing (coherent light with specified parameters, as well as sources of incoherent light. It has been demonstrated that the greatest stimulating effect took place during the irradiation of mycelium with blue light. It has been found that further realization of photobiological effect is largely dependent on the method of cultivation. Irradiation with laser light within all studied wavelength ranges was more conducive to growth, biomass and melanin accumulation in the mushroom mycelium than incoherent light irradiation within the same wavelength range. Light treatment made it possible to significantly reduce the duration of fermentation. The results of studies allow considering lowintensity light in the visible part of the spectrum as a perspective growth and biosynthetic activity regulator of I. obliquus in the biotechnology of its cultivation.

Gallium SPECT detection of neoplastic intravascular obstruction of the superior vena cava

International Nuclear Information System (INIS)

Swayne, L.C.; Kaplan, I.L.

1989-01-01

A rare case of an intravascular neoplastic obstruction of the superior vena cava is discussed. The lesion was detected with gallium single photon emission computed tomography (SPECT) despite a normal appearance on a concurrent radiographic CT study. A computer-generated composite SPECT-CT image confirmed the intravascular localization of the radioisotope, and a subsequent CT-guided transthoracic needle biopsy revealed a poorly differentiated adenocarcinoma

Loss of a putative tumor suppressor locus after gamma-ray-induced neoplastic transformation of HeLa x Skin fibroblast human cell hybrids

International Nuclear Information System (INIS)

Mendonca, M.S.; Redpath, J.L.; Fasching, C.L.

1995-01-01

The nontumorigenic HeLa x skin fibroblast hybrid cell line, CGL1, can be induced to re-express HeLa tumor-associated cell surface antigen, p75-IAP (intestinal alkaline phosphatase), with resulting neoplastic transformation, by exposure to γ radiation. This has allowed the human hybrid system to be developed into a quantitative in vitro model for radiation-induced neoplastic transformation of human cells. Recently, several γ-ray-induced IAP-expression mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 were isolated and all were tumorigenic when injected subcutaneously into nude mice. Control cell lines which were negative for p75-IAP (CONs) were also isolated from irradiated populations, and none were found to be tumorigenic. We have now begun to investigate the molecular basis of radiation-induced neoplastic transformation in this system by studying the potential genetic linkage between p75/IAP expression, tumorigenicity and damage to a putative tumor suppressor locus on fibroblast chromosome 11. Previous analysis of rare spontaneous segregants has indicated that this locus is involved in the regulation of tumorigenicity and in the expression of the HeLa tumor-associated cell surface marker intestinal alkaline phosphatase (p75-IAP) in this system. Therefore, analysis by restriction fragment length polymorphism and chromosome painting have been performed for chromosome 11, and for chromosome 13 as a control, for the p75/IAP-positive GIM and p75/IAP-negative CON cell lines. We report that in five of eight of the GIMs large-scale damage to the fibroblast chromosome 11's is evident (four GIMs have lost one complete copy of a fibroblast chromosome 11 heavily damaged). None of the CONs, however (0/5), have lost a complete copy of either fibroblast chromosome 11. No large-scale damage to the control chromosome 13's was detected in the GIMs or CONs. 49 refs., 3 figs., 2 tabs

Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene

Science.gov (United States)

Ifere, Godwin O.; Equan, Anita; Gordon, Kereen; Nagappan, Peri; Igietseme, Joseph U.; Ananaba, Godwin A.

2010-01-01

Background The purpose of our study was to show the distinction between the apoptotic and anti-proliferative signaling of phytosterols and cholesterol enrichment in prostate cancer cell lines, mediated by the differential transcription of caveolin-1, and N-myc downstream regulated gene1 (NDRG1), a pro-apoptotic androgen-regulated tumor suppressor. Methods PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 72 h, followed by trypan blue dye exclusion measurement of necrosis and cell growth measured with a Coulter counter. Sterol induction of cell growth-suppressor gene expression was evaluated by mRNA transcription using RT-PCR, while cell cycle analysis was performed by FACS analysis. Altered expression of Ndrg1 protein was confirmed by Western blot analysis. Apoptosis was evaluated by real time RT-PCR amplification of P53, Bcl-2 gene and its related pro- and anti-apoptotic family members. Results Physiological doses (16 µM) of cholesterol and phytosterols were not cytotoxic in these cells. Cholesterol enrichment promoted cell growth (Pphytosterols significantly induced growth-suppression (Pphytosterols decreased mitotic subpopulations. We demonstrated for the first time that cholesterols concertedly attenuated the expression of caveolin-1(cav-1) and NDRG1 genes in both prostate cancer cell lines. Phytosterols had the opposite effect by inducing overexpression of cav-1, a known mediator of androgen-dependent signals that presumably control cell growth or apoptosis. Conclusions Cholesterol and phytosterol treatment differentially regulated the growth of prostate cancer cells and the expression of p53 and cav-1, a gene that regulates androgen-regulated signals. These sterols also differentially regulated cell cycle arrest, downstream pro-apoptotic androgen-regulated tumor-suppressor, NDRG1 suggesting that cav-1 may mediate pro-apoptotic NDRG1 signals. Elucidation of the mechanism for sterol modulation of growth and apoptosis signaling

Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

DEFF Research Database (Denmark)

Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

2013-01-01

The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

Science.gov (United States)

Low, Malcolm J.; Otero-Corchon, Veronica; Parlow, Albert F.; Ramirez, Jose L.; Kumar, Ujendra; Patel, Yogesh C.; Rubinstein, Marcelo

2001-01-01

Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth. PMID:11413165

Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

Science.gov (United States)

Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

2012-01-01

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

The effect of plant growth regulators on optimization of tissue culture ...

African Journals Online (AJOL)

Mature seeds of four upland rice cultivars namely Kusan, Lamsan, Selasi and Siam were assessed for callus induction and plant regeneration on different concentrations and combinations of plant growth regulators, incorporated into MS (Murashige and Skoog) basal medium. Callus induction frequency was significantly ...

Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.

Directory of Open Access Journals (Sweden)

Patrick Fischer

2015-08-01

Full Text Available In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP. Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E, is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb, the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila.

Transcription profiling of human MCF10A cells subjected to ionizing radiation and treatment with transforming growth factor beta-1

Data.gov (United States)

National Aeronautics and Space Administration — Transforming growth factor beta-1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis but it can switch to a tumor promoter during neoplastic...

Insulin-like growth factor (IGF)-like peptide and 20-hydroxyecdysone regulate the growth and development of the male genital disk through different mechanisms in the silkmoth, Bombyx mori.

Science.gov (United States)

Fujinaga, Daiki; Kohmura, Yusuke; Okamoto, Naoki; Kataoka, Hiroshi; Mizoguchi, Akira

2017-08-01

It is well established that ecdysteroids play pivotal roles in the regulation of insect molting and metamorphosis. However, the mechanisms by which ecdysteroids regulate the growth and development of adult organs after pupation are poorly understood. Recently, we have identified insulin-like growth factor (IGF)-like peptides (IGFLPs), which are secreted after pupation under the control of 20-hydroxyecdysone (20E). In the silkmoth, Bombyx mori, massive amounts of Bombyx-IGFLP (BIGFLP) are present in the hemolymph during pupal-adult development, suggesting its importance in the regulation of adult tissue growth. Thus, we hypothesized that the growth and development of adult tissues including imaginal disks are regulated by the combined effects of BIGFLP and 20E. In this study, we investigated the growth-promoting effects of BIGFLP and 20E using the male genital disks of B. mori cultured ex vivo, and further analyzed the cell signaling pathways mediating hormone actions. We demonstrate that 20E induces the elongation of genital disks, that both hormones stimulate protein synthesis in an additive manner, and that BIGFLP and 20E exert their effects through the insulin/IGF signaling pathway and mitogen-activated protein kinase pathway, respectively. These results show that the growth and development of the genital disk are coordinately regulated by both BIGFLP and 20E. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-regulated growth of LaVO3 thin films by hybrid molecular beam epitaxy

International Nuclear Information System (INIS)

Zhang, Hai-Tian; Engel-Herbert, Roman; Dedon, Liv R.; Martin, Lane W.

2015-01-01

LaVO 3 thin films were grown on SrTiO 3 (001) by hybrid molecular beam epitaxy. A volatile metalorganic precursor, vanadium oxytriisopropoxide (VTIP), and elemental La were co-supplied in the presence of a molecular oxygen flux. By keeping the La flux fixed and varying the VTIP flux, stoichiometric LaVO 3 films were obtained for a range of cation flux ratios, indicating the presence of a self-regulated growth window. Films grown under stoichiometric conditions were found to have the largest lattice parameter, which decreased monotonically with increasing amounts of excess La or V. Energy dispersive X-ray spectroscopy and Rutherford backscattering measurements were carried out to confirm film compositions. Stoichiometric growth of complex vanadate thin films independent of cation flux ratios expands upon the previously reported self-regulated growth of perovskite titanates using hybrid molecular beam epitaxy, thus demonstrating the general applicability of this growth approach to other complex oxide materials, where a precise control over film stoichiometry is demanded by the application

Plant growth regulators ameliorate or exacerbate abiotic and biotic stress effects on Zea mays kernel weight in a genotype-specific manner

OpenAIRE

Wang, Yishi; Stutts, Lauren; Stapleton, Ann

2016-01-01

Plant growth regulators have documented roles in plant responses to single stresses. In combined-stress environments, plants display novel genetic architecture for growth traits and the response to growth regulators is unclear. We investigated the role of plant growth regulators in combined-stress responses in Zea mays. Twelve maize inbreds were exposed to all combinations of the following stressors: drought, nitrogen, and density stress. Chemical treatments were utilized to alter balances of...

Hormonal regulation of the growth of leaves and inflorescence stalk in Muscari armeniacum Leichtl.

Directory of Open Access Journals (Sweden)

Marian Saniewski

2016-04-01

Full Text Available It is known that chilling of Muscari bulbs is necessary for the growth of the inflorescence stalk and flowering, but not for the growth of leaves. Gibberellic acid (GA accelerated stem growth and flowering in chilled Muscari bulbs. In the present experiment it was shown that in unchilled derooted Muscari bulbs the growth of leaves, but not the growth of the inflorescence stalk, was observed when bulbs were stored in water, GA at a concentration of 50 and 100 mg/L, benzyladenine (BA at a concentration of 25 and 50 mg/L, or a mixture of GA+BA (50+25 mg/L, but abscisic acid (ABA at a concentration of 10 mg/L greatly inhibited the growth of leaves. In chilled derooted Muscari bulbs the growth of leaves and inflorescence stalk was observed when bulbs were stored in water or GA, but BA and GA+BA treatments totally inhibited the growth of the inflorescence stalk without an effect on the growth of leaves. These results clearly showed that the growth of leaves and inflorescence stalk in Muscari bulbs are controlled by plant growth regulators in different ways. ABA totally inhibited the growth of leaves and inflorescence stalk in chilled derooted Muscari bulbs. It was shown that after the excision of the inflorescence bud in cultivated chilled Muscari bulbs, the inflorescence stalk died, but application of indole-3-acetic acid (IAA 0.5% in the place of the removed inflorescence bud induced the growth of the inflorescence stalk. IAA applied under the inflorescence bud inhibited the development of flowers (flower-bud blasting and induced the growth of the inflorescence stalk below the treatment site. These results are discussed with reference to hormonal regulation of stem (stalk growth in tulip, narcissus, hyacinth, and Hippeastrum.

E2F1 regulates cellular growth by mTORC1 signaling.

Directory of Open Access Journals (Sweden)

Sebastian Real

2011-01-01

Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

Experimental control of neoplastic progression in cell populations: Foulds' rules revisited.

OpenAIRE

Rubin, H

1994-01-01

Foulds introduced six rules of tumor progression based on his observations of spontaneous mammary cancer in mice and generalized them to all forms of neoplasia [Foulds, L. (1954) Cancer Res. 14, 327-339 and Foulds, L. (1969) Neoplastic Development (Academic, New York), Vol. 1, preface and pp. 72-74.] Rules III, IV, and V are considered controversial, and research in animals seems inadequate to resolve the controversies. A subline of NIH 3T3 cells undergoes progressive transformation to produc...

Daily changes in temperature, not the circadian clock, regulate growth rate in Brachypodium distachyon.

Directory of Open Access Journals (Sweden)

Dominick A Matos

Full Text Available Plant growth is commonly regulated by external cues such as light, temperature, water availability, and internal cues generated by the circadian clock. Changes in the rate of growth within the course of a day have been observed in the leaves, stems, and roots of numerous species. However, the relative impact of the circadian clock on the growth of grasses has not been thoroughly characterized. We examined the influence of diurnal temperature and light changes, and that of the circadian clock on leaf length growth patterns in Brachypodium distachyon using high-resolution time-lapse imaging. Pronounced changes in growth rate were observed under combined photocyles and thermocycles or with thermocycles alone. A considerably more rapid growth rate was observed at 28°C than 12°C, irrespective of the presence or absence of light. In spite of clear circadian clock regulated gene expression, plants exhibited no change in growth rate under conditions of constant light and temperature, and little or no effect under photocycles alone. Therefore, temperature appears to be the primary cue influencing observed oscillations in growth rate and not the circadian clock or photoreceptor activity. Furthermore, the size of the leaf meristem and final cell length did not change in response to changes in temperature. Therefore, the nearly five-fold difference in growth rate observed across thermocycles can be attributed to proportionate changes in the rate of cell division and expansion. A better understanding of the growth cues in B. distachyon will further our ability to model metabolism and biomass accumulation in grasses.

Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

Directory of Open Access Journals (Sweden)

Heiko Löhr

2018-05-01

Full Text Available Summary: Anorexigenic pro-opiomelanocortin (Pomc/alpha-melanocyte stimulating hormone (αMSH neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful. : The melanocortin system controls energy homeostasis and somatic growth, but the underlying mechanisms are elusive. Löhr et al. identify a functional neural circuit in which Pomc neurons stimulate hypothalamic somatostatin neurons, thereby inhibiting hypophyseal growth hormone production. Excessive feeding and acquired leptin resistance attenuate this pathway, allowing faster somatic growth when food resources are rich. Keywords: Pomc neuron, somatostatin neuron, somatic growth, growth hormone, melanocortin system, high-fat diet, obesity, leptin resistance, zebrafish, mouse

Aberrant Transforming Growth Factor β1 Signaling and SMAD4 Nuclear Translocation Confer Epigenetic Repression of ADAM19 in Ovarian Cancer

Directory of Open Access Journals (Sweden)

Michael W.Y. Chan

2008-09-01

Full Text Available Transforming growth factor-beta (TGF-β/SMAD signaling is a key growth regulatory pathway often dysregulated in ovarian cancer and other malignancies. Although loss of TGF-β–mediated growth inhibition has been shown to contribute to aberrant cell behavior, the epigenetic consequence(s of impaired TGF-β/SMAD signaling on target genes is not well established. In this study, we show that TGF-β1 causes growth inhibition of normal ovarian surface epithelial cells, induction of nuclear translocation SMAD4, and up-regulation of ADAM19 (a disintegrin and metalloprotease domain 19, a newly identified TGF-β1 target gene. Conversely, induction and nuclear translocation of SMAD4 were negligible in ovarian cancer cells refractory to TGF-β1 stimulation, and ADAM19 expression was greatly reduced. Furthermore, in the TGF-β1 refractory cells, an inactive chromatin environment, marked by repressive histone modifications (trimethyl-H3K27 and dimethyl-H3K9 and histone deacetylase, was associated with the ADAM19 promoter region. However, the CpG island found within the promoter and first exon of ADAM19 remained generally unmethylated. Although disrupted growth factor signaling has been linked to epigenetic gene silencing in cancer, this is the first evidence demonstrating that impaired TGF-β1 signaling can result in the formation of a repressive chromatin state and epigenetic suppression of ADAM19. Given the emerging role of ADAMs family proteins in growth factor regulation in normal cells, we suggest that epigenetic dysregulation of ADAM19 may contribute to the neoplastic process in ovarian cancer.

DFsn collaborates with Highwire to down-regulate the Wallenda/DLK kinase and restrain synaptic terminal growth

Directory of Open Access Journals (Sweden)

DiAntonio Aaron

2007-08-01

Full Text Available Abstract Background The growth of new synapses shapes the initial formation and subsequent rearrangement of neural circuitry. Genetic studies have demonstrated that the ubiquitin ligase Highwire restrains synaptic terminal growth by down-regulating the MAP kinase kinase kinase Wallenda/dual leucine zipper kinase (DLK. To investigate the mechanism of Highwire action, we have identified DFsn as a binding partner of Highwire and characterized the roles of DFsn in synapse development, synaptic transmission, and the regulation of Wallenda/DLK kinase abundance. Results We identified DFsn as an F-box protein that binds to the RING-domain ubiquitin ligase Highwire and that can localize to the Drosophila neuromuscular junction. Loss-of-function mutants for DFsn have a phenotype that is very similar to highwire mutants – there is a dramatic overgrowth of synaptic termini, with a large increase in the number of synaptic boutons and branches. In addition, synaptic transmission is impaired in DFsn mutants. Genetic interactions between DFsn and highwire mutants indicate that DFsn and Highwire collaborate to restrain synaptic terminal growth. Finally, DFsn regulates the levels of the Wallenda/DLK kinase, and wallenda is necessary for DFsn-dependent synaptic terminal overgrowth. Conclusion The F-box protein DFsn binds the ubiquitin ligase Highwire and is required to down-regulate the levels of the Wallenda/DLK kinase and restrain synaptic terminal growth. We propose that DFsn and Highwire participate in an evolutionarily conserved ubiquitin ligase complex whose substrates regulate the structure and function of synapses.

Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

Directory of Open Access Journals (Sweden)

Amélie Avet-Rochex

2014-09-01

Full Text Available Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk, which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem

Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

Energy Technology Data Exchange (ETDEWEB)

Kay, Steve A. [Scripps Research Inst., La Jolla, CA (United States); Hazen, Samuel [Scripps Research Inst., San Diego, CA (United States); Mullet, John [Texas A & M Univ., College Station, TX (United States)

2017-11-22

Critical to the development of renewable energy sources from biofuels is the improvement of biomass from energy feedstocks, such as sorghum and maize. The specific goals of this project include 1) characterize the growth and gene expression patterns under diurnal and circadian conditions, 2) select transcription factors associated with growth and build a cis-regulatory network in yeast, and 3) perturb these transcription factors in planta using transgenic Brachypodium and sorghum, and characterize the phenotypic outcomes as they relate to biomass accumulation. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield.

Effects of different plant growth regulators on blueberry fruit quality

Science.gov (United States)

Zhang, X. C.; Zhu, Y. Q.; Wang, Y. N.; Luo, C.; Wang, X.

2017-08-01

In order to understand the effects of different plant growth regulators (PGRs) on blueberry fruit growth, various concentrations of Abscisic acid (ABA), Methyl jasmonate (MJ), Brassinolide (BR), Melatonin (MT) were sprayed on blueberry cv. ‘Brigita’ fruits. The results showed that all the PGRs put into effect on improving the quality of blueberry fruit. Comparing with the control plants no PGR spraying,300 mg/L of MT treatment promoted effectively accumulation of the soluble sugar. ABA 20mg/L treatment in-creased effectively accumulation of anthocyanin, and significantly decreased titratable acid content. The treatment of MJ 10mg/L improved significantly the soluble solid content. The effect of the four PGRs treatments on appearance did not show obvious difference.

Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa

Directory of Open Access Journals (Sweden)

Leonardo Huber Tauil

2014-01-01

Full Text Available Purpose: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carci- noma, colorectal adenoma and non-neoplasic colorectal epithelium. Methods: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal ad- enoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients who died from cardiovascular diseases, without diseases of the large intestine. Samples of different tissues were included in paraffin blocks, and the immunohistochem- ical expression of protein TCF4 was analyzed using the technique of tissue microarray (TMA with polyclonal antibody TCF4. The immunoreactivity was analyzed and classified as positive and negative. Results: The immunohistochemical expression of TCF4 protein was significantly higher (p < 0.01 in colorectal carcinoma than in the non-neoplastic colorectal epithelium and adenoma. There was no difference (p = 0.76 between TCF4 protein immunohistochemical expression in colorectal adenoma and non-neoplastic colorectal tissue. Conclusions: TCF4 protein showed a more intense expression in colorectal carcinoma than in non-neoplastic colorectal epithelium and adenoma, indicating that this protein is in- volved in colorectal carcinogenesis. Resumo: Objetivos: Detectar e quantificar a imunoexpressão da proteína TCF4 no carcinoma e no adenoma colorretal e no epitélio colorretal não neoplásico. Método: Foram estudados 129 indivíduos: 40 com carcinoma colorretal, 52 com adenoma colorretal e 37 com epitélio colorretal não neoplásico. Os tecidos de adenoma e carcinoma colorretais foram representados por amostras da lesão retirada de doentes submetidos a procedimentos cirúrgicos e colonoscópicos, e as amostras de epitélio colorretal não neo- plásico foram retiradas de doentes falecidos por

Growth regulators and substrates for Oncidium baueri Lindl. micropropagation

Directory of Open Access Journals (Sweden)

Daniele Brandstetter Rodrigues

2016-10-01

Full Text Available An adequate concentration of growth regulators as well as the replacement of agar by an alternative medium may be promising from practical and financial points of view to produce orchid plants by micropropagation. The objective of this work was to evaluate different concentrations of growth regulator and alternative substrates for agar replacement in culture medium for in vitro multiplication and rooting of Oncidium baueri. In the explant multiplication phase, two experimental factors were evaluated- various concentrations of 6-benzylaminopurine (BAP (0.0, 1.0, 2.0, and 3.0 mg L-1 and substrates (agar, vermiculite, and coconut fiber added to MS medium. In the rooting phase, different concentrations of indole butyric acid (IBA (0.0, 0.5, 1.0, and 1.5 mg L-1 were added to culture medium containing the same substrate. Six months after the experiments were initiated, the survival percentage, number of leaves, shoots, and roots and length of the aerial part and the major root were evaluated. The results suggested that addition of 1.0 mg L-1 BAP is necessary for the O. baueri in vitro multiplication phase, but IBA is not necessary in the rooting phase. For the substrate, vermiculite is not indicated as an agar replacement. In contrast, coconut fiber can be used in both multiplication and rooting phases of Oncidium baueri in vitro culture.

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Directory of Open Access Journals (Sweden)

Inês Gomes Ferreira

2018-02-01

Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

Science.gov (United States)

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

2014-01-01

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

The effect of plant growth regulators on callus initiation in wormwood ...

African Journals Online (AJOL)

Studies were carried out in the Biotechnology laboratory of Plant Science Department of Ahmadu Bello University Zaria, Nigeria to study the effect of some plant growth regulators on the in vitro initiation of callus using the leaves of Chiyong variety of Artemisia annua. The explants were sterilized and incubated on Murashige ...

Role of Estrogen in Thyroid Function and Growth Regulation

Directory of Open Access Journals (Sweden)

Ana Paula Santin

2011-01-01

Full Text Available Thyroid diseases are more prevalent in women, particularly between puberty and menopause. It is wellknown that estrogen (E has indirect effects on the thyroid economy. Direct effects of this steroid hormone on thyroid cells have been described more recently; so, the aim of the present paper was to review the evidences of these effects on thyroid function and growth regulation, and its mechanisms. The expression and ratios of the two E receptors, α and β, that mediate the genomic effects of E on normal and abnormal thyroid tissue were also reviewed, as well as nongenomic, distinct molecular pathways. Several evidences support the hypothesis that E has a direct role in thyroid follicular cells; understanding its influence on the growth and function of the thyroid in normal and abnormal conditions can potentially provide new targets for the treatment of thyroid diseases.

Pu-erh Tea Inhibits Tumor Cell Growth by Down-Regulating Mutant p53

Science.gov (United States)

Zhao, Lanjun; Jia, Shuting; Tang, Wenru; Sheng, Jun; Luo, Ying

2011-01-01

Pu-erh tea is a kind of fermented tea with the incorporation of microorganisms’ metabolites. Unlike green tea, the chemical characteristics and bioactivities of Pu-erh tea are still not well understood. Using water extracts of Pu-erh tea, we analyzed the tumor cell growth inhibition activities on several genetically engineered mouse tumor cell lines. We found that at the concentration that did not affect wild type mouse embryo fibroblasts (MEFs) growth, Pu-erh tea extracts could inhibit tumor cell growth by down-regulated S phase and cause G1 or G2 arrest. Further study showed that Pu-erh tea extracts down-regulated the expression of mutant p53 in tumor cells at the protein level as well as mRNA level. The same concentration of Pu-erh tea solution did not cause p53 stabilization or activation of its downstream pathways in wild type cells. We also found that Pu-erh tea treatment could slightly down-regulate both HSP70 and HSP90 protein levels in tumor cells. These data revealed the action of Pu-erh tea on tumor cells and provided the possible mechanism for Pu-erh tea action, which explained its selectivity in inhibiting tumor cells without affecting wild type cells. Our data sheds light on the application of Pu-erh tea as an anti-tumor agent with low side effects. PMID:22174618

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

NARCIS (Netherlands)

Haycock, P.C.; Burgess, S.; Nounu, A.; Zheng, J.; Okoli, G.N.; Bowden, J.; Wade, K.H.; Timpson, N.J.; Evans, D.M.; Willeit, P.; Aviv, A.; Gaunt, T.R.; Hemani, G.; Mangino, M.; Ellis, H.P.; Kurian, K.M.; Pooley, K.A.; Eeles, R.A.; Lee, J.E.; Fang, S.; Chen, W.V.; Law, M.H.; Bowdler, L.M.; Iles, M.M.; Yang, Q.; Worrall, B.B.; Markus, H.S.; Hung, R.J.; Amos, C.I.; Spurdle, A.B.; Thompson, D.J.; O'Mara, T.A.; Wolpin, B.; Amundadottir, L.; Stolzenberg-Solomon, R.; Trichopoulou, A.; Onland-Moret, N.C.; Lund, E.; Duell, E.J.; Canzian, F.; Severi, G.; Overvad, K.; Gunter, M.J.; Tumino, R.; Svenson, U.; Rij, A. van; Baas, A.F.; Bown, M.J.; Samani, N.J.; t'Hof, F.N.G. van; Tromp, G.; Jones, G.T.; Kuivaniemi, H.; Elmore, J.R.; Johansson, M.; McKay, J.; Scelo, G.; Carreras-Torres, R.; Gaborieau, V.; Brennan, P.; Bracci, P.M.; Neale, R.E.; Olson, S.H.; Gallinger, S.; Li, D.; Petersen, G.M.; Risch, H.A.; Klein, A.P.; Han, J.; Abnet, C.C.; Freedman, N.D.; Taylor, P.R.; Maris, J.M.; Aben, K.K.H.; Kiemeney, L.A.; Vermeulen, S.H.; Wiencke, J.K.; Walsh, K.M.; Wrensch, M.; Rice, T.; Turnbull, C.; Litchfield, K.; Paternoster, L.; Standl, M.; Abecasis, G.R.; SanGiovanni, J.P.; Li, Y.; Mijatovic, V.; Sapkota, Y.; Low, S.K.; Zondervan, K.T.; Montgomery, G.W.; Nyholt, D.R.; Heel, D.A. van; Hunt, K.; Arking, D.E.; Ashar, F.N.; Sotoodehnia, N.; Woo, D.; et al.,

2017-01-01

Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study,

Improvement of Salt Tolerance in Trigonella foenum-graecum L. var. PEB by Plant Growth Regulators

Directory of Open Access Journals (Sweden)

Anjali Ratnakar

2014-05-01

Full Text Available The crop yield is reduced under saline conditions and this hampers agricultural productivity. The incorporation of plant growth regulators (PGRs during presoaking treatments in many crops has improved seed performance under saline conditions. In order to study the ameliorative effect of plant growth regulators, experiments were conducted to study the variation in organic constituents in the leaves of Trigonella foenum-graecum L. var.PEB, where the seeds were primed with different plant growth regulators and grown under NaCl salinity. After a pre-soaking treatment of six hours in 20 mg L-1 solutions of gibberllic acid (GA3, 6-furfuryladenine (Kinetin and benzyl adenine (BA, the seeds were allowed to germinate and grow for forty-five days under saline conditions. On the analysis of mature leaves, it was observed that chlorophyll a and b, total chlorophyll and protein showed an increase in PGR-treated plants compared to the untreated set. The accumulation of the stress metabolite such as proline and sugars, which increase under saline conditions, showed a significant decrease in the plants pretreated with PGRs.

Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

DEFF Research Database (Denmark)

Münstermann, U; Fritz, G; Seitz, G

1990-01-01

Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

GDP-D-mannose epimerase regulates male gametophyte development, plant growth and leaf senescence in Arabidopsis.

Science.gov (United States)

Qi, Tiancong; Liu, Zhipeng; Fan, Meng; Chen, Yan; Tian, Haixia; Wu, Dewei; Gao, Hua; Ren, Chunmei; Song, Susheng; Xie, Daoxin

2017-09-04

Plant GDP-D-mannose epimerase (GME) converts GDP-D-mannose to GDP-L-galactose, a precursor of both L-ascorbate (vitamin C) and cell wall polysaccharides. However, the genetic functions of GME in Arabidopsis are unclear. In this study, we found that mutations in Arabidopsis GME affect pollen germination, pollen tube elongation, and transmission and development of the male gametophyte through analysis of the heterozygous GME/gme plants and the homozygous gme plants. Arabidopsis gme mutants also exhibit severe growth defects and early leaf senescence. Surprisingly, the defects in male gametophyte in the gme plants are not restored by L-ascorbate, boric acid or GDP-L-galactose, though boric acid rescues the growth defects of the mutants, indicating that GME may regulate male gametophyte development independent of L-ascorbate and GDP-L-galactose. These results reveal key roles for Arabidopsis GME in reproductive development, vegetative growth and leaf senescence, and suggest that GME regulates plant growth and controls male gametophyte development in different manners.

Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

Directory of Open Access Journals (Sweden)

Santiago Vernia

2016-03-01

Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

Plant Growth Regulators as Potential Tools in Aquatic Plant Management: Efficacy and Persistence in Small-Scale Tests

Science.gov (United States)

1994-01-01

gratefully acknowledge the support of the Waterways Experi- ment Station and Drs. Howard Westerdahl and Kurt Getsinger as this research was being conducted...E. Westerdahl , eds., Plant Growth Regulator Society of America, San Antonio, TX, 127-45. Anderson, L. W. J., and Dechoretz, N. (1988). "Bensulfuron...Vegetation Management. J. E. Kaufman and H. E. Westerdahl , eds., Plant Growth Regulator Society of America, San Antonio, TX, 155-86. Herbicide Handbook

Neoplastic causes of abnormal puberty.

Science.gov (United States)

Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

2014-04-01

Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

The claudin gene family: expression in normal and neoplastic tissues

International Nuclear Information System (INIS)

Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

2006-01-01

The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

Orphan nuclear receptor NR4A1 is a negative regulator of DHT-induced rat preantral follicular growth.

Science.gov (United States)

Xue, Kai; Liu, Jia-yin; Murphy, Bruce D; Tsang, Benjamin K

2012-12-01

Nuclear receptor subfamily 4 group A member1 (NR4A1), an orphan nuclear receptor, is involved in the transcriptional regulation of thecal cell androgen biosynthesis and paracrine factor insulin-like 3 (INSL3) expression. Androgens are known to play an important regulatory role in ovarian follicle growth. Using a chronically androgenized rat model, a preantral follicle culture model and virus-mediated gene delivery, we examined the role and regulation of NR4A1 in the androgenic control of preantral follicular growth. In the present study, Ki67 staining was increased in preantral follicles on ovarian sections from 5α-dihydrotestosterone (DHT)-treated rats. Preantral follicles from DHT-treated rats cultured for 4 d exhibited increased growth and up-regulation of mRNA abundance of G(1)/S-specific cyclin-D2 (Ccnd2) and FSH receptor (Fshr). Similarly, DHT (1 μm) increased preantral follicular growth and Ccnd2 and Fshr mRNA abundance in vitro. The NR4A1 expression was high in theca cells and was down-regulated by DHT in vivo and in vitro. Forced expression of NR4A1 augmented preantral follicular growth, androstenedione production, and Insl3 expression in vitro. Inhibiting the action of androgen (with androgen receptor antagonist flutamide) or INSL3 (with INSL3 receptor antagonist INSL3 B-chain) reduced NR4A1-induced preantral follicular growth. Furthermore, NR4A1 overexpression enhanced DHT-induced preantral follicular growth, a response attenuated by inhibiting INSL3. In conclusion, DHT promotes preantral follicular growth and attenuates thecal NR4A1 expression in vivo and in vitro. Our findings are consistent with the notion that NR4A1 serves as an important point of negative feedback to minimize the excessive preantral follicle growth in hyperandrogenism.

A Study of the Pathomorphology of Non-Neoplastic Changes in Canine Mammary Glands

OpenAIRE

Knauer, Steffen

2010-01-01

Whilst neoplasia in canine mammae has been the subject of a considerable number of studies, little is known about non-neoplastic changes of the mammae. The aim of the present study was therefore to conduct pathological anatomical and histopathological examinations of mammary glands in order to draw up a survey of the type and frequency of non-tumorous changes in the lactiferous tissues. The material under examination consis...

Regulation of myostatin expression is associated with growth and muscle development in commercial broiler and DMC muscle

NARCIS (Netherlands)

Dou, Tengfei; Li, Zhengtian; Wang, Kun; Liu, Lixian; Rong, Hua; Xu, Zhiqiang; Huang, Ying; Gu, Dahai; Chen, Xiaobo; Hu, Wenyuan; Zhang, Jiarong; Zhao, Sumei; Jois, Markandeya; Li, Qihua; Ge, Changrong; Pas, te Marinus F.W.; Jia, Junjing

2018-01-01

Myostatin is a negative regulator of skeletal muscle growth. Muscle tissue is the largest tissue in the body and influences body growth. Commercial Avian broiler chickens are selected for high growth rate and muscularity. Daweishan mini chickens are a slow growing small-sized chicken breed. We

Economic growth and energy regulation in the environmental Kuznets curve.

Science.gov (United States)

Lorente, Daniel Balsalobre; Álvarez-Herranz, Agustín

2016-08-01

This study establishes the existence of a pattern of behavior, between economic growth and environmental degradation, consistent with the environmental Kuznets curve (EKC) hypothesis for 17 Organization for Economic Cooperation and Development (OECD) countries between 1990 and 2012. Based on this EKC pattern, it shows that energy regulation measures help reduce per capita greenhouse gas (GHG) emissions. To validate this hypothesis, we also add the explanatory variables: renewable energy promotion, energy innovation processes, and the suppression effect of income level on the contribution of renewable energy sources to total energy consumption. It aims to be a tool for decision-making regarding energy policy. This paper provides a two-stage econometric analysis of instrumental variables with the aim of correcting the existence of endogeneity in the variable GDP per capita, verifying that the instrumental variables used in this research are appropriate for our aim. To this end, it first makes a methodological contribution before incorporating additional variables associated with environmental air pollution into the EKC hypothesis and showing how they positively affect the explanation of the correction in the GHG emission levels. This study concludes that air pollution will not disappear on its own as economic growth increases. Therefore, it is necessary to promote energy regulation measures to reduce environmental pollution.

Genetic activity of plant growth regulators, cartolin and benzilandenin, under ionizing radiation

International Nuclear Information System (INIS)

Vilenskij, E.P.

1987-01-01

Protective effects of a new cytokinin-type growth regulator cartolin (CRT) are established on a genetic test system of waxy-changes in pollen barley grains under acute irradiation of growing plants. It is shown that the CRT effect is similar to that of synthetic cytokinin benziladenin

BRI1 and BAK1 interact with G proteins and regulate sugar-responsive growth and development in Arabidopsis.

Science.gov (United States)

Peng, Yuancheng; Chen, Liangliang; Li, Shengjun; Zhang, Yueying; Xu, Ran; Liu, Zupei; Liu, Wuxia; Kong, Jingjing; Huang, Xiahe; Wang, Yingchun; Cheng, Beijiu; Zheng, Leiying; Li, Yunhai

2018-04-18

Sugars function as signal molecules to regulate growth, development, and gene expression in plants, yeasts, and animals. A coordination of sugar availability with phytohormone signals is crucial for plant growth and development. The molecular link between sugar availability and hormone-dependent plant growth are largely unknown. Here we report that BRI1 and BAK1 are involved in sugar-responsive growth and development. Glucose influences the physical interactions and phosphorylations of BRI1 and BAK1 in a concentration-dependent manner. BRI1 and BAK1 physically interact with G proteins that are essential for mediating sugar signaling. Biochemical data show that BRI1 can phosphorylate G protein β subunit and γ subunits, and BAK1 can phosphorylate G protein γ subunits. Genetic analyses suggest that BRI1 and BAK1 function in a common pathway with G-protein subunits to regulate sugar responses. Thus, our findings reveal an important genetic and molecular mechanism by which BR receptors associate with G proteins to regulate sugar-responsive growth and development.

The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

Directory of Open Access Journals (Sweden)

Brábek Jan

2010-09-01

Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

Directory of Open Access Journals (Sweden)

Giorgi Kharebava

2015-12-01

Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation.

Science.gov (United States)

Jackson, Laura E; Kulkarni, Sucheta; Wang, Huabo; Lu, Jie; Dolezal, James M; Bharathi, Sivakama S; Ranganathan, Sarangarajan; Patel, Mulchand S; Deshpande, Rahul; Alencastro, Frances; Wendell, Stacy G; Goetzman, Eric S; Duncan, Andrew W; Prochownik, Edward V

2017-11-01

Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC "knockout" (KO) animals, the long-term regenerative potential of hepatocytes was unimpaired, and growth of aggressive experimental hepatoblastomas was only modestly slowed in the face of 80%-90% reductions in AcCoA and significant alterations in the levels of key tricarboxylic acid (TCA) cycle intermediates and amino acids. Overall, oxphos activity in KO livers and hepatoblastoma was comparable with that of control counterparts, with evidence that metabolic substrate abnormalities were compensated for by increased mitochondrial mass. These findings demonstrate that the biochemical link between glycolysis and the TCA cycle can be completely severed without affecting normal or neoplastic proliferation, even under the most demanding circumstances. Cancer Res; 77(21); 5795-807. ©2017 AACR . ©2017 American Association for Cancer Research.

Synchronization of developmental processes and defense signaling by growth regulating transcription factors.

Directory of Open Access Journals (Sweden)

Jinyi Liu

Full Text Available Growth regulating factors (GRFs are a conserved class of transcription factor in seed plants. GRFs are involved in various aspects of tissue differentiation and organ development. The implication of GRFs in biotic stress response has also been recently reported, suggesting a role of these transcription factors in coordinating the interaction between developmental processes and defense dynamics. However, the molecular mechanisms by which GRFs mediate the overlaps between defense signaling and developmental pathways are elusive. Here, we report large scale identification of putative target candidates of Arabidopsis GRF1 and GRF3 by comparing mRNA profiles of the grf1/grf2/grf3 triple mutant and those of the transgenic plants overexpressing miR396-resistant version of GRF1 or GRF3. We identified 1,098 and 600 genes as putative targets of GRF1 and GRF3, respectively. Functional classification of the potential target candidates revealed that GRF1 and GRF3 contribute to the regulation of various biological processes associated with defense response and disease resistance. GRF1 and GRF3 participate specifically in the regulation of defense-related transcription factors, cell-wall modifications, cytokinin biosynthesis and signaling, and secondary metabolites accumulation. GRF1 and GRF3 seem to fine-tune the crosstalk between miRNA signaling networks by regulating the expression of several miRNA target genes. In addition, our data suggest that GRF1 and GRF3 may function as negative regulators of gene expression through their association with other transcription factors. Collectively, our data provide new insights into how GRF1 and GRF3 might coordinate the interactions between defense signaling and plant growth and developmental pathways.

Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

DEFF Research Database (Denmark)

Haugen, A; Laerum, O D; Bock, E

1981-01-01

of gestation. The brains of the treated fetuses were transferred to cell culture and underwent neoplastic transformation with a characteristic sequence of phenotypic alterations which could be divided into five different stages. During the first 40 days after explantation (stage I & II) BE induced...

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

Science.gov (United States)

Di Gioia, Sonia; Bianchi, Paolo; Destro, Annarita; Grizzi, Fabio; Malesci, Alberto; Laghi, Luigi; Levrero, Massimo; Morabito, Alberto; Roncalli, Massimo

2006-01-01

Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic (large regenerative, low and high grade dysplastic nodules) and neoplastic (hepatocellular adenoma and carcinoma) growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation was also found in both lesional (focal nodular hyperplasia and hepatocellular adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA) showed a methylation index significantly higher than that detected in focal nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In non-lesional liver also the methylation index gradually increased by ageing (p = 0.002), suggesting a progressive spreading of methylated cells over time. As opposed to RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly

Nitric Oxide Regulates Seedling Growth and Mitochondrial Responses in Aged Oat Seeds

Directory of Open Access Journals (Sweden)

Chunli Mao

2018-04-01

Full Text Available Mitochondria are the source of reactive oxygen species (ROS in plant cells and play a central role in the mitochondrial electron transport chain (ETC and tricarboxylic acid cycle (TCA cycles; however, ROS production and regulation for seed germination, seedling growth, as well as mitochondrial responses to abiotic stress, are not clear. This study was conducted to obtain basic information on seed germination, embryo mitochondrial antioxidant responses, and protein profile changes in artificial aging in oat seeds (Avena sativa L. exposed to exogenous nitric oxide (NO treatment. The results showed that the accumulation of H2O2 in mitochondria increased significantly in aged seeds. Artificial aging can lead to a loss of seed vigor, which was shown by a decline in seed germination and the extension of mean germination time (MGT. Seedling growth was also inhibited. Some enzymes, including catalase (CAT, glutathione reductase (GR, dehydroascorbate reductase (DHAR, and monodehydroascorbate reductase (MDHAR, maintained a lower level in the ascorbate-glutathione (AsA-GSH scavenging system. Proteomic analysis revealed that the expression of some proteins related to the TCA cycle were down-regulated and several enzymes related to mitochondrial ETC were up-regulated. With the application of 0.05 mM NO in aged oat seeds, a protective effect was observed, demonstrated by an improvement in seed vigor and increased H2O2 scavenging ability in mitochondria. There were also higher activities of CAT, GR, MDHAR, and DHAR in the AsA-GSH scavenging system, enhanced TCA cycle-related enzymes (malate dehydrogenase, succinate-CoA ligase, fumarate hydratase, and activated alternative pathways, as the cytochrome pathway was inhibited. Therefore, our results indicated that seedling growth and seed germinability could retain a certain level in aged oat seeds, predominantly depending on the lower NO regulation of the TCA cycle and AsA-GSH. Thus, it could be concluded that the

Effects of reduced-risk pesticides and plant growth regulators on rove beetle (Coleoptera: Staphylinidae) adults.

Science.gov (United States)

Echegaray, Erik R; Cloyd, Raymond A

2012-12-01

In many regions, pest management of greenhouse crops relies on the use of biological control agents; however, pesticides are also widely used, especially when dealing with multiple arthropod pests and attempting to maintain high esthetic standards. As such, there is interest in using biological control agents in conjunction with chemical control. However, the prospects of combining natural enemies and pesticides are not well known in many systems. The rove beetle, Atheta coriaria (Kraatz), is a biological control agent mainly used against fungus gnats (Bradysia spp.). This study evaluated the effects of reduced-risk pesticides and plant growth regulators on A. coriaria adult survival, development, and prey consumption under laboratory conditions. Rove beetle survival was consistently higher when adults were released 24 h after rather than before applying pesticides. The pesticides acetamiprid, lambda-cyhalothrin, and cyfluthrin were harmful to rove beetle adults, whereas Beauveria bassiana (Balsamo) Vuillemin, azadirachtin, and organic oils (cinnamon oils, rosemary oil, thyme oil, and clove oil) were nontoxic to A. coriaria adults. Similarly, the plant growth regulators acymidol, paclobutrazol, and uniconazole were not harmful to rove beetle adults. In addition, B. bassiana, azadirachtin, kinoprene, organic oils, and the plant growth regulators did not negatively affect A. coriaria development. However, B. bassiana did negatively affect adult prey consumption. This study demonstrated that A. coriaria may not be used when applying the pesticides, acetamiprid, lambda-cyhalothrin, and cyfluthrin, whereas organic oils, B. bassiana, azadirachtin, and the plant growth regulators evaluated may be used in conjunction with A. coriaria adults. As such, these compounds may be used in combination with A. coriaria in greenhouse production systems.

Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.

Directory of Open Access Journals (Sweden)

Robert W Tilghman

Full Text Available Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa, cells on soft substrates (150-300 Pa exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins and glycolysis (e.g., phosphofructokinase-1, whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical

Leptin differentially regulates chondrogenesis in mouse vertebral and tibial growth plates.

Science.gov (United States)

Yu, Bo; Jiang, Kaibiao; Chen, Bin; Wang, Hantao; Li, Xinfeng; Liu, Zude

2017-05-31

Leptin plays an important role in mediating chondrogenesis of limb growth plate. Previous studies suggest that bone structures and development of spine and limb are different. The expression of Ob-Rb, the gene that encodes leptin receptors, is vertebral and appendicular region-specific, suggesting the regulation of leptin on VGP and TGP chondrogenesis may be very different. The aim of the present study was to investigate the differential regulation of leptin on the chondrogenesis of vertebral growth plate (VGP) and tibial growth plate (TGP). We compared the VGP and TGP from wild type (C57BL/6) and leptin-deficient (ob/ob) mice. We then generated primary cultures of TGP and VGP chondrocytes. By treating the primary cells with different concentrations of leptin in vitro, we analyzed proliferation and apoptosis of the primary chondrocytes from TGP and VGP. We further measured expression of chondrogenic-related genes in these cells that had been incubated with different doses of leptin. Leptin-deficient mice of 8-week-old had shorter tibial and longer vertebral lengths than the wide type mice. Disturbed columnar structure was observed for TGP but not for VGP. In primary chondrocyte cultures, leptin inhibited VGP chondrocyte proliferation but promoted their apoptosis. Collagen IIA and aggrecan mRNA, and the protein levels of proliferation- and chondrogenesis-related markers, including PCNA, Sox9, and Smad4, were downregulated by leptin in a dose-dependent manner. In contrast, leptin stimulated the proliferation and chondrogenic differentiation of TGP chondrocytes at physiological levels (i.e., 10 and 50 ng/mL) but not at high levels (i.e., 100 and 1000 ng/mL). Leptin exerts a stimulatory effect on the proliferation and chondrogenic differentiation of the long bone growth plate but an inhibitory effect on the spine growth plate. The ongoing study will shed light on the regulatory mechanisms of leptin in bone development and metabolism.

Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas

DEFF Research Database (Denmark)

Jensen, Niels Aagaard; Pedersen, Karen-Marie; Lihme, Frederikke

2003-01-01

Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2-3 weeks of age. The genetically...... engineered murine (GEM) gliomas harbor a molecular signature resembling that of human primary glioblastoma multiforme, including up-regulation of epidermal growth factor receptor and Mdm2. The GEM gliomas seem to originate in an abnormal population of glial fibrillary acidic protein-expressing cells...... the neoplastic process, presumably by inducing the sustained growth of early astroglial cells. This is in contrast to most other transgenic studies in which c-Myc overexpression requires co-operating transgenes for rapid tumor induction....

[Effectiveness of three biological larvicides and of an insect growth regulator against Anopheles arabiensis in Senegal].

Science.gov (United States)

Diédhiou, S M; Konaté, L; Doucouré, S; Samb, B; Niang, E A; Sy, O; Thiaw, O; Konaté, A; Wotodjo, A N; Diallo, M; Gadiaga, L; Sokhna, C; Faye, O

2017-05-01

Urban malaria is a major public health problem in Africa. In Senegal, the environmental changes seem to favor the persistence of malaria transmission in Dakar suburbs by creating, throughout the year, potential breeding sites of malaria vectors. In such a situation and in a context of a growing threat of insecticide resistance in anopheline vectors, the larval control making use of products from biological origin or growth regulators could represent an additional tool to the current strategies developed against anophelines. In this study conducted in 2012, the efficiency and residual effect of three biological larvicides (VectoBac ® WG, Vecto-Max ® CG, and VectoBac ® GR) and an insect growth regulator (MetaLarv™) were evaluated on Anopheles gambiae s.l. larvae in seminatural conditions (experimental station) and natural breeding sites in the suburbs of Dakar. The formulations were tested according to the manufacturer recommendations, namely 0.03 g/m 2 for VectoBac ® WG, 0.5 g/m 2 for VectoBac ® GR, 0.75 g/m 2 for VectoMax ® CG, and 0.5 g/m 2 for MetaLarv™. In experimental station, the treatment with larvicides was effective over a period of 14 days with a mortality ranging between 92% and 100%. The insect growth regulator remained effective up to 55 days with a single emergence recorded in the 27th day after treatment. In natural conditions, a total effectiveness (100% mortality) of larvicides was obtained 48 hours after treatment, then a gradual recolonization of breeding sites was noted. However, the insect growth regulator has reduced adult emergence higher than 80% until the end of follow-up (J28). This study showed a good efficiency of the larvicides and of the growth regulator tested. These works provide current data on potential candidates for the implementation of larval control interventions in addition to that of chemical adulticide for control of urban malaria.

Changes in the physiological activity of soybean (Glycine max L. Merr. under the influence of exogenous growth regulators

Directory of Open Access Journals (Sweden)

Anna Nowak

2015-07-01

Full Text Available In a two-year pot experiment (2008–2009 conducted at the Vegetation Hall, West Pomeranian University of Technology in Szczecin, we investigated the influence of exogenous growth regulators, i.e. indole-3-butyric acid (IBA and 6-benzylaminopurine (BAP and their mixture, on the activity of gas exchange and selected physiological features of soybeans (Glycine max L. Merr.. The experimental factors included the following Polish soybean cultivars: ‘Aldana’, ‘Progres’ and ‘Jutro’. During plant growth, CO2 assimilation (A, transpiration rate (E, stomatal conductance (gs, and substomatal CO2 concentration (ci were determined. Two soybean cultivars, i.e. ‘Jutro’ and ‘Progres’, showed a significant increase in the intensity of assimilation and transpiration after using all kinds of growth regulators as compared with the control plants. It was found that the ‘Jutro’ cultivar, after using a mixture of growth regulators (IBA + BAP, was characterized by the significantly highest CO2 assimilation (A and transpiration (E as well as the highest stomatal conductance (gs. The ‘Aldana’ cultivar, on the other hand, responded by a significant reduction in the transpiration rate, stomatal conductance and subsomatal CO2 concentration. The spraying of the plants with exogenous growth regulators had a significant influence on the increase in the number of stomata and stomatal pore length, mostly on the lower epidermis of the lamina. It was also found that plants from the ‘Jutro’ and ‘Aldana’ cultivars sprayed with IBA and IBA + BAP were characterized by the highest yield, as compared with the control plants. In the case of the ‘Jutro’ cultivar, after using the growth regulators, a positive correlation was observed between the assimilation and transpiration rates and the length of stomata, which in consequence produced increased yields.

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

Science.gov (United States)

DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL  CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.

Science.gov (United States)

Palazzo, E; Kellett, M; Cataisson, C; Gormley, A; Bible, P W; Pietroni, V; Radoja, N; Hwang, J; Blumenberg, M; Yuspa, S H; Morasso, M I

2016-06-16

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.

Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants.

Directory of Open Access Journals (Sweden)

Yumie Takata

Full Text Available Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1 concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85. SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR = 3.95, 95% confidence intervals (CI = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58, but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69. Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1

Alcohol consumption and the neoplastic progression in Barrett's esophagus: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Zhifeng Lou

Full Text Available PURPOSE: In the developed countries, the incidence of esophageal adenocarcinoma (EAC is increasing over recent decades. The purpose of this meta-analysis was to arrive at quantitative conclusions about the contribution of alcohol intakes and the progression of Barrett's esophagus. METHODS: A comprehensive, systematic bibliographic search of medical literature published up to Oct 2013 was conducted to identify relevant studies. A meta-analysis was conducted for alcohol consumption on the Barrett's esophagus progression. RESULTS: A total of 882 cases in 6,867 individuals from 14 observational studies were indemnified in this meta-analysis. The result of this current meta-analysis, including 10 case-control and 4 cohort studies, indicated that alcohol consumption was not associated with the neoplastic progression in Barrett's esophagus (RR, 1.17; 95% CI, 0.93-1.48. When stratified by the study designs, no significant association was detected in either high vs low group or ever vs never group. CONCLUSIONS: Alcohol drinking is not associated with risk of neoplastic progression in Barrett's esophagus. Further well designed studies are needed in this area.

Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes.

Science.gov (United States)

Li, Yuwei; Ahrens, Molly J; Wu, Amy; Liu, Jennifer; Dudley, Andrew T

2011-01-01

For tissues that develop throughout embryogenesis and into postnatal life, the generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity. Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways. We present an integrated model for the regulation of proliferation potential by CamkII activity that has important implications for studies of growth control and adult progenitor/stem cell populations.

Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest.

Science.gov (United States)

Lan, Qiusheng; Li, Shoufeng; Lai, Wei; Xu, Heyang; Zhang, Yang; Zeng, Yujie; Lan, Wenjian; Chu, Zhonghua

2015-08-17

The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.

Expressionof Drosophila FOXO regulates growth and can phenocopy starvation

Directory of Open Access Journals (Sweden)

Lockyer Joseph M

2003-07-01

Full Text Available Abstract Background Components of theinsulin signaling pathway are important regulators of growth. TheFOXO (forkhead box, sub-group "O" transcriptionfactors regulate cellular processes under conditions of low levelsof insulin signaling. Studies in mammalian cell culture show thatactivation of FOXO transcription factors causes cell death or cellcycle arrest. The Caenorhabiditis elegans homologue ofFOXO, Daf-16, is required for the formation of dauer larvae in responseto nutritional stress. In addition, FOXO factors have been implicatedin stress resistance and longevity. Results We have identifiedthe Drosophila melanogaster homologue of FOXO (dFOXO,which is conserved in amino acid sequence compared with the mammalianFOXO homologues and Daf-16. Expression of dFOXO during early larvaldevelopment causes inhibition of larval growth and alterations infeeding behavior. Inhibition of larval growth is reversible upondiscontinuation of dFOXO expression. Expression of dFOXO duringthe third larval instar or at low levels during development leadsto the generation of adults that are reduced in size. Analysis ofthe wings and eyes of these small flies indicates that the reductionin size is due to decreases in cell size and cell number. Overexpressionof dFOXO in the developing eye leads to a characteristic phenotypewith reductions in cell size and cell number. This phenotype canbe rescued by co-expression of upstream insulin signaling components,dPI3K and dAkt, however, this rescue is not seen when FOXO is mutatedto a constitutively active form. Conclusions dFOXO is conservedin both sequence and regulatory mechanisms when compared with otherFOXO homologues. The establishment of Drosophila as a model forthe study of FOXO transcription factors should prove beneficialto determining the biological role of these signaling molecules.The alterations in larval development seen upon overexpression ofdFOXO closely mimic the phenotypic effects of starvation, suggestinga

Role of plant growth regulators on oil yield and biodiesel production of linseed (linum usitatissimum l)

International Nuclear Information System (INIS)

Faizanullah, A.; Bano, A.; Nosheen, A.

2010-01-01

A field experiment was conducted to compare the effect of plant growth regulators (PGRs) viz. kinetin (K), chlorocholine chloride (CCC) and salicylic acid (SA) on seed yield, oil content and oil quality of Linseed (Linum usitatissimum L) cv. Chandni with a new perspective to biodiesel production. The growth regulators (10-6M) were applied as seed soaking for 10 h prior to cultivation. Kinetin significantly increased the number of capsules/plant, seed number/capsule, 1000 seed weight and total seed yield (kg/h). The growth regulators increased the seed oil content maximum being in kinetin and CCC treatments. Kinetin and CCC significantly decreased the oil acid value, free fatty acid content (% oleic acid) and increased the pH of oil. Nevertheless, SA significantly decreased the oil specific gravity and did not alter the pH. Only kinetin significantly increased the oil iodine value. The oil extracted from seeds of kinetin and CCC treated plants showed maximum conversion (% w/w) to methyl esters/biodiesel after transesterification. It can be inferred that PGRs can be utilized successfully for improving the biodiesel yield of linseed. (author)

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

Science.gov (United States)

Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

Tall or short? Slender or thick? A plant strategy for regulating elongation growth of roots by low concentrations of gibberellin.

Science.gov (United States)

Tanimoto, Eiichi

2012-07-01

Since the plant hormone gibberellin (GA) was discovered as a fungal toxin that caused abnormal elongation of rice shoots, the physiological function of GA has mainly been investigated in relation to the regulation of plant height. However, an indispensable role for GA in root growth has been elucidated by using severely GA-depleted plants, either with a gene mutation in GA biosynthesis or which have been treated by an inhibitor of GA biosynthesis. The molecular sequence of GA signalling has also been studied to understand GA functions in root growth. This review addresses research progress on the physiological functions of GA in root growth. Concentration-dependent stimulation of elongation growth by GA is important for the regulation of plant height and root length. Thus the endogenous level of GA and/or the GA sensitivity of shoots and roots plays a role in determining the shoot-to-root ratio of the plant body. Since the shoot-to-root ratio is an important parameter for agricultural production, control of GA production and GA sensitivity may provide a strategy for improving agricultural productivity. The sequence of GA signal transduction has recently been unveiled, and some component molecules are suggested as candidate in planta regulatory sites and as points for the artificial manipulation of GA-mediated growth control. This paper reviews: (1) the breakthrough dose-response experiments that show that root growth is regulated by GA in a lower concentration range than is required for shoot growth; (2) research on the regulation of GA biosynthesis pathways that are known predominantly to control shoot growth; and (3) recent research on GA signalling pathways, including GA receptors, which have been suggested to participate in GA-mediated growth regulation. This provides useful information to suggest a possible strategy for the selective control of shoot and root growth, and to explain how GA plays a role in rosette and liana plants with tall or short, and slender

Crop growth, light utilization and yield of relay intercropped cotton as affected by plant density and a plant growth regulator

NARCIS (Netherlands)

Mao, L.; Zhang, L.; Zhao, X.; Liu, S.; Werf, van der W.; Zhang, S.; Spiertz, J.H.J.; Li, Z.

2014-01-01

Modern cotton cultivation requires high plant densities and compact plants. Here we study planting density and growth regulator effects on plant structure and production of cotton when the cotton is grown in a relay intercrop with wheat, a cultivation system that is widespread in China. Field

Receptor-like kinases as surface regulators for RAC/ROP-mediated pollen tube growth and interaction with the pistil

Science.gov (United States)

Zou, Yanjiao; Aggarwal, Mini; Zheng, Wen-Guang; Wu, Hen-Ming; Cheung, Alice Y.

2011-01-01

Background RAC/ROPs are RHO-type GTPases and are known to play diverse signalling roles in plants. Cytoplasmic RAC/ROPs are recruited to the cell membrane and activated in response to extracellular signals perceived and mediated by cell surface-located signalling assemblies, transducing the signals to regulate cellular processes. More than any other cell types in plants, pollen tubes depend on continuous interactions with an extracellular environment produced by their surrounding tissues as they grow within the female organ pistil to deliver sperm to the female gametophyte for fertilization. Scope We review studies on pollen tube growth that provide compelling evidence indicating that RAC/ROPs are crucial for regulating the cellular processes that underlie the polarized cell growth process. Efforts to identify cell surface regulators that mediate extracellular signals also point to RAC/ROPs being the molecular switches targeted by growth-regulating female factors for modulation to mediate pollination and fertilization. We discuss a large volume of work spanning more than two decades on a family of pollen-specific receptor kinases and some recent studies on members of the FERONIA family of receptor-like kinases (RLKs). Significance The research described shows the crucial roles that two RLK families play in transducing signals from growth regulatory factors to the RAC/ROP switch at the pollen tube apex to mediate and target pollen tube growth to the female gametophyte and signal its disintegration to achieve fertilization once inside the female chamber. PMID:22476487

Post-transcriptional regulation of vascular endothelial growth factor: Implications for tumor angiogenesis

Institute of Scientific and Technical Information of China (English)

Peter S Yoo; Abby L Mulkeen; Charles H Cha

2006-01-01

Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization,translation, and differential cellular localization of various isoforms. Recent advances in our understanding of posttranscriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi)technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.

Starch as a major integrator in the regulation of plant growth

Science.gov (United States)

Sulpice, Ronan; Pyl, Eva-Theresa; Ishihara, Hirofumi; Trenkamp, Sandra; Steinfath, Matthias; Witucka-Wall, Hanna; Gibon, Yves; Usadel, Björn; Poree, Fabien; Piques, Maria Conceição; Von Korff, Maria; Steinhauser, Marie Caroline; Keurentjes, Joost J. B.; Guenther, Manuela; Hoehne, Melanie; Selbig, Joachim; Fernie, Alisdair R.; Altmann, Thomas; Stitt, Mark

2009-01-01

Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite profiling in 94 Arabidopsis accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1-phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production. PMID:19506259

Methodology for evaluating the insect growth regulator (IGR) methoprene incorporated into packaging films

Science.gov (United States)

The insect growth regulator methoprene has been impregnated onto various packaging materials to control stored product insects, and is labeled for use in this manner in the United States. Different methodologies were utilized to evaluate efficacy towards Tribolium castaneum (Herbst), the red flour b...

Fibroblasts from long-lived Snell dwarf mice are resistant to oxygen-induced in vitro growth arrest

DEFF Research Database (Denmark)

Maynard, Scott P; Miller, Richard A

2006-01-01

Snell dwarf mice live longer than controls, and show lower age-adjusted rates of lethal neoplastic diseases. Fibroblast cells from adult dwarf mice are resistant to the lethal effects of oxidative and nonoxidative stresses, including the carcinogen methyl methanesulfonate. We now report that dwar...... in skin fibroblasts by the hormonal milieu of the Snell dwarf lead to resistance to multiple forms of injury, including the oxidative damage that contributes to growth arrest in vitro and neoplasia in intact mice.......Snell dwarf mice live longer than controls, and show lower age-adjusted rates of lethal neoplastic diseases. Fibroblast cells from adult dwarf mice are resistant to the lethal effects of oxidative and nonoxidative stresses, including the carcinogen methyl methanesulfonate. We now report that dwarf...

Membrane-localized ubiquitin ligase ATL15 functions in sugar-responsive growth regulation in Arabidopsis.

Science.gov (United States)

Aoyama, Shoki; Terada, Saki; Sanagi, Miho; Hasegawa, Yoko; Lu, Yu; Morita, Yoshie; Chiba, Yukako; Sato, Takeo; Yamaguchi, Junji

2017-09-09

Ubiquitin ligases play important roles in regulating various cellular processes by modulating the protein function of specific ubiquitination targets. The Arabidopsis Tóxicos en Levadura (ATL) family is a group of plant-specific RING-type ubiquitin ligases that localize to membranes via their N-terminal transmembrane-like domains. To date, 91 ATL isoforms have been identified in the Arabidopsis genome, with several ATLs reported to be involved in regulating plant responses to environmental stresses. However, the functions of most ATLs remain unknown. This study, involving transcriptome database analysis, identifies ATL15 as a sugar responsive ATL gene in Arabidopsis. ATL15 expression was rapidly down-regulated in the presence of sugar. The ATL15 protein showed ubiquitin ligase activity in vitro and localized to plasma membrane and endomembrane compartments. Further genetic analyses demonstrated that the atl15 knockout mutants are insensitive to high glucose concentrations, whereas ATL15 overexpression depresses plant growth. In addition, endogenous glucose and starch amounts were reciprocally affected in the atl15 knockout mutants and the ATL15 overexpressors. These results suggest that ATL15 protein plays a significant role as a membrane-localized ubiquitin ligase that regulates sugar-responsive plant growth in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Neoplastic Nature of Keratocystic Odontogenic Tumor Versus Ameloblastoma

International Nuclear Information System (INIS)

KHALIFA, Gh.A.; SMOKIER, H.M.; ABO-HAGER, E.A.

2010-01-01

Although most of odontogenic tumors are benign, some of them will show locally destructive behavior, as keratocystic odontogenic tumor (KCOT) is now known as a benign but aggressive odontogenic neoplasm. The neoplastic characteristics in KCOT have been suggested from clinical as well as pathologic aspects. Matrix metalloproteinase-2 (MMP-2) is a gelatinase form of the MMPs family, which is a group of proteolytic enzymes that degrade many types of collagen. Cysteine aspartic acid-specific protease-3 (caspase-3) is the most downstream enzyme in the apoptosis-inducing protease pathway and is probably the most clearly associated with cell death. The aim of this study is to evaluate and compare the extracellular degradation potentiality (MMP-2) and apoptosis (caspase-3) of the epithelial lining in KCOT versus radicular cysts and ameloblastoma, in order to reinforce its classification as an odontogenic tumor. Material and Methods: Twenty-six surgical specimens including keratocyst odontogenic tumor (KCOT; n=l 1), ameloblastoma (AB; n=8) and radicular cysts (RC; n=7) were examined for expression of MMP-2 and caspase-3 using the immunohistochemical method. Results: For MMP-2 immuno expression, AB showed the statistically significant highest mean area percentage, followed by KCOT, while RC showed the statistically significant lowest mean area percentage. As for caspase-3, there was no statistically significant difference between KCOT and AB, while RC showed the statistically significantly lowest mean area percentage. Conclusion: Overexpression of MMP-2 protein related to growth and progression of lesions analyzed and may be one of the factors enhancing the recurrence of KCOT and invasion of AB. In addition, the epithelial lining of KCOT showed a high cell turnover reinforcing its classification as an odontogenic tumor

Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2

Directory of Open Access Journals (Sweden)

D'Orazi Gabriella

2008-07-01

Full Text Available Abstract Background Homeodomain-interacting protein kinase-2 (HIPK2 plays an essential role in restraining tumor progression as it may regulate, by itself or within multiprotein complexes, many proteins (mainly transcription factors involved in cell growth and apoptosis. This study takes advantage of the recent finding that HIPK2 may repress the β-catenin transcription activity. Thus, we investigated whether HIPK2 overexpression may down-regulate vascular endothelial growth factor (VEGF levels (a β-catenin target gene and the role of β-catenin in this regulation, in order to consider HIPK2 as a tool for novel anti-tumoral therapeutical approaches. Methods The regulation of VEGF expression by HIPK2 was evaluated by using luciferase assay with VEGF reporter construct, after overexpression of the β-catenin transcription factor. Relative quantification of VEGF and β-catenin mRNAs were assessed by reverse-transcriptase-PCR (RT-PCR analyses, following HIPK2 overexpression, while β-catenin protein levels were evaluated by western immunoblotting. Results HIPK2 overexpression in tumor cells downregulated VEGF mRNA levels and VEGF promoter activity. The VEGF downregulation was partly depending on HIPK2-mediated β-catenin regulation. Thus, HIPK2 could induce β-catenin protein degradation that was prevented by cell treatment with proteasome inhibitor MG132. The β-catenin degradation was dependent on HIPK2 catalytic activity and independent of p53 and glycogen synthase kinase 3β (GSK-3β activities. Conclusion These results suggest that VEGF might be a target of HIPK2, at least in part, through regulation of β-catenin activity. These findings support the function of HIPK2 as tumor suppressor and hypothesise a role for HIPK2 as antiangiogenic tool in tumor therapy approaches.

The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP

Directory of Open Access Journals (Sweden)

Katherine Striedinger

2008-11-01

Full Text Available Neurofibromatosis type 2 (NF2 is an autosomal dominant disorder characterized by the occurrence of schwannomas and meningiomas. Several studies have examined the ability of the NF2 gene product, merlin, to function as a tumor suppressor in diverse cell types; however, little is known about merlin growth regulation in meningiomas. In Drosophila, merlin controls cell proliferation and apoptosis by signaling through the Hippo pathway to inhibit the function of the transcriptional coactivator Yorkie. The Hippo pathway is conserved in mammals. On the basis of these observations, we developed human meningioma cell lines matched for merlin expression to evaluate merlin growth regulation and investigate the relationship between NF2 status and Yes-associated protein (YAP, the mammalian homolog of Yorkie. NF2 loss in meningioma cells was associated with loss of contact-dependent growth inhibition, enhanced anchorage-independent growth and increased cell proliferation due to increased S-phase entry. In addition, merlin loss in both meningioma cell lines and primary tumors resulted in increased YAP expression and nuclear localization. Finally, siRNA-mediated reduction of YAP in NF2-deficient meningioma cells rescued the effects of merlin loss on cell proliferation and S-phase entry. Collectively, these results represent the first demonstration that merlin regulates cell growth in human cancer cells by suppressing YAP.

Regulators of growth plate maturation

NARCIS (Netherlands)

Emons, Joyce Adriana Mathilde

2010-01-01

Estrogen is known to play an important role in longitudinal bone growth and growth plate maturation, but the mechanism by which estrogens exert their effect is not fully understood. In this thesis this role is further explored. Chapter 1 contains a general introduction to longitudinal bone growth

Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype

Directory of Open Access Journals (Sweden)

Shingo Sato

2016-07-01

Full Text Available The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

Effect of growth regulators on 'Brookfield' apple gas diffusion and metabolism under controlled atmosphere storage

Directory of Open Access Journals (Sweden)

Auri Brackmann

2014-05-01

Full Text Available The objective of this work was to evaluate the effect of growth regulators on gas diffusion and on metabolism of 'Brookfield' apple, and to determine their correlation with quality characteristics of fruit stored in controlled atmosphere. A completely randomized design was used with four replicates. After eight months of storage, the effects of water (control, aminoethoxyvinylglycine (AVG, AVG + ethephon, AVG + naphthaleneacetic acid (NAA, ethephon + NAA, sole NAA, 1-MCP, ethylene absorption by potassium permanganate (ABS, AVG + ABS, and of AVG + 1-MCP - applied at different rates and periods - were evaluated on: gas diffusion rate, ethylene production, respiratory rate, internal ethylene concentration, internal CO2 content, mealiness, and intercellular space. Fruit from the control and sole NAA treatments had the highest mealiness occurrence. Growth regulators significantly changed the gaseous diffusion through the pulp of 'Brookfield' apple, mainly in the treatment AVG + ABS, which kept the highest gas diffusion rate. NAA spraying in the field, with or without another growth regulator, increased ripening metabolism by rising ethylene production and respiration rate, and reduced gas diffusion during shelf life. AVG spraying cannot avoid the ethephon effect during the ripening process, and reduces both the internal space and mealiness incidence, but it is not able to induce ethylene production or to increase respiration rates.

Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {in-phase and out-of phase} MR imaging

International Nuclear Information System (INIS)

Ragab, Yasser; Emad, Yasser; Gheita, Tamer; Mansour, Maged; Abou-Zeid, A.; Ferrari, Serge; Rasker, Johannes J.

2009-01-01

Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer

Science.gov (United States)

Cekaite, Lina; Eide, Peter W.; Lind, Guro E.; Skotheim, Rolf I.; Lothe, Ragnhild A.

2016-01-01

Gene expression is in part regulated by microRNAs (miRNAs). This review summarizes the current knowledge of miRNAs in colorectal cancer (CRC); their role as growth regulators, the mechanisms that regulate the miRNAs themselves and the potential of miRNAs as biomarkers. Although thousands of tissue samples and bodily fluids from CRC patients have been investigated for biomarker potential of miRNAs (>160 papers presented in a comprehensive tables), none single miRNA nor miRNA expression signatures are in clinical use for this disease. More than 500 miRNA-target pairs have been identified in CRC and we discuss how these regulatory nodes interconnect and affect signaling pathways in CRC progression. PMID:26623728

Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

Directory of Open Access Journals (Sweden)

Tasić Desanka

2004-01-01

Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance.

Science.gov (United States)

Turney, Stephen G; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B; Goeckeler, Zoe M; Rioux, Robert M; Whitesides, George M; Bridgman, Paul C

2016-02-01

Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. © 2016 Turney et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

Science.gov (United States)

Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

2009-01-01

Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

Synthesis Of 2- (1- Naphthyl) Ethanoic Acid ( Plant Growth Regulator ) From Coal Tar And Its Application

International Nuclear Information System (INIS)

Khin Mooh Theint; Tin Myint Htwe

2011-12-01

Plant growth regulators, which are commonly called as plant hormones, naturally produced non-nutrient chemical compounds involved in growth and development. Among the various kinds of plant growth regulators, 2- (1- Naphthyl ) ethanoic acid especially encourages the root development of the plant. In this work, NAA was successfuly synthesized from naphthalene which was extracted from coal tar. The purity of naphthalene, -Chloromethyl naphthalene, -Naphthyl acetonitrile, - Naphthyl acetic acid or 2 - ( 1-Naphthyl ) ethanoic acid were also confirmed by Thin Layer Chromatography, and by spectroscopy methods. The yield percent of NAA based on naphthalene was found to be 2.1%. The yield percent of naphthaleneFrom coal tar is found to be 4.09%. The effect of NAA on root development was also studied in different concentrations of soy bean (Glycine max)and cow pea (Vigna catjang walp).

HLA‐G modulates the radiosensitivity of human neoplastic cells

International Nuclear Information System (INIS)

Michelin, Severino; Gallegos, Cristina; Baffa Trasci, Sofía; Dubner, Diana; Favier, B.; Carosella, E.D.

2011-01-01

Tumor cells show a very broad range of radiosensitivities. The differential radiosensitivity may depend on many factors, being the efficiency to recognize and/or repair the DNA lesion, and the cell cycle control mechanisms, the most important (Jeggo and Lavin, 2009; Kumala et al., 2003). Human leukocyte antigen‐G (HLA‐G) is a non‐classical HLA class I molecule involved in fetus protection form the maternal immune system, transplant tolerance, and viral and tumoral immune escape (Carosella et al., 2008). It has been determined that gamma radiation modulates HLA‐G expression at the plasma membrane of human melanoma cells. However, its role in tumoral radiosensitivity has not been demonstrated yet. The objective of this work was to determine if the radiosensitivity of human neoplastic cell lines cultured in vitro was mediated by HLA‐G expression. (authors)

Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

Science.gov (United States)

Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

2009-01-01

Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

Directory of Open Access Journals (Sweden)

Eugen Dhimolea

Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

Isolation and biological activity of a new plant growth regulator of Vicia faba L

International Nuclear Information System (INIS)

Sembdner, G.; Dathe, W.; Bergner, C.; Roensch, H.

1983-01-01

Jasmonic acid was identified as a plant growth inhibitor of the pericarp of Vicia faba by means of gas-liquid chromatography, high resolution mass spectrometry as well as 1 H and 13 C NMR. The highest level of jasmonic acid was reached during intensive pericarp growth. Jasmonic acid is a plant growth inhibitor possessing a relative activity in the wheat seedling bioassay of 1-2.5 % compared to ABA (=100%). Contrary to ABA, jasmonic acid does not cause retardation of leaf emergence. In the dwarf rice gibberellin bioassay relative low concentrations of jasmonic acid inhibit both autonomous and GA 3 -stimulated growth. Jasmonic acid does not influence seed germination of Amaranthus caudatus. The possible physiological role of jasmonic acid in the Vicia pericarp and the distribution in plants of this new plant growth regulator type are discussed. (author)

Isolation and biological activity of a new plant growth regulator of Vicia faba L

Energy Technology Data Exchange (ETDEWEB)

Sembdner, G.; Dathe, W.; Bergner, C.; Roensch, H. (Akademie der Wissenschaften der DDR, Halle/Saale. Inst. fuer Biochemie der Pflanzen)

1983-01-01

Jasmonic acid was identified as a plant growth inhibitor of the pericarp of Vicia faba by means of gas-liquid chromatography, high resolution mass spectrometry as well as /sup 1/H and /sup 13/C NMR. The highest level of jasmonic acid was reached during intensive pericarp growth. Jasmonic acid is a plant growth inhibitor possessing a relative activity in the wheat seedling bioassay of 1-2.5 % compared to ABA (=100%). Contrary to ABA, jasmonic acid does not cause retardation of leaf emergence. In the dwarf rice gibberellin bioassay relative low concentrations of jasmonic acid inhibit both autonomous and GA/sub 3/-stimulated growth. Jasmonic acid does not influence seed germination of Amaranthus caudatus. The possible physiological role of jasmonic acid in the Vicia pericarp and the distribution in plants of this new plant growth regulator type are discussed.

Neurofibromin regulates somatic growth through the hypothalamic–pituitary axis

Science.gov (United States)

Hegedus, Balazs; Yeh, Tu-Hsueh; Lee, Da Yong; Emnett, Ryan J.; Li, Jia; Gutmann, David H.

2008-01-01

To study the role of the neurofibromatosis-1 (NF1) gene in mammalian brain development, we recently generated mice in which Nf1 gene inactivation occurs in neuroglial progenitor cells using the brain lipid binding protein (BLBP) promoter. We found that Nf1BLBPCKO mice exhibit significantly reduced body weights and anterior pituitary gland sizes. We further demonstrate that the small anterior pituitary size reflects loss of neurofibromin expression in the hypothalamus, leading to reduced growth hormone releasing hormone, pituitary growth hormone (GH) and liver insulin-like growth factor-1 (IGF1) production. Since neurofibromin both negatively regulates Ras activity and positively modulates cAMP levels, we examined the signaling pathway responsible for these abnormalities. While BLBP-mediated expression of an activated Ras molecule did not recapitulate the body weight and hypothalamic/pituitary defects, treatment of Nf1BLBPCKO mice with rolipram to increase cAMP levels resulted in a partial restoration of the body weight phenotype. Furthermore, conditional expression of the Ras regulatory GAP domain of neurofibromin also did not rescue the body weight or Igf1 mRNA defects in Nf1BLBPCKO mice. Collectively, these data demonstrate a critical role for neurofibromin in hypothalamic–pituitary axis function and provide further insights into the short stature and GH deficits seen in children with NF1. PMID:18614544

Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

Energy Technology Data Exchange (ETDEWEB)

Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

2012-07-15

Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

International Nuclear Information System (INIS)

Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

2012-01-01

Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Science.gov (United States)

Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

2016-04-01

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Expression of a TGF-{beta} regulated cyclin-dependent kinase inhibitor in normal and immortalized airway epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Tierney, L.A.; Bloomfield, C.; Johnson, N.F. [and others

1995-12-01

Tumors arising from epithelial cells, including lung cancers are frequently resistant to factors that regulate growth and differentiation in normal in normal cells. Once such factor is transforming growth factor-{Beta} (TGF-{Beta}). Escape from the growth-inhibitory effects of TGF-{Beta} is thought to be a key step in the transformation of airway epithelial cells. most lung cancer cell lines require serum for growth. In contrast, normal human bronchial epithelial (NHBE) cells are exquisitely sensitive to growth-inhibitory and differentiating effects of TGF-{Beta}. The recent identification of a novel cyclin-dependent kinase inhibitor, p15{sup INK4B}, which is regulated by TGF-{Beta}, suggests a mechanism by which TGF-{Beta} mediates growth arrest in NHBE cells. The purpose of this study was two-fold: (1) to determine if p15{sup INK4B} is induced by TGF-{Beta} in NHBE cells or immortalized bronchial epithelial (R.1) cells and if that induction corresponds to a G1/S cell-cycle arrest; (2) to determine the temporal relationship between p15{sup INK4B} induction, cell-cycle arrest, and the phosphorylation state of the pRB because it is thought that p15{sup INK4B} acts indirectly by preventing phosphorylation of the RB gene product. In this study, expression of p15{sup INK4B} was examined in NHBE cells and R.1 cells at different time intervals following TGF-{Beta} treatment. The expression of this kinase inhibitor and its relationship to the cell and the pRb phosphorylation state were examined in cells that were both sensitive (NHBE) and resistant (R.1) to the effects of TGF-{Beta}. These results suggest that the cyclin-dependent kinase inhibitor, p15{sup INK4B}, is involved in airway epithelial cell differentiation and that loss or reduction of expression plays a role in the resistance of transformed or neoplastic cells to the growth-inhibitory effects of TGF-{Beta}.

Capsule endoscopy in neoplastic diseases

Science.gov (United States)

Pennazio, Marco; Rondonotti, Emanuele; de Franchis, Roberto

2008-01-01

Until recently, diagnosis and management of small-bowel tumors were delayed by the difficulty of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques. An array of new methods has recently been developed, increasing the possibility of detecting these tumors at an earlier stage. Capsule endoscopy (CE) appears to be an ideal tool to recognize the presence of neoplastic lesions along this organ, since it is non-invasive and enables the entire small bowel to be visualized. High-quality images of the small-bowel mucosa may be captured and small and flat lesions recognized, without exposure to radiation. Recent studies on a large population of patients undergoing CE have reported small-bowel tumor frequency only slightly above that reported in previous surgical series (range, 1.6%-2.4%) and have also confirmed that the main clinical indication to CE in patients with small-bowel tumors is obscure gastrointestinal (GI) bleeding. The majority of tumors identified by CE are malignant; many were unsuspected and not found by other methods. However, it remains difficult to identify pathology and tumor type based on the lesion’s endoscopic appearance. Despite its limitations, CE provides crucial information leading in most cases to changes in subsequent patient management. Whether the use of CE in combination with other new diagnostic (MRI or multidetector CT enterography) and therapeutic (Push-and-pull enteroscopy) techniques will lead to earlier diagnosis and treatment of these neoplasms, ultimately resulting in a survival advantage and in cost savings, remains to be determined through carefully-designed studies. PMID:18785274

Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models.

Science.gov (United States)

Yakar, Shoshana; Isaksson, Olle

2016-06-01

The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of light and growth regulators on adventitious bud formation in horseradish (Armoracia rusticana).

Science.gov (United States)

Kamada, H; Tachikawa, Y; Saitou, T; Harada, H

1995-07-01

To clarify that the presence of Ri T-DNA genes are not prerequisite for the light-induced bud formation in horseradish (Armoracia rusticana) hairy roots, leaf and root segments of nontransformed horseradish plants were used as explants. Bud formation from nontransformed tissues was observed in hormone-free medium under 16 h daylight conditions, but not under continuous darkness. To investigate the effects of growth regulators on bud formation, leaf and root explants were treated with auxin (1-naphthaleneacetic acid; NAA) and / or cytokinin (6-benzyl-aminopurine; BA). The most effective treatment in the dark to stimulate bud formation was BA at 1 mg·1(-1). These results show that adventitious bud formation in horseradish can be induced by light and growth regulators, and especially cytokinin, may be involved in bud formation, irrespective of whether the tissues were transformed with Ri T-DNA.

Regulation of DU145 prostate cancer cell growth by Scm-like with four mbt domains 2.

Science.gov (United States)

Lee, Kwanghyun; Na, Wonho; Maeng, Je-Heon; Wu, Hongjin; Ju, Bong-Gun

2013-03-01

Mammalian SFMBTs have been considered to be polycomb group repressors. However, molecular mechanisms underlying mammalian SFMBTs-mediated gene regulation and their biological function have not been characterized. In the present study, we identified YY1 and methylated histones as interacting proteins of human SFMBT2. We also found that human SFMBT2 binds preferentially to methylated histone H3 and H4 that are associated with transcriptional repression. Using DU145 prostate cancer cells as a model, we showed that SFMBT2 has a transcriptional repression activity on HOXB13 gene expression. In addition, occupancy of SFMBT2 coincided with enrichment of diand tri-methylated H3K9 and H4K20 as well as tri-methylated H3K27 at the HOXB13 gene promoter. When SFMBT2 was depleted by siRNA in DU145 prostate cancer cells, significant up-regulation of HOXB13 gene expression and decreased cell growth were observed. Collectively, our findings indicate that human SFMBT2 may regulate cell growth via epigenetic regulation of HOXB13 gene expression in DU145 prostate cancer cells.

Symbiotic regulation of plant growth, development and reproduction

Science.gov (United States)

Rodriguez, R.J.; Freeman, D. Carl; McArthur, E.D.; Kim, Y.-O.; Redman, R.S.

2009-01-01

The growth and development of rice (Oryzae sativa) seedlings was shown to be regulated epigenetically by a fungal endophyte. In contrast to un-inoculated (nonsymbiotic) plants, endophyte colonized (symbiotic) plants preferentially allocated resources into root growth until root hairs were well established. During that time symbiotic roots expanded at five times the rate observed in nonsymbiotic plants. Endophytes also influenced sexual reproduction of mature big sagebrush (Artemisia tridentata) plants. Two spatially distinct big sagebrush subspecies and their hybrids were symbiotic with unique fungal endophytes, despite being separated by only 380 m distance and 60 m elevation. A double reciprocal transplant experiment of parental and hybrid plants, and soils across the hybrid zone showed that fungal endophytes interact with the soils and different plant genotypes to confer enhanced plant reproduction in soil native to the endophyte and reduced reproduction in soil alien to the endophyte. Moreover, the most prevalent endophyte of the hybrid zone reduced the fitness of both parental subspecies. Because these endophytes are passed to the next generation of plants on seed coats, this interaction provides a selective advantage, habitat specificity, and the means of restricting gene flow, thereby making the hybrid zone stable, narrow and potentially leading to speciation. ?? 2009 Landes Bioscience.

Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine.

Science.gov (United States)

Bukovsky, Antonin; Caudle, Michael R; Carson, Ray J; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M

2009-02-13

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.

Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes.

Science.gov (United States)

Suliman, Salwa; Mustafa, Kamal; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Osdal, Tereza; Hamza, Amani O; Sun, Yang; Parajuli, Himalaya; Waag, Thilo; Nickel, Joachim; Johannessen, Anne Christine; McCormack, Emmet; Costea, Daniela Elena

2016-07-01

This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK(Luc)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK(Luc) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK(Luc) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK(Luc) both in vitro in 3D-OT and in vivo in xenografts formed by DOK(Luc) alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK(Luc) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK(Luc), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Enhanced sensitivity to neoplastic transformation by 137Cs γ-rays of cells in the G2-/M-phase age interval

International Nuclear Information System (INIS)

Cao, J.; Wells, R.L.; Elkind, M.M.

1992-01-01

C3H mouse 10T1/2 cells, exposed to low doses of fission-spectrum neutrons, have an enhanced frequency of neoplastic transformation if protracted exposures are used (Hill et al. 1982, 1984a, 1985). To explain this anormaly, a biophysical model was proposed (Elkind 1991 a,b). The unique shape and radiobiological properties of cells in and around mitosis, led to the proposal that the sensitive window is mitosis and possible cells just preceding or just following M phase (Elkind 1991a,b). This study was undertaken using 137 Cs γ-rays. The authors found that late G 2- to M-phase 10T1/2 cells have a maximal sensitivity to neoplastic transformation as well as to killing by 137 Cs γ-rays. (author)

Role of endogenous growth regulators in vernalization of seeds of radish (Raphanus sativus L.

Directory of Open Access Journals (Sweden)

Marian Michniewicz

2014-01-01

Full Text Available In embryos and cotyledons of seeds of the radish cv. `Tetra Iłówiecka' (which needs 20 days of vernalization and cv. 'Saxa' (which flowers without vernalization germinating at a vernalizing temperature of 5°C, the levels of auxins, gibberellins, cytokinins and the aibscisic acid-like inhibitor were determined, The analyses were performed after 5, 10, 15, 20, 25 and 30 days of chilling. The levels of growth regulators were also determined in embryos and cotyledons of seeds germinated at 260C when in the same growth stage as the material taken from chilled seeds. Cold treatment significantly affected the level of all endogenous growth regulators in embryos and cotyledons of both varieties. However, changes in the levels of these substances were not directly connected with the vernalization process. It was found that the vernalization of seeds of 'the radish cv. `Tetra Iłówiecka' increased the level of GAs in leaves, this did not, however, coincide with flower initiation. It is concluded that the role of GAs in flowering of the studied plants is connected rather with photoinduction than with vernalization.

Growth regulation of Legionella Pneumophila in biofilms and amoebae; Wachstumsregulation von Legionella Pneumophila in Biofilmen und Amoeben

Energy Technology Data Exchange (ETDEWEB)

Hilbi, H.

2006-07-01

This final report for the Swiss Federal Office of Energy (SFOE) presents the results of studies made on the regulation of the growth of Legionella Pneumophila bacteria in biofilms and amoebae. In a first project, the formation of biofilms by Legionella Pneumophila bacteria was analysed in static and dynamic systems using a complex growth medium. Under static and dynamic clinical and environmental conditions, the adherence of the biofilms on polystyrene tissue was studied. This was also examined under dynamic flow conditions. In a second part of the project, the regulation of growth of Legionella Pneumophila in amoebae was examined in that changes were made to the genome of the bacteria. The importance of the work for the de-activation of Legionella Pneumophila bacteria in biofilms is noted in the conclusions of the report.

The role of dynamic susceptibility contrast-enhanced perfusion MR imaging in differentiating between infectious and neoplastic focal brain lesions: results from a cohort of 100 consecutive patients.

Directory of Open Access Journals (Sweden)

Valdeci Hélio Floriano

Full Text Available BACKGROUND AND PURPOSE: Differentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes. MATERIALS AND METHODS: DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54 and infectious (n = 46 lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value. RESULTS: Neoplastic lesions had higher rCBV values (4.28±2.11 than infectious lesions (0.63±0.49 (p<0.001. When using an rCBV value <1.3 as the parameter to define infectious lesions, the sensitivity of the method was 97.8% and the specificity was 92.6%, with a positive predictive value of 91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%. CONCLUSION: PWI is a useful complementary tool in distinguishing between infectious and neoplastic brain

Feast and Famine: regulation of black hole growth in low-redshift galaxies

Science.gov (United States)

Kauffmann, Guinevere; Heckman, Timothy M.

2009-07-01

We analyse the observed distribution of Eddington ratios (L/LEdd) as a function of supermassive black hole mass for a large sample of nearby galaxies drawn from the Sloan Digital Sky Survey. We demonstrate that there are two distinct regimes of black hole growth in nearby galaxies. The first is associated with galaxies with significant star formation [M*/starformationrate (SFR) ~ a Hubble time] in their central kiloparsec regions, and is characterized by a broad lognormal distribution of accretion rates peaked at a few per cent of the Eddington limit. In this regime, the Eddington ratio distribution is independent of the mass of the black hole and shows little dependence on the central stellar population of the galaxy. The second regime is associated with galaxies with old central stellar populations (M*/SFR >> a Hubble time), and is characterized by a power-law distribution function of Eddington ratios. In this regime, the time-averaged mass accretion rate on to black holes is proportional to the mass of stars in the galaxy bulge, with a constant of proportionality that depends on the mean stellar age of the stars. This result is once again independent of black hole mass. We show that both the slope of the power law and the decrease in the accretion rate on to black holes in old galaxies are consistent with population synthesis model predictions of the decline in stellar mass loss rates as a function of mean stellar age. Our results lead to a very simple picture of black hole growth in the local Universe. If the supply of cold gas in a galaxy bulge is plentiful, the black hole regulates its own growth at a rate that does not further depend on the properties of the interstellar medium. Once the gas runs out, black hole growth is regulated by the rate at which evolved stars lose their mass.

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

Science.gov (United States)

Haricharan, Svasti; Brown, Powel

2015-06-23

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

Science.gov (United States)

Beger, Hans G; Schwarz, Michael; Poch, Bertram

2012-11-01

Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

MHC class II molecules regulate growth in human T cells

DEFF Research Database (Denmark)

Nielsen, M; Odum, Niels; Bendtzen, K

1994-01-01

MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

Interactive Role of Fungicides and Plant Growth Regulator (Trinexapac on Seed Yield and Oil Quality of Winter Rapeseed

Directory of Open Access Journals (Sweden)

Muhammad Ijaz

2015-09-01

Full Text Available This study was designed to evaluate the role of growth regulator trinexapac and fungicides on growth, yield, and quality of winter rapeseed (Brassica napus L.. The experiment was conducted simultaneously at different locations in Germany using two cultivars of rapeseed. Five different fungicides belonging to the triazole and strobilurin groups, as well as a growth regulator trinexapac, were tested in this study. A total of seven combinations of these fungicides and growth regulator trinexapac were applied at two growth stages of rapeseed. These two stages include green floral bud stage (BBCH 53 and the course of pod development stage (BBCH 65. The results showed that plant height and leaf area index were affected significantly by the application of fungicides. Treatments exhibited induced photosynthetic ability and delayed senescence, which improved the morphological characters and yield components of rape plants at both locations. Triazole, in combination with strobilurin, led to the highest seed yield over other treatments at both experimental locations. Significant effects of fungicides on unsaturated fatty acids of rapeseed oil were observed. Fungicides did not cause any apparent variation in the values of free fatty acids and peroxide of rapeseed oil. Results of our study demonstrate that judicious use of fungicides in rapeseed may help to achieve sustainable farming to obtain higher yield and better quality of rapeseed.

Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention; Neoplasien des Temporomandibulargelenks (TMG). Diagnostik, Differenzialdiagnostik und Intervention

Energy Technology Data Exchange (ETDEWEB)

Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Maeurer, J. [Radiologische Praxis am Prinzregentenplatz, Muenchen (Germany)

2001-09-01

Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [German] Zielsetzung. Vorstellung der Wertigkeit bildgebender Verfahren fuer die diagnostische und interventionelle Radiologie des Temporomandibulargelenks (TMG). Material und Methodik. Die moderne Radiologie des TMG basiert auf dem Einsatz der konventionellen Roentgendiagnostik, der Computertomographie (CT) und der Magnetresonanztomographie (MRT), sowie interventioneller Verfahren wie der Biopsie, vaskulaerer Embolisationsverfahren und tumorablativer Verfahren. Ergebnisse. Als Basisdiagnostik dient die konventionelle Diagnostik in offener und geschlossener Mundposition der Erfassung von Funktionsstoerungen sowie ossaerer Destruktionen. Die CT erweitert das diagnostische Spektrum und verbessert die Differenzialdiagnostik fuer ossifizierende Prozesse. Der Einsatz der MRT erlaubt die Erfassung der Weichteilinfiltration sowie der Gelenkstrukturen. Vaskulaere interventionelle Verfahren dienen der praetherapeutischen Okklusion bzw. der palliativen Tumortherapie in Form der okklusiven Embolisation, der Chemoembolisation, oder auch der Tumorablation. (orig.)

Dicer-like Proteins Regulate the Growth, Conidiation, and Pathogenicity of Colletotrichum gloeosporioides from Hevea brasiliensis

Directory of Open Access Journals (Sweden)

Qiannan Wang

2018-01-01

Full Text Available Colletotrichum gloeosporioides from Hevea brasiliensis is the hemibiotrophic fungi which could cause anthracnose in rubber trees. Dicer like proteins (DCL were the core enzymes for generation of small RNAs. In the present study, the knocking-out mutants of two dicer like proteins encoding genes of C. gloeosporioides were constructed; and functions of two proteins were investigated. The results showed that DCL play important roles in regulating the growth, conidiation and pathogenicity of C. gloeosporioides; and there is a functional redundancy between DCL1 and DCL2. Microscopy analysis and DAB staining revealed that loss of penetration ability into the host cells, instead of the decreased growth rate, was the main cause for the impaired pathogenicity of the ΔDcl1ΔDcl2 double mutant. Proteomics analysis suggested that DCL proteins affected the expression of functional proteins to regulating multiple biological processes of C. gloeosporioides. These data lead to a better understanding of the functions of DCL proteins in regulating the development and pathogenesis of C. gloeosporioides.

From Normalcy to Neoplasia. The Role of Epithelial-Stromal Interactions in Regulating Mammary Growth and Differentiation

Science.gov (United States)

2000-08-01

stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J. Mammary Gland Biol. Neoplasia 2, 393-402. Debatin...Birkedal-Hansen (1999) MT1-MMP- deficient mice develop dwarfism , osteopenia, arthritis, and connective tissue disease due to inadequate collagen...al., 1988). Ligands of the epidermal growth hormonally regulated ductal development during puberty and factor receptor (EGFR) are believed to be

N-methylhemeanthidine chloride, a novel Amaryllidaceae alkaloid, inhibits pancreatic cancer cell proliferation via down-regulating AKT activation

Energy Technology Data Exchange (ETDEWEB)

Guo, Guoli; Yao, Guangmin; Zhan, Guanqun; Hu, Yufeng [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China); Yue, Ming [Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Cheng, Ling; Liu, Yaping; Ye, Qi [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China); Qing, Guoliang [Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Zhang, Yonghui, E-mail: zhangyh@mails.tjmu.edu.cn [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei PR China (China)

2014-11-01

We previously reported the isolation of a novel Amaryllidaceae alkaloid, N-methylhemeanthidine chloride (NMHC), from Zephyranthes candida, which exhibits potent cytotoxicity in a spectrum of tumor cells. However, the mechanism of action remains unclear. Using multiple cell lines derived from human pancreatic cancer, one of the most mortal and refractory human malignancies, we further studied the NMHC-mediated cytotoxicity and found that it induced drastic cytotoxicity in pancreatic cancer cells whereas an insignificant effect on a noncancerous cell line. The NMHC-mediated growth inhibition was more severe than the first-line chemotherapeutic agent gemcitabine, leading to cell cycle arrest, apoptotic death and decreased glycolysis. NMHC exerted its function through down-regulating AKT activation, and the ectopic expression of activated AKT rescued the growth inhibition. Consistently, NMHC injections in a pancreatic cancer xenograft model manifested the anti-tumor effect in vivo. Engrafted tumor cells underwent AKT attenuation and apoptotic death upon treatments. As such, we here demonstrate the AKT inhibition may be one of the mechanisms by which NMHC decreases tumor cell survival rate in vitro and in vivo. Our data thereby suggest that NMHC holds great promise as a potent chemotherapeutic agent against pancreatic cancer and sheds new light on obtaining such agents from natural products toward therapeutic purposes. - Highlights: • N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid. • NMHC exhibits potent anti-neoplastic activity. • NMHC leads to cell cycle arrest, apoptotic death and decreased metabolism. • NMHC down-regulates the AKT signaling pathway.

Effect of Plant Growth Regulators on Leaf Number, Leaf Area and Leaf Dry Matter in Grape

Directory of Open Access Journals (Sweden)

Zahoor Ahmad BHAT

2011-03-01

Full Text Available Influence of phenylureas (CPPU and brassinosteriod (BR along with GA (gibberellic acid were studied on seedless grape vegetative characteristics like leaf number, leaf area and leaf dry matter. Growth regulators were sprayed on the vines either once (7 days after fruit set or 15 days after fruit set or twice (7+15 days after fruit set. CPPU 2 ppm+BR 0.4 ppm+GA 25 ppm produced maximum number of leaves (18.78 while as untreated vines produced least leaf number (16.22 per shoot. Maximum leaf area (129.70 cm2 and dry matter content (26.51% was obtained with higher CPPU (3 ppm and BR (0.4 ppm combination along with GA 25 ppm. Plant growth regulators whether naturally derived or synthetic are used to improve the productivity and quality of grapes. The relatively high value of grapes justifies more expensive inputs. A relatively small improvement in yield or fruit quality can justify the field application of a very costly product. Application of new generation growth regulators like brassinosteroids and phenylureas like CPPU have been reported to increase the leaf number as well as leaf area and dry matter thereby indirectly influencing the fruit yield and quality in grapes.

Graphene quantum dots as enhanced plant growth regulators: effects on coriander and garlic plants.

Science.gov (United States)

Chakravarty, Disha; Erande, Manisha B; Late, Dattatray J

2015-10-01

We report investigations on the use of graphene quantum dots for growth enhancement in coriander (Coriandrum sativam L.) and garlic (Allium sativum) plants. The as-received seeds of coriander and garlic were treated with 0.2 mg mL(-1) of graphene quantum dots for 3 h before planting. Graphene quantum dots enhanced the growth rate in coriander and garlic plants, including leaves, roots, shoots, flowers and fruits, when the seeds were treated with graphene quantum dots. Our investigations open up the opportunity to use graphene quantum dots as plant growth regulators that can be used in a variety of other food plants for high yield. © 2015 Society of Chemical Industry.

Cytokinins as key regulators in plant–microbe–insect interactions: connecting plant growth and defence

NARCIS (Netherlands)

Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

2013-01-01

1. Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. 2. Plants are known to rapidly respond to pathogen and herbivore

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).

Science.gov (United States)

Wolfe, Andrew; Divall, Sara; Wu, Sheng

2014-10-01

The mammalian reproductive hormone axis regulates gonadal steroid hormone levels and gonadal function essential for reproduction. The neuroendocrine control of the axis integrates signals from a wide array of inputs. The regulatory pathways important for mediating these inputs have been the subject of numerous studies. One class of proteins that have been shown to mediate metabolic and growth signals to the CNS includes Insulin and IGF-1. These proteins are structurally related and can exert endocrine and growth factor like action via related receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction has been studied extensively. This review summarizes the in vitro and in vivo models that have been used to study these neuroendocrine structures and the influence of these growth factors on neuroendocrine control of reproduction. Copyright © 2014 Elsevier Inc. All rights reserved.

Abscisic acid regulates root growth under osmotic stress conditions via an interacting hormonal network with cytokinin, ethylene and auxin.

Science.gov (United States)

Rowe, James H; Topping, Jennifer F; Liu, Junli; Lindsey, Keith

2016-07-01

Understanding the mechanisms regulating root development under drought conditions is an important question for plant biology and world agriculture. We examine the effect of osmotic stress on abscisic acid (ABA), cytokinin and ethylene responses and how they mediate auxin transport, distribution and root growth through effects on PIN proteins. We integrate experimental data to construct hormonal crosstalk networks to formulate a systems view of root growth regulation by multiple hormones. Experimental analysis shows: that ABA-dependent and ABA-independent stress responses increase under osmotic stress, but cytokinin responses are only slightly reduced; inhibition of root growth under osmotic stress does not require ethylene signalling, but auxin can rescue root growth and meristem size; osmotic stress modulates auxin transporter levels and localization, reducing root auxin concentrations; PIN1 levels are reduced under stress in an ABA-dependent manner, overriding ethylene effects; and the interplay among ABA, ethylene, cytokinin and auxin is tissue-specific, as evidenced by differential responses of PIN1 and PIN2 to osmotic stress. Combining experimental analysis with network construction reveals that ABA regulates root growth under osmotic stress conditions via an interacting hormonal network with cytokinin, ethylene and auxin. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Vegetative growth response of cotton plants due to growth regulator supply via seeds

Directory of Open Access Journals (Sweden)

João Vitor Ferrari

2015-08-01

Full Text Available The global cotton industry is distinguished by its numerous industrial uses of the plume as well as by high production costs. Excessive vegetative growth can interfere negatively with productivity, and thus, applying growth regulators is essential for the development of the cotton culture. The objective of this study was to evaluate the development and yield of the cotton cultivar FMT 701 with the application of mepiquat chloride to seeds and leaves. The experimental design used a randomized block design with four replications, arranged in bands.The treatments consisted of mepiquat chloride rates (MC (0, 4, 6, 8 and 10 g a.i. kg-1 of seeds applied directly to the cotton seeds and MC management by foliar spray using a 250 mL ha-1 rates that was administered under the following conditions: divided into four applications (35, 45, 55 and 65 days after emergence; as a single application at 70 days; and without the application of the product. The mepiquat chloride applied to cotton seeds controls the initial plant height and stem diameter, while foliar application reduces the height of the plants. After application to seed, foliar spraying MC promotes increase mass of 20 bolls, however no direct influence amount bolls per plant and yield of cotton seed. Higher cotton seed yield was obtained with a rate of 3.4 g a.i. MC kg-1 seeds.

Fibroblast Growth Factor Signaling in Metabolic Regulation.

Science.gov (United States)

Nies, Vera J M; Sancar, Gencer; Liu, Weilin; van Zutphen, Tim; Struik, Dicky; Yu, Ruth T; Atkins, Annette R; Evans, Ronald M; Jonker, Johan W; Downes, Michael Robert

2015-01-01

The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.

Fibroblast growth factor signaling in metabolic regulation

Directory of Open Access Journals (Sweden)

Vera eNies

2016-01-01

Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

A Multilevel Latent Growth Modelling of the Longitudinal Changes in Motivation Regulations in Physical Education

Directory of Open Access Journals (Sweden)

Timo Jaakkola

2015-03-01

Full Text Available The purpose of this study was to examine individual- and classroom-level differences in the longitudinal change in motivational regulations during physical education students’ transition from elementary (Grade 6 across middle school (Grades 7 to 9. A sample of 757 Finnish adolescents (M = 12.71, SD = 0.23 participated in this study. Participants of the study responded to questionnaires collected six times. A multilevel latent growth modelling approach was used to analyze the data. Results showed that motivational regulations in physical education developed at different rates during middle school. More specifically, students’: (a identified regulation increased across Grades 6 to 9; (b amotivation increased during middle school transition from Grade 6 to 7; and (c introjected regulation declined from Grade 8 to 9. Other motivational regulations remained stable across time. The changes in amotivation and introjected regulation were largely due to individual factors, whereas the changes in identified regulation were due to environmental factors.

Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer

Science.gov (United States)

2008-10-01

fibroblast growth factor signaling is down-regulated in prostate cancer. Kwabi-Addo B (2004) Orlando, FL (Oral; mini symposium). • AACR/NCI/EORTC...contains a classic signal peptide PP FRS2 Sos Grb2 Cbl Ras FGFR1-DN MEK ERK STAT3 STAT3 Sprouty PLC - Extracellular stimulus Nucleus P Raf PI3K Receptor... thesis system for reverse transcription-PCR and according to the manufactur- er’s protocol. Real-time PCR was carried out in a Bio-Rad iCycler real

Molecular regulation of aluminum resistance and sulfur nutrition during root growth.

Science.gov (United States)

Alarcón-Poblete, Edith; Inostroza-Blancheteau, Claudio; Alberdi, Miren; Rengel, Zed; Reyes-Díaz, Marjorie

2018-01-01

Aluminum toxicity and sulfate deprivation both regulate microRNA395 expression, repressing its low-affinity sulfate transporter ( SULTR2;1 ) target. Sulfate deprivation also induces the high-affinity sulfate transporter gene ( SULTR12 ), allowing enhanced sulfate uptake. Few studies about the relationships between sulfate, a plant nutrient, and aluminum, a toxic ion, are available; hence, the molecular and physiological processes underpinning this interaction are poorly understood. The Al-sulfate interaction occurs in acidic soils, whereby relatively high concentrations of trivalent toxic aluminum (Al 3+ ) may hamper root growth, limiting uptake of nutrients, including sulfur (S). On the other side, Al 3+ may be detoxified by complexation with sulfate in the acid soil solution as well as in the root-cell vacuoles. In this review, we focus on recent insights into the mechanisms governing plant responses to Al toxicity and its relationship with sulfur nutrition, emphasizing the role of phytohormones, microRNAs, and ion transporters in higher plants. It is known that Al 3+ disturbs gene expression and enzymes involved in biosynthesis of S-containing cysteine in root cells. On the other hand, Al 3+ may induce ethylene biosynthesis, enhance reactive oxygen species production, alter phytohormone transport, trigger root growth inhibition and promote sulfate uptake under S deficiency. MicroRNA395, regulated by both Al toxicity and sulfate deprivation, represses its low-affinity Sulfate Transporter 2;1 (SULTR2;1) target. In addition, sulfate deprivation induces High Affinity Sulfate Transporters (HAST; SULTR1;2), improving sulfate uptake from low-sulfate soil solutions. Identification of new microRNAs and cloning of their target genes are necessary for a better understanding of the role of molecular regulation of plant resistance to Al stress and sulfate deprivation.

Toward epigenetic and gene regulation models of specific language impairment: looking for links among growth, genes, and impairments

Directory of Open Access Journals (Sweden)

Rice Mabel L

2012-11-01

Full Text Available Abstract Children with specific language impairment (SLI are thought to have an inherited form of language impairment that spares other developmental domains. SLI shows strong heritability and recent linkage and association studies have replicated results for candidate genes. Regulatory regions of the genes may be involved. Behavioral growth models of language development of children with SLI reveal that the onset of language is delayed, and the growth trajectories of children with SLI parallel those of younger children without SLI. The rate of language acquisition decelerates in the pre-adolescent period, resulting in immature language levels for the children with SLI that persist into adolescence and beyond. Recent genetic and epigenetic discoveries and models relevant to language impairment are reviewed. T cell regulation of onset, acceleration, and deceleration signaling are described as potential conceptual parallels to the growth timing elements of language acquisition and impairment. A growth signaling disruption (GSD hypothesis is proposed for SLI, which posits that faulty timing mechanisms at the cellular level, intrinsic to neurocortical functioning essential for language onset and growth regulation, are at the core of the growth outcomes of SLI. The GSD highlights the need to document and account for growth patterns over childhood and suggests needed directions for future investigation.

Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by μ-XRF

International Nuclear Information System (INIS)

Silva, M.P.; Oliveira, M.A.; Poletti, M.E.

2012-01-01

Full text: Some trace elements, naturally present in breast tissues, participate in a large number of biological processes, which include among others, activation or inhibition of enzymatic reactions and changes on cell membranes permeability, suggesting that these elements may influence carcinogenic processes. Thus, knowledge of the amounts of these elements and their spatial distribution in normal and neoplastic tissues may help in understanding the role of these elements in the carcinogenic process and tumor progression of breast cancers. Concentrations of trace elements like Ca, Fe, Cu and Zn, previously studied at LNLS using TXRF and conventional XRF, were elevated in neoplastic breast tissues compared to normal tissues. In this study we determined the spatial distribution of these elements in normal and neoplastic breast tissues using μ-XRF technique. We analyzed 22 samples of normal and neoplastic breast tissues (malignant and benign) obtained from paraffin blocks available for study at the Department of Pathology HC-FMRP/USP. From the blocks, a small fraction of material was removed and subjected to histological sections of 60 μm thick made with a microtome. The slices where placed in holder samples and covered with ultralen film. Tissue samples were irradiated with a white beam of synchrotron radiation. The samples were positioned at 45 degrees with respect to the incident beam on a table with 3 freedom degrees (x, y and z), allowing independent positioning of the sample in these directions. The white beam was collimated by a 20 μm microcapillary and samples were fully scanned. At each step, a spectrum was detected for 10 s. The fluorescence emitted by elements present in the sample was detected by a Si (Li) detector with 165 eV at 5.9 keV energy resolution, placed at 90 deg with respect to the incident beam. Results reveal that trace elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman

The Essential Role of Mbd5 in the Regulation of Somatic Growth and Glucose Homeostasis in Mice

Science.gov (United States)

Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

2012-01-01

Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis. PMID:23077600

Effect of two plant growth regulators and illumination conditions in the germination of conserved seeds of Clitoria ternatea

Directory of Open Access Journals (Sweden)

Maribel Quintana

2013-04-01

Full Text Available The seeds viability lost in the seed legume bank of Research Institute of Pastures and Forages (IIPF led to the aim of the work it was to determine the effect of two plant growth regulators (gibberellic acid; GA3 and naphthalene acetic acid; ANA and illumination conditions on the germination of Clitoria ternatea SC-136 conserved seeds. One experiment was performed with two-factor completely randomized design with four replications Five different levels of growth regulators (factor A and two illumination conditions (factor B were evaluated. The variables measured were: total germination percentage (PTG and angular transformation, days to 50% PTG (G50 and the days between 10 and 90% PTG (G10-90. In addition, morphological variables were evaluated. It was found that the addition of plant growth regulators (GA3 and NAA was effective in increasing germination of Clitoria ternatea SC-136 conserved seeds, but not the illumination conditions tested. Combination GA3 (1 mg l-1 and NAA (0.1 mg l-1 to stimulate germination was recommended. Key words: GA3, germplasm, legume, NAA, photoperiod.

Mechanisms of radiation-induced neoplastic cell transformation

Energy Technology Data Exchange (ETDEWEB)

Yang, T.C.H.; Tobias, C.A.

1984-04-01

Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

Mechanisms of radiation-induced neoplastic cell transformation

International Nuclear Information System (INIS)

Yang, T.C.H.; Tobias, C.A.

1984-04-01

Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

Science.gov (United States)

Douglas, Lois M; Wang, Hong X; Konopka, James B

2013-11-26

Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

Directory of Open Access Journals (Sweden)

Leandro eFernandez-Perez

2013-06-01

Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

Money Laundering, Corruption and Growth: An Empirical Rationale for a Global Convergence on Anti-Money Laundering Regulation

OpenAIRE

Cavalcante Veiga, Luiz Humberto; Andrade, Joaquim Pinto

2006-01-01

This paper provides empirical evidence on the impact of anti-money laundering regulations on growth and, it examines the rationale for a global adoption of these rules. The empirical results have led us to confirm a positive relation between low corruption levels and high investment and growth. We approached the impact on growth of money laundering prevention (MLP) initiatives in two ways: first, by verifying that the existence of these initiatives affects the perception of corruption. Second...

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth.

Science.gov (United States)

Carabetta, Valerie J; Greco, Todd M; Tanner, Andrew W; Cristea, Ileana M; Dubnau, David

2016-05-01

N ε -Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. The past decade highlighted N ε -lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis . To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell

A multilevel latent growth modelling of the longitudinal changes in motivation regulations in physical education.

Science.gov (United States)

Jaakkola, Timo; Wang, John; Yli-Piipari, Sami; Liukkonen, Jarmo

2015-03-01

The purpose of this study was to examine individual- and classroom-level differences in the longitudinal change in motivational regulations during physical education students' transition from elementary (Grade 6) across middle school (Grades 7 to 9). A sample of 757 Finnish adolescents (M = 12.71, SD = 0.23) participated in this study. Participants of the study responded to questionnaires collected six times. A multilevel latent growth modelling approach was used to analyze the data. Results showed that motivational regulations in physical education developed at different rates during middle school. More specifically, students': (a) identified regulation increased across Grades 6 to 9; (b) amotivation increased during middle school transition from Grade 6 to 7; and (c) introjected regulation declined from Grade 8 to 9. Other motivational regulations remained stable across time. The changes in amotivation and introjected regulation were largely due to individual factors, whereas the changes in identified regulation were due to environmental factors. Key pointsStudents' identified regulation increased across Grades 6 to 9.Students' amotivation increased across middle school transition from Grade 6 to 7.Students' introjected regulation declined from Grade 8 to 9.Other motivational regulations remained stable across time.

Flow-Regulated Growth of Titanium Dioxide (TiO2 ) Nanotubes in Microfluidics.

Science.gov (United States)

Fan, Rong; Chen, Xinye; Wang, Zihao; Custer, David; Wan, Jiandi

2017-08-01

Electrochemical anodization of titanium (Ti) in a static, bulk condition is used widely to fabricate self-organized TiO 2 nanotube arrays. Such bulk approaches, however, require extended anodization times to obtain long TiO 2 nanotubes and produce only vertically aligned nanotubes. To date, it remains challenging to develop effective strategies to grow long TiO 2 nanotubes in a short period of time, and to control the nanotube orientation. Here, it is shown that the anodic growth of TiO 2 nanotubes is significantly enhanced (≈16-20 times faster) under flow conditions in microfluidics. Flow not only controls the diameter, length, and crystal orientations of TiO 2 nanotubes, but also regulates the spatial distribution of nanotubes inside microfluidic devices. Strikingly, when a Ti thin film is deposited on silicon substrates and anodized in microfluidics, both vertically and horizontally aligned (relative to the bottom substrate) TiO 2 nanotubes can be produced. The results demonstrate previously unidentified roles of flow in the regulation of growth of TiO 2 nanotubes, and provide powerful approaches to effectively grow long, oriented TiO 2 nanotubes, and construct hierarchical TiO 2 nanotube arrays on silicon-based materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Density regulation in Northeast Atlantic fish populations: Density dependence is stronger in recruitment than in somatic growth.

Science.gov (United States)

Zimmermann, Fabian; Ricard, Daniel; Heino, Mikko

2018-05-01

Population regulation is a central concept in ecology, yet in many cases its presence and the underlying mechanisms are difficult to demonstrate. The current paradigm maintains that marine fish populations are predominantly regulated by density-dependent recruitment. While it is known that density-dependent somatic growth can be present too, its general importance remains unknown and most practical applications neglect it. This study aimed to close this gap by for the first time quantifying and comparing density dependence in growth and recruitment over a large set of fish populations. We fitted density-dependent models to time-series data on population size, recruitment and age-specific weight from commercially exploited fish populations in the Northeast Atlantic Ocean and the Baltic Sea. Data were standardized to enable a direct comparison within and among populations, and estimated parameters were used to quantify the impact of density regulation on population biomass. Statistically significant density dependence in recruitment was detected in a large proportion of populations (70%), whereas for density dependence in somatic growth the prevalence of density dependence depended heavily on the method (26% and 69%). Despite age-dependent variability, the density dependence in recruitment was consistently stronger among age groups and between alternative approaches that use weight-at-age or weight increments to assess growth. Estimates of density-dependent reduction in biomass underlined these results: 97% of populations with statistically significant parameters for growth and recruitment showed a larger impact of density-dependent recruitment on population biomass. The results reaffirm the importance of density-dependent recruitment in marine fishes, yet they also show that density dependence in somatic growth is not uncommon. Furthermore, the results are important from an applied perspective because density dependence in somatic growth affects productivity and

Capture of microRNA-bound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling.

Directory of Open Access Journals (Sweden)

Ashish Lal

2011-11-01

Full Text Available A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2 as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4. Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.

Capture of microRNA-bound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling.

Science.gov (United States)

Lal, Ashish; Thomas, Marshall P; Altschuler, Gabriel; Navarro, Francisco; O'Day, Elizabeth; Li, Xiao Ling; Concepcion, Carla; Han, Yoon-Chi; Thiery, Jerome; Rajani, Danielle K; Deutsch, Aaron; Hofmann, Oliver; Ventura, Andrea; Hide, Winston; Lieberman, Judy

2011-11-01

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.

Capture of MicroRNA–Bound mRNAs Identifies the Tumor Suppressor miR-34a as a Regulator of Growth Factor Signaling

Science.gov (United States)

O'Day, Elizabeth; Li, Xiao Ling; Concepcion, Carla; Han, Yoon-Chi; Thiery, Jerome; Rajani, Danielle K.; Deutsch, Aaron; Hofmann, Oliver; Ventura, Andrea; Hide, Winston; Lieberman, Judy

2011-01-01

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ∼90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a–regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division. PMID:22102825

Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

International Nuclear Information System (INIS)

Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

1986-01-01

The specific binding of iodinated epidermal growth factor ([ 125 I]iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites [dissociation constant (Kd) = 0.7-1.8 nM]. Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status

Nutritive values of brassica campestris L. oil as affected by growth regulator treatments

International Nuclear Information System (INIS)

Bano, A.; Khan, N.

2009-01-01

The effects of plant growth regulators, viz. Indole acetic acid (IAA), Gibberellic acid (GA) and Abscisic acid (ABA) were studied on fatty acid compositions, glucosinolate content and protein content of Brassica campestris L subsp. Oleifera (common name yellow sarson). Growth regulators were applied in seed soaking solution as well as foliar spray during vegetative phase and at flowering stage. There were reductions in the amount of long chain fatty acids viz erucic acid, eicosenoic acid and increase in the amount of unsaturated fatty acid viz. linoleic acid by lAA applications. The stimulating effect of lAA which reduced amount of unsaturated fatty acid was more pronounced when applied as foliar spray at vegetative stage. But, foliar spray of ABA during flowering increased the concentration of linoleic acid and reduced the eicosenoic acid and erucic acid. The glucosinolate content was greater in seeds soaked in 10/sup -5/ M lAA than that of control but less in 10/sup -5/ M GA treated seeds than that of control. The ABA treatment (10/sup -5/M) increased the concentration of glucosinolates in the seeds IAA treatments (10/sup -5/M) increased the protein percentage in the seeds. Foliar application of GA (10/sup -5/M) during vegetative growth and ABA (10/sup -5/M) as seed soaking prior to sowing as well as foliar spry during flowering decreased the protein content of seeds. (author)

Effects of sex steroids on expression of genes regulating growth-related mechanisms in rainbow trout (Oncorhynchus mykiss).

Science.gov (United States)

Cleveland, Beth M; Weber, Gregory M

2015-05-15

Effects of a single injection of 17β-estradiol (E2), testosterone (T), or 5β-dihydrotestosterone (DHT) on expression of genes central to the growth hormone (GH)/insulin-like growth factor (IGF) axis, muscle-regulatory factors, transforming growth factor-beta (TGFβ) superfamily signaling cascade, and estrogen receptors were determined in rainbow trout (Oncorhynchus mykiss) liver and white muscle tissue. In liver in addition to regulating GH sensitivity and IGF production, sex steroids also affected expression of IGF binding proteins, as E2, T, and DHT increased expression of igfbp2b and E2 also increased expression of igfbp2 and igfbp4. Regulation of this system also occurred in white muscle in which E2 increased expression of igf1, igf2, and igfbp5b1, suggesting anabolic capacity may be maintained in white muscle in the presence of E2. In contrast, DHT decreased expression of igfbp5b1. DHT and T decreased expression of myogenin, while other muscle regulatory factors were either not affected or responded similarly for all steroid treatments. Genes within the TGFβ superfamily signaling cascade responded to steroid treatment in both liver and muscle, suggesting a regulatory role for sex steroids in the ability to transmit signals initiated by TGFβ superfamily ligands, with a greater number of genes responding in liver than in muscle. Estrogen receptors were also regulated by sex steroids, with era1 expression increasing for all treatments in muscle, but only E2- and T-treatment in liver. E2 reduced expression of erb2 in liver. Collectively, these data identify how physiological mechanisms are regulated by sex steroids in a manner that promotes the disparate effects of androgens and estrogens on growth in salmonids. Published by Elsevier Inc.

The yeast Sks1p kinase signaling network regulates pseudohyphal growth and glucose response.

Directory of Open Access Journals (Sweden)

Cole Johnson

2014-03-01

Full Text Available The yeast Saccharomyces cerevisiae undergoes a dramatic growth transition from its unicellular form to a filamentous state, marked by the formation of pseudohyphal filaments of elongated and connected cells. Yeast pseudohyphal growth is regulated by signaling pathways responsive to reductions in the availability of nitrogen and glucose, but the molecular link between pseudohyphal filamentation and glucose signaling is not fully understood. Here, we identify the glucose-responsive Sks1p kinase as a signaling protein required for pseudohyphal growth induced by nitrogen limitation and coupled nitrogen/glucose limitation. To identify the Sks1p signaling network, we applied mass spectrometry-based quantitative phosphoproteomics, profiling over 900 phosphosites for phosphorylation changes dependent upon Sks1p kinase activity. From this analysis, we report a set of novel phosphorylation sites and highlight Sks1p-dependent phosphorylation in Bud6p, Itr1p, Lrg1p, Npr3p, and Pda1p. In particular, we analyzed the Y309 and S313 phosphosites in the pyruvate dehydrogenase subunit Pda1p; these residues are required for pseudohyphal growth, and Y309A mutants exhibit phenotypes indicative of impaired aerobic respiration and decreased mitochondrial number. Epistasis studies place SKS1 downstream of the G-protein coupled receptor GPR1 and the G-protein RAS2 but upstream of or at the level of cAMP-dependent PKA. The pseudohyphal growth and glucose signaling transcription factors Flo8p, Mss11p, and Rgt1p are required to achieve wild-type SKS1 transcript levels. SKS1 is conserved, and deletion of the SKS1 ortholog SHA3 in the pathogenic fungus Candida albicans results in abnormal colony morphology. Collectively, these results identify Sks1p as an important regulator of filamentation and glucose signaling, with additional relevance towards understanding stress-responsive signaling in C. albicans.

Growth regulation of HeLa cells by 1060 nm photons

International Nuclear Information System (INIS)

Torghele, K. F.

1993-12-01

Living organisms are open systems dominated by electromagnetic interaction. An essential feature of a living system is its cybernetic process which imply their capability of adaptation and sensitivity to internal and external fluctuations. The experimental results show that coherent and incoherent light of 1060 nm wavelength influences the metabolic processes and consequently the proliferation of cancer cell cultures (HeLa). Light induced regulation of HeLa cell growth depends on the cell density, the state of the cell culture and the amount of light irradiation. Best proliferation inhibiting effects can be obtained by application of 200 J/m 2 on HeLa cells in Lag-Phase and a typical cell density of 5.10 4 cells/cm 2 . Proceeding on the singlet oxygen hypothesis (KLIMA, H. et al.; 1990), it is shown mathematically that the dynamical behaviour of the NADH model is influenced by 1060 nm photons. Both, the experimental and the numerical results support our hypothesis: 1060 nm photons regulate the proliferation of HeLa cells. (author)

Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells.

Science.gov (United States)

Inaba, Nobuharu; Ishizawa, Sho; Kimura, Masaki; Fujioka, Kouki; Watanabe, Michiko; Shibasaki, Toshiaki; Manome, Yoshinobu

2010-09-01

Malignant glioma is one of the most intractable diseases in the human body. Rho-kinase (ROCK) is overexpressed and has been proposed as the main cause for the refractoriness of the disease. Since efficacious treatment is required, this study investigated the effect of inhibition of ROCK isoforms. The short hairpin RNA transcription vector was transfected into the RT2 rat glioma cell line and the characteristics of the cells were investigated. The effect of nimustine hydrochloride (ACNU) anti-neoplastic agent on cells was also measured. Inhibition of ROCK isoforms did not alter cell growth. Cell cycle analysis revealed that ROCK1 down-regulation reduced the G(0) phase population and ROCK2 down-regulation reduced the G(2)/M phase population. When ROCK1-down-regulated cells were exposed to ACNU, they demonstrated susceptibility to the agent. The roles of ROCK1 and ROCK2 may be different in glioma cells. Furthermore, the combination of ROCK1 down-regulation and an anti-neoplastic agent may be useful for the therapy of malignant glioma.

Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.

Directory of Open Access Journals (Sweden)

Jingshan Zhao

Full Text Available The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL, a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF signaling and angiogenesis in endothelial cells (ECs. We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.

LeMYC2 acts as a negative regulator of blue light mediated photomorphogenic growth, and promotes the growth of adult tomato plants

Science.gov (United States)

2014-01-01

Background Arabidopsis ZBF1/MYC2bHLH transcription factor is a repressor of photomorphogenesis, and acts as a point of cross talk in light, abscisic acid (ABA) and jasmonic acid (JA) signaling pathways. MYC2 also functions as a positive regulator of lateral root development and flowering time under long day conditions. However, the function of MYC2 in growth and development remains unknown in crop plants. Results Here, we report the functional analyses of LeMYC2 in tomato (Lycopersicon esculentum). The amino acid sequence of LeMYC2 showed extensive homology with Arabidopsis MYC2, containing the conserved bHLH domain. To study the function of LeMYC2 in tomato, overexpression and RNA interference (RNAi) LeMYC2 tomato transgenic plants were generated. Examination of seedling morphology, physiological responses and light regulated gene expression has revealed that LeMYC2 works as a negative regulator of blue light mediated photomorphogenesis. Furthermore, LeMYC2 specifically binds to the G-box of LeRBCS-3A promoter. Overexpression of LeMYC2 has led to increased root length with more number of lateral roots. The tomato plants overexpressing LeMYC2 have reduced internode distance with more branches, and display the opposite morphology to RNAi transgenic lines. Furthermore, this study shows that LeMYC2 promotes ABA and JA responsiveness. Conclusions Collectively, this study highlights that working in light, ABA and JA signaling pathways LeMYC2 works as an important regulator for growth and development in tomato plants. PMID:24483714

Temperature dependence of 1H NMR relaxation time, T2, for intact and neoplastic plant tissues

Science.gov (United States)

Lewa, Czesław J.; Lewa, Maria

Temperature dependences of the spin-spin proton relaxation time, T2, have been shown for normal and tumorous tissues collected from kalus culture Nicotiana tabacum and from the plant Kalanchoe daigremontiana. For neoplastic plant tissues, time T2 was increased compared to that for intact plants, a finding similar to that for animal and human tissues. The temperature dependences obtained were compared to analogous relations observed with animal tissues.

Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI.

Science.gov (United States)

Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P

2013-11-01

The purpose of this study was to assess the correlation between standardized uptake value (SUV) and apparent diffusion coefficient (ADC) of neoplastic lesions in the use of a simultaneous PET/MRI hybrid system. Twenty-four patients with known primary malignancies underwent FDG PET/CT. They then underwent whole-body PET/MRI. Diffusion-weighted imaging was performed with free breathing and a single-shot spin-echo echo-planar imaging sequence with b values of 0, 350, and 750 s/mm(2). Regions of interest were manually drawn along the contours of neoplastic lesions larger than 1 cm, which were clearly identified on PET and diffusion-weighted images. Maximum SUV (SUVmax) on PET/MRI and PET/CT images, mean SUV (SUVmean), minimum ADC (ADCmin), and mean ADC (ADCmean) were recorded on PET/MR images for each FDG-avid neoplastic soft-tissue lesion with a maximum of three lesions per patient. Pearson correlation coefficient was used to asses the following relations: SUVmax versus ADCmin on PET/MR and PET/CT images, SUVmean versus ADCmean, and ratio of SUVmax to mean liver SUV (SUV ratio) versus ADCmin. A subanalysis of patients with progressive disease versus partial treatment response was performed with the ratio of SUVmax to ADCmin for the most metabolically active lesion. Sixty-nine neoplastic lesions (52 nonosseous lesions, 17 bone metastatic lesions) were evaluated. The mean SUVmax from PET/MRI was 7.0 ± 6.0; SUVmean, 5.6 ± 4.6; mean ADCmin, 1.10 ± 0.58; and mean ADCmean, 1.48 ± 0.72. A significant inverse Pearson correlation coefficient was found between PET/MRI SUVmax and ADCmin (r = -0.21, p = 0.04), between SUVmean and ADCmean (r = -0.18, p = 0.07), and between SUV ratio and ADCmin (r = -0.27, p = 0.01). A similar inverse Pearson correlation coefficient was found between the PET/CT SUVmax and ADCmin. Twenty of 24 patients had previously undergone PET/CT; five patients had a partial treatment response, and six had progressive disease according to Response Evaluation

Down-regulation of MHC Class I by the Marek's Disease Virus (MDV) UL49.5 Gene Product Mildly Affects Virulence in a Haplotype-specific Fashion

Science.gov (United States)

Marek’s disease is a devastating neoplastic disease of chickens caused by gallid herpesvirus 2 or Marek’s disease virus (MDV), which is characterized by massive visceral tumors, immune suppression, neurologic syndromes, and peracute deaths. It has been reported that MDV down-regulates surface expre...

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

OpenAIRE

Haricharan, Svasti; Brown, Powel

2015-01-01

This study fundamentally alters our understanding of how TLR4 drives breast cancer. Although TLR4 was previously considered a tumor promoter, we demonstrate a complex, TP53-dependent role for TLR4 in regulating tumor growth. TP53 is a tumor suppressor commonly inactivated across cancer types. In TP53 wild-type cancer cells, TLR4 activation causes secretion of IFN-γ into the microenvironment, resulting in induction of p21 and inhibition of cell growth. Conversely, TLR4 activation in TP53 mutan...

c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Min-Sun; Kim, Sun-Young; Arunachalam, Sankarganesh [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Hwang, Pyoung-Han [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Yi, Ho-Keun [Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Nam, Sang-Yun [Department of Alternative Therapy, School of Alternative Medicine and Health Science, Jeonju University, Jeonju 561-712 (Korea, Republic of); Lee, Dae-Yeol, E-mail: leedy@chonbuk.ac.kr [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of)

2009-07-17

c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways, Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia.

c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells

International Nuclear Information System (INIS)

Kim, Min-Sun; Kim, Sun-Young; Arunachalam, Sankarganesh; Hwang, Pyoung-Han; Yi, Ho-Keun; Nam, Sang-Yun; Lee, Dae-Yeol

2009-01-01

c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways, Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia.

Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

Science.gov (United States)

Brown, Laura D.

2014-01-01

Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present for the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts development of muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or “catch up” postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts towards improving muscle growth early in life in order to prevent the development of chronic metabolic disease later in life. PMID:24532817

Induction of anchorage-independent growth in primary human cells exposed to protons or HZE ions separately or in dual exposures.

Science.gov (United States)

Sutherland, B M; Cuomo, N C; Bennett, P V

2005-10-01

Travelers on space missions will be exposed to a complex radiation environment that includes protons and heavy charged particles. Since protons are present at much higher levels than are heavy ions, the most likely scenario for cellular radiation exposure will be proton exposure followed by a hit by a heavy ion. Although the effects of individual ion species on human cells are being investigated extensively, little is known about the effects of exposure to both radiation types. One useful measure of mammalian cell damage is induction of the ability to grow in a semi-solid agar medium highly inhibitory to the growth of normal human cells, termed neoplastic transformation. Using primary human cells, we evaluated induction of soft-agar growth and survival of cells exposed to protons only or to heavy charged particles (600 MeV/nucleon silicon) only as well as of cells exposed to protons followed after a 4-day interval by silicon ions. Both ions alone efficiently transformed the human cells to anchorage-independent growth. Initial experiments indicate that the dose responses for neoplastic transformation of cells exposed to protons and then after 4 days to silicon ions appear similar to that of cells exposed to silicon ions alone.

Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and Subcutaneous Tissue in Kazakhstan, 2003-2015.

Science.gov (United States)

Igissinov, Nurbek; Kulmirzayeva, Dariyana; Bilyalova, Zarina; Akpolatova, Gulnur; Mamyrbayeva, Marzya; Zhumagaliyeva, Galina

2017-11-01

Arrangement of effective management aimed at improving dermatological services and consistent care of patients with skin diseases depends on understanding the epidemiological situation. This retrospective study presents an epidemiological assessment of non-neoplastic skin and subcutaneous tissue diseases in Kazakhstan registered in 2003-2015. The yearly incidence rate of the diseases among the whole population was in average 3,341.8±121.1 per 100000 population. This represents 4835.0±156.1 for children, 5503.2±141.8 for adolescents and 2646.6±106.7 for adults per 100000 inhabitants. Space and time incidence rate was evaluated according to the administrative division. The overall trend decreased to 3.5% in children to 2.8% in adolescents to 1.9%, and in adults to 3.9%. Considerable variation in rates was seen across the country, with highest rates in East Kazakhstan, Mangystau and Aktobe regions, the lowest - in Atyrau and South-Kazakhstan regions. Non-neoplastic diseases of skin and subcutaneous tissue continue to be an urgent public health problem, especially among children in many regions of Kazakhstan.

Sensitivity to radiation of human normal, hyperthyroid, and neoplastic thyroid epithelial cells in primary culture

International Nuclear Information System (INIS)

Miller, R.C.; Hiraoka, Toshio; Kopecky, K.J.; Nakamura, Nori; Jones, M.P.; Ito, Toshio; Clifton, K.H.

1986-09-01

Samples of thyroid tissue removed surgically from 63 patients were cultured in vitro and X-irradiated to investigate the radiosensitivities of various types of thyroid epithelial cells. A total of 76 samples were obtained, including neoplastic cells from patients with papillary carcinoma (PC) or follicular adenoma (FA), cells from hyperthyroidism (HY) patients, and normal cells from the surgical margins of PC and FA patients. Culturing of the cells was performed in a manner which has been shown to yield a predominance of epithelial cells. Results of colony formation assays indicated that cells from HY and FA patients were the least radiosensitive: when adjusted to the overall geometric mean plating efficiency of 5.5 %, the average mean lethal dose D 0 was 97.6 cGy for HY cells, and 96.7 cGy and 94.3 cGy, respectively, for neoplastic and normal cells from FA patients. Cells from PC patients were more radiosensitive, normal cells having an adjusted average D 0 of 85.0 cGy and PC cells a significantly (p = .001) lower average D 0 of 74.4 cGy. After allowing for this variation by cell type, in vitro radiosensitivity was not significantly related to age at surgery (p = .82) or sex (p = .10). These results suggest that malignant thyroid cells may be especially radiosensitive. (author)

Effects of Training and Feedback on Accuracy of Predicting Rectosigmoid Neoplastic Lesions and Selection of Surveillance Intervals by Endoscopists Performing Optical Diagnosis of Diminutive Polyps.

Science.gov (United States)

Vleugels, Jasper L A; Dijkgraaf, Marcel G W; Hazewinkel, Yark; Wanders, Linda K; Fockens, Paul; Dekker, Evelien

2018-05-01

Real-time differentiation of diminutive polyps (1-5 mm) during endoscopy could replace histopathology analysis. According to guidelines, implementation of optical diagnosis into routine practice would require it to identify rectosigmoid neoplastic lesions with a negative predictive value (NPV) of more than 90%, using histologic findings as a reference, and agreement with histology-based surveillance intervals for more than 90% of cases. We performed a prospective study with 39 endoscopists accredited to perform colonoscopies on participants with positive results from fecal immunochemical tests in the Bowel Cancer Screening Program at 13 centers in the Netherlands. Endoscopists were trained in optical diagnosis using a validated module (Workgroup serrAted polypS and Polyposis). After meeting predefined performance thresholds in the training program, the endoscopists started a 1-year program (continuation phase) in which they performed narrow band imaging analyses during colonoscopies of participants in the screening program and predicted histological findings with confidence levels. The endoscopists were randomly assigned to groups that received feedback or no feedback on the accuracy of their predictions. Primary outcome measures were endoscopists' abilities to identify rectosigmoid neoplastic lesions (using histology as a reference) with NPVs of 90% or more, and selecting surveillance intervals that agreed with those determined by histology for at least 90% of cases. Of 39 endoscopists initially trained, 27 (69%) completed the training program. During the continuation phase, these 27 endoscopists performed 3144 colonoscopies in which 4504 diminutive polyps were removed. The endoscopists identified neoplastic lesions with a pooled NPV of 90.8% (95% confidence interval 88.6-92.6); their proposed surveillance intervals agreed with those determined by histologic analysis for 95.4% of cases (95% confidence interval 94.0-96.6). Findings did not differ between the group

Influence of growth regulators (IBA, BA on anatomical and morphological changes in bromeliads in in vitro culture

Directory of Open Access Journals (Sweden)

Renata Galek

2014-01-01

Full Text Available The subject of study were Tillandsia coronata and Guzmania monostachya. The material has been obtained by means of in vitro propagation. The plants were grown for 18 weeks on various kinds of media. Morphological changes were recorded in both species subjected to action of growth regulators. The changes in plant habit were linked with anatomic build. The effect of cytokinin BA upon growth of the stem pith was found, transversely to its axis, through development of numerous meristematic centres and growth and development of adventitious shoots. Leaves of plant grown on media containing cyto-kinin BA were build of a higher number of cell layers of assimilation parenchyma. In plants grown on media with addition of cytokinin the size of stomatal cells was smaller and was accompanied by analogous changes in size of epidermis cells proper. The bushy type of the plants, caused by presence of cytokinin in medium, resulted from the increase of thickness and breadth of leaves and growth of the stem pith, with simultaneous inhibition of cells' elongation. Auxin IBA did not favour the growth of the existing axillary shoots, but stimulated elongation of the stem pith. The stomata of plants of both species grown on media with addition of auxin were bigger. As result of the applied growth regulators a higher frequency of appearance of binucleate cells was found in parenchyma cells of the stem and leaves in both the species studied.

Brassinosteroids regulate pavement cell growth by mediating BIN2-induced microtubule stabilization.

Science.gov (United States)

Liu, Xiaolei; Yang, Qin; Wang, Yuan; Wang, Linhai; Fu, Ying; Wang, Xuelu

2018-02-23

Brassinosteroids (BRs), a group of plant steroid hormones, play important roles in regulating plant development. The cytoskeleton also affects key developmental processes and a deficiency in BR biosynthesis or signaling leads to abnormal phenotypes similar to those of microtubule-defective mutants. However, how BRs regulate microtubule and cell morphology remains unknown. Here, using liquid chromatography-tandem mass spectrometry, we identified tubulin proteins that interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative regulator of BR responses in plants. In vitro and in vivo pull-down assays confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical microtubules were more sensitive to treatment with the microtubule-disrupting drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2-1, cortical microtubules were insensitive to oryzalin treatment. These results provide important insight into how BR regulates plant pavement cell and leaf growth by mediating the stabilization of microtubules by BIN2.

Detection of occult cancer with [18F]-FDG scintigraphy in case of limbic encephalitis, a rare neurologic para neoplastic syndrome

International Nuclear Information System (INIS)

Kerrou, K.; Aide, N.; Montravers, F.; Grahek, D.; Younsi-Pourtau, N.; Petegnief, Y.; Colombet-Lamau, C.; Beco, V. de; Talbot, J.N.

2003-01-01

Limbic encephalitis is a rare neurologic para-neoplastic syndrome due to the production of anti-neuronal antibodies induced by the presence of a malignant tumour, most frequently a small cell lung cancer: The discovery and the resection of the malignant tissue allows a stabilisation of the neurological syndrome, a complete recovery being impossible when irreversible lesions are present. ( 18 F)-FDG PET may play a determinant role when the cancer is still occult after conventional imaging work-up. We report here on a such patient with evolving limbic encephalitis and no detectable cancer with conventional imaging modalities. ( 18 F)-FDG CDET successfully localised neoplastic small cell lung cancer tissue in the lung. The malignant tumour was not even detectable at surgery and was only confirmed at post surgical histology exactly exactly where it has been spotted by CDET. After surgery, the neurologic syndrome is now steady. (authors)

Exogenously applied plant growth regulators enhance the morpho-physiological growth and yield of rice under high temperature

Directory of Open Access Journals (Sweden)

Shah Fahad

2016-08-01

Full Text Available A two-year experiment was conducted to ascertain the effects of exogenously applied plant growth regulators (PGR on rice growth and yield attributes under high day (HDT and high night temperature (HNT. Two rice cultivars (IR-64 and Huanghuazhan were subjected to temperature treatments in controlled growth chambers and four different combinations of ascorbic acid (Vc, alpha-tocopherol (Ve, brassinosteroids (Br, methyl jasmonates (MeJA and triazoles (Tr were applied. High temperature severely affected rice morphology, and also reduced leaf area, above- and below-ground biomass, photosynthesis, and water use efficiency, while increased the leaf water potential of both rice cultivars. Grain yield and its related attributes except number of panicles, were reduced under high temperature. The HDT posed more negative effects on rice physiological attributes, while HNT was more detrimental for grain formation and yield. The Huanghuazhan performed better than IR-64 under high temperature stress with better growth and higher grain yield. Exogenous application of PGRs was helpful in alleviating the adverse effects of high temperature. Among PGR combinations, the Vc+Ve+MejA+Br was the most effective treatment for both cultivars under high temperature stress. The highest grain production by Vc+Ve+MejA+Br treated plants was due to enhanced photosynthesis, spikelet fertility and grain filling, which compensated the adversities of high temperature stress. Taken together, these results will be of worth for further understanding the adaptation and survival mechanisms of rice to high temperature and will assist in developing heat-resistant rice germplasm in future.

Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro.

Science.gov (United States)

Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

2013-06-01

Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P cancer may confer a growth advantage for neoplastic cells. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men.

Science.gov (United States)

Sjögren, Klara; Leung, Kin-Chuen; Kaplan, Warren; Gardiner-Garden, Margaret; Gibney, James; Ho, Ken K Y

2007-07-01

Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences.

The effect of plant growth regulators and their interaction with electric current on winter wheat development

Czech Academy of Sciences Publication Activity Database

Biesaga-Koscielniak, J.; Koscielniak, J.; Filek, M.; Marcinska, I.; Krekule, Jan; Macháčková, Ivana; Kubon, M.

2010-01-01

Roč. 32, č. 5 (2010), s. 987-995 ISSN 0137-5881 Institutional research plan: CEZ:AV0Z50380511 Keywords : In vitro culture * Plant growth regulators * Electric current Subject RIV: EF - Botanics Impact factor: 1.344, year: 2010

Examining the Predictive Relations between Two Aspects of Self-Regulation and Growth in Preschool Children’s Early Literacy Skills

Science.gov (United States)

Lonigan, Christopher J.; Allan, Darcey M.; Phillips, Beth M.

2016-01-01

There is strong evidence that self-regulatory processes are linked to early academic skills both concurrently and longitudinally. The majority of extant longitudinal studies, however, have been conducted using autoregressive techniques that may not accurately model change across time. The purpose of this study was to examine the unique associations between two components of self-regulation, attention and executive functioning (EF), and growth in early literacy skills over the preschool year using latent-growth-curve analysis. The sample included 1,082 preschool children (M-age = 55.0 months, SD = 3.73). Children completed measures of vocabulary, syntax, phonological awareness, print knowledge, cognitive ability, and self-regulation, and children’s classroom teachers completed a behavior rating measure. To examine the independent relations of the self-regulatory skills and cognitive ability with children’s initial early literacy skills and growth across the preschool year, growth models in which the intercept and slope were simultaneously regressed on each of the predictor variables were examined. Because of the significant relation between intercept and slope for most outcomes, slope was regressed on intercept in the models to allow a determination of direct and indirect effects of the predictors on growth in children’s language and literacy skills across the preschool year. In general, both teacher-rated inattention and directly measured EF were uniquely associated with initial skills level; however, only teacher-rated inattention uniquely predicted growth in early literacy skills. These findings suggest that teacher-ratings of inattention may measure an aspect of self-regulation that is particularly associated with the acquisition of academic skills in early childhood. PMID:27854463

Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

Directory of Open Access Journals (Sweden)

C.M. Souza

2014-10-01

Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

Science.gov (United States)

Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

2015-09-25

In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

Oligosaccharins, brassinolides, and jasmonates: nontraditional regulators of plant growth, development, and gene expression.

Science.gov (United States)

Creelman, R A; Mullet, J E

1997-07-01

Each of the nontraditional plant hormones reviewed in this article, oligosaccharins, brassinolides, and JA, can exert major effects on plant growth and development. However, in many cases, the mechanisms by which these compounds are involved in the endogenous regulation of morphogenesis remain to be established. Nevertheless, the use of mutant or transgenic plants with altered levels or perception of these hormones is leading to phenomenal increases in our understanding of the roles they play in the life cycle of plants. It is likely that in the future, novel modulators of plant growth and development will be identified; some will perhaps be related to the peptide encoded by ENOD40 (Van de Sande et al., 1996), which modifies the action of auxin.

Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

OpenAIRE

Layton, Tracy; Stalens, Cristel; Gunderson, Felizza; Goodison, Steve; Silletti, Steve

2009-01-01

We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC cells in vitro and in situ, and stable reexpression of syk in endogenously syk-negative Panc1 (Panc1/syk) cells retarded their growth in vitro and in vivo and reduced anchorage-independent growth in vitro. Panc1/syk cells exhibited a more differentiated morphology and down-regulated cyclin D1, ak...

Endocrine Regulation of Compensatory Growth in Fish

Directory of Open Access Journals (Sweden)

Eugene T. Won

2013-07-01

Full Text Available Compensatory growth (CG is a period of accelerated growth that occurs following the alleviation of growth-stunting conditions during which an organism can make up for lost growth opportunity and potentially catch-up in size with non-stunted cohorts. Fish show a particularly robust capacity for the response and have been the focus of numerous studies that demonstrate their ability to compensate for periods of fasting once food is made available again. Compensatory growth is characterized by an elevated growth rate resulting from enhanced feed intake, mitogen production and feed conversion efficiency. Because little is known about the underlying mechanisms that drive the response, this review describes the sequential endocrine adaptations that lead to CG; namely during the precedent catabolic phase (fasting that taps endogenous energy reserves, and the following hyperanabolic phase (refeeding when accelerated growth occurs. In order to elicit a CG response, endogenous energy reserves must first be moderately depleted, which alters endocrine profiles that enhance appetite and growth potential. During this catabolic phase, elevated ghrelin and growth hormone (GH production increase appetite and protein-sparing lipolysis, while insulin-like growth factors (IGFs are suppressed, primarily due to hepatic GH resistance. During refeeding, temporal hyperphagia provides an influx of energy and metabolic substrates that are then allocated to somatic growth by resumed IGF signaling. Under the right conditions, refeeding results in hyperanabolism and a steepened growth trajectory relative to constantly fed controls. The response wanes as energy reserves are re-accumulated and homeostasis is restored. We ascribe possible roles for select appetite and growth-regulatory hormones in the context of these catabolic and hyperanabolic phases of the CG response in teleosts, with emphasis on GH, IGFs, cortisol, somatostatin, neuropeptide Y, ghrelin and leptin.

The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.

Science.gov (United States)

Kerchev, Pavel I; Pellny, Till K; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D; Foyer, Christine H

2011-09-01

Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation.

Ligand Receptor-Mediated Regulation of Growth in Plants.

Science.gov (United States)

Haruta, Miyoshi; Sussman, Michael R

2017-01-01

Growth and development of multicellular organisms are coordinately regulated by various signaling pathways involving the communication of inter- and intracellular components. To form the appropriate body patterns, cellular growth and development are modulated by either stimulating or inhibiting these pathways. Hormones and second messengers help to mediate the initiation and/or interaction of the various signaling pathways in all complex multicellular eukaryotes. In plants, hormones include small organic molecules, as well as larger peptides and small proteins, which, as in animals, act as ligands and interact with receptor proteins to trigger rapid biochemical changes and induce the intracellular transcriptional and long-term physiological responses. During the past two decades, the availability of genetic and genomic resources in the model plant species, Arabidopsis thaliana, has greatly helped in the discovery of plant hormone receptors and the components of signal transduction pathways and mechanisms used by these immobile but highly complex organisms. Recently, it has been shown that two of the most important plant hormones, auxin and abscisic acid (ABA), act through signaling pathways that have not yet been recognized in animals. For example, auxins stimulate cell elongation by bringing negatively acting transcriptional repressor proteins to the proteasome to be degraded, thus unleashing the gene expression program required for increasing cell size. The "dormancy" inducing hormone, ABA, binds to soluble receptor proteins and inhibits a specific class of protein phosphatases (PP2C), which activates phosphorylation signaling leading to transcriptional changes needed for the desiccation of the seeds prior to entering dormancy. While these two hormone receptors have no known animal counterparts, there are also many similarities between animal and plant signaling pathways. For example, in plants, the largest single gene family in the genome is the protein kinase

Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

Science.gov (United States)

Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

2014-01-01

We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

Utilization of γ-irradiation technique on plant mutation breeding and plant growth regulation in Tokyo Metropolitan Isotope Research Center

International Nuclear Information System (INIS)

Suda, Hirokatsu

1997-01-01

During about 30-years, we have developed γ-irradiation technique and breeding back pruning method for the study of mutation breeding of ornamental plants. As a result, we have made a wide variety of new mutant lines in chrysanthemum, narcissus, begonia rex, begonia iron cross, winter daphne, zelkova, sweet-scented oleander, abelia, kobus, and have obtained 7 plant patents. By the use of γ-irradiation to plant mutation breeding, we often observed that plants irradiated by low dose of γ-rays showed superior or inferior growth than the of non-irradiated plants. Now, we established the irradiation conditions of γ-rays for mutation breeding and growth of regulation in narcissus, tulip, Enkianthus perulatus Schneid., komatsuna, moyashi, african violet. In most cases, irradiation dose rate is suggested to be a more important factor to induce plant growth regulators than irradiation dose. (author)

Expression of the α2-macroglobulin receptor on human neoplastic fibroblastoid cells

International Nuclear Information System (INIS)

Grofova, M.; Matoska, J.; Bies, J.; Bizik, J.; Vaheri, A.

1995-01-01

The α 2 -macroglobulin membrane-associated receptor ( α 2 MR) has been previously detected on hepatocytes, fibroblast, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors α 2 MR mRNA was detected by Northern blotting. Endocytosis of α 2 MR from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts α 2 MR and its degradation products were detected by immunoblotting. The cells expressing α 2 MR and internalizing α 2 MR were identified as fibroblast both by their morphology and expression of vimentin intermediate filaments. The role and function of α 2 MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed. (author)

Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2

International Nuclear Information System (INIS)

Kumari, Gita; Mahalingam, S.

2009-01-01

Ras GTPase controls the normal cell growth through binding with an array of effector molecules, such as Raf and PI3-kinase in a GTP-dependent manner. RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is frequently down-regulated in various tumor tissues by promoter hypermethylation. In the present study, we demonstrate that RASSF2 shuttles between nucleus and cytoplasm by a signal-mediated process and its export from the nucleus is sensitive to leptomycin B. Amino acids between 240 to 260 in the C-terminus of RASSF2 harbor a functional nuclear export signal (NES), which is necessary and sufficient for efficient export of RASSF2 from the nucleus. Substitution of conserved Ile254, Val257 and Leu259 within the minimal NES impaired RASSF2 export from the nucleus. In addition, wild type but not the nuclear export defective RASSF2 mutant interacts with export receptor, CRM-1 and exported from the nucleus. Surprisingly, we observed nucleolar localization for the nuclear export defective mutant suggesting the possibility that RASSF2 may localize in different cellular compartments transiently in a cell cycle dependent manner and the observed nuclear localization for wild type protein may be due to faster export kinetics from the nucleolus. Furthermore, our data suggest that RASSF2 is specifically phosphorylated by MAPK/ERK-2 and the inhibitors of MAPK pathway impair the phosphorylation and subsequently block the export of RASSF2 from the nucleus. These data clearly suggest that ERK-2 mediated phosphorylation plays an important role in regulating the nucleo-cytoplasmic shuttling of RASSF2. Interestingly, nuclear import defective mutant of RASSF2 failed to induce cell cycle arrest at G1/S phase and apoptosis suggesting that RASSF2 regulates cell growth in a nuclear localization dependent manner. Collectively, these data provided evidence for the first time that MAPK/ERK-2 mediated phosphorylation regulates

Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2

Energy Technology Data Exchange (ETDEWEB)

Kumari, Gita [Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500076 (India); Mahalingam, S., E-mail: mahalingam@iitm.ac.in [Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500076 (India); Department of Biotechnology, Laboratory of Molecular Virology and Cell Biology, Indian Institute of Technology-Madras, Chennai 600 036 (India)

2009-10-01

Ras GTPase controls the normal cell growth through binding with an array of effector molecules, such as Raf and PI3-kinase in a GTP-dependent manner. RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is frequently down-regulated in various tumor tissues by promoter hypermethylation. In the present study, we demonstrate that RASSF2 shuttles between nucleus and cytoplasm by a signal-mediated process and its export from the nucleus is sensitive to leptomycin B. Amino acids between 240 to 260 in the C-terminus of RASSF2 harbor a functional nuclear export signal (NES), which is necessary and sufficient for efficient export of RASSF2 from the nucleus. Substitution of conserved Ile254, Val257 and Leu259 within the minimal NES impaired RASSF2 export from the nucleus. In addition, wild type but not the nuclear export defective RASSF2 mutant interacts with export receptor, CRM-1 and exported from the nucleus. Surprisingly, we observed nucleolar localization for the nuclear export defective mutant suggesting the possibility that RASSF2 may localize in different cellular compartments transiently in a cell cycle dependent manner and the observed nuclear localization for wild type protein may be due to faster export kinetics from the nucleolus. Furthermore, our data suggest that RASSF2 is specifically phosphorylated by MAPK/ERK-2 and the inhibitors of MAPK pathway impair the phosphorylation and subsequently block the export of RASSF2 from the nucleus. These data clearly suggest that ERK-2 mediated phosphorylation plays an important role in regulating the nucleo-cytoplasmic shuttling of RASSF2. Interestingly, nuclear import defective mutant of RASSF2 failed to induce cell cycle arrest at G1/S phase and apoptosis suggesting that RASSF2 regulates cell growth in a nuclear localization dependent manner. Collectively, these data provided evidence for the first time that MAPK/ERK-2 mediated phosphorylation regulates

Flavonols Mediate Root Phototropism and Growth through Regulation of Proliferation-to-Differentiation Transition

OpenAIRE

Silva, Javier; Moreno Risueño, Miguel Ángel; Manzano, Concepción; Téllez Robledo, Bárbara; Navarro Neila, Sara; Carrasco Loba, Víctor; Pollmann, Stephan; Gallego, Javier; Pozo Benito, Juan Carlos del

2016-01-01

Roots normally grow in darkness, but they may be exposed to light. After perceiving light, roots bend to escape from light (root light avoidance) and reduce their growth. How root light avoidance responses are regulated is not well understood. Here, we show that illumination induces the accumulation of flavonols in Arabidopsis thaliana roots. During root illumination, flavonols rapidly accumulate at the side closer to light in the transition zone. This accumulation promotes asymmetrical cell ...

Chondroitin-4-sulfation negatively regulates axonal guidance and growth

Science.gov (United States)

Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

2008-01-01

Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

Science.gov (United States)

Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

1982-01-01

Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

Science.gov (United States)

Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

2011-01-01

We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

Effect of gamma radiation and some growth regulators on ripening and senescence in mango fruits

International Nuclear Information System (INIS)

EL-Kady, S.M.A.

1982-01-01

The present investigation was undertaken during the seasons of 1979 and 1980 to study the effect of gamma irradiation, some growth regulators, benlate and 'vaporgard' on ripening and senescence of 'Hindi Be - Sinnara' mango fruits during storage under room conditions and also to determine the optimum treatment for maximum extension in shelf - life

Synthesis and evaluation of the plant growth regulator property of indolic compounds derived from safrole

International Nuclear Information System (INIS)

Marchi, Irineu; Rebelo, Ricardo Andrade; Rosa, Flavia A. Fernandes da; Maiochi, Riceli A.

2007-01-01

The present work describes the use of piperonal, a derivative of the secondary metabolite safrole, for the synthesis of new 5,6-methylenedioxy substituted indole carboxylic acids structurally related to the indol-3-yl-acetic acid (AIA, I). The route comprises six steps beginning with piperonal with an overall yield of 19%. Compound IX was tested towards its plant growth regulator properties in bioassays specific for auxine activity. The in vitro assays were performed in a germination chamber and were of two types: root growth in germinated seeds of Lactuca sativa, Cucumbis sativus and Raphanus sativus and peciole biotest using Phaseolus vulgaris. (author)

Histone Deacetylase HDA-2 Regulates Trichoderma atroviride Growth, Conidiation, Blue Light Perception, and Oxidative Stress Responses.

Science.gov (United States)

Osorio-Concepción, Macario; Cristóbal-Mondragón, Gema Rosa; Gutiérrez-Medina, Braulio; Casas-Flores, Sergio

2017-02-01

Fungal blue-light photoreceptors have been proposed as integrators of light and oxidative stress. However, additional elements participating in the integrative pathway remain to be identified. In Trichoderma atroviride, the blue-light regulator (BLR) proteins BLR-1 and -2 are known to regulate gene transcription, mycelial growth, and asexual development upon illumination, and recent global transcriptional analysis revealed that the histone deacetylase-encoding gene hda-2 is induced by light. Here, by assessing responses to stimuli in wild-type and Δhda-2 backgrounds, we evaluate the role of HDA-2 in the regulation of genes responsive to light and oxidative stress. Δhda-2 strains present reduced growth, misregulation of the con-1 gene, and absence of conidia in response to light and mechanical injury. We found that the expression of hda-2 is BLR-1 dependent and HDA-2 in turn is essential for the transcription of early and late light-responsive genes that include blr-1, indicating a regulatory feedback loop. When subjected to reactive oxygen species (ROS), Δhda-2 mutants display high sensitivity whereas Δblr strains exhibit the opposite phenotype. Consistently, in the presence of ROS, ROS-related genes show high transcription levels in wild-type and Δblr strains but misregulation in Δhda-2 mutants. Finally, chromatin immunoprecipitations of histone H3 acetylated at Lys9/Lys14 on cat-3 and gst-1 promoters display low accumulation of H3K9K14ac in Δblr and Δhda-2 strains, suggesting indirect regulation of ROS-related genes by HDA-2. Our results point to a mutual dependence between HDA-2 and BLR proteins and reveal the role of these proteins in an intricate gene regulation landscape in response to blue light and ROS. Trichoderma atroviride is a free-living fungus commonly found in soil or colonizing plant roots and is widely used as an agent in biocontrol as it parasitizes other fungi, stimulates plant growth, and induces the plant defense system. To survive in

The Effect of Plant Growth Regulators on Callus Induction and Regeneration of Amygdalus communis

Directory of Open Access Journals (Sweden)

Naimeh SHARIFMOGHADAM

2011-08-01

Full Text Available The Almond (Amygdalus communis is one of the most important and oldest commercial nut crops, belonging to the Rosaceae family. Almond has been used as base material in pharmaceutical, cosmetic, hygienically and food industry. Propagation by tissue culture technique is the most important one in woody plants. In the current research, in vitro optimization of tissue culture and mass production of almond was investigated. In this idea, explants of actively growing shoots were collected and sterilized, then transferred to MS medium with different concentrations and combinations of plant growth regulators. The experiment was done in completely randomized blocks design, with 7 treatment and 30 replications. After 4 weeks, calli induction, proliferation, shoot length and number of shoot per explants were measured. Results showed that the best medium for shoot initiation and proliferation was MS + 0.5 mg/l IAA (Indol-3-Acetic Acid + 1 mg/l BA (Benzyl Adenine. Autumn was the best season for collecting explants. The shoots were transferred to root induction medium with different concentrations of plant growth regulators. The best root induction medium was MS + 0.5 mg/l IBA (Indol Butyric Acid.

Effect of growth regulators application on the quality maintenance of 'Brookfield' apples

Directory of Open Access Journals (Sweden)

Auri Brackmann

2015-01-01

Full Text Available AbstractThe main goal of the present study was to elucidate the effect of growth regulators at harvest and postharvest quality of 'Brookfield' apples stored under controlled atmosphere through a multivariate approach. Thus, an experiment with two steps (field and storage was carried out. The treatments in field were applied with an output of 1,000 L ha–1 of water. The following treatments were tested: Control: only water application; AVG (aminoethoxyvinylglycine: 0.83 kg ha–1 of Retain® applied 30 days before harvest (BH; NAA (naphthalene acetic acid: 40g ha–1of naphthalene acetic acid applied 7 days BH; Ethephon: 2.0 L ha–1 of Ethrel® applied 10 days BH; 1-MCP: 0.625µL L–1 of 1-MCP (1-methylcyclopropene: applied during postharvest (storage; LE (low ethylene: with the allocation of potassium permanganate sachets during postharvest. Fruits treated with AVG in the field showed an opposite response to the fruits with NAA. AVG application followed by another growth regulator (AVG + Ethephon and AVG + NAA showed an advance in maturation, nearing these fruits to the control treatment, this effect is likely related to the higher ethylene production by these fruits compared to fruits with AVG alone. AVG, 1-MCP and LE kept a similar response on quality maintenance. Ethephon application prevented the negative effect of NAA at harvest, but after storage, the combined NAA + ethephon application increased the physiological disorders, reducing internal quality.

Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

Energy Technology Data Exchange (ETDEWEB)

Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

2009-01-01

Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction.

Directory of Open Access Journals (Sweden)

Kimberly R Hagel

Full Text Available Calcium is a primary second messenger in all cells that functions in processes ranging from cellular proliferation to synaptic transmission. Proper regulation of calcium is achieved through numerous mechanisms involving channels, sensors, and buffers notably containing one or more EF-hand calcium binding domains. The Drosophila genome encodes only a single 6 EF-hand domain containing protein, Cbp53E, which is likely the prototypic member of a small family of related mammalian proteins that act as calcium buffers and calcium sensors. Like the mammalian homologs, Cbp53E is broadly though discretely expressed throughout the nervous system. Despite the importance of calcium in neuronal function and growth, nothing is known about Cbp53E's function in neuronal development. To address this deficiency, we generated novel null alleles of Drosophila Cbp53E and examined neuronal development at the well-characterized larval neuromuscular junction. Loss of Cbp53E resulted in increases in axonal branching at both peptidergic and glutamatergic neuronal terminals. This overgrowth could be completely rescued by expression of exogenous Cbp53E. Overexpression of Cbp53E, however, only affected the growth of peptidergic neuronal processes. These findings indicate that Cbp53E plays a significant role in neuronal growth and suggest that it may function in both local synaptic and global cellular mechanisms.

Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {l_brace}in-phase and out-of phase{r_brace} MR imaging

Energy Technology Data Exchange (ETDEWEB)

Ragab, Yasser [Radiology Department, Faculty of Medicine, Cairo University (Egypt); Radiology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yragab61@hotmail.com; Emad, Yasser [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt); Rheumatology and Rehabilitation Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yasseremad68@yahoo.com; Gheita, Tamer [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt)], E-mail: gheitamer@yahoo.com; Mansour, Maged [Oncology Department, Faculty of Medicine, Cairo University (Egypt); Oncology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: magedmansour@yahoo.com; Abou-Zeid, A. [Public Health Department, Faculty of Medicine, Cairo University, Cairo (Egypt)], E-mail: alaabouzeid@yahoo.com; Ferrari, Serge [Division of Bone Diseases, Department of Rehabilitation and Geriatrics, and WHO, Collaborating Center for Osteoporosis Prevention, Geneva University Hospital (Switzerland)], E-mail: serge.ferrari@medecine.unige.ch; Rasker, Johannes J. [Rheumatologist University of Twente, Enschede (Netherlands)], E-mail: j.j.rasker@utwente.nl

2009-10-15

Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

HRE-type genes are regulated by growth-related changes in internal oxygen concentrations during the normal development of potato (Solanum tuberosum) tubers.

Science.gov (United States)

Licausi, Francesco; Giorgi, Federico Manuel; Schmälzlin, Elmar; Usadel, Björn; Perata, Pierdomenico; van Dongen, Joost Thomas; Geigenberger, Peter

2011-11-01

The occurrence of hypoxic conditions in plants not only represents a stress condition but is also associated with the normal development and growth of many organs, leading to adaptive changes in metabolism and growth to prevent internal anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due to their active metabolism and increased resistance to gas diffusion as tubers grow. In the present work, we identified three hypoxia-responsive ERF (StHRE) genes whose expression is regulated by the gradual decrease in oxygen tensions that occur when potato tubers grow larger. Increasing the external oxygen concentration counteracted the modification of StHRE expression during tuber growth, supporting the idea that the actual oxygen levels inside the organs, rather than development itself, are responsible for the regulation of StHRE genes. We identified several sugar metabolism-related genes co-regulated with StHRE genes during tuber development and possibly involved in starch accumulation. All together, our data suggest a possible role for low oxygen in the regulation of sugar metabolism in the potato tuber, similar to what happens in storage tissues during seed development.

Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor.

Science.gov (United States)

Liu, Haizhou; Wang, Shaoyang; Ma, Weimin; Lu, Youguang

2015-12-01

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-β1 is up-regulated in HCC and is thought to play a crucial role in the occurrence and development of HCC. However, the mechanism of TGF-β1-mediated facilitation of malignant growth and invasion remains unclear, although some previous studies highlighted a potential involvement of the connective tissue growth factor (CTGF). Here we demonstrate that the in vitro migration of the HCC cell line SMMC-7721 is increased in the presence of recombinant TGF-β1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-β1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-β1-stimulated migration of SMMC-7721 cells was diminished by siRNA silencing of CTGF. These in vitro observations were validated in a murine xenograft model. In particular, silencing of CTFG diminished the TGF-β1-induced tumorigenesis in experimental animals. In conclusion, TGF-β1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF.

Interobserver agreement for the spine instability neoplastic score varies according to the experience of the evaluator

Directory of Open Access Journals (Sweden)

William Gemio Jacobsen Teixeira

2013-01-01

Full Text Available OBJECTIVES: To evaluate the interobserver agreement for the Neoplastic Spine Instability Score (SINS among spine surgeons with or without experience in vertebral metastasis treatment and physicians in other specialties. METHODS: Case descriptions were produced based on the medical records of 40 patients with vertebral metastases. The descriptions were then published online. Physicians were invited to evaluate the descriptions by answering questions according to the Neoplastic Spine Instability Score (SINS. The agreement among physicians was calculated using the kappa coefficient. RESULTS: Seventeen physicians agreed to participate: three highly experienced spine surgeons, seven less-experienced spine surgeons, three surgeons of other specialties, and four general practitioners (n = 17. The agreement for the final SINS score among all participants was fair, and it varied according to the SINS component. The agreement was substantial for the spine location only. The agreement was higher among experienced surgeons. The agreement was nearly perfect for spinal location among the spine surgeons who were highly experienced in vertebral metastases. CONCLUSIONS: This study demonstrates that the experience of the evaluator has an impact on SINS scale classification. The interobserver agreement was only fair among physicians who were not spine surgeons and among spine surgeons who were not experienced in the treatment of vertebral metastases, which may limit the use of the SINS scale for the screening of unstable lesions by less-experienced evaluators.

Comparison of the circadian variation in cell proliferation in normal and neoplastic colonic epithelial cells.

Science.gov (United States)

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-15

Circadian variations in cell proliferation in normal tissues have been recognised for many years but comparable phenomena in neoplastic tissues appear not to have been reported. Adenomas and carcinomas were induced in mouse colon by injection of dimethylhydrazine (DMH) and cell proliferation in these tumors was measured stathmokinetically. In normal intestine cell proliferation is fastest at night whereas in both adenomas and carcinomas it was found to be slower at night than in the middle of the day. Chemical sympathectomy was found to abolish the circadian variation in tumor cell proliferation.

Neoplastic transformation of hamster embryo cells irradiated in utero and assayed in vitro

International Nuclear Information System (INIS)

Borek, C.; Pain, C.; Mason, H.

1977-01-01

It is stated that induction of neoplastic transformation in vitro by x-rays and neutrons has been reported, and the authors had previously found that transformation by x-rays could be detected at doses as low as 1 R and the rate of transformation increased with dose, reaching a peak of 1% between 150 and 300 R. This frequency of neoplastic transformation in vitro is much higher than the frequency of radiation induced tumors observed after exposing animals to similar doses of radiation. Studies are here reported showing that malignant transformed cells can be obtained from embryos irradiated in utero and assayed in vitro, and that the frequency of transformation is at least tenfold lower than when the irradiations are performed in vitro, and thus closer to the incidence in animals. Hamster embryo cells were used for the studies. Questions that arise are as follows: does the host mediate in modulating transformation by radiation; is there a repair of transforming events before they can be expressed; and how significant is the state of cells during irradiation in determining the rate of transformation. It is known from in vitro studies that cell replication is required for fixation of the transformation. With the in vitro technique cells are seeded as single cells with ample opportunity to divide. In addition they are not in contact with one another, and constitute a mixture of cell types from many tissues. In utero the situation is quite different; the embryonic cells are irradiated as tissues where there is cell to cell contact in tissue-specific arrangements, and where the rate of cell replication varies with the tissue. It remains to be seen which of these factors, if any, is responsible for the lowered yield of transformed cells characteristic of in utero as opposed to in vitro irradiation. (U.K.)

FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

International Nuclear Information System (INIS)

Chiappetta, Gennaro; Pierantoni, Giovanna Maria; Fusco, Alfredo; Ferraro, Angelo; Botti, Gerardo; Monaco, Mario; Pasquinelli, Rosa; Vuttariello, Emilia; Arnaldi, Liliane; Di Bonito, Maurizio; D'Aiuto, Giuseppe

2007-01-01

Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

Proteomic analysis of growth phase-dependent expression of Legionella pneumophila proteins which involves regulation of bacterial virulence traits.

Directory of Open Access Journals (Sweden)

Tsuyoshi Hayashi

Full Text Available Legionella pneumophila, which is a causative pathogen of Legionnaires' disease, expresses its virulent traits in response to growth conditions. In particular, it is known to become virulent at a post-exponential phase in vitro culture. In this study, we performed a proteomic analysis of differences in expression between the exponential phase and post-exponential phase to identify candidates associated with L. pneumophila virulence using 2-Dimentional Fluorescence Difference Gel Electrophoresis (2D-DIGE combined with Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry (MALDI-TOF-MS. Of 68 identified proteins that significantly differed in expression between the two growth phases, 64 were up-regulated at a post-exponential phase. The up-regulated proteins included enzymes related to glycolysis, ketone body biogenesis and poly-3-hydroxybutyrate (PHB biogenesis, suggesting that L. pneumophila may utilize sugars and lipids as energy sources, when amino acids become scarce. Proteins related to motility (flagella components and twitching motility-associated proteins were also up-regulated, predicting that they enhance infectivity of the bacteria in host cells under certain conditions. Furthermore, 9 up-regulated proteins of unknown function were found. Two of them were identified as novel bacterial factors associated with hemolysis of sheep red blood cells (SRBCs. Another 2 were found to be translocated into macrophages via the Icm/Dot type IV secretion apparatus as effector candidates in a reporter assay with Bordetella pertussis adenylate cyclase. The study will be helpful for virulent analysis of L. pneumophila from the viewpoint of physiological or metabolic modulation dependent on growth phase.

In vitro study of the influence of alpha particles irradiation on the pre-neoplastic transformation of rat trachea epithelial cells

International Nuclear Information System (INIS)

Kugel, C.

2001-12-01

Intern contamination by actinide oxide inhalation is potentially one health hazard during the nuclear fuel fabrication process. The aerosol particles can induce pulmonary lesions, such as epithelial cancers in particular. Their toxicity is mainly due to radiotoxicity of α irradiation. The aim of this work was to contribute, by an in vitro model, to the study of the apparition of pre-neoplastic states on epithelial cells after high LET irradiation. Primary cultures of rat tracheal epithelial cells were used. Two rat strain cells, SD TR for Sprague Dawley rats and WF TR for Wistar Furth I Fischer F344 rats, were compared after exposure to a dose range from 0 to 5 Gy. Reproductive cell death, i.e. senescent death, seems to be the main lethal way induced by α and γ irradiations. The nuclear volume of WF TR cells is higher than that of SD TR ones, explaining the higher α radiation-induced lethality of these cells. These WF TR cells are also much sensitive to dose rate and α particles energy. In the same manner, pre-neoplastic transformation rate of the cells seems to depend on the physical parameters of irradiation. But, it mainly varies as a function of cell radiosensitivity, that means cell death. In fact, the transformation rate of sensitive WF TR cells is lower than that of SD TR ones. In term of transformation for SD TR cells, dose-effect relationship fits to a linear and infra linear function after α irradiation, whereas the curve fits to linear and quadratic function after γ irradiation. The Relative Biological Efficiency (RBE) of α particles for lethality and pre-neoplastic transformation were determined for several levels of dose. A constant value of about 3 was found for RBE of lethality whatever the α dose. By contrast, the RBE of transformation has a value of about 10 up to 0.5 Gy and gradually decreases at higher doses to reach a value of 1 at 5 Gy. Similar shapes of dose-effect relationship can be observed for malignant lung tumour induction after

Neoplastic transformation in vitro by low doses of ionizing radiation: Role of adaptive response and bystander effects

International Nuclear Information System (INIS)

Ko, M.; Lao, X.-Y.; Kapadia, R.; Elmore, E.; Redpath, J.L.

2006-01-01

The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation

Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

Directory of Open Access Journals (Sweden)

Darci M Fink

Full Text Available The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery.

EFFECT OF GROWTH REGULATOR MICEFIT ON YIELD OF GARDEN RADISH (RAPHANUS SATIVUS L.

Directory of Open Access Journals (Sweden)

T. M. Seredin

2015-01-01

Full Text Available Micefit is a product developed based on mycorrhizal fungi extracted from roots of swamp ledum. For ecological purposes the Micefit is used for final stage of cleaning of contaminated and polluted land at seed sowing and seedling plating. The effect of growth regulator Micefit on seeds of garden radish depending on different concentrations and exposures. The dependence of garden radish yield on time of treatment and concentration is shown.

Improvement of Nutritional and Bioactive Compound Production by Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), by Spraying Growth Regulators.

Science.gov (United States)

Vi, Minhthuan; Yang, Xueqin; Zeng, Xianlu; Chen, Rui'an; Guo, Liqiong; Lin, Junfang; He, Qianyun; Zheng, Qianwang; Wei, Tao

2018-01-01

Hericium erinaceus is a popular culinary and medicinal mushroom in China because of its broad beneficial effects. In this study we evaluated the effects of stimulation with 7 growth regulators at 5 different concentrations on improving the production of nutritional and bioactive compounds by H. erinaceus. Results showed that among all the tested regulators, gibberellic acid (GA) increased protein content (165%), free amino acids (100%), polysaccharides (108%), and polyphenols (26%). Spraying nephthyl acetic acid increased polysaccharides and triterpenoids to 4.37 and 17.27 g/100 g, respectively. Spraying chitosan significantly increased polyphenols by 42%. The addition of triacontanol, indole acetic acid, and 2,4-dichlorophenoxyacetic acid improved the production of proteins, free amino acids, polysaccharides, and polyphenols, but not to the extent that GA did. These results indicate that adding certain growth regulators can effectively improve the production of nutritional and bioactive compounds in H. erinaceus.

The influences of sugars and plant growth regulators on β-glucan synthesis of G. lucidum mycelium in submerged culture

Science.gov (United States)

Thao, Cao Phuong; Tien, Le Thi Thuy

2017-09-01

β - glucan is intracellular polysaccharide (IPS), extracted from Ganoderma lucidum mycelium that can enhance human immune respond. This study aimed to stimulate the production of β - glucan in G. lucidum mycelium through optimating the carbonhydrates and plant rowth regulators in submerged culture. The results showed that the stimulation or inhibition of IPS production as well as β - glucan biosynthesis could be adjusted depend on the type and concentration of carbonhydrates and plant growth regulators. The supplement of lactose 80 g/L and BA 1 mg/L in medium could cause the highest IPS production (644.478 mg/g DW) and β - glucan increased up to 0.15/DW, that raised twice as much as without plant growth regulators. Futhermore, the optimation of other environmental elements were figured out were completely dark and 150 rpm on rotary shaker. This result could be used as premise for production of β - glucan in pilot.

EFFICIENCY OF COMBINED APPLICATION OF GROWTH REGULATORS «OBEREG» AND «ZAVYAZY» FOR WHITE HEAD CABBAGE

Directory of Open Access Journals (Sweden)

K. L. Alekseeva

2015-01-01

Full Text Available The comparative analysis of different ways of application of the growth regulators “Obereg” and “Zavyazy” for white head cabbage has been conducted. The most effective was the double spraying by the mixed growth regulators at the stage of 6-8 leaves and the stage of the beginning of the forming of head of cabbage (400 g/ha and 60 ml/ha. The time step between the treatments is 30 days. The treatments have speeded up the stage of the industrial ripeness on 5-6 days as compared to control and have increased yield of cabbage. The increasing of the content of dry  atter up to 1%, sugars up to 0.5%,  nd vitamin C up to 1.9% mg% was recorded. The nitrate content in all variants was in range of the maximum permissible concentration.

TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning

Directory of Open Access Journals (Sweden)

Sarah X. Luo

2016-12-01

Full Text Available Neural circuits involving midbrain dopaminergic (DA neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders.

DNA Supercoiling Regulates the Motility of Campylobacter jejuni and Is Altered by Growth in the Presence of Chicken Mucus

Directory of Open Access Journals (Sweden)

Claire Shortt

2016-09-01

Full Text Available Campylobacter jejuni is the leading cause of bacterial gastroenteritis in humans, but relatively little is known about the global regulation of virulence factors during infection of chickens or humans. This study identified DNA supercoiling as playing a key role in regulating motility and flagellar protein production and found that this supercoiling-controlled regulon is induced by growth in chicken mucus. A direct correlation was observed between motility and resting DNA supercoiling levels in different strains of C. jejuni, and relaxation of DNA supercoiling resulted in decreased motility. Transcriptional analysis and Western immunoblotting revealed that a reduction in motility and DNA supercoiling affected the two-component regulatory system FlgRS and was associated with reduced FlgR expression, increased FlgS expression, and aberrant expression of flagellin subunits. Electron microscopy revealed that the flagellar structure remained intact. Growth in the presence of porcine mucin resulted in increased negative supercoiling, increased motility, increased FlgR expression, and reduced FlgS expression. Finally, this supercoiling-dependent regulon was shown to be induced by growth in chicken mucus, and the level of activation was dependent on the source of the mucus from within the chicken intestinal tract. In conclusion, this study reports for the first time the key role played by DNA supercoiling in regulating motility in C. jejuni and indicates that the induction of this supercoiling-induced regulon in response to mucus from different sources could play a critical role in regulating motility in vivo.

Growth of maize coleoptiles in the presence of natural and synthetic growth regulators. Growth correlations

Directory of Open Access Journals (Sweden)

Ewa Raczek

2014-01-01

Full Text Available The effect of natural (IAA, FC, ABA and synthetic (2,4-D growth substances on the increase of the fresh weight of maize coleoptile segments and change of the pH of the incubation medium, accepted here as criteria of maize coleoptile growth, was studied. The growth of maize coleoptiles depended on the concentration of the growth substances, as well as, on the composition of the incubation medium. The highest stimulation of coleoptile growth was seen with FC at a concentration of 10-4M, whereas ABA at 10-3 M gave the highest inhibition of maize coleoptile fresh weight increase and caused alkalization of the medium. The presence of K+ ions in the incubation medium enhanced the stimulatory effect of IAA and FC on the increase of the coleoptile fresh weight, whereas the presence of these ions and phosphate buffer abolished the growth-promoting effect of IAA and FC. The best correlation of the "fresh weight" and "pH" effects was found in the case of the growth of maize coleoptiles in the presence of FC (rxy = 0.67. The inhibition of maize coleoptile growth in the presence of high concentrations of IAA can be explained by the destructive effect of natural auxin at these concentrations on the integrity of mitochondrial membranes, and therefore on the normal functioning of mitochondria.

Diagnostic capabilities of the virtual bronchoscopy at advanced neoplastic process of esophagus with formation of tracheobronchial fistula: Description of a case

Directory of Open Access Journals (Sweden)

M. A. Mitev

2017-09-01

Full Text Available The relevance of the problem is related to the continued increase in the neoplastic processes, and at the same time also to the development and improvement of the endoscopic and CT equipment, and thus expanding the diagnostic capabilities. Purpose: The presented research examines the results of the study of a rare case of ruptured trachea as a result of cancer of the esophagus. Methods: Fiberoptic esophagoscopy (FOE and CT of the chest followed by virtual bronchoscopy on a patient with a ruptured trachea, a 63 year-old man, were performed. Result: Performing MDCT with virtual bronchoscopy, according to this study, is crucial as the sole and complex methodology for the described case in connection with the finding of the trachea-oesophageal fistula and evaluation of the mediastinum and the pulmonary parenchyma. Conclusion: The VB is a successful method equally effective compared to the FB, to diagnose of advanced neoplastic processes.

Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

International Nuclear Information System (INIS)

Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

1986-01-01

Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth.

Science.gov (United States)

Chiappetta, Gennaro; Basile, Anna; Barbieri, Antonio; Falco, Antonia; Rosati, Alessandra; Festa, Michelina; Pasquinelli, Rosa; Califano, Daniela; Palma, Giuseppe; Costanzo, Raffaele; Barcaroli, Daniela; Capunzo, Mario; Franco, Renato; Rocco, Gaetano; Pascale, Maria; Turco, Maria Caterina; De Laurenzi, Vincenzo; Arra, Claudio

2014-08-30

BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy.

Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

Directory of Open Access Journals (Sweden)

Callihan Phillip

2008-12-01

Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

Triiodothyronine regulates cell growth and survival in renal cell cancer.

Science.gov (United States)

Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

2016-10-01

Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.