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Sample records for bcl-2 family members

  1. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald

    2010-01-01

    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti......, spontaneous cellular immune responses against the Bcl-2 family proteins have been identified as frequent features in cancer patients underscoring that these proteins are natural targets for the immune system. Thus, Bcl-2 family may serve as an important and widely applicable target for anti......-cancer immunotherapeutic strategies, alone or in the combination with conventional therapy. Here, we summarize the current knowledge of Bcl-2 family proteins as T-cell antigens, which has set the stage for the first explorative trial using these antigens in therapeutic vaccinations against cancer, and discuss future...

  2. Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae.

    Science.gov (United States)

    Chen, Shao-Rong; Dunigan, David D; Dickman, Martin B

    2003-05-15

    Selected antiapoptotic genes were expressed in baker's yeast (Saccharomyces cerevisiae) to evaluate cytoprotective effects during oxidative stress. When exposed to treatments resulting in the generation of reactive oxygen species (ROS), including H(2)O(2), menadione, or heat shock, wild-type yeast died and exhibited apoptotic-like characteristics, consistent with previous studies. Yeast strains were generated expressing nematode ced-9, human bcl-2, or chicken bcl-xl genes. These transformants tolerated a range of oxidative stresses, did not display features associated with apoptosis, and remained viable under conditions that were lethal to wild-type yeast. Yeast strains expressing a mutant antiapoptotic gene (bcl-2 deltaalpha 5-6), known to be nonfunctional in mammalian cells, were unable to tolerate any of the ROS-generating insults. These data are the first report showing CED-9 has cytoprotective effects against oxidative stress, and add CED-9 to the list of Bcl-2 protein family members that modulate ROS-mediated programmed cell death. In addition, these data indicate that Bcl-2 family members protect wild-type yeast from physiological stresses. Taken together, these data support the concept of the broad evolutionary conservation and functional similarity of the apoptotic processes in eukaryotic organisms.

  3. Bcl-2蛋白家族与运动%Bcl-2 Protein Family Members and Exercises

    Institute of Scientific and Technical Information of China (English)

    吴环成; 贺道远

    2004-01-01

    Bcl-2蛋白家族根据其在细胞凋亡中的作用,分为抑凋亡蛋白和促凋亡蛋白.在骨骼肌细胞和心肌细胞内,Bcl-2家族成员之间形成二聚体,调节细胞是否进入凋亡程序.不同强度的运动对骨骼肌、心肌和淋巴细胞凋亡的影响不尽相同.

  4. BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members.

    Science.gov (United States)

    Hogg, Simon J; Newbold, Andrea; Vervoort, Stephin J; Cluse, Leonie A; Martin, Benjamin P; Gregory, Gareth P; Lefebure, Marcus; Vidacs, Eva; Tothill, Richard W; Bradner, James E; Shortt, Jake; Johnstone, Ricky W

    2016-09-01

    Targeting BET bromodomain proteins using small molecules is an emerging anticancer strategy with clinical evaluation of at least six inhibitors now underway. Although MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional antitumor activities are important. Using the Eμ-Myc model of B-cell lymphoma, we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of proapoptotic (Bim) and antiapoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1-mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. Eμ-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1 resistance phenotype. These studies provide important information on mechanisms of apoptosis induction and resistance to BET-inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. Mol Cancer Ther; 15(9); 2030-41. ©2016 AACR. PMID:27406984

  5. Alternative treatments for melanoma: targeting BCL-2 family members to de-bulk and kill cancer stem cells

    OpenAIRE

    Mukherjee, Nabanita; Schwan, Josianna V.; Fujita, Mayumi; Norris, David A.; Shellman, Yiqun G.

    2015-01-01

    For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30–90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer t...

  6. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update.

    Science.gov (United States)

    Siddiqui, Waseem Ahmad; Ahad, Amjid; Ahsan, Haseeb

    2015-03-01

    Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2). The primary role of Bcl-2 family members is the regulation of apoptosis. Although the structure of Bcl-2 family of proteins was reported nearly 10 years ago, however, it still surprises us with its structural and functional complexity and diversity. A number of studies have demonstrated that Bcl-2 family influences many other cellular processes beyond apoptosis which are generally independent of the regulation of apoptosis, suggesting additional roles for Bcl-2. The disruption of the regulation of apoptosis is a causative event in many diseases. Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the past few years, our understanding of the mechanism of action of Bcl-2 family of proteins and its implications in various pathological conditions has enhanced significantly. The focus of this review is to summarize the current knowledge on the structure and function of Bcl-2 family of proteins in apoptotic cellular processes. A number of drugs have been developed in the past few years that target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of various diseases and their pharmacological significance as effective molecular therapeutic targets is also discussed.

  7. Differential effects of two pro-apoptotic members of the Bcl-2 gene family on murine bone quality

    Science.gov (United States)

    Wise, Lisa Marie

    Bax and Hrk are pro-apoptotic members of the Bcl-2 gene family. Both Bax and Hrk have been previously implicated in ovarian cell survival. Effects on bone cells have also been studied in several members of the Bcl-2 gene family; thus, the focus of this work was to characterize the bone quality of mice deficient in Bax or Hrk. Bone quality of various age groups (3, 6, 12, 6 and 22 months) of Bax-knockout (KO) and Hrk-KO female mice were compared to age-matched control female mice. Additional groups of 6-month mice were ovariectomized (OVX) to determine whether effects are dependent on ovarian function. Dual energy x-ray absorptiometry was performed on all mice to determine bone mineral density (BMD). To evaluate bone mechanical properties, 3-point bending, torsion testing and femoral neck fracture were performed on femora, while compression was performed on individual vertebrae. Mechanical properties were rationalized through evaluation of structural (strut analysis, micro computed tomography), remodeling (histomorphometry, osteoclast staining) and material (back-scattered electron imaging, x-ray diffraction) properties. Aged Bax-KO mice do not experience the loss in BMD, bone mechanics and trabecular bone structural properties typically observed with age. Enhanced ovarian cell numbers in Bax-KO mice likely indirectly leads to this enhanced bone phenotype. Ovariectomy results in the loss of the enhanced trabecular bone phenotype, but does not affect the cortical bone phenotype. As such, cortical bone may be protected from typical OVX effects due to sustained osteoblast function in Bax-KO mice. By contrast, young Hrk-KO mice exhibit higher BMD and trabecular bone structural properties compared to control mice, coupled with a compromised mechanical integrity. This subtle transient osteopetrotic-like phenotype is likely influenced by a potentially augmented osteoblast survival, albeit with a compromised activity. This osteopetrotic-like phenotype, and the effect of Hrk

  8. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics.

    Directory of Open Access Journals (Sweden)

    Dennie T Frederick

    Full Text Available While response rates to BRAF inhibitiors (BRAFi are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation with either vemurafenib or dabrafenib/trametinib combination. The observed changes in mRNA and protein levels with BRAFi treatment led us to hypothesize that combining BRAFi with a BCL-2 inhibitor (the BH3-mimetic navitoclax would improve outcome. We tested this hypothesis in cell lines and in mice. Pretreatment mRNA levels of BCL-2 negatively correlated with maximal tumor regression. Early increases in mRNA levels were seen in BIM, BCL-XL, BID and BCL2-W, as were decreases in MCL-1 and BCL2A. No significant changes were observed with BCL-2. Using reverse phase protein array (RPPA, significant increases in protein levels were found in BIM and BID. No changes in mRNA or protein correlated with response. Concurrent BRAF (PLX4720 and BCL2 (navitoclax inhibition synergistically reduced viability in BRAF mutant cell lines and correlated with down-modulation of MCL-1 and BIM induction after PLX4720 treatment. In xenograft models, navitoclax enhanced the efficacy of PLX4720. The combination of a selective BRAF inhibitor with a BH3-mimetic promises to be an important therapeutic strategy capable of enhancing the clinical efficacy of BRAF inhibition in many patients that might otherwise succumb quickly to de novo resistance. Trial registrations: ClinicalTrials.gov NCT01006980; ClinicalTrials.gov NCT01107418; ClinicalTrials.gov NCT01264380; ClinicalTrials.gov NCT01248936; ClinicalTrials.gov NCT00949702; ClinicalTrials.gov NCT01072175.

  9. Acidosis Sensing Receptor GPR65 Correlates with Anti-Apoptotic Bcl-2 Family Member Expression in CLL Cells: Potential Implications for the CLL Microenvironment

    OpenAIRE

    Rosko, Ashley E.; McColl, Karen S.; Zhong, Fei; Ryder, Christopher B; Chang, Ming-Jin; Sattar, Abdus; Caimi, Paolo F.; Hill, Brian T; Al-harbi, Sayer; Almasan, Alexandru; Distelhorst, Clark W.

    2014-01-01

    The tumor microenvironment is generally an acidic environment, yet the effect of extracellular acidosis on chronic lymphocytic leukemia (CLL) is not well established. Here we are the first to report that the extracellular acid sensing G-protein coupled receptor, GPR65, is expressed in primary CLL cells where its level correlate strongly with anti-apoptotic Bcl-2 family member levels. GPR65 expression is found normally within the lymphoid lineage and has not been previously reported in CLL. We...

  10. Targeting Antiapoptotic Bcl-2 Family Members with Cell-Permeable BH3 Peptides Induces Apoptosis Signaling, Death in Head, Neck Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Rongxiu Li

    2007-10-01

    Full Text Available Head, neck squamous cell carcinomas (HNSCCs are frequently characterized by chemotherapy, radiation resistance, by overexpression of Bcl-XL, an antiapoptotic member of the Bcl-2 protein family. In this report, we examined whether cell-permeable peptides derived from the BH3 domains of proapoptotic Bax, Bad, or Bak could be used to target Bcl-XL and/or Bcl-2 in HNSCC cells, induce apoptotic death in these cells. To render the peptides cell-permeable, Antennapedia (Ant or polyarginine (R8 peptide transduction domain was fused to the amino termini. Fluorescence microscopy of peptide-treated HNSCC cells revealed that the BH3 peptides colocalized with mitochondria, the site of Bcl-XL, Bcl-2 expression. By contrast, a mutant peptide (BaxE BH3 that cannot bind Bcl-XL or Bcl-2 was diffusely localized throughout the cytoplasm. Treatment of three HNSCC cell lines (1483, UM-22A, UM-22B with the wild-type BH3 peptides resulted in loss of viability, induction of apoptosis, as assessed by 3-(4,5-dimethythiazol-2yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS assays, annexin V staining. In general, Ant-conjugated peptides were more potent than R8-conjugated peptides, Bad BH3 peptide was typically more potent than Bax BH3 or Bak BH3. Treatment of purified HNSCC mitochondria with BH3 peptides resulted in robust release of cytochrome c. Thus, the relative apoptosis resistance of HNSCC cells is not due to a deficit in this step of the intrinsic, mitochondrialmediated apoptosis pathway. We conclude that cellpermeable BH3 peptides can be used to target Bcl-XL and/or Bcl-2 in HNSCC, that targeting of these proteins may have therapeutic value in the treatment of this disease.

  11. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis

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    Rooswinkel Rogier

    2009-10-01

    Full Text Available Abstract Background Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity both in vitro and in vivo. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies. Methods We tested the effect of (--gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-XL is known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach. Results AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced. Conclusion Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination

  12. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity both in vitro and in vivo. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies. We tested the effect of (-)-gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-XL is known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach. AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced. Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination therapies

  13. In situ hybridisation detects pro-apoptotic gene expression of a Bcl-2 family member in white syndrome-affected coral.

    Science.gov (United States)

    Ainsworth, T D; Knack, B; Ukani, L; Seneca, F; Weiss, Y; Leggat, W

    2015-12-01

    White syndrome has been described as one of the most prolific diseases on the Great Barrier Reef. Previously, apoptotic cell death has been described as the mechanism driving the characteristic rapid tissue loss associated with this disease, but the molecular mechanisms controlling apoptotic cell death in coral disease have yet to be investigated. In situ methods were used to study the expression patterns of 2 distinct regulators of apoptosis in Acropora hyacinthus tissues undergoing white syndrome and apoptotic cell death. Apoptotic genes within the Bcl-2 family were not localized in apparently healthy coral tissues. However, a Bcl-2 family member (bax-like) was found to localize to cells and tissues affected by white syndrome and those with morphological evidence for apoptosis. A potential up-regulation of pro-apoptotic or bax-like gene expression in tissues with apoptotic cell death adjacent to disease lesions is consistent with apoptosis being the primary cause of rapid tissue loss in coral affected by white syndrome. Pro-apoptotic (bax-like) expression in desmocytes and the basal tissue layer, the calicodermis, distant from the disease lesion suggests that apoptosis may also underlie the sloughing of healthy tissues associated with the characteristic, rapid spread of tissue loss, evident of this disease. This study also shows that in situ hybridisation is an effective tool for studying gene expression in adult corals, and wider application of these methods should allow a better understanding of many aspects of coral biology and disease pathology. PMID:26648107

  14. The flavonoid morin from Moraceae induces apoptosis by modulation of Bcl-2 family members and Fas receptor in HCT 116 cells.

    Science.gov (United States)

    Hyun, Hwang-Bo; Lee, Won Sup; Go, Se-Il; Nagappan, Arulkumar; Park, Cheol; Han, Min Ho; Hong, Su Hyun; Kim, Gonsup; Kim, Gi Young; Cheong, Jaehun; Ryu, Chung Ho; Shin, Sung Chul; Choi, Yung Hyun

    2015-01-01

    It is evident based on literature that flavonoids from fruit can safely modulate cancer cell biology and induce apoptosis. Therefore, we investigated the anticancer activity of morin, a flavonoid which is plentiful in twigs of mulberry focusing on apoptosis, and its mechanisms. Morin upregulated the Fas receptor, and activates caspase-8, -9 and -3 in HCT-116 cells. Morin also activates Bid, and induced the loss of mitochondrial membrane potential (MMP, ∆Ψm) with Bax protein activation and cytochrome c release. In addition, morin induced ROS generation which was not blocked by N-acetylcysteine. Morin also suppressed Bcl-2 and cIAP-1, anti-apoptotic proteins, which may contribute to augmentation of morin-triggered apoptosis. As an upstream signaling pathway, suppressed Akt activity by morin was associated to apoptosis. This study suggests that morin induces caspase-dependent apoptosis through extrinsic pathway by upregulating Fas receptor as well as through the intrinsic pathway by modulating Bcl-2 and IAP family members, and ROS generation, and that Akt is the critical upstream signaling that regulates the apoptotic effect of morin in human colon cancer HCT-116 cells.

  15. Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis

    Science.gov (United States)

    Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W.

    2012-01-01

    Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

  16. The Role of Bcl-2 Family Proteins in Therapy Responses of Malignant Astrocytic Gliomas: Bcl2L12 and Beyond

    Directory of Open Access Journals (Sweden)

    Fotini M. Kouri

    2012-01-01

    Full Text Available Glioblastoma (GBM is a highly aggressive and lethal brain cancer with a median survival of less than two years after diagnosis. Hallmarks of GBM tumors include soaring proliferative indices, high levels of angiogenesis, diffuse invasion into normal brain parenchyma, resistance toward therapy-induced apoptosis, and pseudopallisading necrosis. Despite the recent advances in neurosurgery, radiation therapy, and the development of targeted chemotherapeutic regimes, GBM remains one of the deadliest types of cancer. Particularly, the alkylating agent temozolomide (TMZ in combination with radiation therapy prolonged patient survival only marginally, and clinical studies assessing efficacies of targeted therapies, foremost ATP mimetics inhibiting the activity of receptor tyrosine kinases (RTKs, revealed only few initial responders; tumor recurrence is nearly universal, and salvage therapies to combat such progression remain ineffective. Consequently, myriad preclinical and clinical studies began to define the molecular mechanisms underlying therapy resistance of GBM tumors, and pointed to the Bcl-2 protein family, in particular the atypical member Bcl2-Like 12 (Bcl2L12, as important regulators of therapy-induced cell death. This review will discuss the multi-faceted modi operandi of Bcl-2 family proteins, describe their roles in therapy resistance of malignant glioma, and outline current and future drug development efforts to therapeutically target Bcl-2 proteins.

  17. Prognostic Significance of Apoptosis Related Gene Family bcl-2 in Human Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the prognostic effect of bcl-2 oncogene and its gene family members bax, bcl-x expression in breast cancer patients. Methods: expression of bcl-2, bax proteins in 91 human breast cancer tissue sections were studied by immunohistochemical method. Bcl-x1 mRNA expression in frozen tissues from 16 breast cancer patients were detected using Northern blot method. Results: bcl-2 protein positivity was found in 60/91 (65.9%) patients, and bax positivity 59/91 (64.8%). Bcl-2 and bax expression levels were associated with apoptotic index(AI), histological grade, axillary lymph node metastasis, postoperative local recurrence and metastasis. Bcl-2 expression was related to ER positivity. In univariate analysis for disease free survival (DFS), bcl-2 and bax protein levels, and Al were all found to have prognostic value. The result of Cox's model multivariate analysis showed that bcl-2 protein level was an independent prognostic factor. In 16 frozen breast cancer tissues, 8/16(50%) had higher level of bcl-x1 mRNA, which showed correlation with bcl-2 protein expression and axillary lymph node metastasis. Conclusion: The findings indicate that dysregulated expressions of bcl-2, bax and bcl-x1 apoptosis-related genes, suggestive of serious deregulation of apoptotic process, may contribute to the biologic aggressiveness of breast cancer. Bcl-2 protein is an independent indicator of prognosis in breast cancer patients.

  18. Roscovitine-induced apoptosis in neutrophils and neutrophil progenitors is regulated by the Bcl-2-family members Bim, Puma, Noxa and Mcl-1.

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    Sanjivan Gautam

    Full Text Available Neutrophil granulocyte (neutrophil apoptosis plays a key role in determining inflammation in infectious and non-infectious settings. Recent work has shown that inhibitors of cyclin-dependent kinases (cdk such as roscovitine can potently induce neutrophil apoptosis and reduce inflammation. Using a conditional Hoxb8-expression system we tested the participation of Bcl-2-family proteins to roscovitine-induced apoptosis in mouse neutrophils and in neutrophil progenitor cells. Bcl-2 strongly protected against roscovitine-induced apoptosis in neutrophils. The isolated loss of either Bim or noxa provided significant, partial protection while protection through combined loss of Bim and noxa or Bim and Puma was only slightly greater than this individual loss. The only substantial change in protein levels observed was the loss of Mcl-1, which was not transcriptional and was inhibited by proteasome blockade. In progenitor cells there was no protection by the loss of Bim alone but substantial protection by the loss of both Bim and Puma; surprisingly, strongest protection was seen by the isolated loss of noxa. The pattern of protein expression and Mcl-1-regulation in progenitor cells was very similar to the one observed in differentiated neutrophils. In addition, roscovitine strongly inhibited proliferation in progenitor cells, associated with an accumulation of cells in G2/M-phase.

  19. Significance of Bcl-2 family in tumor progression and therapy%Bcl-2家族在肿瘤进展和治疗中的意义

    Institute of Scientific and Technical Information of China (English)

    朱园园

    2008-01-01

    Bcl-2 family have dual-regulating effects on cell apoptosis mediated by mitoehondrion. The ratio of pro-apoptosis members and anti-apoptosis members closely correlates with tumorigenesis, drug-resist-ance and prognosis. Therefore,Bcl-2 family become important targets in tumor biotherapy. Many strategies have been applied to tumors treatment targeting Bcl-2 family,such as some biological treatment,short peptides and organic small molecules.%Bcl-2家族对于线粒体途径细胞凋亡具有双重调控作用,其促凋亡蛋白与抑凋亡蛋白的比例与肿瘤形成、肿瘤耐药性的产生及预后密切相关.因此,Bcl-2家族成为肿瘤生物治疗中的重要靶点,针对Bcl-2家族的某些生物治疗手段和短肽、有机小分子等新药被开发应用于Bcl-2高表达肿瘤的治疗.

  20. BCL-2 family proteins as regulators of mitochondria metabolism.

    Science.gov (United States)

    Gross, Atan

    2016-08-01

    The BCL-2 family proteins are major regulators of apoptosis, and one of their major sites of action are the mitochondria. Mitochondria are the cellular hubs for metabolism and indeed selected BCL-2 family proteins also possess roles related to mitochondria metabolism and dynamics. Here we discuss the link between mitochondrial metabolism/dynamics and the fate of stem cells, with an emphasis on the role of the BID-MTCH2 pair in regulating this link. We also discuss the possibility that BCL-2 family proteins act as metabolic sensors/messengers coming on and off of mitochondria to "sample" the cytosol and provide the mitochondria with up-to-date metabolic information. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID:26827940

  1. Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation

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    Lowthert Lori

    2012-09-01

    Full Text Available Abstract Background Lithium is considered by many as the gold standard medication in the management of bipolar disorder (BD. However, the clinical response to lithium is heterogeneous, and the molecular basis for this difference in response is unknown. In the present study, we sought to determine how the peripheral blood gene expression profiles of patients with bipolar disorder (BD changed over time following intitiation of treatment with lithium, and whether differences in those profiles over time were related to the clinical response. Methods Illumina Sentrix Beadchip (Human-6v2 microarrays containing > 48,000 transcript probes were used to measure levels of expression of gene-expression in peripheral blood from 20 depressed subjects with BD prior to and every two weeks during 8 weeks of open-label treatment with lithium. Changes in gene-expression were compared between treatment responders (defined as a decrease in the Hamilton Depression Rating Scale of 50% or more and non-responders. Pathway analysis was conducted using GeneGO Metacore software. Results 127 genes showed a differential response in responders vs. non-responders. Pathway analysis showed that regulation of apoptosis was the most significantly affected pathway among these genes. Closer examination of the time-course of changes among BCL2 related genes showed that in lithium-responders, one month after starting treatment with lithium, several anti-apoptotic genes including Bcl2 and insulin receptor substrate 2 (IRS2 were up-regulated, while pro-apoptotic genes, including BCL2-antagonist/killer 1 (BAK1 and BCL2-associated agonist of cell death (BAD, were down-regulated. In contrast, in lithium non-responders, BCL2 and IRS2 were down-regulated, while BAK1 and BAD up-regulated at the one-month time-point. Conclusions These results suggest that differential changes in the balance of pro- and anti- apoptotic gene-expression following treatment with lithium may explain some of

  2. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies

    OpenAIRE

    Bogenberger, J M; Kornblau, S. M.; Pierceall, W E; Lena, R.; Chow, D.; Shi, C-X; Mantei, J; Ahmann, G; Gonzales, I M; A. Choudhary; R. Valdez; Camoriano, J; Fauble, V; Tiedemann, R E; Qiu, Y H

    2014-01-01

    Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-XL, BCL-2 and MCL-1 contribution to 5-Azacytidine activity, siRNA silencing of BCL-XL and MCL-1, but not BCL-2, exhibited variable synergy with 5-Azacytidine in vitro. The BCL-XL, BCL-2 and BCL-w inhibitor ABT-737 sensitize...

  3. Characterization of vNr-13, the first alphaherpesvirus gene of the bcl-2 family

    International Nuclear Information System (INIS)

    The Bcl-2 family, including antiapoptotic and proapoptotic members, plays key regulating roles in programmed cell death. We report the characterization of a new member of the bcl-2 family, encoded by herpesvirus of turkeys (HVT). The product of this gene shares 80% homology with Nr-13, an apoptosis inhibitor, which is overexpressed in avian cells transformed by the v-src oncogene. This new gene, that we propose to call vnr-13, is the first member of the bcl-2 family to be isolated among α-herpesviruses. Results from cells expressing the HVT-vnr-13 gene product show that the encoded protein inhibits apoptosis and also reduces the rate of cellular proliferation. Contrary to all bcl-2 homologues found in γ-herpesvirus, which are intronless, vnr-13 has the same organization as the cellular nr-13 gene. Hence, the HVT vnr-13 gene may have been acquired from a reverse transcriptase product of an unspliced precursor RNA, or via direct recombination with the host chromosomal DNA

  4. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies

    Science.gov (United States)

    Bogenberger, J M; Kornblau, S M; Pierceall, W E; Lena, R; Chow, D; Shi, C-X; Mantei, J; Ahmann, G; Gonzales, I M; Choudhary, A; Valdez, R; Camoriano, J; Fauble, V; Tiedemann, R E; Qiu, Y H; Coombes, K R; Cardone, M; Braggio, E; Yin, H; Azorsa, D O; Mesa, R A; Stewart, A K; Tibes, R

    2014-01-01

    Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-XL, BCL-2 and MCL-1 contribution to 5-Azacytidine activity, siRNA silencing of BCL-XL and MCL-1, but not BCL-2, exhibited variable synergy with 5-Azacytidine in vitro. The BCL-XL, BCL-2 and BCL-w inhibitor ABT-737 sensitized most cell lines more potently compared with the selective BCL-2 inhibitor ABT-199, which synergized with 5-Azacytidine mostly at higher doses. Ex vivo, ABT-737 enhanced 5-Azacytidine activity across primary AML, MDS and MPN specimens. Protein levels of BCL-XL, BCL-2 and MCL-1 in 577 AML patient samples showed overlapping expression across AML FAB subtypes and heterogeneous expression within subtypes, further supporting a concept of dual/multiple BCL-2 family member targeting consistent with RNAi and pharmacologic results. Consequently, silencing of MCL-1 and BCL-XL increased the activity of ABT-199. Functional interrogation of BCL-2 family proteins by BH3 profiling performed on patient samples significantly discriminated clinical response versus resistance to 5-Azacytidine-based therapies. On the basis of these results, we propose a clinical trial of navitoclax (clinical-grade ABT-737) combined with 5-Azacytidine in myeloid malignancies, as well as to prospectively validate BH3 profiling in predicting 5-Azacytidine response. PMID:24451410

  5. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies.

    Science.gov (United States)

    Bogenberger, J M; Kornblau, S M; Pierceall, W E; Lena, R; Chow, D; Shi, C-X; Mantei, J; Ahmann, G; Gonzales, I M; Choudhary, A; Valdez, R; Camoriano, J; Fauble, V; Tiedemann, R E; Qiu, Y H; Coombes, K R; Cardone, M; Braggio, E; Yin, H; Azorsa, D O; Mesa, R A; Stewart, A K; Tibes, R

    2014-08-01

    Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-XL, BCL-2 and MCL-1 contribution to 5-Azacytidine activity, siRNA silencing of BCL-XL and MCL-1, but not BCL-2, exhibited variable synergy with 5-Azacytidine in vitro. The BCL-XL, BCL-2 and BCL-w inhibitor ABT-737 sensitized most cell lines more potently compared with the selective BCL-2 inhibitor ABT-199, which synergized with 5-Azacytidine mostly at higher doses. Ex vivo, ABT-737 enhanced 5-Azacytidine activity across primary AML, MDS and MPN specimens. Protein levels of BCL-XL, BCL-2 and MCL-1 in 577 AML patient samples showed overlapping expression across AML FAB subtypes and heterogeneous expression within subtypes, further supporting a concept of dual/multiple BCL-2 family member targeting consistent with RNAi and pharmacologic results. Consequently, silencing of MCL-1 and BCL-XL increased the activity of ABT-199. Functional interrogation of BCL-2 family proteins by BH3 profiling performed on patient samples significantly discriminated clinical response versus resistance to 5-Azacytidine-based therapies. On the basis of these results, we propose a clinical trial of navitoclax (clinical-grade ABT-737) combined with 5-Azacytidine in myeloid malignancies, as well as to prospectively validate BH3 profiling in predicting 5-Azacytidine response. PMID:24451410

  6. Intrinsic order and disorder in the bcl-2 member harakiri: insights into its proapoptotic activity.

    Directory of Open Access Journals (Sweden)

    Susana Barrera-Vilarmau

    Full Text Available Harakiri is a BH3-only member of the Bcl-2 family that localizes in membranes and induces cell death by binding to prosurvival Bcl-x(L and Bcl-2. The cytosolic domain of Harakiri is largely disorder with residual α-helical conformation according to previous structural studies. As these helical structures could play an important role in Harakiri's function, we have used NMR and circular dichroism to fully characterize them at the residue-atomic level. In addition, we report structural studies on a peptide fragment spanning Harakiri's C-terminal hydrophobic sequence, which potentially operates as a transmembrane domain. We initially checked by enzyme immunoassays and NMR that peptides encompassing different lengths of the cytosolic domain are functional as they bind Bcl-x(L and Bcl-2. The structural data in water indicate that the α-helical conformation is restricted to a 25-residue segment comprising the BH3 domain. However, structure calculation was precluded because of insufficient NMR restraints. To bypass this problem we used alcohol-water mixture to increase structure population and confirmed by NMR that the conformation in both milieus is equivalent. The resulting three-dimensional structure closely resembles that of peptides encompassing the BH3 domain of BH3-only members in complex with their prosurvival partners, suggesting that preformed structural elements in the disordered protein are central to binding. In contrast, the transmembrane domain forms in micelles a monomeric α-helix with a population close to 100%. Its three-dimensional structure here reported reveals features that explain its function as membrane anchor. Altogether these results are used to propose a tentative structural model of how Harakiri works.

  7. Small Molecule Inhibitors of Bcl-2 Family Proteins for Pancreatic Cancer Therapy

    International Nuclear Information System (INIS)

    Pancreatic cancer (PC) has a complex etiology and displays a wide range of cellular escape pathways that allow it to resist different treatment modalities. Crucial signaling molecules that function downstream of the survival pathways, particularly at points where several of these pathways crosstalk, provide valuable targets for the development of novel anti-cancer drugs. Bcl-2 family member proteins are anti-apoptotic molecules that are known to be overexpressed in most cancers including PC. The anti-apoptotic machinery has been linked to the observed resistance developed to chemotherapy and radiation and therefore is important from the targeted drug development point of view. Over the past ten years, our group has extensively studied a series of small molecule inhibitors of Bcl-2 against PC and provide solid preclinical platform for testing such novel drugs in the clinic. This review examines the efficacy, potency, and function of several small molecule inhibitor drugs targeted to the Bcl-2 family of proteins and their preclinical progress against PC. This article further focuses on compounds that have been studied the most and also discusses the anti-cancer potential of newer class of Bcl-2 drugs

  8. Therapeutic Modulation of Apoptosis: Targeting the BCL-2 Family at the Interface of the Mitochondrial Membrane

    Science.gov (United States)

    Nemec, Kathleen N.

    2008-01-01

    A vast portion of human disease results when the process of apoptosis is defective. Disorders resulting from inappropriate cell death range from autoimmune and neurodegenerative conditions to heart disease. Conversely, prevention of apoptosis is the hallmark of cancer and confounds the efficacy of cancer therapeutics. In the search for optimal targets that would enable the control of apoptosis, members of the BCL-2 family of anti- and pro-apoptotic factors have figured prominently. Development of BCL-2 antisense approaches, small molecules, and BH3 peptidomimetics has met with both success and failure. Success-because BCL-2 proteins play essential roles in apoptosis. Failure-because single targets for drug development have limited scope. By examining the activity of the BCL-2 proteins in relation to the mitochondrial landscape and drawing attention to the significant mitochondrial membrane alterations that ensue during apoptosis, we demonstrate the need for a broader based multi-disciplinary approach for the design of novel apoptosis-modulating compounds in the treatment of human disease. PMID:18972587

  9. EXPRESSION AND SIGNIFICANCE OF bcl-2 FAMILY IN AMELOBLASTONA

    Institute of Scientific and Technical Information of China (English)

    WANG Jie; MA Jie; ZHONG Ming; LIU Jing-dong

    2006-01-01

    Objective: To study the expression of bcl-2 and bax in human ameloblastoma (AB), and investigate the role of apoptosis in genesis and development of AB and the relation of apoptosis with the clinic biological characteristics of AB. Methods:BCL-2 and BAX proteins were detected in 75 cases of AB (primary AB 31 cases, recurrent AB 37 cases, malignant AB 7cases) by S-P method. Oral normal mucosa (NOM) and Odontogenic kerotosyst (OKC) were used as controls. Bcl-2 and bax mRNA in 20 cases of AB, 12 cases of OKC were detected by in situ hybridization. Results: The positive ratio of BCL-2protein was 88.0% ( 66/75 ) in AB, 74.3% (26/35) in OKC and 44.4% (4/9) in NOM, respectively (P<0.001). BCL-2 protein was expressed in peripheral cells and a few scattered stellate-shape cells in AB. The positive ratio of BAX protein was 74.7%(56/75)in AB, 65.7%(23/35)in OKC and 77.8%(7/9) in NOM, respectively (P<0.001). BAX protein was expressed in peripheral cells and stellate-shape cells with similar intensity. BCL-2 expression increased in recurrent and AB canceration(P<0.01), while for BAX expression, the positive ratio was higher in recurrent AB, but lower than that of malignant AB. A moderate negative correlation between BCL-2 and BAX protein was found (rk=-0.331, P<0.001).Conclusion: AB has much more apoptosis-inhibiting protein than apoptosis- accelarating protein. Apoptosis plays an important role in genesis, development of AB. The fashion and intensity of bcl-2 and bax expression were different in various tissues and in benign or malignant AB.

  10. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tee, Thiam-Tsui, E-mail: thiamtsu@yahoo.com [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Cheah, Yew-Hoong [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Bioassay Unit, Herbal Medicine Research Center, Institute for Medical Research, Jalan Pahang, Kuala Lumpur (Malaysia); Meenakshii, Nallappan [Biology Department, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Mohd Sharom, Mohd Yusof; Azimahtol Hawariah, Lope Pihie [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer We isolated xanthorrhizol, a sesquiterpenoid compound from Curcuma xanthorrhiza. Black-Right-Pointing-Pointer Xanthorrhizol induced apoptosis in HepG2 cells as observed using SEM. Black-Right-Pointing-Pointer Apoptosis in xanthorrhizol-treated HepG2 cells involved Bcl-2 family proteins. Black-Right-Pointing-Pointer DNA fragmentation was observed in xanthorrhizol-treated HepG2 cells. Black-Right-Pointing-Pointer DNA fragmentation maybe due to cleavage of PARP and DFF45/ICAD proteins. -- Abstract: Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X{sub L} expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

  11. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Highlights: ► We isolated xanthorrhizol, a sesquiterpenoid compound from Curcuma xanthorrhiza. ► Xanthorrhizol induced apoptosis in HepG2 cells as observed using SEM. ► Apoptosis in xanthorrhizol-treated HepG2 cells involved Bcl-2 family proteins. ► DNA fragmentation was observed in xanthorrhizol-treated HepG2 cells. ► DNA fragmentation maybe due to cleavage of PARP and DFF45/ICAD proteins. -- Abstract: Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-XL expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

  12. Phosphatidylinositol 3-kinase is essential for kit ligand-mediated survival, whereas interleukin-3 and flt3 ligand induce expression of antiapoptotic Bcl-2 family genes

    DEFF Research Database (Denmark)

    Karlsson, Richard; Engström, Maria; Jönsson, Maria;

    2003-01-01

    affect the survival. We next established if IL-3 and FL activated antiapoptotic Bcl-2 and the related genes Bcl-XL and Mcl-1. By RNA protection assay and Western blot analysis, we show that all three genes are induced by IL-3, whereas FL induces Bcl-2 and to some extent Bcl-XL. Importantly, KL could not...... sustain their expression. Moreover, use of inhibitors implied that IL-3 was mainly exerting its effect on Bcl-2 at the level of transcription. The addition of LY294002 did not affect the expression of Bcl-2 and Bcl-XL, and thus, we conclude that expression of antiapoptotic Bcl-2 family member genes is not...

  13. Multimodal Interaction with BCL-2 Family Proteins Underlies the Pro-Apoptotic Activity of PUMA BH3

    OpenAIRE

    Edwards, Amanda L.; Gavathiotis, Evripidis; LaBelle, James L.; Braun, Craig R.; Opoku-Nsiah, Kwadwo A.; Bird, Gregory H.; Walensky, Loren D.

    2013-01-01

    PUMA is a pro-apoptotic BCL-2 family member that drives the apoptotic response to a diversity of p53-dependent and independent cellular insults. Deciphering the spectrum of PUMA interactions that confer its context-dependent pro-apoptotic properties remains a high priority goal. Here, we report the synthesis of PUMA SAHBs, structurally-stabilized PUMA BH3 helices that, in addition to broadly targeting anti-apoptotic proteins, directly bind to BAX. NMR, photocrosslinking, and biochemical analy...

  14. Common Patterns of Bcl-2 Family Gene Expression in Two Traumatic Brain Injury Models

    OpenAIRE

    Strauss, Kenneth I.; NARAYAN, RAJ K.; Raghupathi, Ramesh

    2004-01-01

    Cell death/survival following traumatic brain injury (TBI) may be a result of alterations in the intracellular ratio of death and survival factors. Bcl-2 family genes mediate both cell survival and the initiation of cell death. Using lysate RNase protections assays, mRNA expression of the anti-cell death genes Bcl-2 and Bcl-xL, and the pro-cell death gene Bax, was evaluated following experimental brain injuries in adult male Sprague-Dawley rats. Both the lateral fluid-percussion (LFP) and the...

  15. Bid, a widely expressed proapoptotic protein of the Bcl-2 family, displays lipid transfer activity

    DEFF Research Database (Denmark)

    Esposti, M D; Erler, Janine Terra; Hickman, J A;

    2001-01-01

    Bid is an abundant proapoptotic protein of the Bcl-2 family that is crucial for the induction of death receptor-mediated apoptosis in primary tissues such as liver. Bid action has been proposed to involve the relocation of its truncated form, tBid, to mitochondria to facilitate the release of apo...

  16. The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

    Science.gov (United States)

    Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

    2013-02-14

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263. PMID:24900652

  17. Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro- apoptosis members that regulate apoptosis, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by caspase 8 in response to Fas/TNF-R1 death receptor signals. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates downstream caspases. Such a connection between the two apoptosis pathways could be important for induction of apoptosis in certain types of cells and responsible for the pathogenesis of a number of human diseases.

  18. Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk.

    Science.gov (United States)

    Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W

    2012-08-10

    Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

  19. Bcl2 Family Functions as Signaling Target in Nicotine-/NNK-Induced Survival of Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xingming Deng

    2014-01-01

    Full Text Available Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells. In contrast to nicotine, NNK is a more potent carcinogen that not only induces single-strand DNA breaks and oxidative DNA damage but also stimulates survival and proliferation of normal lung epithelial and lung cancer cells. However, the molecular mechanism(s by which nicotine and NNK promote cell survival, proliferation, and lung tumor development remains elusive. The fate of cells (i.e., survival or death is largely decided by the Bcl2 family members. In the past several years, multiple signaling links between nicotine/NNK and Bcl2 family members have been identified that regulate survival and proliferation. This review provides a concise, systematic overview of the current understanding of the role of the pro- or antiapoptotic proteins in cigarette smoking, lung cancer development, and treatment resistance.

  20. Functional Cooperation of the Proapoptotic Bcl2 Family Proteins Bmf and Bim In Vivo ▿

    OpenAIRE

    Hübner, Anette; Cavanagh-Kyros, Julie; Rincon, Mercedes; Richard A Flavell; Davis, Roger J

    2009-01-01

    Bcl2-modifying factor (Bmf) is a member of the BH3-only group of proapoptotic proteins. To test the role of Bmf in vivo, we constructed mice with a series of mutated Bmf alleles that disrupt Bmf expression, prevent Bmf phosphorylation by the c-Jun NH2-terminal kinase (JNK) on Ser74, or mimic Bmf phosphorylation on Ser74. We report that the loss of Bmf causes defects in uterovaginal development, including an imperforate vagina and hydrometrocolpos. We also show that the phosphorylation of Bmf ...

  1. Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different cancer cell types.

    Directory of Open Access Journals (Sweden)

    Audrey Sermeus

    Full Text Available Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIM(EL. BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins abundance or post-translational modifications partly account for chemoresistance. Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by hypoxia involves p53-dependent and -independent pathways and is cell type-dependent. A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ameliorate cancer therapy.

  2. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  3. Minocycline mechanism of neuroprotection involves the Bcl-2 gene family in optic nerve transection.

    Science.gov (United States)

    Levkovitch-Verbin, Hani; Waserzoog, Yael; Vander, Shelly; Makarovsky, Daria; Ilia, Piven

    2014-10-01

    The second-generation tetracycline, minocycline, has been shown to exhibit neuroprotective therapeutic benefits in many neurodegenerative diseases including experimental glaucoma and optic nerve transection (ONT). This study investigated the mechanism underlying minocycline neuroprotection in a model of ONT. ONT was applied unilaterally in 36 Wistar rat eyes. The rats were randomly divided into a minocycline (22 mg/kg/d) treatment group and a saline treatment group (control). Treatment (minocycline or saline) was given by intraperitoneal injections initiated 3 d before ONT and continued daily until the end of the experiment. The involvement of pro-apoptotic, pro-survival and inflammatory pathways was analyzed by quantitative Real-Time Polymerase Chain Reaction at 4 h and 3 d after the transection in both treatment groups. The involvement of Bcl-2 protein was evaluated by immunohistochemistry. We found that Minocycline significantly increased the expression of the antiapoptotic gene bcl-2 4 h after transection (n = 8, p = 0.008) and decreased the expression of Bax at the same time point (n = 8, p = 0.03). Tumor Necrosis Factor α (TNFα), Inhibitor of Apoptosis Protein (IAP1) and Gadd45α were significantly upregulated in the retinas of eyes with ONTs compared to control (n = 10 for each gene, p = 0.02, p = 0.03, p = 0.04, respectively) but this effect was unaffected by minocycline. This study further support that the mechanism underlying minocycline neuroprotection involves the Bcl-2 gene family, suggesting that minocycline has antiapoptotic properties that support its value as a promising neuroprotective drug. PMID:24410139

  4. Effect of chronic intraperitoneal aminoguanidine on memory and expression of Bcl-2 family genes in diabetic rats.

    Science.gov (United States)

    Alipour, Mohsen; Adineh, Fatemeh; Mosatafavi, Hossein; Aminabadi, Azam; Monirinasab, Hananeh; Jafari, Mohammad Reza

    2016-06-01

    Long-term hyperglycemia associates with memory defects via hippocampal cells damaging. The aim of the present study was to examine the effect of 1 month of i.p. injections of AG on passive avoidance learning (PAL) and hippocampal apoptosis in rat. Eighty male rats were divided into 10 groups: control, nondiabetics and STZ-induced diabetics treated with AG (50, 100, 200, and 400 mg/kg, i.p.). PAL and the Bcl-2 family gene expressions were determined. Diabetes resulted in memory and Bcl-2 family gene expression deficits. AG (50 and 100 mg/kg) significantly improved the learning and Bcl-2, Bcl-xl, Bax, and Bak impairment in diabetic rats. However, negative effects were indicated by higher doses of the drug (200 and 400 mg/kg). Present study suggests that 1 month of i.p. injections of lower doses of AG, may improve the impaired cognitive tasks in STZ-induced diabetic rats possibly by modulating Bcl-2 family gene expressions. PMID:27210113

  5. The Action of Bcl-2 Apoptotic Family Proteins and Caspases in Mediating Follicle Atresia in Adult Mouse

    Directory of Open Access Journals (Sweden)

    Liliana Petculescu-Ciochină

    2011-05-01

    Full Text Available Among follicles present on the surface of the ovary only a small part reach ovulation, the majority entering atresia, which is an apoptotic process regulated hormonally in general. Apoptosis (from greek: apo = from, ptosis = falling - is a normal physiological process, genetically programmed cell death, which carries energy consumption by activating a program of internal suicide. This occurs at each stage of follicular development and is accompanied by a significant reduction in the number of follicles present at birth. Development stage-dependent mechanisms coordinate the evolution of follicles, leading to ovulation of a very small number of them. At follicular level apoptosis involves many morphological and biochemical processes that are based on pro-and anti-apoptotic members of Bcl-2 family of proteins (located on mitochondrial outer membrane and caspases. These changes aim internucleosomal DNA fragmentation, cell retraction followed by its wrinkling, cytoskeleton disruption, preservation of cytoplasmic organelles structure and function, loss of intercellular ties with the reduced expression of conexine 43 (key protein of communication junctions between granulose cells, progressive fragmentation of nucleus and cytoplasm, and finally the appearance of apoptotic bodies, and their inclusion by phagocytes, without the involvement of any inflammatory response.

  6. Evaluation of Bcl-2 Family Gene Expression in Hippocampus of 3, 4-methylenedioxymethamphetamine Treated Rats

    Directory of Open Access Journals (Sweden)

    Hamed Hashemi-Nasl

    2012-01-01

    Full Text Available Objective: 3,4-methylenedioxymethamphetamine (MDMA is an illicit, recreational drugthat causes cellular death and neurotoxicity. This study evaluates the effects of differentdoses of MDMA on the expression of apoptosis–related proteins and genes in the hippocampusof adult rats.Materials and Methods: In this expremental study,a total of 20 male Sprague Dawley rats(200-250 g were treated with MDMA (0, 5, 10, 20 mg/kg i.p. twice daily for 7 days. Sevendays after the last administration of MDMA, the rats were killed. Bax and Bcl-2 genesin addition to protein expressions were detected by western blot and reverse transcriptionpolymerasechain reaction (RT-PCR.Results were analyzed using one-way ANOVA andp≤0.05 was considered statistically significant.Results: Our results showed that MDMA caused dose dependent up-regulation of Baxand down-regulation of Bcl-2 in the hippocampus. There was a significant alteration inbcl-2 and bax genes density.Conclusion: Changes in apoptosis-related proteins and respective genes relating to Baxand Bcl-2 might be involved in the molecular mechanism of MDMA-induced apoptosis.

  7. Enhanced apoptotic response to photodynamic therapy after bcl-2 transfection.

    Science.gov (United States)

    Kim, H R; Luo, Y; Li, G; Kessel, D

    1999-07-15

    Apoptosis is a cellular death process involving the sequential activation of a series of caspases, endonucleases, and other enzymes. The initiation of apoptosis can be inhibited by overexpression of bcl-2 and certain other members of a related family of proteins. We examined the effects of bcl-2 overexpression on the apoptotic response to photodynamic therapy (PDT), using aluminum phthalocyanine as the photosensitizing agent. In this study, we compared the immortalized human breast epithelial cell line MCF10A with a subline (MCF10A/bcl-2) transfected with the human bcl-2 gene. The latter was approximately 2-fold more sensitive to the phototoxic effects of PDT. At a 50 mJ/cm2 light dose, photodamage to MCF-10A/bcl-2 resulted in a greater loss of the mitochondrial membrane potential (delta(psi)m), enhanced release of mitochondrial cytochrome c, a more rapid and greater activation of caspase-3, and a greater apoptotic response. Western blot analysis revealed that the transfected cell line showed overexpression of both bcl-2 and bax, and that PDT caused selective destruction of bcl-2, leaving bax unaffected. The greater apoptotic response by the transfected line is, therefore, attributed to the higher bax:bcl-2 ratio after photodamage.

  8. Statins, Bcl-2 and Apoptosis: Cell Death or Cell Protection?

    OpenAIRE

    Wood, W. Gibson; Igbavboa, Urule; Muller, Walter E.; Gunter P. Eckert

    2013-01-01

    Statins have proven their effectiveness in the treatment of cardiovascular disease. This class of drugs has also attracted attention as a potential treatment for dissimilar diseases such as certain types of cancers and neurodegenerative diseases. What appears to be a contradiction is that in the case of cancer, it has been suggested that statins increase apoptosis and alter levels of Bcl-2 family members (e.g., reduce Bcl-2 and increase Bax) whereas, studies mainly using non-cancerous cells r...

  9. Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins.

    Science.gov (United States)

    Kennedy, R Kamaraj; Veena, V; Naik, P Ravindra; Lakshmi, Pragna; Krishna, R; Sudharani, S; Sakthivel, N

    2015-06-01

    Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN instigates apoptosis by mitochondrial intrinsic apoptotic pathway via the overexpression of p53, Bax, cytochrome C release and activation of caspase-3 with the inhibition of oncogenic anti-apoptotic proteins such as PARP and Bcl-2 family proteins (Bcl-2, Bcl-w and Bcl-xL). The in silico docking studies of PCN targeted against the anti-apoptotic members of Bcl-2 family proteins revealed the interaction of PCN with the BH3 domain, which might lead to the induction of apoptosis due to the inhibition of antiapoptotic proteins. Due to its innate inhibition potential of antiapoptotic Bcl-2 family proteins, PCN may be used as potent anticancer agent against both lung and breast cancer.

  10. BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy.

    Science.gov (United States)

    Pedro, Jose Manuel Bravo-San; Wei, Yongjie; Sica, Valentina; Maiuri, Maria Chiara; Zou, Zhongju; Kroemer, Guido; Levine, Beth

    2015-01-01

    Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

  11. Arsenite induces apoptosis in human mesenchymal stem cells by altering Bcl-2 family proteins and by activating intrinsic pathway

    International Nuclear Information System (INIS)

    Purpose: Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs. Methods: MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAsIII) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed. Results: iAsIII induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAsIII in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway. Conclusion: iAsIII can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.

  12. Expression of Bcl-2 inhibited Fas-mediated apoptosis in human hepatocellular carcinoma BEL-7404 cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Apoptosis plays an important role in embryonic development, tissue remodeling, immune regulation and tumor regression. Two groups of molecules (Bcl-2 family and"Death factor"family) are involved in regulating apoptosis. In order to know about the effect of Bcl-2 on apoptosis induced by Fas, a typical member of"Death factor" family, the transfection experiments with expression vectors pcDNA3-fland pcDNA3-bcl-2 were performed in BEL-7404 cells, a human hepatocellular carcinoma cell line which expresses endogenous Fas, but not FasL and Bcl2. The data showed that the expression of FasL in pcDNA3fl transfected hepatoma cells obviously induced the apoptosis of the cells. However, the overexpression of Bcl-2 in pcDNA3bcl-2 transfected 7404/b-16 cells counteracted pcDNA3-fltransient transfection mediated apoptosis. Further study by cotransfection experiments indicated that Bid but not Bax (both were pro-apoptotic proteins of Bcl-2 family) blocked the inhibitory effect of Bcl-2 on Fas-mediated apoptosis. These results suggested that Fas-mediated apoptosis in human hcpatoma cells is possibly regulated by Bcl-2 family proteins via mitochondria pathway.

  13. Assessment of expression of selected Bcl-2 family proteins in lymphoid infiltration in patients with B-cell chronic lymphocytic leukaemia treated with nucleoside analogues.

    Directory of Open Access Journals (Sweden)

    Janusz Kłoczko

    2008-12-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL is characterized by clonal growth and accumulation of mature lymphoid cells due to disturbance in genetically regulated form of cell death called apoptosis. The intrinsic mechanism of apoptosis is controlled by Bcl-2 family proteins. Purine nucleoside analogues induce the apoptosis in cells in a state of quiescence. The aim of the study was to assess expression of selected Bcl-2 family proteins in neoplastic infiltration in bone marrow in patients with B-CLL treated with nucleoside analogues. The study comprised examination of bone marrow obtained routinely by trephine biopsy from 18 patients with B-CLL diagnosed before administration of purine nucleoside analogues treatment and after its completion. Expression of Bcl-2, Bcl-x and Bax proteins was examined. Lymphoid cells in bone marrow were present in all patients before administration of treatment. After treatment in two patients bone marrow was infiltrated in diffuse pattern, whereas other patients presented nodular pattern of infiltration. The difference between stage of infiltration before and after treatment was statistically significant (p<0.002. High percentage of infiltration cells with positive anti Bcl-2 reaction from 42.0% in one patient to 85.33+/-3.06% in four patients before treatment was observed. After treatment percentage of infiltration cells with positive anti Bcl-2 antibody reaction was from 33.0+/-18.38% in two patients to 99.0% in one patient. Positive correlation between stage of infiltration and expression of Bcl-2 protein was confirmed before and after treatment. Such correlations were not observed in case of Bax and Bcl-x. Strong staining of immunohistochemical reaction of cells in lymphoid infiltration with Bcl-2 antibody was confirmed. There was a difference between Bcl-/Bax ratio before and after treatment. Immunohistochemical assessment of expression of Bcl-2 family proteins in cells of lymphoid infiltration in bone

  14. A novel BH3 mimetic efficiently induces apoptosis in melanoma cells through direct binding to anti-apoptotic Bcl-2 family proteins, including phosphorylated Mcl-1.

    Science.gov (United States)

    Liu, Yubo; Xie, Mingzhou; Song, Ting; Sheng, Hongkun; Yu, Xiaoyan; Zhang, Zhichao

    2015-03-01

    The Bcl-2 family modulates sensitivity to chemotherapy in many cancers, including melanoma, in which the RAS/BRAF/MEK/ERK pathway is constitutively activated. Mcl-1, a major anti-apoptotic protein in the Bcl-2 family, is extensively expressed in melanoma and contributes to melanoma's well-documented chemoresistance. Here, we provide the first evidence that Mcl-1 phosphorylation at T163 by ERK1/2 and JNK is associated with the resistance of melanoma cell lines to the existing BH3 mimetics gossypol, S1 and ABT-737, and a novel anti-apoptotic mechanism of phosphorylated Mcl-1 (pMcl-1) is revealed. pMcl-1 antagonized the known BH3 mimetics by sequestering pro-apoptotic proteins that were released from Bcl-2/Mcl-1. Furthermore, an anthraquinone BH3 mimetic, compound 6, was identified to be the first small molecule to that induces endogenous apoptosis in melanoma cells by directly binding Bcl-2, Mcl-1, and pMcl-1 and disrupting the heterodimers of these proteins. Although compound 6 induced upregulation of the pro-apoptotic protein Noxa, its apoptotic induction was independent of Noxa. These data reveal the promising therapeutic potential of targeting pMcl-1 to treat melanoma. Compound 6 is therefore a potent drug that targets pMcl-1 in melanoma.

  15. The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia

    Science.gov (United States)

    Ploner, C; Rainer, J; Niederegger, H; Eduardoff, M; Villunger, A; Geley, S; Kofler, R

    2016-01-01

    Glucocorticoid (GC)-induced apoptosis is essential in the treatment of acute lymphoblastic leukemia (ALL) and related malignancies. Pro- and anti-apoptotic members of the BCL2 family control many forms of apoptotic cell death, but the extent to which this survival ‘rheostat’ is involved in the beneficial effects of GC therapy is not understood. We performed systematic analyses of expression, GC regulation and function of BCL2 molecules in primary ALL lymphoblasts and a corresponding in vitro model. Affymetrix-based expression profiling revealed that the response included regulations of pro-apoptotic and, surprisingly, anti-apoptotic BCL2 family members, and varied among patients, but was dominated by induction of the BH3-only molecules BMF and BCL2L11/Bim and repression of PMAIP1/Noxa. Conditional lentiviral gene overexpression and knock-down by RNA interference in the CCRF-CEM model revealed that induction of Bim, and to a lesser extent that of BMF, was required and sufficient for apoptosis. Although anti-apoptotic BCL2 members were not regulated consistently by GC in the various systems, their overexpression delayed, whereas their knock-down accelerated, GC-induced cell death. Thus, the combined clinical and experimental data suggest that GCs induce both pro- and anti-apoptotic BCL2 family member-dependent pathways, with the outcome depending on cellular context and additional signals feeding into the BCL2 rheostat. PMID:18046449

  16. Dioscin-induced apoptosis of human LNCaP prostate carcinoma cells through activation of caspase-3 and modulation of Bcl-2 protein family.

    Science.gov (United States)

    Chen, Jing; Li, Hui-min; Zhang, Xue-nong; Xiong, Chao-mei; Ruan, Jin-lan

    2014-02-01

    Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin (1, 2 and 4 μmol/L) could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family. PMID:24496691

  17. Affinity purification-mass spectrometry analysis of bcl-2 interactome identified SLIRP as a novel interacting protein.

    Science.gov (United States)

    Trisciuoglio, D; Desideri, M; Farini, V; De Luca, T; Di Martile, M; Tupone, M G; Urbani, A; D'Aguanno, S; Del Bufalo, D

    2016-01-01

    Members of the bcl-2 protein family share regions of sequence similarity, the bcl-2 homology (BH) domains. Bcl-2, the most studied member of this family, has four BH domains, BH1-4, and has a critical role in resistance to antineoplastic drugs by regulating the mitochondrial apoptotic pathway. Moreover, it is also involved in other relevant cellular processes such as tumor progression, angiogenesis and autophagy. Deciphering the network of bcl-2-interacting factors should provide a critical advance in understanding the different functions of bcl-2. Here, we characterized bcl-2 interactome by mass spectrometry in human lung adenocarcinoma cells. In silico functional analysis associated most part of the identified proteins to mitochondrial functions. Among them we identified SRA stem-loop interacting RNA-binding protein, SLIRP, a mitochondrial protein with a relevant role in regulating mitochondrial messenger RNA (mRNA) homeostasis. We validated bcl-2/SLIRP interaction by immunoprecipitation and immunofluorescence experiments in cancer cell lines from different histotypes. We showed that, although SLIRP is not involved in mediating bcl-2 ability to protect from apoptosis and oxidative damage, bcl-2 binds and stabilizes SLIRP protein and regulates mitochondrial mRNA levels. Moreover, we demonstrated that the BH4 domain of bcl-2 has a role in maintaining this binding. PMID:26866271

  18. Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Merino, D; Lok, S W; Visvader, J E; Lindeman, G J

    2016-04-14

    The last three decades have seen significant progress in our understanding of the role of the pro-survival protein BCL-2 and its family members in apoptosis and cancer. BCL-2 and other pro-survival family members including Mcl-1 and BCL-XL have been shown to have a key role in keeping pro-apoptotic 'effector' proteins BAK and BAX in check. They also neutralize a group of 'sensor' proteins (such as BIM), which are triggered by cytotoxic stimuli such as chemotherapy. BCL-2 proteins therefore have a central role as guardians against apoptosis, helping cancer cells to evade cell death. More recently, an increasing number of BH3 mimetics, which bind and neutralize BCL-2 and/or its pro-survival relatives, have been developed. The utility of targeting BCL-2 in hematological malignancies has become evident in early-phase studies, with remarkable clinical responses seen in heavily pretreated patients. As BCL-2 is overexpressed in ~75% of breast cancer, there has been growing interest in determining whether this new class of drug could show similar promise in breast cancer. This review summarizes our current understanding of the role of BCL-2 and its family members in mammary gland development and breast cancer, recent progress in the development of new BH3 mimetics as well as their potential for targeting estrogen receptor-positive breast cancer.

  19. THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

    Institute of Scientific and Technical Information of China (English)

    杨成; 王胜发; 梁桃; 王巨; 王凯; 王柏春

    2001-01-01

    Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression.Methods. Thirty rats were divided into hypoxia group(10%O2, 8h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)technique was used to detect nucleosomal DNA fragmentation of apoptotic cells.In situ hybridization and RT-PCR were used to detect the expression level of bcl-2 and bax.``Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bcl-2 increased whereas bax decreased significantly in the hypoxic group.``Conclusion. The alternation in bcl-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

  20. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    International Nuclear Information System (INIS)

    Highlights: → Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. → The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-XL and Bcl-2. → A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-XL. → The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-XL. → Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-XL and Bcl-2. A structural model of the Bcl-XL/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-XL/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-XL. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  1. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Hwa; Ha, Ji-Hyang [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kim, Yul [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Bae, Kwang-Hee [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Park, Jae-Yong [Department of Physiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Choi, Wan Sung [Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Yoon, Ho Sup [Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511 (Singapore); Park, Sung Goo; Park, Byoung Chul [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Yi, Gwan-Su, E-mail: gsyi@kaist.ac.kr [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Chi, Seung-Wook, E-mail: swchi@kribb.re.kr [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. {yields} The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. {yields} A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-X{sub L}. {yields} The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-X{sub L.} {yields} Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. A structural model of the Bcl-X{sub L}/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-X{sub L}/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-X{sub L}. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  2. New members of Datura family

    CERN Document Server

    Rosaev, Alexey

    2015-01-01

    The problem of origin and age of asteroid families is studied very intensively. Youngest families are most interesting due to possibility of the reconstruction collisional history. Here we report about three new members of Datura Family

  3. Cytotoxicity of carteolol to human corneal epithelial cells by inducing apoptosis via triggering the Bcl-2 family protein-mediated mitochondrial pro-apoptotic pathway.

    Science.gov (United States)

    Shan, Ming; Fan, Ting-Jun

    2016-09-01

    Carteolol is a frequently used nonselective β-adrenoceptor antagonist for glaucoma and ocular hypertension treatment, and its repeated/prolonged usage might be cytotoxic to the cornea, especially the outmost human corneal epithelium (HCEP). The aim of the present study was to characterize the cytotoxicity of carteolol to HCEP and its underlying cellular and molecular mechanisms using an in vitro model of HCEP cells. After HCEP cells were treated with carteolol at concentrations varying from 2% to 0.015625%, the cytotoxicity, apoptosis-inducing effect and pro-apoptotic pathway was investigated, respectively. Our results showed that carteolol at concentrations above 0.03125% induced time- and dose-dependent growth retardation, cytopathic morphological changes and viability decline of HCEP cells. Moreover, carteolol induced G1 phase arrest, plasma membrane permeability elevation, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCEP cells. Furthermore, carteolol also induced activation of caspase-9 and -3, disruption of mitochondrial transmembrane potential, up-regulation the cytoplasmic amount of cytochrome c and apoptosis-inducing factor, and up-regulation of pro-apoptotic Bax and Bad, down-regulation of anti-apoptotic Bcl-2 and Bcl-xL. In conclusion, carteolol above 1/64 of its clinical therapeutic dosage has a time- and dose-dependent cytotoxicity to HCEP cells, which is achieved by inducing apoptosis via triggering Bcl-2 family protein-mediated mitochondrial pro-apoptotic pathway. PMID:27216471

  4. Prometaphase arrest-dependent phosphorylation of Bcl-2 family proteins and activation of mitochondrial apoptotic pathway are associated with 17α-estradiol-induced apoptosis in human Jurkat T cells.

    Science.gov (United States)

    Han, Cho Rong; Jun, Do Youn; Kim, Yoon Hee; Lee, Ji Young; Kim, Young Ho

    2013-10-01

    In Jurkat T cell clone (JT/Neo), G2/M arrest, apoptotic sub-G1 peak, mitochondrial membrane potential (Δψm) loss, and TUNEL-positive DNA fragmentation were induced following exposure to 17α-estradiol (17α-E2), whereas none of these events (except for G2/M arrest) were induced in Jurkat cells overexpressing Bcl-2 (JT/Bcl-2). Under these conditions, phosphorylation at Thr161 and dephosphorylation at Tyr15 of Cdk1, upregulation of cyclin B1 level, histone H1 phosphorylation, Cdc25C phosphorylation at Thr-48, Bcl-2 phosphorylation at Thr-56 and Ser-70, Mcl-1 phosphorylation, and Bim phosphorylation were detected in the presence of Bcl-2 overexpression. However, the 17α-E2-induced upregulation of Bak levels, activation of Bak, activation of caspase-3, and PARP degradation were abrogated by Bcl-2 overexpression. In the presence of the G1/S blocking agent hydroxyurea, 17α-E2 failed to induce G2/M arrest and all apoptotic events including Cdk1 activation and phosphorylation of Bcl-2, Mcl-1 and Bim. The 17α-E2-induced phosphorylation of Bcl-2 family proteins and mitochondrial apoptotic events were suppressed by a Cdk1 inhibitor but not by aurora A and aurora B kinase inhibitors. Immunofluorescence microscopic analysis showed that an aberrant bipolar microtubule array, incomplete chromosome congression at the metaphase plate, and prometaphase arrest, which was reversible, were the underlying factors for 17α-E2-induced mitotic arrest. The in vitro microtubule polymerization assay showed that 17α-E2 could directly inhibit microtubule formation. These results show that the apoptogenic activity of 17α-E2 was due to the impaired mitotic spindle assembly causing prometaphase arrest and prolonged Cdk1 activation, the phosphorylation of Bcl-2, Mcl-1 and Bim, and the activation of Bak and mitochondria-dependent caspase cascade. PMID:23707954

  5. Epstein-Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells

    Institute of Scientific and Technical Information of China (English)

    Qin FU; Chen HE; Zheng-rong MAO

    2013-01-01

    Epstein-Barr virus (EBV),a human gammaherpesvirus carried by more than 90% of the world's population,is associated with malignant tumors such as Burkitt's lymphoma (BL),Hodgkin lymphoma,post-transplant lymphoma,extra-nodal natural killer/T cell lymphoma,and nasopharyngeal and gastric carcinomas in immune-compromised patients.In the process of infection,EBV faces challenges:the host cell environment is harsh,and the survival and apoptosis of host cells are precisely regulated.Only when host cells receive sufficient survival signals may they immortalize.To establish efficiently a lytic or long-term latent infection,EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways.This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors,which decide the fate of the host cell.The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma (Bcl) family are unknown.Still,EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host.We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.

  6. Crizotinib (PF-2341066) induces apoptosis due to downregulation of pSTAT3 and BCL-2 family proteins in NPM-ALK(+) anaplastic large cell lymphoma.

    Science.gov (United States)

    Hamedani, Farid Saei; Cinar, Munevver; Mo, Zhicheng; Cervania, Melissa A; Amin, Hesham M; Alkan, Serhan

    2014-04-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is an aberrant fusion gene product with tyrosine kinase activity and is expressed in substantial subset of anaplastic large cell lymphomas (ALCL). It has been shown that NPM-ALK binds to and activates signal transducer and activator of transcription 3 (STAT3). Although NPM-ALK(+) ALCL overall shows a better prognosis, there is a sub-group of patients who relapses and is resistant to conventional chemotherapeutic regimens. NPM-ALK is a potential target for small molecule kinase inhibitors. Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression. In this study, we have investigated the in vitro effects of Crizotinib in ALCL cell line with NPM-ALK fusion. Crizotinib induced marked downregulation of STAT3 phosphorylation, which was associated with significant apoptotic cell death. Apoptosis induction was attributed to caspase-3 cleavage and marked downregulation of the Bcl-2 family of proteins including MCL-1. These findings implicate that Crizotinib has excellent potential to treat patients with NPM-ALK(+) ALCL through induction of apoptotic cell death and downregulation of major oncogenic proteins in this aggressive lymphoma.

  7. Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor.

    Directory of Open Access Journals (Sweden)

    Giovanni Monaco

    Full Text Available The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R, the primary Ca(2+-release channel in the endoplasmic reticulum (ER. Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca(2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4 has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the distinctive α-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine "hinges" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG. By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced α-helicity, neither bound nor inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the α-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications.

  8. The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca2+ flux from the endoplasmic reticulum to mitochondria

    Science.gov (United States)

    Fouqué, A; Lepvrier, E; Debure, L; Gouriou, Y; Malleter, M; Delcroix, V; Ovize, M; Ducret, T; Li, C; Hammadi, M; Vacher, P; Legembre, P

    2016-01-01

    Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca2+ signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca2+ transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca2+ uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs. PMID:27367565

  9. Toothbrush contamination in family members

    OpenAIRE

    Adolfo Contreras; Roger Arce; Javier Enrique Botero; Adriana Jaramillo; Marisol Betancourt

    2010-01-01

    Objective: The purpose of this study was to determine the bacterial contamination of toothbrushes in family members. Materials and Methods: One hundred and two healthy subjects were included in this descriptive study. Every individual was examined clinically and microbiologically using the CPITN index and collecting subgingival plaque samples. Each participant received a toothbrush for home use and after one month they returned it to the investigators. All toothbrushes were cultured to determ...

  10. Combined transfection of Bcl-2 siRNA and miR-15a oligonucleotides enhanced methotrexate-induced apoptosis in Raji cells

    International Nuclear Information System (INIS)

    B-cell lymphoma 2 (Bcl-2) is an important member of the Bcl-2 family of proteins that regulate the induction of apoptosis. This study aims to investigate whether Bcl-2 small interfering RNA (siRNA) combined with miR-15a oligonucleotides (ODN) could enhance methotrexate (MTX)-induced apoptosis in Raji cells. Chemically synthesized miR-15a ODN and Bcl-2 siRNA were transfected in Raji cells by using a HiPerFect Transfection Reagent and then combined with MTX. Expression levels of Bcl-2 protein were detected by Western blot. Cell proliferation was determined by CCK8 assay. The rate of cell apoptosis was determined by Annexin V/PI double staining. The morphology of apoptotic cells was observed by Hoechst-33 258 staining. After the cells were transfected with miR-15a ODN combined with Bcl-2 siRNA, Bcl-2 protein levels were evidently decreased. CCK8 assay showed that cell proliferation was significantly decreased and was significantly lower in miR-15a ODN combined with Bcl-2 siRNA plus MTX group than in miR-15a ODN with methotrexate group, Bcl-2 siRNA with MTX group, and single MTX group (P<0.05). Hoechst 33258 staining revealed numerous apoptotic cells. AnnexinV/PI double staining showed that the apoptotic rates were (13.13±1.60)%, (34.47±2.96)%, (32.87±3.48)%, and (45.47±2.16)% in MTX, Bcl-2 siRNA plus MTX, miR-15a ODN plus MTX, and miR-15a ODN combined with Bcl-2 siRNA plus MTX groups, respectively. Among these groups, the apoptotic rate of miR-15a ODN combined with Bcl-2 siRNA plus MTX group was the highest; this apoptotic rate was also significantly different from that of miR-15a ODN or Bcl-2 siRNA plus MTX (P<0.05). Bcl-2 siRNA combined with miR-15a ODN could enhance MTX-induced apoptosis in Raji cells. Bcl-2 siRNA and miR-15a combined with MTX may be a useful approach to improve the treatment effects on lymphoma

  11. Toothbrush contamination in family members

    Directory of Open Access Journals (Sweden)

    Adolfo Contreras

    2010-04-01

    Full Text Available Objective: The purpose of this study was to determine the bacterial contamination of toothbrushes in family members. Materials and Methods: One hundred and two healthy subjects were included in this descriptive study. Every individual was examined clinically and microbiologically using the CPITN index and collecting subgingival plaque samples. Each participant received a toothbrush for home use and after one month they returned it to the investigators. All toothbrushes were cultured to determine the presence of periodontopathic bacteria and enteric rods. Wilkoxon signed rank test and t student test (P d"0.05 were used to compare differences in the subgingival microbiota and toothbrush contamination and CPITN index among family members. Results: A high proportion of toothbrushes resulted highly contaminated with enteric rods (P d"0.001 compared to the subgingival environment where periodontopathic bacteria were more prevalent. The most frequent microorganisms found in toothbrushes used by parents and children for one month were Enterobacteriaceae, Pseudomonadaceae species (>50% and Fusobacterium spp (30%. Conclusions: High levels of enteric rods were commonly detected in toothbrushes used for 1 month among members of the families. These opportunistic organisms may have an important role in oral infections including gingivitis and periodontitis. Monthly replacement or disinfection of the toothbrush can reduce the risk of bacterial transmission/translocation and thus diminish the incidence of biofilm associated oral diseases.

  12. Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Vucicevic Ksenija

    2016-04-01

    Full Text Available Background: In chronic lymphocytic leukemia (CLL, in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role.

  13. Apoptosis and the BCL-2 gene family - patterns of expression and prognostic value in STAGE I and II follicular center lymphoma

    International Nuclear Information System (INIS)

    Purpose: The prognostic significance of spontaneous levels of apoptosis and Bcl-2, Bax, and Bcl-x protein expression in follicular center lymphoma (FCL) is unknown. The objectives of this retrospective study were (1) to investigate the relationship between pretreatment apoptosis levels and long-term treatment outcome in patients with Stage I and II FCL; (2) to define the incidence and patterns of Bax and Bcl-x protein expression in human FC; and (3) to determine the relationship of Bcl-2, Bax, and Bcl-x expression with spontaneous apoptosis levels and clinical outcome in localized FCL. Methods and Materials: Between 1974 and 1988, 144 patients with Stage I or II FCL were treated. Hematoxylin and eosin (H and E) stained tissue sections of pretreatment specimens were retrieved for 96 patients. Treatment consisted of regional radiation therapy (XRT) for 25 patients, combined modality therapy (CMT) consisting of combination chemotherapy and XRT for 57 patients, and other treatments for 14 patients. Median follow-up for living patients was nearly 12 years. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells counted and multiplying by 100. Expression of Bcl-2, Bax, and Bcl-x proteins was assessed using immunohistochemistry. Results: The mean and median AI values for the entire group were 0.53 and 0.4, respectively (range: 0-5.2). The AI strongly correlated with cytologic grade, with mean AI values of 0.25 for grade 1, 0.56 for grade 2, and 0.84 for grade 3 (p < 0.0005; Kendall correlation). A positive correlation was present between grouped AI and grouped mitotic index (MI) (p = 0.014). For patients treated with CMT, an AI < 0.4 correlated with improved freedom from relapse (FFR) (p = 0.0145) and overall survival (OS) (p = 0.0081). An AI < 0.4 did not correlate with clinical outcome for the entire cohort or for patients receiving XRT only. Staining of tumor follicles for the Bcl-2 protein was positive, variable

  14. Bim must be able to engage all pro-survival Bcl-2 family members for efficient tumor suppression

    OpenAIRE

    Mérino, D; Strasser, A; Bouillet, P

    2011-01-01

    Over-expression of the transcriptional regulator Myc is thought to be the cause or a contributing factor in the development of a large number of human lymphomas and certain other cancers. Apoptotic cell death constitutes a tumor suppressive mechanism, particularly in the context of Myc over-expression. Accordingly, lymphoma development in Eμ-Myc transgenic mice, which mimic the Myc/IgH chromosomal translocation that causes Burkitt Lymphoma, is accelerated by concomitant over-expression of ant...

  15. Selective Impairment of TH17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes

    Science.gov (United States)

    Iglesias, Marcos; Augustin, Juan Jesús; Alvarez, Pilar; Santiuste, Inés; Postigo, Jorge; Merino, Jesús; Merino, Ramón

    2016-01-01

    The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The purpose of this study was to explore the effect of the T-cell overexpression of BCL2A1, an anti-apoptotic BCL2 family member without an effect on cell cycle progression, in the development of collagen-induced arthritis. Our results demonstrated an attenuated development of arthritis in these transgenic mice. The protective effect was unrelated to the suppressive activity of regulatory T cells but it was associated with a defective activation of p38 mitogen-activated protein kinase in CD4+ cells after in vitro TCR stimulation. In addition, the in vitro and in vivo TH17 differentiation were impaired in BCL2A1 transgenic mice. Taken together, we demonstrated here a previously unknown role for BCL2A1 controlling the activation of CD4+ cells and their differentiation into pathogenic proinflammatory TH17 cells and identified BCL2A1 as a potential target in the control of autoimmune/inflammatory diseases. PMID:27433938

  16. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    Science.gov (United States)

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

  17. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    Science.gov (United States)

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  18. Bcl-2 Retards Cell Cycle Entry through p27Kip1, pRB Relative p130, and Altered E2F Regulation

    OpenAIRE

    Vairo, Gino; Soos, Timothy J.; Upton, Todd M.; Zalvide, Juan; DeCaprio, James A.; Ewen, Mark E.; Koff, Andrew; Adams, Jerry M.

    2000-01-01

    Independent of its antiapoptotic function, Bcl-2 can, through an undetermined mechanism, retard entry into the cell cycle. Cell cycle progression requires the phosphorylation by cyclin-dependent kinases (Cdks) of retinoblastoma protein (pRB) family members to free E2F transcription factors. We have explored whether retarded cycle entry is mediated by the Cdk inhibitor p27 or the pRB family. In quiescent fibroblasts, enforced Bcl-2 expression elevated levels of both p27 and the pRB relative p1...

  19. Methods of Assessment for Affected Family Members

    Science.gov (United States)

    Orford, Jim; Templeton, Lorna; Velleman, Richard; Copello, Alex

    2010-01-01

    The article begins by making the point that a good assessment of the needs and circumstances of family members is important if previous neglect of affected family members is to be reversed. The methods we have used in research studies are then described. They include a lengthy semi-structured interview covering seven topic areas and standard…

  20. A component of green tea (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer

  1. Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy

    OpenAIRE

    Kang, Min H.; Reynolds, C. Patrick

    2009-01-01

    Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic ...

  2. Prognostic value of bcl-2 expression among women with breast cancer in Libya.

    Science.gov (United States)

    Ermiah, Eramah; Buhmeida, Abdelbaset; Khaled, Ben Romdhane; Abdalla, Fathi; Salem, Nada; Pyrhönen, Seppo; Collan, Yrjö

    2013-06-01

    We studied the association of the immunohistochemical bcl-2 expression in Libyan breast cancer with clinicopathological variables and patient outcome. Histological samples from 170 previously untreated primary Libyan breast carcinoma patients were examined. In immunohistochemistry, the NCL-L-bcl-2-486 monoclonal antibody was used. Positive expression of bcl-2 was found in 106 patients (62.4 %). The bcl-2 expression was significantly associated with estrogen receptor (p50 years; p=0.04). Histological subtypes and family history of breast cancer did not have significant relationship with bcl-2. Patients with positive expression of bcl-2 had lower recurrence rate than bcl-2-negative patients and better survival after median follow-up of 47 months. Patients with high bcl-2 staining were associated with the best survival. The role of bcl-2 as an independent predictor of disease-specific survival was assessed in a multivariate survival (Cox) analysis, including age, hormonal status, recurrence, histological grade, and clinical stage variables. Bcl-2 (p<0.0001) and clinical stage (p=0.016) were independent predicators of disease-specific survival. For analysis of disease-free survival, the same variables were entered to the model and only bcl-2 proved to be an independent predictor (p=0.002). Patients with positive expression of bcl-2 were associated with low grade of malignancy, with lower recurrence rate, with lower rate of death, and with longer survival time. Bcl-2 is an independent predictor of breast cancer outcome, and it provides useful prognostic information in Libyan breast cancer. Thus, it could be used with classical clinicopathological factors to improve patient selection for therapy.

  3. bax, but not bcl-2, influences the prognosis of human pancreatic cancer

    OpenAIRE

    Friess, H; Lu, Z; H. Graber; Zimmermann, A.; Adler, G.; Korc, M.; Schmid, R; Buchler, M

    1998-01-01

    Background—bcl-2 and bax belong to the bcl-2-related gene family, which marks a new class of genes that influence apoptosis. The bcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis. 
Aims—To analyse the expression of bcl-2 and bax in pancreatic cancer and correlate the results with clinical parameters. 
Patients—Pancreatic cancer tissue samples were obtained fro...

  4. A Family Affair : Explaining Co-Working By Family Members

    NARCIS (Netherlands)

    Ruijter, Esther de; Lippe, Tanja van der; Raub, Werner; Weessie, Jeroen

    2008-01-01

    This study focuses on co-working by intimate partners and other family members in entrepreneurs’ businesses. We hypothesize that co-working by family is beneficial because it reduces trust problems associated with employment relations. On the other hand, co-working is risky because co-working family

  5. Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct membrane behavior reflecting their functional divergence.

    Directory of Open Access Journals (Sweden)

    Yannis Guillemin

    Full Text Available BACKGROUND: The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. METHODOLOGY/PRINCIPAL FINDINGS: Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. CONCLUSION/SIGNIFICANCE: BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.

  6. Quantitative expression analysis and prognostic significance of the BCL2-associated X gene in nasopharyngeal carcinoma: a retrospective cohort study

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy showing high prevalence in Southeast Asia and North Africa. The BCL2-associated X (BAX) gene encodes the most important pro-apoptotic member of the BCL2 family. We have recently shown that BCL2 and BCL2L12, two other members of the same apoptosis-related family, possess significant prognostic value in NPC. The objective of the current study was to analyze BAX mRNA expression in nasopharyngeal biopsies of NPC patients, and to assess its prognostic potential in this disease. Total RNA was isolated from 88 malignant and 9 hyperplastic nasopharyngeal biopsies, resected from Tunisian patients. After cDNA synthesis by reverse transcription of polyadenylated RNA, BAX mRNA expression was analyzed using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Lower BAX mRNA levels were detected in NPC biopsies than in hyperplastic nasopharyngeal samples. BAX mRNA expression status was associated with low tumor extent, negative regional lymph node status, and absence of distant metastases. Kaplan-Meier survival analysis demonstrated that patients with BAX mRNA-positive NPC have significantly longer disease-free survival (DFS) and overall survival (OS). In accordance with these findings, Cox regression analysis revealed that BAX mRNA expression can be considered as a favorable prognostic indicator of DFS and OS in NPC, independent of their gender, age, tumor histology, tumor extent, and nodal status. Furthermore, NPC patients without distant metastases are less likely to relapse when their primary tumor is BAX mRNA-positive, compared to metastasis-free patients with a BAX-negative nasopharyngeal malignancy. This is the first study examining the potential clinical utility of BAX as a prognostic tumor biomarker in NPC. We provide evidence that BAX mRNA expression can be considered as an independent favorable prognostic indicator of DFS and OS in NPC

  7. Selective peptide inhibitors of antiapoptotic cellular and viral Bcl-2 proteins lead to cytochrome c release during latent Kaposi’s sarcoma-associated herpesvirus infection

    OpenAIRE

    Burrer, Christine M.; Foight, Glenna W.; Keating, Amy E.; Chan, Gary C.

    2015-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with B-cell lymphomas including primary effusion lymphoma and multicentric Castleman’s disease. KSHV establishes latency within B cells by modulating or mimicking the antiapoptotic Bcl-2 family of proteins to promote cell survival. Our previous BH3 profiling analysis, a functional assay that assesses the contribution of Bcl-2 proteins towards cellular survival, identified two Bcl-2 proteins, cellular Mcl-1 and viral KsBcl-2, as pote...

  8. Protection of Bcl-2 by salubrinal

    OpenAIRE

    Kessel, David

    2006-01-01

    The drug salubrinal has been identified as an inhibitor of phosphatases that act on the eukaryotic translation initiation factor 2 subunit (eIF2α). The resulting maintenance of protein phosphorylation results in enhanced protection from the adverse effects of initiators of the unfolded protein response. We found that salubrinal can also interact with the anti-apoptotic protein Bcl-2, inhibiting binding of the non-peptidic antagonist HA14-1 and of a porphycene that can catalyze Bcl-2 photodama...

  9. Targeting glutamine metabolism in multiple myeloma enhances BIM binding to BCL-2 eliciting synthetic lethality to venetoclax.

    Science.gov (United States)

    Bajpai, R; Matulis, S M; Wei, C; Nooka, A K; Von Hollen, H E; Lonial, S; Boise, L H; Shanmugam, M

    2016-07-28

    Multiple myeloma (MM) is a plasma cell malignancy that is largely incurable due to development of resistance to therapy-elicited cell death. Nutrients are intricately connected to maintenance of cellular viability in part by inhibition of apoptosis. We were interested to determine if examination of metabolic regulation of BCL-2 proteins may provide insight on alternative routes to engage apoptosis. MM cells are reliant on glucose and glutamine and withdrawal of either nutrient is associated with varying levels of apoptosis. We and others have demonstrated that glucose maintains levels of key resistance-promoting BCL-2 family member, myeloid cell leukemic factor 1 (MCL-1). Cells continuing to survive in the absence of glucose or glutamine were found to maintain expression of MCL-1 but importantly induce pro-apoptotic BIM expression. One potential mechanism for continued survival despite induction of BIM could be due to binding and sequestration of BIM to alternate pro-survival BCL-2 members. Our investigation revealed that cells surviving glutamine withdrawal in particular, enhance expression and binding of BIM to BCL-2, consequently sensitizing these cells to the BH3 mimetic venetoclax. Glutamine deprivation-driven sensitization to venetoclax can be reversed by metabolic supplementation with TCA cycle intermediate α-ketoglutarate. Inhibition of glucose metabolism with the GLUT4 inhibitor ritonavir elicits variable cytotoxicity in MM that is marginally enhanced with venetoclax treatment, however, targeting glutamine metabolism with 6-diazo-5-oxo-l-norleucine uniformly sensitized MM cell lines and relapse/refractory patient samples to venetoclax. Our studies reveal a potent therapeutic strategy of metabolically driven synthetic lethality involving targeting glutamine metabolism for sensitization to venetoclax in MM. PMID:26640142

  10. Zebrafish bcl2l is a survival factor in thyroid development.

    Science.gov (United States)

    Porreca, Immacolata; De Felice, Elena; Fagman, Henrik; Di Lauro, Roberto; Sordino, Paolo

    2012-06-15

    Regulated cell death, defined in morphological terms as apoptosis, is crucial for organ morphogenesis. While differentiation of the thyroid gland has been extensively studied, nothing is yet known about the survival mechanisms involved in the development of this endocrine gland. Using the zebrafish model system, we aim to understand whether genes belonging to the Bcl-2 family that control apoptosis are implicated in regulation of cell survival during thyroid development. Evidence of strong Bcl-2 gene expression in mouse thyroid precursors prompted us to investigate the functions played by its zebrafish homologs during thyroid development. We show that the bcl2-like (bcl2l) gene is expressed in the zebrafish thyroid primordium. Morpholino-mediated knockdown and mutant analyses revealed that bcl2l is crucial for thyroid cell survival and that this function is tightly modulated by the transcription factors pax2a, nk2.1a and hhex. Also, the bcl2l gene appears to control a caspase-3-dependent apoptotic mechanism during thyroid development. Thyroid precursor cells require an actively maintained survival mechanism to properly proceed through development. The bcl2l gene operates in the inhibition of cell death under direct regulation of a thyroid specific set of transcription factors. This is the first demonstration of an active mechanism to ensure survival of the thyroid primordium during morphogenesis.

  11. The relationship between mental health workers and family members

    NARCIS (Netherlands)

    H.M. van de Bovenkamp; M.J. Trappenburg

    2010-01-01

    Objective To study the relationship between family members and mental health care workers to learn more about the support available to family members of mental health patients. Methods Eighteen interviews were conducted with family members, seven with professionals and two with patients. Observation

  12. Mass relations among family members of quarks and leptons

    CERN Document Server

    Gilani, A H S

    2005-01-01

    The various mass relations among members of quark and lepton families are given. Three mass relations for the charm, beauty, and top quark family members are given and three mass relations for the electron, muon, and tau lepton family members are presented.

  13. Expression of Bcl-2 in cells with different telomerase activities

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Both telomerase and Bcl-2 are important genes in controlling apoptosis. The activation of telomerase and the abnormal regulation of Bcl-2 are also closely related to carcinogenesis. However, little is known about the linkage between telomerase and Bcl-2. The effect of activated telomerase on the expression of Bcl-2 has been investigated. It is demonstrated that in tumor and transformed cells with higher telomerase activity, Bcl-2 expression is significantly lower than that in telomerase negative or less telomerose activity cells. Further study showed that in the telomerase gene-transformed 2BS-fibroblasts, Bcl-2 expression is inhibited significantly while the exogenous telomerase catalytic subunit gene is re-expressed in fibroblasts. Results indicated that there might be a certain linkage between the expression of telomerase and Bcl-2, and overexpression of exogenous telomerase gene might down regulate the expression of Bcl-2.

  14. Cutaneous Anthrax: Evaluation of Five Family Members

    Directory of Open Access Journals (Sweden)

    Suat Zengin

    2016-05-01

    Full Text Available Anthrax is a zoonotic disease of grass-eating animals such as cattle, sheep, goats, and transmitted to humans by infected animals. Declining with each passing day in our country is still an endemic disease. Cutaneous anthrax is 95% of the cases. In this study, 5 patients from the same family who admitted to the emergency department with a complaint of a painless and black colored wound on their hands are discussed and skin anthrax diagnosed. Four male, 1 female family members who cut a cattle a week before were evaluated in the emergency department with a wound on their hands%u2019 backside. One of the patients hospitalized with the diagnosis of anthrax, and accepted to the infectious diseases clinic, and 4 were discharged by outpatient treatment arranged. In controls after two weeks, the patients were fully recovered without complications. Early diagnosis and treatment can show 100% improvement in skin anthrax, suspicious skin lesion and recently animal contact history should be considered in patients.

  15. Research Progress of Galectin-3,Bcl-2 and Embryo Development Termination%Galectin-3和Bcl-2与胚胎停育研究进展

    Institute of Scientific and Technical Information of China (English)

    徐耀辉

    2012-01-01

    Galectin-3 is a member of galectin family,which interacts with intracellular glycoprotein,cell surface molecules and extracellular matrix proteins by its carbohydrate recognition domains, participates the progress of embryo implantation,embryogenesis and placenta formation,and establishes and maintains a close relationship with pregnancy. Inhibitors of apoptosis protein Bcl-2 and Galectin-3 have significant sequence similarity,and may have the same apoptosis pathway,which participates in the growth and differentiation of villous trophoblast cells in people's earlier pregnancy and the process of decidualization of endometrium,in addition,playing a critical role in the villous production,growth,placenta formation and in its tissue structure rebuilding and functional perfection.%Galectin-3 是半乳糖凝集素家族中的一员,能通过其糖识别域与细胞内糖蛋白、细胞表面分子和细胞外基质蛋白相互作用,参与胚胎着床、胚胎发生和胎盘形成等过程,与妊娠成功建立和维持密切相关.凋亡抑制蛋白Bcl-2与Galectin-3有明显的序列相似性,可能存在共同细胞凋亡通路,在人早孕过程中参与了绒毛滋养层细胞的增殖和分化、子宫内膜蜕膜化的过程,在绒毛的发生、发育、胎盘形成和组织结构改建及功能完善等方面发挥着重要作用.

  16. Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets

    DEFF Research Database (Denmark)

    van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H;

    2013-01-01

    The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We co...

  17. Copper Induces Apoptosis of Neuroblastoma Cells Via Post-translational Regulation of the Expression of Bcl-2-family Proteins and the tx Mouse is a Better Model of Hepatic than Brain Cu Toxicity.

    Science.gov (United States)

    Chan, Hsien W; Liu, Tianbing; Verdile, Giuseppe; Bishop, Glenda; Haasl, Ryan J; Smith, Mark A; Perry, George; Martins, Ralph N; Atwood, Craig S

    2008-01-01

    The basic mechanism(s) by which altered Cu homeostasis is toxic to hepatocytes and neurons, the two major cell types affected in copper storage diseases such as Wilson's disease (WD), remain unclear. Using human M17 neuroblastoma cells as a model to examine Cu toxicity, we found that there was a time- and concentration-dependent induction of neuronal death, such that at 24 h there was a approximately 50 % reduction in viability with 25 muM Cu-glycine(2). Cu-glycine(2) (25:50 muM) treatment for 24 h significantly altered the expression of 296 genes, including 8 genes involved with apoptosis (BCL2-associated athanogene 3, BCL2/adenovirus E1B 19kDa interacting protein caspase 5, regulator of Fas-induced apoptosis, V-jun sarcoma virus 17 oncogene homolog, claudin 5, prostaglandin E receptor 3 and protein tyrosine phosphatase, non-receptor type 6). Surprisingly, changes in the expression of more 'traditional' apoptotic genes (Bcl-2, Bax, Bak and Bad) did not vary more than 20 %. To test whether the induction of apoptosis in neuroblastoma cells was via post-translational mechanisms, we measured the protein expression of these apoptotic markers in M17 neuroblastoma cells treated with Cu-glycine(2) (0-100 muM) for 24-48 h. Compared with glycine treated cells, Cu-glycine(2) reduced Bcl-2 expression by 50 %, but increased Bax and Bak expression by 130% and 400 %, respectively. To assess whether Cu also induced apoptotic cell death in a mouse model of WD, we measured the expression of these apoptotic markers in the liver and brain of mice expressing an ATP7b gene mutation (tx(J) mice) at 10 months of age (near the end of their lives when overt liver pathology is displayed). Changes in the liver expression of these apoptotic markers in tx(J) mice compared to background mice mirrored those of Cu treated neuroblastoma cells. In contrast, few changes in apoptotic protein expression were detected in the brain between tx(J) and background mice, indicating the tx(J) mouse is a good

  18. Perceived Family Resources Based on Number of Members with ADHD

    Science.gov (United States)

    Corwin, Melinda; Mulsow, Miriam; Feng, Du

    2012-01-01

    Objective: This study examines how the number of family members with ADHD affects other family members' perceived resources. Method: A total of 40 adolescents diagnosed with ADHD and their mothers, fathers, and adolescent siblings living in the household participated. Hierarchical linear modeling was used to analyze family-level data from a total…

  19. Mutual regulation of Bcl-2 proteins independent of the BH3 domain as shown by the BH3-lacking protein Bcl-x(AK.

    Directory of Open Access Journals (Sweden)

    Michael Plötz

    Full Text Available The BH3 domain of Bcl-2 proteins was regarded as indispensable for apoptosis induction and for mutual regulation of family members. We recently described Bcl-x(AK, a proapoptotic splice product of the bcl-x gene, which lacks BH3 but encloses BH2, BH4 and a transmembrane domain. It remained however unclear, how Bcl-x(AK may trigger apoptosis.For efficient overexpression, Bcl-x(AK was subcloned in an adenoviral vector under Tet-OFF control. The construct resulted in significant apoptosis induction in melanoma and nonmelanoma cell lines with up to 50% apoptotic cells as well as decreased cell proliferation and survival. Disruption of mitochondrial membrane potential, and cytochrome c release clearly indicated activation of the mitochondrial apoptosis pathways. Both Bax and Bak were activated as shown by clustering and conformation analysis. Mitochondrial translocation of Bcl-x(AK appeared as an essential and initial step. Bcl-x(AK was critically dependent on either Bax or Bak, and apoptosis was abrogated in Bax/Bak double knockout conditions as well by overexpression of Bcl-2 or Bcl-x(L. A direct interaction with Bcl-2, Bax, Bad, Noxa or Puma was however not seen by immunoprecipitation. Thus besides BH3-mediated interactions, there exists an additional way for mutual regulation of Bcl-2 proteins, which is independent of the BH3. This pathway appears to play a supplementary role also for other proapoptotic family members, and its unraveling may help to overcome therapy resistance in cancer.

  20. Two independent positive feedbacks and bistability in the Bcl-2 apoptotic switch.

    Directory of Open Access Journals (Sweden)

    Jun Cui

    Full Text Available BACKGROUND: The complex interplay between B-cell lymphoma 2 (Bcl-2 family proteins constitutes a crucial checkpoint in apoptosis. Its detailed molecular mechanism remains controversial. Our former modeling studies have selected the 'Direct Activation Model' as a better explanation for experimental observations. In this paper, we continue to extend this model by adding interactions according to updating experimental findings. METHODOLOGY/PRINCIPAL FINDINGS: Through mathematical simulation we found bistability, a kind of switch, can arise from a positive (double negative feedback in the Bcl-2 interaction network established by anti-apoptotic group of Bcl-2 family proteins. Moreover, Bax/Bak auto-activation as an independent positive feedback can enforce the bistability, and make it more robust to parameter variations. By ensemble stochastic modeling, we also elucidated how intrinsic noise can change ultrasensitive switches into gradual responses. Our modeling result agrees well with recent experimental data where bimodal Bax activation distributions in cell population were found. CONCLUSIONS/SIGNIFICANCE: Along with the growing experimental evidences, our studies successfully elucidate the switch mechanism embedded in the Bcl-2 interaction network and provide insights into pharmacological manipulation of Bcl-2 apoptotic switch as further cancer therapies.

  1. Serum level of IL13 and expression of BCL2 in Behcet's disease

    Directory of Open Access Journals (Sweden)

    Hanan.M.A Darwish*, Sabila Gomaa Mousa** Noha Hamdy

    2006-09-01

    Full Text Available Background BD: BCL2 family is a large family of apoptosis regulating proteins consisting of both blockers and promoters of cell death. Immunological processes and a variety of cytokines may play a role in pathophysiological process. Defective regulation of programmed cell death (apoptosis also play a role in development of Behcet's disease Objective: To investigate the level of BCL2 and IL13in BD and to determine their to relation monitory disease activity. Patients and methods: This study was conducted on thirty patients (15 active and 15 inactive and 15-health control, the activity of BD was evaluated according to international study group for BD disease, using ELISA technique for IL 13 and flow cytometry forBCL2. Results: Elevated serum levels of IL13 in patient with active BD than inactive and both had elevated levels than control(P< 0.01 and also the serum levels of Bcl2 was elevated in patient with active BD than inactive and control(P< 0.01. Concolusion: The data suggested that IL13 and BCL2 could be involved in the pathogenesis of BD and its serum levels can be used as marker to monitor disease activity.

  2. Coping Strategies of Family Members of Hospitalized Psychiatric Patients

    Directory of Open Access Journals (Sweden)

    Phyllis M. Eaton

    2011-01-01

    Full Text Available This exploratory research paper investigated the coping strategies of families of hospitalized psychiatric patients and identified their positive and negative coping strategies. In this paper, the coping strategies of 45 family members were examined using a descriptive, correlational, mixed method research approach. Guided by the Neuman Systems Model and using the Family Crisis Oriented Personal Evaluation Scales and semistructured interviews, this paper found that these family members used more emotion-focused coping strategies than problem-focused coping strategies. The common coping strategies used by family members were communicating with immediate family, acceptance of their situation, passive appraisal, avoidance, and spirituality. The family members also utilized resources and support systems, such as their immediate families, mental health care professionals, and their churches.

  3. Coping Strategies of Family Members of Hospitalized Psychiatric Patients

    OpenAIRE

    Eaton, Phyllis M.; Davis, Bertha L.; Pamela V. Hammond; Condon, Esther H.; McGee, Zina T.

    2011-01-01

    This exploratory research paper investigated the coping strategies of families of hospitalized psychiatric patients and identified their positive and negative coping strategies. In this paper, the coping strategies of 45 family members were examined using a descriptive, correlational, mixed method research approach. Guided by the Neuman Systems Model and using the Family Crisis Oriented Personal Evaluation Scales and semistructured interviews, this paper found that these family members used m...

  4. NF-κB, Bcl-2 and the alcoholic liver disease%NF-κB、Bcl-2与酒精性肝病

    Institute of Scientific and Technical Information of China (English)

    张曦; 王沁

    2011-01-01

    酒精性肝病(ALD)是由于长期过度饮酒而引发的一系列肝脏损害疾病.现研究表明肝细胞的凋亡对该病的发生、发展起着十分重要的作用.其中核因子κB (NF-κB)、B细胞淋巴瘤-2基因(Bcl-2)与ALD关系密切.ALD患者肝细胞内活化的NF-κB,通过刺激大量炎性细胞因子释放,引发肝组织炎症、纤维化、坏死和凋亡,同时通过调控凋亡蛋白酶 (Caspase)、Bcl-2、死亡受体等基因来干预肝细胞凋亡;被激活的Bcl-2,除本身具有抗凋亡功能外,还与NF-κB以复合物的形式发挥抗凋亡作用,同时与同家族促凋亡蛋白Bax以二聚体的形式依比例对肝细胞凋亡发挥抑制或促进作用.肝细胞凋亡和抗凋亡的动态失衡将成为酒精性肝病发病的重要途径之一.%Alcoholic liver disease which causes the liver damage is due to the long series of heavy drinking. Present study shows that the hepatocytes apoptosis plays an important role in the development of ALD. The nuclear factor ΚB (NF-ΚB) and B cell lymphoma-2 genes (Bcl-2) are closely related with the hepatocyte apoptosis. The activate NF-ΚB in the hepatocyte of ALD, not only can stimulate the release of inflammatory cytokines and cause liver inflammation, fibrosis, necrosis and apoptosis, but also can interfere the hepatocyte apoptosis by regulation the caspase (Caspase), Bcl-2, death receptor and other genes. The activated Bcl-2 not only can inhibit apoptosis by itself function, but also can inhibit apoptosis in the form of complex with the activated NF-ΚB. Bcl-2 can be dimer with the same family protein Bax which is the pro-apoptotic protein. The dimer inhibiting or stimulating apoptosis depends on the proportion of Bcl-2 and Bax. Imbalance of stimulating apoptosis and anti-apoptosis will become an important way in the way of ALD pathogenesy.

  5. MDA-7/IL-24 induces Bcl-2 denitrosylation and ubiquitin-degradation involved in cancer cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Hui Tian

    Full Text Available MDA-7/IL-24 was involved in the specific cancer apoptosis through suppression of Bcl-2 expression, which is a key apoptosis regulatory protein of the mitochondrial death pathway. However, the underlying mechanisms of this regulation are unclear. We report here that tumor-selective replicating adenovirus ZD55-IL-24 leads to Bcl-2 S-denitrosylation and concomitant ubiquitination, which take part in the 26S proteasome degradation. IL-24-siRNA completely blocks Bcl-2 ubiquitination via reversion of Bcl-2 S-denitrosylation and protects it from proteasomal degradation which confirmed the significant role of MDA-7/IL-24 in regulating posttranslational modification of Bcl-2 in cancer cells. Nitric oxide (NO is a key regulator of protein S-nitrosylation and denitrosylation. The NO donor, sodium nitroprusside (SNP, down-regulates Bcl-2 S-denitrosylation, attenuates Bcl-2 ubiquitination and subsequently counteracts MDA-7/IL-24 induced cancer cell apoptosis, whereas NO inhibitor 2-(4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO shows the opposite effect. At the same time, these NO modulators fail to affect Bcl-2 phosphorylation, suggesting that NO regulates Bcl-2 stability in a phosphorylation-independent manner. In addition, Bcl-2 S-nitrosylation reduction induced by ZD55-IL-24 was attributed to both iNOS decrease and TrxR1 increase. iNOS-siRNA facilitates Bcl-2 S-denitrosylation and ubiquitin-degradation, whereas the TrxR1 inhibitor auranofin prevents Bcl-2 from denitrosylation and ubiquitination, thus restrains the caspase signal pathway activation and subsequent cancer cell apoptosis. Taken together, our studies reveal that MDA-7/IL-24 induces Bcl-2 S-denitrosylation via regulation of iNOS and TrxR1. Moreover, denitrosylation of Bcl-2 results in its ubiquitination and subsequent caspase protease family activation, as a consequence, apoptosis susceptibility. These findings provide a novel insight into MDA-7/IL-24 induced growth

  6. Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer

    International Nuclear Information System (INIS)

    Pro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. Inhibition of anti-apoptotic Bcl-2 family members therefore represents an appealing strategy to overcome resistance to anti-cancer therapies. The aim of this study was to evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained from a phase I/II trial, and compared these with the effective in vitro concentrations to substantiate therapeutic opportunities. We examined the effect of AT-101, radiation and the combination on apoptosis induction and clonogenic survival in two HNSCC cell lines that express the target proteins. Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear changes and/or by propidium iodide staining and flow-cytometry analysis to quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and radiation was evaluated by calculating the Combination Index (CI) and by performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT-101 levels were measured by HPLC in blood samples collected from patients enrolled in our clinical phase I/II study. These patients with locally advanced HNSCC were treated with standard cisplatin-based chemoradiotherapy and received dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks. In vitro results showed that AT-101 enhances radiation-induced apoptosis with CI’s below 1.0, indicating synergy. This effect was sequence-dependent. Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF37 of 1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis

  7. Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas.

    Science.gov (United States)

    Kapucuoglu, N; Losi, L; Eusebi, V

    1997-01-01

    Bcl-2 and Bax proteins are coded by a family of genes that take part in the manteinance of the balance between cell proliferation rate and programmed cell death in multicellular organisms. The Bax gene acts as promoter of cell death by opposing the death protector effect of the Bcl-2 gene. Expression of the Bcl-2 and Bax proteins has been investigated in 58 cases of duct carcinoma in situ (DCIS) and duct invasive and invasive lobular carcinomas (IC) of the breast. While both proteins were expressed at the same time in normal and benign epithelium, different staining patterns were observed according to the degree of differentiation of the neoplastic epithelium. In well-differentiated DCIS and grade I IC there was a predominance of Bcl-2 protein staining. Grade II lesions co-expressed both proteins. Poorly differentiated DCIS displayed a predominantly Bax protein staining pattern. Therefore, it appears that Bax protein expression, especially in DCIS, relates to more aggressive neoplasms while Bcl-2 protein expression is associated with less aggressive malignant lesions.

  8. Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-γ and altered expression of Bcl-2/Bax

    OpenAIRE

    Pettersson, F; Dalgleish, A G; Bissonnette, R P; Colston, K W

    2002-01-01

    All-trans-retinoic acid and 9-cis-retinoic acid have been reported to have inhibitory effects on pancreatic adenocarcinoma cells and we have shown that this is partly due to induction of apoptosis. In this study, the mechanisms whereby 9-cis-retinoic acid induces apoptosis in these cells were investigated. An involvement of the Bcl-2 family of proteins was shown, such that 9-cis-retinoic acid causes a decrease in the Bcl-2/Bax ratio. Overexpression of Bcl-2 also resulted in inhibition of apop...

  9. Immunogenicity of Bcl-2 in patients with cancer

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Svane, Inge Marie; Kvistborg, Pia;

    2005-01-01

    -2 in cancer and the fact that immune escape by down-regulation or loss of expression of this protein would impair sustained tumor growth makes Bcl-2 a very attractive target for anticancer immunotherapy. Herein, we describe spontaneous T-cell reactivity against Bcl-2 in peripheral blood from...... patients suffering from unrelated tumor types (ie, pancreatic cancer, breast cancer, acute myeloid leukemia [AML], and chronic lymphocytic leukemia [CLL]). Additionally, we show that these Bcl-2-reactive T cells are indeed peptide-specific, cytotoxic effector cells. Thus, Bcl-2 may serve as an important...... and widely applicable target for anticancer immunotherapeutic strategies (eg, in the combination with conventional radiotherapy and chemotherapy)....

  10. Distribution of Candida albicans genotypes among family members

    Science.gov (United States)

    Mehta, S. K.; Stevens, D. A.; Mishra, S. K.; Feroze, F.; Pierson, D. L.

    1999-01-01

    Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast. An enrichment procedure provided a twofold increase in the recovery of C. albicans from mouthwash specimens. Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members. Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis. DNA fingerprinting of C. albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype. No two families shared the same strain, and two or more members of a family commonly shared the same strain. Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families. Genotypes of isolates from husband and wife differed from one another in five families. All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power.

  11. Can pets function as family members?

    Science.gov (United States)

    Cohen, Susan Phillips

    2002-10-01

    This exploratory study investigated how clients of a large urban veterinary center viewed the role of their pet in the famil and how they compared this role to that of humans. In Phase 1, randomly selected clients (N = 201) completed a questionnaire containing scales delineating family relationships and pet attachment. Being either a man or a college graduate was associated with lesser feelings of psychological kinship and intimacy, both with pets and people. Neither living with a partner norhaving a child affected the strength of pet relationships. In Phase 2, 16 participants from Phase I completed a social network instrument and answered questions about family roles and boundaries. Thirteen of the 16 respondents said that there were circumstances in which they would give a scarce drug to their pet in preference to a person outside the family. PMID:12365764

  12. MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.

    Directory of Open Access Journals (Sweden)

    Dan Chen

    Full Text Available The miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in adult tissues, such as dermal wound healing, and a number of disease processes, including cancer. By combining 5 independent genome-wide expression profiling experiments, we identified a panel of 266 unique transcripts that were down-regulated in epithelial cells transfected with miR-99 family members. A comprehensive bioinformatics analysis using 12 different sequence-based microRNA target prediction algorithms revealed that 81 out of these 266 down-regulated transcripts are potential direct targets for the miR-99 family. Confirmation experiments and functional analyses were performed to further assess 6 selected miR-99 target genes, including mammalian Target of rapamycin (mTOR, Homeobox A1 (HOXA1, CTD small phosphatase-like (CTDSPL, N-myristoyltransferase 1 (NMT1, Transmembrane protein 30A (TMEM30A, and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5. HOXA1 is a known proto-oncogene, and it also plays an important role in embryonic development. The direct targeting of the miR-99 family to two candidate binding sequences located in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a ribonucleoprotein-immunoprecipitation (RIP-IP assay. Ectopic transfection of miR-99 family reduced the expression of HOXA1, which, in consequence, down-regulated the expression of its downstream gene (i.e., Bcl-2 and led to reduced proliferation and cell migration, as well as enhanced apoptosis. In summary, we identified a number of high-confidence miR-99 family target genes, including proto-oncogene HOXA1, which may play an important role in regulating epithelial cell proliferation and

  13. Emotional state of family members of adults with retinal degeneration

    Directory of Open Access Journals (Sweden)

    Helena Chacón-López

    2013-10-01

    Full Text Available Various studies have documented the emotional changes that accompany the loss of vision in people with retinal degeneration (such as Retinitis Pigmentosa, but the emotional state of family members who live with them has not been extensively studied. However it is known that chronic diseases have repercussions not only on the well-being and quality of life of those affected, but also on their families, possibly making them more susceptible to depression and/or anxiety. Results from 37 family members tested against a control group (38 people partially supported our hypothesis and revealed that the family members showed higher levels of anxiety, especially the women, whereas partners showed higher scores in depression. The findings indicated that the family members should be receiving some kind of support to help them to resolve problems associated with the progression of the visual pathology.

  14. All in the family? An exploratory study of family member advisors and firm performance

    OpenAIRE

    Naldi, Lucia; Chirico, Francesco; Kellermanns, Franz; Campopiano, Giovanna

    2015-01-01

    This exploratory study investigates the relationship between family members serving in an advising capacity and family firm performance. Integrating the stewardship and agency perspectives, we predict an inverted U-shaped relationship between the number of family advisors and family firm performance. We argue that the generation in control moderates this relationship such that family member advisors have a positive relationship with performance in first-generation family firms and an inverted...

  15. Bcl-2 gene therapy for apoptosis following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-feng; ZHENG Xue-sheng; LIU Wei-guo; FENG Jun-feng

    2006-01-01

    Objective: To investigate the therapeutic effect of Bcl- 2 fusion protein on apoptosis in brain following traumatic brain injury.Methods: Bcl-2 gene was cloned by RT-PCR. Bcl-2 and EGFP genes were linked together and inserted into pAdeno-X vector. This recombinant vector was packaged into infectious adenovirus in HEK293 cells. Ninety Wistar rats were assigned randomly into experimental group(n=45) and control group (n=45). All rats were subjected to traumatic brain injury. Then recombinant adenovirus (for experimental group) or saline (for control group) was injected into the traumatic brain. The expression of Bcl-2 fusion protein was investigated by Western blotting, immunohistochemistry and fluorescence microscopy. Apoptosis in the injured brain was studied by TUNEL. Animals' behavior capacity was evaluated by tiltboard test.Results: In the experimental group, many fluorescent cells were found around the traumatic locus,which were also proven to be Bcl-2-positive by immunohistochemistry. On the contrary, few Bcl-2-positive cells and no fluorescent cell were detected in the control group. Bcl-2 expression of experimental group was much higher than that of control group, which was illustrated by Western blotting. The apoptosis index of experimental group was 0.027 ± 0.005, and that of control group was 0.141±0.025 (P<0.01). Two weeks after injury, animals of the experimental group behaved better than those of the control group.Conclusions: A recombinant adenovirus vector expressing Bcl-2 fusion protein has been constructed. Bcl-2 fusion protein can suppress apoptosis and promote cell survival. Moreover, the behavior recovery of the injured animal is promoted. Bcl-2 fusion protein provides a way to track the target cells in vivo.

  16. Patient and family members perspectives on radioactive iodine treatment

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, P.; Fitch, M.I. [Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario (Canada)

    1999-08-01

    This report documents the findings of a survey of patients who received radioactive iodine therapy and their family members. The main objective of the survey was to gain an understanding of the experience of receiving radioactive iodine from the patient and family's perspective. The data from this study helped to inform the ARCP and GMA as they developed AC-9 - Principles of the management of radionuclide therapies. A survey was distributed to 700 patients and family members through physicians at 8 sites across Canada. Locations included: Newfoundland, Nova Scotia, Ontario (2 sites), Quebec (2 sites), Manitoba and British Columbia. A total of 190 patients and 140 family members returned completed surveys. Data was analyzed separately for individuals treated as inpatients and those treated as outpatients. The results of the survey provided a perspective from patients and families about their experiences regarding radioactive iodine therapy. The data indicate variation in patients' and family members' perspectives about how precautions are to be implemented. Both patients and family members expressed the desire for more information regarding many aspects of the treatment experience. The results have implications for the development of patient information, continuing education (in particular in the areas of precaution), the provision of access to supportive and counselling services, and the importance of looking at the individual situations of patients and their families. (author)

  17. Death at the Worksite: Helping Grieving Family Members

    Science.gov (United States)

    ... Grief at Work Working Through Grief About Us Death at the Worksite: Helping Grieving Family Members By ... fatal heart attacks occur in the workplace. Other deaths — from accidents, for example — can also happen during ...

  18. Understanding type 2 diabetes: including the family member's perspective.

    LENUS (Irish Health Repository)

    White, Patricia

    2012-02-01

    PURPOSE: The purpose of this study was to examine the relationship between psychological and social factors and diabetes outcomes in people with type 2 diabetes and their family members. METHODS: A total of 153 patients with type 2 diabetes were assessed at a diabetes outpatient clinic and postal questionnaires were sent to nominated family members. The measures examined were diabetes knowledge, social support, well-being, and illness perceptions. RESULTS: When compared with those with diabetes, family members reported lower positive well-being and lower levels of satisfaction with support. They also perceived diabetes as a more cyclical illness, which was controlled more by treatment than by the individual. Family members also reported that the person with diabetes was more emotionally distressed and knew more about diabetes than the patient had actually reported himself or herself. There were no differences between the family members of those in good or poor glycaemic control. CONCLUSIONS: This study reinforces the importance of understanding social context and illness beliefs in diabetes management. It also highlights the potential for including family members in discussions and education about diabetes management.

  19. Increased expression of Bcl-2 during mucous cell metaplasia induced by endotoxin and ozone

    Energy Technology Data Exchange (ETDEWEB)

    Tesfaigzi, J.; Ray, L.M.; Hotchkiss, J.A. [Michigan State Univ., East Lansing, MI (United States)] [and others

    1995-12-01

    Apoptosis or programmed cell death is accompanied by characteristic morphological changes that distinguish apoptosis from other forms of cell death. These changes include DNA fragmentation, chromatin condensation, cell shrinkage, cell surface pseudopodia, and finally the cellular collapse into membrane-enclosed apoptotic bodies which are rapidly engulfed by macrophages or neighboring cells. Although the morphological features of apoptotic cells are well studied, the biochemical events that control apoptosis are not understood. Programmed cell death is triggered by a variety of pathways that are initiated by different stimuli including noxious agents, DNA damage, the activation of TNF receptors, or the withdrawl of growth factors. The central process of programmed cell death involves a cascade of biochemical events that begins with the initiation of a family of cysteine proteases, including the interleukin-1-{Beta}-converting enzyme, CPP-32, and Apopain. The ratio of Bax, a death-inducer gene, to Bcl-2, an apoptosis suppressor gene, determines whether or not the main apoptotic pathyway is blocked. Apoptosis is suppressed if the ratio of Bcl-2/Bax is > 1, and cells undergo apoptosis if the ratio is < 1. The overexpression of Bcl-2 has been shown to block the apoptotic program triggered by a variety of agents. Therefore, Bcl-2 must be involved in blocking the central pathway of the cell death program. In conclusion, this study showed that high levels of Bcl-2 were detected in some mucous cells at specific time points during mucous cell metaplasia, and this expression was reduced at later time points or was absent after remodeling of this epithelium.

  20. Global transcriptional regulator TrmB family members in prokaryotes.

    Science.gov (United States)

    Kim, Minwook; Park, Soyoung; Lee, Sung-Jae

    2016-10-01

    Members of the TrmB family act as global transcriptional regulators for the activation or repression of sugar ABC transporters and central sugar metabolic pathways, including glycolytic, gluconeogenic, and other metabolic pathways, and also as chromosomal stabilizers in archaea. As a relatively newly classified transcriptional regulator family, there is limited experimental evidence for their role in Thermococcales, halophilic archaeon Halobacterium salinarum NRC1, and crenarchaea Sulfolobus strains, despite being one of the extending protein families in archaea. Recently, the protein structures of Pyrococcus furiosus TrmB and TrmBL2 were solved, and the transcriptomic data uncovered by microarray and ChIP-Seq were published. In the present review, recent evidence of the functional roles of TrmB family members in archaea is explained and extended to bacteria.

  1. The challenges of reintegration for service members and their families.

    Science.gov (United States)

    Danish, Steven J; Antonides, Bradley J

    2013-10-01

    The ongoing wars in Afghanistan and Iraq have posed a number of reintegration challenges to service members. Much of the research focuses on those service members experiencing psychological problems and being treated at the VA. In this article, we contend that much of the distress service members experience occurs following deployment and is a consequence of the difficulties encountered during their efforts to successfully reintegrate into their families and communities. We propose a new conceptual framework for intervening in this reintegration distress that is psycho-educational in nature as well as a new delivery model for providing such services. An example of this new intervention framework is presented.

  2. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    OpenAIRE

    Xiao, DaLiao; Zhang, Lubo

    2008-01-01

    Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-dependen...

  3. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    OpenAIRE

    DaLiao Xiao, Lubo Zhang

    2008-01-01

    Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-depe...

  4. 42 CFR 31.9 - Dependent members of families; treatment.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Dependent members of families; treatment. 31.9 Section 31.9 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS MEDICAL CARE FOR CERTAIN PERSONNEL OF THE COAST GUARD, NATIONAL OCEAN SURVEY, PUBLIC...

  5. Predictors of later-generation family members' commitment to family enterprises

    OpenAIRE

    Dawson, Alexandra; Sharma, Pramodita; Irving, P. Gregory; Markus, Joel; Chirico, Francesco

    2015-01-01

    This study examines the antecedents of different bases of organizational commitment and intention to stay of later-generation family members who are currently working in their family firm. Evidence from 199 Canadian and Swiss firms indicates that when these individuals' identity and career interests are aligned with their family enterprise, they experience affective commitment. Family expectations are associated with normative commitment. Individuals who are concerned about losing inherited f...

  6. BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis.

    Science.gov (United States)

    Verma, Sharad; Goyal, Sukriti; Tyagi, Chetna; Jamal, Salma; Singh, Aditi; Grover, Abhinav

    2016-06-01

    The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge. PMID:27262527

  7. Modulation of TNF receptor family members to inhibit autoimmune disease.

    Science.gov (United States)

    Weinberg, Andrew D; Montler, Ryan

    2005-04-01

    Certain members of the TNF-receptor family have shown proinflammatory function during immune activation and can be directly involved with the pathogenic effects observed during an autoimmune episode. The TNF-R family members summarized in this review includes: TNF-RI + II, OX40, and 4-1BB and they are expressed on a variety of leukocytes within the body. Studies within the last decade suggest that all of these proteins or their natural ligands can be targeted with various agents designed to diminish clinical signs of disease in autoimmune models. The data from the preclinical models specifically involving TNF-blockade have led to the development of clinical trials for patients with multiple sclerosis and rheumatoid arthritis. This review will chronicle the preclinical development of agents designed to inhibit OX40 and 4-1BB functions in autoimmunity and discuss relevant preclinical and clinical data associated with TNF-blockade. PMID:15853742

  8. EXPRESSION OF BAX AND BCL-2 IN MOUSE OFFSPRING BRAIN AFTER MATERNAL ORAL ADMINIS TRATION OF MONOSODIUM GLUTAMATE

    Institute of Scientific and Technical Information of China (English)

    徐磊; 赵晏; 展淑琴; 王会生; 史文春

    2002-01-01

    Objective To analyze the excitotoxicity of monoso dium glutamate (MSG) in the offspring cerebral cortex and hippocampal subregions after maternal oral administration of MSG. Methods Kunming mi ce were given per os MSG ( 4.0 g/kg ) at 17~21 days of pregnancy and their offs pring behaviors were studied at 10, 20 , 30 days postnatally. By using immunohis tochemical means, the involvement of Bcl-2 and Bax in the glutamate-induced c ell death in cortical and hippocampal neur ons were examined. Cell damage was assessed by direct cell counting. Res ults Administration of monosodium glutamate during the fetal period in mice resulted in a moderate increase in the expression of Bax in principal neuro ns in CA1, CA2, CA3, CA4 and in the cerebral cortex at postpartum 10, 20, 30 day s in the offspring mice, whereas Bcl-2 protein expressions were reduced signif icantly in the same regions as compared with those of controls. Conclusi on These findings suggest that glutamate toxicity results in cellular d eath via an apoptotic mechanism in which the Bcl-2/Bax-alpha molecular comple x may be involved. The glutamate-induced apoptosis appears to be related to the modulation of Bcl-2 family gene products such as Bcl-2 and Bax.

  9. Two faculty members study aging families in Katrina aftermath

    OpenAIRE

    Elliott, Jean

    2006-01-01

    During Hurricane Katrina, the media reported about abandoned nursing home residents, older adults who refused to leave their own abodes, and the needs of grandparent-led families. Since then, however, not much information has been gleaned about the elderly in the devastated region. Researchers Karen Roberto and Tammy Henderson, both faculty members at the Center for Gerontology at Virginia Tech, are teaming with Yoshinori Kamo, a sociology professor from Louisiana State University, to identif...

  10. Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Anti-apoptotic B Cell Lymphoma Gene 2 Family Proteins.

    Science.gov (United States)

    Godoi, Paulo H C; Wilkie-Grantham, Rachel P; Hishiki, Asami; Sano, Renata; Matsuzawa, Yasuko; Yanagi, Hiroko; Munte, Claudia E; Chen, Ya; Yao, Yong; Marassi, Francesca M; Kalbitzer, Hans R; Matsuzawa, Shu-Ichi; Reed, John C

    2016-07-01

    B cell lymphoma gene 2 (Bcl-2) family proteins are key regulators of programmed cell death and important targets for drug discovery. Pro-apoptotic and anti-apoptotic Bcl-2 family proteins reciprocally modulate their activities in large part through protein interactions involving a motif known as BH3 (Bcl-2 homology 3). Nur77 is an orphan member of the nuclear receptor family that lacks a BH3 domain but nevertheless binds certain anti-apoptotic Bcl-2 family proteins (Bcl-2, Bfl-1, and Bcl-B), modulating their effects on apoptosis and autophagy. We used a combination of NMR spectroscopy-based methods, mutagenesis, and functional studies to define the interaction site of a Nur77 peptide on anti-apoptotic Bcl-2 family proteins and reveal a novel interaction surface. Nur77 binds adjacent to the BH3 peptide-binding crevice, suggesting the possibility of cross-talk between these discrete binding sites. Mutagenesis of residues lining the identified interaction site on Bcl-B negated the interaction with Nur77 protein in cells and prevented Nur77-mediated modulation of apoptosis and autophagy. The findings establish a new protein interaction site with the potential to modulate the apoptosis and autophagy mechanisms governed by Bcl-2 family proteins. PMID:27129202

  11. Homologous recombination control by the anti-apoptotic onco-protein Bcl-2

    International Nuclear Information System (INIS)

    This research thesis deals with the different biological mechanisms, notably the repair and apoptosis mechanisms induced by irradiation in cells. After a presentation of the genotoxic stress and DNA repair mechanisms, the author discusses the cellular response to a DNA double-strand break, and the regulation of these response mechanisms (how a cellular response emerges: life or death). The next part deals with the apoptosis (cell death by necrosis or apoptosis), and presents the BCL-2 protein family. Results are then reported on laboratory studies of the effect of this protein family

  12. Organ Donation Campaigns: Perspective of Dialysis Patient's Family Members.

    Directory of Open Access Journals (Sweden)

    Makmor Tumin

    2014-07-01

    Full Text Available Solving the dilemma of the organ shortage in Malaysia requires educating Malaysians about organ donation and transplantation. This paper aims at exploring the average Malaysian households ' preferred channels of campaigns and the preferred campaigners in a family setting, targeting at the dialysis family members.We analyzed the responses of 350 respondents regarding organ donation campaigns. The respondents are 2 family members of 175 dialysis patients from 3 different institutions. The information on respondents' willingness to donate and preferred method and channel of organ donation campaign were collected through questionnaire.Malaysian families have a good tendency to welcome campaigns in both the public and private (their homes spheres. We also found that campaigns facilitated by the electronic media (Television and Radio and executed by experienced doctors are expected to optimize the outcomes of organ donation, in general. Chi-square tests show that there are no significant differences in welcoming campaigns among ethnics. However, ethnics preferences over the campaign methods and campaigners are significantly different (P <0.05.Ethnic differences imply that necessary modifications on the campaign channels and campaigners should also be taken under consideration. By identifying the preferred channel and campaigners, this study hopes to shed some light on the ways to overcome the problem of organ shortage in Malaysia.

  13. Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular Vascularization.

    Directory of Open Access Journals (Sweden)

    Ismail S Zaitoun

    Full Text Available Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/- are small in stature and succumb to renal failure shortly after weaning as a result of renal hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed attenuated retinal vascular development and neovascularization. In vitro studies indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts endothelial and epithelial cell adhesion, migration and extracellular matrix production. However, studies delineating the cell autonomous role Bcl-2 expression plays in the endothelium during vascular development, pruning and remodeling, and neovascularization are lacking. Here we generated mice carrying a conditional Bcl-2 allele (Bcl-2Flox/Flox and VE-cadherin-cre (Bcl-2EC mice. Bcl-2EC mice were of normal stature and lifespan and displayed some but not all of the retinal vascular defects previously observed in global Bcl-2 deficient mice. Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal arteries and premature primary branching of the retinal vasculature, but unlike the global knockout mice, spreading of the retinal superficial vascular layer proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice, although retinal neovascularization accompanying oxygen-induced ischemic retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a significant role during postnatal retinal vascularization, and pathological choroidal but not retinal neovascularization, suggesting vascular bed specific Bcl-2 function in the endothelium.

  14. Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular Vascularization.

    Science.gov (United States)

    Zaitoun, Ismail S; Johnson, Ryan P; Jamali, Nasim; Almomani, Reem; Wang, Shoujian; Sheibani, Nader; Sorenson, Christine M

    2015-01-01

    Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/-) are small in stature and succumb to renal failure shortly after weaning as a result of renal hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed attenuated retinal vascular development and neovascularization. In vitro studies indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts endothelial and epithelial cell adhesion, migration and extracellular matrix production. However, studies delineating the cell autonomous role Bcl-2 expression plays in the endothelium during vascular development, pruning and remodeling, and neovascularization are lacking. Here we generated mice carrying a conditional Bcl-2 allele (Bcl-2Flox/Flox) and VE-cadherin-cre (Bcl-2EC mice). Bcl-2EC mice were of normal stature and lifespan and displayed some but not all of the retinal vascular defects previously observed in global Bcl-2 deficient mice. Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal arteries and premature primary branching of the retinal vasculature, but unlike the global knockout mice, spreading of the retinal superficial vascular layer proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice, although retinal neovascularization accompanying oxygen-induced ischemic retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a significant role during postnatal retinal vascularization, and pathological choroidal but not retinal neovascularization, suggesting vascular bed specific Bcl-2 function in the endothelium. PMID:26444547

  15. [Music in human terminality: the family members' conceptions].

    Science.gov (United States)

    Sales, Catarina Aparecida; da Silva, Vladimir Araujo; Pilger, Calíope; Marcon, Sonia Silva

    2011-03-01

    This qualitative study was performed using the multiple case study method and Heidegger's existential phenomenology for data analysis. The objective was to understand how family members perceive the influence of musical experiences on the physical and mental health of a relative living with a terminal illness. Participants were seven individuals belonging to two families. Data collection was performed through interviews and observation from May to June 2009. Results showed that using music while providing care to beings living with cancer can provide well-being to patients as well as their caregivers. Considering the deficit of leisure and the monotony of the home environment, using music contemplates the philosophical and humanitarian precepts of palliative care, thus being characterized as a complementary resource to nursing care, as besides being a communication resource, it improves the interpersonal relationship between patients and their families. PMID:21445500

  16. SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production

    International Nuclear Information System (INIS)

    Highlights: ► Ro52low HeLa cells are resistant to apoptosis upon various stimulations. ► Ro52 is upregulated by IFN-α, etoposide, or IFN-γ and anti-Fas Ab. ► Ro52-mediated apoptosis is independent of p53. ► Ro52 selectively regulates Bcl-2 expression. -- Abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52’s role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52low HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H2O2- or diamide-induced oxidative stress, IFN-α, IFN-γ and anti-Fas antibody, etoposide, or γ-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.

  17. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    Directory of Open Access Journals (Sweden)

    DaLiao Xiao, Lubo Zhang

    2008-01-01

    Full Text Available Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-dependent decrease in fetal brain weight and brain/body weight ratio (P<0.05. Apoptotic nuclei in fetal brain were increased from 2.6 ± 0.1 (control to 8.1± 0.6 (low dose and 10.4 ± 0.2% (high dose (P<0.05. In accordance, cocaine dose dependently increased activities of caspase-3, caspase-8, and caspase-9 (% of control in the fetal brain by 177%, 155%, 174%, respectively, at 30 mg/kg/day, and by 191%, 176%, 274%, respectively, at 60 mg/kg/day. In contrast, cocaine showed no effect on caspase activities in the maternal brain. Cocaine produced a dose-dependent increase in both Bcl-2 and Bax protein expression in the fetal brain, and increased the ratio of Bax/Bcl-2 at dose of 30 mg/kg/day (P<0.05. Significance: Our study has demonstrated that prenatal cocaine exposure induces apoptosis in the fetal brain, and suggested that up-regulating Bax/Bcl-2 gene expression may be involved in cocaine-induced apoptosis. The increased apoptosis of neuronal cells in the fetal brain is likely to play a key role in cocaine-induced neuronal defects during fetal development.

  18. SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production

    Energy Technology Data Exchange (ETDEWEB)

    Jauharoh, Siti Nur Aisyah [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Faculty of Medicine and Health Science, Syarif Hidayatullah State Islamic University, Jakarta 15412 (Indonesia); Saegusa, Jun; Sugimoto, Takeshi [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Ardianto, Bambang [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Department of Child Health, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55282 (Indonesia); Kasagi, Shimpei; Sugiyama, Daisuke; Kurimoto, Chiyo [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Tokuno, Osamu; Nakamachi, Yuji [Department of Laboratory Medicine, Kobe University Hospital, Hyogo 650-0017 (Japan); Kumagai, Shunichi [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Kawano, Seiji, E-mail: sjkawano@med.kobe-u.ac.jp [Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017 (Japan); Department of Laboratory Medicine, Kobe University Hospital, Hyogo 650-0017 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Ro52{sup low} HeLa cells are resistant to apoptosis upon various stimulations. Black-Right-Pointing-Pointer Ro52 is upregulated by IFN-{alpha}, etoposide, or IFN-{gamma} and anti-Fas Ab. Black-Right-Pointing-Pointer Ro52-mediated apoptosis is independent of p53. Black-Right-Pointing-Pointer Ro52 selectively regulates Bcl-2 expression. -- Abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjoegren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52{sup low} HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H{sub 2}O{sub 2}- or diamide-induced oxidative stress, IFN-{alpha}, IFN-{gamma} and anti-Fas antibody, etoposide, or {gamma}-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.

  19. 77 FR 18143 - Members of a Family for Purpose of Filing a CBP Family Declaration

    Science.gov (United States)

    2012-03-27

    ... relationship within the definition of ``members of a family residing in one household.'' CBP also is proposing... related by blood, marriage, domestic relationship, or adoption cannot be included in the family... not related by blood, marriage, domestic relationship, or adoption will not be included in the...

  20. Caspase Induction and BCL2 Inhibition in Human Adipose Tissue

    Science.gov (United States)

    Tinahones, Francisco José; Coín Aragüez, Leticia; Murri, Mora; Oliva Olivera, Wilfredo; Mayas Torres, María Dolores; Barbarroja, Nuria; Gomez Huelgas, Ricardo; Malagón, Maria M.; El Bekay, Rajaa

    2013-01-01

    OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance. PMID:23193206

  1. Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1

    Directory of Open Access Journals (Sweden)

    Mena Salvador

    2012-01-01

    Full Text Available Abstract Background Bcl-2 is believed to contribute to melanoma chemoresistance. However, expression of Bcl-2 proteins may be different among melanomas. Thus correlations among expression of Bcl-2-related proteins and in vivo melanoma progression, and resistance to combination therapies, was investigated. Methods Human A375 melanoma was injected s.c. into immunodeficient nude mice. Protein expression was studied in tumor samples obtained by laser microdisection. Transfection of siRNA or ectopic overexpression were applied to manipulate proteins which are up- or down-regulated, preferentially, during melanoma progression. Anti-bcl-2 antisense oligonucleotides and chemoradiotherapy (glutathione-depleting agents, paclitaxel protein-binding particles, daunorubicin, X rays were administered in combination. Results In vivo A375 cells down-regulated pro-apoptotic bax expression; and up-regulated anti-apoptotic bcl-2, bcl-xl, and mcl-1, however only Bcl-2 appeared critical for long-term tumor cell survival and progression in vivo. Reduction of Bcl-2, combined with partial therapies, decreased melanoma growth. But only Bcl-2 targeting plus the full combination of chemoradiotherapy eradicated A375 melanoma, and led to long-term survival (> 120 days without recurrence in 80% of mice. Tumor regression was not due to immune stimulation. Hematology and clinical chemistry data were within accepted clinical toxicities. Conclusion Strategies to target Bcl-2, may increase the effectiveness of antitumor therapies against melanomas overexpressing Bcl-2 and likely other Bcl-2-related antiapoptotic proteins.

  2. C8, a new member of the convertase family.

    Science.gov (United States)

    Bruzzaniti, A; Goodge, K; Jay, P; Taviaux, S A; Lam, M H; Berta, P; Martin, T J; Moseley, J M; Gillespie, M T

    1996-01-01

    A novel subtilisin-like protein, PC8, was identified by PCR using degenerate primers to conserved amino acid residues in the catalytic region of members of the prohormone convertase family. PC8 was predicted to be 785 residues long and was structurally related to the mammalian convertases furin, PACE4, PC1 and PC2, sharing more than 50% amino acid identity over the catalytic region with these family members. PC8 possessed the catalytically important Asp, His, Asn and Ser amino acids, the homo B domain of this family of enzymes and a C-terminal hydrophobic sequence indicative of a transmembrane domain. Structurally, PC8 is more related to furin and PACE4 than to PC1 or PC2. Like furin and PACE4, PC8 mRNA was found to be widely expressed; this is in contrast with PC1 and PC2, which have a restricted distribution. Two transcripts, of 4.5 and 3.5 kb, were detected in both human cell lines and rat tissues. Unlike furin and PACE4, both of which map to chromosome 15, PC8 maps to chromosome 11q23-11q24, suggesting that this gene may have resulted from an ancient gene duplication event from either furin or PACE4, or conversely that these genes arose from PC8. PMID:8615762

  3. PC8 [corrected], a new member of the convertase family.

    Science.gov (United States)

    Bruzzaniti, A; Goodge, K; Jay, P; Taviaux, S A; Lam, M H; Berta, P; Martin, T J; Moseley, J M; Gillespie, M T

    1996-03-15

    A novel subtilisin-like protein, PC8, was identified by PCR using degenerate primers to conserved amino acid residues in the catalytic region of members of the prohormone convertase family. PC8 was predicted to be 785 residues long and was structurally related to the mammalian convertases furin, PACE4, PC1 and PC2, sharing more than 50% amino acid identity over the catalytic region with these family members. PC8 possessed the catalytically important Asp, His, Asn and Ser amino acids, the homo B domain of this family of enzymes and a C-terminal hydrophobic sequence indicative of a transmembrane domain. Structurally, PC8 is more related to furin and PACE4 than to PC1 or PC2. Like furin and PACE4, PC8 mRNA was found to be widely expressed; this is in contrast with PC1 and PC2, which have a restricted distribution. Two transcripts, of 4.5 and 3.5 kb, were detected in both human cell lines and rat tissues. Unlike furin and PACE4, both of which map to chromosome 15, PC8 maps to chromosome 11q23-11q24, suggesting that this gene may have resulted from an ancient gene duplication event from either furin or PACE4, or conversely that these genes arose from PC8. PMID:8615762

  4. pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737.

    Science.gov (United States)

    Bertin-Ciftci, J; Barré, B; Le Pen, J; Maillet, L; Couriaud, C; Juin, P; Braun, F

    2013-05-01

    Although Bcl-2 family members control caspase activity by regulating mitochondrial permeability, caspases can, in turn, amplify the apoptotic process upstream of mitochondria by ill-characterized mechanisms. We herein show that treatment with a potent inhibitor of Bcl-2 and Bcl-xL, ABT-737, triggers caspase-dependent induction of the BH3-only protein, Mcl-1 inhibitor, Noxa. RNA interference experiments reveal that induction of Noxa, and subsequent cell death, rely not only on the transcription factor E2F-1 but also on its regulator pRb. In response to ABT-737, pRb is cleaved by caspases into a p68Rb form that still interacts with E2F-1. Moreover, pRb occupies the noxa promoter together with E2F-1, in a caspase-dependent manner upon ABT-737 treatment. Thus, caspases contribute to trigger the mitochondrial apoptotic pathway by coupling Bcl-2/Bcl-xL inhibition to that of Mcl-1, via the pRb/E2F-1-dependent induction of Noxa.

  5. Dioscorealide B from the traditional Thai medicine Hua-Khao-Yen induces apoptosis in MCF-7 human breast cancer cells via modulation of Bax, Bak and Bcl-2 protein expression.

    Science.gov (United States)

    Saekoo, Jiraporn; Graidist, Potchanapond; Leeanansaksiri, Wilairat; Dechsukum, Chavaboon; Itharat, Arunporn

    2010-12-01

    Dioscorealide B is a pharmacologically active compound from the rhizome of the Thai medicinal plant Dioscorea membranacea. Here, we demonstrated that in vitro treatment of dioscorealide B resulted in a cytotoxic effect on MCF-7 human breast cancer cells (IC50 = 2.82 microM). To determine whether this compound induces apoptosis in MCF-7, the Annexin V assay was performed. The data showed that the number of apoptotic cells were increased 7-12 folds over that of the control cells after treatment with various concentrations of dioscorealide B (3, 6 and 12 microM) for 24 hours. Dioscorealide B-induced apoptosis was associated with modulation of the multidomain Bcl-2 family members Bax, Bak and Bcl-2. After treatment with 3 microM dioscorealide B, acceleration of the level of proapoptotic proteins Bax and Bak were observed at 6 hours and 12 hours, respectively, while the decrease in the expression of antiapoptotic protein Bcl-2 was observed 3 hours after the treatment. These effects of dioscorealide B might result in the activation of caspase-8, -9 and -7, which lead to apoptosis in MCF-7 cells. Taken together, the results of this study provide evidence that dioscorealide B possesses an antitumor property against human breast cancer cells and thus provide the molecular basis for the further development of dioscorealide B as a novel chemotherapeutic agent for breast cancer treatment. PMID:21299121

  6. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX

    Institute of Scientific and Technical Information of China (English)

    Bonsu Ku; Chengyu Liang; Jae U Jung; Byung-Ha Oh

    2011-01-01

    Interactions between the BCL-2 family proteins determine the cell's fate to live or die. How they interact with each other to regulate apoptosis remains as an unsettled central issue. So far, the antiapoptotic Bc1-2 proteins are thought to interact with BAX weakly, but the physiological significance of this interaction has been vague.Herein, we show that recombinant BCL-2 and BCL-w interact potently with a BCL-2 homology (BH) 3 domain-containing peptide derived from BAX, exhibiting the dissociation constants of 15 and 23 nM, respectively. To clarify the basis for this strong interaction, we determined the three-dimensional structure of a complex of BCL-2 with a BAX peptide spanning its BH3 domain. It revealed that their interactions extended beyond the canonical BH3 domain and involved three nonconserved charged residues of BAX. A novel BAX variant, containing the alanine substitution of these three residues, had greatly impaired affinity for BCL-2 and BCL-w, hut was otherwise indistinguishable from wild-type BAX. Critically, the apoptotic activity of the BAX variant could not be restrained by BCL-2 and BCL-w, pointing that the observed tight interactions are critical for regulating BAX activation. We also comprehensively quantified the binding affinities between the three BCL-2 subfamily proteins. Collectively, the data show that due to the high affinity of BAX for BCL-2, BCL-w and A1, and of BAK for BCL-XL, MCL-1 and A1, only a subset of BH3-only proteins, commonly including BIM, BID and PUMA, could he expected to free BAX or BAK from the antiapoptotic BCL-2 proteins to elicit apoptosis.

  7. BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations.

    Science.gov (United States)

    Masir, Noraidah; Campbell, Lisa J; Goff, Lindsey K; Jones, Margaret; Marafioti, Teresa; Cordell, Jacqueline; Clear, Andrew J; Lister, T Andrew; Mason, David Y; Lee, Abigail M

    2009-03-01

    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining. PMID:19120369

  8. Pan-Bcl-2 inhibitor obatoclax delays cell cycle progression and blocks migration of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Bruno Christian Koehler

    Full Text Available Despite the fact that new treatment regimes have improved overall survival of patients challenged by colorectal cancer (CRC, prognosis in the metastatic situation is still restricted. The Bcl-2 family of proteins has been identified as promising anti cancer drug target. Even though small molecules targeting Bcl-2 proteins are in clinical trials, little is known regarding their effects on CRC. The aim of this study was to preclinically investigate the value of ABT-737 and Obatoclax as anticancer drugs for CRC treatment. The effects of the BH3-mimetics ABT-737 and Obatoclax on CRC cells were assessed using viability and apoptosis assays. Wound healing migration and boyden chamber invasion assays were applied. 3-dimensional cell cultures were used for long term assessment of invasion and proliferation. Clinically relevant concentrations of pan-Bcl-2 inhibitor Obatoclax did not induce cell death. In contrast, the BH3-mimetic ABT-737 induced apoptosis in a dose dependent manner. Obatoclax caused a cell line specific slowdown of CRC cell growth. Furthermore, Obatoclax, but not ABT-737, recovered E-Cadherin expression and led to impaired migration and invasion of CRC cells. The proliferative capacity and invasiveness of CRC cells was strikingly inhibited by low dose Obatoclax in long term 3-dimensional cell cultures. Obatoclax, but not ABT-737, caused a G1-phase arrest accompanied by a downregulation of Cyclin D1 and upregulation of p27 and p21. Overexpression of Mcl-1, Bcl-xL or Bcl-2 reversed the inhibitory effect of Obatoclax on migration but failed to restore the proliferative capacity of Obatoclax-treated CRC cells. The data presented indicate broad and multifaceted antitumor effects of the pan-Bcl-2 inhibitor Obatoclax on CRC cells. In contrast to ABT-737, Obatoclax inhibited migration, invasion and proliferation in sublethal doses. In summary, this study recommends pan-Bcl-2 inhibition as a promising approach for clinical trials in CRC.

  9. Ekspresi Bcl-2 dan Caspase-3 Pascapaparan Hipoksia Hipobarik Intermiten

    OpenAIRE

    Achmad Hidayat; Kahdar Wiradisastra; Bethy S. Hernowo; Tri Hanggono Achmad

    2011-01-01

    Intermittent hypobaric hypoxia often suffered by cabin crew due to the fact that they are breathing lower pressured air inside the plane cabin. Human body will adapt by binding more oxygen and reducing hypoxia effect. Mitochondria function will be irritated by hypoxia which affect, outer mithochondrial membrane permeability due to decrease of Bcl-2 protein. Later on if hypoxia continues mitochondrial membrane will leaked cytocrome-c will released and apoptotic pathway will occur. The purpose ...

  10. Social stress exacerbates stroke outcome by suppressing Bcl-2 expression

    OpenAIRE

    DeVries, A. Courtney; Joh, Hung-Dong; Bernard, Ora; Hattori, Kimihiko; Hurn, Patricia D.; Traystman, Richard J; Alkayed, Nabil J.

    2001-01-01

    The relationship between stressful life events and the onset of disease is well documented. However, the role of psychological stress as a risk factor for life-threatening cerebrovascular insults such as stroke remains unspecified, but could explain individual variation in stroke outcome. To discover the mechanisms through which psychological stress may alter stroke outcome, we modeled the effects of chronic social intimidation and stress on ischemia-induced bcl-2 ...

  11. Ekspresi Bcl-2 dan Caspase-3 Pascapaparan Hipoksia Hipobarik Intermiten

    Directory of Open Access Journals (Sweden)

    Achmad Hidayat

    2011-12-01

    Full Text Available Intermittent hypobaric hypoxia often suffered by cabin crew due to the fact that they are breathing lower pressured air inside the plane cabin. Human body will adapt by binding more oxygen and reducing hypoxia effect. Mitochondria function will be irritated by hypoxia which affect, outer mithochondrial membrane permeability due to decrease of Bcl-2 protein. Later on if hypoxia continues mitochondrial membrane will leaked cytocrome-c will released and apoptotic pathway will occur. The purpose of this study was to analyze Bcl-2 protein as antiapoptosis and caspase-3 as apoptosis indicator of intermittent hypobaric hypoxia exposure. Experimental study >was subjected to Spraque Dawley male mice during January–April 2010 by exposing them to several intermittent hypobaric hypoxias (one to four treatment in an interval of one week. Protein expression on mice heart cell were detected by immunohistochemistry in the Department of Pathology Anatomy Padjadjaran University-RS Dr. Hasan Sadikin Bandung and western blot methods in Department Biomolecullar Indonesia University Jakarta. Bcl-2 protein expressions increased according with the frequency of intermittent hypobaric hypoxia exposures while a reverse trend was found for caspase-3 protein expressions (rs=-0.448, p=0.013. From the study it can be concluded that apoptosis will be decreased as a result of intermittent hypobaric hypoxia exposures, which occurred from natural adaptation mechanism indicated by decrease of cell apoptosis and cardio protective effect will be emerged.

  12. Estimation of BCL-2 protein in carcinoma of the breast and its clinical correlation in locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Aggarwal Himanshu

    2007-01-01

    Full Text Available The change in expression of apoptotic markers (Bcl-2 and Bax proteins brought about by various chemotherapeutic regimens is being used for its predictive value for assessing response to neoadjuvant chemotherapy (NACT in locally advanced breast carcinoma (LABC. Aims: (1 Estimation of Bcl 2 expression in LABC, (2 Any change in Bcl 2 expression following chemotherapy in LABC, (3 Any relation of Bcl 2 estimation to changes in size of tumor, nodal status, age, and menopausal status. Settings and Design: This was a prospective study of 120 cases of LABC. Materials and Methods: All cases were subjected to biopsy and the tissue was evaluated immunohistochemically for apoptotic marker Bcl-2 family protein. Three cycles of NACT were given at three-weekly intervals. Modified radical mastectomy was performed and the specimens were re-evaluated for any change in the Bcl-2 family protein. The clinical response and immunohistochemical response were correlated and compared. Statistical Analysis: Coefficient of correlation was calculated by Pearson correlation coefficient (P-value. Results: Clinical response, as measured by reduction in the tumor size, was observed in 81 (67.5% patients while immunohistochemical response was observed in 67 (55.8% patients. Correlation between immunohistochemical and clinical response was found to be statistically significant (P = 0.02. Nodal response was seen in 72 (60% patients. There were no patients in the N o group; 22 (53.7% of the N 1 patients were down-staged to N o , while 19 (46.3% remained N 1 . In patients with N 2 disease, 11 (13.9% were down-staged to N o status, 39 (49.4% were down-staged to N 1 status, and 29 (36.7% did not show any response. Immunohistochemical response was observed in 67 (55.8% patients. Correlation between immunohistochemical and nodal responses was also found to be statistically significant (P = 0.03. Conclusions: This significant positive correlation between clinical and immunohistochemical

  13. BH4 domain of bcl-2 protein is required for its proangiogenic function under hypoxic condition.

    Science.gov (United States)

    Gabellini, Chiara; De Luca, Teresa; Trisciuoglio, Daniela; Desideri, Marianna; Di Martile, Marta; Passeri, Daniela; Candiloro, Antonio; Biffoni, Mauro; Rizzo, Maria Giulia; Orlandi, Augusto; Del Bufalo, Donatella

    2013-11-01

    Beyond its classical role as apoptosis inhibitor, bcl-2 protein promotes tumor angiogenesis and the removal of N-terminal bcl-2 homology (BH4) domain abrogates bcl-2-induced hypoxia-inducible factor 1 (HIF-1)-mediated vascular endothelial growth factor (VEGF) expression in hypoxic cancer cells. Using M14 human melanoma cell line and its derivative clones stably overexpressing bcl-2 wild-type or deleted of its BH4 domain, we found that conditioned media (CM) from cells expressing BH4-deleted bcl-2 protein showed a reduced capability to increase in vitro human endothelial cells proliferation and differentiation, and in vivo neovascularization compared with CM from cells overexpressing wild-type bcl-2. Moreover, xenografts derived from cells expressing bcl-2 lacking BH4 domain showed a reduction of metastatic potential compared with tumors derived from wild-type bcl-2 transfectants injection. Stably expressing the Flag-tagged N-terminal sequence of bcl-2 protein, encompassing BH4 domain, we found that this domain is sufficient to enhance the proangiogenic HIF-1/VEGF axis under hypoxic condition. Indeed, lacking of BH4 domain abolishes the interaction between bcl-2 and HIF-1α proteins and the capability of exogenous bcl-2 protein to localize in the nucleus. Moreover, when endoplasmic reticulum-targeted bcl-2 protein is overexpressed in cells, this protein lost the capability to synergize with hypoxia to induce the proangiogenic HIF-1/VEGF axis as shown by wild-type bcl-2 protein. These results demonstrate that BH4 domain of bcl-2 is required for the ability of this protein to increase tumor angiogenesis and progression and indicate that bcl-2 nuclear localization may be required for bcl-2-mediated induction of HIF-1/VEGF axis. PMID:23836782

  14. Physiological role of SLC12 family members in the kidney.

    Science.gov (United States)

    Bazúa-Valenti, Silvana; Castañeda-Bueno, María; Gamba, Gerardo

    2016-07-01

    The solute carrier family 12, as numbered according to Human Genome Organisation (HUGO) nomenclature, encodes the electroneutral cation-coupled chloride cotransporters that are expressed in many cells and tissues; they play key roles in important physiological events, such as cell volume regulation, modulation of the intracellular chloride concentration, and transepithelial ion transport. Most of these family members are expressed in specific regions of the nephron. The Na-K-2Cl cotransporter NKCC2, which is located in the thick ascending limb, and the Na-Cl cotransporter, which is located in the distal convoluted tubule, play important roles in salt reabsorption and serve as the receptors for loop and thiazide diuretics, respectively (Thiazide diuretics are among the most commonly prescribed drugs in the world.). The activity of these transporters correlates with blood pressure levels; thus, their regulation has been a subject of intense research for more than a decade. The K-Cl cotransporters KCC1, KCC3, and KCC4 are expressed in several nephron segments, and their role in renal physiology is less understood but nevertheless important. Evidence suggests that they are involved in modulating proximal tubule glucose reabsorption, thick ascending limb salt reabsorption and collecting duct proton secretion. In this work, we present an overview of the physiological roles of these transporters in the kidney, with particular emphasis on the knowledge gained in the past few years. PMID:27097893

  15. Stigma by association and family burden among family members of people with mental illness : the mediating role of coping

    NARCIS (Netherlands)

    van der Sanden, Remko L M; Pryor, John B; Stutterheim, Sarah E; Kok, Gerjo; Bos, Arjan E R

    2016-01-01

    PURPOSE: When someone has a mental illness, family members may share the experience of stigma. Past research has established that family members' experiences of stigma by association predict psychological distress and lower quality-of-life. METHODS: The present study, conducted with 503 family membe

  16. Impact of Chronic Critical Illness on the Psychological Outcomes of Family Members

    OpenAIRE

    Hickman, Ronald L.; Douglas, Sara L.

    2010-01-01

    The uncertain trajectory of chronic critical illness exposes the patient’s family to heightened levels of psychological distress. Symptoms of psychological distress affect more than half of family members exposed to the patient’s chronic critical illness. Although symptoms often dissipate over time, a significant proportion of family members will remain at moderate to high risk for psychological distress well after the patient’s death or discharge from the intensive care unit. Family members ...

  17. Bcl-2 Knockdown Accelerates T Cell Receptor-Triggered Activation-Induced Cell Death in Jurkat T Cells

    OpenAIRE

    Lee, Yun-Jung; Won, Tae Joon; Hyung, Kyeong Eun; Lee, Mi Ji; Moon, Young-hye; Lee, Ik Hee; Go, Byung Sung; Hwang, Kwang Woo

    2014-01-01

    Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-...

  18. Multiple family member visits to family physicians. Terminology, classification, and implications.

    Science.gov (United States)

    Knishkowy, B; Furst, A; Fassberg, Y; Anor, E; Matthews, S; Paz, Y

    1991-01-01

    A study was designed to investigate "the family as the unit of care" in family medicine consultations from the patient's end of the physician-patient axis, unlike most previous related studies, which have concentrated on it from the physician's perspective. During 2 separate weeks in November 1987 and February 1988, nine Israeli family physicians collected demographic and family-related data concerning the spontaneous visiting patterns generated by 1156 persons (899 patients and 257 nonpatients) who attended 796 separate consultations at their clinics during this time. More than one patient attended 12% of the consultations, and more than one person, patient or nonpatient, was present at 36%. At 31% of the consultations children alone or children and adults were recorded as patients (child consultations), and at 69% only adult patients were present (adult consultations). Adults were recorded as second or third patients at 19% of the child consultations but at only 5% of the adult consultations. The child consultations alone yielded 86% of all the nonpatients documented. Basic terminology and methodology for investigating such multiple family member visits to family physicians is discussed as well as the composition of the different family units encountered and their possible significance. PMID:1985136

  19. Interventions for family members caring for an elder with dementia.

    Science.gov (United States)

    Acton, Gayle J; Winter, Mary A

    2002-01-01

    This chapter reviews 73 published and unpublished research reports of interventions for family members caring for an elder with dementia by nurse researchers and researchers from other disciplines. Reports were identified through searches of MEDLINE, CINAHL, Social Science Index, PsycINFO, ERIC, Social Work Abstracts, American Association of Retired Persons database, CRISP index of the National Institutes of Health, Cochrane Center database, and Dissertation Abstracts using the following search terms: caregiver, caregiving, dementia, Alzheimer's, intervention study, evaluation study, experimental, and quasi-experimental design. Additional keywords were used to narrow or expand the search as necessary. All nursing research was included in the review and nonnursing research was included if published between 1991 and 2001. Studies were included if they used a design that included a treatment and control group or a one-group, pretest-posttest design (ex post facto designs were included if they used a comparison group). Key findings show that approximately 32% of the study outcomes (e.g., burden, depression, knowledge) were changed after intervention in the desired direction. In addition, several problematic issues were identified including small, diverse samples; lack of intervention specificity; diversity in the length, duration, and intensity of the intervention strategies; and problematic outcome measures.

  20. Emotional disorders in pairs of patients and their family members during and after ICU stay.

    Directory of Open Access Journals (Sweden)

    Renata Rego Lins Fumis

    Full Text Available INTRODUCTION: Patients and family members undergo different experiences of suffering from emotional disorders during ICU stay and after ICU discharge. The purpose of this study was to compare the incidence of anxiety, depression and post-traumatic stress disorder (PTSD symptoms in pairs (patient and respective family member, during stay at an open visit ICU and at 30 and 90-days post-ICU discharge. We hypothesized that there was a positive correlation with the severity of symptoms among pairs and different patterns of suffering over time. METHODS: A prospective study was conducted in a 22-bed adult general ICU including patients with >48 hours stay. The Hospital Anxiety and Depression Scale (HADS was completed by the pairs (patients/respective family member. Interviews were made by phone at 30 and 90-days post-ICU discharge using the Impact of Event Scale (IES and the HADS. Multivariate models were constructed to predict IES score at 30 days for patients and family members. RESULTS: Four hundred and seventy one family members and 289 patients were interviewed in the ICU forming 184 pairs for analysis. Regarding HADS score, patients presented less symptoms than family members of patients who survived and who deceased at 30 and 90-days (p<0.001. However, family members of patients who deceased scored higher anxiety and depression symptoms (p = 0.048 at 90-days when compared with family members of patients who survived. Patients and family members at 30-days had a similar IES score, but it was higher in family members at 90-days (p = 0.019. For both family members and patients, age and symptoms of anxiety and depression during ICU were the major determinants for PTSD at 30-days. CONCLUSIONS: Anxiety, depression and PTSD symptoms were higher in family members than in the patients. Furthermore, these symptoms in family members persisted at 3 months, while they decreased in patients.

  1. 5 CFR 734.307 - Campaigning for a spouse or family member.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Campaigning for a spouse or family member... Campaigning for a spouse or family member. An employee covered under this subpart who is the spouse or family..., accept, or receive contributions of money or the paid or unpaid services of a business or corporation,...

  2. The impact of leader-member exchange (LMX) on work-family interference and work-family facilitation

    NARCIS (Netherlands)

    L.G. Tummers (Lars); B.A.C. Bronkhorst (Babette)

    2014-01-01

    markdownabstract__Abstract__ Purpose – We analyze the effects of leadership on work-family spillovers. Specifically, we analyze the relationships between leadership (leader-member exchange, LMX) with one negative work-family spillover effect (work-family interference) and one positive work-family s

  3. Bcl-2 associated with severity of manic symptoms in bipolar patients in a manic phase.

    Science.gov (United States)

    Chen, Wei-Ting; Huang, Tiao-Lai; Tsai, Meng-Chang

    2015-02-28

    B cell lymphoma protein-2 (Bcl-2) may contribute to the pathophysiology of bipolar disorder, and may be involved in the therapeutic action of anti-manic drugs. The aim of this study was to investigate serum levels of Bcl-2 in bipolar patients in a manic phase, and evaluate the Bcl-2 changes after treatment. We consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy subjects; 20 bipolar patients were followed up with treatment. Serum Bcl-2 levels were measured with assay kits. All 20 patients were evaluated by examining the correlation between Bcl-2 levels and Young Mania Rating Scale (YMRS) scores, using Spearman׳s correlation coefficients. The serum Bcl-2 levels in bipolar patients in a manic phase were higher than in healthy subjects, but without a significant difference. The YMRS scores were significantly negatively associated with serum Bcl-2 levels (p=0.042). Bcl-2 levels of the 20 bipolar patients were measured at the end of treatment. Using the Wilcoxon Signed Rank test, we found no significant difference in the Bcl-2 levels of bipolar patients after treatment. Our results suggest that Bcl-2 levels might be an indicator of severity of manic symptoms in bipolar patients in a manic phase. PMID:25563670

  4. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis

    Science.gov (United States)

    Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H. Leighton; Katz, Jonathan D.; Finkelman, Fred D.; Hildeman, David A.

    2007-01-01

    We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2−/− mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim+/−Bcl-2−/− mice, but were largely restored in Bim−/−Bcl-2−/− mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim−/−, T cells. Further, T cells from Bim+/−Bcl-2−/− mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8+ T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4+ T cells did not. In contrast, Bim+/−Bcl-2−/− mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim+/−Bcl-2−/− mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells. PMID:17591857

  5. Cloning and characterization of a second member of the mouse mdr gene family.

    OpenAIRE

    Gros, P.; Raymond, M; Bell, J.; Housman, D

    1988-01-01

    The mammalian mdr gene family comprises a small number of closely related genes. Previously, we have shown that one member, mdr1, has the capacity to convey multidrug resistance to drug-sensitive recipient cells in a gene transfer protocol. However, the functional characteristics of other members of this gene family have not been examined. In this report, we characterize a second member of the mdr gene family which we designated mdr2. We determined the nucleotide sequence corresponding to the...

  6. Racial disparity in capital punishment and its impact on family members of capital defendants.

    Science.gov (United States)

    Schweizer, Jennifer

    2013-01-01

    A review of the literature was conducted to explore the continuing racial disparity in capital punishment and its effects on family members of African American capital defendants. Statistical studies conducted on both the state and national level conclude that racial bias influences all stages of the death penalty process, with race of the victim being one of the most significant factors. This racial bias places an added burden on family members of African American capital defendants. While research has explored the impact of capital punishment on family members of capital defendants, the unique experiences of family members of African American defendants has not been addressed in the research literature.

  7. Clinicopathological significance of Bcl-2 and Bax protein expression in human pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Dong; Jian-Ping Zhou; Hao Zhang; Ke-Jian Guo; Yu-Lin Tian; Yu-Ting Dong

    2005-01-01

    AIM: To assess the clinicopathological significance of the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. METHODS: Fifty-nine surgical specimens of IDCs of the pancreas were stained immunohistochemically to detectpBcl-2 and pBax expressions whose correlation to tumor classification, staging, and prognosis was analyzed by univariate and multivariate analyses. RESULTS: The expression of pBcl-2 and pBax was detected in 21 of 59 (35.6%) and in 29 of 59 (49.2%) patients with IDCs of the pancreas, respectively. Neither pBcl-2 nor pBax alone was correlated to TNM staging and differentiation degree of IDCs of the pancreas according to univariate analysis. By Mantel-Cox test, the median survival time after surgery for pBcl-2(+) and pBcl-2(-) groups were 14.3 and 7.3 mo, respectively (χ2= 9.357, P = 0.002) and that for pBax(+) and pBax(-) groups were 12.9 and 10.2 mo, respectively (χ2= 0.285, P>0.05).Contingency coefficient between pBd-2 and pBax expression was 0.298, indicating that there was correlation between them (χ2= 5.74, P<0.05). The median survival time after surgery for pBd-2(+)pBax(+) and pBcl-2(+)pBax(-) groups were 14.3 and 14.1 mo, respectively, and that for pBcl-2 (-)pBax(+) and pBcl-2(-)pBax(-) groups were 5.9 and 9.9 mo, respectively. There was a significant difference between pBcl-2(+)pBax(+) and pBcl-2(-)pBax(+) (χ2 = 5.06,P<0.05), such was the case for pBcl-2(+)pBax(+) andpBcl-2(-)pBax(-) (χ2= 7.18, P<0.01). Cox proportional hazards model for multivariate analysis was applied, indicating that pBcl-2, TNM staging, age and pBax were high risk factors of post-surgical survival time. CONCLUSION: Both pBcl-2 and pBax have high expression in IDCs of the pancreas, indicating that co-expression of pBcl-2 and pBax is a good indicator of favorable prognosis in IDCs of the pancreas.

  8. Expression of Bcl2 proto-oncogene in primary tumors of the central nervous system.

    Directory of Open Access Journals (Sweden)

    Tyagi D

    2002-07-01

    Full Text Available The present study was addressed to find out the expression of Bcl2 proto-oncogene in tumor tissues derived from 25 patients with primary central nervous system tumors. Brain parenchyma in 8 cases, with deeply located tumor, was also examined for Bcl2 expression which served as control. Both benign and malignant tumors (confirmed by histopathological examination expressed Bcl2 gene product. Tumors exhibited 2-6 fold increase in Bcl2 expression as compared to the normal parenchyma adjacent to some of these tumors studied. However, no correlation was found between the histopathological types of tumor, glial fibrillary acidic protein positivity and degree of Bcl2 expression. Based on this study, we propose that the overexpression of Bcl2 gene product found in primary CNS tumors may be an important molecular event which is known to make the various types of tumor resistant to chemotherapy or radiotherapy.

  9. Genetic variation in BCL2 3'-UTR was associated with lung cancer risk and prognosis in male Chinese population.

    Directory of Open Access Journals (Sweden)

    Ping Xu

    Full Text Available OBJECTIVES: Bcl-2 is a critical apoptosis inhibitor with established carcinogenic potential, and can confer cancer cell resistance to therapeutic treatments by activating anti-apoptotic cellular defense. We hypothesized that genetic variants of BCL2 gene may be associated with lung cancer susceptibility and prognosis. METHODS: Three selected tagSNPs of BCL2 (rs2279115, rs1801018, and rs1564483 were genotyped in 1017 paired male Chinese lung cancer cases and controls by TaqMan assay. The associations of these variants with risk of lung cancer and overall survival of 242 male advanced non-small-cell lung cancer (NSCLC patients were separately investigated. RESULTS: Compared with the BCL2 3'UTR rs1564483GG genotype, the rs1564483GA, AA, and GA+AA genotypes were associated with significantly decreased susceptibilities of lung cancer in male Chinese (adjusted OR = 0.78, 0.73, and 0.76, P = 0.016, 0.038, and 0.007, respectively, while rs1564483A allele has a inverse dose-response relationship with lung cancer risk (P trend = 0.010. These effects were more evident in the elders, smokers, and subjects without family history of cancer (P trend = 0.017, 0.043 and 0.005, respectively. Furthermore, advanced NSCLC males carrying BCL2 rs1564483 GA+AA genotypes had significantly longer median survival time (Long-rank P = 0.036 and decreased death risk (adjusted HR = 0.69, P = 0.027 than patients with rs1564483GG genotype. These effects were more obvious in patients with smoking, stage IIIA, and in patients without surgery but underwent chemotherapy or radiotherapy (adjusted HR = 0.68, 0.49, 0.67, 0.69, 0.50, respectively, all P<0.05. CONCLUSION: The BCL2 3'UTR rs1564483A allele was associated with a decreased lung cancer risk and better survival for advanced NSCLC in male Chinese, which may offer a novel biomarker for identifying high-risk population and predicting clinical outcomes.

  10. 41 CFR 302-11.104 - When must I and/or a member(s) of my immediate family have acquired title interest in my...

    Science.gov (United States)

    2010-07-01

    ... member(s) of my immediate family have acquired title interest in my residence to be eligible for the allowance for expenses incurred in connection with the sale of my residence? 302-11.104 Section 302-11.104... Requirements § 302-11.104 When must I and/or a member(s) of my immediate family have acquired title interest...

  11. Family members' lived experience in the intensive care unit: a phemenological study.

    LENUS (Irish Health Repository)

    McKiernan, Margaret

    2012-01-31

    AIM: To describe the lived experience of family members of patients in the intensive care unit. BACKGROUND: Admission of a critically ill relative to an intensive care unit causes anxiety and stress to family members. Nursing care is initially focused on maintaining the physiological stability of the patient and less on the needs and concerns of family members. Understanding how families make sense of this experience may help nurses focus on the delivery of family centred care. METHODOLOGY: A phenomenological method was used to describe the lived experiences of family members of patients in an intensive care unit. In-depth interviews were conducted with six family members and analysed using qualitative thematic analysis. RESULTS: Four main themes emerged from the data: the need to know, making sense of it all, being there with them and caring and support. Family members needed honest information about the patient\\'s progress and outcome to make the situation more bearable for them. Making sense of the situation was a continuous process which involved tracking and evaluating care given. Being with their relative sustained their family bond and was a way to demonstrate love and support. Caring reassurance provided by the nurses enabled a sense of security. Support was needed by family members to assist them in coping. CONCLUSION: The research provided an insight into how family members viewed the impact of the admission and how they subsequently found ways of dealing with the situation. RELEVANCE TO CLINICAL PRACTICE: Using a holistic approach to nursing assessment and care delivery in intensive care necessitates that nurses interact with and care for family members of patients. Development of a philosophy of family centred care is necessary, with formal assessment of families to take place soon after admission and an appropriate plan of care drawn up at this time.

  12. Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation.

    OpenAIRE

    Jiang, S. X.; Kameya, T.; Sato, Y.; Yanase, N.; Yoshimura, H.; Kodama, T

    1996-01-01

    For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas ...

  13. Study of immunohistochemical demonstration of Bcl-2 protein in ameloblastoma and keratocystic odontogenic tumor

    OpenAIRE

    C S Sindura; Chaitanya Babu; Vijaya Mysorekar; Vinod Kumar

    2013-01-01

    Background: The Bcl-2 (B-cell lymphoma) gene product also known as apoptotic inhibitor is expressed in many normal and tumor tissues. This Bcl-2 gene protects the cell by blocking postmitotic differentiation from apoptosis, thus maintaining the stem cell pool. Objective: To study the expression of Bcl-2 protein in ameloblastoma and keratocystic odontogenic tumor (KCOT) to determine their apoptotic behaviors and to analyze biological nature of KCOT, which has higher proliferative potential and...

  14. Icariin Attenuates OGD/R-Induced Autophagy via Bcl-2-Dependent Cross Talk between Apoptosis and Autophagy in PC12 Cells

    Science.gov (United States)

    2016-01-01

    Icariin (ICA), an active component of Epimedium brevicornum Maxim, exerts a variety of neuroprotective effects such as antiapoptosis. However, the mechanisms underlying antiapoptosis of ICA in neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) are unclear. The B-cell lymphoma-2 (Bcl-2) protein family plays an important role in the regulation of apoptosis and autophagy through Bcl-2-dependent cross talk. Bcl-2 suppresses apoptosis by binding to Bax and inhibits autophagy by binding to Beclin-1 which is an autophagy related protein. In the present study, MTT result showed that ICA increased cell viability significantly in OGD/R treated PC12 cells (P < 0.01). Results of western blotting analysis showed that ICA increased Bcl-2 expression significantly and decreased expressions of Bax, cleaved Caspase-3, Beclin-1, and LC3-II significantly in OGD/R treated PC12 cells (P < 0.01). These results suggest that ICA protects PC12 cells from OGD/R induced autophagy via Bcl-2-dependent cross talk between apoptosis and autophagy. PMID:27610184

  15. Combined Targeting of JAK2 and Bcl-2/Bcl-xL to Cure Mutant JAK2-Driven Malignancies and Overcome Acquired Resistance to JAK2 Inhibitors

    OpenAIRE

    2013-01-01

    Summary To design rational therapies for JAK2-driven hematological malignancies, we functionally dissected the key survival pathways downstream of hyperactive JAK2. In tumors driven by mutant JAK2, Stat1, Stat3, Stat5, and the Pi3k and Mek/Erk pathways were constitutively active, and gene expression profiling of TEL-JAK2 T-ALL cells revealed the upregulation of prosurvival Bcl-2 family genes. Combining the Bcl-2/Bcl-xL inhibitor ABT-737 with JAK2 inhibitors mediated prolonged disease regressi...

  16. BCL2L13 is a mammalian homolog of the yeast mitophagy receptor Atg32.

    Science.gov (United States)

    Otsu, Kinya; Murakawa, Tomokazu; Yamaguchi, Osamu

    2015-01-01

    Although Atg32 is essential for mitophagy in yeast, no mammalian homolog has been identified. Here, we demonstrate that BCL2L13 (BCL2-like 13 [apoptosis facilitator]) is a functional mammalian homolog of Atg32. First, we hypothesized that a mammalian mitophagy receptor will share certain molecular features with Atg32. Using the molecular profile of Atg32 as a search tool, we screened public databases for novel Atg32 functional homologs and identified BCL2L13. BCL2L13 induces mitochondrial fragmentation and mitophagy in HEK293 cells. In BCL2L13, the BH domains are important for fragmentation, whereas the WXXI motif, an LC3 interacting region, is needed for mitophagy. BCL2L13 induces mitochondrial fragmentation and mitophagy even in the absence of DNM1L/Drp1 and PARK2/Parkin, respectively. BCL2L13 is indispensable for mitochondrial damage-induced fragmentation and mitophagy. Furthermore, BCL2L13 induces mitophagy in Atg32-deficient yeast. Induction and/or phosphorylation of BCL2L13 may regulate its activity. Our findings thus open a new chapter in mitophagy research. PMID:26506896

  17. Down-Regulation of Bcl-2 Protein Sensitizes NCI 460 Cells to Radiotherapy-Induced Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Dongmei He; Yuan Zhang; Gexiu Liu

    2006-01-01

    OBJECTIVE To determine whether Bcl-2 protein down-regulation can render NCI-460 cells more susceptible to gamma radiation-induced apoptosis by treatment with antisense oligonucleotide (ASODN) against the coding region of Bcl-2 mRNA.METHODS Cell survival was determined using the trypan blue dye exclusion. Expression of the Bcl-2 protein was assayed using immunofluorescence labeling with fluoresce isothiocyanate. Apoptosis was determined by Giemsa staining and flow cytomertry.RESULTS It was found that Bcl-2 ASODN combined with radiation significantly reduced the number of viable cells (P<0.05). There was no difference in cell survival between a nonsense oligodeoxynucleotide/radiation combination and cells treated with radiation alone. Bcl-2 ASODN combined with radiation significantly inhibited expression of the Bcl-2protein in the NCI-H460 cells (P<0.05). Using Giemsa staining, cells treated with Bcl-2 ASODN combined with radiation at 72 h displayed classic apoptotic changes. Apoptotic rates of the NCI-H460 cells treated with Bcl-2 ASODN combined with radiation significantly increased (P<0.05), compared with either a nonsense oligodeoxynucleotide/radiation combination or radiation-treatment cells alone.CONCLUSION ASODN against the coding region of Bcl-2 mRNA increases radiation-induced apoptosis in NCI-H460 cells.

  18. Antiapoptotic Bcl-2 protein as a potential target for cancer therapy: A mini review.

    Science.gov (United States)

    Jagani, Hitesh; Kasinathan, Narayanan; Meka, Sreenivasa Reddy; Josyula, Venkata Rao

    2016-08-01

    Bcl-2, an antiapoptotic protein, is considered as a potential target in cancer treatment since its oncogenic potential has been proven and is well documented. Antisense technology and RNA interference (RNAi) have been used to reduce the expression of the Bcl-2 gene in many types of cancer cells and are effective as adjuvant therapy along with the chemotherapeutic agents. The lack of appropriate delivery systems is considered to be the main hurdle associated with the RNAi. In this review, we discuss the antiapoptotic Bcl-2 protein, its oncogenic potential, and various approaches utilized to target Bcl-2 including suitable delivery systems employed for successful delivery of siRNA. PMID:25801037

  19. BEX1 promotes imatinib-induced apoptosis by binding to and antagonizing BCL-2.

    Directory of Open Access Journals (Sweden)

    Qian Xiao

    Full Text Available An enhanced anti-apoptotic capacity of tumor cells plays an important role in the process of breakpoint cluster region/Abelson tyrosine kinase gene (BCR/ABL-independent imatinib resistance. We have previously demonstrated that brain expressed X-linked 1 (BEX1 was silenced in secondary imatinib-resistant K562 cells and that re-expression of BEX1 can restore imatinib sensitivity resulting in the induction of apoptosis. However, the mechanism by which BEX1 executes its pro-apoptotic function remains unknown. We identified B-cell lymphoma 2 (BCL-2 as a BEX1-interacting protein using a yeast two-hybrid screen. The interaction between BEX1 and BCL-2 was subsequently confirmed by co-immunoprecipitation assays. Like BCL-2, BEX1 was localized to the mitochondria. The region between 33K and 64Q on BEX1 is important for its localization to the mitochondria and its ability to interact with BCL-2. Additionally, we found that this region is essential for BEX1-regulated imatinib-induced apoptosis. Furthermore, we demonstrated that the interaction between BCL-2 and BEX1 promotes imatinib-induced apoptosis by suppressing the formation of anti-apoptotic BCL-2/BCL-2-associated X protein (BAX heterodimers. Our results revealed an interaction between BEX1 and BCL-2 and a novel mechanism of imatinib resistance mediated by the BEX1/BCL-2 pathway.

  20. EFFECT OF TWO NEW BCL-2 ANTISENSES ON DRUG-SENSITIVITY OF CELLS FROMN LEUKEMIA PATIENTS

    Institute of Scientific and Technical Information of China (English)

    LEI Xiao-yong; ZHANG Huan

    2005-01-01

    Objective:To investigate the effect of two antisense oligonucleotides on cell surviving, bcl-2 expression and apoptosis of leukemia cells. Methods: The experimental assays were performed with cell culture, immunochemistry and flowcytometry. Results: The two antisense oligodeoxynucleotides, combined with Vp16 or Ara-c or DNR, were able to decline the survival rate of myeleukemic cells, downregulate bcl-2 gene expression and induce apoptosis of leukemic cells significantly, as compared with Vp16 or Ara-c or DNR alone. Conclusion: It is possible for the two new bcl-2 antisenses to be developed into clinical trials for leukemia and tumor with bcl-2 gene overexpression.

  1. Predictive value of bcl-2 immunoreactivity in prostate cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Background and purpose: Recent experimental evidence suggests that overexpression of bcl-2, a protein functioning by blocking apoptosis, may influence the treatment outcome in human tumours, including prostate cancer. To test the clinical implications of this hypothesis, tumours from patients with prostate cancer treated with external beam radiotherapy were investigated for bcl-2 immunoreactivity (IR) and correlated with prognosis and treatment outcome. Materials and methods: Bcl-2 IR was evaluated in archival tumour specimens obtained through transurethral resection from 42 patients with localized prostate cancer (T0-T4, N0 and M0). Bcl-2 IR expression was related to stage, grade and cancer-specific survival. Specimens were obtained prior to administrating routine radiotherapy for all patients. Results: Bcl-2 IR was present in 19/42 (45%) tumours. The bcl-2-positive patients had a significantly longer cancer-specific survival than the bcl-2-negative patients (10.3 versus 3.4 years, P<0.04). At follow-up (7-19 years), nine patients were still alive, 26 patients had died of prostate cancer and seven patients had died of other causes. Conclusions: This study indicates that pre-treatment bcl-2 overexpression is related to a favourable outcome in prostate cancer treated with radiotherapy. Low bcl-2 along with a high stage may be a predictor of poor prognosis and these patients might benefit from additional treatment. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  2. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

    International Nuclear Information System (INIS)

    We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

  3. The impact of leader-member exchange (LMX) on work-family interference and work-family facilitation

    NARCIS (Netherlands)

    L.G. Tummers (Lars); B.A.C. Bronkhorst (Babette)

    2014-01-01

    markdownabstract__Abstract__ __Purpose__ – We analyze the effects of leadership on work-family spillovers. Specifically, we analyze the relationships between leadership (leader-member exchange, LMX) with one negative work-family spillover effect (work-family interference) and one positive work-fam

  4. Accommodating family life: mentoring future female faculty members.

    Science.gov (United States)

    Lodish, Harvey F

    2015-03-01

    The demands of family life are crucial factors in successfully retaining women in science. Retention efforts should focus on creating a family-friendly environment within the laboratory and the institute. Based on my own experiences, I suggest ways to attract top young scientists and support their development into leading researchers.

  5. Emotions experienced and coping strategies used by family members of organ donors.

    Science.gov (United States)

    Pelletier, M

    1993-01-01

    In this descriptive study guided by the Lazarus and Folkman (1984) stress and coping theory, donor family members' emotional responses and coping strategies used during the anticipation and confrontation stages of the organ donation experience were explored. Seven families from Eastern Canada who had lost a loved one suddenly and consented to organ donation were interviewed in their homes. The findings clearly showed that family members experienced a variety of emotions and used several different types of coping strategies. The findings of this study contribute to the development of knowledge required to guide nursing interventions to provide sensitive care to family members of organ donors.

  6. Expressions of bcl-2 and P53 protein in Bowen's disease%Bowen病bcl-2及P53蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    张士发; 王良明; 赵丽萍; 许静; 顾绍裘

    2004-01-01

    目的:探讨bcl-2及P53蛋白在Bowen病及Bowen样鳞癌中的表达及其意义.方法:应用免疫组织化学技术对11例Bowen病及3例Bowen样鳞癌bcl-2和/或P53蛋白的表达进行了检测.结果:11例Bowen病中bcl-2蛋白阳性2例(18%),P53蛋白阳性3例(27%);3例Bowen样鳞癌均见bcl-2蛋白表达.Bowen病中bcl-2与P53蛋白表达显著正相关(r=0.769,P<0.05).结论:Bowen病中bcl-2蛋白表达与P53基因突变有关,并参与了Bowen病的进展及向Bowen样鳞癌的演变.

  7. Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis.

    Directory of Open Access Journals (Sweden)

    Takeshi Moriishi

    Full Text Available Bcl2 subfamily proteins, including Bcl2 and Bcl-X(L, inhibit apoptosis. As osteoblast apoptosis is in part responsible for osteoporosis in sex steroid deficiency, glucocorticoid excess, and aging, bone loss might be inhibited by the upregulation of Bcl2; however, the effects of Bcl2 overexpression on osteoblast differentiation and bone development and maintenance have not been fully investigated. To investigate these issues, we established two lines of osteoblast-specific BCL2 transgenic mice. In BCL2 transgenic mice, bone volume was increased at 6 weeks of age but not at 10 weeks of age compared with wild-type mice. The numbers of osteoblasts and osteocytes increased, but osteoid thickness and the bone formation rate were reduced in BCL2 transgenic mice with high expression at 10 weeks of age. The number of BrdU-positive cells was increased but that of TUNEL-positive cells was unaltered at 2 and 6 weeks of age. Osteoblast differentiation was inhibited, as shown by reduced Col1a1 and osteocalcin expression. Osteoblast differentiation of calvarial cells from BCL2 transgenic mice also fell in vitro. Overexpression of BCL2 in primary osteoblasts had no effect on osteoclastogenesis in co-culture with bone marrow cells. Unexpectedly, overexpression of BCL2 in osteoblasts eventually caused osteocyte apoptosis. Osteocytes, which had a reduced number of processes, gradually died with apoptotic structural alterations and the expression of apoptosis-related molecules, and dead osteocytes accumulated in cortical bone. These findings indicate that overexpression of BCL2 in osteoblasts inhibits osteoblast differentiation, reduces osteocyte processes, and causes osteocyte apoptosis.

  8. Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

    Institute of Scientific and Technical Information of China (English)

    Sheng-Mian Li; Shu-Kun Yao; Nobuyoshi Yamamura; Toshitsugu Nakamura

    2003-01-01

    AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors.METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n=21, carcinoma of ampulla of Vater: n=6), and 10 cases of atypical dysplasia.Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity.RESULTS: The expression of Bd-2 was observed in 10 out of 27 (37.0 %) invasive carcinomas, 1 out of 10 clysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30 % (3/10) in dysplasia,and 40 % (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia,with no significant difference in Bcl-2 expression (P=0.1:10),and significant difference in Bax expression (P=0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P=0.012). Bcl-2 expression was correlated to Bax expression (P=0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype,grade of differentiation, or level of invasion.CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part,in the apoptotic activity in extrahepatic biliary carcinoma.

  9. Herpesvirus pan encodes a functional homologue of BHRF1, the Epstein-Barr virus v-Bcl-2

    Directory of Open Access Journals (Sweden)

    Williams Tracey

    2005-02-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV latently infects about 90% of the human population and is associated with benign and malignant diseases of lymphoid and epithelial origin. BHRF1, an early lytic cycle antigen, is an apoptosis suppressing member of the Bcl-2 family. In vitro studies imply that BHRF1 is dispensable for both virus replication and transformation. However, the fact that BHRF1 is highly conserved not only in all EBV isolates studied to date but also in the analogous viruses Herpesvirus papio and Herpesvirus pan that infect baboons and chimpanzees respectively, suggests BHRF1 may play an important role in vivo. Results Herpesvirus papio BHRF1 has been shown to function in an analogous manner to EBV BHRF1 in response to DNA damaging agents in human keratinocytes. In this study we show that the heterologous expression of the previously uncharacterised Herpesvirus pan BHRF1 in the human Burkitt's lymphoma cell line Ramos-BL provides similar anti-apoptotic functions to that of EBV BHRF1 in response to apoptosis triggered by serum withdrawal, etoposide treatment and ultraviolet (UV radiation. We also map the amino acid changes onto the recently solved structure of the EBV BHRF1 and reveal that these changes are unlikely to alter the 3D structure of the protein. Conclusions These findings show that the functional conservation of BHRF1 extends to a lymphoid background, suggesting that the primate virus proteins interact with cellular proteins that are themselves highly conserved across the higher primates. Further weight is added to this suggestion when we show that the difference in amino acid sequences map to regions on the 3D structure of EBV BHRF1 that are unlikely to change the conformation of the protein.

  10. The relationship of adverse childhood experiences to a history of premature death of family members

    OpenAIRE

    Valerie Edwards J; Perry Geraldine S; Giles Wayne H; Felitti Vincent J; Brown David W; Dong Maxia; Anda Robert F; Dube Shanta R

    2009-01-01

    Abstract Background To assess the association between adverse childhood experiences (ACEs), including childhood abuse and neglect, and serious household dysfunction, and premature death of a family member. Because ACEs increase the risk for many of the leading causes of death in adults and tend to be familial and intergenerational, we hypothesized that persons who report having more ACEs would be more likely to have family members at risk of premature death. Methods We used data from 17,337 a...

  11. Parents and Children Only? Acculturation and the Influence of Extended Family Members among Vietnamese Refugees

    OpenAIRE

    Tingvold, Laila; Middelthon, Anne-Lise; Allen, James; Hauff, Edvard

    2011-01-01

    The nuclear family is often the point of departure in much of the existing acculturation research on refugee youth and children of refugees. The influence of other extended family members appears to receive less attention in understanding acculturation processes and intergenerational perspectives. This qualitative study explores the influence of extended family members upon a small sample of Vietnamese refugee parents and their adolescents while they undergo acculturation through their long-t...

  12. The relationship of adverse childhood experiences to a history of premature death of family members

    Directory of Open Access Journals (Sweden)

    Valerie Edwards J

    2009-04-01

    Full Text Available Abstract Background To assess the association between adverse childhood experiences (ACEs, including childhood abuse and neglect, and serious household dysfunction, and premature death of a family member. Because ACEs increase the risk for many of the leading causes of death in adults and tend to be familial and intergenerational, we hypothesized that persons who report having more ACEs would be more likely to have family members at risk of premature death. Methods We used data from 17,337 adult health plan members who completed a survey about 10 types of ACEs and whether a family member died before age 65. The prevalence of family member premature death and its association with ACEs were assessed. Results Family members of respondents who experienced any type of ACEs were more likely to have elevated prevalence for premature death relative to those of respondents without such experience (p Conclusion Adverse childhood experiences may be an indicator of a chaotic family environment that results in an increased risk of premature death among family members.

  13. Expression of bcl-2 in the Epithelial Lining of Odontogenic Keratocysts

    Directory of Open Access Journals (Sweden)

    Gh. Jahanshahi

    2006-03-01

    Full Text Available Statement of Problem: The aggressive nature and high recurrence rate of Odontogenic Keratocysts (OKCs may be due to unknown factors inherent in the epithelium or because of enzymatic activity in the fibrous wall. Bcl-2 protein is characterized by its ability to inhibit apoptosis.Purpose: The aim of the present study was to analyze the expression of bcl-2 protein in OKCs and to compare it with the more common radicular and dentigerous cysts. The possible relationship between inflammation and bcl-2 expression was also investigated.Materials and Methods: Formalin fixed paraffin-embedded tissue sections of 20 OKCs, 20 radicular and 20 dentigerous cysts were immunohistochemically analyzed for immunoreactivity of the bcl-2 protein.Results: Bcl-2 expression was observed in 19 OKCs (95%, one radicular cyst (5%and one dentigerous cyst (5%. There was no statistically significant relationship between inflammation and the number of bcl-2 positive cells. Immunoreactivity was mainly noted in the basal or basal/supra basal layers.Conclusion: Considering the fact that bcl-2 over expression may lead to increased survival of epithelial cells, present study may demonstrate a possible relationship between the aggressive nature of OKC and the intrinsic growth potential of its lining epithelium. Furthermore a basal/supra basal distribution of bcl-2 positive cells was seen in some odontogenic keratocysts which may have a significant impact on the behavior of this cyst.

  14. The effect of radiation on bcl-2 and bax in hyperplastic prostatic tissues

    International Nuclear Information System (INIS)

    Aim: To investigate the expressions of bcl-2 and bax in benign prostatic hyperplasia (BPH) and the effect of β-rays on bcl-2 and bax. Methods: The expressions of bcl-2 and bax are studied by means of immunohistochemical method in 9 normal prostate (NP) and 15 BPH and 35 patients treated with 90Sr/90Y Prostatic Hyperplasia Applicator. Results: The expressions of bcl-2 in epithelia of NP and BPH are higher than that in stroma P<0.01=. The expressions of bcl-2 in epithelia and stroma of BPH are higher than that in NP P<0.01=. The expressions of bax in epithelia of NP are higher than that in BPH P<0.05=. However ,the expressions of bcl-2 in epithelia and stroma of BPH are higher than bax P<0.01 =. Compared with the control group, the expressions of bcl-2 in epithelia and stroma of BPH treated with 90Sr/90Y Prostatic Hyperplasia Applicator decreased and the expressions of bax increased P<0.01=. Conclusion: bcl-2 gene and bax gene play an important role in the regulation of prostatic apoptosis and the treatment of β-rays can accelerate the apoptosis of prostatic tissues. (authors)

  15. Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes

    NARCIS (Netherlands)

    Vaandrager, J W; Schuuring, E; Raap, T; Philippo, K; Kleiverda, K; Kluin, P

    2000-01-01

    Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene

  16. Family resemblance: ten family members with prosopagnosia and within-class object agnosia.

    Science.gov (United States)

    Duchaine, Bradley; Germine, Laura; Nakayama, Ken

    2007-06-01

    We report on neuropsychological testing done with a family in which many members reported severe face recognition impairments. These 10 individuals were high functioning in everyday life and performed normally on tests of low-level vision and high-level cognition. In contrast, they showed clear deficits with tests requiring face memory and judgements of facial similarity. They did not show deficits with all aspects of higher level visual processing as all tested performed normally on a challenging facial emotion recognition task and on a global-local letter identification task. On object memory tasks requiring recognition of particular cars and guns, they showed significant deficits so their recognition impairments were not restricted to facial identity. These results strongly suggest the existence of a genetic condition leading to a selective deficit of visual recognition.

  17. Perceptions of Individual and Family Functioning Among Deployed Female National Guard Members.

    Science.gov (United States)

    Kelly, Patricia J; Cheng, An-Lin; Berkel, LaVerne A; Nilsson, Johanna

    2016-08-01

    Females currently make up 15% of U.S. military service members. Minimal attention has been paid to families of female National Guard members who have been deployed and their subsequent reintegration challenges. This cross-sectional Internet-based survey of female members of four National Guard units compared those who were and were not deployed. Instruments, guided by the variables of the Family Resilience Model, measured individual, family, and deployment-related factors. Bivariate analysis and ordinal logistic regression were done to assess differences between the groups. Of the 239 National Guard members surveyed, deployed women (n = 164) had significantly higher levels of posttraumatic stress disorder (PTSD; p < .001) and lower coping skills (p = .003) than non-deployed women (n = 75). Perceptions of overall family functioning were higher among deployed when compared with never deployed women. Results indicate community interventions that focus on strengthening coping skills of female Guard members would be useful for this population. PMID:27076466

  18. Apoptosis Mediated by HIV Protease is Preceded by Cleavage of Bcl-2

    Science.gov (United States)

    Strack, Peter R.; West Frey, Michelle; Rizzo, Christopher J.; Cordova, Beverly; George, Henry J.; Meade, Raymond; Ho, Siew Peng; Corman, Jeanne; Tritch, Radonna; Korant, Bruce D.

    1996-09-01

    Expression of the human immunodeficiency virus type 1 (HIV) protease in cultured cells leads to apoptosis, preceded by cleavage of bcl-2, a key negative regulator of cell death. In contrast, a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes, while reducing the yields of viral structural proteins, infectivity, and tumor necrosis factor α . We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2, leading to oxidative stress-dependent activation of NFkappa B, a cellular factor required for HIV transcription, and ultimately to cell death. Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site.

  19. MicroRNA-125b Induces Cancer Cell Apoptosis Through Suppression of Bcl-2 Expression

    Institute of Scientific and Technical Information of China (English)

    Aihua Zhao; Quan Zeng; Xiaoyan Xie; unnian Zhou; Wen Yue; Yali Li; Xuetao Pei

    2012-01-01

    MicroRNAs (miRNAs) are small,noncoding RNAs which can often act as an oncogene or a tumor suppressor.Several miRNAs are associated with the development of hepatocellular carcinoma (HCC).We demonstrated that miR-125b significantly suppresses HCC cell proliferation and promotes apoptosis by inhibiting the gene expression of the anti-apoptotic protein,Bcl-2.Bioinformatic analysis indicated that the 3'UTR of Bcl-2 has binding sites for miR-125b.Luciferase reporter assay confirmed the ability of miR-125b to dramatically suppress Bcl-2 transcription,suggesting that Bcl-2 is a target gene for miR-125b.We concluded that miR-125b acts as a tumor suppressor in hepatic tumor development by targeting Bcl-2 and inducing cancer cell apoptosis.

  20. Family Benefits In Member States Of The European Union: A Comparative Perspective

    Directory of Open Access Journals (Sweden)

    Stănescu Simona Maria

    2015-06-01

    Full Text Available The article intends to be a screening of family benefits in the 28 Member States of the European Union (EU and to contribute to the research of shared trends with respect to family approach in these countries. Four types of family benefits including eight distinctive categories are analysed: child-benefit, child care allowances, child-raising allowances, and other benefits (birth and adoption grants, allowance for single parents, special allowances for children with disabilities, advance payments for maintenance and other allowances. The paper is based on primary and secondary analysis of 28 sets of national data provided through the European Union's Mutual Information System on Social Protection (MISSOC. Three categories of member states are considered: founder member states of the EU, other “old” member states, and the new Central and Eastern ones. Chronological development of national regulations with impact on family benefits is analysed in connection with the moment of becoming a member state. Various forms of family benefits legislation and their main subjects of interest are further researched. The last part of the article looks at the coverage of family benefits. Seven member states operate in this respect based on regulations adopted before EU accession. Belgium, Finland, and Lithuania have the “most preserved” family regulations per category of member states. The first three topics of family regulations are: child, family, and allowance / benefit. The most frequently provided family benefits are: birth and adoption grants, and special allowance for children with disabilities. All eight family benefits are provided in France, Finland, Hungary, and Slovenia. Only two types of family benefits are available in Ireland, Spain, and Cyprus.

  1. The distinct role of guanine nucleotide exchange factor Vav1 in Bcl-2 transcription and apoptosis inhibition in Jurkat leukemia T cells

    Institute of Scientific and Technical Information of China (English)

    Jie YIN; Ya-juan WAN; Shi-yang LI; Ming-juan DU; Cui-zhu ZHANG; Xing-long ZHOU; You-jia CAO

    2011-01-01

    Aim: To investigate a novel function of proto-oncogene Vavl in the apoptosis of human leukemia Jurkat cells.Methods: Jurkat cells,Jurkat-derived vavl-null cells(J.Vavl)and Vavl-reconstituted J.WT cells were treated with a Fas agonist antibody,IgM clone CH11.Apoptosis was determined using propidium iodide(PI)staining,Annexin-V staining,DNA fragmentation,cleavage of caspase 3/caspase 8,and poly(ADP-ribose)polymerase(PARP).Mitochondria transmembrane potential(Δψm)was measured using DiOC6(3)staining.Transcription and expression of the Bcl-2 family of proteins were evaluated using semi-quantitative RT-PCR and Western blot,respectively.Bcl-2 promoter activity was analyzed using luciferase reporter assays.Results: Cells lacking Vav1 were more sensitive to Fas-mediated apoptosis than Jurkat and J.WT cells.J.Vav1 cells lost mitochondria transmembrane potential(Δψm)more rapidly upon Fas induction.These phenotypes could be rescued by re-expression of Vav1 in J.Vav1 cells.The expression of Vav1 increased the transcription of pro-survival Bcl-2.The guanine nucleotide exchange activity of Vav1was required for enhancing Bcl-2 promoter activity,and the Vav1 downstream substrate,small GTPase Rac2,was likely involved in the control of Bcl-2 expression.Conclusion: Vav1 protects Jurkat cells from Fas-mediated apoptosis by promoting Bcl-2 transcription through its GEF activity.

  2. Gli1 maintains cell survival by up-regulating IGFBP6 and Bcl-2 through promoter regions in parallel manner in pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Xu Xuan-Fu

    2009-01-01

    Full Text Available Background: Aberrant activation of Hedgehog (Hh signaling pathway has been reported to be related to malignant biological behavior of pancreatic cancer but its mechanism is unclear yet. Since IGF pathway and Bcl-2 family are involved in proliferation and apoptosis of pancreatic cancer cells, we hypothesize that they are possibly associated with Hh pathway. Materials and Methods: We studied the relationship of Shh-Gli1 signaling pathway with proliferation and apoptosis of pancreatic cancer cells and the regulation of transcription factor Gli1 to insulin-like growth factor binding protein 6 (IGFBP6 and Bcl-2 genes at the level of transcription. Results: Sonic hedgehog (Shh, Smoothened (Smo, patched and Gli1 were expressed in pancreatic cancer cells. Cyclopamine inhibited cell proliferation at low concentration and induced apoptosis at high concentration. Effect of RNA interference (RNAi for Gli1 to cell survival is mainly due to proliferation inhibition though involved in apoptosis. The transcription factor Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes and the levels of IGFBP6, proliferating cell nuclear antigen (PCNA and Bcl-2 messenger RNA (mRNA were decreased as well as Gli1 mRNA significantly by cyclopamine or RNAi in cultured pancreatic cancer cells (p < 0.01. Finally PCNA, IGFBP6 and Bcl-2 mRNA were upregulated as well as Shh or Gli1 in pancreatic cancer tissues (p < 0.01. Conclusions: Our study reveals that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes in a parallel manner in pancreatic cancer cells and suggests it may be one of the mechanisms of Shh-Gli1 signaling pathway in pancreatic cancer.

  3. A unified nomenclature of NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER family members in plants.

    Science.gov (United States)

    Léran, Sophie; Varala, Kranthi; Boyer, Jean-Christophe; Chiurazzi, Maurizio; Crawford, Nigel; Daniel-Vedele, Françoise; David, Laure; Dickstein, Rebecca; Fernandez, Emilio; Forde, Brian; Gassmann, Walter; Geiger, Dietmar; Gojon, Alain; Gong, Ji-Ming; Halkier, Barbara A; Harris, Jeanne M; Hedrich, Rainer; Limami, Anis M; Rentsch, Doris; Seo, Mitsunori; Tsay, Yi-Fang; Zhang, Mingyong; Coruzzi, Gloria; Lacombe, Benoît

    2014-01-01

    Members of the plant NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER (NRT1/PTR) family display protein sequence homology with the SLC15/PepT/PTR/POT family of peptide transporters in animals. In comparison to their animal and bacterial counterparts, these plant proteins transport a wide variety of substrates: nitrate, peptides, amino acids, dicarboxylates, glucosinolates, IAA, and ABA. The phylogenetic relationship of the members of the NRT1/PTR family in 31 fully sequenced plant genomes allowed the identification of unambiguous clades, defining eight subfamilies. The phylogenetic tree was used to determine a unified nomenclature of this family named NPF, for NRT1/PTR FAMILY. We propose that the members should be named accordingly: NPFX.Y, where X denotes the subfamily and Y the individual member within the species.

  4. 41 CFR 302-3.226 - Will the Government reimburse me if I am not eligible to return with my immediate family member(s...

    Science.gov (United States)

    2010-07-01

    ... reimburse me if I am not eligible to return with my immediate family member(s) to the U.S. and choose to... Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Prior Return of Immediate Family Members § 302-3.226 Will the...

  5. 41 CFR 302-3.203 - If I am transferring in the interest of the Government and my employed immediate family member(s...

    Science.gov (United States)

    2010-07-01

    ... the interest of the Government and my employed immediate family member(s) transfer is not in the... ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of Transfers Relocation of Two Or More Employed Immediate Family Members § 302-3.203 If I am transferring in the interest of the Government and my...

  6. Cyclic beta-glucans of members of the family Rhizobiaceae.

    OpenAIRE

    Breedveld, M. W.; Miller, K. J.

    1994-01-01

    Cyclic beta-glucans are low-molecular-weight cell surface carbohydrates that are found almost exclusively in bacteria of the Rhizobiaceae family. These glucans are major cellular constituents, and under certain culture conditions their levels may reach up to 20% of the total cellular dry weight. In Agrobacterium and Rhizobium species, these molecules contain between 17 and 40 glucose residues linked solely by beta-(1,2) glycosidic bonds. In Bradyrhizobium species, the cyclic beta-glucans are ...

  7. A critical review of Singapore's policies aimed at supporting families caring for older members.

    Science.gov (United States)

    Mehta, Kalyani K

    2006-01-01

    This article critically examines the family-oriented social policies of the Singapore government aimed at supporting families caring for older members. The sectors focused on are financial security, health, and housing. Singaporeans have been reminded that the family should be the first line of defense for aging families, followed by the community - the state would step in as the last resort. Drawing from recent research and examination of the state policies, the author argues that more should be done to help family caregivers looking after elder relatives. Recommendations for innovative ways to recognize and reward family carers conclude the paper.

  8. 听神经瘤BCL-2蛋白及bcl-2/JH融合基因的研究☆%Detection of BCL-2 protooncogene protein expression and the related bcl-2(mbr)/JH fusion gene from archival paraffin-embedded tissue from acoustic neuromas.

    Institute of Scientific and Technical Information of China (English)

    刘绍明; 李龄; 刘鹏翀

    2001-01-01

    目的评价石蜡包埋听神经瘤组织中BGL-2蛋白表达及相关的bcl-2(mbr)/JH融合基因改变,以探讨bcl-2癌基因在听神经瘤发病中的可能意义.方法免疫组化检测石蜡包埋组织中BCL-2蛋白的表达;提取石蜡包埋组织的DNA,PCR检测bcl-2(mbr)/JH融合基因.结果本组40例听神经瘤,BCL-2蛋白表达阳性27例(67.5%),bcl-2(mbr)/JH融合基因检出阳性19例(47.5%).结论听神经瘤中存在BCL-2蛋白的高表达及t(14;18)染色体易位,提示雪旺氏细胞凋亡抑制可能是听神经瘤发病的分子病理基础之一.

  9. Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders.

    Science.gov (United States)

    Vyas, S; Javoy-Agid, F; Herrero, M T; Strada, O; Boissiere, F; Hibner, U; Agid, Y

    1997-07-01

    The expression of the protooncogene bcl-2, an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated.

  10. Study on the Regulation of Bcl-2 Gene on Rat Spermatogenic Cells Apoptosis in Transcription Level

    Institute of Scientific and Technical Information of China (English)

    董强; 杨宇如; 黄明孔; 李虹; 张卫东; 徐震波

    2000-01-01

    Objective To detect the change of Bcl-2 gene expression in the apopototic process of spermatogenic cells in rat with vasoligation and vasostomy, and to find out the relationship between the transcription of Bcl-2 and the apoptosis of spermatognic cells.Materials & Methods Sixty adult male Sprague-Dawley rats in 3 groups were operated with vasoligation and vasostomy. Then hybridization in situ with hypersensitive Bcl-2 RNA probe was used to detect the change of Bcl-2 mRNA.Results The transcription of Bcl-2 gene in spermatogenic cells was obviously inhibited in the vasoligation group compared with that in the control group (P<0. 05), and the transcription in the vasostomy group showed no difference from that of the control group.Conclusion Bcl-2 gene has an anti-apoptotic effect in rats with vasostomy, and there was a transcriptional regulation of Bcl-2 gene in rat spermatogenic cell during the period of pre-vasoligation to post-vasoligation and to post-vasosotomy.

  11. Communicating prognostic uncertainty in potential end-of-life contexts: experiences of family members

    OpenAIRE

    Krawczyk, Marian; Gallagher, Romayne

    2016-01-01

    Background This article reports on the concept of “communicating prognostic uncertainty” which emerged from a mixed methods survey asking family members to rank their satisfaction in seven domains of hospital end-of-life care. Methods Open-ended questions were embedded within a previously validated survey asking family members about satisfaction with end-of-life care. The purpose was to understand, in the participants’ own words, the connection between their numerical rankings of satisfaction...

  12. Compassion Fatigue: An Application of the Concept to Informal Caregivers of Family Members with Dementia

    OpenAIRE

    Anderson, Ruth A.; Day, Jennifer R.

    2011-01-01

    Introduction. Compassion fatigue is a concept used with increasing frequency in the nursing literature. The objective of this paper is to identify common themes across the literature and to apply these themes, and an existing model of compassion fatigue, to informal caregivers for family members with dementia. Findings. Caregivers for family members with dementia may be at risk for developing compassion fatigue. The model of compassion fatigue provides an informative framework for understandi...

  13. Expression of Bcl-2 Gene in Primary Breast Cancer and its Correlation with Some Prognostic Factors

    Directory of Open Access Journals (Sweden)

    * A. Tavakoli, M.D

    Full Text Available Abstract Background and purpose: The breast cancer is the most common malignancy in women. Bcl-2 expression has been determined in more than half of the cases of breast cancer. The purpose of this study was to determine the expression of bcl-2 gene in primary breast cancer and its correlation with grade, stage and axillary lymph node involvement.Materials and Methods: The study was a cross-sectional one that was performed on 75 patients with breast cancer admitted to Mostafa Khomeini hospital (2000-2005. After preparing the samples, a tissue section from each sample was obtained. One of the tumoral sections and one of the lymph node sections were stained using H & E. We determined the type of the tumor, the number of lymph nodes, the stage and the grade of the tumor. We studied Bcl-2 with polyclonal antibody by IHC.Results: Our study showed that 69.3% of patients had hymph node involvment. In addition, 41.3% of samples were positive for Bcl-2, 58.7% of samples were in stage II and many patients (42.7% were in grade III. In this study, we didn’t find any relationship between bcl-2 and stage and lymph node involvment. We also found a significant association between bcl-2 and grade (P<0.006. Also, high bcl-2 expression was more frequent in high-grade tumor.Conclusion: According to the results obtained from earlier studies and our study, it seems that bcl2 is a prognostic factor in breast cancer. But further investigations with more specimens and long-time follow-up are required to clarify the exact role of Bcl-2 in the prognosis of breast cancer.

  14. Psychiatric worker and family members: pathways towards co-operation networks within psychiatric assistance services

    Directory of Open Access Journals (Sweden)

    Silvia Carbone

    2014-03-01

    Full Text Available The family’s role in patient care was greatly altered by Law 180. This law, introduced in Italy in 1978, led to a gradual phasing out of custodial treatment for psychiatric patients. This different mindset, which views the family as an alternative to institutionalization, leads to it being seen as an essential entity in the setting up of community service dynamics. We interviewed health professionals in order to understand obstacles of collaboration between family members and mental health care workers. The goal was to uncover actions that promote collaboration and help build alliances between families and psychiatric workers. Results showed that health professionals view the family as a therapeutic resource. Despite this view, family members were rarely included in patient treatment. The reasons is: the structures have a theoretical orientation of collaboration with the family but, for nurses not are organized a few meeting spaces with family members. Services should create moments, such as multi-family groups or groups of information, managed by nurses and not only by doctors. These occasions it might facilitate the knowledge between professionals and family members.

  15. The Many Faces of Military Families: Unique Features of the Lives of Female Service Members.

    Science.gov (United States)

    Southwell, Kenona H; MacDermid Wadsworth, Shelley M

    2016-01-01

    Female service members' family structures differ from the traditional male service member-female spouse composition of military families. Consequently, this mixed-methods study reviewed demographic data, empirical evidence, and presented findings from secondary analyses of the 2010 wave of the Military Family Life Project regarding structural differences in male and female service members' families and perceptions and experiences of military spouses. In addition, to gain an understanding of the influence of women's service on their family functioning, we conducted in-depth telephone interviews with 20 civilian husbands residing in 11 states around the United States. Empirical evidence suggests service women had higher rates or remarriage and divorce than service men. Women were also more likely than men to be part of nontraditional family forms. Civilian husbands of female service members, however, reported lower marital satisfaction, less support from the community, and less satisfaction with the military lifestyle than military wives. Husbands' accounts indicated that their families experienced both benefits and challenges from wives' service. Integration in the military community and separation presented major challenges for women's families. Implications of benefits and challenges of women's service for their families are discussed. PMID:26741904

  16. Everyday Living with Diabetes Described by Family Members of Adult People with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Tuula-Maria Rintala

    2013-01-01

    Full Text Available The aim of this study was to explore family members’ experiences of everyday life in families with adult people living with type 1 diabetes. The grounded theory method was used to gather and analyse data from the interviews of nineteen family members. Six concepts describing the family members’ views on everyday living with diabetes were generated on the basis of the data. Everyday life with diabetes is described as being intertwined with hypoglycemia. Becoming acquainted with diabetes takes place little by little. Being involved in the management and watching self-management from the sidelines are concepts describing family members’ participation in the daily management of diabetes. The family members are also integrating diabetes into everyday life. Living on an emotional roller-coaster tells about the thoughts and feelings that family members experience. Family members of adult people with diabetes are involved in the management of the diabetes in many ways and experience many concerns. The family members’ point of view is important to take into consideration when developing education for adults with diabetes.

  17. Supporting conversations between individuals with dementia and their family members.

    Science.gov (United States)

    Karlsson, Eva; Axelsson, Karin; Zingmark, Karin; Fahlander, Kjell; Sävenstedt, Stefan

    2014-02-01

    Remembrance of recent events is a major problem for individuals with dementia. Consequently, this article explores the process of acceptance and integration of a digital photograph diary (DPD) as a tool for remembrance of and conversations about daily life events. A design for multiple case studies was used. Seven couples, in which one individual in the couple had Alzheimer's disease, tested the DPD for 6 months. Data were collected in three sequences with interviews, observations, and screening instruments. In the analysis, all data were integrated to find common patterns of content. Some couples became regular users, while others used the DPD more sporadically. Factors contributing to regular use were how the DPD matched expectations, actual use, support, experienced usefulness, and reactions from family and friends. For those couples who became regular users, the DPD facilitated their conversation about recent daily activities. PMID:24066788

  18. Expression of OX40 and Bcl-2 in allergic rhinitis%OX40及Bcl-2在变应性鼻炎中的表达

    Institute of Scientific and Technical Information of China (English)

    赵建东; 李伟; 王彦君; 陈雪梅

    2008-01-01

    目的:探讨OX40及Bcl-2在变应性鼻炎(AR)发病机制中的可能作用.方法:取23例AR患者(AR组)和20例单纯鼻中隔偏曲患者(对照组)为研究对象,应用免疫组织化学技术分别检测OX40及Bel-2的表达,并分析OX40与Bcl-2表达的相关性.结果:在AR患者鼻黏膜中,OX40及Bcl-2的表达都显著上调,除CD4+T细胞外,均在鼻黏膜上皮细胞、腺体细胞、血管内皮细胞呈显著性表达(均P<0.01).平均吸收度值(A值)OX40为0.239 4±0.033 5,Bcl-2为0.237 3±0.042 1,与对照组相比,均P<0.01.AR患者鼻黏膜中OX40与Bcl-2的表达呈正相关(r=0.869 0,P<0.05).结论:AR患者存在OX40共刺激分子的异常表达,Bcl-2在鼻黏膜组织中表达异常增高.

  19. Bcl-2、Caspase-3、Survivin与银屑病的研究进展%Research Progress of Bcl-2,Caspase-3,Survivin and Psoriasis

    Institute of Scientific and Technical Information of China (English)

    秦兰英; 邢卫斌; 叶文静

    2013-01-01

    Bcl-2, caspase-3, survivin genes are important genes in the process of apoptosis, playing important roles in psoriasis keratinocyte apoptosis. Bcl-2 is a kind of apoptosis suppressor gene, which can prolong life period of cells. Caspase-3 can promote cell apoptosis. Survivin is one of the strongest anti-apopto-sis factor discovered so far,which can inhibit cell apoptosis and promote cell proliferation. Psoriasis lesions contain less Bcl-2, more caspase-3 and survivin. Interaction between them may result in the shortened life period and fastened apoptosis in psoriasis keratinocy,and cells proliferation is obvious,which maintains the benign proliferative state of psoriasis epidermis.%Bcl-2、caspase-3、survivin是细胞凋亡过程中重要的调控基因,在银屑病角质形成细胞凋亡中,三种蛋白起着非常重要的作用.Bcl-2是一种凋亡抑制基因,可延长细胞的生存期,caspase-3可促进细胞凋亡,survivin是迄今发现最强的凋亡抑制因子,具有抑制细胞凋亡、促进细胞增殖的作用,在银屑病皮损中Bcl-2呈低表达,caspase-3、survivin呈高表达,三种蛋白的相互作用,可能导致银屑病角质形成细胞的生存期缩短、凋亡速度加快,同时细胞增殖明显,从而维持银屑病表皮的良性增生状态.

  20. Routine HIV Testing of Family Members of Hospitalized Patients in Nigeria

    Directory of Open Access Journals (Sweden)

    Olusegun Busari

    2012-04-01

    Full Text Available Background: HIV testing for family members of HIV-positive patients may enhance disclosure of status of spouses, encourage family social support and improve access to HIV services. Objective was to employ the approach of routine HIV testing to determine the prevalence of HIV among family members of both HIV positive and negative patients on admission in a federal HIV treatment designated hospital in Western Nigeria Methodology: This prospective study was conducted between January 2006 and June 2009. Ethical clearance was obtained from the Research and Ethics committee of the hospital prior to the study. Informed consent was obtained from each participant. HIV testing was offered to consenting family members of HIV positive and negative patients on admission. The family members included spouses, children of patients, parents of paediatric patients and other family members. Analysis was done in frequencies and percentages Results: 162 family members of 184 patients were tested. Spouses were, 81 (50.0%; fathers, 14 (8.6%; mothers, 20 (12.3%; children, 19 (11.7% and others family members, 28 (17.3%. 151 (93.2% of testers were first timers. Majority of those tested (82.1% had post-test counseling. The overall HIV prevalence was 12.3% (20/162. HIV prevalence within different family members was 14.8% (12/81, 20% (4/20, 7.1% (1/14, 10.5% (2/19 and 3.6% (1/28 for spouses, mothers, fathers, children and others respectively.In addition, the prevalence of HIV among family members of HIV positive and negative patients was 15.6% (14/90 and 8.3% (6/72 respectively. Of 12 spouses that were positive, 7 (13.5% were HIV-discordant; and in 71.4% (5/7 of discordant couples, the spouse was positive while the patient on admission was negative. Conclusion: The results indicate that routine HIV testing of family members of patients on admission is a strategy for identification of vast number of HIV infected persons. This method is not only innovative, but also a novel

  1. CHIS - Information concerning the health insurance of frontalier workers who are family members of a CHIS main member

    CERN Multimedia

    2014-01-01

    We recently informed you that the Organization was still in discussions with the Host State authorities to clarify the situation regarding the health insurance of frontalier workers who are family members (as defined in the Staff Rules and Regulations) of a CHIS main member, and that we were hoping to arrive at a solution soon.   After extensive exchanges, we finally obtained a response a few days ago from the Swiss authorities, with which we are fully satisfied and which we can summarise as follows: 1) Frontalier workers who are currently using the CHIS as their basic health insurance can continue to do so. 2) Family members who become frontalier workers, or those who have not yet exercised their “right to choose” (droit d’option) can opt to use the CHIS as their basic health insurance. To this end, they must complete the form regarding the health insurance of frontaliers, ticking the LAMal box and submitting their certificate of CHIS membership (available from U...

  2. SMI of Bcl-2 TW-37 is active across a spectrum of B-cell tumors irrespective of their proliferative and differentiation status.

    Science.gov (United States)

    Al-Katib, Ayad M; Sun, Yuan; Goustin, Anton Scott; Azmi, Asfar Sohail; Chen, Ben; Aboukameel, Amro; Mohammad, Ramzi M

    2009-02-16

    The Bcl-2 family of proteins is critical to the life and death of malignant B-lymphocytes. Interfering with their activity using small-molecule inhibitors (SMI) is being explored as a new therapeutic strategy for treating B-cell tumors. We evaluated the efficacy of TW-37, a non-peptidic SMI of Bcl-2 against a range spectrum of human B-cell lines, fresh patient samples and animal xenograft models. Multiple cytochemical and molecular approaches such as acridine orange/ethidium bromide assay for apoptosis, co-immunoprecipitation of complexes and western blot analysis, caspase luminescent activity assay and apoptotic DNA fragmentation assay were used to demonstrate the effect of TW-37 on different B-cell lines, patient derived samples, as well as in animal xenograft models. Nanomolar concentrations of TW-37 were able to induce apoptosis in both fresh samples and established cell lines with IC50 in most cases of 165-320 nM. Apoptosis was independent of proliferative status or pathological classification of B-cell tumor. TW-37 was able to block Bim-Bcl-XL and Bim-Mcl-1 heterodimerization and induced apoptosis via activation of caspases -9, -3, PARP and DNA fragmentation. TW-37 administered to tumor-bearing SCID mice led to significant tumor growth inhibition (T/C), tumor growth delay (T-C) and Log10kill, when used at its maximum tolerated dose (40 mg/kg x 3 days) via tail vein. TW-37 failed to induce changes in the Bcl-2 proteins levels suggesting that assessment of baseline Bcl-2 family proteins can be used to predict response to the drug. These findings indicate activity of TW-37 across the spectrum of human B-cell tumors and support the concept of targeting the Bcl-2 system as a therapeutic strategy regardless of the stage of B-cell differentiation.

  3. Combined Targeting of JAK2 and Bcl-2/Bcl-xL to Cure Mutant JAK2-Driven Malignancies and Overcome Acquired Resistance to JAK2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Michaela Waibel

    2013-11-01

    Full Text Available To design rational therapies for JAK2-driven hematological malignancies, we functionally dissected the key survival pathways downstream of hyperactive JAK2. In tumors driven by mutant JAK2, Stat1, Stat3, Stat5, and the Pi3k and Mek/Erk pathways were constitutively active, and gene expression profiling of TEL-JAK2 T-ALL cells revealed the upregulation of prosurvival Bcl-2 family genes. Combining the Bcl-2/Bcl-xL inhibitor ABT-737 with JAK2 inhibitors mediated prolonged disease regressions and cures in mice bearing primary human and mouse JAK2 mutant tumors. Moreover, combined targeting of JAK2 and Bcl-2/Bcl-xL was able to circumvent and overcome acquired resistance to single-agent JAK2 inhibitor treatment. Thus, inhibiting the oncogenic JAK2 signaling network at two nodal points, at the initiating stage (JAK2 and the effector stage (Bcl-2/Bcl-xL, is highly effective and provides a clearly superior therapeutic benefit than targeting just one node. Therefore, we have defined a potentially curative treatment for hematological malignancies expressing constitutively active JAK2.

  4. Counseling Family Members of Addicts/Alcoholics: The Stages of Change Model

    Science.gov (United States)

    van Wormer, Katherine

    2008-01-01

    This article adapts the stages of change model, a model in which specific interventions of harm reduction are directed toward the client's readiness for treatment, as a guiding framework for counseling family members of alcoholics/addicts. Interventions at each stage of the family's readiness for change, from precontemplation to action, are…

  5. 76 FR 67384 - Extending Religious and Family Member FICA and FUTA Exceptions To Disregard Entities

    Science.gov (United States)

    2011-11-01

    ... Internal Revenue Service 26 CFR Parts 31 and 301 RIN 1545-BJ06 Extending Religious and Family Member FICA... Advocacy of the Small Business Administration for comment on its impact on small business. Comments and... and addition read as follows: Sec. 31.3121(b)(3)-1 Family Employment. * * * * * (c) [The text of...

  6. Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis

    International Nuclear Information System (INIS)

    The Bag (Bcl-2 associated athanogene) family of proteins consists of 6 members sharing a common, single-copied Bag domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in the Bag family since it consists of 5 Bag domains covering the whole protein. Bag proteins like Bag1 and Bag3 have been implicated in tumor growth and survival but it is not known whether Bag5 also exhibits this function. Bag5 mRNA and protein expression levels were investigated in prostate cancer patient samples using real-time PCR and immunoblot analyses. In addition immunohistological studies were carried out to determine the expression of Bag5 in tissue arrays. Analysis of Bag5 gene expression was carried out using one-way ANOVA and Bonferroni’s Multiple Comparison test. The mean values of the Bag5 stained cells in the tissue array was analyzed by Mann-Whitney test. Functional studies of the role of Bag5 in prostate cancer cell lines was performed using overexpression and RNA interference analyses. Our results show that Bag5 is overexpressed in malignant prostate tissue compared to benign samples. In addition we could show that Bag5 levels are increased following endoplasmic reticulum (ER)-stress induction, and Bag5 relocates from the cytoplasm to the ER during this process. We also demonstrate that Bag5 interacts with the ER-resident chaperone GRP78/BiP and enhances its ATPase activity. Bag5 overexpression in 22Rv.1 prostate cancer cells inhibited ER-stress induced apoptosis in the unfolded protein response by suppressing PERK-eIF2-ATF4 activity while enhancing the IRE1-Xbp1 axis of this pathway. Cells expressing high levels of Bag5 showed reduced sensitivity to apoptosis induced by different agents while Bag5 downregulation resulted in increased stress-induced cell death. We have therefore shown that Bag5 is overexpressed in prostate cancer and plays a role in ER-stress induced apoptosis. Furthermore we have identified GRP78/BiP as a novel

  7. How family members manage risk around functional decline: the autonomy management process in households facing dementia.

    Science.gov (United States)

    Berry, Brandon; Apesoa-Varano, Ester Carolina; Gomez, Yarin

    2015-04-01

    Most dementia research investigates the social context of declining ability through studies of decision-making around medical treatment and end-of-life care. This study seeks to fill an important gap in research about how family members manage the risks of functional decline at home. Drawing on three waves of in-depth interviewing in 2012-2014, it investigates how family members in US households manage decline in an affected individual's natural range of daily activities over time. The findings show that early on in the study period affected individuals were perceived to have awareness of their decline and routinely drew on family members for support. Support transformed when family members detected that the individual's deficit awareness had diminished, creating a corresponding increase in risk of self-harm around everyday activities. With a loss of confidence in the individual's ability to regulate his or her own activities to avoid these risks, family members employed unilateral practices to manage the individual's autonomy around his or her activity involvements. These practices typically involved various deceits and ruses to discourage elders from engaging in activities perceived as potentially dangerous. The study concludes by discussing the implications that the social context of interpretive work around awareness and risk plays an important role in how families perceive an elder's functional ability and manage his or her activity involvements.

  8. Rotational Properties of the Haumea Family Members and Candidates: Short-term Variability.

    Science.gov (United States)

    Thirouin, Audrey; Sheppard, Scott S.; Noll, Keith S.; Moskovitz, Nicholas A.; Ortiz, Jose Luis; Doressoundiram, Alain

    2016-06-01

    Haumea is one of the most interesting and intriguing trans-Neptunian objects (TNOs). It is a large, bright, fast rotator, and its spectrum indicates nearly pure water ice on the surface. It has at least two satellites and a dynamically related family of more than 10 TNOs with very similar proper orbital parameters and similar surface properties. The Haumean family is the only one currently known in the trans-Neptunian belt. Various models have been proposed, but the formation of the family remains poorly understood. In this work, we have investigated the rotational properties of the family members and unconfirmed family candidates with short-term variability studies, and report the most complete review to date. We present results based on five years of observations and report the short-term variability of five family members and seven candidates. The mean rotational periods, from Maxwellian fits to the frequency distributions, are 6.27 ± 1.19 hr for the confirmed family members, 6.44 ± 1.16 hr for the candidates, and 7.65 ± 0.54 hr for other TNOs (without relation to the family). According to our study, there is a possibility that Haumea family members rotate faster than other TNOs; however, the sample of family members is still too limited for a secure conclusion. We also highlight the fast rotation of 2002 GH32. This object has a 0.36 ± 0.02 mag amplitude lightcurve and a rotational period of about 3.98 hr. Assuming 2002 GH32 is a triaxial object in hydrostatic equilibrium, we derive a lower limit to the density of 2.56 g cm‑3. This density is similar to Haumea’s and much more dense than other small TNO densities.

  9. A PRELIMINARY STUDY ON SURVIVIN AND BCL-2 EXPRESSION IN CERVICAL CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To study the expression of a novel inhibitor of apptosis and survivin in cervical carcinoma and its relationship to the expression of Bcl-2.Methods Using SP immunohistochemical technique, we examined the expression of survivin and Bcl-2 in 59 cervical invasive squamous cell carcinomas.Results Survivin was expressed in 41 of 59 cases(69.5%) of cervical carcinomas. In contrast, no expression of survivin in normal cervical tissues was observed. Overexpression of survivin was related to the tumor grade and clinical stage. Survivin positive cases were strongly associated with Bcl-2 expression(80% versus 35.7%;P<0.005).Conclusion Apoptosis inhibition by survivin abnormal expression, alone or in cooperation with Bcl-2, may participate in the onset and progression of cervical carcinoma. Survivin is a new diagnostic/therapeutic target in cervical cancer.

  10. Progress in BCL2 inhibition for patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Tam, Constantine S; Seymour, John F; Roberts, Andrew W

    2016-04-01

    The prosurvival protein BCL2 is uniformly expressed in chronic lymphocytic leukemia (CLL), and enables leukemia cell survival in the face of cytotoxic treatment and increasing genomic, metabolic, and oxidative stresses. The therapeutic potential of BCL2 inhibition was first observed in the clinic following BCL2 antisense therapy. Subsequently, a number of small molecule inhibitors were developed to mimic the function of the pro-apoptotic BH3-only proteins (BH3-mimetics). These molecules are now in late-phase clinical trials and demonstrate potent activity, including the occurrence of acute tumor lysis syndrome in subjects with multiply relapsed, chemorefractory CLL. In this review, we discuss the history and summarize current knowledge regarding BCL2 inhibition as therapy of CLL. PMID:27040706

  11. Expression of Survivin in pancreatic cancer and its correlation to expression of Bcl-2

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo Qiao; Yu-Qing Zhang; Yu-Chun Yin; Zui Tan

    2004-01-01

    AIM: To investigate the expression of Survivin in pancreatic cancer and its correlation to the expression of Bcl-2.METHODS: Survivin and Bcl-2 expressions were examined by immunohistochemistry in 42 tissue samples from pancreatic cancer and 10 from normal pancrease. RESULTS: No survivin expression was detected in the tissue samples from normal pancrease, while it was detected in 34 of 42 tissue samples from pancreatic cancer (81.95%).There was a correlation between survivin expression and differentiation and stages of pancreatic cancer. Survivin positive cases were strongly correlated to Bcl-2 expression (28/30 vs 6/12, P<0.05).CONCLUSION: Overexpression of survivin plays an important role in the development and progression of pancreatic cancer, and correlates to the expression of Bcl-2. Survivin expression can be used as a prognostic factor.

  12. Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors

    DEFF Research Database (Denmark)

    Wang, Mingjun; Johansen, Britta; Nissen, Mogens H;

    2006-01-01

    A large number of human tumor-associated antigen-derived peptides have been identified that are recognized by CTLs in a MHC-I restricted fashion. The apoptosis inhibitory protein Bcl2 is overexpressed in many human cancers as part of their neoplastic phenotype. Since inhibition or loss of Bcl2...... expression might impair tumor growth and survival, this protein may serve as a rational target for vaccine-induced CTL responses. By Western blot technique, we screened a panel of established human tumor cell lines for proteins involved in the apoptotic process. Two of eight tumor cell lines, a B lymphoma...... (Loukes) and a colon carcinoma (CCL220) cell line showed increased Bcl2 protein expression whereas the majority of tumor cell lines expressed proapoptotic proteins. Neither fibroblasts nor peripheral blood mononuclear cells showed Bcl2 expression. An HLA-A*0201 restricted CTL epitope was deduced in silica...

  13. Niclosamide, an anti-helminthic molecule, downregulates the retroviral oncoprotein Tax and pro-survival Bcl-2 proteins in HTLV-1-transformed T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Di [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Yuan, Yunsheng [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai (China); Chen, Li [Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou (China); Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Liu, Xin; Belani, Chandra [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Cheng, Hua, E-mail: hcheng@ihv.umaryland.edu [Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2015-08-14

    Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancy and is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein, Tax, which plays a key role in transactivating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival, proliferation and transformation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis. We here show that niclosamide, an anti-helminthic molecule, induced apoptosis of HTLV-1-transformed T cells. Niclosamide facilitated degradation of the Tax protein in proteasome. Consistent with niclosamide-mediated Tax degradation, this compound inhibited activities of MAPK/ERK1/2 and IκB kinases. In addition, niclosamide downregulated Stat3 and pro-survival Bcl-2 family members such as Mcl-1 and repressed the viral gene transcription of HTLV-1 through induction of Tax degradation. Since Tax, Stat3 and Mcl-1 are crucial molecules for promoting survival and growth of HTLV-1-transformed T cells, our findings demonstrate a novel mechanism of niclosamide in inducing Tax degradation and downregulating various cellular pro-survival molecules, thereby promoting apoptosis of HTLV-1-associated leukemia cells. - Highlights: • Niclosamide is a promising therapeutic candidate for adult T cell leukemia. • Niclosamide employs a novel mechanism through proteasomal degradation of Tax. • Niclosamide downregulates certain cellular pro-survival molecules.

  14. Effect of Bcl-2 rs956572 polymorphism on age-related gray matter volume changes.

    Directory of Open Access Journals (Sweden)

    Mu-En Liu

    Full Text Available The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female with a mean age of 56.2±22.0 years (range: 21-92. Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001. Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum.

  15. Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of oligodendroglioma.

    Science.gov (United States)

    Doucette, Tiffany; Yang, Yuhui; Zhang, Wei; Fuller, Gregory N; Suki, Dima; Fults, Daniel W; Rao, Ganesh

    2011-11-01

    A significant subset of gliomas arises after activation of the proproliferative platelet-derived growth factor (PDGF) pathway. The progression of low-grade gliomas to more malignant tumors may be due to oncogenic cellular programs combining with those suppressing apoptosis. Antiapoptotic genes are overexpressed in a variety of cancers, and the antiapoptotic gene, BCL2, is associated with treatment resistance and tumor recurrence in gliomas. However, the impact of antiapoptotic gene expression to tumor formation and progression is unclear. We overexpressed Bcl-2 in a PDGFB-dependent mouse model of oligodendroglioma, a common glioma subtype, to assess its effect in vivo. We hypothesized that the antiapoptotic effect would complement the proproliferative effect of PDGFB to promote tumor formation and progression to anaplastic oligodendroglioma (AO). Here, we show that coexpression of PDGFB and Bcl-2 results in a higher overall tumor formation rate compared to PDGFB alone. Coexpression of PDGFB and Bcl-2 promotes progression to AO with prominent foci of necrosis, a feature of high-grade gliomas. Median tumor latency was shorter in mice injected with PDGFB and Bcl-2 compared to those injected with PDGFB alone. Although independent expression of Bcl-2 was insufficient to induce tumors, suppression of apoptosis (detected by cleaved caspase-3 expression) was more pronounced in AOs induced by PDGFB and Bcl-2 compared to those induced by PDGFB alone. Tumor cell proliferation (detected by phosphohistone H3 activity) was also more robust in high-grade tumors induced by PDGFB and Bcl-2. Our results indicate that suppressed apoptosis enhances oligodendroglioma formation and engenders a more malignant phenotype.

  16. Effect of β Radiation on Bcl-2 and Bax Expressions in Benign Prostate Hyperplasia Tissues

    Institute of Scientific and Technical Information of China (English)

    MA Qing-jie; GAO Shi; ZHAO Jie; GU Xin-quan; CAI Shan-yu; ZHAO Guo-qing

    2008-01-01

    The authors chose specimens from nine normal prostate tissues(NP group),15 benign prostate hyperplasia(BPH) prostates(BPH group),and 35 BPH prostates that had been treated with 90Sr/90Y Prostatic Hyperplasia Applicator(exposure group),The expressions of bcl-2 and bax in stroma and epithelia of prostate tissues were demonstrated by means of immunohistochemical staining,and the staining positive rate was semiquantatively determined,so as to observe the expression of bcl-2 and bax genes in the prostate tissues of normal individuals and BPH patients,before and after β radiation,and to evaluate the influence of β radiation on bcl-2 and bax expressions,The expressions of gene bcl-2 in the prostate epithelia of NP and BPH are significantly higher than those in the prostate stroma(P<0.01),However,the expressions of bcl-2 in the prostate epithelia and stroma of the BPH group are obviously higher than those in the NP group(P<0.01),The expression of gene bax in the prostate epithelia of the NP group is higher than that in the BPH group(P<0.05),However,bcl-2 expressions in the prostate epithelia and stroma of the BPH group are significantly higher than the bax expressions(P<0.01),Compared with those of the NP group,the expressions of bcl-2 in the prostate epithelia and stroma of the exposure group decrease remarkably,even as the expressions of the bax notably increase(P<0.01),Thus,the administration of β radiation can remarkably affect bcl-2 and bax gene expressions,to regulate cell apoptosis,in the prostate tissues of BPH.

  17. Increase of bcl-2 Protein Expression in Aggressive Basal Cell Carcinoma of Head and Neck

    OpenAIRE

    Cláudia CAZAL; ELY Mariana Roesch; Ana Paula Veras SOBRAL; Wilton Wilney Nascimento PADILHA

    2006-01-01

    Objective: The aim of this study was to verify the bcl-2 protein expression in 22 cutaneous basal cell carcinomas (BCC) of the head and neck, and to compare it with its aggressive behavior. Method: Tumors were histologically classified in non-aggressive (BCC 1) and aggressive (BCC 2) and then submitted to the immunohistochemistry technique with the streptavidin-biotin peroxidase method using the anti-bcl-2 antibody. Results: After proceeding to morphological analysis, sixteen tumors (72.7%) w...

  18. Ki67-BCL2 index in prognosis of malignant peritoneal mesothelioma

    OpenAIRE

    Pillai, Krishna; Mohammad H Pourgholami; Chua, Terence C.; Morris, David L.

    2013-01-01

    Background: malignant peritoneal mesothelioma (MPM) is a rare peritoneal mesothelial neoplasm. Ki67 and BCL2 are established prognostic markers in several cancers. High Ki67 expression indicates tumour progression, whilst similar expression of BCL2 retards tumour replication. Traditionally, prognosis in MPM is gauged with a single biomarker assessed separately in a dichotomous manner. Here, we examine prognosis with dual biomarkers incorporated in a model to predict survival. Materials and me...

  19. Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its Biological Significance

    OpenAIRE

    Wei, Wei; Wang, Yanqin; YU, XIAOMING; Ye, Lan; Jiang, Yuhua; Cheng, Yufeng

    2015-01-01

    Background The pathogenesis of esophagus carcinoma involves a cascade process consisting of multiple factors and accumulation of gene mutations. It is known that vascular endothelial growth factor (VEGF) mainly regulates de novo vascular formation while B-cell lymphoma-2 (BCL-2) gene exerts a tumor-suppressing effect. The prominent expression of VEGFA and BCL-2 genes, along with the most famous tumor-suppressor gene, TP53, raise the possibly of gene interaction. This study therefore investiga...

  20. bcl-2 expression is not associated with survival in metastatic cutaneous melanoma: A historical cohort study

    Directory of Open Access Journals (Sweden)

    Corleta Oly C

    2008-06-01

    Full Text Available Abstract Background Programmed cell death (apoptosis has been implicated in tumor development and may affect the metastatic potential of tumor cells. The role of bcl-2, a proto-oncogene that inhibits apoptosis, has been studied in several malignancies, including cutaneous melanoma (CM. The purpose of this study was to evaluate the immunohistochemical expression of bcl-2 in 35 regional lymph node, 28 subcutaneous and 17 visceral CM metastases, correlating the findings with patient survival. Methods In a historical cohort study patient survival was correlated with the expression of bcl-2 in regional lymph node, subcutaneous and visceral metastases of CM. Eighty slides containing surgical specimens from 50 patients diagnosed with stage III and IV CM, 28 male (56% and 22 female (44%, were analyzed. Mean age at diagnosis was 43 years (16–74 years; median = 42 years. Mean Breslow depth was 5.01 mm (0.4–27.5 mm. The slides were submitted to immunohistochemical reaction using anti-bcl-2 monoclonal antibody and classified according to the degree of staining ( 50% of tumor cells stained. The relationship between bcl-2 protein expression and survival for each type of metastasis, gender and age at initial diagnosis was analyzed. Results Mean overall survival was 33.9 months after the diagnosis of the initial metastatic lesion (range: 0 to 131 months. Twenty-four out of 50 patients (48% had died from CM by the end of the study period. bcl-2 expression was detected in 74.3, 85.7 and 82.4% of lymph node, subcutaneous and visceral metastases, respectively. After univariate and multivariate analyses, no correlation was found between positive bcl-2 expression and overall survival for the types of metastases evaluated. Conclusion The immunohistochemical expression of bcl-2 in metastasis alone is not a prognostic marker for CM.

  1. EGFR and Bcl-2 in gastric mucosa of children infected with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Ewa Ryszczuk

    2016-03-01

    Full Text Available Aim: The aim of the study was to evaluate the expression of EGFR and Bcl-2 proteins as inhibitory markers of apoptosis in surface epithelial cells and gland cells of antral gastric mucosa in children infected with Helicobacter pylori according to the severity and activity of antral gastritis and to assess the correlation between the number of cells expressing EGFR and the number of cells expressing Bcl-2 in H. pylori infected children. Materials and methods: The study included 44 children: 68.2% with chronic gastritis and positive IgG against H. pylori, and 31.8% with functional disorders of the gastrointestinal tract and with normal IgG against H. pylori. The evaluation of EGFR expression in gastric mucosa was performed immunohistochemically using monoclonal mouse anti-EGFR antibody. The polyclonal antibody was used to determine the expression of anti-Bcl-2. Results: A significant increase in the number of cells expressing EGFR and Bcl-2 protein was found in the epithelial cells in severe as well as mild and moderate gastritis in the group of children infected with H. pylori. An increase in the number of cells expressing EGFR and Bcl-2 protein was also found in the epithelial cells in group I according to the activity of gastritis. There was a statistically significant positive correlation between the numbers of cells expressing EGFR and Bcl-2 in H. pylori infected children. Conclusion: Increased expression of EGFR and Bcl-2 proteins in the epithelial cells and a statistically significant positive correlation between the numbers of cells expressing EGFR and Bcl-2 in H. pylori infected children could suggest increased regeneration abilities of gastric mucosa.

  2. The organ donor family members' perception of stressful situations during the organ donation experience.

    Science.gov (United States)

    Pelletier, M

    1992-01-01

    The purpose of this study was to determine what the individual organ/tissue donor family members appraised as most stressful during the anticipation, confrontation and post-confrontation stages of the organ-donation process. The Lazarus and Folkman stress and coping theory guided the development and interpretation of the study. Family members who had lost a loved one suddenly and consented to donation in 1988 were interviewed. Data were analysed by means of content analysis. Findings showed that family members appraised different types of stressful situations during the three stages. The most frequently reported stressful situations centred around the threat of losing a loved one, confirmation of brain death, failure of the health professionals to identify the loved one as a potential donor and to approach the family regarding organ donation, and adjusting to the many changes associated with the loss. Significantly, five families requested donation, while two readily consented when approached. All family members reported that organ donation had helped with their grief. The findings of this study contribute to the development of knowledge required to guide nursing interventions to provide sensitive care to donors and their families.

  3. c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2

    Institute of Scientific and Technical Information of China (English)

    Xiaoming Wang; Yafeng Zhang; Gang Xiao; Xiang Gao; Xiaolong Liu

    2009-01-01

    T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for posi-tive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene (lEG) c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-l-binding site in the Bcl-2 promoter. In c-Fos transgenic (Fos-Tg) mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive (SP) thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified e-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.

  4. A Urinary Bcl-2 Surface Acoustic Wave Biosensor for Early Ovarian Cancer Detection

    Directory of Open Access Journals (Sweden)

    Nathan D. Gallant

    2012-05-01

    Full Text Available In this study, the design, fabrication, surface functionalization and experimental characterization of an ultrasonic MEMS biosensor for urinary anti-apoptotic protein B-cell lymphoma 2 (Bcl-2 detection with sub ng/mL sensitivity is presented. It was previously shown that urinary Bcl-2 levels are reliably elevated during early and late stages of ovarian cancer. Our biosensor uses shear horizontal (SH surface acoustic waves (SAWs on surface functionalized ST-cut Quartz to quantify the mass loading change by protein adhesion to the delay path. SH-SAWs were generated and received by a pair of micro-fabricated interdigital transducers (IDTs separated by a judiciously designed delay path. The delay path was surface-functionalized with monoclonal antibodies, ODMS, Protein A/G and Pluronic F127 for optimal Bcl-2 capture with minimal non-specific adsorption. Bcl-2 concentrations were quantified by the resulting resonance frequency shift detected by a custom designed resonator circuit. The target sensitivity for diagnosis and identifying the stage of ovarian cancer was successfully achieved with demonstrated Bcl-2 detection capability of 500 pg/mL. It was also shown that resonance frequency shift increases linearly with increasing Bcl-2 concentration.

  5. THE EXPRESSION AND CLINICAL VALUE OF APOPTOSIS CONTROL GENE Bcl-2 AND Bax IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jun; YAO Zhen-xiang; ZHANG Jing

    1999-01-01

    Objective: To study the expression and clinical value of apoptosis control gene bcl-2 and bax in breast cancer.Methods: Protein bax and bcl-2 in 41 breast cancers obtained from operations in our hospital in 1996 were detected using ABC immunohistochemical stain assay and compared with 10 cases with normal breast tissues.Results: The positive rate of bax in normal breast tissue was 90% and in breast cancer was 59%, with a significant statistical difference between them (P<0.05), but there was no statistical difference in bcl-2 protein expression. Among the 41 breast cancer, the group with lymph node metastasis (21 cases) had obviously low bax expression (43%) and high bcl-2 expression (76%), showing significant difference to the group without lymph node metastasis (P<0.05).Conclusion: The antiapoptosis function of bcl-2 was stronger than bax in breast cancer. Protein bax and bcl-2 assay may be useful in understanding the biological behaviors of breast cancer.

  6. Studies of Liposomal bcl-2 Antisense Oligode-oxynucleofide Induction of Apoptosis in Raji Cells

    Institute of Scientific and Technical Information of China (English)

    DongmeiHe; HuanZhong

    2004-01-01

    OBJECTIVE To explore the effect of liposomal G3139 and transfected antisense phosphorothioate oligodeoxynucleotides directed against the coding region of the bcl-2 messenger RNA and the translation site on apoptosis in Raji cells.METHODS Cytotoxic effects were measured by use of the MTT method; The expression levels of Bcl-2 protein were assayed by immunofiuorescence using a fluoresce isothiocyanate label. Apoptosis was determined by morphological observation and flow cytometric analysis.RESULTS The 2 antisense oligonucleotides and G3139 can reduce Bcl-2 protein levels and Raji cell viability (IC50=4.54, 4.72 and 4.26 μmol/L, respectively), and induce apoptosis. A scrambled sequence control oligonucleotide and empty liposomes did not alter cell viability, Bcl-2 protein expression or apoptosis rates. There was no difference in reducing Bcl-2 protein levels and apoptosis rates found among the 3 antisense oligonucleotides.CONCLUSION The 2 antisense oligodeoxynucleotides of bcl-2 messenger RNA can effectively induce apoptosis of Raji cells. The 2 antisense sequences and G3139 have a similarity in their antisense effect.

  7. Expression of P16 protein and Bcl-2 protein in malignant eyelid tumors

    Institute of Scientific and Technical Information of China (English)

    牛膺筠; 周占宇; 刘夫玲; 王红云

    2002-01-01

    Objective To investigate the relationship between P16 gene (the tumor suppressor gene) and the bcl-2 gene (the apoptosis inhibitor gene) and the incidence and development of malignant eyelid tumors. Methods The streptavidin-biotin-peroxidase complex immunohistochemistry method was used to study the expression of P16 gene and the bcl-2 gene in 96 cases of malignant eyelid tumors. Results Among the 96 cases, there were 40 basal cell carcinomas (BCCs), 33 squamous carcinomas and 23 sebaceous carcinoma, with P16 protein positive (nuclear staining) rates 70%, 54.6% and 56.5%, respectively. The P16 positive rate was negatively correlated with the degree of tumor histological differentiation, and the rate difference between the high differentiated carcinomas was significant (P<0.05). Positive Bcl-2 protein expression was detected in the cytoplasm. All 40 BCC cases were Bcl-2 positive, and nearly all of the tumor cells showed positive cytoplasmic expression, while in the 33 squamous cell carcinoma cases only one showed positive focal reaction, and the staining in the other 32 cases was relatively faint. None of the 23 sebaceous carcinomas expressed Bcl-2. Conclusions The expression of the P16 protein was related to the occurrence and degree of differentiation of malignant eyelid tumors. The overexpression of the Bcl-2 protein suggests that suppression of apoptosis might play a role in the tumorigenesis of BCC.

  8. Radiation dose to family members of hyperthyroidism and thyroid cancer patients treated with 131I

    International Nuclear Information System (INIS)

    The thermoluminescence dosemeter (TLD) was used for measuring radiation dose to family members of thyrotoxicosis and thyroid cancer patients treated with 131I using CaSO4:Dy discs. There were 45 family members of thyrotoxicosis patients, who were divided into two groups with 22 in the first and 23 in the second group. Radiation safety instructions were the same for both the groups except in the second group where the patients were advised to use a separate bed at home for the first 3 d of dose administration. An activity ranging from 185 to 500 MBq was administered to these patients. The whole-body dose to family members ranged from 0.4 to 2.4 mSv (mean 1.1 mSv) in the first group and 0-1.9 mSv (mean 0.6 mSv) in the second group. A total of 297 family members of thyroid cancer patients were studied for whole-body dose estimation. An activity ranging from 0.925 to 7.4 GBq was administered to the thyroid cancer patients. The family members were divided into three groups depending upon the mode of transport and facilities available at home to avoid close proximity with the patient. Group A with 25 family members received a dose ranging from 0 to 0.9 mSv (mean 0.4 mSv), group B with 96 family members received a dose ranging from 0 to 8.5 mSv (mean 0.8 mSv) and group C with 176 family members received a dose ranging from 0 to 5.0 mSv (mean 0.8 mSv). The thyroid monitoring was also done in 103 family members who attended the patients in isolation wards for >2 d. Thyroid dose in them ranged from 0 to 2.5 mGy (mean 0.1 mGy). (authors)

  9. Effects of cognitive-behavioral treatment for weight loss in family members.

    Science.gov (United States)

    Rossini, Raffaella; Moscatiello, Simona; Tarrini, Giulietta; Di Domizio, Silvia; Soverini, Valentina; Romano, Andreina; Mazzotti, Arianna; Dalle Grave, Riccardo; Marchesini, Giulio

    2011-11-01

    The possibility that lifestyle changes may be shared by the family members of subjects with obesity attending cognitive-behavioral treatment (CBT) for weight loss has been scarcely evaluated. The purpose of this study was to measure the changes in body weight, lifestyle habits, and stage of change toward physical activity in the family members of 149 subjects with overweight/obesity enrolled into a weekly group CBT for weight management in the years 2007-2008. 230 adult (aged >18 years) family members (129 spouses, 72 children (43 female, 29 male), 29 with a different family relationship) completed a self-administered questionnaire at baseline and soon after the end of the completion of their relatives' program (approximately 6 months later). The questionnaire consisted of qualitative information regarding food choices, estimation of energy and food intake, self-report of height and weight, and motivation toward physical activity. At baseline, self-reported body mass index was normal in 115 cases, in the range 25 to 29.9 in 80 and ≥30 in 35. Following CBT of their relatives, the family members significantly reduced their average daily energy intake (-232 kcal/day; Pfat meat (-24 kcal, P=0.002), refined carbohydrates (-16 kcal, Pbiscuits (-23 kcal, P=0.005), chocolate (-7 kcal, P=0.024), and nonalcoholic beverages (fruit juices and carbonated drinks; -10 kcal; P=0.013), whereas fruit consumption was increased (+10 kcal; P=0.023). There was also a shift in the stage of change toward exercising. Body mass index changes of family members and CBT subjects were significantly correlated, mainly within spouses. In conclusion, CBT for weight loss positively influences the lifestyle habits of family members of participants, reducing energy intake and promoting a more favorable attitude toward physical activity.

  10. Parents and Children Only? Acculturation and the Influence of Extended Family Members among Vietnamese Refugees.

    Science.gov (United States)

    Tingvold, Laila; Middelthon, Anne-Lise; Allen, James; Hauff, Edvard

    2012-03-01

    The nuclear family is often the point of departure in much of the existing acculturation research on refugee youth and children of refugees. The influence of other extended family members appears to receive less attention in understanding acculturation processes and intergenerational perspectives. This qualitative study explores the influence of extended family members upon a small sample of Vietnamese refugee parents and their adolescents while they undergo acculturation through their long-term resettlement process in Norway. With repeated interviews over a time span of 3 years, we identified situations and processes in family life in which extended kin become particularly activated and influential. Vietnamese refugee families in Norway keep close contact with extended kin even in the face of geographical distance to kin remaining in Vietnam, or globally dispersed. Aunts, uncles, and cousins are experienced as significant persons in the lives of many adolescents. Additionally, birth order of parents can often influence relationship dynamics among siblings and siblings children. Extended kin surfaced as especially important and influential at critical stages and crisis situations in family life. Extended family, and in particular, parental siblings play important roles in the acculturation experience and family functioning of Vietnamese refugee families in Norway. This has important implications for the study of Vietnamese and other refugee and immigrant families in acculturation research. PMID:24510190

  11. Variations in Conflictual Family Issues by Adolescent Pubertal Status, Gender, and Family Member.

    Science.gov (United States)

    Papini, Dennis R.

    Conflictual family issues appearing during adolescence have not been adequately dimensionalized. In addition to this problem, researchers have focused on age-related variations in family conflicts without investigating other characteristics. A study was conducted to describe organized domains of conflictual family issues and to describe variations…

  12. Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino; Francesco Scopacasa; Annamaria Colao; Domenico Capone; Marianna Tarantino; Ernesto Grimaldi; Silvia Savastano

    2011-01-01

    AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH). METHODS: Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT) strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008). γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of

  13. The role and experiences of family members during the rehabilitation of mentally ill offenders.

    Science.gov (United States)

    Rowaert, Sara; Vandevelde, Stijn; Lemmens, Gilbert; Vanderplasschen, Wouter; Vander Beken, Tom; Vander Laenen, Freya; Audenaert, Kurt

    2016-03-01

    Taking care of a family member with a mental illness imposes a burden on various aspects of family life. This burden may be enhanced if the mentally ill individual has a criminal history. This paper aims to summarize the scientific literature dealing with the experiences, needs and burdens of families of mentally ill offenders. We aim to explore the roles that family members play in the rehabilitation of their relative and review the families' needs and burdens. Finally, we aim to investigate whether or not the family strengths are considered in the literature. A literature search in line with the PRISMA statement for systematic reviews and with the recommendations for an integrative review was performed in the ISI Web of Science, PubMed, Elsevier Science Direct and ProQuest databases. Limited research has been carried out into the experiences, needs and burdens of families of mentally ill offenders, with only eight studies fulfilling the inclusion criteria. Families of mentally ill offenders experience more stress than those of mentally ill individuals with no judicial involvement. This is because of the fact that these family members have to deal with both mental health services and judicial systems. The eight retrieved studies focus on needs and burdens, with little reference to strengths or capabilities. The review has highlighted the need for further research into the needs and burdens of families with mentally ill offenders, with a focus on strengths rather than an exclusively problem-oriented perspective. It is important that families become more involved in the health and social care of their relatives to avoid being considered 'second patients'. PMID:26756851

  14. Rotational properties of the Haumea family members and candidates: Short-term variability

    CERN Document Server

    Thirouin, Audrey; Noll, Keith S; Moskovitz, Nicholas A; Ortiz, Jose-Luis; Doressoundiram, Alain

    2016-01-01

    Haumea is one of the most interesting and intriguing transneptunian objects (TNOs). It is a large, bright, fast rotator, and its spectrum indicates nearly pure water ice on the surface. It has at least two satellites and a dynamically related family of more than ten TNOs with very similar proper orbital parameters and similar surface properties. The Haumean family is the only one currently known in the transneptunian belt. Various models have been proposed but the formation of the family remains poorly understood. In this work, we have investigated the rotational properties of the family members and unconfirmed family candidates with short-term variability studies, and report the most complete review to date. We present results based on five years of observations and report the short-term variability of five family members, and seven candidates. The mean rotational periods, from Maxwellian fits to the frequency distributions, are 6.27+/-1.19 h for the confirmed family members, 6.44+/-1.16 h for the candidates...

  15. The Significance and Correlation of SODD and Bcl-2 Protein Expression in Acute Leukemia of Children

    Institute of Scientific and Technical Information of China (English)

    Hongfang Tao; Qun Hu; Liuqing Zhang; Aiguo Liu; Shuangyou Liu; Ying Hu

    2006-01-01

    OBJECTIVE To explore the expression of SODD and bcl-2 proteins in bone marrow cells of children with acute leukemia (AL), and to examine the relationship of their expression with the classification, clinical features,therapeutic effect and prognosis for AL patients.METHODS Using the SABC immunohistochemical staining method, the expression of SODD and bcl-2 proteins in the bone marrow cells of 86 AL cases was determined. The patients were studied based on the following groups: 1) a first-visiting group; 2) a refractory-relapse group(some patients were sensitive to therapy but then suffered a recurrence);3) a complete-remission group (CR); 4) a high risk (HR) and 5) standard risk (SR) group; 6) a control group of patients with non-hematological diseases.RESULTS The positive rates of SODD and bcl-2 expression in the firstvisit, refractory-relapse and CR groups were significantly higher (P<0.05)compared to the control group. There was no significant difference in the expression of SODD or bcl-2 proteins between an acute lymphoblastic leukemia (ALL) group and acute nonlymphoblastic leukemia (ANLL)group (t=1.874, t=1.583, P>0.05). The positive rates of SODD and bcl-2expression in the patients who developed complete remission after chemotherapy were significantly lower (t=2.054, t=2.703, P<0.05) compared to the first-visit pediatric patients. The expression of the SODD protein in the refractory-relapse group was notably higher compared to the group treated initially (t=-1.081, P<0.05). A high expression of the bcl-2 protein was found in both the first-visit and refractory-relapse groups, with no significant difference found between the two groups (t=-1.196, P>0.05), whereas the percentage of bcl-2 positive cells in the refractory-relapse group (45%~87%) was significantly higher compared to the first-visit group (5%~62%). The positive expression of the SODD and bcl-2 proteins in the high-risk (HR) group were both significantly higher than the SR group (t=-3

  16. Expression patterns of SH3BGR family members in zebrafish development.

    Science.gov (United States)

    Tong, Fang; Zhang, Mingming; Guo, Xiaoling; Shi, Hongshun; Li, Li; Guan, Wen; Wang, Haihe; Yang, Shulan

    2016-07-01

    SH3 domain-binding glutamic acid-rich (SH3BGR) gene family is composed of SH3BGR, SH3BGRL, SH3BGRL2, and SH3BGRL3 which encodes a cluster of small thioredoxin-like proteins and shares a Src homology 3 (SH3) domain. However, biological functions of SH3BGR family members are largely elusive. Given that zebrafish (Danio rerio) sh3bgrl, sh3bgrl2, sh3bgrl3, and sh3bgr are evolutionally identical to their corresponding human orthologues, we analyzed the spatiotemporal expression of SH3BGR family members in zebrafish embryonic development stages by in situ hybridization. Our results revealed that except sh3bgrl, other members are all maternally expressed, especially for sh3bgrl3 that is strongly expressed from one-cell stage to juvenile fishes. In situ expression patterns of SH3BGR members are similar in the very early developmental stages, including with commonly strong expression in intestines, olfactory bulbs, and neuromasts for neural system building up. Organ-specific expressions are also demonstrated, of which sh3bgr is uniquely expressed in sarcomere, and sh3bgrl3 in liver. sh3bgrl and sh3bgrl2 are similarly expressed in intestines, notochords, and neuromasts after 12-h post-fertilization of embryos. Eventually, messenger RNAs (mRNAs) of all sh3bgr members are mainly constrained into intestines of juvenile fishes. Collectively, our study clarified the expression patterns of sh3bgr family members in diverse organogenesis in embryonic development and indicates that SH3BGR members may play predominant roles in neural system development and in maintenance of normal function of digestive organs, especially for intestine homeostasis. However, their expression patterns are varied with the development stages and organ types, suggesting that the aberrant expression of these members would result in multiple diseases. PMID:27233781

  17. The Janus kinase family and signaling through members of the cytokine receptor superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Ihle, J.N. [St. Jude Children`s Research Hospital, Memphis, TN (United States)

    1994-12-31

    Many cytokines initiate cellular responses through their interaction with members of the cytokine receptor superfamily which contain no catalytic domains in their cytoplasmic domains. Irrespective, ligand binding induces tyrosine phosphorylation, which requires a membrane proximal region of the cytoplasmic domain. Recent studies have shown that members of the Janus kinase (JAK) family of protein tyrosine kinases associate with the membrane proximal region, are rapidly tyrosine phosphorylated following ligand binding and their in vitro kinase activity is activated. The JAKs are 130-kDa proteins which lack SH2/SH3 domains and contain two kinase domains, an active domain and a second kinase-like domain. Individual receptors associate with, or require, one or more of the three known family members including JAK1, JAK2, and tyk2. Substrates of the JAKs include the 91-kDa and 113-kDa proteins of the interferon-stimulated transcription complex ISGF3. These proteins, when tyrosine phosphorylated, migrate to the nucleus and participate in the activation of gene transcription. Recent evidence suggests that the 91- and 113-kDa proteins are members of a large family of genes that are potential substrates of JAK family members and may regulate a variety of genes involved in cell growth, differentiation or function. 42 refs.

  18. Study of immunohistochemical demonstration of Bcl-2 protein in ameloblastoma and keratocystic odontogenic tumor

    Directory of Open Access Journals (Sweden)

    C S Sindura

    2013-01-01

    Full Text Available Background: The Bcl-2 (B-cell lymphoma gene product also known as apoptotic inhibitor is expressed in many normal and tumor tissues. This Bcl-2 gene protects the cell by blocking postmitotic differentiation from apoptosis, thus maintaining the stem cell pool. Objective: To study the expression of Bcl-2 protein in ameloblastoma and keratocystic odontogenic tumor (KCOT to determine their apoptotic behaviors and to analyze biological nature of KCOT, which has higher proliferative potential and aggressive clinical behavior like odontogenic tumors. Materials and Methods: Formalin-fixed paraffin sections of ameloblastoma (n = 20 and KCOT (n = 20 are considered for immunohistochemical analysis using monoclonal antibody against antihuman Bcl-2 oncoprotein. Lymphomas (n = 3 were used as controls. Statistical Analysis: The statistical analysis was performed using software package of social science version 16.The data were analyzed using Chi-square test and Student′s t test. In all the above tests, P < 0.05 was accepted as statistically significant. Results: The positive ratio of Bcl-2 was 85% (17/20 in ameloblastoma, 85% (17/20 in KCOT and 100% (3/3 in lymphomas. Bcl-2 was expressed in peripheral cells and few scattered cells of stellate reticulum in ameloblastoma. KCOT showed strong positivity for Bcl-2 mainly in the basal layer. Interpretation and Conclusion: The present study demonstrates the aggressive nature of KCOT and intrinsic growth potential of its lining epithelium. This study clearly demonstrates that KCOT like ameloblastoma demonstrates aggressive clinical and noticeable invasive behavior. Therefore, it is now considered as no longer a developmental cyst but as odontogenic tumor.

  19. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHAO Dan-ping; DING Xiao-wen; PENG Jia-ping; ZHENG Yi-xiong; ZHANG Su-zhan

    2005-01-01

    Objective: This study was designed to detect the expression ofbcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. Methods: Immunohistochemistry method was used to detect the expression ofbcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. Results: Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(-) had the best prognosis. This group was significantly associated with earlier Dukes' stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. Conclusion: The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

  20. Immunohistochemical expression of Bcl-2 in oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    S Juneja

    2015-01-01

    Full Text Available BACKGROUND: The B cell lymphoma-2 gene is a proto-oncogene whose protein product inhibits apoptosis. Its role is associated with keeping cells alive, but not by stimulating them to proliferation, as other proto-oncogenes do. Increased expression of protein product of Bcl-2 gene appears in the early phase of carcinogenesis leading to apoptosis impairment and in consequence to the progression of neoplastic changes. OBJECTIVE: To evaluate and compare the expression of Bcl-2 protein in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. MATERIALS AND METHODS: Sixty cases of formalin-fixed paraffin-embedded archival specimens comprising of 30 cases of leukoplakia with oral epithelial dysplasia and 30 cases of OSCC were taken for immunohistochemical analysis using monoclonal antibody against anti-human Bcl-2 oncoprotein. RESULTS: Immunostaining for Bcl-2 protein was identified in basal and parabasal layers as granular cytoplasmic staining in oral epithelial dysplasia. In OSCC, Bcl-2 immunoreactivity was most prominent in the peripheral cells of the infiltrating tumor islands which diminished toward the center in well-differentiated and moderately differentiated OSCC, whereas stronger and more diffuse expression of Bcl-2 oncoprotein was seen in poorly differentiated OSCC. Overall positivity of 26.7% (8/30 was observed in oral epithelial dysplasia and 30% (9/30 in OSCC in this study. INTERPRETATION AND CONCLUSION: Altered expression of Bcl-2 oncoprotein may be an early molecular event which leads to prolonged cell survival, increased chances of accumulation of genetic alterations, and subsequent increase in malignant transformation potential.

  1. COMBINING WORK WITH CARING FOR ELDERLY FAMILY MEMBER IN POLAND (CHOSEN ISSUES

    Directory of Open Access Journals (Sweden)

    Lukasz Jurek

    2016-07-01

    Full Text Available The problem of combining work with caring for elderly family members is becoming an increasingly important matter due to demographic (population ageing and social (increasing economic activity of women changes that are currently in progress. The aim of the article is to present selected issues related to the professional situation of people taking care for their elderly family members. The primary focus of the study is reasons for not working of non-working caregivers, and professional problems of working caregivers

  2. Marriage & Family Therapy Faculty Memberâ s Balance of Work and Personal Life

    OpenAIRE

    Matheson, Jennifer L.

    2002-01-01

    This mixed-method study examines the work and personal life balance of Marriage & Family Therapy faculty members across the U.S., 16 of whom were interviewed to gain a deeper understanding of their work and personal life balance issues. Of those, six felt they had good balance, six felt they had poor balance, and four were â middle of the road.â More men than women felt they had good balance. Faculty members indicated external and internal indicators such as family and workplace message...

  3. Social consequence on the families where a member is drug addicted.

    OpenAIRE

    RUDOVÁ, Lucie

    2007-01-01

    Abstract {--} Social consequence on the families where a member is drug addicted This current issue is considered to pose a social phenomenon of significant consequence. Together with further social problems of the day, drug addiction and its impacts rank worldwide among the most burning issues, particularly in terms of their reflection in the media. Recently, the issue of drug legalisation has often been discussed widely in the media leaving the impact of drug addiction on the families stric...

  4. Involvement of the family members in caring of patients an acute care setting

    Directory of Open Access Journals (Sweden)

    A Bhalla

    2014-01-01

    Full Text Available Background: Family members are critical partners in the plan of care for patients both in the hospital and at home. Involving the members of the family in acute care can help the nursing staff in emergency. The present study was aimed to find out the role of the family members while caring for the patients admitted in emergency unit of a tertiary care hospital. Materials and Methods: A total of 400 family members of the patients were conveniently selected. Only one member per family was interviewed and their role in taking care of the patient in acute care setting was evaluated. Results: The mean age of patients admitted in acute care setting was 46.6 yrs ± 18.8 with the age range of 18-84 years. Majority (39% of the patients were in the age group of 31-60 years. More than half of the caregivers of patients were males and 88% of them were first-degree relatives. The major tasks performed by the caregivers during the patient care was communicating with doctors/ nursing staff (98%, cleaning and dressing the patient (94%, feeding the patient (90%, procuring medication and other supplies (88%, administering oral medications (74%, changing position and helping for back care (65%, shifting the patients for investigations (60%, collecting reports (35% and providing physiotherapy (25%. Conclusions: The results of the study concluded that family involvement in acute care setting can help the nursing staff in taking care of the patient in acute care setting and it also provides the opportunity for preparing them for after care of the patients at home following discharge.

  5. Effect of Bcl-2 and caspase-3 on calcium distribution in apoptosis of HL-60 cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Apoptosis manifests in two major execution programs downstream of the death signal: the caspase pathway and organelle dysfunction. An important antiapoptosis factor, Bcl-2 protein, contributes in caspase pathway of apoptosis. Calcium, an important intracellular signal element in cells, is also observed to have changes during apoptosis, which maybe affected by Bcl2 protein. We have previously reported that in Harringtonine (HT) induced apoptosis of HL-60 cells, there's a change of intracellular calcium distribution, moving from cytoplast especially Golgi's apparatus to nucleus and accumulating there with the highest concentration. We report here that caspase-3 becomes activated in HT-induced apoptosis of HL-60 cells, which can be inhibited by overexpression of Bcl-2 protein. No sign of apoptosis or intracellular calcium movement from Golgi's apparatus to nucleus in HL-60 cells overexpressing Bcl-2 or treated with Ac-DEVD-CHO, a specific inhibitor of caspase-3. The results indicate that activated caspase-3 can promote the movement of intracellular calcium from Golgi's apparatus to nucleus, and the process is inhibited by Ac-DEVD-CHO (inhibitor of caspas-3), and that Bcl-2 can inhibit the movement and accumulation of intracellular calcium in nucleus through its inhibition on caspase3. Calcium relocalization in apoptosis seems to be irreversible, which is different from the intracellular calcium changes caused by growth factor.

  6. Increase of bcl-2 Protein Expression in Aggressive Basal Cell Carcinoma of Head and Neck

    Directory of Open Access Journals (Sweden)

    Cláudia CAZAL

    2006-09-01

    Full Text Available Objective: The aim of this study was to verify the bcl-2 protein expression in 22 cutaneous basal cell carcinomas (BCC of the head and neck, and to compare it with its aggressive behavior. Method: Tumors were histologically classified in non-aggressive (BCC 1 and aggressive (BCC 2 and then submitted to the immunohistochemistry technique with the streptavidin-biotin peroxidase method using the anti-bcl-2 antibody. Results: After proceeding to morphological analysis, sixteen tumors (72.7% were considered aggressive and six (27.3% non-aggressive. Immunohistochemistry analysis showed that thirteen (59.1% lesions were positive staining and nine (40.9% were negative to the bcl-2 protein. Considering the positive lesions, 12 (92.3% were aggressive and one (7.7% non-aggressive. The relation between bcl-2 protein staining and the tumor aggressiveness was statistically significant (p<0.05 - Fisher's exact Test. Conclusion: The results suggest a relationship between the bcl-2 protein expression and the histological aggressiveness grade in the BCC of the head and neck group studied may exist.

  7. Bcl-2-dependent upregulation of autophagy by sequestosome 1/p62 in vitro

    Institute of Scientific and Technical Information of China (English)

    Liang ZHOU; Hong-feng WANG; Hai-gang REN; Dong CHEN; Feng GAO; Qing-song HU; Chen FU

    2013-01-01

    To investigate whether sequestosome 1/p62 (p62),a key cargo adaptor protein involved in both the ubiquitin-proteasome system and the autophagy-lysosome system,could directly regulate autophagy in vitro.Methods:HEK 293 cells or HeLa cells were transfected with p62-expressing plasmids or siRNA targeting p62.The cells or the cell lysates were subsequently subjected to immunofluorescence assay,immunoprecipitation assay,or immunoblot analysis.In vitro pulldown assay was used to study the interaction of p62 with Bcl-2.Results:Overexpression of p62 significantly increased the basal level of autophagy in both HEK 293 cells and HeLa cells,whereas knockdown of p62 significantly decreased the basal level of autophagy.In vitro pulldown assay showed that p62 directly interacted with Bcl-2.It was observed in HeLa cells that p62 co-localized with Bcl-2.Furthermore,knockdown of p62 in HEK 293 cells significantly increased the amount of Beclin 1 that co-immunoprecipitated with Bcl-2.Conclusion:p62 induces autophagy by disrupting the association between Bcl-2 and Beclin 1.

  8. Immunolocalization of Bcl-2 oncoprotein in amlodipine-induced gingival overgrowth

    Directory of Open Access Journals (Sweden)

    Lalitha Tanjore Arunachalam

    2013-01-01

    Full Text Available Background: Drug-induced gingival overgrowth (DIGO is one of the unwanted side effects of amlodipine therapy, but the pathogenesis still remains unclear. Apoptosis, which plays a ubiquitous role in tissue homeostasis, including gingiva, may be involved in the development of gingival enlargement. Aims and Objectives: (i To study the distribution of Bcl-2 in healthy and overgrown gingival tissues. (ii To compare and correlate the Bcl-2 expression in gingival samples from subjects on amlodipine therapy to the findings in healthy controls. Materials and Methods: A total of 25 subjects were recruited for the study - 15 hypertensive patients and 10 systemically healthy subjects. Both the groups were analyzed for Bcl-2 expression using immunohistochemistry. Results: Few of the control specimens showed weak positivity to Bcl-2 antibody, with the distribution limited to the basal cell layers alone, whereas 10 hyperplastic specimens expressed Bcl-2 and, unlike the control group, the distribution pattern was seen in both basal and suprabasal layers. Conclusion: The results indicate that the pathogenesis of amlodipine-induced gingival overgrowth might involve inhibition of apoptosis, especially with morphogenesis of hyperplastic gingival epithelia.

  9. THE OVEREXPRESSION OF APOPTOSIS -RELATED GENES OF P53 AND BCL-2 IN CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the significance of overexpression of P53 and bcl-2 protein in carcinogenesis of cervix. Methods 10 cases of cervical intraepithelial neoplasis(CIN) and 57 cases of invasive cancer were investigated with immunohistochemistry technique. Results The overexpresion of P53 protein in CIN and cervical cancer was significantly higher than that of control, respectively (P<0.01). But there was no significant difference between CIN and cervical cancer(P>0. 05). The immunoreactivity of bcl-2 in CIN was much more higher than that of control (P<0.05). The positive rate and immunoreactivity of bcl-2 in cervical carcinoma were both remarkably higher than those of control (P<0. 01) ,but there was no significant difference between CIN and cervical carcinoma (P>0. 05). It was also found that there was a remarkably positive correlation between the overexpression of bcl-2 and P53 (P<0.01). Conclusion Because of the loss of wtP53 function,the expression of bcl-2 can not be down-reguated,which is associated with the pathogenesis and development of cervical carcinoma.

  10. Removal of the BH4 Domain from Bcl-2 Protein Triggers an Autophagic Process that Impairs Tumor Growth12

    Science.gov (United States)

    Trisciuoglio, Daniela; De Luca, Teresa; Desideri, Marianna; Passeri, Daniela; Gabellini, Chiara; Scarpino, Stefania; Liang, Chengyu; Orlandi, Augusto; Del Bufalo, Donatella

    2013-01-01

    Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2) protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4) domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1) the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2) Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3) BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein. PMID:23479509

  11. Removal of the BH4 Domain from Bcl-2 Protein Triggers an Autophagic Process that Impairs Tumor Growth

    Directory of Open Access Journals (Sweden)

    Daniela Trisciuoglio

    2013-03-01

    Full Text Available Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2 protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4 domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1 the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2 Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3 BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein.

  12. Removal of the BH4 domain from Bcl-2 protein triggers an autophagic process that impairs tumor growth.

    Science.gov (United States)

    Trisciuoglio, Daniela; De Luca, Teresa; Desideri, Marianna; Passeri, Daniela; Gabellini, Chiara; Scarpino, Stefania; Liang, Chengyu; Orlandi, Augusto; Del Bufalo, Donatella

    2013-03-01

    Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2) protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4) domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1) the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2) Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3) BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein. PMID:23479509

  13. Antisense bcl-2 treatment increases programmed cell death in non-small cell lung cancer cell lines.

    Science.gov (United States)

    Koty, P P; Zhang, H; Levitt, M L

    1999-02-01

    Programmed cell death (PCD) is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the ratio of PCD inducers (Bax) or inhibitors (Bcl-2). An abnormally high ratio of Bcl-2 to Bax prevents PCD, thus contributing to resistance to chemotherapeutic agents, many of which are capable of inducing PCD. Non-small cell lung cancer (NSCLC) cells demonstrate resistance to these PCD-inducing agents. If Bcl-2 prevents NSCLC cells from entering the PCD pathway, then reducing the amount of endogenous Bcl-2 product may allow these cells to spontaneously enter the PCD pathway. Our purpose was to determine the effects of bcl-2 antisense treatment on the levels of programmed cell death in NSCLC cells. First, we determined whether bcl-2 and bax mRNA were expressed in three morphologically distinct NSCLC cell lines: NCI-H226 (squamous), NCI-H358 (adenocarcinoma), and NCI-H596 (adenosquamous). Cells were then exposed to synthetic antisense bcl-2 oligonucleotide treatment, after which programmed cell death was determined, as evidenced by DNA fragmentation. Bcl-2 protein expression was detected immunohistochemically. All three NSCLC cell lines expressed both bcl-2 and bax mRNA and had functional PCD pathways. Synthetic antisense bcl-2 oligonucleotide treatment resulted in decreased Bcl-2 levels, reduced cell proliferation, decreased cell viability, and increased levels of spontaneous PCD. This represents the first evidence that decreasing Bcl-2 in three morphologically distinct NSCLC cell lines allows the cells to spontaneously enter a PCD pathway. It also indicates the potential therapeutic use of antisense bcl-2 in the treatment of NSCLC. PMID:10217615

  14. Social Support of Indonesian and U.S. Children and Adolescents by Family Members and Friends.

    Science.gov (United States)

    French, Doran C.; Rianasari, Meta; Pidada, Sri; Nelwan, Peter; Buhrmester, Duane

    2001-01-01

    Assessed multiple features of social support provided by mothers, fathers, siblings, and friends to Indonesian and U.S. elementary and junior high school students. Found that Indonesian youth ranked family members higher and friends lower on companionship and satisfaction than did U.S. youth. Friends were seen as the primary sources of intimacy in…

  15. The impact of childhood experiences and family members outside the household on residential environment choices

    NARCIS (Netherlands)

    M. Blaauboer

    2011-01-01

    Choices of urban, suburban or rural residential environments have often been studied from a life-course perspective. In this paper, an examination is made of the influence of childhood experiences and of residential environment choices of family members outside the household. It is argued that socia

  16. Factors Affecting Burden of South Koreans Providing Care to Disabled Older Family Members

    Science.gov (United States)

    Lee, Minhong; Yoon, Eunkyung; Kropf, Nancy P.

    2007-01-01

    This study examined the determinants of caregiving burden among South Koreans who care for their disabled older family members. A sample of 1,000 primary caregivers taken from the Comprehensive Study for Elderly Welfare Policy in Seoul, South Korea was analyzed. Independent variables included the demographic characteristics of caregivers and care…

  17. Photo of family members of STS-5 commander, Vance D. Brand

    Science.gov (United States)

    1982-01-01

    Erik Brand and his mother Beverly are seen in a photo of family members of STS-5 commander Vance D. Brand. Erik holds a small model of the space shuttle with its solid rocket boosters and external fuel tank still attached.

  18. Posttraumatic Symptoms in Japanese Bereaved Family Members with Special Regard to Suicide and Homicide Cases

    Science.gov (United States)

    Ogata, Kohske; Ishikawa, Takaki; Michiue, Tomomi; Nishi, Yuko; Maeda, Hitoshi

    2011-01-01

    The authors investigated posttraumatic stress disorder (PTSD) symptoms in Japanese bereaved family members using a questionnaire. Participants were bereaved as a result of suicide and homicide (n = 51 and 49, respectively), with natural death (n = 56) as a control; and their relationships to the deceased were parent-child (n = 79), conjugal (n =…

  19. Self-Concept and Depression among Children Who Experienced the Death of a Family Member

    Science.gov (United States)

    Nguyen, Hong T.; Scott, Amy N.

    2013-01-01

    The present study investigates the moderating effects of physical and academic self-concept on depression among children who experienced the death of a family member. Data from Phase III of the National Institute of Child Health and Human Development Study of Early Child Care was used in the present study. Having a higher physical self-concept…

  20. 42 CFR 31.10 - Dependent members of families; use of Service facilities.

    Science.gov (United States)

    2010-10-01

    ..., PUBLIC HEALTH SERVICE, AND FORMER LIGHTHOUSE SERVICE Provisions Applicable to Coast Guard, National Ocean... 42 Public Health 1 2010-10-01 2010-10-01 false Dependent members of families; use of Service facilities. 31.10 Section 31.10 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN...

  1. 77 FR 61775 - Agency Information Collection Activities: Petition for Qualifying Family Member of a U-1...

    Science.gov (United States)

    2012-10-11

    ... Register on June 27, 2012, at 77 FR 38308 with a correction published on July 6, 2012, at 77 FR 40078... members may apply for adjustment of status or seek immigrant visas, the U-1 nonimmigrant who has been granted adjustment of status must file an immigrant petition on behalf of the qualifying family...

  2. Chipmunk parvovirus is distinct from members in the genus Erythrovirus of the family Parvoviridae.

    Directory of Open Access Journals (Sweden)

    Zhaojun Chen

    Full Text Available The transcription profile of chipmunk parvovirus (ChpPV, a tentative member of the genus Erythrovirus in the subfamily Parvovirinae of the family Parvoviridae, was characterized by transfecting a nearly full-length genome. We found that it is unique from the profiles of human parvovirus B19 and simian parvovirus, the members in the genus Erythrovirus so far characterized, in that the small RNA transcripts were not processed for encoding small non-structural proteins. However, like the large non-structural protein NS1 of the human parvovirus B19, the ChpPV NS1 is a potent inducer of apoptosis. Further phylogenetic analysis of ChpPV with other parvoviruses in the subfamily Parvovirinae indicates that ChpPV is distinct from the members in genus Erythrovirus. Thus, we conclude that ChpPV may represent a new genus in the family Parvoviridae.

  3. ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

    Science.gov (United States)

    Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

    1997-05-23

    Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling. PMID:9153189

  4. Bcl-2、Bax及M30在Bowen病中的表达%Expression of Bcl-2、 Bax and M30 in Bowen's disease

    Institute of Scientific and Technical Information of China (English)

    张敏; 张谊之; 王琳; 李俸媛

    2002-01-01

    为了研究细胞凋亡与Bowen病发病的关系,我们采用免疫组化方法检测了28例Bowen病皮损中Bcl-2、Bax及M30的表达.结果发现M30及Bax染色阳性分别见于4例和8例表皮角质形成细胞,Bcl-2在10例表皮角质形成细胞和12例真皮淋巴细胞呈阳性表达;Bcl-2表达阳性率高于Bax,但无统计学差异(χ2=2.1053,P>0.05);M30与Bax表达显著正相关(r=0.6455,P0.05).提示Bowen病发病可能与表皮角质形成细胞凋亡降低有关.

  5. Relationship of service members' deployment trauma, PTSD symptoms, and experiential avoidance to postdeployment family reengagement.

    Science.gov (United States)

    Brockman, Callie; Snyder, James; Gewirtz, Abigail; Gird, Suzanne R; Quattlebaum, Jamie; Schmidt, Nicole; Pauldine, Michael R; Elish, Katie; Schrepferman, Lynn; Hayes, Charles; Zettle, Robert; DeGarmo, David

    2016-02-01

    This research examined whether military service members' deployment-related trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and experiential avoidance are associated with their observed levels of positive social engagement, social withdrawal, reactivity-coercion, and distress avoidance during postdeployment family interaction. Self reports of deployment related trauma, postdeployment PTSD symptoms, and experiential avoidance were collected from 184 men who were deployed to the Middle East conflicts, were partnered, and had a child between 4 and 13 years of age. Video samples of parent-child and partner problem solving and conversations about deployment issues were collected, and were rated by trained observers to assess service members' positive engagement, social withdrawal, reactivity-coercion, and distress avoidance, as well as spouse and child negative affect and behavior. Service members' experiential avoidance was reliably associated with less observed positive engagement and more observed withdrawal and distress avoidance after controlling for spouse and child negative affect and behavior during ongoing interaction. Service members' experiential avoidance also diminished significant associations between service members' PTSD symptoms and their observed behavior. The results are discussed in terms of how service members' psychological acceptance promotes family resilience and adaption to the multiple contextual challenges and role transitions associated with military deployment. Implications for parenting and marital interventions are described. PMID:26437144

  6. Relationship of service members' deployment trauma, PTSD symptoms, and experiential avoidance to postdeployment family reengagement.

    Science.gov (United States)

    Brockman, Callie; Snyder, James; Gewirtz, Abigail; Gird, Suzanne R; Quattlebaum, Jamie; Schmidt, Nicole; Pauldine, Michael R; Elish, Katie; Schrepferman, Lynn; Hayes, Charles; Zettle, Robert; DeGarmo, David

    2016-02-01

    This research examined whether military service members' deployment-related trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and experiential avoidance are associated with their observed levels of positive social engagement, social withdrawal, reactivity-coercion, and distress avoidance during postdeployment family interaction. Self reports of deployment related trauma, postdeployment PTSD symptoms, and experiential avoidance were collected from 184 men who were deployed to the Middle East conflicts, were partnered, and had a child between 4 and 13 years of age. Video samples of parent-child and partner problem solving and conversations about deployment issues were collected, and were rated by trained observers to assess service members' positive engagement, social withdrawal, reactivity-coercion, and distress avoidance, as well as spouse and child negative affect and behavior. Service members' experiential avoidance was reliably associated with less observed positive engagement and more observed withdrawal and distress avoidance after controlling for spouse and child negative affect and behavior during ongoing interaction. Service members' experiential avoidance also diminished significant associations between service members' PTSD symptoms and their observed behavior. The results are discussed in terms of how service members' psychological acceptance promotes family resilience and adaption to the multiple contextual challenges and role transitions associated with military deployment. Implications for parenting and marital interventions are described.

  7. Postnatal roles of glial cell line-derived neurotrophic factor family members in nociceptors plasticity

    Institute of Scientific and Technical Information of China (English)

    Sacha A. Malin; Brian M. Davis

    2008-01-01

    The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family,which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV 1, to produce long-lasting hyperalgesia.

  8. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2

    Science.gov (United States)

    Wang, Xiaoming; Zhou, Minran; Fu, Yue; Sun, Ting; Chen, Jin; Qin, Xuemei; Yu, Yuan; Jia, Jihui; Chen, Chunyan

    2016-01-01

    Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression. PMID:27008505

  9. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

    Directory of Open Access Journals (Sweden)

    Xiaoming Wang

    Full Text Available Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL, adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2 was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

  10. Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Cheng, Tian-Lu [Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lin, Shinne-Ren [Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Long-Sen, E-mail: lschang@mail.nsysu.edu.tw [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)

    2015-04-01

    Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression.

  11. Immunohistochemical Study Of Bcl-2 Protein And Estrogen Receptor-Alpha Expression In Benign Prostatic Hyperplasia And Prostatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed H. Abel-Rahman- Ghada A. Abdel-Aziz*- Ali Emad S** Abdel

    2004-12-01

    Full Text Available The human prostate, a male sexual accessory tissue involved in seminal fluid production, has a remarkably high incidence of hyperplastic and neoplastic disease. The present study was carried out on one hundred and twenty (120 specimens divided into two groups; group 1: Included forty cases of benign prostatic hyperplasia (BPH and group 2: Included sixty cases of prostatic adenocarcinoma (PC (22 were low grade; GS: 2-6 and 38 were high grade; GS: 7-10,in addition to twenty cases of histologically normal prostates taken as controls. Immunohistochemical technique was applied to detect Bcl-2 as well as ER positivity in all specimens. Group 1 showed the following profile: ER (+ in all cases (100%, Bcl-2 (- in 95%, ER (+ / Bcl-2 (+ in 95%, ER (- / Bcl-2 (+ in 0%, ER (+ / Bcl-2 (- in 5% and ER (- / Bcl-2 (- in 0% of cases while group 2 showed the following profile: ER (+ in 30%, Bcl-2 (+ in 21.7%, ER (+ / Bcl-2 (+ in 15%, ER (- / Bcl-2 (+ in 6.7%, ER (+ / Bcl-2 (- in 15% and ER (- / Bcl-2 (- in 70% of cases. The mean epithelial ER -immunolabeling was, however, significantly increased in group 2 than in group 1 (P < 0.05 which, in turn, being higher than the normal cases (P<0.05 . Among group 2 , the mean ER was significantly more in high grade than in low grade tumors (P < 0.05, however, the mean ER immunolabeling revealed no significant correlation with T-stage (P = 0.219 or with the clinical stage (P = 0.391. In contrast, the Bcl-2 immunostaining was statistically higher in group 1 than in group 2 (P < 0.05 and showed a significant correlation with T stage (P < 0.05 although the study displayed no significant correlation between Bcl-2 immunopositivity and either Gleason score (P = 0.125 or the histologic grade (P = 0.146. In addition, combined ER (+/ Bcl 2 (+ immunoreactivity demonstrated the aggressive subgroup of PC cases more accurately than either ER (+ or Bcl-2 (+ alone. Finally, multivariate analysis showed that the Bcl-2, proved to be an

  12. Development of bcl-2 mRNA repressor of apoptosis in human fetal central nervous system%人胎儿中枢神经系统凋亡抑制因子bcl-2mRNA的发育

    Institute of Scientific and Technical Information of China (English)

    李泽桂; 蔡文琴

    2003-01-01

    目的研究人胎儿中枢神经系统凋亡抑制因子 bcl-2 mRNA 的发育表达.方法用地高辛标记的bcl-2 cRNA 探针原位杂交组织化学技术,检测了12~39周胎儿中枢神经系统内bcl-2 mRNA的表达情况. 结果①在所检测的各脑区均有bcl-2 mRNA表达.第12周,有强阳性的bcl-2 mRNA出现在脊髓、延髓的运动神经元、大脑额叶的皮质板; 小脑和大脑室层的bcl-2 mRNA表达较弱.bcl-2 mRNA的水平一般是随胎龄的增长而下降,至第39周表达最弱.②bcl-2 mRNA主要在神经元表达.结论在人胎儿神经系统发育中表达的bcl-2可能与编程性细胞死亡有关.

  13. Suppression of bcl-2 Gene by RNA Interference Increases Chemosensitivity to Cisplatin in Nasopharyngeal Carcinoma Cell Line CNE1

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua YIN; Cai-Ping REN; Feng LI; Xu-Yu YANG; Hui LI; Ming ZHAO; Kai-Tai YAO

    2004-01-01

    To explore the effect of suppressing BCL-2 expression using RNA interference (RNAi) technique in nasopharyngeal carcinoma cell line CNE1. CNE1 cell lines stably expressing shRNAs targeted bcl-2 and GL3 gene were established and gene expression inhibition was assessed by Western blotting analysis. The effect of suppressing bcl-2 by RNAi on cell growth was studied, the apoptosis induction and the sensitization of CNE 1 cells to cisplatin were quantified by MTT assay and flow cytometry. The results showed that: stable transfection of CNE 1 cells with vectors expressing shRNAs against bcl-2 decreased the expression of BCL-2 protein; suppression of BCL-2 expression did not affect cell proliferation but could increase the chemosensitivity to cisplatin in CNE1 cells. This will help physicians to make some clinical trials of gene therapy on nasopharyngeal carcinoma by RNAi.

  14. Differential expression of Bcl-2 and Bax during gastric ischemia-reperfusion of rats

    Institute of Scientific and Technical Information of China (English)

    Wei-Li Qiao; Guang-Ming Wang; Yue Shi; Jin-Xia Wu; You-Jian Qi; Jian-Fu Zhang; Hong Sun; Chang-Dong Yan

    2011-01-01

    AIM: To investigate expression of Bcl-2 and Bax in gastric ischemia-reperfusion (GI-R) and involvement of extracellular signal-regulated kinase (ERK) 1/2 activation.METHODS: The GI-R model was established by ligature of the celiac artery for 30 min and reperfusion in Sprague-Dawley rats. Rats were assigned to groups in accordancewith their evaluation period: control, 0, 0.5, 1, 3, 6, 24,48, and 72 h. Expression and distribution of Bcl-2 and Bax proteins were analyzed by immunohistochemistry and western blotting in gastric tissue samples after sacrifice.RESULTS: Compared with controls, the percentage of positive cells and protein levels of Bcl-2 decreased in the early phases of reperfusion, reached its minimumat 1 h (P < 0.05); it then increased, reaching its peak at 24 h of reperfusion (P < 0.05). The pattern of Bax expression was opposite to that of Bcl-2. Bax expressionincreased after reperfusion, with its peak at 1 h of reperfusion (P < 0.05), and then it decreased gradually to a minimum at 24 h after reperfusion (P < 0.05).On the other hand, inhibition of activation of ERK1/2 induced by PD98059, a specific upstream MEK inhibitor,had significant effects on Bcl-2 and Bax in GI-R.Compared with GI-R treatment only at 3 h of reperfusion,PD98059 reduced the number of Bcl-2 positive cells (0.58% of R3h group, P < 0.05) and Bcl-2 proteinlevel (74% of R3h group, P < 0.05) but increased the number of Bax-positive cells (1.33-fold vs R3h group, P< 0.05) and Bax protein level (1.35-fold of R3h group,P < 0.05).CONCLUSION: These results indicated that the Bcl-2 and Bax played a pivotal role in the gastric mucosal I-R injury and repair by activation of ERK1/2.

  15. MicroRNA-146a Induced by Hypoxia Promotes Chondrocyte Autophagy through Bcl-2

    Directory of Open Access Journals (Sweden)

    Fei Zhang

    2015-10-01

    Full Text Available Background/Aims: There have been many studies on the etiology of osteoarthritis (OA with regard to the function of inflammatory cytokines, the process of cartilage degradation, the function of miR-146a, hypoxia stimulation and autophagy in OA chondrocytes, but there have been no reports on the relationship between miR-146a and autophagy in cartilage, especially under hypoxia. This study aimed to confirm the relationship of miR-146a and autophagy in cartilage under hypoxia. Methods: Chondrocytes were treated by hypoxia gradients, and the main factors including HIF-1α, HIF-2α, miR-146a and Bcl-2 and autophagy markers ULK-1, ATG-5 were detected by quantitative PCR (Q-PCR and western blotting. The autophagy marker LC-3 was detected by immunofluorescence. The reciprocal effects between miR-146a and Bcl-2 were confirmed by several combinations of shRNAs and adenovirus-gene systems followed by Q-PCR and western blot detection. Results: Hypoxia maintained the chondrocytes phenotype and promoted autophagy and miR-146a expression via HIF-1α, but not HIF-2α, while miR-146a did not reversely affect HIF-1α. The autophagy induced by hypoxia through HIF-1α, miR-146a and Bcl-2. Simply, hypoxia induced HIF-1α, and HIF-1α increased miR-146a, but miR-146a suppressed Bcl-2, an autophagy inhibitor. While Bcl-2 affected neither HIF-1α nor miR-146a. The absence of both HIF-1α and miR-146a or Bcl-2 over-expression inhibited hypoxia-induced autophagy. Conclusion: HIF-1α, miR-146a and Bcl-2 play crucial roles during hypoxia-induced autophagy, Hypoxia, HIF-1α and miR-146a promote chondrocytes autophagy via depressing Bcl-2. We conclude that miR-146a may serve as a novel therapeutic target for protecting cartilage from degeneration in OA.

  16. Temporal Alterations in Cellular Bax:Bcl-2 Ratio following Traumatic Brain Injury in the Rat

    OpenAIRE

    Raghupathi, Ramesh; Strauss, Kenneth I.; Zhang, Chen; Krajewski, Stanislaw; Reed, John C.; McIntosh, Tracy K.

    2003-01-01

    Cell death/survival following CNS injury may be a result of alterations in the intracellular ratio of death and survival factors. Using immunohistochemistry, Western analysis and in situ hybridization, the expression of the anti-cell death protein, Bcl-2, and the pro-cell death protein, Bax, was evaluated following lateral fluid-percussion (FP) brain injury of moderate severity (2.3–2.6 atm) in adult male Sprague-Dawley rats. By 2 h post-injury, a marked reduction of cellular Bcl-2-immunoreac...

  17. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  18. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    Energy Technology Data Exchange (ETDEWEB)

    Shekhar, Tanmay M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Green, Maja M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Department of Anatomy & Neuroscience, The University of Melbourne, Parkville 3010 (Australia); Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia)

    2015-07-15

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  19. Cancer in the Family: Review of the Psychosocial Perspectives of Patients and Family Members

    Science.gov (United States)

    Mitschke, Diane B.

    2008-01-01

    As advances in cancer care have led to more treatment options and longer survival for cancer patients, a focus on quality of life for patients and their families has gained importance. This review provides a discussion of stress and coping theory, documents the relevance of this topic area for social work practice, and illuminates the results of a…

  20. Redefining Residential: Family-Driven Care in Residential Treatment--Family Members Speak

    Science.gov (United States)

    Residential Treatment for Children & Youth, 2009

    2009-01-01

    This is the sixth in a series of papers issued by the American Association of Children's Residential Centers (AACRC) regarding emerging and best practices in the field of residential treatment for children, youth, and families. AACRC is a long standing national association focused exclusively on practice and policy issues related to the provision…

  1. Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

    Directory of Open Access Journals (Sweden)

    Koch Wolfgang

    2008-07-01

    Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

  2. Involvement of PI3K and MAPK Signaling in bcl-2-induced Vascular Endothelial Growth Factor Expression in Melanoma Cells

    Science.gov (United States)

    Trisciuoglio, Daniela; Iervolino, Angela; Zupi, Gabriella; Del Bufalo, Donatella

    2005-01-01

    We have previously demonstrated that bcl-2 overexpression in tumor cells exposed to hypoxia increases the expression of vascular endothelial growth factor (VEGF) gene through the hypoxia-inducible factor-1 (HIF-1). In this article, we demonstrate that exposure of bcl-2 overexpressing melanoma cells to hypoxia induced phosphorylation of AKT and extracellular signal-regulated kinase (ERK)1/2 proteins. On the contrary, no modulation of these pathways by bcl-2 was observed under normoxic conditions. When HIF-1α expression was reduced by RNA interference, AKT and ERK1/2 phosphorylation were still induced by bcl-2. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia. No differences were observed between control and bcl-2-overexpressing cells in normoxia, in terms of VEGF protein secretion and in response to PI3K and MAPK inhibitors. We also demonstrated that RNA interference-mediated down-regulation of bcl-2 expression resulted in a decrease in the ERK1/2 phosphorylation and VEGF secretion only in bcl-2-overexpressing cell exposed to hypoxia but not in control cells. In conclusion, our results indicate, for the first time, that bcl-2 synergizes with hypoxia to promote expression of angiogenesis factors in melanoma cells through both PI3K- and MAPK-dependent pathways. PMID:15987743

  3. Removal of the BH4 Domain from Bcl-2 Protein Triggers an Autophagic Process that Impairs Tumor Growth12

    OpenAIRE

    Trisciuoglio, Daniela; De Luca, Teresa; Desideri, Marianna; Passeri, Daniela; Gabellini, Chiara; Scarpino, Stefania; Liang, Chengyu; Orlandi, Augusto; Del Bufalo, Donatella

    2013-01-01

    Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2) protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4) domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. I...

  4. Identification, structure, and differential expression of members of a BURP domain containing protein family in soybean.

    Science.gov (United States)

    Granger, Cheryl; Coryell, Virginia; Khanna, Anupama; Keim, Paul; Vodkin, Lila; Shoemaker, Randy C

    2002-08-01

    Expressed sequence tags (ESTs) exhibiting homology to a BURP domain containing gene family were identified from the Glycine max (L.) Merr. EST database. These ESTs were assembled into 16 contigs of variable sizes and lengths. Consistent with the structure of known BURP domain containing proteins, the translation products exhibit a modular structure consisting of a C-terminal BURP domain, an N-terminal signal sequence, and a variable internal region. The soybean family members exhibit 35-98% similarity in a -100-amino-acid C-terminal region, and a phylogenetic tree constructed using this region shows that some soybean family members group together in closely related pairs, triplets, and quartets, whereas others remain as singletons. The structure of these groups suggests that multiple gene duplication events occurred during the evolutionary history of this family. The depth and diversity of G. max EST libraries allowed tissue-specific expression patterns of the putative soybean BURPs to be examined. Consistent with known BURP proteins, the newly identified soybean BURPs have diverse expression patterns. Furthermore, putative paralogs can have both spatially and quantitatively distinct expression patterns. We discuss the functional and evolutionary implications of these findings, as well as the utility of EST-based analyses for identifying and characterizing gene families. PMID:12175072

  5. Impact of Close Family Members on Older Adults’ Early Response to Depression Treatment

    Science.gov (United States)

    Martire, Lynn M.; Schulz, Richard; Reynolds, Charles F.; Morse, Jennifer Q.; Butters, Meryl A.; Hinrichsen, Gregory A.

    2009-01-01

    This study of 130 depressed older adults and their spouses or adult children examined the impact of caregiver burden specific to patients’ depressive symptoms on patients’ response to antidepressant treatment. Primary care patients completed medical, psychiatric, and neuropsychological assessments prior to treatment, and interviews were conducted with their identified family member. As hypothesized, caregivers’ depression-specific burden predicted greater depression severity for the patient at the 6th week of treatment after accounting for patients’ pretreatment characteristics, caregivers’ depressive symptoms, and caregivers’ relationship satisfaction. Future research may identify family attitudes and behaviors that stem from burden and compromise older adults’ ability to recover from depression. PMID:18573018

  6. Effects of Nerve Growth Factor on Bcl-2 Protein after Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    汤长华; 曹晓建; 王道新

    2002-01-01

    Objective To explore the protective mechanisms of nerve growth factor( NGF) ou spinal cord injury(SCI) and provide theoretical basis for its clinical application. MethodsThe SCI of Wistar rats was done by Allens weight dropping way by a 10 g × 2.5 cm impact on theposterior of spinal cord T8 NGF ( 3 g/L, 20d) or normal saline was injected to treatment group ratsthrough catheter into subarachnoid space at 0,2,4,8,12 and 24 h after SCI. The expression of bcl-2 protein levels in rat spinal cord was detected by immunohistoclemistry. Results The strong expres-sion sequence of bcl-2 protein was found in spinal cord of normal rat group. The levels of bcl-2 pro-tein after SCI in NGF treatment group increased more significantly than those in normal saline treatmentgroup (P<0. 01). Conclusion NGF could protect injured spinal cord by stimulating bcl-2 pro-tein expression and suppressing apoptosis after SCI.

  7. Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis

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    Özdemir B Handan

    2006-06-01

    Full Text Available Abstract Background Apoptosis, or programmed cell death is a form of physiological cell death. It is increased or decreased in the presence of infection, inflammation or tissue remodelling. Previous studies suggest that apoptosis is involved in the pathogenesis of inflammatory periodontal disease. The aim of the present study was to investigate the clinical features and known indicators of apoptosis (p53, Bcl-2, Caspase-3 in patients with generalized aggressive periodontitis (GAP Methods Eight patients with GAP, who had sites with probing depths (PD > 5 mm, and 10 periodontally-healthy persons were included in the study. Clinical examinations and PD were performed, and the plaque index and gingival index were recorded. Gingival tissues biopsies were obtained from active site of each patient and from healthy individuals. The expression of caspase-3, Bcl-2, and p53 was evaluated by immunohistochemistry Results There were no significant differences between GAP and control group with respect to levels of caspase-3 and p53 expression (P > 0.05. Contrary, the frequency of grade 3 expression of Bcl-2 was higher in GAP group than the control group. Conclusion The higher frequency of Bcl-2 expression in GAP group indicates and delayed apoptosis can lead to increasing resident inflammatory cells in periodontal tissues and resulting in progressive periodontal destruction.

  8. miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer

    Science.gov (United States)

    Sacconi, A; Biagioni, F; Canu, V; Mori, F; Di Benedetto, A; Lorenzon, L; Ercolani, C; Di Agostino, S; Cambria, A M; Germoni, S; Grasso, G; Blandino, R; Panebianco, V; Ziparo, V; Federici, O; Muti, P; Strano, S; Carboni, F; Mottolese, M; Diodoro, M; Pescarmona, E; Garofalo, A; Blandino, G

    2012-01-01

    Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Here, we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out of 123 tumoral and matched uninvolved peritumoral gastric specimens from three independent European subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. miR-204 falls into a group of eight miRs differentially expressed between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic value and correlates with increased staining of Bcl-2 protein in tumoral specimens. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil. Altogether, these findings suggest that modulation of aberrant expression of miR-204, which in turn releases oncogenic Bcl-2 protein activity might hold promise for preventive and therapeutic strategies of GC. PMID:23152059

  9. Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.

    Directory of Open Access Journals (Sweden)

    Jihye Kim

    Full Text Available Recent reports have shown that cannabinoid 1 receptors (CB1Rs are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.

  10. CO-EXPRESSIONS OF SURVIVIN GENE,BCL-2 AND BAX PROTEINS IN OVARIAN CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    林蓓; 张淑兰; 赵长清

    2004-01-01

    Objective To characterize the cellular properties of ovarian cancer, we examined the correlation between the expression of apoptosis-related gene survivin and those of Bcl-2 and Bar proteins. Methods Expressions of survivin mRNA, and Bcl-2 and Bax proteins in 35 cases of ovarian carcinoma, 10 cases of borderline carcinoma, 10 cases of benign tumors and 10 cases of normal tissue were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry SABC method, respectively. Results Expression of survivin gene was detected in a significantly greater proportion in ovarian carcinoma and borderline carcinoma than those in benign tumors and normal tissues. Although there was no relationship between expression of survivin gene and FIGO stage, histologic grade, pathological type and lymphatic metastasis, expressions of Bcl-2 and Bar proteins were positively and negatively correlated with that of survivin gene, respectively. Conclusion Survivin may play an important role in pathogenesis of ovarian carcinoma, with a synergistic role of apoptosis-related gene Bcl-2protein and an antagonistic role of Bax protein in formation and progression of ovarian carcinoma.

  11. Small interfering RNA of cyclooxygenase-2 induces growth inhibition and apoptosis independently of Bcl-2 in human myeloma RPMI8226 cells

    Institute of Scientific and Technical Information of China (English)

    Qiu-bai LI; Zhi-chao CHEN; Yong YOU; Ping ZOU

    2007-01-01

    Aim: To investigate the effects of small interfering RNA of cyclooxygenase-2 (COX-2) on the proliferation and apoptosis of human multiple myeloma RPMI8226 cells and its relation with the Bcl-2 family in vitro. Methods: Transcription and expression of COX-2 in human myeloma RPMI8226 cells were checked by RT-PCR and Western blot analysis, respectively. The COX-2 siRNA fragment targeting exon 5 of COX-2 gene was transfected into the cells with the Amaxa nucleofection technique. The inhibition of cell growth was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was estimated by Annexin-V/propidium iodide double-labeled cytometry and confirmed by termi-nal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Bcl-2 and Bax expression was evaluated by Western blot analysis. Results: The COX-2 siRNA fragment could be successfully transfected into RPMI8226 cells, which resulted in the significant inhibition of transcription and expression of COX-2 in the myeloma cells. Proliferation of the transfected cells was inhibited and apoptosis was induced (6.52%±0.32%, 12.53%±2.52%, 24.39%±3.51% and 36.48%±4.96% for 0, 12, 24, and 48 h, respectively) in a time-dependent manner (P<0.01), However, the expression of Bcl-2 and Bax in the RPMI8226 cells had no significant changes after nucleofection. Conclusion: COX-2 siRNA transfection can suppress COX-2 expression in human myeloma RPMI8226 cells, which leads to growth inhibition and apoptosis independent of Bcl-2.

  12. Folie a Famille: Delusional parasitosis affecting all the members of a family

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    Daniel Elizabeth

    2004-09-01

    Full Text Available Delusional parasitosis (Ekbom syndrome is an uncommon psychiatric disorder that presents with a delusion of being infested with parasites. Treatment of this condition is difficult as patients with this paranoid disorder reject psychiatric diagnosis and treatment and often consult a dermatologist. Sharing the delusional beliefs of the paranoid patient by other people living in close emotional bonding with him/her could occur. We report here the clinically interesting phenomenon of delusion of parasitosis occurring simultaneously in all the members of a family. There was a pathological bonding between the members of the family who all presented to the dermatologist and rejected treatment. Dermatologists need to be aware of this uncommon clinical picture.

  13. Marriage and family therapy faculty members' balance of work and personal life.

    Science.gov (United States)

    Matheson, Jennifer L; Rosen, Karen H

    2012-04-01

    A sense of imbalance is common among both professors and therapists, though few studies have been published examining the work and personal life balance of those who work in both professions simultaneously. Using in-depth telephone interviews, this study examined the work and personal life balance of 16 marriage and family therapy (MFT) faculty members. Results showed that six were satisfied with their balance, six were dissatisfied, and four were "middle of the road." Men, older participants, and those who were in their career longer were more likely to report feeling satisfied with their balance. Internal indicators of their balance included family and workplace messages, health indicators, feelings of contentment, and congruence with personal values. Child and relationship status, tenure status, and gender issues also impacted their sense of balance. Specific balance enhancers and reducers were highlighted, and participants discussed coping strategies and recommendations for other MFT faculty members. Clinical, training, and career implications are discussed. PMID:22512300

  14. Cloning and characterization of a novel member of human β-1,4-galactosyltransferase gene family

    Institute of Scientific and Technical Information of China (English)

    范玉新; 余龙; 张琪; 江萤; 戴方彦; 陈驰原; 屠强; 毕安定; 许月芳; 赵寿元

    1999-01-01

    By using the EST strategy for identifying novel members belonging to homologous gene families, a novel full-length cDNA encoding a protein significantly homologous to UDP-Gal: N-acetylglucosamine β-1, 4-galactosyltransferase (GAlT) was isolated from a human testis cDNA library. A nucleotide sequence of 2 173 bp long was determined to contain an open reading frame of 1032 nucleotides (344 amino acids). In view of the homology to members of the galactosyltransferase gene family and especially the closest relationship to Gallus gallus GalT type I (CK I), the predicted product of the novel cDNA was designated as human β-1, 4-galactosyltransferase homolog I (HumGT-H1). Its mRNA is present in different degrees in 16 tissues examined. Southern analysis of human genomic DNA revealed its locus on chromosome 3.

  15. Compassion Fatigue: An Application of the Concept to Informal Caregivers of Family Members with Dementia

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    Jennifer R. Day

    2011-01-01

    Full Text Available Introduction. Compassion fatigue is a concept used with increasing frequency in the nursing literature. The objective of this paper is to identify common themes across the literature and to apply these themes, and an existing model of compassion fatigue, to informal caregivers for family members with dementia. Findings. Caregivers for family members with dementia may be at risk for developing compassion fatigue. The model of compassion fatigue provides an informative framework for understanding compassion fatigue in the informal caregiver population. Limitations of the model when applied to this population were identified as traumatic memories and the emotional relationship between parent and child, suggesting areas for future research. Conclusions. Research is needed to better understand the impact of compassion fatigue on informal caregivers through qualitative interviews, to identify informal caregivers at risk for compassion fatigue, and to provide an empirical basis for developing nursing interventions for caregivers experiencing compassion fatigue.

  16. Family Quality of Life from the Perspectives of Individual Family Members: A Korean-American Family and Deafness

    Science.gov (United States)

    Hong, Joo Young; Turnbull, Ann

    2013-01-01

    Beginning in the mid-to-late 1980s, the focus on individual quality of life expanded to family quality of life (FQOL) in the field of intellectual disabilities. However, few studies examined FQOL for families who have children with hearing loss. Furthermore, most studies focused on mothers' perceptions of FQOL. The purpose of this study is to…

  17. Expression of activator protein-1 (AP-1) family members in breast cancer

    International Nuclear Information System (INIS)

    The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer

  18. Habitat Segregation and Biochemical Activities of Marine Members of the Family Vibrionaceae

    OpenAIRE

    Simidu, Usio; Tsukamoto, Kumiko

    1985-01-01

    A comparative study of marine members of the family Vibrionaceae with the technique of numerical taxonomy revealed habitat segregation as well as a cosmopolitan nature of species distribution among the vibrios in different marine environments. The bacterial strains analyzed were isolated from seawater, sediments, phyto- and zooplankton, and fish in the Indian Ocean, the South and East China Sea, and West Pacific Ocean, and coastal areas of Japan. A total of 155 morphological, physiological, a...

  19. Prevalence of Helicobacter pylori in Children and Their Family Members in a District in Turkey

    OpenAIRE

    CEYLAN, Abdullah; Kırımi, Ercan; Tuncer, Oğuz; Türkdoğan, Kürşat; Arıyuca, Sevil; Ceylan, Nesrin

    2007-01-01

    The aim of this study was to determine the prevalence of Helicobacter pylori among children and their family members and to evaluate some epidemiologic characteristics. The study included 275 children, aged 1-15 year(s), suffering from different gastrointestinal complaints. Blood serology and stool antigen testing were used for the diagnosis of infection due to H. pylori. Sixty-five (23.6%) of the 275 children were positive for H. pylori, and this positivity had a significantly increasing cor...

  20. Pulmonary hyalinizing granuloma detected in a family member after confirmation of tuberculosis in his father.

    Science.gov (United States)

    Matsuoka, Katsunari; Imanishi, Naoko; Matsuoka, Takahisa; Nagai, Shinjiro; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is an uncommon lung disease that usually presents as bilateral multiple nodules, and more rarely as a solitary nodule. An exaggerated immune response to antigenic stimuli resulting from infection or an autoimmune process has been suggested as the cause of PHG. Here, we describe a rare case of solitary PHG that was detected in a family member after tuberculosis had been confirmed in his father, without any background of infectious disease or autoimmune abnormality. PMID:23903707

  1. Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family

    OpenAIRE

    Anwar, Sabina; Peters, Owen; Millership, Steven; Ninkina, Natalia; Doig, Natalie; Connor-Robson, Natalie; Threlfell, Sarah; Kooner, Gurdeep; Deacon, Robert M.; Bannerman, David M.; Bolam, J. Paul; Chandra, Sreeganga S.; Cragg, Stephanie J.; Wade-Martins, Richard; Buchman, Vladimir L.

    2011-01-01

    The synucleins (α, β and γ) are highly homologous proteins thought to play a role in regulating neurotransmission and are found abundantly in presynaptic terminals. To overcome functional overlap between synuclein proteins and to understand their role in presynaptic signalling from mesostriatal dopaminergic neurons, we produced mice lacking all three members of the synuclein family. The effect on the mesostriatal system was assessed in adult (4-14 month old) animals using a combination of beh...

  2. Draft Genome Sequence of Tokyovirus, a Member of the Family Marseilleviridae Isolated from the Arakawa River of Tokyo, Japan

    Science.gov (United States)

    2016-01-01

    Members of the Marseilleviridae family are large DNA viruses with icosahedral particles that infect Acanthamoeba cells. This report presents a new Marseilleviridae family member discovered in a water/soil sample from a river in Tokyo, named Tokyovirus, with genome size of 370 to 380 kb. PMID:27284144

  3. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

    International Nuclear Information System (INIS)

    Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients

  4. Association between family members of dialysis patients and chronic kidney disease: a multicenter study in China

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    Kong Xianglei

    2013-01-01

    Full Text Available Abstract Background Family members of patients with end stage renal disease were reported to have an increased prevalence of chronic kidney disease (CKD. However, studies differentiated genetic and non-genetic family members are limited. We sought to investigate the prevalence of CKD among fist-degree relatives and spouses of dialysis patients in China. Methods Seventeen dialysis facilities from 4 cities of China including 1062 first-degree relatives and 450 spouses of dialysis patients were enrolled. Sex- and age- matched controls were randomly selected from a representative sample of general population in Beijing. CKD was defined as decreased estimated glomerular (eGFR 2 or albuminuria. Results The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis spouses were compared with their counterpart controls, which was 3.8% vs. 7.8% (P 2, albuminuria and the overall prevalence of CKD in dialysis relatives were also compared with their counterpart controls, which was 1.5% vs. 2.4% (P = 0.12, 14.4% vs. 8.4% (P  Conclusions The association between being family members of dialysis patients and presence of CKD is different between first-degree relatives and spouses. The underlying mechanisms deserve further investigation.

  5. Ginsenoside Rh2 Mitigates Pediatric Leukemia Through Suppression of Bcl-2 in Leukemia Cells

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    Xiaoru Wang

    2015-09-01

    Full Text Available Background/Aims: Acute myeloid leukemia (AML is a severe malignant cancer worldwide, in both adult and pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia remains challenging. Ginsenoside Rh2 (GRh2 is a well-characterized component in red ginseng, and has established therapeutic effects for different diseases, although whether GRh2 may have a therapeutic effect on pediatric leukemia has not been investigated. Methods: We examined the effects of GRh2 on the survival of mice in an acute leukemia model. We analyzed the effects of GRh2 on the cell viability of leukemia cell lines in vitro, using a CCK-8 assay and an MTT assay. We analyzed the effects of GRh2 on the apoptosis of leukemia cell lines in vitro, by flow cytometry. We analyzed the levels of Bcl-2 and microRNA-21 (miR-21 in GRh2-treated leukemia cells. Prediction of binding between miR-21 and 3'-UTR of Bcl-2 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: GRh2 significantly prolonged the survival of mice with pediatric leukemia. GRh2 significantly decreased the viability of leukemia cells in vitro, through induction of apoptosis. GRh2 significantly decreased the levels of an anti-apoptotic protein Bcl-2 in leukemia cells, possibly through induction of miR-21, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. Conclusion: GRh2 may be an effective treatment for pediatric leukemia, and GRh2 may induce apoptosis of leukemia cells through miR-21-modulated suppression of Bcl-2.

  6. PPAR-γ Silencing Inhibits the Apoptosis of A549 Cells by Upregulating Bcl-2

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    Jingyu YANG

    2013-03-01

    Full Text Available Background and objective Drug resistance is the one of primary causes of death in patients with lung cancer, PPAR-γ could induce the apoptosis and reverse drug resistance. The aim of this study is to investigate the expression of PPAR-γ on cisplatin sensitivity and apoptosis response of human lung cancer cell line A549. Methods Reconstruction of PPAR-γ silencing A549 cells (A549/PPAR-γ(- by siRNA. MTT assay was employed to determine the effect of cisplatin on the proliferation of A549/PPAR-γ(-, flow cytometry to determine the effect of cisplatin on the cell apoptosis, Western blot to determine the change of phosphorylation of Akt, caspase-3 and expression of bcl-2/bax. Finally, RT-PCR was employed to determine the transcriptional level of bcl-2. Results Two PPAR-γ silencing A549 cell clones were established successfully, and the expression of PPAR-γ was downregulated significantly as confirmed by RT-PCR and Western blot. After PPAR-γ silencing, the resistance of these two A549 clones to cisplatin was increased by 1.29-fold and 1.60-fold respectively. Flow cytometry showed that the apoptosis rate was decreased, and Western Blot showed that the phosphorylation of Akt and expression of bcl-2/bax were upregulated, caspase-3 was downregulated. Finally, RT-PCR showed that the transcriptional level of bcl-2 was upregulated as well. Conclusion Downregulation of PPAR-γ in A549 cells led to increase of cisplatin resistance. One of the mechanisms was upregulatin of phosphorylation of Akt and expression of bcl-2, which inhibited the apoptosis of cells. The downregulation of PPAR-γ is a possible mechanism that leads to the clinical drug resistance of cancer.

  7. Autophagy blockade sensitizes the anticancer activity of CA-4 via JNK-Bcl-2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yangling; Luo, Peihua; Wang, Jincheng; Dai, Jiabin; Yang, Xiaochun; Wu, Honghai; Yang, Bo, E-mail: yang924@zju.edu.cn; He, Qiaojun, E-mail: qiaojunhe@zju.edu.cn

    2014-01-15

    Combretastatin A-4 (CA-4) has already entered clinical trials of solid tumors over ten years. However, the limited anticancer activity and dose-dependent toxicity restrict its clinical application. Here, we offered convincing evidence that CA-4 induced autophagy in various cancer cells, which was demonstrated by acridine orange staining of intracellular acidic vesicles, the degradation of p62, the conversion of LC3-I to LC3-II and GFP-LC3 punctate fluorescence. Interestingly, CA-4-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitors (3-methyladenine and bafilomycin A1) or small interfering RNAs against the autophagic genes (Atg5 and Beclin 1). The enhanced anticancer activity of CA-4 and 3-MA was further confirmed in the SGC-7901 xenograft tumor model. These findings suggested that CA-4-elicited autophagic response played a protective role that impeded the eventual cell death while autophagy inhibition was expected to improve chemotherapeutic efficacy of CA-4. Meanwhile, CA-4 treatment led to phosphorylation/activation of JNK and JNK-dependent phosphorylation of Bcl-2. Importantly, JNK inhibitor or JNK siRNA inhibited autophagy but promoted CA-4-induced apoptosis, indicating a key requirement of JNK-Bcl-2 pathway in the activation of autophagy by CA-4. We also identified that pretreatment of Bcl-2 inhibitor (ABT-737) could significantly enhance anticancer activity of CA-4 due to inhibition of autophagy. Taken together, our data suggested that the JNK-Bcl-2 pathway was considered as the critical regulator of CA-4-induced protective autophagy and a potential drug target for chemotherapeutic combination. - Highlights: • Autophagy inhibition could be a potential for combretastatin A-4 antitumor efficacy. • The JNK-Bcl-2 pathway plays a critical role in CA-4-induced autophagy. • ABT-737 enhances CA-4 anticancer activity due to inhibition of autophagy.

  8. Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients

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    Pentilas Nikolaos

    2010-04-01

    Full Text Available Abstract Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited. p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers, using beta-actin as internal control. Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals. Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038, while bcl2 protein levels were not statistically different between the two groups. Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01, whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups. On the other hand, bcl2 expression did not differ between the two groups in all three cell types. The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients. Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD.

  9. Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

    International Nuclear Information System (INIS)

    Tissue factor (TF) is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa), initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry) respectively. Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. We surmise that this TF

  10. Expression of Ki-67, Bcl-2 and Bax in the First Trimester Abortion Materials

    Directory of Open Access Journals (Sweden)

    Ender DÜZCAN

    2010-01-01

    Full Text Available Objective: The aim of this study was to investigate possible similar or different mechanisms in recurrent and spontaneous abortion by evaluating immunohistochemical correlation between proliferation marker Ki-67, and apoptosis markers Bcl-2 and Bax in the fetal trophoblasts and maternal deciduas from abortion material.Material and Method: Eighty samples of curettage materials from 65 abortion patients histopathologically diagnosed “decidua showing Arias-Stella reaction and chorionic villi” or only “decidua showing Arias-Stella reaction” were included in the study. Hematoxylin&Eosin stained sections from all cases were re-evaluated and further stained immunohistochemically using antibodies against Ki-67, Bcl-2 and Bax.Results: Proliferation rate evaluated by Ki-67 expression both in the cytotrophoblastic cells and decidua was found to be significantly lower in spontaneous and recurrent abortions compared to evacuation abortion. The extent of Bcl-2 expression in syncytiotrophoblastic cells covering villous stroma was also decreased in spontaneous abortion. There were no significant differences between spontaneous and recurrent abortions in terms of Bcl-2 expression in syncytiotrophoblasts and Ki-67 proliferation index in cytotrophoblastic cells or decidua. Bax staining showed minimal decidual expression in a few spontaneous and recurrent abortions.Conclusion: We concluded that proliferation rate was decreased in fetal villous cytotrophoblasts and maternal deciduas in spontaneous and recurrent abortions. We also proposed that loss of Bcl-2 expression in syncytiotrophoblasts may cause abortion in a subset of cases. However, the data from spontaneous and recurrent abortions did not not support the presence of different mechanisms in both groups.

  11. bcl-2在受损面神经运动神经元中的表达与定位%Expression of bcl-2 in facial motoneurons and its ultrastructural localization following facial nerve injury

    Institute of Scientific and Technical Information of China (English)

    戴春富; 黄新生; 王正敏; 李宽俨; 赵晖

    2001-01-01

    Objective To explore the expression of bcl-2 in facial motoneurons and its subcellular distribution. Methods Wistar rats were used in this study. Facial nerve transection was performed at stylomastoid foramen or internal acoustic meatus. Facial nerve crush was made at stylomastiod foramen. The animal survived for 1, 3, 7, 15, 30 and 60 days respectively. Facial nucleus was treated with bcl-2 monoclonal antibody or bcl-2 DIG-labelling probe and studied with immunohistochemstry and in situ hybridization. The bcl-2 positive motoneuron was investigated with immuno-electron microscope. Results It was demonstrated that bcl-2 protein level was corresponded with bcl-2 mRNA expression. The level of bcl-2 expression in facial motoneurons was high in normal facial nerve. It increased on the first day and declined on the third day post-transection in facial motoneuron. It reached the lowest level on the 15th days following facial nerve injury (P0.05). After facial nerve transected, the reduction of bcl-2 expression was more significant when facial nerve transected close to facial nucleus than that far from facial nucleus (P0.05)。bcl-2的表达同损伤程度和损伤部位有关(0.01bcl-2 mRNA和bcl-2蛋白表达一致。免疫电镜发现bcl-2蛋白主要定位于神经元胞体中的线粒体、内质网和核膜上。结论 bcl-2转录和翻译可能同面神经核团中运动神经元胞体的死亡相关。通过转基因技术调节bcl-2基因的表达,可能为临床面瘫的治疗提供新的手段。

  12. Expression and significance of β-catenin,Bcl-2 and Bax in basal cell carcinoma%β-catenin和Bcl-2、Bax蛋白在皮肤基底细胞癌中的表达和意义

    Institute of Scientific and Technical Information of China (English)

    黄卡特; 吕明芬; 徐云升; 邹炳辉

    2010-01-01

    目的:探讨皮肤基底细胞癌(basal cell carcinoma,BCC)中β-catenin和Bcl-2、Bax蛋白的表达与BCC发生发展的关系.方法:采用免疫组化方法检测BCC组织切片中β-catenin和Bcl -2、Bax蛋白的表达.结果:48例BCC标本中β-catenin蛋白的异常表达率为91.67%,Bcl -2、Bax蛋白的表达率分别为89.58%、62.5%,且Bcl-2与Bax蛋白的表达呈负相关.结论:β-catenin和Bcl-2、Bax蛋白的异常表达在BCC的发生、发展中起重要作用.

  13. Number of Family Members, a New Influencing Factor to Affect the Risk of Melamine-Associated Urinary Stones

    Directory of Open Access Journals (Sweden)

    Changjiang Liu

    2013-06-01

    Full Text Available Melamine is a new risk of urinary stones. Gansu province is a heavily affected area and has large population and underdeveloped economy. We hypothesized that number of family members and family income may play significant roles in the formation of urinary stones. A case-control study was performed among 190 infants. Results showed that the case group had less numbers of family members than the control (4.4 vs. 5.6, respectively. The multivariate logistic regression analysis indicated that number of family members was an independent influencing factor associated with urinary stones (OR, 0.606; 95% CI, 0.411-0.893; P = 0.011. Family income, however, did not exhibit a significant difference. Observed results suggested that number of family members was a new and significant influencing factor to affect the risk of melamine-associated urinary stones.

  14. An innovative program of counseling family members and friends of seropositive haemophiliacs.

    Science.gov (United States)

    Greenblat, C S; Katz, S; Gagnon, J H; Shannon, D

    1989-01-01

    This paper describes current efforts to construct a set of innovative educational and skill building materials targetted at groups of persons with HIV infection, those at risk for HIV, their families and friends, and health professionals. The ENCOUNTERS family of interactive simulations is designed to provide participants with the necessary communication and behavioral skills to deepen their understanding of HIV, to improve their interaction with others in their interpersonal environment, and to more effectively manage stress generated by HIV concerns The ENCOUNTERS family of simulations are built on the principles of role play, but adds to them principles of simulation gaming. The former technique is strengthened by offering active participation for all group members, increased structure, and the opportunity for participants to take different perspectives on an issue of concern in a supportive small group environment. PMID:2488583

  15. Assessing family members' motivational readiness and decision making for consenting to cadaveric organ donation.

    Science.gov (United States)

    Robbins, M L; Levesque, D A; Redding, C A; Johnson, J L; Prochaska, J O; Rohr, M S; Peters, T G

    2001-09-01

    This study assessed the applicability of two important components of the transtheoretical model of behavior change (TTM) to family consent for cadaveric organ donation. Men and women (N = 169), who consented or refused to donate the organs of a family member, completed a telephone survey reflecting the stage of change and decisional balance constructs. Psychometric analyses resulted in a two-factor decisional balance scale: a seven-item scale representing negative perceptions of consent (cons), and a seven-item scale representing positive perceptions of consent (pros). The pros and cons were significantly associated with stage of readiness for donation consent and with the family consent decision. Research utilizing this measure has the potential to enhance intervention programs to increase donation consent rates. PMID:22049451

  16. PE-1, a novel ETS oncogene family member, localizes to chromosome 1q21-q23

    Energy Technology Data Exchange (ETDEWEB)

    Klemsz, M.; Hromas, R.; Bruno, E.; Hoffman, R. (Indiana Univ., Indianapolis, IN (United States)); Raskind, W. (Univ. of Washington School of Medicine, Seattle, WA (United States))

    1994-03-15

    The v-ets oncogene family shares a conserved peptide motif called the ETS domain that mediates sequence-specific DNA binding. This motif is unique among transcription factor families. Using partially degenerate oligonucleotides from conserved regions of the ETS domain and the polymerase chain reaction, the authors isolated a new member of v-ets family designated PE-1 from HL60 cells. PE-1 was expressed as an approximately 7.5-kb transcript in most cell lines tested. In the hairy cell leukemia line Eskol, there was an additional 1.8-kb transcript observed. PE-1 was the most common ETS domain gene found in CD34[sup +]HLA-DR[sup [minus

  17. Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Kramer, M.H.H.; Hermans, J; Wijburg, E; Philippo, K; Geelen, E; van Krieken, J.H.J.M.; de Jong, D; Maartense, E; Schuuring, E; Kluin, P M

    1998-01-01

    Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the pr

  18. p53 family members regulate the expression of the apolipoprotein D gene.

    Science.gov (United States)

    Sasaki, Yasushi; Negishi, Hideaki; Koyama, Ryota; Anbo, Naoki; Ohori, Kanae; Idogawa, Masashi; Mita, Hiroaki; Toyota, Minoru; Imai, Kohzoh; Shinomura, Yasuhisa; Tokino, Takashi

    2009-01-01

    p73 and p63 are members of the p53 gene family that play an important role in development and homeostasis, mainly by regulating transcription of a variety of genes. We report here that apolipoprotein D (apoD), a member of the lipocalin superfamily of lipid transport proteins, is a direct transcriptional target of the p53 family member genes. We found that the expression of apoD was specifically up-regulated by either TAp73 or TAp63 but not significantly by p53. In addition, apoD transcription is activated in response to cisplatin in a manner dependent on endogenous p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abolishes induction of apoD transcription following cisplatin treatment. We also identified a p73/p63-binding site in the promoter of the apoD gene that is responsive to the p53 family members. The ectopic expression of TAp73 as well as the addition of recombinant human apoD to culture medium induced the osteoblastic differentiation of the human osteosarcoma cell line Saos-2, as assessed by alkaline phosphatase activity. Importantly, apoD knockdown abrogated p73-mediated alkaline phosphatase induction. Moreover, TAp73-mediated apoD expression was able to induce morphological differentiation, as well as expression of neuronal markers, in the human neuroblastoma cell line SH-SY5Y. These results suggest that apoD induction may mediate the activity of p73 in normal development. PMID:19001418

  19. Intra-familial prevalence of hepatitis B virologic markers in HBsAg positive family members in Nahavand, Iran

    Institute of Scientific and Technical Information of China (English)

    Amir Houshang Mohammad Alizadeh; Mitra Ranjbar; Shahin Ansari; Seyed Moayed Alavian; Hamid Mohaghegh Shalmani; Leila Hekmat; Mohammad Reza Zali

    2005-01-01

    AIM: To determine the prevalence of hepatitis B in Nahavand and evaluate the HBsAg positive prevalence in families with a member who was confirmed to have HBV infection.METHODS: This study was performed in two phases. In the first phase, 1 824 subjects in Nahavand city were selected. The interviewers visited the houses of chosen families to fill the questionnaire and take the blood samples.All subjects signed an informed consent before interviews and blood sampling. The samples were evaluated for HBV virologic markers. In the second phase, 115 HBsAg-positive cases were enrolled and evaluated for HBV virologic markers.RESULTS: The prevalence of positive HBsAg in Nahavand was 2.3%. The most frequent relatives of index cases were sons and daughters (32.2% and 23.5% respectively).Twelve (11%) of all family members were HBsAg positive.Fifty (56.2%) were isolated HBsAb positive and only one person (2.5%) was isolated HBcAb positive. The higher rates of HBsAg marker were detected in the brothers (1-25%) and fathers (1-12.5%). The infection rate in husbands and wives of index cases was 10%. Only two (16.7%) of all HBsAg-positive participants reported previous HBV vaccination.CONCLUSION: The prevalence of intra-familial HBV infection is lower in Nahavand of Iran compared to other studies.More attention should be paid to HBV vaccination and risk-lowering activities.

  20. Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization.

    Science.gov (United States)

    Romero, F; Martínez-A, C; Camonis, J; Rebollo, A

    1999-01-01

    We searched for proteins that interact with Ras in interleukin (IL)-2-stimulated or IL-2-deprived cells, and found that the transcription factor Aiolos interacts with Ras. The Ras-Aiolos interaction was confirmed in vitro and in vivo by co-immunoprecipitation. Indirect immunofluorescence shows that IL-2 controls the cellular distribution of Aiolos and induces its tyrosine phosphorylation, required for dissociation from Ras. We also identified functional Aiolos-binding sites in the Bcl-2 promoter, which are able to activate the luciferase reporter gene. Mutation of Aiolos-binding sites within the Bcl-2 promoter inhibits transactivation of the reporter gene luciferase, suggesting direct control of Bcl-2 expression by Aiolos. Co-transfection experiments confirm that Aiolos induces Bcl-2 expression and prevents apoptosis in IL-2-deprived cells. We propose a model for the regulation of Bcl-2 expression via Aiolos. PMID:10369681

  1. Magnitude of the smoking problem, knowledge, attitude and practice, among family members of primary school students

    Directory of Open Access Journals (Sweden)

    Babak Nakhostin-Roohi

    2013-06-01

    Full Text Available Background: smoking is a very important public health problem, urgently requiring immediate and effective measures due to its harmful effect on health. The purpose of this study was to collect baseline information about the magnitude of smoking problem, knowledge, attitude, and practice among family members of primary school students in the northwest region of Iran.Methods: of 55 680 primary school students (the 3th, 4th and 5th grades, 7.1% (n=3 954 were selected using randomized multi-stage cluster sampling. Data collection was conducted in April, May, and June 2011, by means of a self-administered two-page questionnaire.Results: a total of 3 954 students (57.6% boys and 42.3% girls with the mean age of 10.46±1.09 years were evaluated. According to our data, the prevalence of cigarette smoking among fathers was more than other family members (27.1% versus 17.8% whereas the prevalence of water pipe smoking among fathers and other family members was almost similar (9.2% and 9.7% respectively. None of the smoking type was prevalent among mothers (cigarette: 1% and water pipe: 1.1%. Considerable numbers of all students under study had been exposed to secondhand smoke at home (cigarette: 19.8% and water pipe: 7.7%.Conclusions: considering our findings, two procedures recommended to prevail the problem are to provide greater education about hazards of tobacco consumption among students and their family; and to legislate new laws by officials to ban tobacco use at home.

  2. A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899

    Directory of Open Access Journals (Sweden)

    Carducci Michael

    2010-02-01

    Full Text Available Abstract Background To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA/interferon-alpha2b (IFN with paclitaxel (TAX, or mitoxantrone, estramustine and vinorelbine (MEV will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC. Methods 70 patients were treated with either MEV (Arm A in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B. Patients were assessed for response, toxicity, quality of life (QOL, and the effect of treatment on Bcl-2 levels in peripheral blood mononuclear cells (PBMC. Results The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d., and a significantly lower level of QOL than Arm A (p = 0.01. As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03. Conclusions Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy. Trial Registration Clinical Trials Registration number: CDR0000067865

  3. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer

    International Nuclear Information System (INIS)

    A number of protein markers have been investigated as prognostic adjuncts in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. Recently, we showed that BCL2 protein expression had prognostic power independent of current used standards. Here, we present the results of a meta-analysis of the association between BCL2 expression and both disease free survival (DFS) and overall survival (OS) in female breast cancer. Reports published in 1994–2006 were selected for the meta-analysis using a search of PubMed. Studies that investigated the role of BCL2 expression by immunohistochemistry with a sample size greater than 100 were included. Seventeen papers reported the results of 18 different series including 5,892 cases with an average median follow-up of 92.1 months. Eight studies investigated DFS unadjusted for other variables in 2,285 cases. The relative hazard estimates ranged from 0.85 – 3.03 with a combined random effects estimate of 1.66 (95%CI 1.25 – 2.22). The effect of BCL2 on DFS adjusted for other prognostic factors was reported in 11 studies and the pooled random effects hazard ratio estimate was 1.58 (95%CI 1.29–1.94). OS was investigated unadjusted for other variables in eight studies incorporating 3,910 cases. The hazard estimates ranged from 0.99–4.31 with a pooled estimate of risk of 1.64 (95%CI 1.36–2.0). OS adjusted for other parameters was evaluated in nine series comprising 3,624 cases and the estimates for these studies ranged from 1.10 to 2.49 with a pooled estimate of 1.37 (95%CI 1.19–1.58). The meta-analysis strongly supports the prognostic role of BCL2 as assessed by immunohistochemistry in breast cancer and shows that this effect is independent of lymph node status, tumour size and tumour grade as well as a range of other biological variables on multi-variate analysis. Large prospective studies are now needed to establish the clinical utility of BCL2 as an independent

  4. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer

    Directory of Open Access Journals (Sweden)

    Pharoah Paul DP

    2008-05-01

    Full Text Available Abstract Background A number of protein markers have been investigated as prognostic adjuncts in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. Recently, we showed that BCL2 protein expression had prognostic power independent of current used standards. Here, we present the results of a meta-analysis of the association between BCL2 expression and both disease free survival (DFS and overall survival (OS in female breast cancer. Methods Reports published in 1994–2006 were selected for the meta-analysis using a search of PubMed. Studies that investigated the role of BCL2 expression by immunohistochemistry with a sample size greater than 100 were included. Seventeen papers reported the results of 18 different series including 5,892 cases with an average median follow-up of 92.1 months. Results Eight studies investigated DFS unadjusted for other variables in 2,285 cases. The relative hazard estimates ranged from 0.85 – 3.03 with a combined random effects estimate of 1.66 (95%CI 1.25 – 2.22. The effect of BCL2 on DFS adjusted for other prognostic factors was reported in 11 studies and the pooled random effects hazard ratio estimate was 1.58 (95%CI 1.29–1.94. OS was investigated unadjusted for other variables in eight studies incorporating 3,910 cases. The hazard estimates ranged from 0.99–4.31 with a pooled estimate of risk of 1.64 (95%CI 1.36–2.0. OS adjusted for other parameters was evaluated in nine series comprising 3,624 cases and the estimates for these studies ranged from 1.10 to 2.49 with a pooled estimate of 1.37 (95%CI 1.19–1.58. Conclusion The meta-analysis strongly supports the prognostic role of BCL2 as assessed by immunohistochemistry in breast cancer and shows that this effect is independent of lymph node status, tumour size and tumour grade as well as a range of other biological variables on multi-variate analysis. Large prospective studies are now needed to

  5. Bcl-2 and Ki-67 Expression in Young Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Arsenal Alikanoðlu

    2012-09-01

    Full Text Available Aim:  Incidence of breast cancer increases with age and nearly 85% of them are diagnosed after the age of 50. Clinical outcome of breast cancer  in young patients is worse than older patients. The aim of this study is to search  the  difference in expression of bcl-2 and Ki-67 between young and older women with breast cancer, and  if there is any; its clinical importance. Material and Method: This study includes 15 patients under the age of 35 years old (Group A and 30  patients over the age of 35 years (Group B  all of whom were diagnosed with  breast carcinoma at Antalya Education and Research Hospital between 2008-2011. Results:  Bcl-2 expression was found  positive in 33 (73.3%  and negative in 12  (26.7%  patients.  There were no difference in expression of bcl-2 between Group A and Group B patients (p:0.475. A meaningful  relationship was observed  between expression of bcl-2 and hormon receptors , being more significant in ER (p:0.001,p<0.001. Ki-67 proliferation index was found negative in 8 patients (17.8%, low in  10 patients (22.2% and high in  27  patients (60%. No relationship was found in Ki-67 proliferation index between Group A and Group B patients (p:0.555. There were no meaningful relationship between  Ki-67 proliferation index and bcl-2 expression (p:0.736. In Group A patients a more advanced stage disease was observed. Discussion: DNA microarray studies established that different molecular subtypes in breast cancer are related with different clinical outcome. In our study, no difference was found in bcl-2 and Ki-67 expression searched by immunohistochemical method , between very young (Group A and  other (Group B patients.

  6. 应用bcl-2基因及GDNF治疗大鼠脑缺血的研究%The Effect of bcl-2 Gene and GDNF of Rats after Focal Cerebral Ischemia Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    ZHOU Tie-zhu; FU Xia

    2009-01-01

    目的 观察胶质细胞源性神经营养因子(GDNF)与bcl-2基因对大鼠局灶性脑缺血再灌注损伤(CIRI)的影响.方法 取健康Wistar大鼠40只,采用Longa改良栓线法制成大脑中动脉闭塞(MCAO)模型,缺血2 h后再灌注,随机分4组:对照组、bcl-2组、GDNF组、bcl-2+GDNF组,于再灌注3 h后经侧脑室注射GDNF 10μl、经颈动脉注射pLXSN-bcl-2质粒10μg,MCAO后3d(n=5),14 d(n=5),通过免疫组化染色检测bcl-2蛋白和GDNF的表达情况,TUNEL法检测细胞凋亡情况.结果 bcl-2+GDNF组bcl-2蛋白表达与GDNF表达水平均较其他组表达明显增加(P<0.05),bcl-2组、GDNF组较对照组明显增加(P<0.05);脑内细胞凋亡GDNF+bcl-2组较其他组明显减少(P<0.05),bcl-2组、GDNF组较对照组明显减少(P<0.05).结论 bcl-2基因和GDNF可能通过减少神经细胞凋亡,促进bcl-2与GDNF蛋白表达,增强对局灶性缺血脑组织的保护能力,加速中枢神经损伤的修复;bcl-2基因与GDNF协同作用,促使神经细胞在脑内的凋亡进一步减少,从而避免脑缺血再灌注后脑细胞进一步损伤.

  7. Methionine adenosyltransferase α2 sumoylation positively regulate Bcl-2 expression in human colon and liver cancer cells.

    Science.gov (United States)

    Tomasi, Maria Lauda; Ryoo, Minjung; Ramani, Komal; Tomasi, Ivan; Giordano, Pasquale; Mato, José M; Lu, Shelly C

    2015-11-10

    Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and inhibits apoptosis via Bcl-2 by unknown mechanism. Methionine adenosyltransferase 2A (MAT2A) encodes for MATα2, the catalytic subunit of the MATII isoenzyme that synthesizes S-adenosylmethionine (SAMe). Ubc9, Bcl-2 and MAT2A expression are up-regulated in several malignancies. Exogenous SAMe decreases Ubc9 and MAT2A expression and is pro-apoptotic in liver and colon cancer cells. Here we investigated whether there is interplay between Ubc9, MAT2A and Bcl-2. We used human colon and liver cancer cell lines RKO and HepG2, respectively, and confirmed key finding in colon cancer specimens. We found MATα2 can regulate Bcl-2 expression at multiple levels. MATα2 binds to Bcl-2 promoter to activate its transcription. This effect is independent of SAMe as MATα2 catalytic mutant was also effective. MATα2 also directly interacts with Bcl-2 to enhance its protein stability. MATα2's effect on Bcl-2 requires Ubc9 as MATα2's stability is influenced by sumoylation at K340, K372 and K394. Overexpressing wild type (but not less stable MATα2 sumoylation mutants) protected from 5-fluorouracil-induced apoptosis in both colon and liver cancer cells. Colon cancer have higher levels of sumoylated MATα2, total MATα2, Ubc9 and Bcl-2 and higher MATα2 binding to the Bcl-2 P2 promoter. Taken together, Ubc9's protective effect on apoptosis may be mediated at least in part by sumoylating and stabilizing MATα2 protein, which in turn positively maintains Bcl-2 expression. These interactions feed forward to further enhance growth and survival of the cancer cell.

  8. Characterization of obstructive airway disease in family members of probands with Asthma - An algorithm for the diagnosis of asthma

    NARCIS (Netherlands)

    Panhuysen, CIM; Bleecker, ER; Koeter, GH; Meyers, DA; Postma, DS

    1998-01-01

    To investigate the genetic susceptibility to asthma, we developed an algorithm to classify the phenotype of each family member enrolled in a family study on the genetics of asthma. This algorithm was applied to 92 two-and three-generation families, identified through a subject (proband) with asthma

  9. Complete nucleotide sequence of rose yellow leaf virus, a new member of the family Tombusviridae.

    Science.gov (United States)

    Mollov, Dimitre; Lockhart, Ben; Zlesak, David C

    2014-10-01

    The genome of the rose yellow leaf virus (RYLV) has been determined to be 3918 nucleotides long and to contain seven open reading frames (ORFs). ORF1 encodes a 27-kDa peptide (p27). ORF2 shares a common start codon with ORF1 and continues through the amber stop codon of p27 to encode an 87-kDa (p87) protein that has amino acid similarity to the RNA-dependent RNA polymerase (RdRp) of members of the family Tombusviridae. ORFs 3 and 4 have no significant amino acid similarity to known functional viral ORFs. ORF5 encodes a 6-kDa (p6) protein that has similarity to movement proteins of members of the Tombusviridae. ORF5A has no conventional start codon and overlaps with p6. A putative +1 frameshift mechanism allows p6 translation to continue through the stop codon and results in a 12-kDa protein that has high homology to the carmovirus p13 movement protein. The 37-kDa protein encoded by ORF6 has amino acid sequence similarity to coat proteins (CP) of members of the Tombusviridae. ORF7 has no significant amino acid similarity to known viral ORFs. Phylogenetic analysis of the RdRp amino acid sequences grouped RYLV together with the unclassified Rosa rugosa leaf distortion virus (RrLDV), pelargonium line pattern virus (PLPV), and pelargonium chlorotic ring pattern virus (PCRPV) in a distinct subgroup of the family Tombusviridae. PMID:24838852

  10. The Importance of Older Family Members in Providing Social Resources and Promoting Cancer Screening in Families with a Hereditary Cancer Syndrome

    Science.gov (United States)

    Ashida, Sato; Hadley, Donald W.; Goergen, Andrea F.; Skapinsky, Kaley F.; Devlin, Hillary C.; Koehly, Laura M.

    2011-01-01

    Purpose: This study evaluates the role of older family members as providers of social resources within familial network systems affected by an inherited cancer susceptibility syndrome. Design and Methods: Respondents who previously participated in a study that involved genetic counseling and testing for Lynch syndrome and their family network…

  11. The Influence of Family Therapy on Flexibility and Cohesion among Family Members Seeking Male Residential Treatment for Adolescent and Young Adult Substance Abuse

    Science.gov (United States)

    Marlowe, Stephanie L.

    2011-01-01

    The present study investigated within a substance abuse treatment center the influence of family therapy on flexibility and cohesion among family members. Past studies have suggested adolescents who abuse substances exist in families who have a lack of balance of flexibility and cohesion. Unfortunately, few studies have examined the influence of…

  12. Protein-protein interactions of PDE4 family members - Functions, interactions and therapeutic value.

    Science.gov (United States)

    Klussmann, Enno

    2016-07-01

    The second messenger cyclic adenosine monophosphate (cAMP) is ubiquitous and directs a plethora of functions in all cells. Although theoretically freely diffusible through the cell from the site of its synthesis it is not evenly distributed. It rather is shaped into gradients and these gradients are established by phospodiesterases (PDEs), the only enzymes that hydrolyse cAMP and thereby terminate cAMP signalling upstream of cAMP's effector systems. Miles D. Houslay has devoted most of his scientific life highly successfully to a particular family of PDEs, the PDE4 family. The family is encoded by four genes and gives rise to around 20 enzymes, all with different functions. M. Houslay has discovered many of these functions and realised early on that PDE4 family enzymes are attractive drug targets in a variety of human diseases, but not their catalytic activity as that is encoded in conserved domains in all family members. He postulated that targeting the intracellular location would provide the specificity that modern innovative drugs require to improve disease conditions with fewer side effects than conventional drugs. Due to the wealth of M. Houslay's work, this article can only summarize some of his discoveries and, therefore, focuses on protein-protein interactions of PDE4. The aim is to discuss functions of selected protein-protein interactions and peptide spot technology, which M. Houslay introduced into the PDE4 field for identifying interacting domains. The therapeutic potential of PDE4 interactions will also be discussed. PMID:26498857

  13. Prevalence of Helicobacter pylori in Children and Their Family Members in a District in Turkey

    Science.gov (United States)

    Ceylan, Abdullah; Kırımi, Ercan; Tuncer, Oğuz; Türkdoğan, Kürşat; Arıyuca, Sevil; Ceylan, Nesrin

    2007-01-01

    The aim of this study was to determine the prevalence of Helicobacter pylori among children and their family members and to evaluate some epidemiologic characteristics. The study included 275 children, aged 1-15 year(s), suffering from different gastrointestinal complaints. Blood serology and stool antigen testing were used for the diagnosis of infection due to H. pylori. Sixty-five (23.6%) of the 275 children were positive for H. pylori, and this positivity had a significantly increasing correlation with age (p<0.001). H. pylori-associated infection was observed among 45 (69.2%) and 17 (8%) mothers in the H. pylori-infected and non-infected groups respectively (p<0.0001). Most children and their families infected with H. pylori were living in an urban area. The findings suggest that infection due to H. pylori is a problem for this district area, and all children having any gastrointestinal complaints should be examined whether H. pylori was prevalent among their family members. PMID:18402185

  14. Sun protection and sunbathing practices among at-risk family members of patients with melanoma

    Directory of Open Access Journals (Sweden)

    Heckman Carolyn J

    2011-02-01

    Full Text Available Abstract Background Despite the increased level of familial risk, research indicates that family members of patients with melanoma engage in relatively low levels of sun protection and high levels of sun exposure. The goal of this study was to evaluate a broad range of demographic, medical, psychological, knowledge, and social influence correlates of sun protection and sunbathing practices among first-degree relatives (FDRs of melanoma patients and to determine if correlates of sun protection and sunbathing were unique. Methods We evaluated correlates of sun protection and sunbathing among FDRs of melanoma patients who were at increased disease risk due to low compliance with sun protection and skin surveillance behaviors. Participants (N = 545 completed a phone survey. Results FDRs who reported higher sun protection had a higher education level, lower benefits of sunbathing, greater sunscreen self-efficacy, greater concerns about photo-aging and greater sun protection norms. FDRs who reported higher sunbathing were younger, more likely to be female, endorsed fewer sunscreen barriers, perceived more benefits of sunbathing, had lower image norms for tanness, and endorsed higher sunbathing norms. Conclusion Interventions for family members at risk for melanoma might benefit from improving sun protection self-efficacy, reducing perceived sunbathing benefits, and targeting normative influences to sunbathe.

  15. Compostibacillus humi gen. nov., sp. nov., a member of the family Bacillaceae, isolated from sludge compost.

    Science.gov (United States)

    Yu, Zhen; Wen, Junlin; Yang, Guiqin; Liu, Jing; Zhou, Shungui

    2015-02-01

    Two novel Gram-staining-positive, rod-shaped, endospore-forming and moderately thermophilic bacteria, designated strains DX-3(T) and GIESS002, were isolated from sludge composts from Guangdong Province, China. Analysis of 16S rRNA gene sequences revealed that the isolates were closely related to each other with extremely high similarity (99.6 %), and were members of the family Bacillaceae. However, these two isolates formed a novel phylogenetic branch within this family. Their closest relatives were the members of the genera Ornithinibacillus, Oceanobacillus and Virgibacillus. Cells of both strains were facultatively anaerobic and catalase- and oxidase-positive. The cell-wall peptidoglycan type was A1γ (meso-diaminopimelic acid direct). The predominant isoprenoid quinone was MK-7. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The major cellular fatty acid was iso-C15 : 0. The DNA G+C content was 43.2-43.7 mol%. The results of a polyphasic taxonomic study indicated that strains DX-3(T) and GIESS002 represent a novel species in a new genus in the family Bacillaceae, order Bacillales, for which the name Compostibacillus humi gen. nov., sp. nov. is proposed. The type strain is DX-3(T) ( = KCTC 33104(T) = CGMCC 1.12360(T)). PMID:25358510

  16. HEALTH STATUS OF THE CHILDREN AND THE ADULT MEMBERS OF THE LARGE FAMILIES LIVING IN RURAL AREAS

    OpenAIRE

    Shishkina Irina Vladimirovna; Kapitonov Vladimir Phedorovih; Susloparova Rimma Yevgenyevna

    2012-01-01

    To study the health status of the children and the adult members of the large families living in rural areas we surveyed 770 children and 393 their parents of 204 large families. From among surveyed families 87,7 % made traditional families, and 12,3 % made single-parent families. It was found out that: - the level of general and primary morbidity of the mothers of single-parent families in 1.1 times exceeds the level of traditional families and earlier known in 1,2 times; the rank structure ...

  17. 视网膜母细胞瘤Bcl-2和Bax基因蛋白质表达%Expression of Bcl-2 and Bax gene protein in retinoblastoma

    Institute of Scientific and Technical Information of China (English)

    张小猛; 庞利民; 张晓光

    2000-01-01

    目的:研究凋亡及凋亡调控基因Bcl-2/Bax和视网膜母细胞瘤(Retinoblastoma,RB)的发生、发展及退化的关系.方法:收集36例RB标本,对其分别进行Bcl-2和Bax基因的蛋白质免疫组织化学染色.对其表达情况和染色强度进行观察.结果:①Bcl-2在分化型RB中表达比较好;②Bax在未分化型和分化型中表达都比较好.结论:①分化型和未分化型RB中都有Bcl-2/Bax基因蛋白表达;②随RB恶性度的增加,Bcl-2的表达逐渐减弱;Bax的表达无明显改变.③分化型RB受Bcl-2和Bax基因共同控制;未分化型RB受Bax基因调控,Bcl-2基因发挥很少的作用.

  18. Maximal sequence length of exact match between members from a gene family during early evolution

    Institute of Scientific and Technical Information of China (English)

    WEN Xiao; GUO Xing-yi; FAN Long-jiang

    2005-01-01

    Mutation (substitution, deletion, insertion, etc.) in nucleotide acid causes the maximal sequence lengths of exact match (MALE) between paralogous members from a duplicate event to become shorter during evolution. In this work, MALE changes between members of 26 gene families from four representative species (Arabidopsis thaliana, Oryza sativa, Mus musculus and Homo sapiens) were investigated. Comparative study ofparalogous' MALE and amino acid substitution rate (dA<0.5)indicated that a close relationship existed between them. The results suggested that MALE could be a sound evolutionary scale for the divergent time for paralogous genes during their early evolution. A reference table between MALE and divergent time for the four species was set up, which would be useful widely, for large-scale genome alignment and comparison. As an example, detection of large-scale duplication events of rice genome based on the table was illustrated.

  19. Sequencing and molecular modeling identifies candidate members of Caliciviridae family in bats.

    Science.gov (United States)

    Kemenesi, Gábor; Gellért, Ákos; Dallos, Bianka; Görföl, Tamás; Boldogh, Sándor; Estók, Péter; Marton, Szilvia; Oldal, Miklós; Martella, Vito; Bányai, Krisztián; Jakab, Ferenc

    2016-07-01

    Emerging viral diseases represent an ongoing challenge for globalized world and bats constitute an immense, partially explored, reservoir of potentially zoonotic viruses. Caliciviruses are important human and animal pathogens and, as observed for human noroviruses, they may impact on human health on a global scale. By screening fecal samples of bats in Hungary, calicivirus RNA was identified in the samples of Myotis daubentonii and Eptesicus serotinus bats. In order to characterize more in detail the bat caliciviruses, large portions of the genome sequence of the viruses were determined. Phylogenetic analyses and molecular modeling identified firmly the two viruses as candidate members within the Caliciviridae family, with one calicivirus strain resembling members of the Sapovirus genus and the other bat calicivirus being more related to porcine caliciviruses of the proposed genus Valovirus. This data serves the effort for detecting reservoir hosts for potential emerging viruses and recognize important evolutionary relationships. PMID:27085289

  20. Autophagy Regulates the Post-Translational Cleavage of BCL-2 and Promotes Neuronal Survival

    Directory of Open Access Journals (Sweden)

    Laura Lossi

    2010-01-01

    Full Text Available B-cell lymphoma 2 protein (BCL-2 is one of the more widely investigated anti-apoptotic protein in mammals, and its levels are critical for protecting from programmed cell death. We report here that the cellular content of BCL-2 is regulated at post-translational level along the autophagy/lysosome pathways in organotypic cultures of post-natal mouse cerebellar cortex. Specifically this mechanism appears to be effective in the cerebellar granule cells (CGCs that are known to undergo massive programmed cell death (apoptosis during post-natal maturation. By the use of specific agonists/antagonist of calcium channels at the endoplasmic reticulum it was possible to understand the pivotal role of calcium release from intracellular stores in CGC neuroprotection. The more general significance of these findings is supported by a very recent study Niemann-Pick transgenic mice.

  1. 14-3-3 family members act coordinately to regulate mitotic progression.

    Science.gov (United States)

    Dalal, Sorab N; Yaffe, Michael B; DeCaprio, James A

    2004-05-01

    The mitosis promoting phosphatase, cdc25C, is a target of both the DNA replication and DNA damage checkpoint pathways. These pathways regulate cdc25C function, in part, by promoting the association of cdc25C with 14-3-3 proteins, which results in the retention of cdc25C in the cytoplasm. To determine which 14-3-3 proteins were required to regulate cdc25C function, we tested the ability of various 14-3-3 family members to form a complex with and negatively regulate cdc25C in human cells. Two 14-3-3 family members, 14-3-3epsilon and 14-3-3gamma specifically formed a complex with cdc25C but not with the 14-3-3 binding defective cdc25C mutant, S216A. In addition, 14-3-3epsilon and 14-3-3gamma inhibited the ability of cdc25C, but not the S216A mutant, to induce premature chromatin condensation (PCC) in U-2OS cells. These results suggested that the reduction in PCC by 14-3-3epsilon and 14-3-3gamma was due to inhibition of cdc25C function. In contrast, 14-3-3sigma was unable to form a complex with cdc25C, but was able to inhibit the ability of both wild type cdc25C and S216A to induce PCC. This suggests that 14-3-3sigma regulates entry into mitosis independently of cdc25C and 14-3-3epsilon and 14-3-3gamma. Thus, specific members of the 14-3-3 family of proteins may act coordinately to maintain the DNA replication checkpoint by regulating the activity of different cell cycle proteins. PMID:15107609

  2. Al-Anon Family Groups’ Newcomers and Members: Concerns about the Drinkers in their Lives

    Science.gov (United States)

    Timko, Christine; Cronkite, Ruth; Laudet, Alexandre; Kaskutas, Lee Ann; Roth, Jeffrey; Moos, Rudolf H

    2015-01-01

    Background and Objectives Despite Al-Anon’s widespread availability and use, knowledge is lacking about the drinkers in attendees’ lives. We filled this gap by describing and comparing Al-Anon newcomers’ and members’ reports about their “main drinker” (main person prompting initial attendance). Methods Al-Anon’s World Service Office mailed a random sample of groups, yielding completed surveys from newcomers (N = 362) and stable members (N = 265). Results Newcomers’ and members’ drinkers generally were comparable. They had known their drinker for an average of 22 years and been concerned about his or her’s drinking for 9 years; about 50% had daily contact with the drinker. Most reported negative relationship aspects (drinker gets on your nerves; you disagree about important things). Newcomers had more concern about the drinker’s alcohol use than members did, and were more likely to report their drinkers’ driving under the influence. Drinkers’ most frequent problem due to drinking was family arguments, and most common source of help was 12-step groups, with lower rates among drinkers of newcomers. Concerns spurring initial Al-Anon attendance were the drinker’s poor quality of life, relationships, and psychological status; goals for initial attendance reflected these concerns. Discussion and Conclusions The drinker’s alcohol use was of less concern in prompting initial Al-Anon attendance, and, accordingly, the drinker’s reduced drinking was a less frequently endorsed goal of attendance. Scientific Significance Family treatments for substance use problems might expand interventions and outcome domains beyond abstinence and relationship satisfaction to include the drinker’s quality of life and psychological symptoms and in turn relieve concerns of family members. PMID:24628725

  3. Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To understand the role and significance of side population (SP) cells from hepatocellular carcinoma (HCC) in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells.METHODS: We used flow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium (MTT) assay and investigated the expression of p53, bd-2 and bax genes during denutrition,by RT-PCR and immunofluorescence staining.RESULTS: The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively.SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells.CONCLUSION: It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the field of anticancer therapy.

  4. Influence of neurotrophin-3 on Bcl-2 and Bax expressions in spinal cord injury of rats

    Institute of Scientific and Technical Information of China (English)

    GUO Shu-zhang; JIANG Tao; REN Xian-jun

    2007-01-01

    Objective:To study the protective mechanisms of neurotrophin-3 (NT-3) on the spinal cord injury.Methods:Totally 105 SD rats were randomly divided into 3 groups:control group,experimental group and sham operation group.Rats from the former 2 groups were inflicted to animal model of acute spinal cord injury according to Allen's (WD) by situating a thin plastic tube in the subarachnoid space below the injury level for perfusion.Rats in experimental group received 20μl NT-3 (200 ng) from the tube at 0,4,8,12,24 h and 3,7 d after injury,and those in control group got an equal volume of normal saline at the same time.The animals in sham operation group only received opening vertebral plate and tube was put in subarachnoid space.The rats were sacrificed at 4,8,12,24 h and 3,7,14 d post injury (n=5).The expression levels of Bcl-2 and Bax proteins in spinal cord of rats were detected by immunohistochemistry assay.Results:The level of Bax protein in control group significantly increased as compared with those in sham operation group, and the peak reached at 8 h after spinal cord injury.The Bcl-2 proteins were always weakly positive.The Bax proteins in NT-3 group significantly decreased but the Bcl-2 proteins obviously increased as compared with those in control group.Conclusion:NT-3 can protect spinal cord from injury in vivo.One of the mechanisms is that NT-3 can inhibit abnormal expression of Bax protein,and increase the expression of Bcl-2 protein,then inhibit apoptosis after spinal cord injury.

  5. IMPORTANCE OF APOPTOSIS MARKERS (MDM2, BCL-2 AND Bax) IN CONVENTIONAL RENAL CELL CARCINOMA.

    Science.gov (United States)

    Saker, Z; Tsintsadze, O; Jiqia, I; Managadze, L; Chkhotua, A

    2015-12-01

    The goal of the current study was to analyze the expression of Bcl-2, MDM2 and Bax in benign and malignant renal tissue samples and assess their possible association with different clinical parameters. Prognostic significance of the markers in recurrence-free and cancer-specific survivals has also been evaluated. Activity of MDM2, Bcl-2 and Bax was evaluated in: 24 normal human kidney tissues resected from the patients of different ages (range: 21-80 years), and in 52 conventional RCC samples. Intensity of the markers' expression was compared between the groups and correlation was analyzed with different clinical parameters. Activity of anti-apoptotic MDM2 and Bcl-2 was significantly elevated while activity of pro-apoptotic Bax was decreased in RCC as compared with normal kidney tissues. Bax expression was positively correlated with patient age. Significant association has been detected between the evaluated markers and cancer clinical parameters like: tumor stage, grade, lymph node and distant metastases. The markers' activity was associates with the tumor morphological features, in particular: presence of tumor necrosis and microvascular invasion. Disease recurrence and 5-year patient survival were associated with the markers' activity. Cox regression analyses have shown that tumor size, pathological stage and grade are the risk factors for disease recurrence and patient death. Expression of MDM2 and Bcl-2 is significantly up-regulated, while Bax is down-regulated in RCC as compared with normal kidney tissue. Intensity of the markers'activities is associated with the tumor pathological and clinical parameters (stage, grade, lymph node and distant metastases, tumor recurrence and patient survival). Further studies with more patients and longer follow-up will uncover the clinical importance of the evaluated markers in RCC. PMID:26719546

  6. Evaluation of CD40, its ligand CD40L and Bcl-2 in psoriatic patients

    Directory of Open Access Journals (Sweden)

    Bożena Chodynicka

    2012-04-01

    Full Text Available Psoriasis is a chronic, recurrent, inflammatory disease. Recent investigations indicate an autoimmune pathogenesis of the disease. Apoptosis plays an important role in the regulation of immune mechanisms in many autoimmune diseases. Although CD40, CD40L, and Bcl-2 have already been studied in psoriatic skin lesions, little is known about their circulating forms. The aim of the present study was to evaluate the serum concentrations of Bcl-2, soluble CD40 and CD40L in psoriatic patients. The study was performed using ELISA kits in 39 psoriatic patients before treatment and after two weeks of topical ointment. Data was analyzed with respect to severity of psoriasis, duration of the disease, and coexisting psoriatic arthritis. Our results revealed that serum concentrations of soluble CD40 and CD40L before and after treatment were significantly higher (p < 0.01 and p < 0.001 in patients with psoriasis compared to the control group. Topical treatment of psoriatic lesions with dithranol ointment failed to decrease serum of CD40 and CD40L, which has not been described until now. There was no significant difference in serum Bcl-2 concentration between the compared groups. We did not find significant differences in serum concentrations of Bcl-2, CD40 or CD40L between patients with mild or severe psoriasis, nor any correlation between disease duration and the presence of psoriatic arthritis symptoms. Our data indicates upregulation of the CD40/CD40L system in psoriatic patients despite topical treatment and suggests their possible role in the pathogenesis of psoriasis.

  7. Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats

    OpenAIRE

    Liu, Guangyi; Tao WANG; WANG, TINGING; Song, Jinming; Zhou, Zhen

    2013-01-01

    Neuron apoptosis is known to mediate a change of ethology following cerebral ischemia-reperfusion injury in rats. Additionally, Bcl-2, Bax and caspase-3 proteins may exert a significant effect on neuron injury. The aim of this study was to investigate the role, mechanism of action and clinical significance of these proteins in neuron apoptosis and functional impairment following cerebral ischemia-reperfusion injury in rats. Sixty male healthy adult Wistar rats were randomly assigned into cont...

  8. Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?

    OpenAIRE

    Pillai, Krishna; Mohammad H Pourgholami; Chua, Terence C.; Morris, David L.

    2013-01-01

    Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, several prognostic factors have been identified in MPM patients and this has prompted the development of new therapies and patient management. Since BCL2, an antiapoptotic oncoprotein, is a fav...

  9. Prognostic value of mitotic index and Bcl2 expression in male breast cancer.

    OpenAIRE

    Lacle, M.M.; van der Pol, C.C.; Witkamp, A. J.; van der Wall, E.; van Diest, P.J.

    2013-01-01

    The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic v...

  10. Effect of Exercise Training on Bcl-2 and Bax Gene Expression in the Rat Heart

    Directory of Open Access Journals (Sweden)

    Jafari

    2015-10-01

    Full Text Available Background Apoptosis or programmed cell death plays an important role in the development of cardiovascular diseases, particularly heart failure. Current evidence suggests that exercise training may alter apoptosis-related signaling in sensitive somatic tissues such as the myocardium. Objectives The aim of this study was to assess the effect of exercise training on Bcl-2 and Bax genes expression as key molecules involved in intrinsic pathway of apoptosis in the rat heart. Materials and Methods This study was conducted with a two-group experimental design (animal model and sixteen three-month-old male rats were selected and randomly divided to two groups of exercise training (n = 8 and control (n = 8. Rats in the trained group participated in an exercise training program for 12 weeks (10 – 60 m min-1, 24 – 33 min d-1, 15%. The rat hearts were removed forty-eight hours after the last training session. RNA extraction and synthesis of cDNA was done, and Bax and Bcl2 genes expression was analyzed through the Real Time-Polymerase Chain Reaction (RT-PCR. Kolmogorov-Smirnov and independent t-test were applied for statistical analysis of the data (P 0.05. However, Bcl2 expression was higher in the trained group compared to the control group (11%. Conclusions In general, it seems that three-month exercise training was effective in reducing cardiac mitochondrial pro-apoptotic protein. However, considering the results of the Bcl2 gene expression, more researches are needed to identify effects of exercise trainings on indices of myocardial apoptosis.

  11. Effect of Exercise Training on Bcl-2 and Bax Gene Expression in the Rat Heart

    OpenAIRE

    Jafari; Pourrazi; Nikookheslat; Baradaran

    2015-01-01

    Background Apoptosis or programmed cell death plays an important role in the development of cardiovascular diseases, particularly heart failure. Current evidence suggests that exercise training may alter apoptosis-related signaling in sensitive somatic tissues such as the myocardium. Objectives The aim of this study was to assess the effect of exercise training on Bcl-2 and Bax genes expression as key molecules involved in intrins...

  12. Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae.

    OpenAIRE

    Barillas-Mury, C; Charlesworth, A.; Gross, I; Richman, A; Hoffmann, J A; Kafatos, F C

    1996-01-01

    A novel rel family member, Gambif1 (gambiae immune factor 1), has been cloned from the human malaria vector, Anopheles gambiae, and shown to be most similar to Drosophila Dorsal and Dif. Gambif1 protein is translocated to the nucleus in fat body cells in response to bacterial challenge, although the mRNA is present at low levels at all developmental stages and is not induced by infection. DNA binding activity to the kappaB-like sites in the A.gambiae Defensin and the Drosophila Diptericin and...

  13. Differential expression of members of the E2F family of transcription factors in rodent testes

    Directory of Open Access Journals (Sweden)

    Toppari Jorma

    2006-12-01

    Full Text Available Abstract Background The E2F family of transcription factors is required for the activation or repression of differentially expressed gene programs during the cell cycle in normal and abnormal development of tissues. We previously determined that members of the retinoblastoma protein family that interacts with the E2F family are differentially expressed and localized in almost all the different cell types and tissues of the testis and in response to known endocrine disruptors. In this study, the cell-specific and stage-specific expression of members of the E2F proteins has been elucidated. Methods We used immunohistochemical (IHC analysis of tissue sections and Western blot analysis of proteins, from whole testis and microdissected stages of seminiferous tubules to study the differential expression of the E2F proteins. Results For most of the five E2F family members studied, the localizations appear conserved in the two most commonly studied rodent models, mice and rats, with some notable differences. Comparisons between wild type and E2F-1 knockout mice revealed that the level of E2F-1 protein is stage-specific and most abundant in leptotene to early pachytene spermatocytes of stages IX to XI of mouse while strong staining of E2F-1 in some cells close to the basal lamina of rat tubules suggest that it may also be expressed in undifferentiated spermatogonia. The age-dependent development of a Sertoli-cell-only phenotype in seminiferous tubules of E2F-1 knockout males corroborates this, and indicates that E2F-1 is required for spermatogonial stem cell renewal. Interestingly, E2F-3 appears in both terminally differentiated Sertoli cells, as well as spermatogonial cells in the differentiative pathway, while the remaining member of the activating E2Fs, E2F-2 is most concentrated in spermatocytes of mid to late prophase of meiosis. Comparisons between wildtype and E2F-4 knockout mice demonstrated that the level of E2F-4 protein displays a distinct

  14. The Human Laminin Receptor is a Member of the Integrin Family of Cell Adhesion Receptors

    Science.gov (United States)

    Gehlsen, Kurt R.; Dillner, Lena; Engvall, Eva; Ruoslahti, Erkki

    1988-09-01

    A receptor for the adhesive basement membrane protein, laminin, was isolated from human glioblastoma cells by affinity chromatography on laminin. This receptor has a heterodimeric structure similar to that of receptors for other extracellular matrix proteins such as fibronectin and vitronectin. Incorporation of the laminin receptor into liposomal membranes makes it possible for liposomes to attach to surfaces coated with laminin. The receptor liposomes also attached to some extent to surfaces coated with fibronectin, but not with other matrix proteins. These properties identify the laminin receptor as a member of the integrin family of cell adhesion receptors.

  15. Hemoglobin Q-Iran detected in family members from Northern Iran: a case report

    OpenAIRE

    Khorshidi Mohammad; Roshan Payam; Bayat Nooshin; Mahdavi Mohammad; Najmabadi Hossein

    2012-01-01

    Abstract Introduction Hemoglobin Q-Iran (α75Asp→His) is an important member of the hemoglobin Q family, molecularly characterized by the replacement of aspartic acid by histidine. The first report of hemoglobin Q-Iran and the nomenclature of this hemoglobinopathy dates back to 1970. Iran is known as a country with a high prevalence of α- and β-thalassemia and different types of hemoglobinopathy. Many of these variants are yet to be identified as the practice of molecular laboratory techniques...

  16. Complex Determinants in Specific Members of the Mannose Receptor Family Govern Collagen Endocytosis

    DEFF Research Database (Denmark)

    Jürgensen, Henrik J; Johansson, Kristina; Madsen, Daniel H;

    2014-01-01

    Members of the well-conserved mannose receptor (MR) protein family have been functionally implicated in diverse biological and pathological processes. Importantly, a proposed common function is the internalization of collagen for intracellular degradation occurring during bone development, cancer...... in PLA2R or DEC-205. However, we also found that an active FN-II domain was not a sufficient determinant to allow collagen internalization through these receptors. Nevertheless, this ability could be acquired by the transfer of a larger segment of uPARAP/Endo180 (the Cys-rich domain, the FN-II domain...

  17. Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3

    International Nuclear Information System (INIS)

    The fibroblast growth factors are a family of polypeptide growth factors involved in a variety of activities including mitogenesis, angiogenesis, and wound healing. Fibroblast growth factor receptors (FGFRs) have previously been identified in chicken, mouse, and human and have been shown to contain an extracellular domain with either two or three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tyrosine kinase domain. The authors have isolated a human cDNA for another tyrosine kinase receptor that is highly homologous to the previously described FGFR. Expression of this receptor cDNA in COS cells directs the expression of a 125-kDa glycoprotein. They demonstrate that this cDNA encodes a biologically active receptor by showing that human acidic and basic fibroblast growth factors activate this receptor as measured by 45Ca2+ efflux assays. These data establish the existence of an additional member of the FGFR family that they have named FGFR-3

  18. Care for the adult family members of victims of unexpected cardiac death.

    Science.gov (United States)

    Zalenski, Robert; Gillum, Richard F; Quest, Tammie E; Griffith, James L

    2006-12-01

    More than 300,000 sudden coronary deaths occur annually in the United States, despite declining cardiovascular death rates. In 2000, deaths from heart disease left an estimated 190,156 new widows and 68,493 new widowers. A major unanswered question for emergency providers is whether the immediate care of the loved ones left behind by the deceased should be a therapeutic task for the staff of the emergency department in the aftermath of a fatal cardiac arrest. Based on a review of the literature, the authors suggest that more research is needed to answer this question, to assess the current immediate needs and care of survivors, and to find ways to improve care of the surviving family of unexpected cardiac death victims. This would include improving quality of death disclosure, improving care for relatives during cardiopulmonary resuscitation of their family member, and improved methods of referral for services for prevention of psychological and cardiovascular morbidity during bereavement. PMID:16946285

  19. Bcl-2/MDM2 Dual Inhibitors Based on Universal Pyramid-Like α-Helical Mimetics.

    Science.gov (United States)

    Wang, Ziqian; Song, Ting; Feng, Yingang; Guo, Zongwei; Fan, Yudan; Xu, Wenjie; Liu, Lu; Wang, Anhui; Zhang, Zhichao

    2016-04-14

    No α-helical mimetic that exhibits Bcl-2/MDM2 dual inhibition has been rationally designed due to the different helicities of the α-helixes at their binding interfaces. Herein, we extracted a one-turn α-helix-mimicking ortho-triarene unit from o-phenylene foldamers. Linking benzamide substrates with a rotatable C-N bond, we constructed a novel semirigid pyramid-like scaffold that could support its two-turn α-helix mimicry without aromatic stacking interactions and could adopt the different dihedral angles of the key residues of p53 and BH3-only peptides. On the basis of this universal scaffold, a series of substituent groups were installed to capture the key residues of both p53TAD and BimBH3 and balance the differences of the bulks between them. Identified by FP, ITC, and NMR spectroscopy, a compound 6e (zq-1) that directly binds to Mcl-1, Bcl-2, and MDM2 with balanced submicromolar affinities was obtained. Cell-based experiments demonstrated its antitumor ability through Bcl-2/MDM2 dual inhibition simultaneously.

  20. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

    Science.gov (United States)

    Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

    2006-02-01

    HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

  1. Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

    International Nuclear Information System (INIS)

    Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients

  2. The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Vogler, Meike, E-mail: mv62@le.ac.uk [MRC Toxicology Unit, University of Leicester, LE1 9HN Leicester (United Kingdom); Dickens, David, E-mail: David.Dickens@liverpool.ac.uk [Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GL Liverpool (United Kingdom); Dyer, Martin J.S., E-mail: mjsd1@le.ac.uk [MRC Toxicology Unit, University of Leicester, LE1 9HN Leicester (United Kingdom); Owen, Andrew, E-mail: aowen@liverpool.ac.uk [Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GL Liverpool (United Kingdom); Pirmohamed, Munir, E-mail: munirp@liv.ac.uk [Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GL Liverpool (United Kingdom); Cohen, Gerald M., E-mail: gmc2@le.ac.uk [MRC Toxicology Unit, University of Leicester, LE1 9HN Leicester (United Kingdom)

    2011-05-06

    Highlights: {yields} The BCL2-inhibitor ABT-263 is a substrate for P-glycoprotein. {yields} Apoptosis is inhibited by P-glycoprotein expression. {yields} Overexpression of P-glycoprotein may contribute to resistance to ABT-263 or ABT-737. -- Abstract: Inhibition of BCL2 proteins is one of the most promising new approaches to targeted cancer therapy resulting in the induction of apoptosis. Amongst the most specific BCL2-inhibitors identified are ABT-737 and ABT-263. However, targeted therapy is often only effective for a limited amount of time because of the occurrence of drug resistance. In this study, the interaction of BCL2-inhibitors with the drug efflux transporter P-glycoprotein was investigated. Using {sup 3}H labelled ABT-263, we found that cells with high P-glycoprotein activity accumulated less drug. In addition, cells with increased P-glycoprotein expression were more resistant to apoptosis induced by either ABT-737 or ABT-263. Addition of tariquidar or verapamil sensitized the cells to BCL2-inhibitor treatment, resulting in higher apoptosis. Our data suggest that the BCL2-inhibitors ABT-737 and ABT-263 are substrates for P-glycoprotein. Over-expression of P-glycoprotein may be, at least partly, responsible for resistance to these BCL2-inhibitors.

  3. Effect of low dose radiation on P53 and Bcl-2 protein expression in spermatogenic cells of mouse testis

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of low dose radiation (LDR) with different dose of X-rays on P53 and Bcl-2 protein expression in spermatogenic cells of male Kunming mouse testis. Methods: The relationships between time-effect and dose-effect of P53 and Bcl-2 protein expression positive rate in spermatogenic cells of mouse testis after LDR with different dose of X-rays were studied with immunohistochemical technique (SABC). Results: P53 and Bcl-2 protein expressed in spermatogonia and spermatocytes in varying degrees, the positive rate of spermatogonia was obviously superior to that of spermatocytes. With the increase of irradiation dose, the expression of P53 protein showed a increasing tendency, however, the P53 protein expression of spermatozoa scarcely occurred after LDR. Bcl-2 protein was primarily expressed in spermatozoa. With the increase of irradiation dose, the positive rate of Bcl-2 protein expression showed a downregulated tendency. However, the Bcl-2 protein expression of spermatogonia and spermatocytes scarcely occurred after LDR. Conclusion: The expressions of P53 and Bcl-2 may have regular changes in mouse testis induced by LDR, which may provide a experimental evidence for the mechanism study of spermatogonic cell apoptosis induced selectively by ionizing radiation

  4. Combined expression of gastrointestinal hormone SP and anti-apoptosis geneBcl-2 in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Ling Feng; Qin Xian Zhang; Sheng Lei Li

    2000-01-01

    AIM To study the combined expression of gastrointestinal hormone substance P and anti-apoptosis gene Bcl-2 in gastric carcinoma and its significance.METHODS Substance P and Bcl-2 protein expression was examined by the S-P immunohistochemicalmethod in 33 cases of gastric carcinoma, 17 adjacent the carcinoma and 13 normal gastric mucoma.RESULTS Positive expression of SP in gastric carcinoma was higher than that of both adjacent and normalmucosa (P 0.05). The expression of bcl-2 both in gastric carcinoma and adjacent tissues werehigher than that of normal gastric mucosa (P< 0.05-0.01). But the positive expression of Bcl-2 had nostatistical significance between gastric carcinoma and adjacent tissues.CONCLUSION Both gastrointestinal hormone SP and Bcl-2 gene have synergistic expression in gastriccarcinoma, indicating that they all take part in the occurrence of gastric carcinoma. Abnormal expression ofBcl-2 gene occurred in benign gastric pathological changes, once they become carcinoma, the positiveexpression of cell is no more increased, possibly because that there is no more increase of the intensity of Bcl-2 inhibition of cell apoptosis.

  5. Exploitation and characterization of three versatile amidase super family members from Delftia tsuruhatensis ZJB-05174.

    Science.gov (United States)

    Wu, Zhe-Ming; Zheng, Ren-Chao; Zheng, Yu-Guo

    2016-05-01

    Amidases can be assigned into two families according to their amino acid sequences. Three amidases (Dt-Amis) were mined and identified from genome of Delftia tsuruhatensis. Homology analysis demonstrated that Dt-Ami 2 and Dt-Ami 6 belonged to amidase signature (AS) family, while Dt-Ami 7 belonged to nitrilase superfamily. AS amidases were shown to hydrolyze a wide spectrum of amides. Kinetic analysis demonstrated that the extension of chain length of aliphatic amides considerably decreased the Km values, and the turnover numbers (kcat) were high with linear aliphatic amides as substrates. Dt-Ami 2 showed maximum activity near a quite alkaline pH (11.0) and exhibited opposite enantioselectivity to Dt-Ami 6. Furthermore, a novel bioprocess for hydrolysis of 1-cyanocyclohexaneacetamide was developed using Dt-Ami 6 as biocatalyst, resulting in >99% conversion within 1.5h at a substrate loading of 100g/L by 0.5g/L of Escherichia coli cells. On the other hand, nitrilase superfamily amidase only hydrolyzed aliphatic amides. The Km values of Dt-Ami 7 were considerably increased with the extension of chain length of aliphatic amides. The characterized enzymes from different families showed distinct biochemical characteristics and catalytic properties, leading to a better understanding of the two super amidase family members. PMID:26992798

  6. Effect of U-74389G on apoptosis and bcl-2 expression following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    骆纯; 卢亦成; 朱诚; 江基尧

    2003-01-01

    Objective: To investigate the relationship between oxidative stress and apoptosis and bcl-2 expression following traumatic brain injury (TBI). Methods: Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury (FPBI) of moderate severity. U-74389G (20 mg/kg) were administered intravenously before FPBI. The neurological functions were measured by beam-walk task (BWT) and beam-balance task (BBT). In addition to morphological evidence of apoptosis, TUNEL histochemistry was used to identify DNA fragmentation in situ with both light and electron microscopic levels. The internucleosomal fragments of DNA in apoptotic cells were examined using agarose gel electrophoresis. Bcl-2 protein expression was detected by immunohistochemistry. Results: The scores of BWT and BBT were significantly improved (P<0.01) in the treated animals. The treatment significantly reduced the number of apoptotic cells that was counted in the areas of the injured hemisphere at various time points following TBI. No DNA ladder was detected in the treated rats. Bcl-2 expression was observed in the cerebral cortex, subcortical white matter, dentate gyrus, hippocampal CA1 and CA3 region ipsilateral to injured hemisphere. Bcl-2 positive cells displayed normal nuclear morphology; Little Bcl-2 positive cells revealed morphological feature of apoptosis or necrosis. The immunoreactivity of Bcl-2 protein decreased significantly in the hippocampus ipsilateral impact site as early as 6 h post-injury. During 1-3 d after injury, the bcl-2 protein expression decreased relatively slow. In the U-74389G treated groups, the downregulation of bcl-2 expression was halted. Conclusion: In this model, apoptosis is associated with an activation of lipid peroxidation. U-74389G may block oxidative stress and halt the downregulation of bcl-2 expression. These may be one of the molecular mechanisms of the neuro-protective effects by U-74389G.

  7. Effect of silencing Bcl-2 expression by small interfering RNA on radiosensitivity of gastric cancer BGC823 cells

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Liu; Chun-Lei Lu

    2013-01-01

    Objective: To explore the influence of silencing Bcl-2 expression by small interfering RNA (siRNA) on Bcl-2 protein expression, cell apoptosis rate and radiosensitivity of gastric cancer BGC823 cells. Methods: siRNA segment for Bcl-2 gene was designed and synthesized, then was induced into gastric cancer BGC 823 cells by liposome transfection. Bcl-2 protein expression was detected by Western Blotting. After X radiation, flow cytometry and clone forming assay were used to determine the effects of RNA interference on BGC823 cell apoptosis rate and radiosensitivity.Result:After the transfection of Bcl-2 siRNA, the positive expression rate of Bcl-2 protein in BGC823 cells was (35.45±2.35)%. Compared with the control group and negative siRNA transfection group, the rate was significantly decreased (P<0.01). The apoptosis rate of BGC823-RNAi cell was (10.81±0.91)%, which was significantly higher than the control group and negative siRNA transfection group (P<0.01). After 48h X radiation, the apoptosis rate of BGC823-RNAi was (28.91 ±1.40)%, which was significantly higher than the control group and the group without radiation (P<0.01). During clone forming assay D0, Dq and SF2 values in Bcl-2 siRNA1 transfection group were all lower than those in the control group. The radiosensitivity ratio was 1.28 (the ratio of D0) and 1.60 (the ratio of Dq). Conclusions: Specific siRNA of Bcl-2 gene can effectively inhibit the expression of Bcl-2 gene, enhance the radiosensitivity and apoptosis of gastric cancer BGC823 cells, having good clinical application perspective.

  8. Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Alvarado Carlos S

    2008-03-01

    Full Text Available Abstract Background Tissue factor (TF is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa, initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Methods Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry respectively. Results Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. Conclusion This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting

  9. Japanese Bereaved Family Members' Perspectives of Palliative Care Units and Palliative Care: J-HOPE Study Results.

    Science.gov (United States)

    Kinoshita, Satomi; Miyashita, Mitsunori; Morita, Tatsuya; Sato, Kazuki; Shoji, Ayaka; Chiba, Yurika; Miyazaki, Tamana; Tsuneto, Satoru; Shima, Yasuo

    2016-06-01

    The study purpose was to understand the perspectives of bereaved family members regarding palliative care unit (PCU) and palliative care and to compare perceptions of PCU before admission and after bereavement. A cross-sectional questionnaire survey was conducted, and the perceptions of 454 and 424 bereaved family members were obtained regarding PCU and palliative care, respectively. Family members were significantly more likely to have positive perceptions after bereavement (ranging from 73% to 80%) compared to before admission (ranging from 62% to 71%). Bereaved family members who were satisfied with medical care in the PCU had a positive perception of the PCU and palliative care after bereavement. Respondents younger than 65 years of age were significantly more likely to have negative perceptions of PCU and palliative care.

  10. Japanese Bereaved Family Members' Perspectives of Palliative Care Units and Palliative Care: J-HOPE Study Results.

    Science.gov (United States)

    Kinoshita, Satomi; Miyashita, Mitsunori; Morita, Tatsuya; Sato, Kazuki; Shoji, Ayaka; Chiba, Yurika; Miyazaki, Tamana; Tsuneto, Satoru; Shima, Yasuo

    2016-06-01

    The study purpose was to understand the perspectives of bereaved family members regarding palliative care unit (PCU) and palliative care and to compare perceptions of PCU before admission and after bereavement. A cross-sectional questionnaire survey was conducted, and the perceptions of 454 and 424 bereaved family members were obtained regarding PCU and palliative care, respectively. Family members were significantly more likely to have positive perceptions after bereavement (ranging from 73% to 80%) compared to before admission (ranging from 62% to 71%). Bereaved family members who were satisfied with medical care in the PCU had a positive perception of the PCU and palliative care after bereavement. Respondents younger than 65 years of age were significantly more likely to have negative perceptions of PCU and palliative care. PMID:25852202

  11. Correlates of Caregiver Burden among Family Members of Patients with Schizophrenia in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Increase Ibukun Adeosun

    2013-01-01

    Full Text Available Family members of patients with schizophrenia have enormous roles in the care of their patients, which could negatively impact their well being. Development of interventions targeted at alleviating the burden of informal care giving is hinged on the recognition of the factors associated with the various dimensions of burden. This study determined the correlates of caregiver burden among family members of patients with schizophrenia in Lagos, Nigeria. The study instruments included the Zarit burden interview (ZBI and the positive and negative syndrome scale for schizophrenia (PANSS. Exploratory factor analysis of the ZBI produced a five-factor structure with “financial/physical strain”, “time/dependence strain”, “emotional strain”, “uncertainty”, and “self-criticism” domains. On multiple regression analyses, total PANSS scores, poor social support, and lower educational levels of caregivers were predictive of higher burden scores on the “financial/physical strain”, “time/dependence”, and “emotional strain” domains. Longer duration of illness, shorter patient-caregiver contact time, and being a female caregiver were predictive of higher burden scores on the “uncertainty”, “self-criticism”, and “emotional strain” domains, respectively. There is need for interventions to alleviate the burden on caregivers of patients with schizophrenia in Nigeria. These strategies must include comprehensive social support and improve access to services for patients and their caregivers.

  12. Correlates of Caregiver Burden among Family Members of Patients with Schizophrenia in Lagos, Nigeria.

    Science.gov (United States)

    Adeosun, Increase Ibukun

    2013-01-01

    Family members of patients with schizophrenia have enormous roles in the care of their patients, which could negatively impact their well being. Development of interventions targeted at alleviating the burden of informal care giving is hinged on the recognition of the factors associated with the various dimensions of burden. This study determined the correlates of caregiver burden among family members of patients with schizophrenia in Lagos, Nigeria. The study instruments included the Zarit burden interview (ZBI) and the positive and negative syndrome scale for schizophrenia (PANSS). Exploratory factor analysis of the ZBI produced a five-factor structure with "financial/physical strain", "time/dependence strain", "emotional strain", "uncertainty", and "self-criticism" domains. On multiple regression analyses, total PANSS scores, poor social support, and lower educational levels of caregivers were predictive of higher burden scores on the "financial/physical strain", "time/dependence", and "emotional strain" domains. Longer duration of illness, shorter patient-caregiver contact time, and being a female caregiver were predictive of higher burden scores on the "uncertainty", "self-criticism", and "emotional strain" domains, respectively. There is need for interventions to alleviate the burden on caregivers of patients with schizophrenia in Nigeria. These strategies must include comprehensive social support and improve access to services for patients and their caregivers.

  13. A novel fibroblast growth factor receptor family member promotes neuronal outgrowth and synaptic plasticity in aplysia.

    Science.gov (United States)

    Pollak, Daniela D; Minh, Bui Quang; Cicvaric, Ana; Monje, Francisco J

    2014-11-01

    Fibroblast Growth Factor (FGF) Receptors (FGFRs) regulate essential biological processes, including embryogenesis, angiogenesis, cellular growth and memory-related long-term synaptic plasticity. Whereas canonical FGFRs depend exclusively on extracellular Immunoglobulin (Ig)-like domains for ligand binding, other receptor types, including members of the tropomyosin-receptor-kinase (Trk) family, use either Ig-like or Leucine-Rich Repeat (LRR) motifs, or both. Little is known, however, about the evolutionary events leading to the differential incorporation of LRR domains into Ig-containing tyrosine kinase receptors. Moreover, although FGFRs have been identified in many vertebrate species, few reports describe their existence in invertebrates. Information about the biological relevance of invertebrate FGFRs and evolutionary divergences between them and their vertebrate counterparts is therefore limited. Here, we characterized ApLRRTK, a neuronal cell-surface protein recently identified in Aplysia. We unveiled ApLRRTK as the first member of the FGFRs family deprived of Ig-like domains that instead contains extracellular LRR domains. We describe that ApLRRTK exhibits properties typical of canonical vertebrate FGFRs, including promotion of FGF activity, enhancement of neuritic outgrowth and signaling via MAPK and the transcription factor CREB. ApLRRTK also enhanced the synaptic efficiency of neurons known to mediate in vivo memory-related defensive behaviors. These data reveal a novel molecular regulator of neuronal function in invertebrates, provide the first evolutionary linkage between LRR proteins and FGFRs and unveil an unprecedented mechanism of FGFR gene diversification in primeval central nervous systems.

  14. Two members of the Ustilago maydis velvet family influence teliospore development and virulence on maize seedlings.

    Science.gov (United States)

    Karakkat, Brijesh B; Gold, Scott E; Covert, Sarah F

    2013-12-01

    Members of the fungal-specific velvet protein family regulate sexual and asexual spore production in the Ascomycota. We predicted, therefore, that velvet homologs in the basidiomycetous plant pathogen Ustilago maydis would regulate sexual spore development, which is also associated with plant disease progression in this fungus. To test this hypothesis, we studied the function of three U. maydis velvet genes, umv1, umv2 and umv3. Using a gene replacement strategy, deletion mutants were made in all three genes in compatible haploid strains, and additionally for umv1 and umv2 in the solopathogenic strain, SG200. None of the mutants showed novel morphological phenotypes during yeast-like, in vitro growth. However, the Δumv1 mutants failed to induce galls or teliospores in maize. Chlorazol black E staining of leaves infected with Δumv1 dikaryons revealed that the Δumv1 hyphae did not proliferate normally and were blocked developmentally before teliospore formation. The Δumv2 mutants were able to induce galls and teliospores in maize, but were slow to do so and thus reduced in virulence. The Δumv3 mutants were not affected in teliospore formation or disease progression. Complementation of the Δumv1 and Δumv2 mutations in the SG200 background produced disease indices similar to those of SG200. These results indicate that two U. maydis velvet family members, umv1 and umv2, are important for normal teliospore development and disease progression in maize seedlings.

  15. EXPRESSIONS OF P53, PROLIFERATING CELL NUCLEAR ANITIGEN, BCL-2 PROTEIN AND THEIR SIGNIFICANCE IN SALIVARY ADENOID CYSTIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effects of P53, PCNA, Bcl-2 protein and their relationship in salivary adenoid cystic carcinoma(SACC). Methods These proteins were examined by immunohistochemistry. Results Overexpressions of P53 and PCNA were revealed in ACC samples, they were higher than those in (polymorphous adenomas) PA, but expression of Bcl-2 protein was not different between ACC and PA. In 3 subtypes of ACC, expressions of 3 proteins were different. Conclusion Mutations of P53, Bcl-2 may be involed in the occurrence of SACC, expression of PCNA and mutation of P53 may coexist in the development of the SACC.

  16. Caspase Family Proteases and Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ting-Jun FAN; Li-Hui HAN; Ri-Shan CONG; Jin LIANG

    2005-01-01

    Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is regulated in an orderly way by a series of signal cascades under certain circumstances. The caspase-cascade system plays vital roles in the induction, transduction and amplification of intracellular apoptotic signals. Caspases, closely associated with apoptosis, are aspartate-specific cysteine proteases and members of the interleukin-1β-converting enzyme family. The activation and function of caspases, involved in the delicate caspase-cascade system, are regulated by various kinds of molecules, such as the inhibitor of apoptosis protein, Bcl-2 family proteins, calpain,and Ca2+. Based on the latest research, the members of the caspase family, caspase-cascade system and caspase-regulating molecules involved in apoptosis are reviewed.

  17. A model of psychological ownership in next-generation members of family-owned firms: A qualitative study

    OpenAIRE

    Ceja, Lucia; Tapies, Josep

    2011-01-01

    The present research study is intended to provide further insights into the psychological ownership experienced by next-generation members in relation to their family firms. As this is still a very young area of research, explorative research is needed. Therefore, a mixed-methods qualitative investigation, using a sample of 20 next-generation members of family-owned firms of different sizes, generational stages and business sectors, was performed. Through interpretative phenomenological and e...

  18. ROLE OF ATP BINDING CASSETTE SUB-FAMILY MEMBER 2 (ABCG2) IN MOUSE EMBRYONIC STEM CELL DEVELOPMENT.

    Science.gov (United States)

    ATP binding cassette sub-family member 2 (ABCG2), is a member of the ABC transporter superfamily and a principal xenobiotic transporter. ABCG2 is also highly expressed in certain stem cell populations where it is thought to be related to stem cell plasticity, although the role o...

  19. Evolutionary, structural and functional interplay of the IκB family members.

    Directory of Open Access Journals (Sweden)

    Shaherin Basith

    Full Text Available A primary level of control for nuclear factor kappa B (NF-κB is effected through its interactions with the inhibitor protein, inhibitor of kappa B (IκB. Several lines of evidence confirm the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. Therefore, we performed a comprehensive bioinformatics analysis to understand the evolutionary history and intrinsic functional diversity of IκB family members. Phylogenetic relationships were constructed to trace the evolution of the IκB family genes. Our phylogenetic analysis revealed 10 IκB subfamily members that clustered into 5 major clades. Since the ankyrin (ANK domain appears to be more ancient than the Rel homology domain (RHD, our phylogenetic analysis suggests that some undefined ancestral set of ANK repeats acquired an RHD before any duplication and was later duplicated and then diverged into the different IκB subfamilies. Functional analysis identified several functionally divergent sites in the ANK repeat domains (ARDs and revealed that this region has undergone strong purifying selection, suggesting its functional importance in IκB genes. Structural analysis showed that the major variations in the number of ANK repeats and high conformational changes in the finger loop ARD region contribute to the differing binding partner specificities, thereby leading to distinct IκB functions. In summary, our study has provided useful information about the phylogeny and structural and functional divergence of the IκB family. Additionally, we identified a number of amino acid sites that contribute to the predicted functional divergence of these proteins.

  20. Impacts of parasites in early life: contrasting effects on juvenile growth for different family members.

    Directory of Open Access Journals (Sweden)

    Thomas E Reed

    Full Text Available Parasitism experienced early in ontogeny can have a major impact on host growth, development and future fitness, but whether siblings are affected equally by parasitism is poorly understood. In birds, hatching asynchrony induced by hormonal or behavioural mechanisms largely under parental control might predispose young to respond to infection in different ways. Here we show that parasites can have different consequences for offspring depending on their position in the family hierarchy. We experimentally treated European Shag (Phalacrocorax aristoteli nestlings with the broad-spectrum anti-parasite drug ivermectin and compared their growth rates with nestlings from control broods. Average growth rates measured over the period of linear growth (10 days to 30 days of age and survival did not differ for nestlings from treated and control broods. However, when considering individuals within broods, parasite treatment reversed the patterns of growth for individual family members: last-hatched nestlings grew significantly slower than their siblings in control nests but grew faster in treated nests. This was at the expense of their earlier-hatched brood-mates, who showed an overall growth rate reduction relative to last-hatched nestlings in treated nests. These results highlight the importance of exploring individual variation in the costs of infection and suggest that parasites could be a key factor modulating within-family dynamics, sibling competition and developmental trajectories from an early age.

  1. Consumption and Sources of Dietary Salt in Family Members in Beijing

    Directory of Open Access Journals (Sweden)

    Fang Zhao

    2015-04-01

    Full Text Available In China, few people are aware of the amount and source of their salt intake. We conducted a survey to investigate the consumption and sources of dietary salt using the “one-week salt estimation method” by weighing cooking salt and major salt-containing food, and estimating salt intake during dining out based on established evidence. Nine hundred and three families (1981 adults and 971 children with students in eight primary or junior high schools in urban and suburban Beijing were recruited. On average, the daily dietary salt intake of family members in Beijing was 11.0 (standard deviation: 6.2 g for children and adolescents (under 18 years old, 15.2 (9.1 g for adults (18 to 59 years old, and 10.2 (4.8 g for senior citizens (60 years old and over, respectively. Overall, 60.5% of dietary salt was consumed at home, and 39.5% consumed outside the home. Approximately 90% of the salt intake came from cooking (household cooking and cafeteria or restaurant cooking, while less than 10% came from processed food. In conclusion, the dietary salt intake in Beijing families far surpassed the recommended amounts by World Health Organization, with both household cooking and dining-out as main sources of salt consumption. More targeted interventions, especially education about major sources of salt and corresponding methods for salt reduction should be taken to reduce the risks associated with a high salt diet.

  2. Retroelements versus APOBEC3 family members: No great escape from the magnificent seven

    Directory of Open Access Journals (Sweden)

    Juan F Arias

    2012-08-01

    Full Text Available Retroelements comprise a large and successful family of transposable genetic elements that, through intensive infiltration, have shaped the genomes of humans and other mammals over millions of years. In fact, retrotransposons now account for approximately 45% of the human genome. Based on their genomic mobility, some retroelements are known to be the cause of genetic diseases, not only in germ and embryonic stem cells but also in somatic cells, posing a threat to genomic stability throughout all cellular populations. In response, mammals have developed intrinsic immunity mechanisms that provide resistance against the threat of the deleterious effects of retrotransposition. Among these, seven members of the APOBEC3 (A3 family of cytidine deaminases serve as highly active, intrinsic, antiretroviral host factors. Certain A3 proteins effectively counteract infections of retroviruses such as HIV-1, as well as those of other virus families, while also blocking the transposition of retroelements. Based on their preferential expression in the germ cells, in which retrotransposons may be active, it is likely that A3 proteins were acquired through mammalian evolution primarily to inhibit retrotransposition and thereby maintain genomic stability in these cells. This review summarizes the recent advances in our understanding of the interplay between the retroelements currently active in the human genome and the anti-retroelement A3 proteins.

  3. The actions of Bcl-2 on anti-ischemic neuron injury and the effects of anti-ischemic drugs on Bcl-2%Bcl-2在缺血性神经细胞损伤中的作用及药物的影响

    Institute of Scientific and Technical Information of China (English)

    张予阳; 史琳琳; 郝冬海; 潘丽红

    2010-01-01

    Bcl-2基因是线虫c-elegans的抗凋亡基因Ced-9的人类同源基因,可参与调控细胞凋亡过程,包括抑制脑缺血半影区的神经细胞凋亡.该文就Bcl-2抗缺血性神经细胞损伤的作用和可能机制,以及抗脑缺血药物对Bcl-2的影响作一综述.

  4. Striving to be prepared for the painful: Management strategies following a family member's diagnosis of advanced cancer

    Directory of Open Access Journals (Sweden)

    Hedberg Berith

    2011-10-01

    Full Text Available Abstract Background Cancer has consequences not only for the sick person but also for those who have a close relationship with that person. Greater knowledge about how family members manage the situation in the period immediately following the diagnosis means greater opportunity to provide the best possible support for the family. The purpose of this study was to explore management strategies that family members use when the patient is in the early stage of treatment for advanced cancer. Methods Twenty family members of cancer patients were included in the study shortly after the diagnosis. The patients had been diagnosed 8-14 weeks earlier with advanced lung cancer or gastrointestinal cancer. The data were collected in interviews with family members and subjected to qualitative latent content analysis. Through the identification of similarities and dissimilarities in the units of meaning, abstraction into codes and sub-themes became possible. The sub-themes were then brought together in one overarching theme. Results The overall function of management strategies is expressed in the theme Striving to be prepared for the painful. The family members prepare themselves mentally for the anticipated tragedy. Family relationships become increasingly important, and family members want to spend all their time together. They try to banish thoughts of the impending death and want to live as normal a life as possible. It becomes important to family members to live in the present and save their energy for the time when they will need it the most. How participants handle their worries, anxiety and sadness can be categorized into seven sub-themes or management strategies: Making things easier in everyday life, Banishing thoughts about the approaching loss, Living in the present, Adjusting to the sick person's situation, Distracting oneself by being with others, Shielding the family from grief, and Attempting to maintain hope. Conclusions The findings revealed

  5. Studies on Cytotoxicity of Glaucocalyxin A, C and Its Relation with Bcl-2 Protein%蓝萼甲、丙素细胞毒活性及其与Bcl-2蛋白关系的研究

    Institute of Scientific and Technical Information of China (English)

    嵇源源; 高立文; 张健; 王剑文

    2013-01-01

    目的:研究蓝萼甲素(GLA)和蓝萼丙素(GLC)对15株不同类型的肿瘤细胞的细胞毒性差异以及与Bcl-2蛋白的关系.方法:采用MTT法检测细胞存活率;用Western Blotting检测细胞凋亡关键蛋白Bcl-2的表达;应用分子对接Autodock程序,将GLA和GLC与Bcl-2蛋白进行分子对接,比较其结合的差异性.结果:用MTT法结果表明GLA对所选用的15株肿瘤细胞均有显著的抑制作用,而相同浓度的GLC对15株肿瘤细胞的生存率没有影响;用分子对接法结果显示GLA与Bcl-2蛋白的结合自由能和ki值均低于GLC.结论:GLA更易与Bcl-2蛋白结合从而抑制Bcl-2蛋白的功能,促进细胞凋亡.

  6. Expression of P53, P21/WAF/CIP, BCL-2, BAX, BCL-X, and BAK in radiation-induced apoptosis in testicular germ cell tumor lines

    International Nuclear Information System (INIS)

    Purpose: Testicular germ cell tumors (TGCTs) represent one of the few tumor types that are curable by antineoplastic therapy, probably due to the high sensitivity of this neoplasm to induction of apoptosis by chemotherapeutic agents and/or ionizing radiation. Here, we tested cell susceptibility to radiation-induced apoptosis in a panel of TGCT cell lines and attempted to correlate this with the known potentially relevant molecular determinants (p53 gene status and Bcl-2 family proteins) of apoptosis. Methods and Materials: Induction of apoptosis by γ-radiation was morphologically recognized in NT2, NCCIT, S2, and 2102 EP using Hoechst/PI staining and additionally confirmed by Western blot analysis of PARP cleavage. The p53 gene status was estimated by sequence analysis. Expression of p21/WAF/CIP was determined by Northern blot analysis and immunoblotting was used to monitor p53, Bax, Bcl-2, Bcl-x, and Bak protein levels. In vitro colony formation was studied to establish clonogenic survival curves. Results: NT2 and NCCIT appeared to be susceptible for radiation-induced apoptosis, contrasting 2102 EP and S2 which were highly resistant. Sequence analysis showed that NT2, S2, and 2102 EP are homozygous for wild-type p53 (wtp53), whereas NCCIT contains mutant p53 (mtp53). NT2 and 2102 EP cells showed radiation-induced p53 upregulation, while NCCIT (mtp53) and S2 (no p53 protein) cells did not. Consistently, γ-radiation-induced DNA damage resulted in a p53-dependent transactivation of the p21/WAF/CIP gene in NT2 and 2102 EP, but not in mtp53-containing NCCIT cells and p53 nonexpressing S2 cells. Constitutive expression of Bax, Bcl-2, Bcl-x, and Bak was not affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis. A discrepancy was found between apoptosis and reproductive death. Conclusions: The present study revealed that: i) the presence of wtp53 may not be absolutely required for the hypersensitivity for radiation

  7. 29 CFR 779.234 - Establishments whose only regular employees are the owner or members of his immediate family.

    Science.gov (United States)

    2010-07-01

    ... or members of his immediate family. 779.234 Section 779.234 Labor Regulations Relating to Labor... Employment to Which the Act May Apply; Enterprise Coverage Leased Departments, Franchise and Other Business... family. Section 3(s) provides that any “establishment which has as its only regular employees the...

  8. The effect of Bcl-2 gene silencing on the sensitivity of cell line A549 to chemotherapeutic drugs

    Institute of Scientific and Technical Information of China (English)

    王姣琦

    2013-01-01

    Objective To investigate the effects of miRNA-mediated down-regulation of the Bcl-2gene on the chemotherapeutic sensitivities and mRNA transcriptions of sensitivity associated genes in human lung adenocarcinoma cell

  9. Bcl-2 GENE REARRANGEMENT DETERMINED BY PCR AS A MEAN TO DETECT MINIMAL RESIDUAL DISEASE IN MALIGNANT LYMPHOMAS

    Institute of Scientific and Technical Information of China (English)

    XIANG Zhi-fu; LU Yu-ying; LAI Yong-rong; CHEN Yan; LI Hui-yu; ZOU Ping

    1999-01-01

    Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase chain reaction (PCR) to detect bcl-2 gene rearrangement and using serial dilution method to define the sensitivity of PCR. Results: In 9 different malignant lymphoma cell lines, Su-DHL-4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was 1:105. In 16 patients with follicular lymphoma, the peripheral blood and bone marrow were PCR positive in 4 cases both at initial diagnosis and after complete remission. Conclusion:Detection of bcl-2 gene rearrangement by PCR provides a sensitive and specific assay of minimal residual disease.It is helpful to improve staging of disease, prognosis and evaluation of the treatment results.

  10. [Dexamethasone affect on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors].

    Science.gov (United States)

    Fatkhullina, A R; Abramov, S N; Skibo, Iu V; Abramova, Z I

    2014-01-01

    Synthetic glucocorticoids are able to activate apoptosis in the cells by regulating the transcription of the respective genes. Effect of dexamethasone on apoptosis is an established fact. However, its influence on another program of cell death autophagy, is currently unproven. Therefore, in this paper we have analyzed the influence of dexamethasone on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors. The results showed that dexamethasone reduced the expression of bcl-2 and mTOR genes. However, the nature of the effect of dexamethasone on mTOR and bcl-2 expression was different: the expression of bcl-2 gene in the long-term cultivation was maintained at the same reduced level, while the expression of mTOR was first reduced and then increased.

  11. The Expression of Apoptosis-Related Genes Bcl-2 and Bax Protein and Apoptosis Positivity in Cervical Carcinoma during Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZHAODongli; SHIJingsen; LIMingzhong; SONGLiping; WANGShuwen

    2005-01-01

    Objective: To evaluate the apoptosis positivity, the expression of Bcl-2. bax proteins in 30 patients with squamous cell cervix carcinoma before and after radiotherapy. Methods: By using immunohistochemical and TDT-dUTP nick end labelling techniques. 30 cases of squamous cell cervical carcinoma were analyzed. Results: The apoptosis positivity before and after irradiation was 76.7%, and 100% respectively, with the difference being significant (P<0.05); The positive rates of Bcl-2 protein before and after irradiation were 73.3% and 46.7% respectively, with the difference being significant (P<0.05): The positive rates of bax protein before and after irradiation were 86% and 100 respectively, with the difference being significant (P<0.05). Conclusion: bax and Bcl-2 protein play an important role in apoptosis induced by fractionated radiation therapy. Apoptosis induced by irradiation is contributed to upregulation of bax protein or downregulation of Bcl-2 protein.

  12. Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

    Directory of Open Access Journals (Sweden)

    Nabilah Muhammad Nadzri

    2013-01-01

    Full Text Available Zerumbone (ZER isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD to enhance ZER’s solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.

  13. Persea declinata (Bl. Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

    Directory of Open Access Journals (Sweden)

    Putri Narrima

    2014-01-01

    Full Text Available Persea declinata (Bl. Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill, which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl. Kosterm bark methanolic crude extract (PDM. PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

  14. Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation.

    Science.gov (United States)

    Narrima, Putri; Paydar, Mohammadjavad; Looi, Chung Yeng; Wong, Yi Li; Taha, Hairin; Wong, Won Fen; Ali Mohd, Mustafa; Hadi, A Hamid A

    2014-01-01

    Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development. PMID:24808916

  15. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cekanova, Maria, E-mail: mcekanov@utk.edu [Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Fernando, Romaine I. [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Siriwardhana, Nalin [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Sukhthankar, Mugdha [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Parra, Columba de la [Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States); Woraratphoka, Jirayus [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Malone, Christine [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Ström, Anders [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Baek, Seung J. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Wade, Paul A. [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Saxton, Arnold M. [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Donnell, Robert M. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Pestell, Richard G. [Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); and others

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.

  16. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    International Nuclear Information System (INIS)

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis

  17. Apoptosis in haematological cancer : regulation by mitochondria, the BCL-2 family and IAPs

    NARCIS (Netherlands)

    Graaf, Aniek Odorica de

    2006-01-01

    This thesis describes a number of studies that investigated several aspects of apoptosis in lymphoid malignancies. Resistance to apoptosis is an important asset of cancer cells, which allows them to evade cell death signals instigated by the changes they undergo during transformation, such as genet

  18. Evaluation of Bcl-2 Family Gene Expression in Hippocampus of 3, 4-methylenedioxymethamphetamine Treated Rats

    OpenAIRE

    Hamed Hashemi-Nasl; Mohammad Taghi Joghataei; Alireza Samzadeh-Kermani; Seyed Behnamedin Jameie; Mansoure Soleimani; Ali Samadikuchaksaraei; Mohammad Hassan Farhadi; Kazem Mousavizadeh; Sara Soleimani Asl; Mehdi Mehdizadeh

    2012-01-01

    Objective: 3,4-methylenedioxymethamphetamine (MDMA) is an illicit, recreational drug that causes cellular death and neurotoxicity. This study evaluates the effects of different doses of MDMA on the expression of apoptosis–related proteins and genes in the hippocampus of adult rats. Materials and Methods: In this expremental study,a total of 20 male Sprague Dawley rats (200-250 g ) were treated with MDMA (0, 5, 10, 20 mg/kg i.p. twice daily) for 7 days. Seven days after the last administration...

  19. Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation.

    OpenAIRE

    F. Pezzella(Istituto Nazionale di Fisica Nucleare, Sezione di Napoli, Complesso Universitario di Monte S. Angelo ed. 6, via Cintia, 80126 Napoli, Italy); Tse, A G; Cordell, J L; Pulford, K. A.; Gatter, K C; Mason, D Y

    1990-01-01

    It has been reported previously that the bcl-2 protooncogene protein is detectable in neoplastic cells from cases of human lymphoma in which the 14;18 chromosomal translocation is present, but not in lymphomas that lack this chromosomal rearrangement or in normal lymphoid tissue. In the present study we confirmed, by immunohistologic labeling with polyclonal and monoclonal antibodies, that bcl-2 protein is strongly expressed in many cases of follicular lymphoma and that these neoplastic folli...

  20. Correlations in survivin expression with the expression of p53 and bcl-2 in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Al-Joudi, F S; Iskandar, Z A; Imran, A K

    2007-09-01

    This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (pfashion, implying that many of these cases may share common abnormalities. PMID:18041310

  1. p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

    OpenAIRE

    Shanmugam, Chandrakumar; Katkoori, Venkat R.; Jhala, Nirag C.; Grizzle, William E.; Gene P Siegal; Manne, Upender

    2008-01-01

    For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of p53 (p53nac) and Bcl-2 expression are prognostic indicators. To understand their role in the progression of CRC we evaluated 90 CRCs and their contiguous adenomatous components (CAdCs) for immunohistochemical expression of these markers. In general, p53nac and Bcl-2 expression was significantly increased when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs that demonstrated p53nac conti...

  2. THE EXPERIMENTAL STUDY ON THE CELL APOPTOSIS AND EXPRESSION OF BCL-2 PROTEIN IN INTRACEREBRAL HEMORRHAGE IN MODEL OF RATS

    Institute of Scientific and Technical Information of China (English)

    Bao Gang; Guo Ning; Zhang Zhonglin; Chen Wei; Bao Dehu

    2006-01-01

    Otjective To study whether there is the apoptosis of neural cells and the expressionof Bcl-2 protein in intracerebral hemorrhage (ICH) in model of rats, for the further understanding the mechanism of the delayed damage of the neural cells around the hematoma after ICH. Methods Fifty SD rats were randomly divided into 5 groups, ten in each. With the Group A as the control, the rest 40 were used to set up intracerebral hemorrhage model. The brains were taken out at 12th, 24th, 48th and 72th hours, respectively. Apoptosis cells were detected with terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and the expression of Bcl-2 protein was detected with immunochemical stainging methed (SP). Results In the control group, no apoptosis cells and Bcl-2protein were detected. In rest groups, the apoptosis cells and Bcl-2 protein were expressed in different degree.Apoptosis rates verified and corresponded with the time after ICH, with the peak at 48th -72th hour after hemorrhage.The peak rate of apoptosis cells was (24. 50± 2.69)% and Bcl-2 protein expression was (20. 76 ± 1.97)% . There was significant difference between the experimental groups and control (P<0.05), and no linear relationship between the apoptosis rate and the expression of Bcl-2 protein. Conclusion Apoptosis may be an important factor in the secondary trauma of ICH. There is a time leg after hemorrhage. All this is instructive to clinical treatment in time. Bcl-2 protein keeps increasing in a certain time after hemorrhage, but not synchronize with the cell apoptosis. This indicates that bcl-2 has the effect to reduce the apoptosis of neural cells.

  3. C-MYC and BCL2 translocation frequency in diffuse large B-cell lymphomas: A study of 97 patients

    Directory of Open Access Journals (Sweden)

    Bahar Akkaya

    2016-01-01

    Full Text Available Purpose: Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. MYC and BCL2 rearrangements have been reported in a proportion of DLBCLs, where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC and BCL2 translocations in DLBCL and assess the prognostic impact in DLBCL patients. Materials and Methods:   In the present study, we evaluated the expression patterns of CD 10, BCL6, and MUM 1 by immunohistochemistry in 121 cases with DLBCL in tissue microarray (TMA: 62 cases in germinal center B-cells (GCBs; and 59 cases in activated B-cells (ABCs of which 60 were females and 61 were males. MYC and BCL2 rearrangements were investigated by interphase fluorescence in situ hybridization on TMAs in 97 DLBCLs. Result: MYC rearrangements were observed in 11 of 97 cases. There was no association with other clinical features, including age, sex, and nodal/extranodal disease. MYC rearrangement was associated with significantly worse overall survival (P < 0.01. BCL2 rearrangements were observed in 14 of 97 cases. There was no association with other clinical features including age and sex. BCL2 rearrangement had a worse outcome (P < 0.01. MYC and BCL2 rearrangements were observed in 3 of 97 cases with the age of  53 (female, 53, 63 years old, respectively, died in 24, 18, and 35 months after the diagnosis. Two cases had primary nodal and one case primary extranodal presentations. All these patients had stage IV disease. Conclusion: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, and more mechanism-based therapy should be explored. Targeted therapies involving these rearrangements and its associated pathways may change the fate of DLBCLs. Analysis of MYC gene rearrangement along with BCL2 is critical in the identification of high-risk patients with poor prognosis.

  4. Effects of Treatment with Platinum Azidothymidine and Azidothymidine on Telomerase Activity and Bcl-2 Concentration in Hepatocellular Carcinoma- Induced Rats

    OpenAIRE

    Sabokrouh, Abdolreza; Goodarzi, Mohammad Taghi; Vaisi-raygani, Asad; Shohreh KHATAMI*; TAGHIZADEH-JAHED, MASOUD

    2014-01-01

    Background Telomerase activity increases in cancer cells. Bcl-2 is an antiapoptotic factor that its concentration grows in many cancer cells including hepato-cellular carcinoma cells. In this study, an attempt was made to investigate the effects of a new synthetic compound, platinum azidothymidine (Pt-AZT) on treatment of rats with Hepatocellular Carcinoma (HCC) and to compare its effects with azidothymidine (AZT) in alteration of telomerase activity and Bcl-2 concentration in HCC. Methods He...

  5. Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene.

    OpenAIRE

    Strasser, A.; Harris, A W; von Boehmer, H; Cory, S

    1994-01-01

    To explore the role of bcl-2 in T-cell development, a bcl-2 transgene was introduced into mice expressing a T-cell receptor (TCR) transgene encoding reactivity for the mouse male antigen HY presented by the H-2Db class I antigen of the major histocompatibility complex (MHC). Normal thymic development is contingent on the ability of immature thymocytes to interact with self-MHC molecules presented by thymic stroma (positive selection). Thus, thymocyte numbers are low in femal...

  6. Memantine prevents cognitive impairment and reduces Bcl-2 and caspase 8 immunoreactivity in rats injected with amyloid β1-40.

    Science.gov (United States)

    Miguel-Hidalgo, José Javier; Paul, Ian A; Wanzo, Valerie; Banerjee, Pradeep K

    2012-10-01

    Amyloid-beta peptides (Aβ) can trigger apoptotic cascades in neurons. We found previously that memantine, an uncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors approved for the treatment of moderate to severe Alzheimer's disease, can prevent neurodegeneration induced by intracranial Aβ(1-40) injection. In this study, we tested the hypothesis that memantine prevents Aβ(1-40)-mediated cognitive impairment, neurodegeneration, and apoptosis of hippocampal neurons in rats. In addition, we hypothesized that Aβ(1-40) injection would induce changes in the levels of one or more apoptosis-related proteins, and that these changes would be attenuated by memantine treatment. Female Sprague-Dawley rats were administered memantine (continuous subcutaneous application, 9.6-14.4mg/kg/day; n=8) or vehicle (water; n=8) for 9 days. Two days after treatment initiation, the animals were bilaterally injected with Aβ(1-40) into the CA1/DG region of the hippocampus, subjected to active avoidance testing for 7 days, and sacrificed for immunohistochemical examination of four caspases (3, 6, 8, and 9) and three proteins of the Bcl-2 family (Bcl-2, Bax, and Bad). Injection of Aβ resulted in neurodegeneration, DNA fragmentation, increased Bcl-2 immunostaining, and significantly impaired performance in an active avoidance task, all which were significantly attenuated in rats treated with memantine. No differences in immunoreactivity of caspases 3, 6, 8, and 9 were discovered between groups after 7 days. Additional experiments demonstrated that an increase in caspase 8 immunostaining, observed 3 days after Aβ(1-40) injection, was significantly attenuated in memantine-treated rats. These data suggest that, in rats, memantine can prevent amyloid-triggered expression of apoptosis-related markers and concomitant cognitive deficits. PMID:22824463

  7. Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A.

    Science.gov (United States)

    Mohan, Syam; Abdelwahab, Siddig Ibrahim; Kamalidehghan, Behnam; Syam, Suvitha; May, Koh Sue; Harmal, Nabil Saad Mohammed; Shafifiyaz, Noor; Hadi, A Hamid A; Hashim, Najihah Mohd; Rahmani, Mawardi; Taha, Manal Mohamed Elhassan; Cheah, Shiau-Chuen; Zajmi, Asdren

    2012-08-15

    The plant Artocarpus obtusus is a tropical plant that belongs to the family Moraceae. In the present study a xanthone compound Pyranocycloartobiloxanthone A (PA) was isolated from this plant and the apoptosis mechanism was investigated. PA induced cytotoxicity was observed using MTT assay. High content screening (HCS) was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Reactive oxygen species formation was investigated on treated cells by using fluorescent analysis. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition mRNA levels of Bax and Bcl2 were also checked using RT-PCR. Caspase 3/7, 8 and 9 were measured for their induction while treatment. The involvement of NF-κB was analyzed using HCS assay. The results showed that PA possesses the characteristics of selectively inducing cell death of tumor cells as no inhibition was observed in non-tumorigenic cells even at 30 μg/ml. Treatment of MCF7 cells with PA induced apoptosis with cell death-transducing signals, that regulate the MMP by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of cytochrome c triggered the activation of caspases-9, then activates downstream executioner caspase-3/7 and consequently cleaved specific substrates leading to apoptotic changes. This form of apoptosis was found closely associated with the extrinsic pathway caspase (caspase-8) and inhibition of translocation of NF-κB from cytoplasm to nucleus. The results demonstrated that PA induced apoptosis of MCF7 cells through NF-κB and Bcl2/Bax signaling pathways with the involvement of caspases.

  8. The Facilitators and Barriers to Communication between Nurses and Family Member in Intensive Care Unit in Kerman, Iran

    OpenAIRE

    Laleh loghmani; Fariba borhani; Abbas Abbaszadeh

    2014-01-01

    Introduction: The communication between nurses and patients' families is commun- ication significantly impacts patient well-being as well as the quality and outcome of nursing care, this study aimed to demonstrated the facilitators and barriers which influence the role of communication among Iranian nurses and families member in ICU. Methods: This study was conducted by the grounded theory method. Participants comprised eight registered nurses and ten families. Patients were admitted to the ...

  9. In the aftermath of teenage suicide: A qualitative study of the psychosocial consequences for the surviving family members

    OpenAIRE

    Johansson Lars; Lindqvist Per; Karlsson Urban

    2008-01-01

    Abstract Background Studies of family reactions following teenage suicide are hampered by the psychological difficulties of approaching families and recruiting an unbiased sample of study subjects. By using a small but consecutive series of cases, we examined the qualitative aspects of loosing a teenage family member due to suicide. Such an understanding is important for future organisation of proper programs that provide professional support in the grief process. Methods From a large project...

  10. Thalassaemia: a study on the perception of patients and family members.

    Science.gov (United States)

    Wahab, I Abdul; Naznin, M; Nora, M Z; Suzanah, A R; Zulaiho, M; Faszrul, A R Aidl; Kamaruzaman, W S

    2011-10-01

    Marked improvement in the management of thalassaemia has not been matched by progress in psychosocial rehabilitation as thalassaemia continues to pose challenges to patients and their family members. Few studies have been carried out in Malaysia to look at such issues. This study is therefore to explore the concerns, beliefs and feelings about thalassaemia. It was conducted in the year 2009 over 7 months on "focus groups", in patients aged 8-22 years and parents attending Paediatric Clinic of Tengku Ampuan Afzan Hospital, Kuantan, Pahang. Results showed that concerns and adverse impact were related to lower grades in education, poor self-image, less chance of employment, marriage, financial burden and social integration. Compliance to subcutaneous iron chelator was poor. There were various concerns related to blood transfusion therapy. It is evident that thalassaemia greatly affects the psychosocial dimensions and a more structured long term psychosocial support is needed to improve quality of life of patients. PMID:22299552

  11. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.

    Science.gov (United States)

    Wang, Kun; Zhou, Bing; Kuo, Yien-Ming; Zemansky, Jason; Gitschier, Jane

    2002-07-01

    The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an approximately 3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as "hZIP4," which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc.

  12. Phenylboronic acid-functionalized polyamidoamine-mediated Bcl-2 siRNA delivery for inhibiting the cell proliferation.

    Science.gov (United States)

    Wu, Di; Yang, Jiebing; Xing, Zhen; Han, Haobo; Wang, Tingting; Zhang, Aijun; Yang, Yan; Li, Quanshun

    2016-10-01

    In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG5k-Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment. PMID:27371891

  13. Bcl-2 and N-Myc Coexpression Increases IGF-IR and Features of Malignant Growth in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Rama Jasty

    2001-01-01

    Full Text Available The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB2, Bcl2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR.

  14. Association of BCL2-938C>A genetic polymorphism with glioma risk in Chinese Han population.

    Science.gov (United States)

    Li, Wei; Qian, Chunfa; Wang, Linxiong; Teng, Hong; Zhang, Li

    2014-03-01

    Glioma is the most common type of primary brain malignancy in adults. The anti-apoptotic protein B-cell lymphoma 2 (BCL2) has been implicated in the pathogenesis of glioma. This study aimed to evaluate the potential association between BCL2-938C>A genetic polymorphism and glioma susceptibility. This case-control study was conducted in Chinese Han populations consisting of 248 glioma cases and 252 cancer-free controls. The BCL2-938C>A genetic polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data suggested that the genotype/allele of BCL2-938C>A polymorphism were statistically associated with the increased risk of glioma where the risk of glioma for genotype AA or allele A is significantly higher than wild genotype CC (odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.21-4.10, p = 0.009) or allele C (OR = 1.39, 95% CI 1.06-1.82, p = 0.016), respectively. In addition, the BCL2-938AA genotype was significantly more common in patients with glioblastoma and in patients with grade IV glioma. Our findings indicate that the BCL2-938C>A polymorphism is associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.

  15. Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival

    Institute of Scientific and Technical Information of China (English)

    De-Sheng Wang; Yu Li; Ke-Feng Dou; Kai-Zong Li; Zhen-Shun Song

    2006-01-01

    BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas-mediated cell death and to prolong recipient survival. METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft. RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group. CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

  16. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio

    Directory of Open Access Journals (Sweden)

    Azimahtol Hawariah LP

    2007-04-01

    Full Text Available Abstract Background Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines. Results Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 μg/ml. The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells. Conclusion Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.

  17. Telomerase activity, estrogen receptors (α, β), Bcl-2 expression in human breast cancer and treatment response

    International Nuclear Information System (INIS)

    The mechanism for maintaining telomere integrity is controlled by telomerase, a ribonucleoprotein enzyme that specifically restores telomere sequences, lost during replication by means of an intrinsic RNA component as a template for polymerization. Among the telomerase subunits, hTERT (human telomerase reverse transcriptase) is expressed concomitantly with the activation of telomerase. The role of estrogens and their receptors in the transcriptional regulation of hTERT has been demonstrated. The current study determines the possible association between telomerase activity, the expression of both molecular forms of estrogen receptor (ERα and ERβ) and the protein bcl-2, and their relative associations with clinical parameters. Tissue samples from 44 patients with breast cancer were used to assess telomerase activity using the TRAP method and the expression of ERα, ERβ and bcl-2 by means of immunocytochemical techniques. Telomerase activity was detected in 59% of the 44 breast tumors examined. Telomerase activity ranged from 0 to 49.93 units of total product generated (TPG). A correlation was found between telomerase activity and differentiation grade (p = 0.03). The only significant independent marker of response to treatment was clinical stage. We found differences between the frequency of expression of ERα (88%) and ERβ (36%) (p = 0.007); bcl-2 was expressed in 79.5% of invasive breast carcinomas. We also found a significant correlation between low levels of telomerase activity and a lack of ERβ expression (p = 0.03). Lower telomerase activity was found among tumors that did not express estrogen receptor beta. This is the first published study demonstrating that the absence of expression of ERβ is associated with low levels of telomerase activity

  18. Induction of apoptosis in HepG2 cells by solanine and Bcl-2 protein.

    Science.gov (United States)

    Ji, Y B; Gao, S Y; Ji, C F; Zou, X

    2008-01-17

    The nightshade (Solanum nigrum Linn.) has been widely used in Chinese traditional medicine as a remedy for the treatment of digestive system cancer. The anti-tumor activity of solanine, a steroid alkaloid isolated from the nightshade has been demonstrated. To observe the effect of anti-tumor and mechanism of solanine. The MTT assay was used to evaluate the IC(50) on the three digestive system tumor cell lines. The effect on the morphology was observed with a laser confocal microscopy; the rate of apoptosis and the cell cycle were measured using flow cytometry (FCM); the expression of Bcl-2 protein was measured by Western blot. The results show that the IC(50) for HepG(2), SGC-7901, and LS-174 were 14.47, >50, and >50 microg/ml, respectively; the morphology of cells in the negative control was normal; for the treated groups, typical signs for apoptosis were found. The rate of apoptosis in HepG(2) cells induced by solanine was found to be 6.0, 14.4, 17.3, 18.9, and 32.2%, respectively. Observation of the cell cycle showed that cells in the G(2)/M phases disappeared while the number of cells in the S phase increased significantly for treated groups. Western blot showed that solanine decreased the expression of Bcl-2 protein. Therefore, the target of solanine in inducing apoptosis in HepG(2) cells seems to be mediated by the inhibition in the expression of Bcl-2 protein.

  19. Rapamycin increases pCREB, Bcl-2, and VEGF-A through ERK under normoxia

    Institute of Scientific and Technical Information of China (English)

    Yudong Liu; Qixin Zheng; Hongbin Wu; Xiaodong Guo; Jingfeng Li; Shaofei Hao

    2013-01-01

    Rapamycin may serve as a new anti-osteosarcoma (OSA) agent due to its ability to inhibit the metastatic behavior of OSA.However,only limited benefit is observed in rodent studies and clinical trials using rapamycin as a single agent in the treatment of OSA.The target of rapamycin,mammalian target of rapamycin has multiple biological functions and may be linked with the kinases that mediate the phosphorylation of cyclic AMP-responsive element-binding (CREB) protein,an import factor in tumor progression.By employing an OSA cell line MG-63,we investigated how rapamycin regulates the phosphorylation of CREB (pCREB) at Ser133 and the expressions of two putative CREB targets,B-cell lymphoma 2 (Bcl-2)and vascular endothelial growth factor-A (VEGF-A).Under normoxia,we found that rapamycin (100nM)induced an increase of pCREB that was prevented by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 or cAMP-dependent protein kinase (PKA) inhibitor H89.However,H89 enhanced Akt phosphorylation and did not decrease the cell viability upon rapamycin treatment.In contrast,U0126 did not enhance Akt phosphorylation and decreased the cell viability upon rapamycin treatment.Moreover,U0126 prevented the rapamycin-induced increase of Bcl-2 and VEGF-A levels.Under hypoxia,rapamycin effectively prevented the hypoxia-induced increase of pCREB,Bcl-2,and VEGF-A.Our study demonstrated that rapamycin might be less effective in treating OSA cells under normoxia and provided the rationale for a combination of rapamycin and MEK/ERK inhibitor in the treatment of OSA.

  20. Targeting γ-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.

    Science.gov (United States)

    Su, Minfei; Mei, Yang; Sanishvili, Ruslan; Levine, Beth; Colbert, Christopher L; Sinha, Sangita

    2014-03-21

    γ-herpesviruses (γHVs) are common human pathogens that encode homologs of the anti-apoptotic cellular Bcl-2 proteins, which are critical to viral reactivation and oncogenic transformation. The murine γHV68 provides a tractable in vivo model for understanding general features of these important human pathogens. Bcl-XL, a cellular Bcl-2 homolog, and the murine γHV68 Bcl-2 homolog, M11, both bind to a BH3 domain within the key autophagy effector Beclin 1 with comparable affinities, resulting in the down-regulation of Beclin 1-mediated autophagy. Despite this similarity, differences in residues lining the binding site of M11 and Bcl-XL dictate varying affinities for the different BH3 domain-containing proteins. Here we delineate Beclin 1 differential specificity determinants for binding to M11 or Bcl-XL by quantifying autophagy levels in cells expressing different Beclin 1 mutants and either M11 or Bcl-XL, and we show that a G120E/D121A Beclin 1 mutant selectively prevents down-regulation of Beclin 1-mediated autophagy by Bcl-XL, but not by M11. We use isothermal titration calorimetry to identify a Beclin 1 BH3 domain-derived peptide that selectively binds to M11, but not to Bcl-XL. The x-ray crystal structure of this peptide bound to M11 reveals the mechanism by which the M11 BH3 domain-binding groove accommodates this M11-specific peptide. This information was used to develop a cell-permeable peptide inhibitor that selectively inhibits M11-mediated, but not Bcl-XL-mediated, down-regulation of autophagy.

  1. Functional conservation among members of the Salmonella typhimurium InvA family of proteins.

    Science.gov (United States)

    Ginocchio, C C; Galán, J E

    1995-02-01

    InvA, which is essential for Salmonella spp. to enter cultured epithelial cells, is a member of a family of proteins involved in either flagellar biosynthesis or the secretion of virulence determinants by a number of plant and mammalian pathogens. The predicted overall secondary structures of these proteins show significant similarities and indicate a modular construction with a hydrophobic amino-terminal half, consisting of six to eight potential transmembrane domains, and a hydrophilic carboxy terminus which is predicted to reside in the cytoplasm. These proteins can be aligned over the entire length of their polypeptide sequences, with the highest degree of homology found in the amino terminus and clusters of conserved residues in the carboxy terminus. We examined the functional conservation among members of this protein family by assessing the ability of MxiA of Shigella flexneri and LcrD of Yersinia pseudotuberculosis to restore invasiveness to an invA mutant of Salmonella typhimurium. We found that MxiA was able to complement the entry defect of the invA mutant strain of S. typhimurium. In contrast, LcrD failed to complement the same strain. However, a plasmid carrying a gene encoding a chimeric protein consisting of the amino terminus of LcrD and the carboxy terminus of InvA complemented the defect of the Salmonella invA mutant. These results indicate that the secretory systems in which these proteins participate are functionally similar and that the Salmonella and Shigella systems are very closely related. These data also suggest that determinants of specificity may be located at the carboxy termini of these proteins.

  2. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    Energy Technology Data Exchange (ETDEWEB)

    Duangtum, Natapol [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Junking, Mutita; Sawasdee, Nunghathai [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Cheunsuchon, Boonyarit [Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Limjindaporn, Thawornchai, E-mail: limjindaporn@yahoo.com [Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai, E-mail: grpye@mahidol.ac.th [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand)

    2011-09-16

    Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.

  3. Oncogenic intra-p53 family member interactions in human cancers

    Directory of Open Access Journals (Sweden)

    Maria eFerraiuolo

    2016-03-01

    Full Text Available The p53 gene family members p53, p73 and p63 display several isoforms derived from the presence of internal promoters and alternative splicing events. They are structural homologues but hold peculiar functional properties. p53, p73 and p63 are tumor suppressor genes that promote differentiation, senescence and apoptosis. p53, unlike p73 and p63, is frequently mutated in cancer often displaying oncogenic gain of function (GOF activities correlated with the induction of proliferation, invasion, chemoresistance and genomic instability in cancer cells. These oncogenic functions are promoted either by the aberrant transcriptional cooperation of mutant p53 (mutp53 with transcription cofactors (e.g., NF-Y, E2F1, Vitamin D Receptor (VDR, Ets-1, NF-kB and YAP or by the interaction with the p53 family members, p73 and p63, determining their functional inactivation. The instauration of these aberrant transcriptional networks leads to increased cell growth, low activation of DNA damage response pathways (DNA damage response (DDR, DNA double-strand breaks (DSBs response, enhanced invasion and high chemoresistance to different conventional chemotherapeutic treatments. Several studies have clearly shown that different cancers harboring mutant p53 proteins exhibit a poor prognosis when compared to those carrying wild type p53 (wt-p53 protein. The interference of mutantp53/p73 and/or mutantp53/p63 interactions, thereby restoring p53, p73 and p63 tumor suppression functions, could be among the potential therapeutic strategies for the treatment of mutant p53 human cancers.

  4. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    International Nuclear Information System (INIS)

    Highlights: → Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). → The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. → The co-localization between kAE and KIF3B was detected in human kidney tissues. → A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. → KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of α-intercalated cells of the kidney collecting duct leads to the defect of the Cl-/HCO3- exchange and the failure of proton (H+) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney α-intercalated cells.

  5. Effect of captopril and paraquat on expression of p53 and Bcl-2 genes and proteins in rat lung tissue using RT-PCR and immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Azizi E

    2008-10-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Paraquat is an herbicide produced and used prevalently worldwide. Studies have shown that lung fibrosis induced by paraquat can be prevented or delayed by certain antioxidants, iron chelating agents, melatonin, and, recently, blood pressure lowering drugs such as captopril."n"n Methods: The protective effects of captopril on paraquat toxicity were studied using RT-PCR and immunohistochemistry to determine the gene and protein expression of p53 and Bcl-2 in lung tissue samples from rats treated with captopril before and after exposure to paraquat."n"n Results: We found no significant difference in the gene and protein expression of p53 in different tissue samples, except for mRNA levels in the lung tissue of captopril-treated rats. However, the protein expression of Bcl-2 is greater in tissue from rats exposed to paraquat alone and paraquat together with pre- and posttreatment with captopril compared to tissue from untreated control rats and from those treated with captopril alone, which can be due to inflammatory responses of lung tissue. By RT-PCR, we were unable to detect Bcl-2 in lung tissue samples."n"n Conclusion: These results show that paraquat does not induce significant DNA damage; therefore, the

  6. Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients

    Directory of Open Access Journals (Sweden)

    Elainy Patricia Lino Gasparotto

    2011-12-01

    Full Text Available Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV. This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005. CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020; while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19 compared with controls (1.39 and 2.01, p=0.006 and p=0.020. CD34+ cells in PV patients showed an elevated Bid expression (14.4 in comparison with healthy subjects (1.0; p=0.002. Patients' leukocytes showed an A1 augmentation (7.41, p=0.001 and a reduced expression of Bax (0.19; p=0.040 and Bad (0.2; p=0.030. There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV. Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005. Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020 e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19 em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0

  7. Bcl-2 and Ki-67 Expression in Young Women with Breast Cancer

    OpenAIRE

    Arsenal Alikanoðlu

    2012-01-01

    Aim:  Incidence of breast cancer increases with age and nearly 85% of them are diagnosed after the age of 50. Clinical outcome of breast cancer  in young patients is worse than older patients. The aim of this study is to search  the  difference in expression of bcl-2 and Ki-67 between young and older women with breast cancer, and  if there is any; its clinical importance. Material and Method: This study includes 15 patients under the age of 35 years old (Group A) and ...

  8. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family

    DEFF Research Database (Denmark)

    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A;

    2007-01-01

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low densit...... to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins. Udgivelsesdato: 2007-Mar-27......Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density...... lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited...

  9. Pushing or pulling of the business by family members: A study of family businesses in Sri Lanka

    OpenAIRE

    Kuruppuge, Ravindra Hewa; Gregar, Aleš

    2015-01-01

    A number of family business researches affirm benefits of family involvement to the business while some of other studies assure only detriments of family involvement. When comparative studies of family businesses begin to surface on the family involvement in business, there is that irritating question on what effect is brought about by family involvement to the business. Therefore, the purpose of this study is to explore business advantages and disadvantages generated by family involvement in...

  10. 雌激素对大鼠胸腺细胞凋亡及Bcl-2、Bax表达的影响%Effects of estrogen on apoptosis and expression of Bcl-2 and Bax in rat thymus

    Institute of Scientific and Technical Information of China (English)

    李雅娜; 孙研; 崔春红; 殷彦君

    2011-01-01

    目的:探讨苯甲酸雌二醇对大鼠胸腺Bcl-2和Bax表达及细胞凋亡的影响及其机制.方法:雌性大鼠行卵巢切除术,给予苯甲酸雌二醇后,观察胸腺指数的变化,Hochest33342荧光染色及透射电镜标本观察胸腺细胞凋亡情况,免疫组织化学检测胸腺组织中Bcl-2和Bax的表达情况,原位杂交技术检测Bcl-2、Bax m RNA的表达情况.结果:双侧卵巢切除组大鼠胸腺指数较假手术组增加,双侧卵巢切除+雌激素组大鼠胸腺指数较双侧卵巢切除组减小;假手术组和双侧卵巢切除组大鼠胸腺组织中以正常胸腺细胞为主,偶见凋亡细胞或凋亡小体,双侧卵巢切除+雌激素组可见较多凋亡细胞和凋亡小体;双侧卵巢切除+雌激素组大鼠胸腺组织中Bcl-2表达较双侧卵巢切除组和假手术组增高明显降低,而Bax表达呈现相反趋势;Bcl-2 mRNA、Bax mRNA的表达与Bcl-2、Bax的表达呈一致性.结论:雌激素可以降低大鼠胸腺指数,抑制胸腺组织中Bcl-2的表达,促进Bax的表达,从而诱导大鼠胸腺细胞凋亡,促进雌性大鼠胸腺退化.%Objective-. To explore the effects of estrogen on the apoptosis and the expression of Bcl-2 and Bax in rat thymus. Methods-. The rats performed with ovariectomy were injected with estradiol benzoate. Thymus was obtained 7 days after the injection. Thymic indexes were measured. Apoptosis of the thymus was detected after Hochest 33342 staining and examined under an electron microscope. The expression of Bcl-2 and Bax in the thymus was detected with a immunohistochemical method. The expression of Bcl-2 mRNA and Bax mRNA in the thymus was detected by in situ hybridization. The test was taken in statistical treatment. Results: The thymus quality index in ovariectomy group was higher than that in the model control group. The thymus quality index of rats injected with estradiol benzoate was reduced respectively. Apoptotic cells and apoptotic bodies were found in the

  11. Expression and significance of Bcl-2 gene and Bax gene in lung cancer%凋亡相关基因bcl-2和bax在肺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    郭雷; 王福昌; 杨五计

    2001-01-01

    To study the relationship between expression of bcl-2 and baxgene and lung cancer.The bcl-2 and bax gene expression in 51 lung cancer tissues and tissues near cancer were deteeted by immunohistochemical SP method.The positive degree of bcl-2 gene expression in lung cancer was higher than that in tissues near cancer.The positive degree of bax gene expression in lung cancer was lower than that in tissues near cancer.Both differences were very significant(P<0.01).There was no correlations between the immunoreactivity of bcl-2 and bax gene and histology,gender,smoking history,clinical subtypes,stage and lymphatic metastasis(P>0.05).It suggests that bcl-2 and bax gene may play an important role in tumorgenesis and tumor development.The detection and determination of bcl-2 and bax gene in preinvasive lesions may contribute to the early diagnosis of lung cancer.Some drugs can down-regulate bcl-2 expression and speed apoptosis so as to improve the sensitivity to chemical therapy and radiation.%为探讨B细胞淋巴瘤/白血病-2(bcl-2)基因及其同源类似物bax基因的表达与肺癌发生的关系,应用免疫组化SP法检测了51例肺癌患者的肺癌标本及其癌旁组织中bcl-2、bax的表达。结果显示,bcl-2在肺癌中染色比在癌旁组织中深,bax在肺癌中染色比在癌旁组织中浅,两者之间均有极显著差异(P<0.01);bcl-2、bax表达与肺癌的组织分型、患者的性别、吸烟史、临床分型、分期及淋巴结转移无关(P>0.05)。提示:①bcl-2、bax在肺癌发生中具有重要作用。②在癌前病变组织中检测并比较bcl-2和bax的表达,有利于肺癌的早期诊断。③可通过药物使bcl-2表达降低,促进凋亡,提高患者对放、化疗的敏感性。

  12. A Grounded Theory of Students' Long-Distance Coping With a Family Member's Cancer.

    Science.gov (United States)

    Basinger, Erin D; Wehrman, Erin C; Delaney, Amy L; McAninch, Kelly G

    2015-08-01

    In this study, we explore how family members cope with one source of stress-cancer diagnosis and treatment. We suggest that coping away from one's family is characterized by constraints that are not common to proximal coping. We conducted six focus groups with college students (N = 21) at a university in the United States to investigate their long-distance coping experiences and used grounded theory methods to develop a model of college students' long-distance coping. Negotiating the tension between being here (at school) and being there (at home) was central to their experiences. Participants described four manifestations of their negotiation between here and there (i.e., expressing/hiding emotion, longing to care for the patient there/avoiding responsibility here, feeling shock at degeneration there/escaping degeneration by being here, and lacking information from there) and three strategies they used to cope (i.e., being here and withdrawing, being here and doing school, and seeking/not seeking support). PMID:25794524

  13. Organic anion transporter (Slc22a) family members as mediators of toxicity

    International Nuclear Information System (INIS)

    Exposure of the body to toxic organic anions is unavoidable and occurs from both intentional and unintentional sources. Many hormones, neurotransmitters, and waste products of cellular metabolism, or their metabolites, are organic anions. The same is true for a wide variety of medications, herbicides, pesticides, plant and animal toxins, and industrial chemicals and solvents. Rapid and efficient elimination of these substances is often the body's best defense for limiting both systemic exposure and the duration of their pharmacological or toxicological effects. For organic anions, active transepithelial transport across the renal proximal tubule followed by elimination via the urine is a major pathway in this detoxification process. Accordingly, a large number of organic anion transport proteins belonging to several different gene families have been identified and found to be expressed in the proximal nephron. The function of these transporters, in combination with the high volume of renal blood flow, predisposes the kidney to increased toxic susceptibility. Understanding how the kidney mediates the transport of organic anions is integral to achieving desired therapeutic outcomes in response to drug interactions and chemical exposures, to understanding the progression of some disease states, and to predicting the influence of genetic variation upon these processes. This review will focus on the organic anion transporter (OAT) family and discuss the known members, their mechanisms of action, subcellular localization, and current evidence implicating their function as a determinant of the toxicity of certain endogenous and xenobiotic agents

  14. Identification and antimicrobial resistance of members from the Enterobacteriaceae family isolated from canaries (Serinus canaria

    Directory of Open Access Journals (Sweden)

    Ruben V. Horn

    2015-06-01

    Full Text Available Abstract: The Enterobacteriaceae family contains potentially zoonotic bacteria, and their presence in canaries is often reported, though the current status of these in bird flocks is unknown. Therefore, this study aimed to identify the most common genera of enterobacteria from canaries (Serinus canaria and their antimicrobial resistance profiles. From February to June of 2013, a total of 387 cloacal swab samples from eight domiciliary breeding locations of Fortaleza city, Brazil, were collected and 58 necropsies were performed in canaries, which belonged to the Laboratory of Ornithological Studies. The samples were submitted to microbiological procedure using buffered peptone water and MacConkey agar. Colonies were selected according to their morphological characteristics on selective agar and submitted for biochemical identification and antimicrobial susceptibility. A total of 61 isolates were obtained, of which 42 were from cloacal swabs and 19 from necropsies. The most isolated bacteria was Escherichia coli with twenty five strains, followed by fourteen Klebsiellaspp., twelve Enterobacterspp., seven Pantoea agglomerans, two Serratiaspp. and one Proteus mirabilis. The antimicrobial to which the strains presented most resistance was sulfonamides with 55.7%, followed by ampicillin with 54.1% and tetracycline with 39.3%. The total of multidrug-resistant bacteria (MDR was 34 (55.7%. In conclusion, canaries harbor members of the Enterobacteriaceae family and common strains present a high antimicrobial resistance rate, with a high frequency of MDR bacteria.

  15. Integration analysis of MKK and MAPK family members highlights potential MAPK signaling modules in cotton.

    Science.gov (United States)

    Zhang, Xueying; Xu, Xiaoyang; Yu, Yujia; Chen, Chuan; Wang, Jing; Cai, Caiping; Guo, Wangzhen

    2016-01-01

    Mitogen-activated protein kinase (MAPK) cascades play a crucial role in plant growth and development, as well as their biotic and abiotic stress responses. As a nodal point of the MAPK cascade, the MKK gene family has not been systematically studied in cotton. Here, we identified 11 putative MKK genes in the Gossypium raimondii genome. Phylogenetic analysis showed that the MKKs were supported by architectures of conserved protein motifs. Expression patterns of MKKs under hormone treatments or abiotic stresses revealed their diverse functions in stress responses. Based on a yeast two hybrid, a total of 63 interactive pairs of MKKs and MAPKs were identified in cotton. Among these, 40 interactive pairs were newly identified compared to that reported previously in Arabidopsis. Integration analysis of the interaction network and expression patterns of MKK and MAPK family members revealed 13 potential MAPK signaling modules that are involved in the complicated cross-talk between hormones and abiotic stresses. Taken together, our data enhance the understanding of the evolution and function of MAPK cascades in cotton, and lay the foundation for the improvement of various defense responses that use MAPK signaling modules in the future. PMID:27417377

  16. Cloning and characterization of DcLEA1, a new member of carrot LEA gene family

    Institute of Scientific and Technical Information of China (English)

    LIU Yiming; DIAO Fengqiu; ZHANG Lei; HUANG Meijuan; WU Naihu

    2005-01-01

    Using a modified cDNA representational difference analysis (RDA) method, a LEA gene fragment was isolated from the regulated carrot somatic embryo, which was used as the probe to screen the cDNA library of the regulated carrot somatic embryo and the genomic library constructed by the method of altering osmotic pressure. Sequence analysis showed that it is homologous to LEA gene family and designated as DcLEA1 (GenBank number: AF308739), a new member of the carrot LEA gene family. Its transcription region contains 5′ UTR, two exons, one intron and 3′ UTR region; its coding region is 480 bp long, coding for 159 amino acids and one stop codon. Northern hybridization indicated that DcLEA1 gene was not expressed in the adult carrot but expressed at high levels in the regulated carrot somatic embryo. In carrot somatic embryo which had been deregulated for 12 hours, the expression levels dropped rapidly; with the prolongation of deregulation, the radicle of carrot somatic embryo began to stretch, and the expression level of DcLEA1 gene increased. This phenomenon is similar to the expression pattern of LEA gene in the course of dormancy and germination of the seed; thus suggesting that the sucrose regulation-deregulation system of the carrot somatic embryo can be used to mimic plant seed dormancy and germination and can also be used to study the molecular mechanisms of these two biological processes.

  17. Longitudinal Trajectories of Health Related Quality of Life in Danish Family Members of Individuals with Severe Brain Injury

    DEFF Research Database (Denmark)

    Norup, Anne; Snipes, Daniel J.; Siert, Lars;

    2013-01-01

    Scant research has examined health-related quality of life (HRQoL) in family members of patients with severe brain injury, even less has been done in Scandinavian countries, and none has examined this construct longitudinally. The current study therefore used multilevel modelling to investigate...... the trajectories of HRQoL in 94 Danish family members of patients with severe brain injury at five time points, beginning at the patient's stay in a neuro intensive care unit through one year after injury. The family members’ HRQoL scores significantly and strongly increased over time, and Role Limitations...... – Emotional scores were higher when patients had high Rancho Los Amigos Scale scores at admission to early intensive rehabilitation in hospital. These results suggest that the acute and sub-acute periods after brain injury are an extremely difficult time psychologically for many families, and family...

  18. Bcl-2 regulates HIF-1alpha protein stabilization in hypoxic melanoma cells via the molecular chaperone HSP90.

    Directory of Open Access Journals (Sweden)

    Daniela Trisciuoglio

    Full Text Available BACKGROUND: Hypoxia-Inducible Factor 1 (HIF-1 is a transcription factor that is a critical mediator of the cellular response to hypoxia. Enhanced levels of HIF-1alpha, the oxygen-regulated subunit of HIF-1, is often associated with increased tumour angiogenesis, metastasis, therapeutic resistance and poor prognosis. It is in this context that we previously demonstrated that under hypoxia, bcl-2 protein promotes HIF-1/Vascular Endothelial Growth Factor (VEGF-mediated tumour angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: By using human melanoma cell lines and their stable or transient derivative bcl-2 overexpressing cells, the current study identified HIF-1alpha protein stabilization as a key regulator for the induction of HIF-1 by bcl-2 under hypoxia. We also demonstrated that bcl-2-induced accumulation of HIF-1alpha protein during hypoxia was not due to an increased gene transcription or protein synthesis. In fact, it was related to a modulation of HIF-1alpha protein expression at a post-translational level, indeed its degradation rate was faster in the control lines than in bcl-2 transfectants. The bcl-2-induced HIF-1alpha stabilization in response to low oxygen tension conditions was achieved through the impairment of ubiquitin-dependent HIF-1alpha degradation involving the molecular chaperone HSP90, but it was not dependent on the prolyl hydroxylation of HIF-1alpha protein. We also showed that bcl-2, HIF-1alpha and HSP90 proteins form a tri-complex that may contribute to enhancing the stability of the HIF-1alpha protein in bcl-2 overexpressing clones under hypoxic conditions. Finally, by using genetic and pharmacological approaches we proved that HSP90 is involved in bcl-2-dependent stabilization of HIF-1alpha protein during hypoxia, and in particular the isoform HSP90beta is the main player in this phenomenon. CONCLUSIONS/SIGNIFICANCE: We identified the stabilization of HIF-1alpha protein as a mechanism through which bcl-2 induces the

  19. Bcl-2 Regulates HIF-1α Protein Stabilization in Hypoxic Melanoma Cells via the Molecular Chaperone HSP90

    Science.gov (United States)

    Trisciuoglio, Daniela; Gabellini, Chiara; Desideri, Marianna; Ziparo, Elio; Zupi, Gabriella; Del Bufalo, Donatella

    2010-01-01

    Background Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that is a critical mediator of the cellular response to hypoxia. Enhanced levels of HIF-1α, the oxygen-regulated subunit of HIF-1, is often associated with increased tumour angiogenesis, metastasis, therapeutic resistance and poor prognosis. It is in this context that we previously demonstrated that under hypoxia, bcl-2 protein promotes HIF-1/Vascular Endothelial Growth Factor (VEGF)-mediated tumour angiogenesis. Methodology/Principal Findings By using human melanoma cell lines and their stable or transient derivative bcl-2 overexpressing cells, the current study identified HIF-1α protein stabilization as a key regulator for the induction of HIF-1 by bcl-2 under hypoxia. We also demonstrated that bcl-2-induced accumulation of HIF-1α protein during hypoxia was not due to an increased gene transcription or protein synthesis. In fact, it was related to a modulation of HIF-1α protein expression at a post-translational level, indeed its degradation rate was faster in the control lines than in bcl-2 transfectants. The bcl-2-induced HIF-1α stabilization in response to low oxygen tension conditions was achieved through the impairment of ubiquitin-dependent HIF-1α degradation involving the molecular chaperone HSP90, but it was not dependent on the prolyl hydroxylation of HIF-1α protein. We also showed that bcl-2, HIF-1α and HSP90 proteins form a tri-complex that may contribute to enhancing the stability of the HIF-1α protein in bcl-2 overexpressing clones under hypoxic conditions. Finally, by using genetic and pharmacological approaches we proved that HSP90 is involved in bcl-2-dependent stabilization of HIF-1α protein during hypoxia, and in particular the isoform HSP90β is the main player in this phenomenon. Conclusions/Significance We identified the stabilization of HIF-1α protein as a mechanism through which bcl-2 induces the activation of HIF-1 in hypoxic tumour cells involving the

  20. Lentiviral-mediated delivery of Bcl-2 or GDNF protects against excitotoxicity in the rat hippocampus.

    Science.gov (United States)

    Wong, Liang-Fong; Ralph, G Scott; Walmsley, Lucy E; Bienemann, Alison S; Parham, Stephen; Kingsman, Susan M; Uney, James B; Mazarakis, Nicholas D

    2005-01-01

    Nutrient deprivation during ischemia leads to severe insult to neurons causing widespread excitotoxic damage in specific brain regions such as the hippocampus. One possible strategy for preventing neurodegeneration is to express therapeutic proteins in the brain to protect against excitotoxicity. We investigated the utility of equine infectious anemia virus (EIAV)-based vectors as genetic tools for delivery of therapeutic proteins in an in vivo excitotoxicity model. The efficacy of these vectors at preventing cellular loss in target brain areas following excitotoxic insult was also assessed. EIAV vectors generated to overexpress the human antiapoptotic Bcl-2 or growth factor glial-derived neurotrophic factor (GDNF) genes protected against glutamate-induced toxicity in cultured hippocampal neurons. In an in vivo excitotoxicity model, adult Wistar rats received a unilateral dose of the glutamate receptor agonist N-methyl-D-aspartate to the hippocampus that induced a large lesion in the CA1 region. Neuronal loss could not be protected by prior transduction of a control vector expressing beta-galactosidase. In contrast, EIAV-mediated expression of Bcl-2 and GDNF significantly reduced lesion size thus protecting the hippocampus from excitotoxic damage. These results demonstrate that EIAV vectors can be effectively used to deliver putative neuroprotective genes to target brain areas and prevent cellular loss in the event of a neurological insult. Therefore these lentiviral vectors provide potential therapeutic tools for use in cases of acute neurotrauma such as cerebral ischemia. PMID:15585409

  1. Targeting BCL-2 and ABL/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Leonard, Jessica T; Rowley, Joelle S J; Eide, Christopher A; Traer, Elie; Hayes-Lattin, Brandon; Loriaux, Marc; Spurgeon, Stephen E; Druker, Brian J; Tyner, Jeffrey W; Chang, Bill H

    2016-08-31

    Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies. We demonstrate that the combination of TKIs with venetoclax is highly synergistic in vitro, decreasing cell viability and inducing apoptosis in Ph(+)ALL. Furthermore, the multikinase inhibitors dasatinib and ponatinib appear to have the added advantage of inducing Lck/Yes novel tyrosine kinase (LYN)-mediated proapoptotic BCL-2-like protein 11 (BIM) expression and inhibiting up-regulation of antiapoptotic myeloid cell leukemia 1 (MCL-1), thereby potentially overcoming the development of venetoclax resistance. Evaluation of the dasatinib-venetoclax combination for the treatment of primary Ph(+)ALL patient samples in xenografted immunodeficient mice confirmed the tolerability of this drug combination and demonstrated its superior antileukemic efficacy compared to either agent alone. These data suggest that the combination of dasatinib and venetoclax has the potential to improve the treatment of Ph(+)ALL and should be further evaluated for patient care. PMID:27582059

  2. Bcl-2 Expression in the Aortas of Model Rats with Aldosterone-Producing Adenomas%Bcl-2在醛固酮腺瘤模型大鼠主动脉中的表达

    Institute of Scientific and Technical Information of China (English)

    闫永吉; 陈戬; 刘建和; 张劲松; 姜永明; 王光; 张海燕

    2011-01-01

    目的:观察醛固酮对主动脉Bcl-2表达的影响.方法:32只SD大鼠随机均分为4组:①空白溶剂设为对照(60%丙二醇+10%乙醇+30%双蒸水);②醛固酮腺瘤:泵入醛固酮(1μg/h);③醛固酮腺瘤+依普利酮组:依普利酮(100 mg·kg-1·d-1);④醛固酮腺瘤+肼苯哒嗪组:肼苯哒嗪(25 mg·kg-1·d-1).渗透泵内分别注入醛固酮或空白溶剂,然后将其埋植于大鼠背部皮下.8周后,免疫组织化学和免疫印迹检测主动脉Bcl-2的表达.结果:与对照组相比,腺瘤组大鼠主动脉Bcl-2表达显著减少(P<0.05);依普利酮能够拮抗醛固酮对Bcl-2表达的抑制作用(P<0.05).结论:醛固酮通过抑制Bcl-2表达,调节细胞凋亡状态,可能是醛固酮诱导主动脉重构的机制之一.%Objective: To observe the effect of aldosterone on Bcl-2 expression in the aorta. Methods: Thirtytwo male rats were randomly divided into 4 groups; vehicle (control), aldosterone-producing adenoma, aldosterone-producing adenoma plus eplerenone or hydralazine. They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle. After 8 weeks, Bcl-2 was examined by immunohistochemistry and Western blotting. Results:Compared with controls, the model rats with aldosterone-producing adenoma exhibited decreased aortic expression of Bcl-2. This effect of aldosterone was significantly reversed after co-treatment with eplerenone but not with hydralazine. Conclusions:This study's findings suggest that aldosterone directly suppresses aortic expression of Bcl-2 that may play an important role in aldosterone-induced aortic remodeling.

  3. Expression and Significance of Bcl-2, Bax, Fas and Caspase-3 in Different Phases of Human Hemangioma

    Institute of Scientific and Technical Information of China (English)

    YANG Hong; DENG Chenguo; SHEN Shengguo; ZHANG Duanlian; YUYing

    2006-01-01

    The relationship between Bcl-2, Bax, Fas, caspase-3 and development of hemangioma and the molecular mechanism was investigated. By using immunohistochemical S-P method, proliferating cell nuclear antigen was detected. According to the classification of Mulliken in combination with PCNA expression, 27 cases were identified as proliferating hemangioma and 22 cases as involutive hemangioma. Five normal skin tissues around the tumor tissue served as controls. By using immunohistochemical technique, the expression of Bcl-2, Bax, Fax and Caspase-3 was detected. The cells expressing Bcl-2, Bax, Fax and cappase-3 were identified as hemangioma endothelia by immunohistochemical staining of Ⅷ factor. The average absorbance (A) and average positive area rate of Bcl-2, Bax, Fas and caspase-3 expression were measured by using HPIAS-2000 imaging analysis system. The results showed that the expression of Bcl-2 in the endothelia of proliferating hemangioma was significantly higher that in involutive degenerative hemangioma endothelia and vascular endothelia of normal skin tissue (P<0.01). The expression of Bax, Fas and Caspase-3 in the endothelia of involutive hemangioma was obviously higher than in the endothelia of proliferating hemangioma and normal skin tissue (P<0.01). The expression of BAx and Fas in endothelia of proliferating hemangioma was higher than in those of normal skin tissue (P<0.05). It was suggested that Bcl-2,Bax, Fas and caspase-3 might be involved in the development and involution of hemangioma. Bcl-2 could promote the growth of hemangioma by inhibiting apoptosis of endothelia. Bax, Fas and caspase-3 promote the switch of hemangioma from proliferation to involution by inducing the apoptosis of hemangioma endothelia.

  4. The bcl-2, bax gene expression and apoptosis of continuous low-dose-rate irradiation on PC-3 transplanting tumor

    International Nuclear Information System (INIS)

    Objective: The aim of this study was to investigate bcl-2, bax expression and apoptosis of continuous low-dose-rate irradiation on prostate cancer (PC)-3 transplanting tumor. Methods: The expression of bcl-2 and bax associated with apoptosis between experiment and control groups were analyzed using immunohistochemistry at 48, 96 and 192 h after two 125I seed sources implanting model. The correlation between apoptosis and the ratio of bax/bcl-2 was analyzed using Bi-variable linear correlation. SPSS 11.0 was used to analyse the data. Results: The bcl-2 expression in experiment group began to down-regulated significantly after 125I seed irradiation for 48 h as compared with control(t=2.500, P=0.067), though it was not reached to statistical significance. At 96 and 192 h after irradiation, significantly low expression of bcl- 2 were noted (t=4.950, 3.464; P=0.008 and 0.026). In contrast, significantly over expression of bax was noted at 48, 96 and 192 h after 12si irradiation (t=3.334,4.025,5.292;P=0.029, 0.016 and 0.006). The apoptotic index (AI) for PC-3 at 48, 96 and 192 h after 125I irradiation were 22.3%, 21.7% and 30.7%, which was significantly higher than controls when at 96 and 192 h after 125I irradiation (P= 0.016 and 0.036). Moreover, positive correlation was noted between AI and bax/bcl-2 ratio (r=0.784, P= 0.012). Conclusion: Low-dose-rate irradiation could down-regulate the expression of bcl-2, up-regulate the expression of bax and induced PC-3 cells apoptosis. (authors)

  5. Associations of MMP-2, BAX, and Bcl-2 mRNA and Protein Expressions with Development of Atrial Fibrillation.

    Science.gov (United States)

    Diao, Shu-Ling; Xu, Hui-Pu; Zhang, Bei; Ma, Bao-Xin; Liu, Xian-Liang

    2016-01-01

    BACKGROUND To examine changes of mRNA and protein expressions of MMP-2, Bcl-2, and BAX in atrial fibrillation (AF) patients, and investigate the correlations among these 3 biomarkers. MATERIAL AND METHODS Rheumatic heart disease patients (n=158) undergoing cardiac surgical procedures for mitral valve repair or replacement were included as the AF group (n=123), containing paroxysmal AF (n=42), persistent AF (n=36), and permanent AF (n=45). Rheumatic heart disease patients with sinus rhythm (SR) (n=35) were enrolled as the SR group (control group). Immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) were applied to detect the protein and mRNA expression levels of MMP-2, Bcl-2, and BAX. Apoptosis was observed with light and electron microscopes and detected by TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS Compared with the SR group, the left atrial diameters (LADs), protein and mRNA expression levels of MMP-2 and BAX, apoptotic index (AI), and Bcl-2/BAX ratio were evidently increased in the 3 AF groups, but protein and mRNA expression levels of Bcl-2 decreased in the AF groups (all P<0.05). Correlation analysis found that MMP-2 protein expression levels was positively correlated with BAX expression, but negatively correlated with Bcl-2 expression levels. CONCLUSIONS Our study results suggest that elevated MMP-2 expression and disturbance balance of Bcl-2/BAX expressions may be associated with the development and maintenance of AF. MMP-2 may be involved in the development of AF through promoting BAX expressions and inhibiting Bcl-2. PMID:27141955

  6. Youth’s narratives about family members smoking: parenting the parent- it’s not fair!

    Directory of Open Access Journals (Sweden)

    Woodgate Roberta L

    2012-11-01

    Full Text Available Abstract Background Successful cancer prevention policies and programming for youth must be based on a solid understanding of youth’s conceptualization of cancer and cancer prevention. Accordingly, a qualitative study examining youth’s perspectives of cancer and its prevention was undertaken. Not surprisingly, smoking (i.e., tobacco cigarette smoking was one of the dominant lines of discourse in the youth’s narratives. This paper reports findings of how youth conceptualize smoking with attention to their perspectives on parental and family-related smoking issues and experiences. Methods Seventy-five Canadian youth ranging in age from 11–19 years participated in the study. Six of the 75 youth had a history of smoking and 29 had parents with a history of smoking. Youth were involved in traditional ethnographic methods of interviewing and photovoice. Data analysis involved multiple levels of analysis congruent with ethnography. Results Youth’s perspectives of parents and other family members’ cigarette smoking around them was salient as represented by the theme: It’s not fair. Youth struggled to make sense of why parents would smoke around their children and perceived their smoking as an unjust act. The theme was supported by four subthemes: 1 parenting the parent about the dangers of smoking; 2 the good/bad parent; 3 distancing family relationships; and 4 the prisoner. Instead of being talked to about smoking it was more common for youth to share stories of talking to their parents about the dangers of smoking. Parents who did not smoke were seen by youth as the good parent, as opposed to the bad parent who smoked. Smoking was an agent that altered relationships with parents and other family members. Youth who lived in homes where they were exposed to cigarette smoke felt like a trapped prisoner. Conclusions Further research is needed to investigate youth’s perceptions about parental cigarette smoking as well as possible linkages

  7. Facebook as a tool for communication, collaboration, and informal knowledge exchange among members of a multisite family health team

    Science.gov (United States)

    Lofters, Aisha K; Slater, Morgan B; Nicholas Angl, Emily; Leung, Fok-Han

    2016-01-01

    Objective To implement and evaluate a private Facebook group for members of a large Ontario multisite Family Health Team (FHT) to facilitate improved communication and collaboration. Design Program implementation and subsequent survey of team members. Setting A large multisite FHT in Toronto, Ontario. Participants Health professionals of the FHT. Main outcome measures Usage patterns and self-reported perceptions of the Facebook group by team members. Results At the time of the evaluation survey, the Facebook group had 43 members (37.4% of all FHT members). Activity in the group was never high, and posts by team members who were not among the researchers were infrequent throughout the study period. The content of posts fell into two broad categories: 1) information that might be useful to various team members and 2) questions posed by team members that others might be able to answer. Of the 26 team members (22.6%) who completed the evaluation survey, many reported that they never logged into the Facebook page (16 respondents), and never used it to communicate with team members outside of their own site of practice (19 respondents). Only six respondents reported no concerns with using Facebook as a professional communication tool; the most frequent concerns were regarding personal and patient privacy. Conclusion The use of social media by health care practitioners is becoming ubiquitous. However, the issues of privacy concerns and determining how to use social media without adding to provider workload must be addressed to make it a useful tool in health care. PMID:26869796

  8. Exploring biological and pathological functions of TGFβ family member activin C

    International Nuclear Information System (INIS)

    Activins and their antagonists inhibins are cytokines of the transforming growth factor β family (TGFβ), with important regulatory functions in a wide array of physiological processes. Activins are homo- or heterodimers consisting of two disulfide-linked β subunits, four mammalian activin β subunits - βA, βB, βC, βE - have been identified in mammalian cells. Inhibins in contrast are heterodimers composed of an β subunit and a β subunit. Whereas the expression of βA and βB subunits is high and widely distributed in many organs, the βC and βE subunits are predominantly expressed in the liver. Activin A is by far the best investigated activin. It has been implicated for instance in reproductive biology, embryonic development, homeostasis, inflammation and tissue repair. In the liver it contributes to regulation of cell growth, apoptosis and tissue architecture. Additionally, deregulation of activin A signaling accounts for pathologic conditions such as hepatic inflammation, fibrosis and carcinogenesis. The biological functions of the other family members and their involvement in liver biology and diseases are still poorly understood. The first part of this work deals with the mRNA expression pattern of the complete inhibin gene family to obtain novel insights into possible functions of activins and inhibins in human hepatocellular carcinogenesis. Using quantitative real-time PCR analysis we found strongly increased inhibin β subunit expression comparing samples of hepatocellular carcinoma and tumor surrounding tissue to samples from healthy donors. All four β subunits were expressed in normal and patient samples, whereas expression of βB subunit increased from normal to malignant samples. This study is the first to report a significant relation of the inhibin β and inhibin βB mRNA levels to human hepatocellular carcinoma. Furthermore, these data, different from those in rodent model systems, suggest a tumor promoting role of inhibin and activin

  9. A conserved role for syndecan family members in the regulation of whole-body energy metabolism.

    Directory of Open Access Journals (Sweden)

    Maria De Luca

    syndecan family members play a key role in the regulation of body metabolism.

  10. Identification of the salmon somatolactin receptor, a new member of the cytokine receptor family.

    Science.gov (United States)

    Fukada, Haruhisa; Ozaki, Yuichi; Pierce, Andrew L; Adachi, Shinji; Yamauchi, Kohei; Hara, Akihiko; Swanson, Penny; Dickhoff, Walton W

    2005-05-01

    Somatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so far has been found only in fish. Compared with GH and PRL, the primary structure of SL is highly conserved among divergent fish species, suggesting it has an important function and a discriminating receptor that constrains structural change. However, SL functions are poorly understood, and receptors for SL have not yet been identified. During cloning of GH receptor cDNA from salmon, we found a variant with relatively high (38-58%) sequence identity to vertebrate GH receptors and low (28-33%) identity to PRL receptors; however, the recombinant protein encoding the extracellular domain showed only weak binding of GH. Ligand binding of the recombinant extracellular domain for this receptor confirmed that the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common features of a GH receptor including FGEFS motif, six cysteine residues in the extracellular domain, a single transmembrane region, and Box 1 and 2 regions in the intracellular domain. These structural characteristics place the SLR in the cytokine receptor type I homodimeric group, which includes receptors for GH, PRL, erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver and fat, supporting the notion that a major function of SL is regulation of lipid metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and target tissues in fish, and perhaps novel members of this receptor family in other vertebrates. PMID:15718271

  11. Heterogeneous breakpoints on the immunoglobulin genes are involved in fusion with the 5' region of BCL2 in B-cell tumors.

    Science.gov (United States)

    Yonetani, N; Ueda, C; Akasaka, T; Nishikori, M; Uchiyama, T; Ohno, H

    2001-09-01

    The 5' flanking region of the BCL2 gene (5'-BCL2) is a breakpoint cluster of rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21) affecting the 3' region of BCL2, 5'-BCL2 can fuse to not only the heavy chain gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and sequencing of a total of eleven 5'-BCL2 / IGs junctional areas of B-cell tumors, which were amplified by long-distance polymerase chain reaction-based assays. The breakpoints on 5'-BCL2 were distributed from 378 to 2312 bp upstream of the translational initiation site and, reflecting the alteration of regulatory sequences of BCL2, 5'-BCL2 / IGs-positive cells showed markedly higher levels of BCL2 expression than those of t(14;18)-positive cells. In contrast, the breakpoints on the IGs were variable. Two 5'-BCL2 / IGH and two 5'-BCL2 / IGLkappa junctions occurred 5' of the joining (J) segments, suggesting operation of an erroneous variable (V) / diversity (D) / J and V / J rearrangement mechanism. However, two other 5'-BCL2 / IGH junctions affected switch regions, and the kappa-deleting element, which is located 24 kb downstream of the constant region of IGLkappa, followed the 5'-BCL2 in another case. One 5'-BCL2 / IGLkappa and two 5'-BCL2 / IGLlambda junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5'-BCL2 fused 3' of a Vlambda gene that was upstream of another Vlambda / Jlambda complex carrying a non-producing configuration, indicating that the receptor editing mechanism was likely involved in this rearrangement. Our study revealed heterogeneous anatomy of the 5'-BCL2 / IGs fusion gene leading to transcriptional activation of BCL2, and suggested that the mechanisms underlying the formation of this particular oncogene / IGs recombination are not identical to those of t(14;18).

  12. Bcl-2基因与神经生长因子(NGF)抑制神经细胞凋亡的研究%Abaissement role of bcl-2 gene and NGF on the apoptosis of nerve cel s

    Institute of Scientific and Technical Information of China (English)

    韩贵和; 魏威; 顾军

    2013-01-01

    目的探讨原癌基因bcl-2与神经生长因子(NGF)联合应用对抑制神经细胞凋亡的协同作用。方法培养PC12细胞至对数生长期,用100感染复数(multiplicity of infection,MOI)的携带bcl-2基因的慢病毒质粒及未携带bcl-2基因的慢病毒质粒感染PC12细胞。再将其分为A、B、C、D、E、F六组,A组为bcl-2-PC12细胞培养液中不加H2O2及NGF(bcl-2-PC12组);B组为bcl-2-PC12细胞培养液中加H2O2(bcl-2-PC12+ H2O2组);C组为bcl-2-PC12细胞培养液中加H2O2及NGF(bcl-2-PC12+ H2O2+NGF组)。D组为NC-PC12细胞培养液中不加H2O2及NGF(NC-PC12组);E组为NC-PC12细胞培养液中加H2O2(NC-PC12+H2O2组);F组为NC-PC12细胞培养液中加H2O2及NGF(NC-PC12+ H2O2+NGF组)。应用流式细胞仪检测各组细胞的凋亡率,采用BCA(bicinchoninic acid)法检测bcl-2基因表达蛋白浓度,数据进行统计学分析。结果 A组细胞凋亡率较D组低(u=2.16,0.02bcl-2基因表达蛋白浓度高于D组(t=2.87,0.005bcl-2基因及NGF均对正常神经细胞的凋亡有抑制作用,能够增强神经细胞的抗损伤能力,二者联合应用时具有协同作用。%Objective To approach synergia abaissement role of the proto-oncogene bcl-2 and NGF on the apoptosis of nerve cells.Methods PC12 cells were cultured to the logarithmic growth phase,slow virus plasmid carrying the bcl-2 gene and slow virus plasmid infected respectively PC12 cells by 100 MOI.Then they were divided into six groups(groupA,groupB,groupC ,groupD,groupE and groupF ). Group A:PC12 cells with slow virus plasmid carrying the bcl-2 gene.Group B: PC

  13. Expression of the Bcl-2 apoptotic marker in cats diagnosed with inflammatory bowel disease and gastrointestinal lymphoma.

    Science.gov (United States)

    Swanson, Christine M; Smedley, Rebecca C; Saavedra, Paulo Vilar; Kiupel, Matti; Kitchell, Barbara E

    2012-10-01

    Immunolabeling for the critical lymphocyte survival factor, Bcl-2, of intestinal biopsies from cats with histologic evidence of inflammatory bowel disease (IBD) or gastrointestinal (GI) lymphoma was evaluated to determine if expression differed significantly between these two disease processes. Immunolabeling for Bcl-2 was performed on small intestinal endoscopic or full thickness biopsy sections from 55 cats. Diagnosis of IBD, T-cell lymphoma or B-cell lymphoma was established previously. The percentage of infiltrating lymphocytes that were positively labeled for Bcl-2 was subjectively determined for each case. Eight cats were diagnosed with IBD and 47 cats with lymphoma. A significantly higher percentage of cells were positively immunolabeled for Bcl-2 in cats with GI lymphoma [median (range); 90 (5-95)%] compared with cats with IBD [60 (15-95)%] (P = 0.029). However, the overall degree of positive immunolabeling in both groups tended to be high. This over-expression of Bcl-2 may prove useful as a therapeutic target for IBD and GI lymphoma in cats.

  14. Study of Bcl-2 siRNA Enhancement of Sensitivity of HL-60 Cells to All Trans Retinoic Acid

    Institute of Scientific and Technical Information of China (English)

    Haiyan Hu; Yuan Zhang; Dongmei He

    2008-01-01

    OBJECTIVE To study whether siRNA targeting against the Bcl-2gene can enhance sensitivity of HL-60 cells to all trans retinoic acid (ATRA).METHODS siRNA, which is a leading sequence selected by previous experiments, was transferred into HL-60 cells. At 6 h after transfection, the cells were cultured with ATRA. The cell growth of the HL-60 cells was measured by the MTT assay at 24,48, 72 h. The level of the Bcl-2 protein and ROS (reactive oxygen species) as well as membrane potential of the mitochondria were determined by flowcytometry.RESULTS siRNA significantly increased the inhibitory effect of ATRA on growth of the HL-60 cells. The combination of siRNA with ATRA resulted in a decrease in the Bcl-2 protein level and an increase in the ROS level as well as significantly lowering the mitochondrial membrane potential of the HL-60 cells (P < 0.05).CONCLUSION Effective siRNA targeting of Bcl-2 increases the sensitivity of HL-60 leukemic cells to ATRA by inhibiting the expression of the Bcl-2 protein.

  15. Di-(2-ethylhexyl) phthalate induces apoptosis of GC-2spd cells via TR4/Bcl-2 pathway.

    Science.gov (United States)

    Zhu, Lishan; Lu, Jinchang; Tang, Xiao; Fu, Guoqing; Duan, Peng; Quan, Chao; Zhang, Ling; Zhang, Zhibing; Chang, Wei; Shi, Yuqin

    2016-06-01

    Di-(2-ethylhexyl) phthalate (DEHP) is a widely used environmental endocrine disruptor. Many studies have reported that DEHP exposure causes reproductive toxicity and cells apoptosis. However, the mechanism by which DEHP exposure causes male reproductive toxicity remains unknown. This study investigated the role of the testicular orphan nuclear receptor4 (TR4)/Bcl-2 pathway in apoptosis induced by DEHP, which resulted in reproductive damage. To elucidate the mechanism underpinning the male reproductive toxicity of DEHP, we sought to investigate apoptotic effects, expression levels of TR4/Bcl-2 pathway in GC-2spd cells, including TR4, Bcl-2 and caspase-3. GC-2spd cells were exposed to various concentrations of DEHP (0, 50, 100, or 200μM). The results indicated that, with the increase of the concentrations of DEHP, the survival rate of cell decreased gradually. DEHP exposure at over 100μM significantly induced apoptotic cell death. DEHP decreased SOD and GSH-Px activity in 200μM group. Compared to the control group, the mRNA levels of caspase-3 increased significantly, however, Bcl-2 mRNA decreased (PBcl-2 and procaspase-3 protein levels. Taken together, these results lead us to speculate that in vitro exposure to DEHP might induce apoptosis in GC-2spd cells through the TR4/Bcl-2 pathway. PMID:27084994

  16. 奥曲肽对人肝星状细胞凋亡及Bcl-2/Bax表达的影响%Effects of octreotide on the apoptosis of human HSCs and expression of Bcl-2/Bax in HSCs

    Institute of Scientific and Technical Information of China (English)

    李春艳; 贾丽萍; 石蕾; 周贤

    2015-01-01

    Objective To investigate the effects of octreotide on the apoptosis of human hepatic stellate cells (HSCs) and expression of Bcl-2/Bax in HSCs,and to reveal the mechanism underlying octreotide against hepatic fibrosis. Methods HSCs lines (HSC-LX2) were incubated with different concentrations of octreotide for 24 and 48 hours. Cell apoptosis was evaluated by Fitc-tunel fluorescence staining. Bcl-2 and Bax protein exoression in HSC-LX2 was detected by immunocytochemistry. Meanwhile, Bcl-2 protein of HSC-LX2 were detected by Western blot assay. Results Octreotide could promote the apoptosis of HSC-LX2, and the apoptosis rate was significantly increased with the concentration of octreotide(P < 0.05). The HSC-LX2 were incubated with the same concentration of octreotide for 24 and 48 hours, the cell apoptosis rate of 48-hour octreotide treatment was significantly higher than that of 24-hour octreotide treatment (P < 0.05). The immunocytochemistry result indicated that octreotide could significantly decrease Bcl-2 expression and increase Bax expression in HSC-LX2 (P<0.05); Western blot assay showed that octreotide could also significantly inhibit Bcl-2 expression in HSC-LX2 (P<0.05). Conclusions Octreotide could induce the apoptosis of HSCs in a dose-and time-dependent manner, the mechanism of octreotide inducing HSCs apoptosis might be associated with down-regulation of Bcl-2 and upregulation of Bax in HSC.%目的:观察奥曲肽对活化人肝星状细胞凋亡和凋亡相关蛋白Bcl-2/Bax 表达的影响,探讨奥曲肽抗肝纤维化可能的作用机制。方法:不同浓度的奥曲肽作用于传代的人肝星状细胞株(HSC-LX2)24 h、48 h后,应用FITC-TUNEL检测各组细胞凋亡,应用免疫细胞化学法检测HSC-LX2中Bcl-2、Bax蛋白表达,应用Western-blot法检测HSC-LX2中Bcl-2蛋白表达。结果:奥曲肽可促进HSC-LX2细胞调亡,细胞凋亡率随奥曲肽浓度增加而增高(P <0.05);与24 h比较,相

  17. Facebook as a tool for communication, collaboration, and informal knowledge exchange among members of a multisite family health team

    OpenAIRE

    Lofters AK; Slater MB; Nicholas Angl E; Leung FH

    2016-01-01

    Aisha K Lofters,1,2 Morgan B Slater,1 Emily Nicholas Angl,1 Fok-Han Leung1 1Department of Family and Community Medicine, 2Centre for Research on Inner City Health, Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada Objective: To implement and evaluate a private Facebook group for members of a large Ontario multisite Family Health Team (FHT) to facilitate improved communication and collaboration. Design: Program implementation and subseq...

  18. Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity.

    OpenAIRE

    Mor, A.; Chartrel, N; Vaudry, H.; Nicolas, P

    1994-01-01

    Pancreatic polypeptide, peptide tyrosine-tyrosine (PYY), and neuropeptide tyrosine (NPY), three members of a family of structurally related peptides, are mainly expressed in the endocrine pancreas, in endocrine cells of the gut, and in the brain, respectively. In the present study, we have isolated a peptide of the pancreatic polypeptide family from the skin of the South American arboreal frog Phyllomedusa bicolor. The primary structure of the peptide was established as Tyr-Pro-Pro-Lys-Pro-Gl...

  19. Associations between violent video gaming, empathic concern, and prosocial behavior toward strangers, friends, and family members.

    Science.gov (United States)

    Fraser, Ashley M; Padilla-Walker, Laura M; Coyne, Sarah M; Nelson, Larry J; Stockdale, Laura A

    2012-05-01

    Exposure to media violence, including violent video gaming, can have a cognitive desensitization effect, lowering empathic concern for others in need. Since emerging adulthood offers increased opportunities to volunteer, strengthen relationships, and initiate new relationships, decreases in empathic concern and prosocial behavior may prove inhibitive to optimal development during this time. For these reasons, the current study investigated associations between violent video gaming, empathic responding, and prosocial behavior enacted toward strangers, friends, and family members. Participants consisted of 780 emerging adults (M age = 19.60, SD = 1.86, range = 18–29, 69% female, 69% Caucasian) from four universities in the United States. Results showed small to moderate effects between playing violent video gaming and lowered empathic concern for both males and females. In addition, lowered empathic concern partially mediated the pathways between violent video gaming and prosocial behavior toward all three targets (at the level of a trend for females), but was most strongly associated with lower prosocial behavior toward strangers. Discussion highlights how violent video gaming is associated with lower levels of prosocial behavior through the mechanism of decreased empathic concern, how this association can affect prosocial behavior differently across target, and finally what implications this might have for development during emerging adulthood. PMID:22302216

  20. Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis.

    Directory of Open Access Journals (Sweden)

    Sebastian Hofmann

    Full Text Available BACKGROUND: Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation--platelet adhesion and aggregation--have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation. OBJECTIVE: The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice. METHODS AND RESULTS: We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. Cd84(-/- platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of Cd84(-/- mice. In vivo, Cd84(-/- mice exhibited unaltered hemostatic function and arterial thro