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Sample records for cancer-related runx2 protein

  1. Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression.

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    Pockwinse, Shirwin M; Kota, Krishna P; Quaresma, Alexandre J C; Imbalzano, Anthony N; Lian, Jane B; van Wijnen, Andre J; Stein, Janet L; Stein, Gary S; Nickerson, Jeffrey A

    2011-05-01

    The nuclear matrix bound transcription factor RUNX2 is a lineage-specific developmental regulator that is linked to cancer. We have previously shown that RUNX2 controls transcription of both RNA polymerase II genes and RNA polymerase I-dependent ribosomal RNA genes. RUNX2 is epigenetically retained through mitosis on both classes of target genes in condensed chromosomes. We have used fluorescence recovery after photobleaching to measure the relative binding kinetics of enhanced green fluorescent protein (EGFP)-RUNX2 at transcription sites in the nucleus and nucleoli during interphase, as well as on mitotic chromosomes. RUNX2 becomes more strongly bound as cells go from interphase through prophase, with a doubling of the most tightly bound "immobile fraction." RUNX2 exchange then becomes much more facile during metaphase to telophase. During interphase the less tightly bound pool of RUNX2 exchanges more slowly at nucleoli than at subnuclear foci, and the non-exchanging immobile fraction is greater in nucleoli. These results are consistent with a model in which the molecular mechanism of RUNX2 binding is different at protein-coding and ribosomal RNA genes. The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased binding affinity of RUNX2 at mitotic chromosomes may reflect its epigenetic function in "bookmarking" of target genes in cancer cells. Copyright © 2010 Wiley-Liss, Inc.

  2. The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono-ubiquitination manner during osteogenic differentiation.

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    Zhu, Wei; He, Xinyu; Hua, Yue; Li, Qian; Wang, Jiyong; Gan, Xiaoqing

    2017-07-07

    Poly-ubiquitination-mediated RUNX2 degradation is an important cause of age- and inflammation-related bone loss. NEDD4 family E3 ubiquitin protein ligases are thought to be the major regulators of RUNX2 poly-ubiquitination. However, we observed a mono-ubiquitination of RUNX2 that was catalyzed by WWP2, a member of the NEDD4 family of E3 ubiquitin ligases. WWP2 has been reported to catalyze the mono-ubiquitination of Goosecoid in chondrocytes, facilitating craniofacial skeleton development. In this study, we found that osteogenic differentiation of mesenchymal stem cells promoted WWP2 expression and nuclear accumulation. Knockdown of Wwp2 in mesenchymal stem cells and osteoblasts led to significant deficiencies of osteogenesis, including decreased mineral deposition and down-regulation of osteogenic marker genes. Co-immunoprecipitation experiments showed the interaction of WWP2 with RUNX2 in vitro and in vivo Mono-ubiquitination by WWP2 leads to RUNX2 transactivation, as evidenced by the wild type of WWP2, but not its ubiquitin ligase-dead mutant, augmenting RUNX2-reponsive reporter activity. Moreover, deletion of WWP2-dependent mono-ubiquitination resulted in striking defects of RUNX2 osteoblastic activity. In addition, ectopic expression of the constitutively active type 1A bone morphogenetic protein receptor enhanced WWP2-dependent RUNX2 ubiquitination and transactivation, demonstrating a regulatory role of bone morphogenetic protein signaling in the WWP2-RUNX2 axis. Taken together, our results provide evidence that WWP2 serves as a positive regulator of osteogenesis by augmenting RUNX2 transactivation in a non-proteolytic mono-ubiquitination manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation.

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    Baniwal, Sanjeev K; Little, Gillian H; Chimge, Nyam-Osor; Frenkel, Baruch

    2012-05-01

    Prolactin-Induced Protein (PIP) is a small polypeptide expressed by breast and prostate cancer (BCa, PCa) cells. However, both the regulation of PIP expression and its function in cancer cells are poorly understood. Using BCa and PCa cells, we found that Runx2, a pro-metastatic transcription factor, functionally interacts with the Androgen Receptor (AR) to regulate PIP expression. Runx2 expression in C4-2B PCa cells synergized with AR to promote PIP expression, whereas its knockdown in T47D BCa cells abrogated basal as well as hormone stimulated PIP expression. Chromatin immunoprecipitation (ChIP) assays showed that Runx2 and AR co-occupied an enhancer element located ∼11 kb upstream of the PIP open reading frame, and that Runx2 facilitated AR recruitment to the enhancer. PIP knockdown in T47D cells compromised DHT-stimulated expression of multiple AR target genes including PSA, FKBP5, FASN, and SGK1. The inhibition of AR activity due to loss of PIP was attributable at least in part to abrogation of its nuclear translocation. PIP knockdown also suppressed T47D cell proliferation driven by either serum growth factors or dihydrotestosterone (DHT). Our data suggest that Runx2 controls a positive feedback loop between androgen signaling and PIP, and pharmacological inhibition of PIP may be useful to treat PIP positive tumors. Copyright © 2011 Wiley Periodicals, Inc.

  4. Regulatory effects of bone morphogenetic protein-4 on tumour necrosis factor-α-suppressed Runx2 and osteoprotegerin expression in cementoblasts.

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    Wang, Yunlong; He, Hong; Cao, Zhengguo; Fang, Yi; Du, Mingyuan; Liu, Zhijian

    2017-08-01

    Root resorption is a common phenomenon presented in periodontitis and orthodontic treatment, both of which are accompanied by an elevated TNF-α expression level in the periodontal tissues. Previously, we proved that TNF-α showed an inhibitory effect on cementoblast differentiation, mineralization and proliferation. However, the effect of TNF-α on Runx2 and osteoprotegerin (OPG) expression remains undetermined. This study aimed to identify the influence of TNF-α on Runx2 and OPG expression in cementoblasts and to test whether BMP-2,-4,-6,-7 would affect TNF-α-regulated Runx2 and OPG. An immortalized murine cementoblast cell line OCCM-30 was used in this study. The expression of Runx2 and OPG were examined by qRT-PCR after stimulating cells with TNF-α. The role of signalling pathways, including MAPK, PI3K-Akt and NF-κB, were studied with the use of specific inhibitors. Cells were treated with TNF-α in combination with BMP-2,-4,-6 or -7, then the expression of Runx2 and OPG, the activity of MAPK and NF-κB pathways, and the proliferation ability were evaluated by qRT-PCR, Western blot and MTS assay respectively. TNF-α inhibited Runx2 and OPG mRNAs in OCCM-30 cells, and the inhibitory effects were further aggravated by blocking p38 MAPK or NF-κB pathway. TNF-α-inhibited Runx2 and OPG were up-regulated by BMP-4. The p38 MAPK and Erk1/2 pathways were further activated by the combined treatment of BMP-4 and TNF-α compared with TNF-α alone. Finally, the TNF-α-suppressed proliferation was not obviously affected by BMP-2,-4,-6 or -7. TNF-α inhibited Runx2 and OPG in cementoblasts, and the p38 MAPK and NF-κB pathways acted in a negative-feedback way to attenuate the inhibitory effects. TNF-α-inhibited Runx2 and OPG could be effectively up-regulated by BMP-4; however, further investigations are needed to fully elaborate the underlying mechanisms. © 2017 John Wiley & Sons Ltd.

  5. Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.

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    Yumiko Togo

    Full Text Available Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1.

  6. RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors

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    Zhang, He-Yu; Jin, Long; Stilling, Gail A.; Ruebel, Katharina H.; Coonse, Kendra; Tanizaki, Yoshinori; Raz, Avraham

    2010-01-01

    Galectin-3 is expressed in a cell-type specific manner in human pituitary tumors and may have a role in pituitary tumor development. In this study, we hypothesized that Galectin-3 is regulated by RUNX proteins in pituitary tumors. Transcription factor prediction programs revealed several putative binding sites in the LGALS3 (Galectin-3 gene) promoter region. A human pituitary cell line HP75 was used as a model to study LGALS3 and RUNX interactions using Chromatin immunoprecipitation assay and electrophoresis mobility shift assay. Two binding sites for RUNX1 and one binding site for RUNX2 were identified in the LGALS3 promoter region. LGALS3 promoter was further cloned into a luciferase reporter, and the experiments showed that both RUNX1 and RUNX2 upregulated LGALS3. Knock-down of either RUNX1 or RUNX2 by siRNA resulted in a significant downregulation of Galectin-3 expression and decreased cell proliferation in the HP 75 cell line. Immunohistochemistry showed a close correlation between Galectin-3 expression and RUNX1/RUNX2 level in pituitary tumors. These results demonstrate a novel binding target for RUNX1 and RUNX2 proteins and suggest that Galectin-3 is regulated by RUNX1 and RUNX2 in human pituitary tumor cells by direct binding to the promoter region of LGALS3 and thus may contribute to pituitary tumor progression. PMID:19020999

  7. Transcription factor Runx2 knockdown regulates colon cancer transplantation tumor growth in vitro: an experimental study

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    Bin Xu1

    2017-05-01

    Full Text Available Objective: To study the effect of transcription factor Runx2 knockdown on colon cancer transplantation tumor growth in vitro. Methods: Colon cancer cell lines HT29 were cultured and transfected with negative control (NC - shRNA plasmids and Runx2-shRNA plasmids respectively, the colon cancer cells transfected with shRNA were subcutaneously injected into C57 nude mice, and they were included in NC group and Runx2 knockdown group respectively. 1 week, 2 weeks and 3 weeks after model establishment, serum was collected to determine the contents of tumor markers, and tumor lesions were collected to determine proliferation and apoptosis gene expression. Results: CCSA-2, CEA and CA19-9 levels in serum as well as Rac1, Wnt3a, PLD2 and FAM96B protein expression in transplantation tumor lesions of Runx2 knockdown group were significantly lower than those of NC group while MS4A12, ASPP2 and Fas protein expression in transplantation tumor lesions of Runx2 knockdown group were significantly higher than those of NC group. Conclusion: Transcription factor Runx2 knockdown could inhibit the colon cancer transplantation tumor growth in vitro.

  8. mTOR/Raptor signaling is critical for skeletogenesis in mice through the regulation of Runx2 expression.

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    Dai, Qinggang; Xu, Zhan; Ma, Xuhui; Niu, Ningning; Zhou, Siru; Xie, Furong; Jiang, Lingyong; Wang, Jun; Zou, Weiguo

    2017-11-01

    The mammalian target of rapamycin (mTOR)/regulatory-associated protein of mTOR (Raptor) pathway transmits and integrates different signals including growth factors, nutrients, and energy metabolism. Nearly all these signals have been found to play roles in skeletal biology. However, the contribution of mTOR/Raptor to osteoblast biology in vivo remains to be elucidated as the conclusions of recent studies are controversial. Here we report that mice with a deficiency of either mTOR or Raptor in preosteoblasts exhibited clavicular hypoplasia and delayed fontanelle fusion, similar to those found in human patients with cleidocranial dysplasia (CCD) haploinsufficient for the transcription factor runt-related transcription factor 2 (Runx2) or those identified in Runx2 +/- mice. Mechanistic analysis revealed that the mTOR-Raptor-S6K1 axis regulates Runx2 expression through phosphorylation of estrogen receptor α, which binds to Distal-less homeobox 5 (DLX5) and augments the activity of Runx2 enhancer. Moreover, heterozygous mutation of raptor in osteoblasts aggravates the bone defects observed in Runx2 +/- mice, indicating a genetic interaction between Raptor and Runx2. Collectively, these findings reveal that mTOR/Raptor signaling is essential for bone formation in vivo through the regulation of Runx2 expression. These results also suggest that a selective mTOR/Raptor antagonist, which has been developed for treatment of many diseases, may have the side effect of causing bone loss.

  9. Loss of RASSF1A synergizes with deregulated RUNX2 signaling in tumorigenesis.

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    van der Weyden, Louise; Papaspyropoulos, Angelos; Poulogiannis, George; Rust, Alistair G; Rashid, Mamunur; Adams, David J; Arends, Mark J; O'Neill, Eric

    2012-08-01

    The tumor suppressor gene RASSF1A is inactivated through point mutation or promoter hypermethylation in many human cancers. In this study, we conducted a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Rassf1a-null mice to identify candidate genes that collaborate with loss of Rassf1a in tumorigenesis. We identified 10 genes, including the transcription factor Runx2, a transcriptional partner of Yes-associated protein (YAP1) that displays tumor suppressive activity through competing with the oncogenic TEA domain family of transcription factors (TEAD) for YAP1 association. While loss of RASSF1A promoted the formation of oncogenic YAP1-TEAD complexes, the combined loss of both RASSF1A and RUNX2 further increased YAP1-TEAD levels, showing that loss of RASSF1A, together with RUNX2, is consistent with the multistep model of tumorigenesis. Clinically, RUNX2 expression was frequently downregulated in various cancers, and reduced RUNX2 expression was associated with poor survival in patients with diffuse large B-cell or atypical Burkitt/Burkitt-like lymphomas. Interestingly, decreased expression levels of RASSF1 and RUNX2 were observed in both precursor T-cell acute lymphoblastic leukemia and colorectal cancer, further supporting the hypothesis that dual regulation of YAP1-TEAD promotes oncogenic activity. Together, our findings provide evidence that loss of RASSF1A expression switches YAP1 from a tumor suppressor to an oncogene through regulating its association with transcription factors, thereby suggesting a novel mechanism for RASSF1A-mediated tumor suppression. ©2012 AACR.

  10. Dental Follicle Cells Participate in Tooth Eruption via the RUNX2-MiR-31-SATB2 Loop.

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    Ge, J; Guo, S; Fu, Y; Zhou, P; Zhang, P; Du, Y; Li, M; Cheng, J; Jiang, H

    2015-07-01

    Cleidocranial dysplasia (CCD) is characterized by the runt-related transcription factor 2 (RUNX2) mutation, which results in delayed tooth eruption due to disturbed functions of dental follicle. Accumulating evidence has revealed a key regulatory circuit, including RUNX2, miR-31, and special AT-rich binding protein 2 (SATB2) acting in concert in mesenchymal stem cell homeostasis and functions. However, whether such a regulatory loop works in dental follicle cells (DFCs) remains unknown. Herein, we investigated the roles of RUNX2-miR-31-SATB2 in DFCs from patients with CCD (DFCs-CCD) to advance our understanding regarding physical tooth eruption. We identified a novel mutation on exon 5 (c.634T>G, p.T212P) in RUNX2 via exome sequencing in the CCD patient with typical clinical presentations. Compared with DFCs from healthy donors, DFCs-CCD displayed significantly lower osteogenic, osteoclast-inductive, and matrix-degrading capacities and had lower RUNX2 (a transcriptional inhibitor of miR-31), higher miR-31, and downregulated SATB2. Lower ratios of RANKL/OPG and RANKL/RANK, as well as decreased expression of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 2 (MMP2), would lead to inactivation of osteoclasts and suppression of bone matrix remodeling in DFCs-CCD. Furthermore, the roles of the RUNX2-miR-31-SATB2 loop in DFCs-CCD were revealed by endogenous miR-31 knockdown, which resulted in increased SATB2 and RUNX2, as well as osteoclast-inductive and matrix degradation capacities. Conversely, SATB2, RUNX2, MMP9, MMP2, and osteoclast-inductive factors expression declined upon ectopic miR-31 overexpression in normal DFCs. Importantly, neonatal mice with in vivo siRUNX2 delivery exhibited less activated osteoclasts around dental follicles and delayed tooth eruption. Together, these results suggest that RUNX2 mutation/haploinsufficiency disturbs osteoclast-inductive signaling in DFCs, which may be responsible for delayed tooth eruption in CCD patients

  11. RUNX2 mutations in Taiwanese patients with cleidocranial dysplasia

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    Wei-De Lin

    2011-01-01

    Full Text Available Cleidocranial dysplasia (CCD is an autosomal dominant human skeletal disorder comprising hypoplastic clavicles, wide cranial sutures, supernumerary teeth, short stature, and other skeletal abnormalities. It is known that mutations in the human RUNX2 gene mapped at 6p21 are responsible for CCD. We analyzed the mutation patterns of the RUNX2 gene by direct sequencing in six Taiwanese index cases with typical CCD. One of the patients was a familial case and the others were sporadic cases. Sequencing identified four mutations. Three were caused by single nucleotide substitutions, which created a nonsense (p.R391X, two were missense mutations (p.R190W, p.R225Q, and the forth was a novel mutation (c.1119delC, a one-base deletion. Real time quantitative PCR adapted to determine copy numbers of the promoter, all exons and the 3'UTR region of the RUNX2 gene detected the deletion of a single allele in a sporadic case. The results extend the spectrum of RUNX2 mutations in CCD patients and indicate that complete deletions of the RUNX2 gene should be considered in those CCD patients lacking a point mutation detected by direct sequencing.

  12. The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis

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    Francis, W.R.; Owens, S.E.; Wilde, C.; Pallister, I.; Kanamarlapudi, V.; Zou, W.; Xia, Z.

    2014-01-01

    Highlights: • ERα36 is the predominant ERα isoform involved in bone regulation in human BMSC. • ERα36 mRNA is significantly upregulated during the process of osteogenesis. • The pattern of ERα36 and runx2 mRNA expression is similar during osteogenesis. • ERα36 appears to be co-localised with runx2 during osteogenesis. - Abstract: During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments

  13. RUNX2 tandem repeats and the evolution of facial length in placental mammals

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    Pointer Marie A

    2012-06-01

    Full Text Available Abstract Background When simple sequence repeats are integrated into functional genes, they can potentially act as evolutionary ‘tuning knobs’, supplying abundant genetic variation with minimal risk of pleiotropic deleterious effects. The genetic basis of variation in facial shape and length represents a possible example of this phenomenon. Runt-related transcription factor 2 (RUNX2, which is involved in osteoblast differentiation, contains a functionally-important tandem repeat of glutamine and alanine amino acids. The ratio of glutamines to alanines (the QA ratio in this protein seemingly influences the regulation of bone development. Notably, in domestic breeds of dog, and in carnivorans in general, the ratio of glutamines to alanines is strongly correlated with facial length. Results In this study we examine whether this correlation holds true across placental mammals, particularly those mammals for which facial length is highly variable and related to adaptive behavior and lifestyle (e.g., primates, afrotherians, xenarthrans. We obtained relative facial length measurements and RUNX2 sequences for 41 mammalian species representing 12 orders. Using both a phylogenetic generalized least squares model and a recently-developed Bayesian comparative method, we tested for a correlation between genetic and morphometric data while controlling for phylogeny, evolutionary rates, and divergence times. Non-carnivoran taxa generally had substantially lower glutamine-alanine ratios than carnivorans (primates and xenarthrans with means of 1.34 and 1.25, respectively, compared to a mean of 3.1 for carnivorans, and we found no correlation between RUNX2 sequence and face length across placental mammals. Conclusions Results of our diverse comparative phylogenetic analyses indicate that QA ratio does not consistently correlate with face length across the 41 mammalian taxa considered. Thus, although RUNX2 might function as a ‘tuning knob’ modifying face

  14. SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2.

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    Kayvan Zainabadi

    Full Text Available Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differentiation. Reciprocally, treatment with a SIRT1 agonist promotes osteoblast differentiation, as well as the expression of runx2 downstream targets, in a SIRT1-dependent manner. Biochemical and luciferase reporter assays demonstrate that SIRT1 interacts with and promotes the transactivation potential of RUNX2. Intriguingly, mice treated with the SIRT1 agonist, resveratrol, show similar increases in the expression of RUNX2 targets in their calvaria (bone tissue, validating SIRT1 as a physiologically relevant regulator of RUNX2.

  15. Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.

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    Zhang, Xin; Ma, Yong; Fu, Xin; Liu, Qiang; Shao, Zhenxing; Dai, Linghui; Pi, Yanbin; Hu, Xiaoqing; Zhang, Jiying; Duan, Xiaoning; Chen, Wenqing; Chen, Ping; Zhou, Chunyan; Ao, Yingfang

    2016-01-08

    Runx2 is a powerful osteo-inductive factor and adipose-derived stem cells (ADSCs) are multipotent. However, it is unknown whether Runx2-overexpressing ADSCs (Runx2-ADSCs) could promote anterior cruciate ligament (ACL) reconstruction. We evaluated the effect of Runx2-ADSCs on ACL reconstruction in vitro and in vivo. mRNA expressions of osteocalcin (OCN), bone sialoprotein (BSP) and collagen I (COLI) increased over time in Runx2-ADSCs. Runx2 overexpression inhibited LPL and PPARγ mRNA expressions. Runx2 induced alkaline phosphatase activity markedly. In nude mice injected with Runx2-ADSCs, promoted bone formation was detected by X-rays 8 weeks after injection. The healing of tendon-to-bone in a rabbit model of ACL reconstruction treated with Runx2-ADSCs, fibrin glue only and an RNAi targeting Runx2, was evaluated with CT 3D reconstruction, histological analysis and biomechanical methods. CT showed a greater degree of new bone formation around the bone tunnel in the group treated with Runx2-ADSCs compared with the fibrin glue group and RNAi Runx2 group. Histology showed that treatment with Runx2-ADSCs led to a rapid and significant increase at the tendon-to-bone compared with the control groups. Biomechanical tests demonstrated higher tendon pullout strength in the Runx2-ADSCs group at early time points. The healing of the attachment in ACL reconstruction was enhanced by Runx2-ADSCs.

  16. Runx2 modified dental pulp stem cells (DPSCs) enhance new bone formation during rapid distraction osteogenesis (DO).

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    Feng, Guijuan; Zhang, Jinlong; Feng, Xingmei; Wu, Senbin; Huang, Dan; Hu, Jing; Zhu, Songsong; Song, Donghui

    Distraction osteogenesis (DO) remains a major challenge in orthopedic and craniofacial surgery. The transplantion of mesenchymal stem cells (MSCs) could reduce the treatment period and the associated complications by increasing new bone formation during long-bone DO. Runt-related transcription factor 2 (Runx2) encodes a nuclear protein that is a pivotal regulator of osteoblast differentiation. It significantly stimulates calcium accumulation and alkaline phosphatase (ALP) activity in dental pulp stem cells (DPSCs). In this study, we investigated the effects of gene therapy using Runx2 on new bone formation during tibia DO of rabbits. The distraction gap of the rabbits was injected with adenovirus (Adv)-Runx2-green fluorescent protein (GFP)-transfected DPSCs (overexpression group, Group OE) or Adv-GFP-transfected DPSCs (negative control group, Group NC). Rabbits in the control group (Groups CON) were injected with physiologic saline. The generation of new bone tissue in the distraction gap was studied by radiographic examination, micro-computed tomography (CT) evaluation, histological analyze, and Mechanical testing at weeks 8 in the consolidation period. Excellent bone formation in the distracted callus was observed in Group OE and Group NC. Moreover, the OE group showed better bone formation and the highest bone mineral density (BMD) and bone mineral content (BMC). Group CON animals showed inadequate bone formation in the distracted callus compared to the other groups. The results suggest that gene therapy using Runx2-modified DPSCs was more effective during bone deposition and new bone formation in tibia DO. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  17. Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling.

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    Zhang, Peng; Wu, Yuqiong; Jiang, Zonglai; Jiang, Lingyong; Fang, Bing

    2012-06-01

    Mechanical stimuli are responsible for bone remodeling during orthodontic tooth movement. The role of mechanical stimulation in the regulation of the fate of bone mesenchymal stem cells (BMSCs) is of interest in bone regeneration and tissue engineering applications. However, the signaling pathway involved in strain-induced biochemical events in BMSCs is not well established and can be controversial. This study investigated strain-induced proliferation and differentiation of BMSCs, as well as the mechanism of mechanotransduction. BMSCs were exposed to continuous mechanical strain (CMS) of 10% at 1 Hz. The results showed that CMS reduced the proliferation of BMSCs and stimulated osteogenic differentiation by activating Runx2, followed by increased alkaline phosphatase (ALP) activity and mRNA expression of osteogenesis-related genes (ALP, collagen type I and osteocalcin). Furthermore, the phosphorylation level of extracellular regulated protein kinase (ERK)1/2 increased significantly at the onset of strain. However, the presence of U0126, a selective inhibitor of ERK1/2, blocked the induction of Runx2 and subsequent osteogenic events. These findings demonstrate that CMS regulated Runx2 activation and favored osteoblast differentiation through activation of the ERK1/2 signaling pathway. These results will contribute to a better understanding of strain-induced bone remodeling and will form the basis for the correct choice of applied force in orthodontic treatment.

  18. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

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    Takashi Watanabe

    Full Text Available Mastermind-like 1 (MAML1 is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2 from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/- embryos at embryonic day 16.5 (E16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1 and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1 expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1(-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

  19. Epigenetic Control of Prostate Cancer Metastasis: Role of Runx2 Phosphorylation

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    2015-05-01

    be subject to any penalty for fail ing to comply with a collection of information if it does not display a currently valid OMB control number...Metastasis: Role of Runx2 Phosphorylation Study Site Information: PI: Renny T. Franceschi, Ph.D. Department of Periodontics and Oral Medicine University...Suppression of androgen-independent prostate cancer cell aggressiveness by FTY720: validating Runx2 as a potential antimetastatic drug screening platform

  20. Deletions of the RUNX2 Gene are present in about 10% of Individuals with Cleidocranial Dysplasia

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    Ott , Claus Eric; Leschik , Gundula; Trotier , Fabienne; Brueton , Louise; Brunner , Han G.; Brussel , Wim; GUILLEN-NAVARRO , ENCARNA; Haase , Claudia; Kohlhase , Juergen; Kotzot , Dieter; Lane , Andrew; Lee-Kirsch , Min Ae; Morlot , Susanne; Simon , Marleen EH; Steichen-Gersdorf , Elisabeth

    2010-01-01

    Abstract Cleidocranial Dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by hypoplastic or absent clavicles, increased head circumference, large fontanels, dental anomalies, and short stature. Hand malformations are also common. Mutations in RUNX2 cause CCD, but are not identified in all CCD patients. In this study we screened 135 unrelated patients with the clinical diagnosis of CCD for RUNX2 mutations by sequencing analysis and demonstrated 82 mutations 48 ...

  1. RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity

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    Michaël Chopin

    2016-04-01

    Full Text Available Plasmacytoid dendritic cells (pDCs represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-α expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections.

  2. JNK/ERK-AP-1/Runx2 induction "paves the way" to cartilage load-ignited chondroblastic differentiation.

    Science.gov (United States)

    Papachristou, Dionysios J; Pirttiniemi, Pertti; Kantomaa, Tuomo; Papavassiliou, Athanasios G; Basdra, Efthimia K

    2005-09-01

    Chondro-osteogenesis and subsequently skeletal morphology are greatly influenced by mechanical loads. The exact mechanism(s) by which mechanical stimuli are transduced in chondrocytes remains obscure and appears to be equally complex with similar signal transducing systems. Here we investigated whether and to what extent the MAPK (JNK/ERK)-AP-1/Runx2 signaling pathways are engaged in this phenomenon, and assessed their involvement in the functional biology of articular cartilage. For this purpose, 14-day-old female Wistar rats were divided into 2 groups: the first group was fed hard diet (simulating physiologic temporomandibular joint (TMJ) loading), while the second group was fed soft diet (reduced TMJ loading). On day 21 (experiment initiation day - weaning day), biopsies from condyles of both groups were obtained after 6, 12 and 48 h of functional TMJ loading. Immunohistochemical methodology was employed to evaluate the expression levels of pc-Jun, c-Fos, JNK2, p-JNK, p-ERK and Runx2 due to alteration in functional load. Our data demsonstrate that the protein levels of all the aforementioned molecules were markedly increased in animals fed with the hard diet, throughout the experimental procedure. These results indicate that functional cartilage loading induces the AP-1 and Runx2 transcription factors through the JNK and ERK MAPK cascades. In as much as the above signaling mediators/effectors are considered to be crucial in the differentiation/maturation process of cartilage tissue, we pose that functional mechanical loading of condylar cartilage serves to "fine tune" chondroblastic differentiation/maturation.

  3. Integrin αvβ3 and CD44 pathways in metastatic prostate cancer cells support osteoclastogenesis via a Runx2/Smad 5/receptor activator of NF-κB ligand signaling axis

    Directory of Open Access Journals (Sweden)

    Gupta Aditi

    2012-09-01

    Full Text Available Abstract Background Bone loss and pathological fractures are common skeletal complications associated with androgen deprivation therapy and bone metastases in prostate cancer patients. We have previously demonstrated that prostate cancer cells secrete receptor activator of NF-kB ligand (RANKL, a protein essential for osteoclast differentiation and activation. However, the mechanism(s by which RANKL is produced remains to be determined. The objective of this study is to gain insight into the molecular mechanisms controlling RANKL expression in metastatic prostate cancer cells. Results We show here that phosphorylation of Smad 5 by integrin αvβ3 and RUNX2 by CD44 signaling, respectively, regulates RANKL expression in human-derived PC3 prostate cancer cells isolated from bone metastasis. We found that RUNX2 intranuclear targeting is mediated by phosphorylation of Smad 5. Indeed, Smad5 knock-down via RNA interference and inhibition of Smad 5 phosphorylation by an αv inhibitor reduced RUNX2 nuclear localization and RANKL expression. Similarly, knockdown of CD44 or RUNX2 attenuated the expression of RANKL. As a result, conditioned media from these cells failed to support osteoclast differentiation in vitro. Immunohistochemistry analysis of tissue microarray sections containing primary prostatic tumor (grade2-4 detected predominant localization of RUNX2 and phosphorylated Smad 5 in the nuclei. Immunoblotting analyses of nuclear lysates from prostate tumor tissue corroborate these observations. Conclusions Collectively, we show that CD44 signaling regulates phosphorylation of RUNX2. Localization of RUNX2 in the nucleus requires phosphorylation of Smad-5 by integrin αvβ3 signaling. Our results suggest possible integration of two different pathways in the expression of RANKL. These observations imply a novel mechanistic insight into the role of these proteins in bone loss associated with bone metastases in patients with prostate cancer.

  4. Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis

    Directory of Open Access Journals (Sweden)

    Kenichi Mishima

    2015-12-01

    Full Text Available The transcription factor, runt-related transcription factor 2 (Runx2, plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP-transforming growth factor-beta (TGF-β activated kinase-1 (TAK1–p38 mitogen-activated protein kinase (MAPK pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6 and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD. Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation.

  5. Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis.

    Science.gov (United States)

    Mishima, Kenichi; Kitoh, Hiroshi; Ohkawara, Bisei; Okuno, Tatsuya; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2015-12-01

    The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6) and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD). Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation.

  6. Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme.

    Science.gov (United States)

    Holleville, Nicolas; Matéos, Stéphanie; Bontoux, Martine; Bollerot, Karine; Monsoro-Burq, Anne-Hélène

    2007-04-15

    Craniofacial bones derive from cephalic neural crest, by endochondral or intramembranous ossification. Here, we address the role of the homeobox transcription factor Dlx5 during the initial steps of calvaria membranous differentiation and we show that Dlx5 elicits Runx2 induction and full osteoblast differentiation in embryonic suture mesenchyme grown "in vitro". First, we compare Dlx5 expression to bone-related gene expression in the developing skull and mandibular bones. We classify genes into three groups related to consecutive steps of ossification. Secondly, we study Dlx5 activity in osteoblast precursors, by transfecting Dlx5 into skull mesenchyme dissected prior to the onset of either Dlx5 and Runx2 expression or osteogenesis. We find that Dlx5 does not modify the proliferation rate or the expression of suture markers in the immature calvaria cells. Rather, Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis "in vivo". Thirdly, we show that BMP signaling activates Dlx5, Runx2, and alkaline phosphatase in those primary cultures and that a dominant-negative Dlx factor interferes with the ability of the BMP pathway to activate Runx2 expression. Together, these data suggest a pivotal role of Dlx5 and related Dlx factors in the onset of differentiation of chick calvaria osteoblasts.

  7. A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Min Hwa Shin

    2016-02-01

    Full Text Available The inactivation of p53 creates a major challenge for inducing apoptosis in cancer cells. An attractive strategy is to identify and subsequently target the survival signals in p53 defective cancer cells. Here we uncover a RUNX2-mediated survival signal in p53 defective cancer cells. The inhibition of this signal induces apoptosis in cancer cells but not non-transformed cells. Using the CRISPR technology, we demonstrate that p53 loss enhances the apoptosis caused by RUNX2 knockdown. Mechanistically, RUNX2 provides the survival signal partially through inducing MYC transcription. Cancer cells have high levels of activating histone marks on the MYC locus and concomitant high MYC expression. RUNX2 knockdown decreases the levels of these histone modifications and the recruitment of the Menin/MLL1 (mixed lineage leukemia 1 complex to the MYC locus. Two inhibitors of the Menin/MLL1 complex induce apoptosis in p53 defective cancer cells. Together, we identify a RUNX2-mediated epigenetic mechanism of the survival of p53 defective cancer cells and provide a proof-of-principle that the inhibition of this epigenetic axis is a promising strategy to kill p53 defective cancer cells.

  8. A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells.

    Science.gov (United States)

    Shin, Min Hwa; He, Yunlong; Marrogi, Eryney; Piperdi, Sajida; Ren, Ling; Khanna, Chand; Gorlick, Richard; Liu, Chengyu; Huang, Jing

    2016-02-01

    The inactivation of p53 creates a major challenge for inducing apoptosis in cancer cells. An attractive strategy is to identify and subsequently target the survival signals in p53 defective cancer cells. Here we uncover a RUNX2-mediated survival signal in p53 defective cancer cells. The inhibition of this signal induces apoptosis in cancer cells but not non-transformed cells. Using the CRISPR technology, we demonstrate that p53 loss enhances the apoptosis caused by RUNX2 knockdown. Mechanistically, RUNX2 provides the survival signal partially through inducing MYC transcription. Cancer cells have high levels of activating histone marks on the MYC locus and concomitant high MYC expression. RUNX2 knockdown decreases the levels of these histone modifications and the recruitment of the Menin/MLL1 (mixed lineage leukemia 1) complex to the MYC locus. Two inhibitors of the Menin/MLL1 complex induce apoptosis in p53 defective cancer cells. Together, we identify a RUNX2-mediated epigenetic mechanism of the survival of p53 defective cancer cells and provide a proof-of-principle that the inhibition of this epigenetic axis is a promising strategy to kill p53 defective cancer cells.

  9. RUNX-2, OPN and OCN expression induced by grey and white mineral trioxide aggregate in normal and hypertensive rats.

    Science.gov (United States)

    Martins, C M; de Azevedo Queiroz, I O; Ervolino, E; Cintra, L T A; Gomes-Filho, J E

    2017-11-16

    To investigate whether hypertension affects mineralization associated with white and grey mineral trioxide aggregate (MTA Angelus ® ) implanted subcutaneously into rats by assaying osteoblastic biomarkers. Polyethylene tubes containing grey MTA Angelus ® , white MTA Angelus ® , intermediate restorative material (IRM; positive control) or an empty tube (negative control) were implanted into the dorsal connective tissue of spontaneous hypertensive (n = 12) and Wistar (normotensive; n = 10) rats. Half of the rats in each group were killed after 7 days, and the remaining after 30 days. Tubes with surrounding tissue were removed, and immunostaining was performed to detect RUNX-2, OPN and OCN proteins. The normality of data was analysed using the Shapiro-Wilk test. Comparison of two independent groups was performed using the Mann-Whitney U-test, to detect a significant difference. A post hoc test accounting for multiple comparisons was performed following Tukey's test (P MTA materials were associated with immunolabelling for RUNX-2 from low to moderate, which was less than that observed at normal blood pressure and the 7-day groups (P MTA conditions was considered low after both 7 and 30 days for the hypertensive condition, and was less than that in animals with normal blood pressure after 30 days (P MTA. Thus, hypertension can jeopardize the mineralization ability of MTA and may have a negative impact on endodontic treatment outcomes. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  10. Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women

    Directory of Open Access Journals (Sweden)

    Elza I Auerkari

    2014-04-01

    Full Text Available Objectives: Osteoporosis is a metabolic bone disease of reduced bone mass density (BMD and elevated risk of fracture due to an imbalance in bone formation and resorption. The risk and incidence of osteoporosis increase towards advanced age, particularly in postmenopausal women, and the risk is known to be affected by the variation in the expression of the associated regulatory genes. This work aimed to clarify the impact of variation in RUNX2 (runt domain transcription factor 2, which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding single-nucleotide polymorphism within RUNX2 promoter (P1 and risk of osteoporosis in postmenopausal Indonesian women. Methods: Using DNA sampling from blood, the variation at the single-nucleotide polymorphism (-330, G→T, rs59983488 at the RUNX2 P1 promoter was investigated using polymerase chain reaction–restriction fragment length polymorphism for 180 consenting postmenopausal Indonesian women. The subjects were examined for bone mass density and classification to normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Chi-square testing and logistic regression were mainly used for statistical assessment. Results: The results showed a general trend with increased risk of osteoporosis associated with the genotype TT (mutant type and the corresponding T allele of the tested polymorphism of RUNX2 promoter P1. The trend was, however, not significant in multivariate testing adjusted for age and time after menopause. Conclusion: To confirm the potential risk with TT genotype would require testing of a much larger sample of subjects. As the tested single-nucleotide polymorphism only represents one of the relevant candidate locations of RUNX2, the results are taken nevertheless to suggest an impact by overall RUNX2 variation in the risk of osteoporosis in Indonesian postmenopausal women.

  11. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Wang

    Full Text Available Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT primary cultures derived from serous epithelial ovarian cancer (EOC patients, when compared to primary cultures derived from matched primary (prior to CT tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  12. Deletion of Osr2 Partially Rescues Tooth Development in Runx2 Mutant Mice.

    Science.gov (United States)

    Kwon, H J E; Park, E K; Jia, S; Liu, H; Lan, Y; Jiang, R

    2015-08-01

    Tooth organogenesis depends on genetically programmed sequential and reciprocal inductive interactions between the dental epithelium and neural crest-derived mesenchyme. Previous studies showed that the Msx1 and Runx2 transcription factors are required for activation of odontogenic signals, including Bmp4 and Fgf3, in the early tooth mesenchyme to drive tooth morphogenesis through the bud-to-cap transition and that Runx2 acts downstream of Msx1 to activate Fgf3 expression. Recent studies identified Osr2 as a repressor of tooth development and showed that inactivation of Osr2 rescued molar tooth morphogenesis in the Msx1(-/-) mutant mice as well as in mice with neural crest-specific inactivation of Bmp4. Here we show that Runx2 expression is expanded in the tooth bud mesenchyme in Osr2(-/-) mutant mouse embryos and is partially restored in the tooth mesenchyme in Msx1(-/-)Osr2(-/-) mutants in comparison with Msx1(-/-) and wild-type embryos. Whereas mandibular molar development arrested at the bud stage and maxillary molar development arrested at the bud-to-cap transition in Runx2(-/-) mutant mice, both mandibular and maxillary molar tooth germs progressed to the early bell stage, with rescued expression of Msx1 and Bmp4 in the dental papilla as well as expression of Bmp4, p21, and Shh in the primary enamel knot in the Osr2(-/-)Runx2(-/-) compound mutants. In contrast to the Msx1(-/-)Osr2(-/-) compound mutants, which exhibit nearly normal first molar morphogenesis, the Osr2(-/-)Runx2(-/-) compound mutant embryos failed to activate the expression of Fgf3 and Fgf10 in the dental papilla and exhibited significant deficit in cell proliferation in both the dental epithelium and mesenchyme in comparison with the control embryos. These data indicate that Runx2 synergizes with Msx1 to drive tooth morphogenesis through the bud-to-cap transition and that Runx2 controls continued tooth growth and morphogenesis beyond the cap stage through activation of Fgf3 and Fgf10 expression

  13. Functional relevance of the BMD-associated polymorphism rs312009: novel involvement of RUNX2 in LRP5 transcriptional regulation.

    Science.gov (United States)

    Agueda, Lídia; Velázquez-Cruz, Rafael; Urreizti, Roser; Yoskovitz, Guy; Sarrión, Patricia; Jurado, Susana; Güerri, Roberto; Garcia-Giralt, Natàlia; Nogués, Xavier; Mellibovsky, Leonardo; Díez-Pérez, Adolfo; Marie, Pierre J; Balcells, Susana; Grinberg, Daniel

    2011-05-01

    LRP5 is an osteoporosis susceptibility gene. Association analyses reveal that individual single-nucleotide polymorphisms (SNPs) determine variation in bone mineral density (BMD) among individuals as well as fracture risk. In a previous study, we identified a lumbar spine BMD-associated SNP, rs312009, located in the LRP5 5' region. A RUNX2 binding site was identified in this region by gel-shift experiments. Here we test the functionality of this SNP and examine whether RUNX2 is indeed a regulator of LRP5 expression. Gene reporter assays were used to test rs312009 functionality. Bioinformatic predictive tools and gel-shift and gene reporter assays were used to identify and characterize additional RUNX2 binding elements in the 3.3-kb region upstream of LRP5. Allelic differences in the transcriptional activity of rs312009 were observed in two osteoblastic cell lines, the T allele being a better transcriber than the C allele. RUNX2 cotransfection in HeLa cells revealed that the LRP5 5' region responded to RUNX2 in a dose-dependent manner and that the previously identified RUNX2 binding site participated in this response. Also, RUNX2 inhibition by RNAi led to nearly 60% reduction of endogenous LRP5 mRNA in U-2 OS cells. Four other RUNX2 binding sites were identified in the 5' region of LRP5. Luciferase experiments revealed the involvement of each of them in the RUNX2 response. The allelic differences observed point to the involvement of rs312009 as a functional SNP in the observed association. To our knowledge, this is the first time that the direct action of RUNX2 on LRP5 has been described. This adds evidence to previously described links between two important bone-regulating systems: the RUNX2 transcription-factor cascade and the Wnt signaling pathway. Copyright © 2011 American Society for Bone and Mineral Research.

  14. A novel Alu-mediated microdeletion in the RUNX2 gene in a ...

    Indian Academy of Sciences (India)

    YUNZHU QIAN

    2018-02-24

    Feb 24, 2018 ... clavicle dysplasia, delayed closure of cranial sutures, and short stature; while his hands were normal. Sequencing analysis of the entire coding region of the RUNX2 gene revealed no pathogenic changes; however, copy-number analysis with the Affymetrix HD array found ∼500 kb genomic microdeletion.

  15. Lyophilized Platelet-Rich Fibrin (PRF Promotes Craniofacial Bone Regeneration through Runx2

    Directory of Open Access Journals (Sweden)

    Qi Li

    2014-05-01

    Full Text Available Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF. LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2 expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001 when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  16. microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells

    DEFF Research Database (Denmark)

    Hamam, D; Ali, D; Vishnubalaji, R

    2014-01-01

    The molecular mechanisms promoting lineage-specific commitment of human mesenchymal (skeletal or stromal) stem cells (hMSCs) into adipocytes (ADs) are not fully understood. Thus, we performed global microRNA (miRNA) and gene expression profiling during adipocytic differentiation of h......MSC, and utilized bioinformatics as well as functional and biochemical assays, and identified several novel miRNAs differentially expressed during adipogenesis. Among these, miR-320 family (miR-320a, 320b, 320c, 320d and 320e) were ~2.2-3.0-fold upregulated. Overexpression of miR-320c in hMSC enhanced adipocytic...... differentiation and accelerated formation of mature ADs in ex vivo cultures. Integrated analysis of bioinformatics and global gene expression profiling in miR-320c overexpressing cells and during adipocytic differentiation of hMSC identified several biologically relevant gene targets for miR-320c including RUNX2...

  17. The balancing act of transcription factors C-1-1 and Runx2 in articular cartilage development

    International Nuclear Information System (INIS)

    In previous studies we found that the ets transcription factor C-1-1 is involved in articular chondrocyte development, and we and others found that the transcription factor Runx2 is required for growth plate chondrocyte maturation and ossification. We determined here whether the two factors exert reciprocal influences on their expression and function and in so doing, steer chondrocyte developmental paths. Virally driven Runx2 over-expression in cultured chick chondrocytes did indeed lead to decreased C-1-1 expression, accompanied by decreased expression of articular cartilage marker tenascin-C, decreased proliferation, and increased expression of maturation marker collagen X. In good agreement, over-expression of a dominant-negative Runx2 form had opposite phenotypic consequences. When C-1-1 itself was over-expressed in chondrocytes already undergoing maturation, maturation was halted and the cells became small, rich in tenascin-C, and mitotically quite active. To extend these observations, we misexpressed C-1-1 in mouse cartilage and found that it caused a severe inhibition of chondrocyte maturation and widespread tenascin-C expression. In sum, C-1-1 and Runx2 do influence their respective expression patterns. The factors are powerful chondrocyte regulators and their functional interrelationships may be important for steering the cells toward alternative developmental paths

  18. Transcription and immunolocalization of Runx2/Cbfa1/Pebp2alphaA in developing rodent and human craniofacial tissues: further evidence suggesting osteoclasts phagocytose osteocytes

    NARCIS (Netherlands)

    Bronckers, Antonius L. J. J.; Sasaguri, Kenichi; Engelse, Marten A.

    2003-01-01

    Runx2/Cbfa1 is a transcription factor, essential for the osteogenic/chondrogenic and odontogenic lineage. Three isoforms of Cbfa1 have been identified, type I (Pebp2alphaA isoform), type II (til-1 isoform), and type III (Osf2 isoform). Here we examined the expression of the Runx2/Cbfa1 during

  19. Exclusion of MYF5, GSC, RUNX2, and TCOF1 mutation in a case of cerebro-costo-mandibular syndrome.

    Science.gov (United States)

    Su, Pen-Hua; Chen, Jia-Yuh; Chiang, Chin-Lung; Ng, Yan-Yan; Chen, Suh-Jen

    2010-04-01

    Cerebro-costo-mandibular syndrome (CCMS) is an uncommon multiple congenital anomaly syndrome characterized by severe micrognathia, posterior rib-gap defects, and developmental delay. The cause of CCMS is unknown. Genes hypothesized to have a causal role in CCMS, include myogenic factor 5 (MYF5), goosecoid homeobox (GSC) and runt-related transcription factor 2 (RUNX2) [formerly known as core-binding factor (CBFA1)]. We report an infant with typical features of CCMS who, on prenatal ultrasound, was found to have severe micrognathia. We present the first image by three-dimensional computed tomography of posterior rib-defect, and we exclude mutations of the MYF5, GSC, RUNX2, and TCOF1 genes in our patient. Further molecular studies are needed to evaluate the cause of CCMS.

  20. Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice.

    Science.gov (United States)

    Yoda, Shuichi; Suda, Naoto; Kitahara, Yutaka; Komori, Toshihisa; Ohyama, Kimie

    2004-06-01

    Genetic studies have recently identified a mutation of one allele of runt-related gene 2 (RUNX2/CBFA1) as the cause for an autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD), which is characterised by hypoplasia of the clavicles and calvariae and widened sutures and fontanelles. In addition, CCD is frequently affected with multiple supernumerary teeth and the impaction and delayed eruption of teeth, the causes of all these dental abnormalities are still unknown. To clarify the cellular mechanism of the delayed tooth eruption in CCD, the process of tooth eruption was examined in heterozygous Runx2/Cbfa1 (mouse homolog of RUNX2/CBFA1) knockout mice, known to mimic most of the bone abnormalities of CCD. The timing of the appearance of maxillary and mandibular teeth into the oral cavity was significantly delayed in heterozygous mutant mice compared with wild-type mice. From postnatal days 8 to 10, an active alveolar bone resorption and a marked increase of the osteoclast surfaces was observed in the eruption pathway of both genotypes, but this increase was significantly suppressed in the mutant mice. In contrast, the osteoclast surfaces did not show a significant difference between the two genotypes in the future cortical area of femora. These results suggest that haploinsufficiency of Runx2/Cbfa1 does not effect the femoral bone remodelling but is insufficient for the active alveolar bone resorption essential for the prompt timing of tooth eruption. These results also suggest the possibility that impaired recruitment of osteoclasts is one of the cellular mechanisms of delayed tooth eruption in CCD patients.

  1. Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females.

    Directory of Open Access Journals (Sweden)

    Nigel A Morrison

    Full Text Available Runt related transcription factor 2 (RUNX2 is a key regulator of osteoblast differentiation. Several variations within the RUNX2 gene have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18 bp deletion within the polyalanine tract (17A>11A of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of distal radius and bones of intramembranous origin compared to bones of endochondral origin (p = 0.0001. In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p = 0.01, suggesting decreased bone turnover. The transactivation function of the 11A allele showed a minor quantitative decrease. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.

  2. Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction

    Science.gov (United States)

    Tan, Li-Duan; Du, Xin; Li, Xiao-Qing; He, Rui; Wang, Qing-Shan; Feng, Yu-Mei

    2016-01-01

    Bone is one of the most common organs of breast cancer metastasis. Cancer cells that mimic osteoblasts by expressing bone matrix proteins and factors have a higher likelihood of metastasizing to bone. However, the molecular mechanisms of osteomimicry formation of cancer cells remain undefined. Herein, we identified a set of bone-related genes (BRGs) that are ectopically co-expressed in primary breast cancer tissues and determined that osteomimetic feature is obtained due to the osteoblast-like transformation of epithelial breast cancer cells that have undergone epithelial-mesenchymal transition (EMT) followed by bone morphogenetic protein-2 (BMP2) stimulation. Furthermore, we demonstrated that breast cancer cells that transformed into osteoblast-like cells with high expression of BRGs showed enhanced chemotaxis, adhesion, proliferation and multidrug resistance in an osteoblast-mimic bone microenvironment in vitro. During these processes, runt-related transcription factor 2 (RUNX2) functioned as a master mediator by suppressing or activating the transcription of BRGs that underlie the dynamic antagonism between the TGF-β/SMAD and BMP/SMAD signaling pathways in breast cancer cells. Our findings suggest a novel mechanism of osteomimicry formation that arises in primary breast tumors, which may explain the propensity of breast cancer to metastasize to the skeleton and contribute to potential strategies for predicting and targeting breast cancer bone metastasis and multidrug resistance. PMID:27806311

  3. NOTCH1, HIF1A and other cancer-related proteins in lung tissue from uranium miners--variation by occupational exposure and subtype of lung cancer.

    Directory of Open Access Journals (Sweden)

    Beate Pesch

    Full Text Available BACKGROUND: Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative exposure to these carcinogens with NOTCH1, HIF1A and other cancer-specific proteins in lung tissue from uranium miners. METHODOLOGY/PRINCIPAL FINDINGS: Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy repository by type of lung tissue, comprising adenocarcinoma (AdCa, squamous cell carcinoma (SqCC, small cell lung cancer (SCLC, and cancer-free tissue. Within each stratum, we additionally stratified by low or high level of exposure to radon or arsenic. Lifetime exposure to radon and arsenic was estimated using a quantitative job-exposure matrix developed for uranium mining. For 22 cancer-related proteins, immunohistochemical scores were calculated from the intensity and percentage of stained cells. We explored the associations of these scores with cumulative exposure to radon and arsenic with Spearman rank correlation coefficients (r(s. Occupational exposure was associated with an up-regulation of NOTCH1 (radon r(s = 0.18, 95% CI 0.02-0.33; arsenic: r(s = 0.23, 95% CI 0.07-0.38. Moreover, we investigated whether these cancer-related proteins can classify lung cancer using supervised and unsupervised classification. MUC1 classified lung cancer from cancer-free tissue with a failure rate of 2.1%. A two-protein signature discriminated SCLC (HIF1A low, AdCa (NKX2-1 high, and SqCC (NKX2-1 low with a failure rate of 8.4%. CONCLUSIONS/SIGNIFICANCE: These results suggest that the radiation-sensitive protein NOTCH1 can be up-regulated in lung tissue from uranium miners by level of exposure to pulmonary carcinogens. We evaluated a three-protein signature consisting of a physiological protein (MUC1, a cancer-specific protein (HIF1A, and a lineage-specific protein (NKX2-1 that could discriminate lung cancer and its major subtypes with a low failure rate.

  4. Epigenetic Signatures at the RUNX2-P1 and Sp7 Gene Promoters Control Osteogenic Lineage Commitment of Umbilical Cord-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Sepulveda, Hugo; Aguilar, Rodrigo; Prieto, Catalina P; Bustos, Francisco; Aedo, Sócrates; Lattus, José; van Zundert, Brigitte; Palma, Veronica; Montecino, Martin

    2017-09-01

    Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particularly, epigenetic control operating at the promoter regions of the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not yet been described in WJ-MSCs. Via quantitative PCR profiling and chromatin immunoprecipitation (ChIP) studies, here we analyze the ability of WJ-MSCs to engage osteoblast lineage. In undifferentiated WJ-MSCs, RUNX2/P57 P1, and SP7 promoters are found deprived of significant levels of the histone post-translational marks that are normally associated with transcriptionally active genes (H3ac, H3K27ac, and H3K4me3). Moreover, the RUNX2 P1 promoter lacks two relevant histone repressive marks (H3K9me3 and H3K27me3). Importantly, RUNX2 P1 promoter is found highly enriched in the H3K4me1 mark, which has been shown recently to mediate gene repression of key regulatory genes. Upon induction of WJ-MSCs osteogenic differentiation, we found that RUNX2/P57, but not SP7 gene expression is strongly activated, in a process that is accompanied by enrichment of activating histone marks (H3K4me3, H3ac, and H3K27ac) at the P1 promoter region. Histone mark analysis showed that SP7 gene promoter is robustly enriched in epigenetic repressive marks that may explain its poor transcriptional response to osteoblast differentiating media. Together, these results point to critical regulatory steps during epigenetic control of WJ-MSCs osteogenic lineage commitment that are relevant for future applications in regenerative medicine. J. Cell. Physiol. 232: 2519-2527, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Role of ox-PAPCs in the differentiation of mesenchymal stem cells (MSCs and Runx2 and PPARγ2 expression in MSCs-like of osteoporotic patients.

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    Maria Teresa Valenti

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs can differentiate into osteoblasts and adipocytes and conditions causing bone loss may induce a switch from the osteoblast to adipocyte lineage. In addition, the expression of Runx2 and the PPARγ2 transcription factor genes is essential for cellular commitment to an osteogenic and adipogenic differentiation, respectively. Modified lipoproteins derived from the oxidation of arachidonate-containing phospholipids (ox-PAPCs: POVPC, PGPC and PEIPC are considered important factors in atherogenesis. METHODOLOGY: We investigated the effect of ox-PAPCs on osteogenesis and adipogenesis in human mesenchymal stem cells (hMSCs. In particular, we analyzed the transcription factor Runx2 and the PPARγ2 gene expression during osteogenic and adipogenic differentiation in absence and in presence of ox-PAPCs. We also analyzed gene expression level in a panel of osteoblastic and adipogenic differentiation markers. In addition, as circulating blood cells can be used as a "sentinel" that responds to changes in the macro- or micro-environment, we analyzed the Runx2 and the PPARγ2 gene expression in MSCs-like and ox-PAPC levels in serum of osteoporotic patients (OPs. Finally, we examined the effects of sera obtained from OPs in hMSCs comparing the results with age-matched normal donors (NDs. PRINCIPAL FINDINGS: Quantitative RT-PCR demonstrated that ox-PAPCs enhanced PPARγ2 and adipogenic gene expression and reduced Runx2 and osteoblast differentiation marker gene expression in differentiating hMSCs. In OPs, ox-PAPC levels and PPARγ2 expression were higher than in NDs, whereas Runx2 was lower than in ND circulant MSCs-like. CONCLUSIONS: Ox-PAPCs affect the osteogenic differentiation by promoting adipogenic differentiation and this effect may appear involved in bone loss in OPs.

  6. MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation.

    Science.gov (United States)

    Ko, Jih-Yang; Chuang, Pei-Chin; Ke, Huei-Jin; Chen, Yu-Shan; Sun, Yi-Chih; Wang, Feng-Sheng

    2015-12-01

    Glucocorticoid treatment reportedly increases the morbidity of osteoporotic or osteonecrotic disorders. Exacerbated bone acquisition and escalated marrow adipogenesis are prominent pathological features of glucocorticoid-mediated skeletal disorders. MicroRNAs reportedly modulate tissue metabolism and remodeling. This study was undertaken to investigate the biological roles of microRNA-29a (miR-29a) in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis. Transgenic mice overexpressing miR-29a precursor or wild-type mice were given methylprednisolone. Bone mass, microarchitecture and histology were assessed by dual energy X-ray absorptiometry, μCT and histomorphometry. Differential gene expression and signaling components were delineated by quantitative RT-PCR and immunoblotting. Glucocorticoid treatment accelerated bone loss and marrow fat accumulation in association with decreased miR-29a expression. The miR-29a transgenic mice had high bone mineral density, trabecular microarchitecture and cortical thickness. miR-29a overexpression mitigated the glucocorticoid-induced impediment of bone mass, skeletal microstructure integrity and mineralization reaction and attenuated fatty marrow histopathology. Ex vivo, miR-29a increased osteogenic differentiation capacity and alleviated the glucocorticoid-induced promotion of adipocyte formation in primary bone-marrow mesenchymal progenitor cell cultures. Through inhibition of histone deacetylase 4 (HDAC4) expression, miR-29a restored acetylated Runx2 and β-catenin abundances and reduced RANKL, leptin and glucocorticoid receptor expression in glucocorticoid-mediated osteoporosis bone tissues. Taken together, glucocorticoid suppression of miR-29a signaling disturbed the balances between osteogenic and adipogenic activities, and thereby interrupted bone formation and skeletal homeostasis. miR-29a inhibition of HDAC4 stabilized the acetylation state of Runx2 and β-catenin that ameliorated the

  7. Differential expression of cancer-related proteins in paired breast milk samples from women with breast cancer.

    Science.gov (United States)

    Arcaro, Kathleen F; Browne, Eva P; Qin, Wenyi; Zhang, Ke; Anderton, Douglas L; Sauter, Edward R

    2012-11-01

    Breast cancer risk increases during pregnancy and remains elevated for a number of years thereafter. Cancer-associated proteins that are secreted into breast milk may provide a means to detect cancer in the lactating breast or to assess future breast cancer risk. To determine whether proteins linked to breast cancer would be differentially expressed in matched (both breasts from each participant) human milk samples collected from women with unilateral breast cancer. Five cancer-associated proteins (basic fibroblast growth factor [bFGF], YKL-40, neutrophil gelatinase-associated lipocalin, and transforming growth factor β1 and β2) were analyzed in milk provided by 5 lactating women, 4 of whom were known to have cancer in 1 breast (and the opposite breast clinically disease free) at the time of milk collection and 1 who developed breast cancer 2 years after milk collection. Expression was significantly higher for TGFβ2 (P = .03) and bFGF (P =.03) in the breasts with cancer. These proteins may play a role in assessing a woman's risk of pregnancy-associated breast cancer. Because of variable protein concentration among patients and the limited sample size, the results are considered preliminary.

  8. MOTILITY-ASSOCIATED PROTEINS IN OVARIAN CANCER: RELATION WITH CLINICAL-MORPHOLOGICAL PARAMETERS AND NEOADJUVANT CHEMOTHERAPY RESPONSE

    Directory of Open Access Journals (Sweden)

    N. V. Yunusova

    2013-01-01

    Full Text Available The expression of motility-associated proteins in 18 patients with epithelial ovarian cancer was investigated. The study of actin-binding proteins (Arp3, gelsolin, cofilin-1 and thymosin-β4 and p45 Ser β-catenin revealed peculiarities of their expression with respect to clinicalmorphological parameters of ovarian cancer. Differences in cofilin expression with respect to histological type of the tumor were shown. The expression levels of Arp3, the most important protein of Arp2/3 actin-branching complex, and cofilin, which is able to break down actin filaments, were higher in  peritoneal metastases than in omental metastases. It was found that the level of p45 Ser β-catenin and the percentage of cells expressing gelsolin and thymosin-4 were associated with pathological response to neoadjuvant chemotherapy (NACH and were significantly higher in patients with complete and partial responses as compared to those observed in patients with no response. The obtained results can be used for identification of new prognostic factors, metastasis markers and predictive marker of pathological response after NACT.

  9. Fragment-based in silico modeling of multi-target inhibitors against breast cancer-related proteins.

    Science.gov (United States)

    Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2017-08-01

    Breast cancer is the most frequent cancer reported in women, being responsible for hundreds of thousands of deaths. Chemotherapy has proven to be effective against this malignant neoplasm depending on different biological factors such as the histopathology, grade, and stage, among others. However, breast cancer cells have become resistant to current chemotherapeutic regimens, urging the discovery of new anti-breast cancer drugs. Computational approaches have the potential to offer promising alternatives to accelerate the search for potent and versatile anti-breast cancer agents. In the present work, we introduce the first multitasking (mtk) computational model devoted to the in silico fragment-based design of new molecules with high inhibitory activity against 19 different proteins involved in breast cancer. The mtk-computational model was created from a dataset formed by 24,285 cases, and it exhibited accuracy around 93% in both training and prediction (test) sets. Several molecular fragments were extracted from the molecules present in the dataset, and their quantitative contributions to the inhibitory activities against all the proteins under study were calculated. The combined use of the fragment contributions and the physicochemical interpretations of the different molecular descriptors in the mtk-computational model allowed the design of eight new molecular entities not reported in our dataset. These molecules were predicted as potent multi-target inhibitors against all the proteins, and they exhibited a desirable druglikeness according to the Lipinski's rule of five and its variants.

  10. Biosynthesis of collagen I, II, RUNX2 and lubricin at different time points of chondrogenic differentiation in a 3D in vitro model of human mesenchymal stem cells derived from adipose tissue.

    Science.gov (United States)

    Musumeci, Giuseppe; Mobasheri, Ali; Trovato, Francesca Maria; Szychlinska, Marta Anna; Graziano, Adriana Carol Eleonora; Lo Furno, Debora; Avola, Rosanna; Mangano, Sebastiano; Giuffrida, Rosario; Cardile, Venera

    2014-10-01

    The first aim of the study was to identify the most appropriate time for differentiation of adipose tissue derived mesenchymal stem cells (MSCs) to chondrocytes, through the self-assembly process. For this purpose, the expression of some chondrocyte markers, such as collagen type I, collagen type II, RUNX2 and lubricin was investigated at different times (7, 14, 21 and 28 days) of chondrogenic differentiation of MSCs, by using immunohistochemistry and Western blot analysis. The second aim of the study was to demonstrate that the expression of lubricin, such as the expression of collagen type II, could be a possible biomarker for the detection of chondrocytes well-being and viability in the natural self-assembling constructs, called 'cell pellets'. Histology (hematoxylin and eosin) and histochemistry (alcian blue staining) methods were used to assess the chondrogenic differentiation of MSCs. The results showed that after 21 days the differentiated chondrocytes, when compared with MSCs cultured without chondrogenic medium (CD44, CD90 and CD105 positive; CD45, CD14 and CD34 negative), were able to produce significant quantities of collagen type I, collagen type II, and lubricin, suggesting hyaline cartilage formation. During the differentiation phase, the cells showed a reduced expression of RUNX2, a protein expressed by osteoblasts. Our studies demonstrated that 21 days is the optimum time for the implantation of chondrocytes differentiated from adipose tissue-derived MSCs. This information could be useful for the future development of cell-based repair therapies for degenerative diseases of articular cartilage. Copyright © 2014 Elsevier GmbH. All rights reserved.

  11. Macrolactin F inhibits RANKL-mediated osteoclastogenesis by suppressing Akt, MAPK and NFATc1 pathways and promotes osteoblastogenesis through a BMP-2/smad/Akt/Runx2 signaling pathway.

    Science.gov (United States)

    Li, Liang; Sapkota, Mahesh; Gao, Ming; Choi, Hyukjae; Soh, Yunjo

    2017-11-15

    The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts. In the current study, macrolactin F (MF) was investigated for novel biological activity on the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages (BMMs). We found that RANKL-induced osteoclast formation and differentiation from BMMs was significantly inhibited by MF in a dose-dependent manner without cytotoxicity. RANKL-induced F-actin ring formation and bone resorption activity in BMMs which was attenuated by MF. In addition, MF suppressed the expression of osteoclast-related genes, including c-myc, RANK, tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T cells c1 (NFATc1), cathepsin K and matrix metalloproteinase 9 (MMP9). Furthermore, the protein expression NFATc1, c-Fos, MMP9, cathepsin K and phosphorylation of Jun N-terminal kinase (JNK), p38 and Akt were also down-regulated by MF treatment. Interestingly, MF promoted pre-osteoblast cell differentiation on Alizarin Red-mineralization activity, alkaline phosphatase (ALP) activity, and the expression of osteoblastogenic markers including Runx2, Osterix, Smad4, ALP, type I collagen alpha 1 (Col1α), osteopontin (OPN), and osteocalcin (OCN) via activation of the BMP-2/smad/Akt/Runx2 pathway on MC3T3-E1. Taken together, these results indicate that MF may be useful as a therapeutic agent to enhance bone health and treat osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification.

    Science.gov (United States)

    Yu, Cong; Li, Lifu; Xie, Fei; Guo, Shichao; Liu, Fayuan; Dong, Nianguo; Wang, Yongjun

    2018-01-01

    Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a vital role in cardiovascular physiology and pathology. Although the lncRNA TUG1 is implicated in atherosclerosis, its function in calcific aortic valve disease (CAVD) remains unknown. In this study, we found that TUG1 was highly expressed in human aortic valves and primary valve interstitial cells (VICs). Moreover, TUG1 knockdown induced inhibition of osteoblast differentiation in CAVD both in vitro and in vivo. Mechanistically, silencing of TUG1 increased the expression of miR-204-5p and subsequently inhibited Runx2 expression at the post-transcriptional level. Importantly, TUG1 directly interacted with miR-204-5p and downregulation of miR-204-5p efficiently reversed the suppression of Runx2 induced by TUG1 short hairpin RNA (shRNA). Thus, TUG1 positively regulated the expression of Runx2, through sponging miR-204-5p, and promoted osteogenic differentiation in CAVD. All together, the evidence generated by our study elucidates the role of lncRNA TUG1 as a miRNA sponge in CAVD, and sheds new light on lncRNA-directed diagnostics and therapeutics in CAVD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  13. Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

    Directory of Open Access Journals (Sweden)

    Kristin Reiche

    located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes.

  14. Accumulation-associated Protein Gene and TGF-beta 1 Affects the Formation of Lung Cancer-related Biological Material Staphylococcus Epidermidis Biofilm

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    Ying CHEN

    2014-04-01

    Full Text Available Background and objective This study was conducted to evaluate the effects of the accumulation-associated protein (Aap gene and transform growth factor-beta 1 (TGF-β1 on the biofilm formation of lung cancer-related Staphylococcus epidermidis (SE. Methods Species identification was performed to isolate SE strains from clinically implanted materials in lung cancer patients. Stable genetic aggregated proteins, which are associated with negative and positive isolates, were obtained. The biofilm-formation ability of the SE Aap gene was determined by PCR. Density gradient method was used to extract peripheral blood mononuclear cells from patients with non-small cell lung cancer. After 30 h, these cells were co-cultured with A549 at different TGF-β1 concentrations. The supernatant was then combined with SE Aap+ and SE Aap- strains and co-cultured with a medical silicone rubber. A semi-quantitative adhesion test was performed for each bacterial biofilm formation. Scanning electron microscopy was also conducted to observe the microcosmic condition of this material on the bacterial biofilm surface. Results The Aap gene was closely related to SE biofilm formation. At 10 ng/mL, 20 ng/mL, and 40 ng/mL, SE Aap+ biofilm on the medical silicone rubber surface was thicker in the TGF-β1 group than in the control group. No significant differences were found between TGF-β1 groups. For the SE Aap- strains, no evident biofilm was formed in TGF-β1 and control groups. Conclusion In plant material-related infection of lung cancer patients, SE Aap+ strain easily forms biofilm. Furthermore, TGF-β1 was conducive for the biofilm formation of SE Aap+ strains.

  15. The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2 and Production of Matrix Metalloproteinase (MMP-13 in Chondrocytes in Osteoarthritis

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    Koh Terauchi

    2016-06-01

    Full Text Available Aging is one of the major pathologic factors associated with osteoarthritis (OA. Recently, numerous reports have demonstrated the impact of sirtuin-1 (Sirt1, which is the NAD-dependent deacetylase, on human aging. It has been demonstrated that Sirt1 induces osteogenic and chondrogenic differentiation of mesenchymal stem cells. However, the role of Sirt1 in the OA chondrocytes still remains unknown. We postulated that Sirt1 regulates a hypertrophic chondrocyte lineage and degeneration of articular cartilage through the activation of osteogenic transcriptional activator Runx2 and matrix metalloproteinase (MMP-13 in OA chondrocytes. To verify whether sirtuin-1 (Sirt1 regulates chondrocyte activity in OA, we studied expressions of Sirt1, Runx2 and production of MMP-13, and their associations in human OA chondrocytes. The expression of Sirt1 was ubiquitously observed in osteoarthritic chondrocytes; in contrast, Runx2 expressed in the osteophyte region in patients with OA and OA model mice. OA relating catabolic factor IL-1βincreased the expression of Runx2 in OA chondrocytes. OA chondrocytes, which were pretreated with Sirt1 inhibitor, inhibited the IL-1β-induced expression of Runx2 compared to the control. Since the Runx2 is a promotor of MMP-13 expression, Sirt1 inactivation may inhibit the Runx2 expression and the resultant down-regulation of MMP-13 production in chondrocytes. Our findings suggest thatSirt1 may regulate the expression of Runx2, which is the osteogenic transcription factor, and the production of MMP-13 from chondrocytes in OA. Since Sirt1 activity is known to be affected by several stresses, including inflammation and oxidative stress, as well as aging, SIRT may be involved in the development of OA.

  16. Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

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    Rama Garimella

    2017-03-01

    Full Text Available Osteosarcoma (OS is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a inflammation and immunity; (b formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium, quantity of gap junctions and skeletogenesis; (c bone mineral density; and (d cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles. Ingenuity pathway analysis revealed significant reduction in Runx2 target genes such as fibroblast growth factor -1, -12 (FGF1 and FGF12, bone morphogenetic factor-1 (BMP1, SWI/SNF related, matrix associated actin dependent regulator of chromatin subfamily a, member 4 (SMARCA4, Matrix extracellular phosphoglycoprotein (MEPE, Integrin, β4 (ITGBP4, Matrix Metalloproteinase -1, -28 (MMP1 and MMP28, and signal transducer and activator of transcription-4 (STAT4 in vitamin D treated 143B OS cells. These genes interact with the inflammation, oxidative stress and membrane vesicle biogenesis gene networks. Vitamin D not only inhibited the expression of Runx2 target genes MMP1, MMP28 and kallikrein related peptidase-7 (KLK7, but also migration and invasion of 143B OS cells. Vitamin D regulated Runx2 target genes or their products represent potential therapeutic targets and laboratory biomarkers for applications in translational oncology.

  17. In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells

    International Nuclear Information System (INIS)

    Fu, Jianjiang; Wang, Wei; Liu, Yu-Hui; Lu, Hong; Luo, Yongming

    2011-01-01

    LGD1069 (Targretin ® ) is a selective retinoid X receptor (RXR) ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes. Human umbilical vein endothelial cells (HUVECs) were used for in vitro study. MTT assay and Sulforhodamine B assay were used for cell viability assay; the tube formation assay was used to investigate the effect of LGD1069 on angiogenesis in vitro. In vitro adhesion, migration and invasion of HUVEC cells were analyzed by Matrigel adhesion, migration and invasion assay. Gene expressions were measured by RT-PCR and Western blot analysis. Our data showed here that LGD1069 inhibited the activation of TGF-β/Smad pathway significantly. Furthermore, it was demonstrated that expression of Runx2 was suppressed pronouncedly during incubation with LGD1069. Runx2 is a DNA-binding transcription factor which plays a master role in tumor-induced angiogenesis and cancer cells metastasis by interaction with the TGF-β/Smad pathway of transcriptional modulators. Our results suggested that LGD1069 may impair angiogenic and metastatic potential induced by tumor cells through suppressing expression of Runx2 directly on human endothelial cells, which may point out new pathway through which LGD1069 display anti-angiogenic properties, and provide new molecular evidence to support LGD1069 as a potent anti-metastatic agent in cancer therapy

  18. Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells.

    Science.gov (United States)

    Garimella, Rama; Tadikonda, Priyanka; Tawfik, Ossama; Gunewardena, Sumedha; Rowe, Peter; Van Veldhuizen, Peter

    2017-03-16

    Osteosarcoma (OS) is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a) inflammation and immunity; (b) formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium), quantity of gap junctions and skeletogenesis; (c) bone mineral density; and (d) cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles. Ingenuity pathway analysis revealed significant reduction in Runx2 target genes such as fibroblast growth factor -1, -12 ( FGF1 and FGF12 ), bone morphogenetic factor-1 ( BMP1 ), SWI/SNF related, matrix associated actin dependent regulator of chromatin subfamily a, member 4 ( SMARCA4 ), Matrix extracellular phosphoglycoprotein ( MEPE ), Integrin, β4 ( ITGBP4 ), Matrix Metalloproteinase -1, -28 ( MMP1 and MMP28 ), and signal transducer and activator of transcription-4 ( STAT4 ) in vitamin D treated 143B OS cells. These genes interact with the inflammation, oxidative stress and membrane vesicle biogenesis gene networks. Vitamin D not only inhibited the expression of Runx2 target genes MMP1 , MMP28 and kallikrein related peptidase-7 ( KLK7 ), but also migration and invasion of 143B OS cells. Vitamin D regulated Runx2 target genes or their products represent potential therapeutic targets and laboratory biomarkers for applications in translational oncology.

  19. Cancer-related anemia

    International Nuclear Information System (INIS)

    Abdel-Rzaeq, Hikmat N.

    2004-01-01

    Anemia is the most common hematological abnormality in cancer patients is often under-recognized and undertreated. The pathogenesis of cancer anemia is complex and most of time multifactorial; involving factors related to the tumor itself or its therapy. While anemia can be present in a wide range of symptoms, involing almost every organ, it is beleived that it contributes much to cancer-related-fatigue, one of the most common symptoms in cancer patients. In addition there is increasing evidence to suggest that anemia is an independent factor adversely affecting tumor reponse and patient survival. While blood transfusion was the only option to treat cancer related anemia, the use of recombinant human erythropoietin (rHuEPO) is becomig the new standard of care, more so with the recent studies demonstrating the feasibility of a sigle weekly injection .Things are even getting better with the recent approval of a new form of rHuEPO; Darbepoetin an analogue with a 3-fold longer half-life. In addition to its effects in raising homoglobin, several well controlled studies demonstrated decrease in transfusion requirementsand better qualify of life assessed objectively using standard assesments scales. (author)

  20. Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

    Science.gov (United States)

    Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

    2015-01-01

    Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

  1. Multi-analyte profiling and pathway analysis of plasma for proteins associated with cancer-related fatigue syndrome in disease-free breast cancer patients after primary treatment.

    Science.gov (United States)

    Minton, O; Coulton, G R; Stone, P

    2014-12-01

    A significant number of women treated for breast cancer develop long-term fatigue afterwards. Previous research has suggested that fatigue may be due to a prolonged inflammatory response. However, there are conflicting results and the exact nature of the disturbance remains unclear. To identify inflammatory markers associated with fatigue. We recruited women from a breast cancer follow-up clinic and categorised them on the basis of a diagnostic interview as to whether they met the criteria for cancer-related fatigue syndrome (cases) or not (controls). We took plasma samples from each participant to analyse subsequently using a panel of 88 biological markers. 90 samples were analysed in total (45 cases and 45 controls). A factorial analysis of variance (using age as a fixed factor) demonstrated a number of differences in inflammatory cytokines. There were 28 significantly different analytes in total. Granulocyte colony stimulating factor was the most significantly different analyte (pfatigue syndrome is associated with an increased pro-inflammatory immune response. Our findings indicate that these cytokine changes could underpin the subjective symptoms, such as perceived muscle weakness and concentration difficulties, experienced by women who feel fatigued after treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Martin

    Full Text Available Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for determining a patients' prognosis is measurement of histopathologic tumor necrosis following pre-operative neo-adjuvant chemotherapy. Unfavourable prognosis is indicated by less than 90% estimated necrosis of the tumor. Neither genetic testing nor molecular biomarkers for diagnosis and prognosis have been described for osteosarcomas. We used the novel nanoString mRNA digital expression analysis system to analyse gene expression in 32 patients with sporadic paediatric osteosarcoma. This system used specific molecular barcodes to quantify expression of a set of 17 genes associated with osteosarcoma tumorigenesis. Five genes, from this panel, which encoded the bone differentiation regulator RUNX2, the cell cycle regulator CDC5L, the TP53 transcriptional inactivator MDM2, the DNA helicase RECQL4, and the cyclin-dependent kinase gene CDK4, were differentially expressed in tumors that responded poorly to neo-adjuvant chemotherapy. Analysis of the signalling relationships of these genes, as well as other expression markers of osteosarcoma, indicated that gene networks linked to RB1, TP53, PI3K, PTEN/Akt, myc and RECQL4 are associated with osteosarcoma. The discovery of these networks provides a basis for further experimental studies of role of the five genes (RUNX2, CDC5L, MDM2, RECQL4, and CDK4 in differential response to chemotherapy.

  3. Prolactin/androgen-inducible carboxypeptidase-D increases with nitrotyrosine and Ki67 for breast cancer progression in vivo, and upregulates progression markers VEGF-C and Runx2 in vitro.

    Science.gov (United States)

    Thomas, Lynn N; Chedrawe, Emily R; Barnes, Penelope J; Too, Catherine K L

    2017-07-01

    Carboxypeptidase-D (CPD) cleaves C-terminal arginine (Arg) to produce nitric oxide (NO). Upregulation of CPD and NO by 17β-estradiol, prolactin (PRL), and androgen increases survival of human breast cancer (BCa) cells in vitro. To demonstrate similar events in vivo, CPD, nitrotyrosine (NT, hallmark of NO action), androgen receptor (AR), prolactin receptor (PRLR), and phospho-Stat5a (for activated PRLR) levels were evaluated in benign and malignant human breast tissues, and correlated with cell proliferation (Ki67) and BCa progression (Cullin-3) biomarkers. Paraffin-embedded breast tissues were analyzed by immunohistochemistry (IHC). BCa progression markers in human MCF-7 and T47D BCa cell lines treated with NO donor SIN-1 or PRL, ±CPD inhibitors were analyzed by RT-qPCR and immunoblotting. IHC showed progressive increases in CPD, NT, Ki67, and Cullin-3 from low levels in benign tissues to high levels in ductal carcinoma in situ, low-grade, high-grade, and triple-negative BCa. CPD and NT staining were closely associated, implicating CPD in NO production. Phospho-Stat5a increased significantly from benign to high-grade BCa and was mostly nuclear. AR and PRLR were abundant in benign breast and BCa, including triple-negative tumors. SIN-1 and PRL increased VEGF-C and Runx2, but not Cullin-3, in BCa cell lines. PRL induction of VEGF-C and Runx2 was inhibited partly by CPD inhibitors, implicating NO, produced by PRL-regulated CPD, in BCa progression. The CPD-Arg-NO pathway contributes to BCa progression in vitro and in vivo. PRL/androgen activation of the pathway support combined AR and PRLR blockade as an additional therapy for BCa.

  4. Isoquercitrin and polyphosphate co-enhance mineralization of human osteoblast-like SaOS-2 cells via separate activation of two RUNX2 cofactors AFT6 and Ets1.

    Science.gov (United States)

    Wang, Xiaohong; Schröder, Heinz C; Feng, Qingling; Diehl-Seifert, Bärbel; Grebenjuk, Vladislav A; Müller, Werner E G

    2014-06-01

    Isoquercitrin, a dietary phytoestrogen, is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. Here we studied the combined effects of isoquercitrin, a cell membrane permeable 3-O-glucoside of quercetin, and polyphosphate [polyP], a naturally occurring inorganic polymer inducing bone formation, on mineralization of human osteoblast-like SaOS-2 cells. Both compounds isoquercitrin and polyP induce at non-toxic concentrations the mineralization process of SaOS-2 cells. Co-incubation experiments revealed that isoquercitrin (at 0.1 and 0.3μM), if given simultaneously with polyP (as Ca(2+) salt; at 3, 10, 30 and 100μM) amplifies the mineralization-enhancing effect of the inorganic polymer. The biomineralization process induced by isoquercitrin and polyP is based on two different modes of action. After incubation of the cells with isoquercitrin or polyP the expression of the Runt-related transcription factor 2 [RUNX2] is significantly upregulated. In addition, isoquercitrin causes a strong increase of the steady-state-levels of the two co-activators of RUNX2, the activating transcription factor 6 [ATF6] and the Ets oncogene homolog 1 [Ets1]. The activating effect of isoquercitrin occurs via a signal transduction pathway involving ATF6, and by that, is independent from the induction cascade initiated by polyP. This conclusion is supported by the finding that isoquercitrin upregulates the expression of the gene encoding for osteocalcin, while polyP strongly increases the expression of the Ets1 gene and of the alkaline phosphatase. We show that the two compounds, polyP and isoquercitrin, have a co-enhancing effect on bone mineral formation and in turn might be of potential therapeutic value for prevention/treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Getting the Facts: Cancer-Related Fatigue

    Science.gov (United States)

    ... and depression, that can cause cancer-related fatigue. Cancer treatment such as chemotherapy, radiation therapy, stem cell transplantation, and biologic therapy are often associated with fatigue. Anemia (a ...

  6. Role of PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis

    Science.gov (United States)

    2009-09-01

    of Runx2 family (24) and TEAD /TEF family (25), the proapoptotic protein p73 (26, 27), and is involved in ErbB4 signaling (28). In the present study...A, Kaneko KJ, Shu H, Zhao Y, DePamphilis ML 2001 TEAD /TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein

  7. [Cancer-related fatigue. Psychosocial support].

    Science.gov (United States)

    de Vries, U; Reif, K; Petermann, F

    2012-03-01

    Cancer-related fatigue is a subjective sensation of uncontrollable physical, emotional and/or cognitive tiredness and weakness, which occurs in the context of cancer or cancer-treatment. Cancer-related fatigue occurs at all stages of cancer treatment and can persist long after medical treatment. It profoundly affects patients' quality of life and limits their personal, social, and occupational lives. Cancer-related fatigue is also associated with significant levels of distress, and it imposes financial burdens by limiting a patient's ability to work. Current psychosocial interventions with strong or sufficient evidence include physical training, cognitive-behavioral training, relaxation techniques, psychoeducation and patient education. This article gives an overview of currently available psychosocial interventions and information on their implementation.

  8. Role of the PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis

    Science.gov (United States)

    2007-03-01

    that YAP may regulate transcription (23) by acting as a coactivator for several transcription factors including members of Runx2 family (24) and TEAD ...DePamphilis ML 2001 TEAD /TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein local- ized in the cytoplasm

  9. Cancer-related fatigue treatment: An overview

    Directory of Open Access Journals (Sweden)

    Hemanth Mohandas

    2017-01-01

    Full Text Available Cancer-related fatigue is a symptom of cancer where most patients or the general practitioners tend to misinterpret due to the insufficient understanding or knowledge of cancer-related fatigue (CRF. This paper will provide a better perspective for the patients and the health professionals on how to manage and handle CRF for both mild and severe fatigue patients. Articles were selected from the searches of PubMed database that had the terms “randomized controlled trials,” “cancer,” “fatigue,” “pharmacologic treatment,” and “nonpharmacologic treatment” using both Mesh terms and keywords. The authors have reviewed the current hypothesis and evidence of the detailed etiology of the CRF present in the literature for healthier management, directives, and strategies to improve the treatment of cancer-related fatigue. An algorithm has been blueprinted on screening, and management, of the CRF, and various kinds of effective treatments and assessment tools have been briefly studied and explained. Although many strategies seemed promising, the quality of randomized controlled trials is generally quite low in studies, making it difficult to draw conclusions about the effectiveness of each self-care strategies. Therefore, future studies require better design and reporting of methodological issues to ensure evidence-based self-care recommendations for people receiving cancer treatment.

  10. Stereotactic mesencephalotomy for cancer - related facial pain.

    Science.gov (United States)

    Kim, Deok-Ryeong; Lee, Sang-Won; Son, Byung-Chul

    2014-07-01

    Cancer-related facial pain refractory to pharmacologic management or nondestructive means is a major indication for destructive pain surgery. Stereotactic mesencephalotomy can be a valuable procedure in the management of cancer pain involving the upper extremities or the face, with the assistance of magnetic resonance imaging (MRI) and electrophysiologic mapping. A 72-year-old man presented with a 3-year history of intractable left-sided facial pain. When pharmacologic and nondestructive measures failed to provide pain alleviation, he was reexamined and diagnosed with inoperable hard palate cancer with intracranial extension. During the concurrent chemoradiation treatment, his cancer-related facial pain was aggravated and became medically intractable. After careful consideration, MRI-based stereotactic mesencephalotomy was performed at a point 5 mm behind the posterior commissure, 6 mm lateral to and 5 mm below the intercommissural plane using a 2-mm electrode, with the temperature of the electrode raised to 80℃ for 60 seconds. Up until now, the pain has been relatively well-controlled by intermittent intraventricular morphine injection and oral opioids, with the pain level remaining at visual analogue scale 4 or 5. Stereotactic mesencephalotomy with the use of high-resolution MRI and electrophysiologic localization is a valuable procedure in patients with cancer-related facial pain.

  11. The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways.

    Science.gov (United States)

    Sun, Yahui; Ma, Chenkai; Halgamuge, Saman

    2017-12-28

    Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases.

  12. Urological cancer related to familial syndromes

    Directory of Open Access Journals (Sweden)

    Walter Henriques da Costa

    Full Text Available ABSTRACT Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC, succinate dehydrogenase kidney cancer (SDH-RCC, and more recently BAP1 germline mutation related RCC. Among tumors from the bladder or renal pelvis, some studies had reinforced the role of germline mutations in mismatch repair (MMR genes, especially in young patients. In prostate adenocarcinoma, besides mutations in BRCA1 and BRCA2 genes that are known to increase the incidence of high-risk cancer in young patients, new studies have shown mutation in other gene such as HOXB13 and also polymorphisms in MYC, MSMB, KLK2 and KLK3 that can be related to hereditary prostate cancer. Finally, tumors from testis that showed an increased in 8 - 10-fold in siblings and 4 - 6-fold in sons of germ cell tumors (TGCT patients, have been related to alteration in X chromosome. Also genome wide association studies GWAS pointed new genes that can also be related to increase of this susceptibility.

  13. Statin use and reduced cancer-related mortality

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G; Bojesen, Stig E

    2012-01-01

    A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality....

  14. Diarrhea: Cancer-Related Causes and How to Cope

    Science.gov (United States)

    Diarrhea: Cancer-related causes and how to cope Knowing which diarrhea signs and symptoms are routine and which are ... stomach cramps. The frequent trips to the bathroom. Diarrhea is an unpleasant but common side effect in ...

  15. Oxycodone for cancer-related pain.

    Science.gov (United States)

    Schmidt-Hansen, Mia; Bennett, Michael I; Arnold, Stephanie; Bromham, Nathan; Hilgart, Jennifer S

    2017-08-22

    Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated version of the original Cochrane review published in 2015, Issue 2 on oxycodone for cancer-related pain. To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2016. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions. We included randomised controlled trials (parallel group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference. Two review authors independently extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall quality of the evidence using GRADE. For this update, we identified six new studies (1258 participants

  16. Psychological factors and psychosocial interventions for cancer related pain.

    Science.gov (United States)

    Ciucă, Andrada; Băban, Adriana

    2017-06-01

    The present paper is aimed at briefly presenting psychological factors involved in cancer related pain and what psychosocial interventions are efficient in reducing it. Cancer related pain is a complex experience and the most integrative and recommended approach is the biopsychosocial model. It has been proved that chronic pain is more strongly related to psychological factors than to treatment or illness related factors. Psychological factors influencing pain experience can be intuitively grouped starting with awareness of pain (i.e., attentional factor), then with evaluation of pain (i.e., cognitive factors) which is leading to feelings (i.e., emotional factors), and behaviours (i.e., coping strategies) regarding pain. Psychosocial interventions (i.e., skill based and education based interventions) have strong evidence that is effective in reducing cancer related pain.

  17. Cancer-related fatigue : Predictors and effects of rehabilitation

    NARCIS (Netherlands)

    van Weert, Ellen; Hoekstra-Weebers, Josette; Otter, Renee; Postema, Klaas; Sanderman, Robbert; van der Schans, Cees

    Background. The aims of the study were to examine the effects of a multidimensional rehabilitation program on cancer-related fatigue, to examine concurrent predictors of fatigue, and to investigate whether change in fatigue over time was associated with change in predictors. Methods. Sample: 72

  18. Breast Cancer-Related Lymphedema: Implications for Family Leisure Participation

    Science.gov (United States)

    Radina, M. Elise

    2009-01-01

    An estimated 20% of breast cancer survivors face the chronic condition of breast cancer-related lymphedema. This study explored the ways in which women with this condition experienced changes in their participation in family leisure as one indicator of family functioning. Participants (N = 27) were interviewed regarding lifestyles before and after…

  19. Supervised exercise reduces cancer-related fatigue: a systematic review

    OpenAIRE

    Meneses-Ech??vez, Jos?? F.; Gonz??lez Jim??nez, Emilio; Ram??rez-V??lez, Robinson

    2015-01-01

    Question: Does supervised physical activity reduce cancer-related fatigue? Design: Systematic review with meta-analysis of randomised trials. Participants: People diagnosed with any type of cancer, without restriction to a particular stage of diagnosis or treatment. Intervention: Supervised physical activity interventions (eg, aerobic, resistance and stretching exercise), defined as any planned or structured body movement causing an increase in energy expenditure, designed to maintain or enha...

  20. Effect of aerobic exercise on cancer-related fatigue

    Directory of Open Access Journals (Sweden)

    Jaivika Govindbhai Patel

    2017-01-01

    Full Text Available Background: Fatigue is the most common side effect of cancer treatment with chemotherapy and/or radiation therapy, selected biologic response modifiers. The main purpose of this study is to evaluate the effects of aerobic exercise on cancer-related fatigue in patients of the solid tumor after chemotherapy and radiotherapy. Methods: After screening for cancer-related fatigue, 34 patients fulfilled the inclusive criteria and were assigned into two groups (n = 17 recruited in the intervention group and n = 17 in control group. The intervention group received aerobic exercise program which included treadmill walking with low to moderate intensity (50%–70% of maximum heart rate, for 20–40 min/day for 5 days/week. Control group were taught stretching exercises of hamstrings, gastrocnemius, and soleus (to be done at home and were encouraged to remain active. Outcome measures such as brief fatigue inventory (BFI, 6-min walk test, and functional assessment of cancer therapy-general (FACT-G were taken at baseline and after 6-weeks. Results: The data were analyzed using the Wilcoxon matched-pairs signed rank test for within group and Mann–Whitney U-test for between group comparisons. The results of this study showed that there was a significant reduction in cancer-related fatigue BFI score (P < 0.0001,, also there was significant improvement in the physical performance as in 6-min walk distance (P < 0.0001 and quality of life, FACT-G score (P = 0.0001. Conclusion: Aerobic exercise for 6 weeks has beneficial effects on cancer-related fatigue in patients with solid tumor after chemotherapy and/or radiotherapy.

  1. Objective and subjective predictors of cancer-related stress symptoms in testicular cancer survivors

    NARCIS (Netherlands)

    Fleer, Joke; Sleijfer, Dirk; Hoekstra, Harald; Tuinman, Marrit; Klip, Ed; Hoekstra-Weebers, Josette

    2006-01-01

    Objective: (1) To investigate cancer-related stress symptoms among testicular cancer survivors (TCSs), (2) to gain insight into the relationship Of sociodemographic and cancer-related variables with cancer-related stress symptoms and (3) to assess whether objective and subjective aspects of cancer

  2. Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

    International Nuclear Information System (INIS)

    Carmona-Rodriguez, Bruno; Alvarez-Perez, Marco Antonio; Narayanan, A. Sampath; Zeichner-David, Margarita; Reyes-Gasga, Jose; Molina-Guarneros, Juan; Garcia-Hernandez, Ana Lilia; Suarez-Franco, Jose Luis; Chavarria, Ivet Gil; Villarreal-Ramirez, Eduardo; Arzate, Higinio

    2007-01-01

    We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation

  3. Spinal cord stimulation for cancer-related pain in adults.

    Science.gov (United States)

    Peng, Lihua; Min, Su; Zejun, Zhou; Wei, Ke; Bennett, Michael I

    2015-06-29

    This is an update of a review first published in The Cochrane Library in Issue 3, 2013. Cancer-related pain places a heavy burden on public health with related high expenditure. Severe pain is associated with a decreased quality of life in patients with cancer. A significant proportion of patients with cancer-related pain are under-treated. There is a need for more effective control of cancer-related pain. Spinal cord stimulation (SCS) may have a role in pain management. The effectiveness and safety of SCS for patients with cancer-related pain is currently unknown. This systematic review evaluated the effectiveness of SCS for cancer-related pain compared with standard care using conventional analgesic medication. We also appraised risk and potential adverse events associated with the use of SCS. This is an update of a review first published in The Cochrane Library in Issue 3, 2013. The search strategy for the update was the same as in the original review. We searched the following bibliographic databases in order to identify relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and CBM (Chinese Biomedical Database) in October 2014. We also handsearched relevant journals. There were no language restrictions. We planned to include randomised controlled trials (RCTs) that directly compared SCS with other interventions with regards to the effectiveness of pain management. We also planned to include cross-over trials that compared SCS with another treatment. We planned to identify non-randomised controlled trials but these would only be included if no RCTs could be found. The literature search for the update of this review found 121 potentially eligible articles. The initial search strategy yielded 430 articles. By scrutinising titles and abstracts, we found 412 articles irrelevant to the analytical purpose of this systematic review due to different scopes of diseases or different methods of intervention

  4. Supervised exercise reduces cancer-related fatigue: a systematic review

    Directory of Open Access Journals (Sweden)

    José F Meneses-Echávez

    2015-01-01

    Full Text Available Question: Does supervised physical activity reduce cancer-related fatigue? Design: Systematic review with meta-analysis of randomised trials. Participants: People diagnosed with any type of cancer, without restriction to a particular stage of diagnosis or treatment. Intervention: Supervised physical activity interventions (eg, aerobic, resistance and stretching exercise, defined as any planned or structured body movement causing an increase in energy expenditure, designed to maintain or enhance health-related outcomes, and performed with systematic frequency, intensity and duration. Outcome measures: The primary outcome measure was fatigue. Secondary outcomes were physical and functional wellbeing assessed using the Functional Assessment of Cancer Therapy Fatigue Scale, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Piper Fatigue Scale, Schwartz Cancer Fatigue Scale and the Multidimensional Fatigue Inventory. Methodological quality, including risk of bias of the studies, was evaluated using the PEDro Scale. Results: Eleven studies involving 1530 participants were included in the review. The assessment of quality showed a mean score of 6.5 (SD 1.1, indicating a low overall risk of bias. The pooled effect on fatigue, calculated as a standardised mean difference (SMD using a random-effects model, was –1.69 (95% CI –2.99 to –0.39. Beneficial reductions in fatigue were also found with combined aerobic and resistance training with supervision (SMD = –0.41, 95% CI –0.70 to –0.13 and with combined aerobic, resistance and stretching training with supervision (SMD = –0.67, 95% CI –1.17 to –0.17. Conclusion: Supervised physical activity interventions reduce cancer-related fatigue. These findings suggest that combined aerobic and resistance exercise regimens with or without stretching should be included as part of rehabilitation programs for people who have been diagnosed with cancer

  5. Managing cancer-related pain in critical care settings.

    Science.gov (United States)

    Dolan, Elisabeth A; Paice, Judith A; Wile, Sally

    2011-01-01

    Pain is a common symptom experienced by individuals who are in treatment for cancer and becomes more prevalent for those with more advanced stages of malignancy. Critical care nurses are essential in the management of cancer-related pain, which is a challenging problem when individuals who have a cancer diagnosis are admitted to the intensive care unit for emergent conditions. Regular, thorough, and patient-appropriate assessments by experienced critical care nurses guide selection of treatment modalities, including pharmacologic and nonpharmacologic techniques. In addition, existential pain necessitates spiritual care intervention, and involvement of other appropriate interdisciplinary team members can result in improved management of all types of pain experienced by critically ill individuals with cancer.

  6. Lymphoedema management in breast cancer-related lymphoedema.

    Science.gov (United States)

    Jones, Joanne

    2013-04-01

    Due to developments in diagnosis and treatment of breast cancer, survival rates are rising. This leads to a population of mainly women, who also experience breast cancer-related lymphoedema (BCRL). Long after the cancer has been treated, lymphoedema persists at a time when individuals have returned to work. Large limb volumes can present a problem to these individuals and innovative treatments are needed, in order to retain as much normality as possible and reduce excessive limb volumes that patients can experience with lymphoedema long after treatment. It is also important that these treatments do not disrupt daily living and, for some, work-life balance. With the introduction of wrap around compression systems and collaborative working with the patient, it is possible to achieve an acceptable outcome to those patients with these issues. This approach leads to patient satisfaction and stabilisation of limb volume to within acceptable limits for these patients, in conjunction with the therapist.

  7. Basic research on cancer related to radiation associated medical researches

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong In; Hwang, Dae Yong; Bang, Ho Yoon [and others

    2000-12-01

    Basic Research on Cancer related to Radiation Associated Medical Researches including 1. Establishment of animal model of colorectal cancer liver metastasis and measurement of angiogenesis, 2. Tissue expression of Tie-1 and Tie-2 in human colorectal cancer, 3. Enhancement of G2/Mphase Cell Fraction by Adenovirus-mediated p53 Gene Transfer in Ovarian Cancer Cell Lines, 4. Clinical Characteristics of the patients with Non-B Non-C Hepatocellular Carcinoma and Frequency of HBV, HCV and TTV Viremia in these Patients, 5. Significance of serum iron and ferritin in patients with stomach cancer, 6. Telomerase assay for early detection of lung cancer, 7. Study on the Usefulness of Aldehyde dehydrogenase-2 Genotyping for Risk Group of Alcohol-related Cancer Screening, 8. Gene therapy using hepatoma specific promoter, 9. Study on the Influence of DNA repair gene, XRCC1 Genotypes on the Risk of Head and Neck Cancer were performed.

  8. Basic research on cancer related to radiation associated medical researches

    International Nuclear Information System (INIS)

    Lee, Jong In; Hwang, Dae Yong; Bang, Ho Yoon

    2000-12-01

    Basic Research on Cancer related to Radiation Associated Medical Researches including 1. Establishment of animal model of colorectal cancer liver metastasis and measurement of angiogenesis, 2. Tissue expression of Tie-1 and Tie-2 in human colorectal cancer, 3. Enhancement of G2/Mphase Cell Fraction by Adenovirus-mediated p53 Gene Transfer in Ovarian Cancer Cell Lines, 4. Clinical Characteristics of the patients with Non-B Non-C Hepatocellular Carcinoma and Frequency of HBV, HCV and TTV Viremia in these Patients, 5. Significance of serum iron and ferritin in patients with stomach cancer, 6. Telomerase assay for early detection of lung cancer, 7. Study on the Usefulness of Aldehyde dehydrogenase-2 Genotyping for Risk Group of Alcohol-related Cancer Screening, 8. Gene therapy using hepatoma specific promoter, 9. Study on the Influence of DNA repair gene, XRCC1 Genotypes on the Risk of Head and Neck Cancer were performed

  9. Prediction of oncogenic interactions and cancer-related signaling networks based on network topology.

    Directory of Open Access Journals (Sweden)

    Marcio Luis Acencio

    Full Text Available Cancer has been increasingly recognized as a systems biology disease since many investigators have demonstrated that this malignant phenotype emerges from abnormal protein-protein, regulatory and metabolic interactions induced by simultaneous structural and regulatory changes in multiple genes and pathways. Therefore, the identification of oncogenic interactions and cancer-related signaling networks is crucial for better understanding cancer. As experimental techniques for determining such interactions and signaling networks are labor-intensive and time-consuming, the development of a computational approach capable to accomplish this task would be of great value. For this purpose, we present here a novel computational approach based on network topology and machine learning capable to predict oncogenic interactions and extract relevant cancer-related signaling subnetworks from an integrated network of human genes interactions (INHGI. This approach, called graph2sig, is twofold: first, it assigns oncogenic scores to all interactions in the INHGI and then these oncogenic scores are used as edge weights to extract oncogenic signaling subnetworks from INHGI. Regarding the prediction of oncogenic interactions, we showed that graph2sig is able to recover 89% of known oncogenic interactions with a precision of 77%. Moreover, the interactions that received high oncogenic scores are enriched in genes for which mutations have been causally implicated in cancer. We also demonstrated that graph2sig is potentially useful in extracting oncogenic signaling subnetworks: more than 80% of constructed subnetworks contain more than 50% of original interactions in their corresponding oncogenic linear pathways present in the KEGG PATHWAY database. In addition, the potential oncogenic signaling subnetworks discovered by graph2sig are supported by experimental evidence. Taken together, these results suggest that graph2sig can be a useful tool for investigators involved

  10. Supervised exercise reduces cancer-related fatigue: a systematic review.

    Science.gov (United States)

    Meneses-Echávez, José F; González-Jiménez, Emilio; Ramírez-Vélez, Robinson

    2015-01-01

    Does supervised physical activity reduce cancer-related fatigue? Systematic review with meta-analysis of randomised trials. People diagnosed with any type of cancer, without restriction to a particular stage of diagnosis or treatment. Supervised physical activity interventions (eg, aerobic, resistance and stretching exercise), defined as any planned or structured body movement causing an increase in energy expenditure, designed to maintain or enhance health-related outcomes, and performed with systematic frequency, intensity and duration. The primary outcome measure was fatigue. Secondary outcomes were physical and functional wellbeing assessed using the Functional Assessment of Cancer Therapy Fatigue Scale, European Organisation for Research and Treatment of Cancer Quality of Life QUESTIONnaire, Piper Fatigue Scale, Schwartz Cancer Fatigue Scale and the Multidimensional Fatigue Inventory. Methodological quality, including risk of bias of the studies, was evaluated using the PEDro Scale. Eleven studies involving 1530 participants were included in the review. The assessment of quality showed a mean score of 6.5 (SD 1.1), indicating a low overall risk of bias. The pooled effect on fatigue, calculated as a standardised mean difference (SMD) using a random-effects model, was -1.69 (95% CI -2.99 to -0.39). Beneficial reductions in fatigue were also found with combined aerobic and resistance training with supervision (SMD=-0.41, 95% CI -0.70 to -0.13) and with combined aerobic, resistance and stretching training with supervision (SMD=-0.67, 95% CI -1.17 to -0.17). Supervised physical activity interventions reduce cancer-related fatigue. These findings suggest that combined aerobic and resistance exercise regimens with or without stretching should be included as part of rehabilitation programs for people who have been diagnosed with cancer. PROSPERO CRD42013005803. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

  11. Cancer related fatigue: implementing guidelines for optimal management.

    Science.gov (United States)

    Pearson, Elizabeth J M; Morris, Meg E; McKinstry, Carol E

    2017-07-18

    Cancer-related fatigue (CRF) is a key concern for people living with cancer and can impair physical functioning and activities of daily living. Evidence-based guidelines for CRF are available, yet inconsistently implemented globally. This study aimed to identify barriers and enablers to applying a cancer fatigue guideline and to derive implementation strategies. A mixed-method study explored the feasibility of implementing the CRF guideline developed by the Canadian Association for Psychosocial Oncology (CAPO). Health professionals, managers and consumers from different practice settings participated in a modified Delphi study with two survey rounds. A reference group informed the design of the study including the surveys. The first round focused on guideline characteristics, compatibility with current practice and experience, and behaviour change. The second survey built upon and triangulated the first round. Forty-five health practitioners and managers, and 68 cancer survivors completed the surveys. More than 75% of participants endorsed the CAPO cancer related fatigue guidelines. Some respondents perceived a lack of resources for accessible and expert fatigue management services. Further barriers to guideline implementation included complexity, limited practical details for some elements, and lack of clinical tools such as assessment tools or patient education materials. Recommendations to enhance guideline applicability centred around four main themes: (1) balancing the level of detail in the CAPO guideline with ease of use, (2) defining roles of different professional disciplines in CRF management, (3) how best to integrate CRF management into policy and practice, (4) how best to ensure a consumer-focused approach to CRF management. Translating current knowledge on optimal management of CRF into clinical practice can be enhanced by the adoption of valid guidelines. This study indicates that it is feasible to adopt the CAPO guidelines. Clinical application may

  12. Weight lifting in women with breast-cancer-related lymphedema.

    Science.gov (United States)

    Schmitz, Kathryn H; Ahmed, Rehana L; Troxel, Andrea; Cheville, Andrea; Smith, Rebecca; Lewis-Grant, Lorita; Bryan, Cathy J; Williams-Smith, Catherine T; Greene, Quincy P

    2009-08-13

    Weight lifting has generally been proscribed for women with breast-cancer-related lymphedema, preventing them from obtaining the well-established health benefits of weight lifting, including increases in bone density. We performed a randomized, controlled trial of twice-weekly progressive weight lifting involving 141 breast-cancer survivors with stable lymphedema of the arm. The primary outcome was the change in arm and hand swelling at 1 year, as measured through displaced water volume of the affected and unaffected limbs. Secondary outcomes included the incidence of exacerbations of lymphedema, number and severity of lymphedema symptoms, and muscle strength. Participants were required to wear a well-fitted compression garment while weight lifting. The proportion of women who had an increase of 5% or more in limb swelling was similar in the weight-lifting group (11%) and the control group (12%) (cumulative incidence ratio, 1.00; 95% confidence interval, 0.88 to 1.13). As compared with the control group, the weight-lifting group had greater improvements in self-reported severity of lymphedema symptoms (P=0.03) and upper- and lower-body strength (Pweight lifting had no significant effect on limb swelling and resulted in a decreased incidence of exacerbations of lymphedema, reduced symptoms, and increased strength. (ClinicalTrials.gov number, NCT00194363.) 2009 Massachusetts Medical Society

  13. Traditional Chinese medical comprehensive therapy for cancer-related fatigue.

    Science.gov (United States)

    Yang, Lu; Li, Tian-Tian; Chu, Yu-Ting; Chen, Ke; Tian, Shao-Dan; Chen, Xin-Yi; Yang, Guo-Wang

    2016-01-01

    Cancer-related fatigue (CRF) is a common and one of the most severe symptom in the period of onset, diagnosis, treatment and rehabilitation process of cancer. But there are no confirmed measures to relieve this problem at present. Traditional Chinese medical comprehensive therapy has its advantages in dealing with this condition. Based on the research status of CRF, the following problems have been analyzed and solved: the term of CRF has been defined and recommended, and the definition has been made clear; the disease mechanism is proposed, i.e. healthy qi has been impaired in the long-term disease duration, in the process of surgery, chemotherapy, radiotherapy and biology disturbing; it is clear that the clinical manifestations are related to six Chinese medicine patterns: decreased functioning of the Pi (Spleen) and Wei (Stomach), deficiency of the Pi with dampness retention, deficiency of the Xin (Heart) and Pi, disharmony between the Gan (Liver) and Pi, deficiency of the Pi and Shen (Kidney), and deficiency of the Fei (Lung) and Shen. Based on its severity, the mild patients are advised to have non-drug psychological intervention and sleep treatment in cooperation with appropriate exercise; diet therapy are recommended to moderate patients together with sleep treatment and acupuncture, severe patients are recommended to have herbal treatment based on pattern differentiation together with physiological sleep therapy.

  14. Cancer-related fatigue in palliative care: a global perspective.

    Science.gov (United States)

    Vilchynska, Tetyana; Beard, Barbara

    2016-05-01

    Cancer-related fatigue (CRF) in a palliative care setting is a distressing symptom that can have a negative impact on a patient's quality of life. A range of setting- and disease-specific factors, unknown aetiology and absence of unilateral guidelines make CRF treatment a challenge for clinicians. In the absence of high-quality evidence in favour of any pharmacological and nonpharmacological measures, except exercise, cognitive behavioural therapy and psychosocial interventions, a personalised integrative oncology approach can lead to effective management. Findings suggest adoption of a severity-based symptom-stage adjusted CRF management care pathway, highlighting best practices to illustrate the lived experience of this symptom. Overcoming barriers by staff training, patient education, facilitating communication and patients' self-care, will increase CRF management effectiveness. Future CRF multisymptom or multidimensional nature investigation trials of its underlying mechanisms and new pharmacological and nonpharmacological strategies applied separately or in combination, will help reveal the best approach to CRF diagnosis, assessment and management.

  15. Exercise, sleep and cancer-related fatigue: Are they related?

    Science.gov (United States)

    Medysky, Mary E; Temesi, John; Culos-Reed, Susan Nicole; Millet, Guillaume Y

    2017-04-01

    Cancer-related fatigue (CRF) is a commonly reported and debilitating side effect of cancer and/or cancer treatment. Sleep disorders are also highly reported in the cancer population; however it is unknown if sleep is associated with fatigue. In the general population, exercise has been shown to improve sleep, however in the cancer population this idea is under investigation. The primary purposes of this review were to: (i) review the prevalence and causes of sleep disorders in cancer patients and survivors, (ii) examine the relationship between sleep and CRF and (iii) review the impact of exercise interventions on sleep in cancer patients and survivors. A scoping review of the literature was conducted regarding exercise interventions in cancer patients and survivors with sleep as at least one outcome measure. A search of the literature revealed limited studies (n=21) assessing the effect of exercise on sleep disorders in the cancer population. Methodological issues are evident because assessing sleep is often not the main outcome of interest. The reviewed studies revealed that exercise positively impacts sleep quality and quantity. There seems to be possible relationship between sleep disorders, exercise and CRF. Further investigation of this relationship is necessary, specifically using objective measurement tools, in large, controlled studies, focusing on sleep as the primary outcome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Parris, Toshima Z; Aziz, Luaay; Kovács, Anikó; Hajizadeh, Shahin; Nemes, Szilárd; Semaan, May; Chen, Chang Yan; Karlsson, Per; Helou, Khalil

    2014-01-01

    Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness. To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models. We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively. Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients

  17. [Exercise Therapy for Children with Cancer Related Fatigue].

    Science.gov (United States)

    Jung, M; Zepf, N; Fuchs, B

    2016-05-01

    Cancer Related Fatigue (CRF) is known as one of the strongest and incriminating side effects of cancer for adults and children. By now there is a lack of valid assessments and sufficient therapy in pediatric oncology. For children it is a tough challenge to accept this overwhelming tiredness and lower activity level in their daily life routines. First positive effects in CFR therapy were found by adults, but this specific scientific field is very young and therefore mostly unexplored. 4 databases for medical and therapeutic journals were systematically searched for RCTs, CCTs and CTs. Systematic reviews were analyzed as well. All studies were carried out in pediatric oncology and deal with exercise therapy. The enclosed studies were valued by PEDro-Scale. Only a handful papers about a potential reduction of CRF in pediatrics could be found, one RCT, 2 CCTs and one CT. No additional results could be found. To summarize the 4 papers, it can be stated that the duration of intervention depends between 2 days and 12 weeks. Also there are differences between the option inpatient and outpatient programs, as well as with or without supervising. The exercise therapy mostly consists of strength and endurance training in combination with warm-up and cool-down programs. This review underlines the importance of developing new assessments. Especially bigger groups of participants should be analyzed with the scope on individualized, supervised program. So far, CRF is underestimated in pediatric oncology and it is very crucial to identify the symptoms. This could lead to an improvement in quality of life. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Classification of Cancer-related Death Certificates using Machine Learning

    Directory of Open Access Journals (Sweden)

    Luke Butt

    2013-05-01

    Full Text Available BackgroundCancer monitoring and prevention relies on the critical aspect of timely notification of cancer cases. However, the abstraction and classification of cancer from the free-text of pathology reports and other relevant documents, such as death certificates, exist as complex and time-consuming activities.AimsIn this paper, approaches for the automatic detection of notifiable cancer cases as the cause of death from free-text death certificates supplied to Cancer Registries are investigated.Method A number of machine learning classifiers were studied. Features were extracted using natural language techniques and the Medtex toolkit. The numerous features encompassed stemmed words, bi-grams, and concepts from the SNOMED CT medical terminology. The baseline consisted of a keyword spotter using keywords extracted from the long description of ICD-10 cancer related codes.ResultsDeath certificates with notifiable cancer listed as the cause of death can be effectively identified with the methods studied in this paper. A Support Vector Machine (SVM classifier achieved best performance with an overall F-measure of 0.9866 when evaluated on a set of 5,000 free-text death certificates using the token stem feature set. The SNOMED CT concept plus token stem feature set reached the lowest variance (0.0032 and false negative rate (0.0297 while achieving an F-measure of 0.9864. The SVM classifier accounts for the first 18 of the top 40 evaluated runs, and entails the most robust classifier with a variance of 0.001141, half the variance of the other classifiers.ConclusionThe selection of features significantly produced the most influences on the performance of the classifiers, although the type of classifier employed also affects performance. In contrast, the feature weighting schema created a negligible effect on performance. Specifically, it is found that stemmed tokens with or without SNOMED CT concepts create the most effective feature when combined with

  19. A coach in your pocket: on chronic cancer-related fatigue and physical behavior

    NARCIS (Netherlands)

    Wolvers, Marije D.J.

    2017-01-01

    Fatigue is a common and distressing long-term consequence of cancer. Chronic cancer-related fatigue affects work ability, hampers in maintaining social relations, and impacts patients’ well-being. Most treatments for chronic cancer-related fatigue focus to some extend on changing physical behavior,

  20. Cancer-Related Post-traumatic Stress (PDQ®)—Patient Version

    Science.gov (United States)

    Cancer-related post-traumatic stress can occur any time from diagnosis to after treatment ends. Shock, fear, helplessness, or horror can be felt by cancer patients and lead to cancer-related post-traumatic stress. Learn about the causes and ways doctors can help manage these symptoms of distress in this expert-reviewed summary.

  1. Impact of systemic inflammation on the relationship between insulin resistance and all-cause and cancer-related mortality.

    Science.gov (United States)

    Lee, Da Young; Rhee, Eun-Jung; Chang, Yoosoo; Sohn, Chong Il; Shin, Ho-Cheol; Ryu, Seungho; Lee, Won-Young

    2017-11-27

    Insulin resistance and inflammation play an important role in a variety of chronic diseases. We investigated the influence of systemic inflammation on the relationship between insulin resistance and mortality risk in apparently healthy adults. This study examined the mortality outcomes for 165,849 Koreans enrolled in a health-screening program. The subjects were divided into four groups according to their homeostatic model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) levels: group 0, HOMA-IR HOMA-IR ≥75% and hs-CRP HOMA-IR HOMA-IR ≥75% and hs-CRP ≥2.0mg/L. The Cox proportional hazard models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease, and cancer-related mortality. During the follow-up period of 1,417,325.6 person-years, a total of 1316 deaths (182 from cardiovascular disease) occurred. The multivariate-adjusted HRs for all-cause mortality were significantly higher in groups 2 (HR 1.40; 95% CI: 1.19-1.64) and group 3 (HR 1.68; 95% CI: 1.34-2.10) than that in group 0. For cardiovascular mortality, the sex-adjusted hazards were also significantly higher in groups 2 and 3 than that in group 0; however, this increased risk disappeared during multivariate analysis. Groups 2 and 3 had significantly higher risk for cancer-related mortality than group 0, with multivariate-adjusted hazard ratios of 1.48 (95% CI: 1.18-1.86) and 1.84 (95% CI: 1.35-2.51), respectively. Systemic inflammation can be used to stratify the subjects according to the all-cause and cancer-related mortality risks, irrespective of the insulin-resistance status. And this tendency is most pronounced in cancer-related mortality. Copyright © 2017. Published by Elsevier Inc.

  2. Efficacy and Safety of Two Methadone Titration Methods for the Treatment of Cancer-Related Pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain).

    Science.gov (United States)

    Poulain, Philippe; Berleur, Marie-Pierre; Lefki, Shimsi; Lefebvre, Danièle; Chvetzoff, Gisèle; Serra, Eric; Tremellat, Fibra; Derniaux, Alain; Filbet, Marilène

    2016-11-01

    In the European Association for Palliative Care recommendations for cancer pain management, there was no consensus regarding the indications, titration, or monitoring of methadone. This national, randomized, multicenter trial aimed to compare two methadone titration methods (stop-and-go vs. progressive) in patients with cancer-related pain who were inadequately relieved by or intolerant to Level 3 opioids. The primary end point was the rate of success/failure at Day 4, defined as pain relief (reduction of at least two points on the visual scale and a pain score methods were considered equally easy to perform by nearly 60% of the clinicians. Methadone is an effective and sustainable second-line alternative opioid for the treatment of cancer-related pain. The methods of titration are comparable in terms of efficacy, safety, and ease of use. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  3. Relationship between cancer-related fatigue and physical activity in inpatient cancer rehabilitation.

    Science.gov (United States)

    Kummer, Franziska; Catuogno, Silvio; Perseus, Josef M; Bloch, Wilhelm; Baumann, Freerk T

    2013-08-01

    Fatigue is a serious problem for the majority of patients with cancer. In this context, several studies have shown benefits of physical activity during and following treatment. However, uncertainties remain regarding the optimal type and duration of physical activity. Therefore, this study examined the relationship between cancer-related fatigue and physical activity in the course of inpatient rehabilitation. Fatigue (Multidimensional Fatigue Inventory) and physical activity (Freiburg Questionnaire of Physical Activity) were assessed in a consecutive series of 35 patients with cancer attending oncological inpatient rehabilitation during a six-month study period. The three-week rehabilitation program included daily exercise therapy consisting of aerobic endurance training, moderate resistance training, coordination exercises, relaxation training and individual physiotherapy. At discharge, a significant improvement in each dimension of cancer-related fatigue (p=0.001-0.003) and a significant increase of physical activity levels (p=0.001) were observed. A small, but significant negative correlation was found between cancer-related fatigue and the level of physical activity (R=-0.438, p=0.004). The largest effects were associated with a weekly energy expenditure of 3000 kcal through physical activity. The results support a non-linear dose-response relationship between cancer-related fatigue and physical activity. Since this is the first study providing specific exercise recommendations for an effective treatment of cancer-related fatigue in the context of inpatient rehabilitation, further research is required to validate the observed trends.

  4. Chinese herbal medicine for cancer-related fatigue: a systematic review of randomized clinical trials.

    Science.gov (United States)

    Su, Chun-Xiang; Wang, Li-Qiong; Grant, Suzanne J; Liu, Jian-Ping

    2014-06-01

    To assess the effectiveness and safety of Chinese herbal medicine for the treatment of cancer-related fatigue. We systematically searched seven electronic databases and two trial registries for randomized clinical trials of Chinese herbal medicine for cancer-related fatigue. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data were synthesized using RevMan 5.2 software. A total of 10 trials involving 751 participants with cancer-related fatigue were identified and the methodological quality of the included trials was generally poor. Chinese herbal medicine used alone or in combination with chemotherapy or supportive care showed significant relief in cancer-related fatigue compared to placebo, chemotherapy or supportive care based on single trials. Chinese herbal medicine plus chemotherapy or supportive care was superior to chemotherapy or supportive care in improving quality of life. Data from one trial demonstrated Chinese herbal medicine exerted a greater beneficial effect on relieving anxiety but no difference in alleviating depression. Seven trials reported adverse events and no severe adverse effects were found in Chinese herbal medicine groups. The findings from limited number of trials suggest that Chinese herbal medicine seems to be effective and safe in the treatment of cancer-related fatigue. However, the current evidence is insufficient to draw a confirmative conclusion due to the poor methodological quality of included trials. Thus, conducting rigorously designed trials on potential Chinese herbal medicine is warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Human cancer protein-protein interaction network: a structural perspective.

    Directory of Open Access Journals (Sweden)

    Gozde Kar

    2009-12-01

    Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

  6. Resilience and positive affect contribute to lower cancer-related fatigue among Chinese patients with gastric cancer.

    Science.gov (United States)

    Zou, Guiyuan; Li, Ye; Xu, Ruicai; Li, Ping

    2018-04-01

    To investigate the prevalence of cancer-related fatigue and explore the relationship between resilience, positive affect, and fatigue among Chinese patients with gastric cancer. Cancer-related fatigue is the most distressing symptom reported frequently by cancer patients during both treatment and survival phases. Resilience and positive affect as vital protective factors against cancer-related fatigue have been examined, but the underlying psychological mechanisms are not well understood. A cross-sectional study. Two hundred and three gastric cancer patients were enrolled from three hospitals in China. The Cancer Fatigue Scale, the positive affect subscale of the Positive and Negative Affect Schedule and the Connor-Davidson Resilience Scale (CD-RISC10) were administered. Hierarchical linear regression modelling was conducted to examine the association between resilience and cancer-related fatigue, and the mediating effect of positive affect. The incidence of clinically relevant fatigue among patients with gastric cancer was 91.6%. Regression analysis showed that resilience was negatively associated with cancer-related fatigue, explaining 15.4% of variance in cancer-related fatigue. Mediation analysis showed that high resilience was associated with increased positive affect, which was associated with decreased cancer-related fatigue. Cancer-related fatigue is prevalent among patients with gastric cancer. Positive affect may mediate the relationship between resilience and cancer-related fatigue. Interventions that attend to resilience training and promotion of positive affect may be the focus for future clinical and research endeavours. © 2017 John Wiley & Sons Ltd.

  7. Death Anxiety and Cancer-Related Stigma: A Terror Management Analysis

    Science.gov (United States)

    Mosher, Catherine E.; Danoff-Burg, Sharon

    2007-01-01

    In a study designed to examine correlates of cancer-related stigma, 405 college students were assigned randomly to listen to an audiotaped interview in which the target's cancer type and smoking status were manipulated. In the lung cancer conditions, target gender also was manipulated. Social distance and emotional responses differed according to…

  8. Higher vascular endothelial growth factor-C concentration in plasma is associated with increased forearm capillary filtration capacity in breast cancer-related lymphedema

    DEFF Research Database (Denmark)

    Jensen, Mads Radmer; Simonsen, Lene; Karlsmark, Tonny

    2015-01-01

    shown that the forearm capillary filtration coefficient (CFC) is increased bilaterally in BCRL. In this study, we aimed to elucidate if increased CFC is associated with low-grade inflammation and/or vascular endothelial growth factor-c (VEGF-C) signaling. Fourteen patients with unilateral BCRL and nine......Breast cancer-related lymphedema (BCRL) is a frequent, chronic and debilitating swelling that mainly affects the ipsilateral arm and develops as a complication to breast cancer treatment. The pathophysiology is elusive opposing development of means for prediction and treatment. We have earlier...... increased forearm CFC in BCRL subjects. Interstitially increased MCP-1 levels may augment local microvascular protein permeability in BCRL....

  9. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

    International Nuclear Information System (INIS)

    Wu, Mingsong; Tu, Tao; Huang, Yunchao; Cao, Yi

    2013-01-01

    two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer

  10. Intolerance of uncertainty, cognitive complaints, and cancer-related distress in prostate cancer survivors.

    Science.gov (United States)

    Eisenberg, Stacy A; Kurita, Keiko; Taylor-Ford, Megan; Agus, David B; Gross, Mitchell E; Meyerowitz, Beth E

    2015-02-01

    Prostate cancer survivors have reported cognitive complaints following treatment, and these difficulties may be associated with survivors' ongoing cancer-related distress. Intolerance of uncertainty may exacerbate this hypothesized relationship by predisposing individuals to approach uncertain situations such as cancer survivorship in an inflexible and negative manner. We investigated whether greater cognitive complaints and higher intolerance of uncertainty would interact in their relation to more cancer-related distress symptoms. This cross-sectional, questionnaire-based study included 67 prostate cancer survivors who were 3 to 5 years post treatment. Hierarchical multiple regression analyses tested the extent to which intolerance of uncertainty, cognitive complaints, and their interaction were associated with cancer-related distress (measured with the Impact of Event Scale-Revised; IES-R) after adjusting for age, education, physical symptoms, and fear of cancer recurrence. Intolerance of uncertainty was positively associated with the IES-R avoidance and hyperarousal subscales. More cognitive complaints were associated with higher scores on the IES-R hyperarousal subscale. The interaction of intolerance of uncertainty and cognitive complaints was significantly associated with IES-R intrusion, such that greater cognitive complaints were associated with greater intrusive thoughts in survivors high in intolerance of uncertainty but not those low in it. Prostate cancer survivors who report cognitive difficulties or who find uncertainty uncomfortable and unacceptable may be at greater risk for cancer-related distress, even 3 to 5 years after completing treatment. It may be beneficial to address both cognitive complaints and intolerance of uncertainty in psychosocial interventions. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Upper extremity function and quality of life in patients with breast cancer related lymphedema.

    Science.gov (United States)

    Bojinović-Rodić, Dragana; Popović-Petrović, Svetlana; Tomić, Sanja; Markez, Stanislava; Živanić, Dobrinka

    2016-09-01

    Upper limb lymphedema is one of the most frequent chronic complications after breast cancer treatment with a significant impact on the upper extremity function and quality of life (QoL). The aim of this study was to estimate health-related quality of life (HRQoL) in patients with breast-cancer-related lymphedema and its correlation with upper limb function and the size of edema. The cross-sectional study included 54 breast-cancer-related lymphedema patients. The quality of life was evaluated by the Short Form 36-Item Health Survey (SF-36). Upper limb function was assessed by the Quick Disability of the Arm, Shoulder and Hand questionnaire (Quick DASH). The size of lymphedema was determined by the arm circumference. The higher HRQoL score was assessed for mental health (47.0 ± 12.2) than for physical one (42.2 ± 7.5). The highest values of SF-36 were found in the domains of Mental Health (67.7 ± 22.9) and Social Function (70.1 ± 23.1). The lowest scores were registered in the domains of Role Physical (46.9 ± 39.1) and General Health (49.3 ± 20.1). Upper extremity function statistically significantly correlated with the domains Role Physical, Bodily Pain and Physical Composite Summary and also, with the domain Role Emotional (p 0.05). Physical disability in patients with breast cancer-related lymphedema influences quality of life more than mental health. Upper limb function has a significant impact on quality of life, not only on the physical, but also on the mental component. The presence of breast-cancer-related lymphedema certainly affects upper limb function and quality of life, but in this study no significant correlation between the size of edema and quality of life was found.

  12. Upper extremity function and quality of life in patients with breast cancer related lymphedema

    Directory of Open Access Journals (Sweden)

    Bojinović-Rodić Dragana

    2016-01-01

    Full Text Available Background/Aim. Upper limb lymphedema is one of the most frequent chronic complications after breast cancer treatment with a significant impact on the upper extremity function and quality of life (QoL. The aim of this study was to estimate health-related quality of life (HRQoL in patients with breast-cancer-related lymphedema and its correlation with upper limb function and the size of edema. Methods. The cross-sectional study included 54 breast-cancer-related lymphedema patients. The quality of life was evaluated by the Short Form 36-Item Health Survey (SF-36. Upper limb function was assessed by the Quick Disability of the Arm, Shoulder and Hand questionnaire (Quick DASH. The size of lymphedema was determined by the arm circumference. Results. The higher HRQoL score was assessed for mental health (47.0 ± 12.2 than for physical one (42.2 ± 7.5. The highest values of SF-36 were found in the domains of Mental Health (67.7 ± 22.9 and Social Function (70.1 ± 23.1. The lowest scores were registered in the domains of Role Physical (46.9 ± 39.1 and General Health (49.3 ± 20.1. Upper extremity function statistically significantly correlated with the domains Role Physical, Bodily Pain and Physical Composite Summary and also, with the domain Role Emotional (p 0.05. Conclusions. Physical disability in patients with breast cancer-related lymphedema influences quality of life more than mental health. Upper limb function has a significant impact on quality of life, not only on the physical, but also on the mental component. The presence of breast-cancer-related lymphedema certainly affects upper limb function and quality of life, but in this study no significant correlation between the size of edema and quality of life was found.

  13. AWARENESS OF PHYSICAL THERAPY REHABILITATION FOR BREAST CANCER RELATED LYMPHEDEMA AMONG MEDICAL ONCOLOGY TEAM - A SURVEY

    OpenAIRE

    Mullai; Dhinakaran; Chanchal Gautam; Clarence Samuel

    2013-01-01

    Objective:To analyses the awareness of physical therapy rehabilitation for breast cancer related lymphedemaamong medical oncology team member.Method and materials:The data was contents of 12 custom made questionnaires which distributed and collectedfrom 34 medical oncology team members who are working in CMC & H, DMC & H, Chandigarh PGI,Results:Nearly 100 % of clinical oncologist and Radiation oncologist were aware about physical therapyrehabilitation and nearly 80% of Surgeon and Physician w...

  14. Lung cancer patients frequently visit the emergency room for cancer-related and -unrelated issues

    OpenAIRE

    KOTAJIMA, FUTOSHI; KOBAYASHI, KUNIHIKO; SAKAGUCHI, HIROZO; NEMOTO, MANABU

    2014-01-01

    Lung cancer patients visit the emergency room (ER) for cancer-related and -unrelated reasons more often compared to patients with other types of cancer. This results in increased admissions and deaths in the ER. In this study, we retrospectively reviewed the characteristics of lung cancer patients visiting the ER in order to optimize the utilization of emergency medical services and improve the patients’ quality of life. Lung cancer patients visiting the ER of a single institution over a 2-ye...

  15. Systematic review and meta-analysis of acupuncture to reduce cancer-related pain.

    Science.gov (United States)

    Chiu, H Y; Hsieh, Y J; Tsai, P S

    2017-03-01

    We conducted a systematic review and meta-analysis to evaluate the effects of acupuncture on malignancy-related, chemotherapy (CT)- or radiation therapy (RT)-induced, surgery-induced, and hormone therapy (HT)-induced pain. Randomised controlled trials (RCTs) examining the effects of acupuncture on cancer-related pain were reached from the EMBASE, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, Airiti library, Taiwan Electrical Periodical Service, Wanfang Data (a Chinese database) and China Knowledge Resource Integrated Database from inception through June 2014. Heterogeneity, moderator analysis, publication bias and risk of bias associated with the included studies were examined. A total of 29 RCTs yielding 36 effect sizes were included. The overall effect of acupuncture on cancer-related pain was -0.45 [95% confidence interval (CI) = -0.63 to -0.26]. The subanalysis indicated that acupuncture relieved malignancy-related and surgery-induced pain [effect size (g) = -0.71, and -0.40; 95% CI = -0.94 to -0.48, and -0.69 to -0.10] but not CT- or RT-induced and HT-induced pain (g = -0.05, and -0.64, 95% CI = -0.33 to 0.24, and -1.55 to 0.27). Acupuncture is effective in relieving cancer-related pain, particularly malignancy-related and surgery-induced pain. Our findings suggest that acupuncture can be adopted as part of a multimodal approach for reducing cancer-related pain. © 2016 John Wiley & Sons Ltd.

  16. Cancer-Related Stress and Complementary and Alternative Medicine: A Review

    Directory of Open Access Journals (Sweden)

    Kavita D. Chandwani

    2012-01-01

    Full Text Available A cancer diagnosis elicits strong psychophysiological reactions that characterize stress. Stress is experienced by all patients but is usually not discussed during patient-healthcare professional interaction; thus underdiagnosed, very few are referred to support services. The prevalence of CAM use in patients with history of cancer is growing. The purpose of the paper is to review the aspects of cancer-related stress and interventions of commonly used complementary and alternative techniques/products for amelioration of cancer-related stress. Feasibility of intervention of several CAM techniques and products commonly used by cancer patients and survivors has been established in some cancer populations. Efficacy of some CAM techniques and products in reducing stress has been documented as well as stress-related symptoms in patients with cancer such as mindfulness-based stress reduction, yoga, Tai Chi Chuan, acupuncture, energy-based techniques, and physical activity. Much of the research limitations include small study samples and variety of intervention length and content. Efficacy and safety of many CAM techniques and some herbs and vitamin B and D supplements need to be confirmed in further studies using scientific methodology. Several complementary and alternative medicine therapies could be integrated into standard cancer care to ameliorate cancer-related stress.

  17. Cancer Communication on Social Media: Examining How Cancer Caregivers Use Facebook for Cancer-Related Communication.

    Science.gov (United States)

    Gage-Bouchard, Elizabeth A; LaValley, Susan; Mollica, Michelle; Beaupin, Lynda Kwon

    Americans are increasingly using social media (such as Facebook, YouTube, and Twitter) for health-related communication. Much of the previous research on social media and health communication has focused on Facebook groups related to a specific disease or Facebook pages related to an advocacy organization. Less is known about how people communicate about cancer on personal Facebook pages. In this study, we expand upon previous research by examining how cancer caregivers use personal Facebook pages for cancer-related communication. We examined themes in cancer-related exchanges through a content analysis of 12 months of data from 18 publically available Facebook pages hosted by parents of children with acute lymphoblastic leukemia (15 852 total posts). Six themes emerged: (1) documenting the cancer journey, (2) sharing emotional strain associated with caregiving, (3) promoting awareness and advocacy about pediatric cancer, (4) fundraising, (5) mobilizing support, and (6) expressing gratitude for support. Building upon previous research documenting the increasing use of social media for health-related communication and support, our findings show that personal Facebook pages offer a platform for cancer caregivers to share their cancer-related experiences, promote advocacy and awareness, and mobilize social support. Providers must recognize the importance of social media as a vehicle for support and communication for families of children with cancer. Nurses should educate parents on how to appraise information obtained through Facebook using evidence-based guidelines. Providers can encourage caregivers to use Facebook as a tool for communication, information, and support.

  18. Effects of scheduled exercise on cancer-related fatigue in women with early breast cancer.

    Science.gov (United States)

    Husebø, Anne Marie Lunde; Dyrstad, Sindre Mikal; Mjaaland, Ingvil; Søreide, Jon Arne; Bru, Edvin

    2014-01-01

    While physical activity during cancer treatment is found beneficial for breast cancer patients, evidence indicates ambiguous findings concerning effects of scheduled exercise programs on treatment-related symptoms. This study investigated effects of a scheduled home-based exercise intervention in breast cancer patients during adjuvant chemotherapy, on cancer-related fatigue, physical fitness, and activity level. Sixty-seven women were randomized to an exercise intervention group (n = 33, performed strength training 3x/week and 30 minutes brisk walking/day) and a control group (n = 34, performed their regular physical activity level). Data collection was performed at baseline, at completion of chemotherapy (Post₁), and 6-month postchemotherapy (Post₂). Exercise levels were slightly higher in the scheduled exercise group than in the control group. In both groups, cancer-related fatigue increased at Post₁ but returned to baseline at Post₂. Physical fitness and activity levels decreased at Post₁ but were significantly improved at Post₂. Significant differences between intervention and control groups were not found. The findings suggest that generally recommended physical activity levels are enough to relief cancer-related fatigue and restore physical capacity in breast cancer patients during adjuvant chemotherapy, although one cannot rule out that results reflect diminishing treatment side effects over time.

  19. Effects of Scheduled Exercise on Cancer-Related Fatigue in Women with Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Anne Marie Lunde Husebø

    2014-01-01

    Full Text Available While physical activity during cancer treatment is found beneficial for breast cancer patients, evidence indicates ambiguous findings concerning effects of scheduled exercise programs on treatment-related symptoms. This study investigated effects of a scheduled home-based exercise intervention in breast cancer patients during adjuvant chemotherapy, on cancer-related fatigue, physical fitness, and activity level. Sixty-seven women were randomized to an exercise intervention group (n=33, performed strength training 3x/week and 30 minutes brisk walking/day and a control group (n=34, performed their regular physical activity level. Data collection was performed at baseline, at completion of chemotherapy (Post1, and 6-month postchemotherapy (Post2. Exercise levels were slightly higher in the scheduled exercise group than in the control group. In both groups, cancer-related fatigue increased at Post1 but returned to baseline at Post2. Physical fitness and activity levels decreased at Post1 but were significantly improved at Post2. Significant differences between intervention and control groups were not found. The findings suggest that generally recommended physical activity levels are enough to relief cancer-related fatigue and restore physical capacity in breast cancer patients during adjuvant chemotherapy, although one cannot rule out that results reflect diminishing treatment side effects over time.

  20. Exercise for the management of cancer-related fatigue in adults.

    Science.gov (United States)

    Cramp, Fiona; Byron-Daniel, James

    2012-11-14

    Cancer-related fatigue is recognised as an important symptom associated with cancer and its treatment. A number of studies have investigated the effects of physical activity in reducing cancer-related fatigue. This is an updated version of the original Cochrane review published in The Cochrane Library (2008, Issue 1). The original review identified some benefits of physical activity on fatigue in cancer both during and after adjuvant treatment. We identified a number of limitations in the evidence, providing clear justification for an updated review. To evaluate the effect of exercise on cancer-related fatigue both during and after cancer treatment. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL (1982 to March 2011), British Nursing Index (January 1984 to March 2011), AMED (1985 to March 2011), SIGLE (1980 to March 2011) and Dissertation Abstracts International (1861 to March 2011) using key words. We also searched reference lists off all studies identified for inclusion and relevant reviews. In addition, we handsearched relevant journals and contacted experts in the field of cancer-related fatigue. We sought and included randomised controlled trials (RCTs) that investigated the effect of exercise on cancer-related fatigue in adults. Two review authors independently assessed the risk of bias of studies and extracted data based upon predefined criteria. Where data were available we performed meta-analyses for fatigue using a random-effects model. For this update we identified a total of 56 studies (4068 participants) for inclusion (28 from the original search and 28 from the updated search), with the majority carried out in participants with breast cancer (28 studies). A meta-analysis of all fatigue data, incorporating 38 comparisons, provided data for 1461 participants who received an exercise intervention and 1187 control participants. At the end of the

  1. Aberrant DNA methylation of cancer-related genes in giant breast fibroadenoma: a case report

    Directory of Open Access Journals (Sweden)

    Orozco Javier I

    2011-10-01

    Full Text Available Abstract Introduction Giant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands in promoter regions is known to be involved in the silencing of genes (for example, tumor-suppressor genes and appears to be an early event in the etiology of breast carcinogenesis. Only hypermethylation of p16INK4a has been reported in non-giant breast fibroadenoma. In this particular case, there are no previously published data on epigenetic alterations in giant fibroadenomas. Our previous results, based on the analysis of 49 cancer-related CpG islands have confirmed that the aberrant methylation is specific to malignant breast tumors and that it is completely absent in normal breast tissue and breast fibroadenomas. Case presentation A 13-year-old Hispanic girl was referred after she had noted a progressive development of a mass in her left breast. On physical examination, a 10 × 10 cm lump was detected and axillary lymph nodes were not enlarged. After surgical removal the lump was diagnosed as a giant fibroadenoma. Because of the high growth rate of this benign tumor, we decided to analyze the methylation status of 49 CpG islands related to cell growth control. We have identified the methylation of five cancer-related CpG islands in the giant fibroadenoma tissue: ESR1, MGMT, WT-1, BRCA2 and CD44. Conclusion In this case report we show for the first time the methylation analysis of a giant fibroadenoma. The detection of methylation of these five cancer-related regions indicates substantial epigenomic differences with non-giant fibroadenomas. Epigenetic alterations could explain the higher growth rate of this tumor. Our data contribute to the growing knowledge of aberrant methylation in breast diseases. In this particular case, there exist no previous data regarding the role of methylation in giant fibroadenomas, considered by definition as a benign breast lesion.

  2. Comparison of Genetic Variants in Cancer-Related Genes between Chinese Hui and Han Populations.

    Science.gov (United States)

    Tian, Chaoyong; Chen, Zhiqiang; Ma, Xixian; Yang, Ming; Wang, Zhizhong; Dong, Ying; Yang, Ting; Yang, Wenjun

    2015-01-01

    The Chinese Hui population, as the second largest minority ethnic group in China, may have a different genetic background from Han people because of its unique demographic history. In this study, we aimed to identify genetic differences between Han and Hui Chinese from the Ningxia region of China by comparing eighteen single nucleotide polymorphisms in cancer-related genes. DNA samples were collected from 99 Hui and 145 Han people from the Ningxia Hui Autonomous Region in China, and SNPs were detected using an improved multiplex ligase detection reaction method. Genotyping data from six 1000 Genomes Project population samples (99 Utah residents with northern and western European ancestry (CEU), 107 Toscani in Italy (TSI), 108 Yoruba in Ibadan (YRI), 61 of African ancestry in the southwestern US (ASW), 103 Han Chinese in Beijing (CHB), and 104 Japanese in Tokyo (JPT)) were also included in this study. Differences in the distribution of alleles among the populations were assessed using χ2 tests, and FST was used to measure the degree of population differentiation. We found that the genetic diversity of many SNPs in cancer-related genes in the Hui Chinese in Ningxia was different from that in the Han Chinese in Ningxia. For example, the allele frequencies of four SNPs (rs13361707, rs2274223, rs465498, and rs753955) showed different genetic distributions (pHui. Five SNPs (rs730506, rs13361707, rs2274223, rs465498 and rs753955) had different FST values (FST>0.000) between the Hui and Han populations. These results suggest that some SNPs associated with cancer-related genes vary among different Chinese ethnic groups. We suggest that population differences should be carefully considered in evaluating cancer risk and prognosis as well as the efficacy of cancer therapy.

  3. Methodology for the Model-based Small Area Estimates of Cancer-Related Knowledge - Small Area Estimates

    Science.gov (United States)

    The HINTS is designed to produce reliable estimates at the national and regional levels. GIS maps using HINTS data have been used to provide a visual representation of possible geographic relationships in HINTS cancer-related variables.

  4. Initial Study on Cancer-Related Cognitive Dysfunction With the Implementation of QEEG

    Directory of Open Access Journals (Sweden)

    Żołubak Magda

    2017-09-01

    Full Text Available Chemotherapy is one of the most common treatments used in cancer therapy despite its serious side effects, which remain a huge concern. To the most common side effects (apart from weight and hair loss include memory and concentration problems as well as changes in taste. This paper presents a very preliminary study (with only one elderly female subject participating focusing on cognitive dysfunction after chemotherapy in breast cancer. This phenomenon, called Cancer-Related Cognitive Dysfunction (CRCD, is a frequent occurrence. The obtained results prove the impact of chemotherapy on the participant’s ability to concentrate. The QEEG method and digital data analysis were used as the measurement methods.

  5. Screening for cancer-related distress: Summary of evidence from tools to programmes

    DEFF Research Database (Denmark)

    Bidstrup, P. E.; Johansen, C.; Mitchell, A. J.

    2011-01-01

    Introduction. A number of studies have addressed the development and testing of tools for measuring cancer-related distress. Except for studies of diagnostic validity, knowledge on the effect of screening for psychological distress on psychological well-being is limited. We aimed to describe...... and critically discuss the findings of randomized trials of the effect of screening and to identify components necessary for future studies of the effectiveness of screening programmes. Methods. A search was made of the Embase/Medline and Web of Knowledge abstract databases from inception to September 2010. Our...

  6. Treatment of breast cancer-related lymphedema with adipose-derived regenerative cells and fat grafts

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2017-01-01

    Breast cancer-related lymphedema (BCRL) is a debilitating late complication with a lack of treatment opportunities. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with freshly isolated adipose-derived...... regenerative cells (ADRC) for treating lymphedema with 6 months follow-up. Ten BCRL patients were included. ADRC was injected directly into the axillary region, which was combined with a scar-releasing fat graft procedure. Primary endpoints were change in arm volume. Secondary endpoints were change in patient...

  7. The Cancer Loneliness Scale and Cancer-related Negative Social Expectations Scale: development and validation.

    Science.gov (United States)

    Adams, Rebecca N; Mosher, Catherine E; Rand, Kevin L; Hirsh, Adam T; Monahan, Patrick O; Abonour, Rafat; Kroenke, Kurt

    2017-07-01

    Loneliness is a known risk factor for poor mental and physical health outcomes and quality of life in the general population, and preliminary research suggests that loneliness is linked to poorer health outcomes in cancer patients as well. Various aspects of the cancer experience contribute to patients feeling alone and misunderstood. Furthermore, loneliness theory suggests that negative social expectations, which may specifically relate to the cancer experience, precipitate and sustain loneliness. Cancer-specific tools are needed to assess key constructs of this theory. In the current study, we developed and tested measures of (1) loneliness attributed to cancer (i.e., cancer-related loneliness) and (2) negative social expectations related to cancer. First, we developed the items for the measures based on theory, prior research, and expert feedback. Next, we assessed the measures' psychometric properties (i.e., internal consistency and construct validity) in a diverse sample of cancer patients. The final products included a 7-item unidimensional Cancer Loneliness Scale and a 5-item unidimensional Cancer-related Negative Social Expectations Scale. Evidence of excellent reliability and validity was found for both measures. The resulting measures have both clinical and research utility.

  8. Influence of Exergaming on the Perception of Cancer-Related Fatigue.

    Science.gov (United States)

    da Silva Alves, Ricardo; Iunes, Denise Hollanda; Pereira, Isabela Carvalho; Borges, Juliana Bassalobre Carvalho; Nogueira, Denismar Alves; Silva, Andreia Maria; Lobato, Daniel Ferreira Moreira; Carvalho, Leonardo Cesar

    2017-04-01

    Exercise is recommended for cancer patients to reduce fatigue and improve quality of life. This study's aim is to evaluate the influence of an exergaming protocol on cancer-related fatigue, muscle fatigue, and muscle strength in cancer patients. We conducted a quasi-experimental control study using exergaming in all groups through an Xbox360 Kinect™ console, two to three times per week, for 20 sessions. Three groups were created: cancer patients in chemotherapy and/or radiotherapy group (CRG; n:15), cancer patients after chemotherapy and/or radiotherapy (CAG; n:15), and a control group (CG; n:15). They were assessed for cancer-related fatigue using the fatigue subscale of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. To assess dorsiflexor and plantar flexor muscle functioning, we used median frequency (MDF) of the surface electromyography and muscle strength using a dynamometer. The assessments were performed preintervention (EV0), after 10 sessions (EV1), and after 20 sessions (EV2). With an exergaming protocol, CRG and CAG showed a reduction in related fatigue compared with CG (P fatigue, including muscle fatigue, and increasing muscle strength in patients' legs.

  9. Association between cancer literacy and cancer-related behaviour: evidence from Ticino, Switzerland

    Directory of Open Access Journals (Sweden)

    Nicola Diviani

    2014-07-01

    Full Text Available Background. This paper details the role of different dimensions of health literacy in the relationship between health literacy and cancer-related health behaviours. In particular, Cancer Literacy is studied as an exemplar of a dimension of health literacy beyond basic reading and writing skills. The link between functional health literacy, Cancer Literacy and cancer-related health behaviours is investigated in a sample of Ticino (Switzerland residents (n=639. Design and methods. Detailed data is collected about respondents’ functional health literacy, Cancer Literacy, cancer information seeking behaviour, engagement in cancer preventive behaviours, participation to cancer screenings, and intention to adhere to current screening recommendations. Results. Results confirm the added value of Cancer Literacy – compared to functional health literacy – in explaining people’s cancer information seeking behaviour, their participation to several cancer screenings and their screening intention, underscoring the need to take into account dimensions of health literacy beyond basic functional skills. Conclusions. From a public health perspective, findings provide further evidence on the importance of adapting informational and educational communication intervention designed to improve cancer prevention and screening to different audiences.

  10. [Supervised physical activity interventions in the management of cancer-related fatigue: a systematic review].

    Science.gov (United States)

    Meneses-Echavez, Jose F; González-Jiménez, Emilio; Correa, Jorge E; Ramírez-Vélez, Robinson

    2014-09-01

    Cancer-related fatigue is the most common and distressing symptom among cancer survivors; physical activity has been proposed as a safe and effective intervention to control it. This study aimed to determine the effectiveness of supervised physical activity interventions for the management of cancer-related fatigue (CRF). Systematic review of randomized controlled trials. Adults (>20 years old) diagnosed with any type of cancer regardless of treatment or diagnosis stage. Physical activity interventions (aerobic and resistance training) supervised by health professionals. CRF was the primary outcome measure, whilst secondary outcomes included depression, the comparison between supervised and non-supervised interventions, physical and functional wellbeing. Risk of bias and methodological quality were evaluated using the PEDro scale. Fourteen studies (n=14) were included (n=1638) with low risk of bias (PEDro mean score=6,5 ± 1). Supervised physical activity significantly improved CRF; similar results were found for resistance training. Further, supervised physical activity was more effective than conventional care for improving CRF among breast cancer. Supervised physical activity interventions provide an overall reduction on CRF. These findings suggest that guidelines of aerobic and resistance training should be included in oncologic rehabilitation programs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  11. HIGH INTENSITY PHYSICAL TRAINING EXERCISE PROGRAM IN IMPROVING BREAST CANCER RELATED FATIGUE

    Directory of Open Access Journals (Sweden)

    Intsar S. Wake

    2016-02-01

    Full Text Available Background: Breast cancer is a prevalent disease that requires intense and prolonged treatments. Because of improved detection and treatment options, the mortality rate from breast cancer has decreased, greatly increasing the number of survivors who are living with the disease and its side effects. Fatigue is one of the most common debilitating symptoms experienced by patients with cancer. It is a persistent feeling of exhaustion and decreased physical and mental capacity unrelieved by rest or sleep. The purpose of current study was to evaluate the effect of high intensity physical training exercise program in improving breast cancer related fatigue. Methods: Forty six patients suffering from breast cancer related fatigue, were randomly divided into two groups of equal number. Exercise group (E; received high intensity physical training program while Control group (C received usual medical care and kept their habitual activity. The intensity of fatigue and quality of life score were measured at the beginning and after eight weeks of treatment. Results: Results of the study showed that there was significant reduction of fatigue after eight weeks in exercise (E group more than control group with the percentage of improvement was 53%, 2% respectively. As regard to QOL measurements, there was significant increase of QOL score after treatment in exercise (E group more than control group with the percentage of improvement was 43%, 3% respectively. Conclusion: High intensity physical exercise program may have beneficial effects in reduction of fatigue intensity and thereby improving quality of life in breast cancer patient.

  12. Laboratory and biometric predictors of cancer-related mortality in an insured population.

    Science.gov (United States)

    Palmier, James; Lanzrath, Brian J

    2012-01-01

    Identification of statistically significant laboratory and biometric predictors of cancer-related mortality among insured individuals. Numerous clinical studies have identified correlations between various laboratory results and physical measurements and cancer risk, often of a uni-variate nature. A study of life insurance claims has permitted a broad multivariate analysis of laboratory and biometric risk factors for cancer mortality in an insured population. Of the applicants with complete laboratory and physical measurement profiles, 1.25 million were available and followed for an average of 4.7 years. Dates of 518 life insurance claims resulting from cancer deaths were recorded, and the resulting data set analyzed by multivariate Cox Proportional Hazards regression to identify statistically significant predictors of cancer-related mortality among insured individuals. Among demographic variables, cancer deaths were found to be strongly associated with age and tobacco use, but not with gender. Among serum and urine analytes, liver function tests (principally GGT and ALP), hypocholesterolemia, proteinurea, and low fructosamine were found to be independently predictive of cancer mortality. Among physical measurement variables, there was a positive relationship between cancer mortality risk and height and relatively weak relationships with pulse and blood pressure. Weight and body mass index (BMI) were not statistically significant covariates. The findings highlight the potential value of laboratory analytes and biometric measurements to cancer risk assessment including low to low-normal values in analytes (particularly cholesterol and fructosamine) whose diagnostic value in clinical practice and underwriting may be advantageous.

  13. Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: A Systematic Review

    Science.gov (United States)

    Pron, Gaylene; Holubowich, Corinne; Kaulback, Kellee

    2016-01-01

    Background Cancers that metastasize to the spine and primary cancers such as multiple myeloma can result in vertebral compression fractures or instability. Conservative strategies, including bed rest, bracing, and analgesic use, can be ineffective, resulting in continued pain and progressive functional disability limiting mobility and self-care. Surgery is not usually an option for cancer patients in advanced disease states because of their poor medical health or functional status and limited life expectancy. The objectives of this review were to evaluate the effectiveness and safety of percutaneous image-guided vertebral augmentation techniques, vertebroplasty and kyphoplasty, for palliation of cancer-related vertebral compression fractures. Methods We performed a systematic literature search for studies on vertebral augmentation of cancer-related vertebral compression fractures published from January 1, 2000, to October 2014; abstracts were screened by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Owing to the heterogeneity of the clinical reports, we performed a narrative synthesis based on an analytical framework constructed for the type of cancer-related vertebral fractures and the diversity of the vertebral augmentation interventions. Results The evidence review identified 3,391 citations, of which 111 clinical reports (4,235 patients) evaluated the effectiveness of vertebroplasty (78 reports, 2,545 patients) or kyphoplasty (33 reports, 1,690 patients) for patients with mixed primary spinal metastatic cancers, multiple myeloma, or hemangiomas. Overall the mean pain intensity scores often reported within 48 hours of vertebral augmentation (kyphoplasty or vertebroplasty), were significantly reduced. Analgesic use, although variably reported, usually involved parallel decreases, particularly in opioids, and mean pain-related disability scores were also significantly improved. In a randomized controlled

  14. Body image mediates the effect of cancer-related stigmatization on depression

    DEFF Research Database (Denmark)

    Esser, Peter; Mehnert, Anja; Johansen, Christoffer

    2018-01-01

    OBJECTIVE: Because cancer-related stigmatization is prevalent but difficult to change, research on its impact on psychological burden and respective intervening variables is needed. Therefore, we investigated the effect of stigmatization on depressive symptomatology and whether body image mediates...... and the indirect effects exerted via the 2 body image scales rejecting body evaluation and vital body dynamics. RESULTS: Among the 858 cancer patients recruited (breast: n = 297; prostate: n = 268; colorectal: n = 168; lung: n = 125), stigmatization showed total effects on depressive symptomatology across all......, the mediating effect of rejecting body evaluation was significantly larger than the effect of vital body dynamics (dtotal sample = .02, 95%-CI: 0.01-0.04). CONCLUSIONS: Perceived stigmatization is an important and generalizable risk factor for depressive symptomatology among cancer patients. Apart from...

  15. Energy Through Motion: An Activity Intervention for Cancer-Related Fatigue in an Ambulatory Infusion Center
.

    Science.gov (United States)

    Abbott, Linda; Hooke, Mary Catherine

    2017-10-01

    Cancer-related fatigue (CRF) occurs in most people with cancer undergoing chemotherapy. Physical activity (PA) is safe and effective in reducing CRF in people with cancer. 
. This project involved the implementation and evaluation of a three-month PA program to maintain or improve CRF and quality of life.
. Activity trackers and resistance bands were provided to participants. Verbal instruction, printed material, activity videos, and text messages were used in this program. Participants completed a fatigue assessment; self-reported PA measure; and measure of attitudes, beliefs, and knowledge about sustaining regular PA pre- and postimplementation.
. 51 patients enrolled in the study, and 39 completed the program. Participants' fatigue did not worsen significantly during the three months, and self-reported activity levels increased, but not significantly. The activity tracker, text messages, and personal connection with nursing staff were reported to be helpful.

  16. Microfluidics-mediated assembly of functional nanoparticles for cancer-related pharmaceutical applications

    Science.gov (United States)

    Feng, Qiang; Sun, Jiashu; Jiang, Xingyu

    2016-06-01

    The controlled synthesis of functional nanoparticles with tunable structures and properties has been extensively investigated for cancer treatment and diagnosis. Among a variety of methods for fabrication of nanoparticles, microfluidics-based synthesis enables enhanced mixing and precise fluidic modulation inside microchannels, thus allowing for the flow-mediated production of nanoparticles in a controllable manner. This review focuses on recent advances of using microfluidic devices for the synthesis of drug-loaded nanoparticles with specific characteristics (such as size, composite, surface modification, structure and rigidity) for enhanced cancer treatment and diagnosis as well as to investigate the bio-nanoparticle interaction. The discussion on microfluidics-based synthesis may shed light on the rational design of functional nanoparticles for cancer-related pharmaceutical applications.

  17. Use and Taxonomy of Social Media in Cancer-Related Research: A Systematic Review

    Science.gov (United States)

    Klasko, Lynne; Davis, Stacy N.; Gwede, Clement K.; Wells, Kristen J.; Kumar, Ambuj; Lopez, Natalia; Meade, Cathy D.

    2014-01-01

    Little is known about how social media are used in cancer care. We conducted a systematic review of the use and taxonomy of social media in cancer-related studies, in PubMed, Web of Knowledge, CINAHL, and Google Scholar. We located 1350 articles published through October 2013; 69 met study inclusion criteria. Early research (1996–2007) was predominantly descriptive studies of online forums. Later, researchers began analyzing blogs, videos shared on YouTube, and social networking sites. Most studies (n = 62) were descriptive, and only 7 reported intervention studies published since 2010. Future research should include more intervention studies to determine how social media can influence behavior, and more empirical research is needed on how social media may be used to reduce health disparities. PMID:24832403

  18. Men at increased risk of developing breast cancer: language preferences for naming a cancer-related mutation.

    Science.gov (United States)

    Wakefield, Claire E; Juan, Anne S; Kasparian, Nadine A

    2009-06-01

    Patients attending familial cancer clinics may find the term "mutation" offensive and potentially stigmatizing, yet there is little consensus in the literature as to the most appropriate alternative terms to describe a cancer-related mutation to individuals considering genetic testing for cancer risk. This study aimed to describe a cancer-related mutation in a rare group of familial cancer clinic patients: men at increased risk of carrying a breast cancer-related mutation. Twenty-seven men completed a self-report questionnaire that assessed their preferences for language to describe a cancer-related mutation. Overall, men were most likely to spontaneously suggest the term "faulty gene" to describe a cancer-related mutation when asked an open-ended question about their language preferences. When asked to rate the term "faulty gene" in comparison to the terms "altered gene," "mutation," "nonworking gene," "malfunctioning gene," and "gene change," the term "faulty gene" received the highest mean preference rating in this sample of men at increased risk of developing breast cancer. This area of investigation remains controversial and would benefit from more formal and larger-scale investigations of the language preferences of individuals at increased risk of developing cancer.

  19. Cancer-related hair loss: a selective review of the alopecia research literature.

    Science.gov (United States)

    Dua, Priya; Heiland, Mark F; Kracen, Amanda C; Deshields, Teresa L

    2017-04-01

    Alopecia is a common side effect of cancer treatment, affecting approximately 65% of patients. Healthcare providers and allied staff recognize that alopecia is distressing for people with cancer; however, they are often unaware of the extent of distress or the great efforts expended by patients to cope with hair loss. This study reviews the existing literature regarding the psychosocial impact of alopecia on cancer survivors and the coping strategies they use to manage hair loss. We searched for studies examining the psychosocial effects of alopecia on cancer survivors using PubMed and PsycInfo databases and Google Scholar. A total of 36 peer-reviewed articles were deemed relevant to be included in this review. In this review, alopecia was consistently ranked as one of the most distressing side effects of cancer treatment. Survivors report that hair loss disrupts how they experience their bodies, interact with others, and conceptualize their body image beyond treatment. Although upsetting for both genders, the scarce literature that exists suggests that there may be some gender-specific aspects of experiencing cancer-related hair loss. Cancer survivors cope with alopecia in numerous ways and often rely on strategies such as concealment, social support, social avoidance, information seeking, and behavioral rehearsal. Treatment-induced alopecia negatively affects millions of survivors each year in unique and nuanced ways. We hope that survivors' healthcare providers and loved ones may better appreciate the psychosocial challenges they experience related to hair loss, as well as the strategies they use to cope. Further research is much needed to better understand cancer-related alopecia. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Cancer-related identities in people diagnosed during late adolescence and young adulthood.

    Science.gov (United States)

    Cho, Dalnim; Park, Crystal L

    2015-09-01

    Identity labels with which people diagnosed with cancer identify may have important implications for post-cancer adjustment, yet little is known about these identities, and virtually nothing about them in people diagnosed during late adolescence and young adulthood (LAYA). We examined (1) the extent to which LAYA participants endorse different identities, (2) relations between identities and subsequent adjustment (positive/negative impact of cancer, quality of life, health behaviours), and (3) coping as mediating identity-adjustment links. A longitudinal study in which 120 participants at Time 1 (T1) and 84 participants at Time 2 (T2; 1 year later) were assessed. Participants had been diagnosed between ages 15 and 39. Demographics, cancer-related variables, adjustment, and identities (victim/patient/someone who has had cancer/survivor/conqueror/member of the cancer community) were measured. Late adolescence and young adulthoods with cancer identify with a variety of terms. At both time points, someone who has had cancer was the most highly endorsed identity. Survivor and member of the cancer community were also frequently chosen. Generally, T1 survivor, conqueror, and member of the cancer community identities were positively correlated with T2 adjustment, whereas victim and patient identities were negatively correlated with T2 adjustment. Both T1 member of the cancer community identity and T2 emotional expression coping independently and positively predicted T2 positive self-evaluation even when T1 positive self-evaluation was controlled. Forming empowering identities (e.g., survivor) and emphasizing community identity (member of the cancer community) appear helpful to post-cancer adjustment. Future studies need to examine cancer-related identities and mechanisms explaining identity-adjustment links in this understudied group. © 2014 The British Psychological Society.

  1. Multidisciplinary Approaches to the Management of Breast-Cancer-Related Lymphedema

    Directory of Open Access Journals (Sweden)

    Solmaz Fakhari

    2013-07-01

    Full Text Available Breast-cancer-related lymphedema is a significant morbidity mostly observed following primary treatments for breast cancer (surgery, radiation, and chemotherapy (1. Multiple complications might accompany lymphedema including cosmetic deformity, psychological disorders, consistent pain, and consequently decreased quality of life. Treatment  mostly focuses on reducing edema and its subsequent pain; however, no definite treatment has been hitherto introduced (2. Surgical approaches in the management of lymphedema are efficient including physiologic methods (e.g. flap interposition, lymph transfer, and lymphatic bypass and reductive techniques (e.g. liposuction (3. While the former mostly targets at reducing lymphedema through restoring lymphatic drainage, the latter aims at removing fibrofatty tissues which contribute to lymph stasis. Microsurgical variation of lymphatic bypass has gained popularity, in which the accumulated lymph in the lymphedematous limb is redirected. Non-surgical approaches are also practiced in most cases. Comprehensive decongestive therapy, consisting of skin care, exercise, special bandaging and massage, is the most frequently used non-surgical approach efficacy of which could be enhanced in combination with self-management strategies (4. Recently newer techniques have been introduced to tackle lymphedema and its associated pain. Manual lymph drainage, stellate ganglion block, acupuncture, deep oscillation, and pneumatic compression have been efficiently used in several studies. Moreover, significant short-term progress has been reported following other modalities such as low-level laser therapy (5. The complexity of breast-cancer-related lymphedema and its complications necessitates a multidisciplinary approach with the primary goal of easing the burden of the disease on the breast cancer patients. In addition, developing special guidelines encompassing these multidisciplinary approaches and providing educational and

  2. Effects of yoga on cancer-related fatigue and global side-effect burden in older cancer survivors.

    Science.gov (United States)

    Sprod, Lisa K; Fernandez, Isabel D; Janelsins, Michelle C; Peppone, Luke J; Atkins, James N; Giguere, Jeffrey; Block, Robert; Mustian, Karen M

    2015-01-01

    Sixty percent of cancer survivors are 65years of age or older. Cancer and its treatments lead to cancer-related fatigue and many other side effects, in turn, creating substantial global side-effect burden (total burden from all side effects) which, ultimately, compromises functional independence and quality of life. Various modes of exercise, such as yoga, reduce cancer-related fatigue and global side-effect burden in younger cancer survivors, but no studies have specifically examined the effects of yoga on older cancer survivors. The purpose of this study was to assess the effects of a 4-week yoga intervention (Yoga for Cancer Survivors: YOCAS©®) on overall cancer-related fatigue, and due to its multidimensional nature, the subdomains of cancer-related fatigue (general, physical, emotional, and mental) and global side-effect burden in older cancer survivors. We conducted a secondary analysis on data from a multicenter phase III randomized controlled clinical trial with 2 arms (standard care and standard care plus a 4-week YOCAS©® intervention). The sample for this secondary analysis was 97 older cancer survivors (≥60years of age), between 2months and 2years post-treatment, who participated in the original trial. Participants in the YOCAS©® intervention arm reported significantly lower cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden than participants in the standard care arm following the 4-week intervention period (peffective standardized yoga intervention for reducing cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden among older cancer survivors. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Preparedness and Cancer-Related Symptom Management among Cancer Survivors in the First Year Post-Treatment.

    Science.gov (United States)

    Leach, Corinne R; Troeschel, Alyssa N; Wiatrek, Dawn; Stanton, Annette L; Diefenbach, Michael; Stein, Kevin D; Sharpe, Katherine; Portier, Kenneth

    2017-08-01

    Many cancer survivors feel unprepared for the physical and psychosocial challenges that accompany the post-treatment care transition (i.e., re-entry phase), including management of cancer-related symptoms. Few studies have investigated personal and contextual factors associated with the extent of preparedness for re-entry or how they are related to cancer-related symptom management. Data from the American Cancer Society's Cancer Survivor Transition Study examined (1) characteristics of breast, prostate, and colorectal cancer survivors (n = 1188) within the first year of completing treatment who are most and least prepared for re-entry; and (2) how preparedness level and other characteristics are related to cancer-related symptom management. Stanton and colleagues' [1] conceptual model of survivorship guided the selection of interpersonal/environmental, individual, and disease/treatment-related characteristics as potential contributors to levels of preparedness and cancer-related symptom management using regression tree and multivariate linear regression analyses. Survivors, on average, felt moderately prepared for the transition to post-treatment care. Lowest levels of preparedness were found among survivors with relatively high depressive symptoms, low perceived quality of oncology-provided survivorship care, and limited discussion about potential side effects with a health professional. Poorer symptom management was associated with younger age, having more comorbid conditions, and lower preparedness, social support, and spirituality. Survivors who feel unprepared for the transition to post-treatment care report poorer cancer-related symptom management. Identification of factors associated with low perceived preparedness and poor cancer-related symptom management will assist in risk stratification and development of tailored interventions to meet the needs of cancer survivors during re-entry.

  4. Low-intensity pulsed ultrasound affects RUNX2 immunopositive osteogenic cells in delayed clinical fracture healing

    NARCIS (Netherlands)

    Rutten, S.; Nolte, P.A.; Korstjens, C.M.; Klein-Nulend, J.

    2009-01-01

    Introduction: Osteogenic cell proliferation and differentiation play an important role in adequate fracture healing, and is target for osteoinductive therapies in delayed fracture healing. The aim of this study was to investigate whether low-intensity pulsed ultrasound enhances fracture healing at

  5. Streptococcal toxic-shock syndrome due to Streptococcus dysgalactiae subspecies equisimilis in breast cancer-related lymphedema: a case report.

    Science.gov (United States)

    Sumazaki, Makoto; Saito, Fumi; Ogata, Hideaki; Yoshida, Miho; Kubota, Yorichika; Magoshi, Syunsuke; Kaneko, Hironori

    2017-07-14

    Breast cancer-related lymphedema often causes cellulitis and is one of the most common complications after breast cancer surgery. Streptococci are the major pathogens underlying such cellulitis. Among the streptococci, the importance of the Lancefield groups C and G is underappreciated; most cases involve Streptococcus dysgalactiae subspecies equisimilis. Despite having a relatively weak toxicity compared with group A streptococci, Streptococcus dysgalactiae subspecies equisimilis is associated with a mortality rate that is as high as that of group A streptococci in cases of invasive infection because Streptococcus dysgalactiae subspecies equisimilis mainly affects elderly individuals who already have various comorbidities. An 83-year-old Japanese woman with breast cancer-related lymphedema in her left upper limb was referred to our hospital with high fever and acute pain with erythema in her left arm. She showed septic shock with disseminated intravascular coagulation. Blood culture showed positive results for Streptococcus dysgalactiae subspecies equisimilis, confirming a diagnosis of streptococcal toxic-shock syndrome. She survived after successful intensive care. To the best of our knowledge, this case represents the first report of Streptococcus dysgalactiae subspecies equisimilis-induced streptococcal toxic-shock syndrome in a patient with breast cancer-related lymphedema. Breast cancer-related lymphedema is a common problem, and we must pay attention to invasive streptococcal soft tissue infections, particularly in elderly patients with chronic disease.

  6. Reevaluating the role of antidepressants in cancer-related depression: a systematic review and meta-analysis.

    Science.gov (United States)

    Riblet, Natalie; Larson, Robin; Watts, Bradley V; Holtzheimer, Paul

    2014-01-01

    Prior reviews evaluating the role of antidepressants in cancer-related depression have drawn conflicting conclusions. These reviews have also not explored differences in efficacy and tolerability between antidepressants. We conducted a meta-analysis to address these limitations. We searched Medline (1948-2013), the Cochrane Library (1800-2013), the Cumulative Index to Nursing and Allied Health Literature (1986-2013), ClinicalTrials.gov (2013) and meeting abstracts. We included randomized trials comparing antidepressants to placebo or no treatment for cancer-related depression. We used random effects to calculate standardized mean differences (SMD). Of 5178 potentially eligible citations, 9 trials (1169 subjects) met inclusion criteria. Trials of mianserin found a robust reduction in depression scores at ≥4 weeks of treatment (SMD: 0.60, 95% confidence interval (CI): 0.24-0.95). Similar, but less robust, results were observed with paroxetine (SMD: 0.22, 95% CI: 0.01-0.42) and fluoxetine (SMD 0.34, 95% CI: 0.02-0.66). Conversely, there was no advantage with amitriptyline or desipramine. Compared to placebo, the odds of dropping out due to side effect were higher with fluoxetine and paroxetine and lower with mianserin. Methodological quality was moderate. Paroxetine, fluoxetine and mianserin improve cancer-related depression but may vary in efficacy and tolerability. High-quality, randomized trials of newer antidepressant agents are needed to identify optimal treatments for managing cancer-related depression. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The effects of a six-week supervised multimodal exercise intervention during chemotherapy on cancer-related fatigue

    DEFF Research Database (Denmark)

    Andersen, Christina; Rørth, Mikael; Ejlertsen, Bent

    2013-01-01

    Cancer related fatigue (CRF) is a common problem for cancer patients across diagnoses during chemotherapy and is associated with physical inactivity, lower functional level and lack of energy. Few RCT exercise intervention studies have included cancer patients undergoing chemotherapy. The objecti...

  8. Cancer Information Seeking and Cancer-Related Health Outcomes: A Scoping Review of the Health Information National Trends Survey Literature.

    Science.gov (United States)

    Wigfall, Lisa T; Friedman, Daniela B

    2016-09-01

    Cancer is a leading cause of death among adults in the United States. Only 54% of U.S. adults reported seeking cancer information in 2014. Cancer information seeking has been positively associated with cancer-related health outcomes such as screening adherence. We conducted a scoping review of studies that used data from the Health Information National Trends Survey (HINTS) in order to examine cancer information seeking in depth and the relationship between cancer information seeking and cancer-related health outcomes. We searched five databases and the HINTS website. The search yielded a total of 274 article titles. After review of 114 de-duplicated titles, 66 abstracts, and 50 articles, 22 studies met inclusion criteria. Cancer information seeking was the outcome in only four studies. The other 18 studies focused on a cancer-related health outcome. Cancer beliefs, health knowledge, and information seeking experience were positive predictors of cancer information seeking. Cancer-related awareness, knowledge, beliefs, preventive behaviors, and screening adherence were higher among cancer information seekers. Results from this review can inform other research study designs and primary data collection focused on specific cancer sites or aimed at populations not represented or underrepresented in the HINTS data (e.g., minority populations, those with lower socioeconomic status).

  9. Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema in the Pathways Study.

    Science.gov (United States)

    Kwan, Marilyn L; Yao, Song; Lee, Valerie S; Roh, Janise M; Zhu, Qianqian; Ergas, Isaac J; Liu, Qian; Zhang, Yali; Kutner, Susan E; Quesenberry, Charles P; Ambrosone, Christine B; Kushi, Lawrence H

    2016-08-01

    Breast cancer-related lymphedema (BCRL) is a serious chronic condition after breast cancer (BC) surgery and treatment. It is unclear if BCRL risk varies by race/ethnicity. In a multiethnic prospective cohort study of 2953 BC patients, we examined the association of self-reported BCRL status with self-reported race/ethnicity and estimated genetic ancestry. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up starting 6 months post-BC diagnosis. Estimates were further stratified by body mass index (BMI). By 48 months of follow-up, 342 (11.6 %) women reported having BCRL. Younger age at BC diagnosis, higher BMI at baseline, and lower physical activity were associated with greater BCRL risk. African American (AA) women had a 2-fold increased risk of BCRL compared with White women (HR = 2.04; 95 % CI 1.35-3.08). African genetic ancestry was also associated with an increased risk (HR = 2.50; 95 % CI 1.43, 4.36). Both risks were attenuated but remained elevated after adjusting for known risk factors and became more pronounced when restricted to the nonobese women (adjusted HR = 2.31 for AA and HR = 3.70 for African ancestry, both p ancestry data, with a potential ancestry-obesity interaction.

  10. Analyses of the studies on cancer-related quality of life published in Korea

    International Nuclear Information System (INIS)

    Lee, Eun Hyun; Park, Hee Boong; Kim, Myung Wook; Kang, Sung Hee; Chun, Mi Son; Lee, Hye Jin; Lee, Won Hee

    2002-01-01

    The purpose of the present study was to analyze and evaluate prior studies published in Korea on the cancer-related quality of life, in order to make recommendations for further research. A total of 31 studies were selected from three different databases. The selected studies were analyzed according to 11 criteria, such as site of cancer, domain, independent variable, research design, self/proxy rating, single/battery instrument, translation/back translation, reliability, validity, scoring, and findings. Of the 31 studies, approximately half of them were conducted using a mixed cancer group of patient. Many of the studies asserted that the concept of quality of life had a multidimensional attribute. Approximately 30% were longitudinal design studies giving information about the changes in quality of life. In all studies, except one, patients directly rated their level of quality of life. With respect to the questionnaires used for measuring the quality of life, most studies did not consider whether or not their reliability and validity had been established. In addition, when using questionnaires developed in other languages, no studies employed a translation/back-translation technique. All studies used sum or total scoring methods when calculating the level of quality of life. The types of variables tested for their influence on quality of life were quite limited. It is recommended that longitudinal design studies be performed, using methods of data collection whose validity and reliability has been confirmed, and that studies be conducted to identify new variables having an influence on the quality of life

  11. Chronic cancer-related fatigue in long-term survivors of testicular cancer.

    Science.gov (United States)

    Orre, Ingrid J; Fosså, Sophie D; Murison, Robert; Bremnes, Roy; Dahl, Olav; Klepp, Olbjørn; Loge, Jon H; Wist, Erik; Dahl, Alv A

    2008-04-01

    High prevalence of cancer-related fatigue (CRF) has been reported among many groups of cancer survivors when compared to the general population. However, this topic has rarely been studied in long-term survivors of testicular cancer (TCSs). The present multi-centre study examines the prevalence of chronic CRF in Norwegian TCSs compared to chronic general fatigue (GF) in the Norwegian general population, and associations between a variety of relevant variables and CRF in TCSs. Participants were 1431 TCSs, aged 18-75, at an average of 11 years posttreatment (range 4.5-21 years), and a sample of 1080 age-matched men from the general Norwegian population (GenPop). The participants responded to a mailed questionnaire that included the Fatigue Questionnaire for the assessment of chronic CRF and chronic GF. The prevalence of chronic CRF was 17.1% (95% CI 15.2-19.1%) among TCSs compared to 9.7% of chronic GF in GenPop (95% CI 8.0-11.5%). Regression analyses showed that poor quality of life (QOL), various psychosocial and somatic problems, and neuroticism were highly associated with presence of chronic CRF in TCSs. Chronic CRF is far more common among TCSs than chronic GF in the general population and is associated with poor QOL and multiple psychological and somatic health problems. As a consequence, fatigue should be in focus during routine follow-ups as well as later in the general medical care of TCSs.

  12. Effects of yoga on arm volume among women with breast cancer related lymphedema: A pilot study.

    Science.gov (United States)

    Fisher, Mary Insana; Donahoe-Fillmore, Betsy; Leach, Laura; O'Malley, Colleen; Paeplow, Cheryl; Prescott, Tess; Merriman, Harold

    2014-10-01

    Lymphedema affects 3-58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at baseline, half-way, and at the conclusion of yoga practice. Arm volume significantly decreased from baseline (2423.3 ml ± 597.2) to final measures (2370.8 ml ± 577.2) (p = .02). No significant changes in QOL (p = .12), self-reported arm function (p = .34), or hand grip strength (p = .26) were found. Yoga may be beneficial in the management of lymphedema. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Cancer-related fatigue in adolescents and young adults: A systematic review of the literature.

    Science.gov (United States)

    Nowe, E; Stöbel-Richter, Y; Sender, A; Leuteritz, K; Friedrich, M; Geue, K

    2017-10-01

    Adolescents and young adults with cancer (AYA) represent a specific age cohort dealing with the disease in a stage of life characterized by development, upheavals, and establishment. The aim of this study was to point out the state of research on how AYA are affected by cancer-related fatigue (CRF). Twelve articles were included. CRF was found to be higher in AYA than in either of the comparison groups, healthy peers and older cancer patients. Most included studies did not measure CRF with multidimensional, fatigue-specific instruments. We found a gap in research concerning CRF in AYA. The existing findings suggest that CRF is a significant issue for AYA cancer patients. However, less is known about the prevalence, severity, and impact of CRF in AYA, and their treatment. This should be considered in future research, and risk and prevention factors should be ascertained. Multidimensional and fatigue-specific measuring tools should be used to do this. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Cancer-related pain management: A review of knowledge and attitudes of healthcare professionals.

    Science.gov (United States)

    Kasasbeh, M A M; McCabe, C; Payne, S

    2017-11-01

    Cancer-related pain (CRP) is common and many patients continue to experience pain in spite of advances in pain management modalities. The lack of knowledge, inadequate assessment of CRP and/or organisational factors, such as lack of time due to heavy workload, can be a barrier to effective pain management of healthcare professionals. The purpose was to examine the evidence with regard to the knowledge and attitudes towards practice of healthcare professionals in relation to CRP management. A search of the literature (1999-2015) was conducted searching databases and journals including CINAHL, MEDLINE, PsycINFO, PubMed, Science Direct and Wiley-Blackwell. The initial search revealed a total of 99 articles and following removal of those that did not meet the inclusion criteria, 19 articles were included in the final review. Recognition of the widespread under treatment of CRP has prompted recent corrective efforts in terms of education from healthcare professionals, however, there is a continuing deficit in healthcare professionals' knowledge with regard to CRP management and indicated that healthcare professionals still have negative attitudes that hinder the delivery of quality care to patients suffering from CRP. Further research on how and where education on this topic should be delivered is required. © 2016 John Wiley & Sons Ltd.

  15. Recommendations for high-priority research on cancer-related fatigue in children and adults.

    Science.gov (United States)

    Barsevick, Andrea M; Irwin, Michael R; Hinds, Pamela; Miller, Andrew; Berger, Ann; Jacobsen, Paul; Ancoli-Israel, Sonia; Reeve, Bryce B; Mustian, Karen; O'Mara, Ann; Lai, Jin-Shei; Fisch, Michael; Cella, David

    2013-10-02

    Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current case definition to reflect more rigorous criteria, adopting the Patient Reported Outcomes Measurement Information System fatigue scales as standard measures of CRF, and linking legacy measures to the scales. With regard to the biology of CRF, the group identified the need for longitudinal research to examine biobehavioral mechanisms underlying CRF and testing mechanistic hypotheses within the context of intervention research. To address clinical trial issues, recommendations included using only placebo-controlled trial designs. setting eligibility to minimize sample heterogeneity or enable subgroup analysis, establishing a CRF severity threshold for participation in clinical trials, conducting dissemination trials of efficacious interventions (such as exercise), and combining nonpharmacologic and pharmacologic interventions to exploit the potential synergy between these approaches. Accomplishing these goals has the potential to advance the science of CRF and improve the clinical management of this troubling symptom.

  16. Targeted sequencing of cancer-related genes in colorectal cancer using next-generation sequencing.

    Directory of Open Access Journals (Sweden)

    Sae-Won Han

    Full Text Available Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in cancer. We have established a targeted sequencing platform using next-generation sequencing (NGS technology for clinical use, which can provide mutation and copy number variation data. NGS was performed with paired-end library enriched with exons of 183 cancer-related genes. Normal and tumor tissue pairs of 60 colorectal adenocarcinomas were used to test feasibility. Somatic mutation and copy number alteration were analyzed. A total of 526 somatic non-synonymous sequence variations were found in 113 genes. Among these, 278 single nucleotide variations were 232 different somatic point mutations. 216 SNV were 79 known single nucleotide polymorphisms in the dbSNP. 32 indels were 28 different indel mutations. Median number of mutated gene per tumor was 4 (range 0-23. Copy number gain (>X2 fold was found in 65 genes in 40 patients, whereas copy number loss (

  17. Estimation of baseline lifetime risk of developed cancer related to radiation exposure in China

    International Nuclear Information System (INIS)

    Li Xiaoliang; Niu Haowei; Sun Quanfu; Ma Weidong

    2011-01-01

    Objective: To introduce the general international method for estimation of lifetime risk of developed cancer, and to estimate the lifetime risk baseline values of several kinds of cancers related to radiation exposures in China. Methods: The risk estimation was based on the data from Chinese Cancer Registry Annual Report (2010) and China Population and Employment Statistics Yearbook (2009), and made according to the method previously published by National Cancer Institute (NCI) in USA. Results: The lifetime risk of all cancer in China in 2007 was estimated to be 27.77%, that of lung cancer 5.96%, that of breast cancer for female 3.34%, that of all leukemia 0.14%, that of thyroid cancer 0.37%. The lifetime risks of all cancer were estimated to be 32.74% for males and 24.73% for females, and that was 36.47% for urban residents and 26.79% for rural people. Conclusions: The lifetime risk of all cancer for males in 2007 was about 1.25 times as much as that for females. The value of all cancer for urban residents was about 1.35 times as much as that for rural residents. The lifetime risk of developed cancers in 2007 in China is lower than that in the developed countries,such as Japan. (authors)

  18. Effects of Exercise Interventions and Physical Activity Behavior on Cancer Related Cognitive Impairments: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Philipp Zimmer

    2016-01-01

    Full Text Available This systematic review analyzes current data on effects of exercise interventions and physical activity behavior on objective and subjective cancer related cognitive impairments (CRCI. Out of the 19 studies which met all inclusion criteria, five RCTs investigated rodents, whereas the other 14 trials explored humans and these included six RCTs, one controlled trial, two prospective noncontrolled trials, one case series, one observational study, and three cross-sectional studies. The results from animal models revealed positive effects of exercise during and after chemotherapy or radiation on structural alterations of the central nervous system, physiological as well as neuropsychological outcomes. The overall study quality in patient studies was poor. The current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs (e.g., Yoga with benefits on self-perceived cognitive functions as well as a reduction of chronic inflammation for breast cancer patients in the aftercare. Exercise potentially contributes to the prevention and rehabilitation of CRCI. Additional RCTs with standardized neuropsychological assessments and controlling for potential confounders are needed to confirm and expand preliminary findings.

  19. The approach of cancer related fatigue in rehabilitation medicine: Part II – Therapeutic interventions

    Directory of Open Access Journals (Sweden)

    Salca Amalia

    2015-09-01

    Full Text Available Starting with patient’ diagnose and continuing throughout the treatment and thereafter, cancer-related fatigue (CRF is a distressing and disabling symptom, highly prevalent across the cancer continuum2. This is a review article mainly focusing on the rehabilitation objectives and interventions in CRF, and implementation issues, according to the report of an NCCN member institution4. Implementation is the most problematic, considering the large number of patients to whom it is addressed to and the variety of pathologies within this group of patients. The onset of CRF is difficult to establish, because of the limitations of reporting this symptom4, but it is a valuable predictor in prognosis. The main interventions in rehabilitation applicable to these patients are discussed in correlation to the objectives of each phase of therapeutic management in cancer: pre-operatory, before, during or after radio and/or chemotherapy Conclusion: Rehabilitation interventions should be applied to all patients diagnosed with cancer, according to their phase of oncologic treatment and the objectives. This should be practiced as preventive measure, but as a therapeutic one to, considering the high incidence of CFR before diagnose.

  20. A proteomics based approach for the identification of gastric cancer related markers.

    Science.gov (United States)

    Sheikh, Ishfaq A; Mirza, Zeenat; Ali, Ashraf; Aliev, Gjumrakch; Ashraf, Ghulam Md

    2016-01-01

    Gastric cancer (GC) is the amongst the most common cancer types causing second largest number of cancer related deaths globally. GC is characterized as an aggressive malignancy which is very tough to be detected at an early stage. GC has been defined as a complex, multistep process involving multiple genetic and epigenetic alterations leading to aberrant expression of key regulating factors. GC according to WHO has been defined as malignant epithelial tumors of the gastric mucosa with glandular differentiation. About one half of the GCs are located in the lower stomach, and remaining is located in the corpus and fundus of the stomach (20%), lesser curvature (20%), cardia (10%) and greater curvature (3%). GC has been classified into intestinal and diffuse types based on epidemiological and clinico- and histopathological features. The etiology of GC is multifactorial and includes dietary as well as non-dietary factors. Despite a lot of research efforts, GC remains to be the cancer without clear symptoms at onset, poor prognosis, with metastasis and recurrence. Thus, there is an urgent need for identifying novel and diagnostic GC biomarkers and techniques with high sensitivity and specificity. In the present review, we provide a synopsis of proteomics based GC biomarkers discovered from various cancerous specimens such as blood, gastric fluid, tissues, cells and H. pylori infected cancer cell lines. The advent of proteomics based GC biomarkers will be a great asset for the early detection and treatment of GC.

  1. Trends in Adult Cancer-Related Emergency Department Utilization: An Analysis of Data From the Nationwide Emergency Department Sample.

    Science.gov (United States)

    Rivera, Donna R; Gallicchio, Lisa; Brown, Jeremy; Liu, Benmei; Kyriacou, Demetrios N; Shelburne, Nonniekaye

    2017-10-12

    The emergency department (ED) is used to manage cancer-related complications among the 15.5 million people living with cancer in the United States. However, ED utilization patterns by the population of US adults with cancer have not been previously evaluated or described in published literature. To estimate the proportion of US ED visits made by adults with a cancer diagnosis, understand the clinical presentation of adult patients with cancer in the ED, and examine factors related to inpatient admission within this population. Nationally representative data comprised of 7 survey cycles (January 2006-December 2012) from the Nationwide Emergency Department Sample were analyzed. Identification of adult (age ≥18 years) cancer-related visits was based on Clinical Classifications Software diagnoses documented during the ED visit. Weighted frequencies and proportions of ED visits among adult patients with cancer by demographic, geographic, and clinical characteristics were calculated. Weighted multivariable logistic regression was used to examine the associations between inpatient admission and key demographic and clinical variables for adult cancer-related ED visits. Adult cancer-related ED utilization patterns; identification of primary reason for ED visit; patient-related factors associated with inpatient admission from the ED. Among an estimated 696 million weighted adult ED visits from January 2006 to December 2012, 29.5 million (4.2%) were made by a patient with a cancer diagnosis. The most common cancers associated with an ED visit were breast, prostate, and lung cancer, and most common primary reasons for visit were pneumonia (4.5%), nonspecific chest pain (3.7%), and urinary tract infection (3.2%). Adult cancer-related ED visits resulted in inpatient admissions more frequently (59.7%) than non-cancer-related visits (16.3%) (P adults, breast, prostate, and lung cancer were the most common cancer diagnoses presenting to the ED. Pneumonia was the most common

  2. A systematic review of complementary and alternative medicine interventions for the management of cancer-related fatigue.

    Science.gov (United States)

    Finnegan-John, Jennifer; Molassiotis, Alex; Richardson, Alison; Ream, Emma

    2013-07-01

    Fatigue, experienced by patients during and following cancer treatment, is a significant clinical problem. It is a prevalent and distressing symptom yet pharmacological interventions are used little and confer limited benefit for patients. However, many cancer patients use some form of complementary and alternative medicine (CAM), and some evidence suggests it may relieve fatigue. A systematic review was conducted to appraise the effectiveness of CAM interventions in ameliorating cancer-related fatigue. Systematic searches of biomedical, nursing, and specialist CAM databases were conducted, including Medline, Embase, and AMED. Included papers described interventions classified as CAM by the National Centre of Complementary and Alternative Medicine and evaluated through randomized controlled trial (RCT) or quasi-experimental design. Twenty studies were eligible for the review, of which 15 were RCTs. Forms of CAM interventions examined included acupuncture, massage, yoga, and relaxation training. The review identified some limited evidence suggesting hypnosis and ginseng may prevent rises in cancer-related fatigue in people undergoing treatment for cancer and acupuncture and that biofield healing may reduce cancer-related fatigue following cancer treatments. Evidence to date suggests that multivitamins are ineffective at reducing cancer-related fatigue. However, trials incorporated within the review varied greatly in quality; most were methodologically weak and at high risk of bias. Consequently, there is currently insufficient evidence to conclude with certainty the effectiveness or otherwise of CAM in reducing cancer-related fatigue. The design and methods employed in future trials of CAM should be more rigorous; increasing the strength of evidence should be a priority.

  3. Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis.

    Science.gov (United States)

    Puetz, Timothy W; Herring, Matthew P

    2012-08-01

    Exercise-induced improvements in cancer-related fatigue may be moderated differentially in patients during and following treatment. These effects have not been reviewed systematically. In accordance with PRISMA guidelines, the population effect size for exercise training on cancer-related fatigue during and following treatment was estimated and the extent to which the effect is differentiated across the time course of treatment and recovery was determined. Articles published before August 2011 were retrieved using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science databases. Seventy studies involving 4881 cancer patients during or following treatment were selected. Articles included a cancer-related fatigue outcome measured at baseline and post-intervention and randomized allocation to exercise or non-exercise comparison. From August to October 2011, Hedges' d effect sizes were computed, study quality was evaluated, and random effects models were used to estimate sampling error and population variance. Exercise significantly reduced cancer-related fatigue by a mean effect Δ (95% CI) of 0.32 (0.21, 0.43) and 0.38 (0.21, 0.54) during and following cancer treatment, respectively. During treatment, patients with lower baseline fatigue scores and higher exercise adherence realized the largest improvements. Following treatment, improvements were largest for trials with longer durations between treatment completion and exercise initiation, trials with shorter exercise program lengths, and trials using wait-list comparisons. Exercise reduces cancer-related fatigue among patients during and following cancer treatment. These effects are moderated differentially over the time course of treatment and recovery. Exercise has a palliative effect in patients during treatment and a recuperative effect post-treatment. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Cancer-related fatigue and associated disability in post-treatment cancer survivors.

    Science.gov (United States)

    Jones, Jennifer M; Olson, Karin; Catton, Pamela; Catton, Charles N; Fleshner, Neil E; Krzyzanowska, Monika K; McCready, David R; Wong, Rebecca K S; Jiang, Haiyan; Howell, Doris

    2016-02-01

    Cancer-related fatigue (CRF) is the most prevalent and distressing symptom among cancer patients and survivors. However, research on its prevalence and related disability in the post-treatment survivorship period remains limited. We sought to describe the occurrence of CRF within three time points in the post-treatment survivorship trajectory. A self-administered mail-based questionnaire which included the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and the World Health Organisation Disability Assessment Schedule 2.0 was sent to three cohorts of disease-free breast, prostate or colorectal cancer survivors (6-18 months; 2-3 years; and 5-6 years post-treatment). Clinical information was extracted from chart review. Frequencies of significant fatigue by diagnostic group and time cohorts were studied and compared. Multivariate logistic regressions were conducted to examine the associations between CRF and demographic, clinical, and psychosocial variables. One thousand two hundred ninety-four questionnaire packages were returned (63 % response rate). A total of 29 % (95 % CI [27 % to 32 %]) of the sample reported significant fatigue (FACT-F ≤34), and this was associated with much higher levels of disability (p Breast (40 % [35 % to 44 %]) and colorectal (33 % [27 % to 38 %]) cancer survivors had significantly higher rates of fatigue compared with the prostate group (17 % [14 % to 21 %]) (p cancer survivors up to 6 years post-treatment, and this is associated with high levels of disability. Clinicians need to be aware of the chronicity of CRF and assess for it routinely in medical practice. While there is no gold standard treatment, non-pharmacological interventions with established efficacy can reduce its severity and possibly minimize its disabling impact on patient functioning. Attention must be paid to the co-occurrence and need for possible treatment of depression and other co-occurring physical symptoms as contributing factors.

  5. Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

    Directory of Open Access Journals (Sweden)

    Mantovani G

    2013-08-01

    Full Text Available Giovanni Mantovani, Clelia Madeddu, Antonio Macciò Department of Medical Oncology, University of Cagliari, Cagliari, Italy Abstract: Cancer-related anorexia and cachexia syndrome (CACS is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing

  6. Cancer-related internet information communication between oncologists and patients with breast cancer: a qualitative study.

    Science.gov (United States)

    Shen, Megan Johnson; Dyson, Robert C; D'Agostino, Thomas A; Ostroff, Jamie S; Dickler, Maura N; Heerdt, Alexandra S; Bylund, Carma L

    2015-11-01

    Many patients with cancer search out information about their cancer on the internet, thus affecting their relationship with their oncologists. An in-depth analysis of patient-physician communication about information obtained from the internet is currently lacking. We audio-recorded visits of patients with breast cancer and their oncologists where internet information was expected to be discussed. Inductive thematic text analysis was used to identify qualitative themes from these conversations. Twenty-one patients self-reported discussing cancer-related internet information (CRII) with their oncologists; 16 audio recordings contained detectable discussions of CRII and were analyzed. Results indicated that oncologists and patients initiated CRII discussions implicitly and explicitly. Oncologists responded positively to patient-initiated CRII discussions by (1) acknowledging their limited expertise/knowledge, (2) encouraging/approving using the internet as an information resource, (3) providing information/guidance on the proper use of internet searches, (4) discussing the pros and cons of relevant treatment options, or (5) giving information. Finally, patients reacted to the CRII discussions by (1) indicating that they only used reputable sources/websites, (2) asking for further explanation of information, (3) expressing continued concern, or (4) asking for the oncologist's opinion or recommendation. These results indicate that the majority of patients introduce internet information implicitly, in order to guard against any threat to their self-esteem. Physicians, in turn, seem to respond in a supportive fashion to reduce any threat experienced. Future interventions may consider providing prescription-based guidance on how to navigate the internet as a health information resource and to encourage patients to bring these topics up with their oncologist. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Development of a honey based tonic syrup for cancer-related fatigue

    Directory of Open Access Journals (Sweden)

    R. Norouzian

    2017-11-01

    Full Text Available Background and objectives: Cancer-related fatigue (CRF is the most common and distressing symptom that affects overall quality of life of cancer patients. Due to the multi-factorial etiology, there is currently no “gold standard” for treatment of CRF. Considering the growing importance of national traditional medicines, natural remedies are viewed as playing distinctive role. “Jollab” is a natural syrup prescribed by Iranian traditional medicine (ITM scholars as tonic especially for the cardiovascular system. “Jollab” can consist of several ingredients although almost all traditional recipes include saffron and rose water as well as sugar or honey. The aim of this research was to develop a honey based “Jollab” and evaluate hydroxymethylfurfural (HMF, a product of fructose decomposition, as an indicator of heating effect on honey. Methods: Several “Jollab” formulations with different proportions of honey and rose water were prepared using deslagging procedure through direct or indirect heating. The HMF content of the formulation was measured according to International Honey Commission (IHC method. Results: “Jollab” was formulated with saffron (0.1%, honey (57.1% and rose water (42.8%. Two-thirds of the rose water was evaporated during deslagging procedure through direct heating (up to 95 °C and the remaining was added to the honey at the end of the process. Moreover, the HMF content of the prepared Jollab was 64.47±5.49 mg/kg which meets ICH standards. Conclusion: The developed honey based Jollab could be considered as a safe formulation for further studies in the field of CRF due to the acceptable HMF content.

  8. Translation research: 'Back on Track', a multiprofessional rehabilitation service for cancer-related fatigue.

    Science.gov (United States)

    Gracey, J H; Watson, M; Payne, C; Rankin, J; Dunwoody, L

    2016-03-01

    To assess the effectiveness and acceptability of an individually tailored rehabilitation intervention for patients with cancer-related fatigue (CRF). Eighteen individuals, (16 female, two male, aged 40-83 years), who self-reported CRF (above four on a 10-point Likert scale) took part in an 8 week physical activity intervention weekly review and optional gym-based support. Fifteen participants had a primary diagnosis of breast cancer and along with the other participants had multiple myeloma, colorectal or prostate cancer. All participants took part in a goal-oriented walking and muscle strengthening programme with dietary advice and psychological support based on the Transtheoretical Model (TTM) of behaviour change. Effectiveness was assessed by physical and psychological outcomes. Focus groups with participants and individual interviews with the professionals delivering the intervention explored the feasibility and acceptability of the intervention. Statistically significant improvements were seen in the primary outcome of fatigue and on the secondary outcomes of physical function, depression and in triceps skin fold thickness reduction. Participants endorsed the intervention as being highly acceptable, holistic and as important as medical treatments for cancer. The importance of team working was highlighted as key to service delivery and success. A multidisciplinary home-based tailored intervention with optional weekly gym attendance is acceptable to people with CRF, improving physical and psychosocial outcomes. Study limitations and suggestions for further research are discussed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Causes of Shoulder Pain in Women with Breast Cancer-Related Lymphedema: A Pilot Study

    Science.gov (United States)

    Jeong, Ho Joong; Hwang, Ki Hun; Kim, Ghi Chan

    2011-01-01

    Purpose To inform on shoulder pathology and to identify the disabilities and level of quality of life (QOL) associated with shoulder pain in patients with breast cancer-related lymphedema (BCRL). Materials and Methods Using patient history, physical examination, and ultrasound (US), we classified patients with BCRL into the following three groups: no pain with normal ultrasound (US), pain with normal US, and pain with abnormal US. We evaluated shoulder pathology using US, pain intensity using a visual analogue scale (VAS), and functional disability using the Korean version of the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire. For assessment of QOL, we used the Korean version of the brief form of the World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF). Results 28.9% of patients had no pain and normal US, 31.6% had pain with normal US, and 39.5% had pain with abnormal US. The US findings for those with pain and abnormal US revealed the following: 53.3% had a supraspinatus tear, 13.3% had biceps tenosynovitis, 13.3% had acromioclavicular arthritis, 13.3% had subdeltoid bursitis, and 53.3% had adhesive capsulitis. Patients with shoulder pain and abnormal US findings had significantly higher mean DASH and pain scores. Pain scores were positively correlated with DASH scores and negatively correlated with QOL. Conclusion We found that BCRL with shoulder pain and evidence of shoulder pathology on US was associated with reduced QOL and increased disability. Proper diagnosis and treatment of shoulder pain are necessary to improve QOL and decrease disability in patients with BCRL. PMID:21623610

  10. Developing an Integrative Treatment Program for Cancer-Related Fatigue Using Stakeholder Engagement - A Qualitative Study.

    Science.gov (United States)

    Canella, Claudia; Mikolasek, Michael; Rostock, Matthias; Beyer, Jörg; Guckenberger, Matthias; Jenewein, Josef; Linka, Esther; Six, Claudia; Stoll, Sarah; Stupp, Roger; Witt, Claudia M

    2017-11-01

    Although cancer-related fatigue (CRF) has gained increased attention in the past decade, it remains difficult to treat. An integrative approach combining conventional and complementary medicine interventions seems highly promising. Treatment programs are more likely to be effective if the needs and interests of the people involved are well represented. This can be achieved through stakeholder engagement. The aim of the study was to develop an integrative CRF treatment program using stakeholder engagement and to compare it to an expert version. In a qualitative study, a total of 22 stakeholders (4 oncologists, 1 radiation-oncologist, 1 psycho-oncologist, 5 nurses/nurse experts, 9 patients, 1 patient family member, 1 representative of a local Swiss Cancer League) were interviewed either face-to-face or in a focus group setting. For data analysis, qualitative content analysis was used. With stakeholder engagement, the integrative CRF treatment program was adapted to usual care using a prioritizing approach and allowing more patient choice. Unlike the expert version, in which all intervention options were on the same level, the stakeholder engagement process resulted in a program with 3 different levels. The first level includes mandatory nonpharmacological interventions, the second includes nonpharmacological choice-based interventions, and the third includes pharmacological interventions for severe CRF. The resulting stakeholder based integrative CRF treatment program was implemented as clinical practice guideline at our clinic (Institute for Complementary and Integrative Medicine, University Hospital Zurich). Through the stakeholder engagement approach, we integrated the needs and preferences of people who are directly affected by CRF. This resulted in an integrative CRF treatment program with graded recommendations for interventions and therefore potentially greater sustainability in a usual care setting.

  11. Randomized Trial of a Social Networking Intervention for Cancer-Related Distress.

    Science.gov (United States)

    Owen, Jason E; O'Carroll Bantum, Erin; Pagano, Ian S; Stanton, Annette

    2017-10-01

    Web and mobile technologies appear to hold promise for delivering evidence-informed and evidence-based intervention to cancer survivors and others living with trauma and other psychological concerns. Health-space.net was developed as a comprehensive online social networking and coping skills training program for cancer survivors living with distress. The purpose of this study was to evaluate the effects of a 12-week social networking intervention on distress, depression, anxiety, vigor, and fatigue in cancer survivors reporting high levels of cancer-related distress. We recruited 347 participants from a local cancer registry and internet, and all were randomized to either a 12-week waiting list control group or to immediate access to the intervention. Intervention participants received secure access to the study website, which provided extensive social networking capabilities and coping skills training exercises facilitated by a professional facilitator. Across time, the prevalence of clinically significant depression symptoms declined from 67 to 34 % in both conditions. The health-space.net intervention had greater declines in fatigue than the waitlist control group, but the intervention did not improve outcomes for depression, trauma-related anxiety symptoms, or overall mood disturbance. For those with more severe levels of anxiety at baseline, greater engagement with the intervention was associated with higher levels of symptom reduction over time. The intervention resulted in small but significant effects on fatigue but not other primary or secondary outcomes. Results suggest that this social networking intervention may be most effective for those who have distress that is not associated with high levels of anxiety symptoms or very poor overall psychological functioning. The trial was registered with the ClinicalTrials.gov database ( ClinicalTrials.gov #NCT01976949).

  12. Multimodal therapy concept and aerobic training in breast cancer patients with chronic cancer-related fatigue.

    Science.gov (United States)

    Kröz, Matthias; Fink, Matthias; Reif, Marcus; Grobbecker, Siglinde; Zerm, Roland; Quetz, Michaele; Frühwirth, Matthias; Brinkhaus, Benno; Bartsch, Christian; Girke, Matthias; Gutenbrunner, Christoph

    2013-07-01

    HYPOTHESE: Cancer-related fatigue (CRF) and sleep disorders are some of the most wearing and common symptoms in disease-free breast cancer patients (BC). Aerobic training (AT) is the treatment with the best available evidence, even though it seems to be insufficient with regards to improvements in cognitive fatigue. We introduced a new multimodal therapy concept (MM) consisting of psycho-, sleep-education and new approaches based on anthroposophic medicine such as eurythmy and painting therapy. This pilot study will test the implementation of MM and yield first results of the MM and AE in our centres. 31 out of 34 patients suffering from BC and CRF were fully assessed in a ten-week intervention study. 21 patients chose MM and 10 decided on AT. CRF was measured with the help of the Cancer Fatigue Scale (CFS-D), and the global quality of sleep was measured with the Pittsburgh Sleep Quality Index (PSQI). We also captured autonomic regulation (aR) and patients' satisfaction with questionnaires. Statistical analysis was done with SAS 9.1.3 for windows. The new MM therapy can be implemented with high satisfaction among patients. Significant improvements were found in the MM group with regards to CFS-D, global quality of sleep, sleep efficiency (PSQI), aR and rest/activity regulation compared to baseline (all pfatigue was seen in either group. The multimodal therapy concept was feasible and improved cancer fatigue, sleep quality, autonomic and rest-/activity regulation in breast cancer patients. It may therefore constitute a valuable treatment option in addition to aerobic training for BC patients with CRF. A further study with larger sample size needs to be carried out to assess the efficacy of combined multimodal-aerobic therapy.

  13. Factors Associated With the Development of Breast Cancer-Related Lymphedema After Whole-Breast Irradiation

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    Shah, Chirag; Wilkinson, John Ben; Baschnagel, Andrew [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Ghilezan, Mihai [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); William Beaumont School of Medicine, Oakland University, Royal Oak, MI (United States); Riutta, Justin; Dekhne, Nayana; Balaraman, Savitha [Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI (United States); William Beaumont School of Medicine, Oakland University, Royal Oak, MI (United States); Mitchell, Christina; Wallace, Michelle [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Vicini, Frank, E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI (United States); William Beaumont School of Medicine, Oakland University, Royal Oak, MI (United States)

    2012-07-15

    Purpose: To determine the rates of breast cancer-related lymphedema (BCRL) in patients undergoing whole-breast irradiation as part of breast-conserving therapy (BCT) and to identify clinical, pathologic, and treatment factors associated with its development. Methods and Materials: A total of 1,861 patients with breast cancer were treated at William Beaumont Hospital with whole-breast irradiation as part of their BCT from January 1980 to February 2006, with 1,497 patients available for analysis. Determination of BCRL was based on clinical assessment. Differences in clinical, pathologic, and treatment characteristics between patients with BCRL and those without BCRL were evaluated, and the actuarial rates of BCRL by regional irradiation technique were determined. Results: The actuarial rate of any BCRL was 7.4% for the entire cohort and 9.9%, 14.7%, and 8.3% for patients receiving a supraclavicular field, posterior axillary boost, and internal mammary irradiation, respectively. BCRL was more likely to develop in patients with advanced nodal status (11.4% vs. 6.3%, p = 0.001), those who had a greater number of lymph nodes removed (14 nodes) (9.5% vs. 6.0%, p = 0.01), those who had extracapsular extension (13.4% vs. 6.9%, p = 0.009), those with Grade II/III disease (10.8% vs. 2.9%, p < 0.001), and those who received adjuvant chemotherapy (10.5% vs. 6.7%, p = 0.02). Regional irradiation showed small increases in the rates of BCRL (p = not significant). Conclusions: These results suggest that clinically detectable BCRL will develop after traditional BCT in up to 10% of patients. High-risk subgroups include patients with advanced nodal status, those with more nodes removed, and those who receive chemotherapy, with patients receiving regional irradiation showing a trend toward increased rates.

  14. Myoelectrical Manifestation of Fatigue Less Prominent in Patients with Cancer Related Fatigue

    Science.gov (United States)

    Kisiel-Sajewicz, Katarzyna; Siemionow, Vlodek; Seyidova-Khoshknabi, Dilara; Davis, Mellar P.; Wyant, Alexandria; Ranganathan, Vinoth K.; Walsh, Declan; Yan, Jin H.; Hou, Juliet; Yue, Guang H.

    2013-01-01

    Purpose A lack of fatigue-related muscle contractile property changes at time of perceived physical exhaustion and greater central than peripheral fatigue detected by twitch interpolation technique have recently been reported in cancer survivors with fatigue symptoms. Based on these observations, it was hypothesized that compared to healthy people, myoelectrical manifestation of fatigue in the performing muscles would be less significant in these individuals while sustaining a prolonged motor task to self-perceived exhaustion (SPE) since their central fatigue was more prominent. The purpose of this study was to test this hypothesis by examining electromyographic (EMG) signal changes during fatiguing muscle performance. Methods Twelve individuals who had advanced solid cancer and cancer-related fatigue (CRF), and 12 age- and gender-matched healthy controls performed a sustained elbow flexion at 30% maximal voluntary contraction till SPE. Amplitude and mean power frequency (MPF) of EMG signals of the biceps brachii, brachioradialis, and triceps brachii muscles were evaluated when the individuals experienced minimal, moderate, and severe fatigue. Results CRF patients perceived physical “exhaustion” significantly sooner than the controls. The myoelectrical manifestation of muscular fatigue assessed by EMG amplitude and MPF was less significant in CRF than controls. The lower MPF even at minimal fatigue stage in CRF may indicate pathophysiologic condition of the muscle. Conclusions CRF patients experience less myoelectrical manifestation of muscle fatigue than healthy individuals near the time of SPE. The data suggest that central nervous system fatigue plays a more important role in limiting endurance-type of motor performance in patients with CRF. PMID:24391800

  15. Effects of warm acupuncture on breast cancer-related chronic lymphedema: a randomized controlled trial.

    Science.gov (United States)

    Yao, C; Xu, Y; Chen, L; Jiang, H; Ki, C S; Byun, J S; Bian, W

    2016-02-01

    Effective treatment for breast cancer-related chronic lymphedema (bcrl) remains a clinical challenge. Acupuncture and moxibustion treatments have been shown to be beneficial and safe for treating bcrl. In the present randomized controlled trial, we compared the effectiveness of combined acupuncture and moxibustion ("warm acupuncture") with that of diosmin in bcrl. Breast cancer patients who met the inclusion and exclusion criteria (n = 30) were randomized to experimental and control groups (15 per group). On alternate days, patients in the experimental group received 30 minutes of acupuncture at 6 acupoints, with 3 of the needles each being topped by a 3-cm moxa stick. The control treatment was diosmin 900 mg 3 times daily. The control and experimental treatments were administered for 30 days. Outcome measures included arm circumferences (index of effectiveness), range of motion [rom (shoulder joint function)], quality of life, clinical safety, and adverse events. Measured by the index of effectiveness, bcrl improved by 51.46% in the experimental group and by 26.27% in the control group (p extorsion in the experimental group improved significantly; they did not change in the control group. Self-reported quality of life was significantly better with warm acupuncture than with diosmin. No adverse effects were reported during the treatment period, and laboratory examinations for clinical safety fell within the normal ranges. Compared with diosmin, warm acupuncture treatment can effectively reduce the degree of bcrl at the specific acupoints treated and can promote quality of life. Warm acupuncture showed good clinical safety, without any adverse effects on blood or the cardiovascular system.

  16. Cancer-Related Information Seeking Among Cancer Survivors: Trends Over a Decade (2003-2013).

    Science.gov (United States)

    Finney Rutten, Lila J; Agunwamba, Amenah A; Wilson, Patrick; Chawla, Neetu; Vieux, Sana; Blanch-Hartigan, Danielle; Arora, Neeraj K; Blake, Kelly; Hesse, Bradford W

    2016-06-01

    The demonstrated benefits of information seeking for cancer patients, coupled with increases in information availability, underscore the importance of monitoring patient information seeking experiences over time. We compared information seeking among cancer survivors to those with a family history of cancer and those with no history of cancer. We identified characteristics associated with greater information seeking among cancer survivors, key sources of cancer-related information, and changes in information source use over time. Data from five iterations of the Health Information National Trends Survey (HINTS) spanning 2003 to 2013 were merged and analyzed. Frequencies, cross-tabulations, multivariate logistic regression, and multinomial regression analyses were conducted. All data were weighted to provide representative estimates of the adult US population. Cancer information seeking was reported most frequently by cancer survivors (69.8 %). The percentage of cancer survivors who reported information seeking increased from 66.8 % in 2003 to 80.8 % in 2013. Cancer information seeking was independently associated with age, education, and income; seeking was less likely among older adults, those with less education, and those with lower incomes. Compared to respondents in 2003, those in 2005 (odds ratio (OR) = 0.40, 95 % confidence interval (CI) = 0.24-0.65) and 2008 (OR = .43, 95 % CI = 0.26-0.70) were about half as likely to use the Internet as the first source of cancer information compared to a healthcare provider. Despite overall increases in cancer information seeking and access to health information from a variety of sources, healthcare providers remain a key source of health information for cancer survivors.

  17. Cancer-related Fatigue and its Relationship with Demographic and Clinical Characteristics

    Directory of Open Access Journals (Sweden)

    Maryam Chehrehgosha

    2013-10-01

    Full Text Available Background and objectives: Fatigue experience is a psychological experience therefore, the relevant caregivers’ acquaintance with this issueis the most important step in offering optimal care for the patients. Accordingly, this study was conductedto determine Cancer-related Fatigue and its Relationship with Demographic and Clinical Characteristics inCancer Patients.A cancer diagnosis is a highly undesirable event for anyone.Methods: characteristics form and the Multidimensional Fatigue Inventory. The data were analyzed with the SPSS-18 software and t-test and ANOVA and tukey post hoc test were used.In this analytical study, 150 cancer patients visiting the oncology unit, the Shafa Radiotherapy Center,and Gorgan’s 5th Azar Teaching Hospital in 2012, who were selected with a purposive sampling method,participated in the study for 4 months. The required information was collected using a demographic and clinicalResults: of treatment, 51.3% used chemotherapy-surgery-radiotherapy regimen, 24.7% surgery-chemotherapy regimen,14% used chemotherapy, 7.3% used radiotherapy, and 2.7% used surgery. The overall mean scoreof fatigue was 54.65±8.78 from 100. The variables of residence (P=0. 018, the duration of marriage(P=0.018, the treatment regimen type (P<0.001, and the family’s economic status (P<0.000 were found toThe patients’ mean age was 48.39±1.5 Of the patients, 55.3% had undergone less than 12 monthshave a significant relationship with fatigue.Conclusion: Psychological interventions, besides physical caring and nursing interventions play a significantrole in the all-inclusive management of cancer patients’ problems, in particular, their fatigue.

  18. Breast Cancer-Related Arm Lymphedema: Incidence Rates, Diagnostic Techniques, Optimal Management and Risk Reduction Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Chirag [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Vicini, Frank A., E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-11-15

    As more women survive breast cancer, long-term toxicities affecting their quality of life, such as lymphedema (LE) of the arm, gain importance. Although numerous studies have attempted to determine incidence rates, identify optimal diagnostic tests, enumerate efficacious treatment strategies and outline risk reduction guidelines for breast cancer-related lymphedema (BCRL), few groups have consistently agreed on any of these issues. As a result, standardized recommendations are still lacking. This review will summarize the latest data addressing all of these concerns in order to provide patients and health care providers with optimal, contemporary recommendations. Published incidence rates for BCRL vary substantially with a range of 2-65% based on surgical technique, axillary sampling method, radiation therapy fields treated, and the use of chemotherapy. Newer clinical assessment tools can potentially identify BCRL in patients with subclinical disease with prospective data suggesting that early diagnosis and management with noninvasive therapy can lead to excellent outcomes. Multiple therapies exist with treatments defined by the severity of BCRL present. Currently, the standard of care for BCRL in patients with significant LE is complex decongestive physiotherapy (CDP). Contemporary data also suggest that a multidisciplinary approach to the management of BCRL should begin prior to definitive treatment for breast cancer employing patient-specific surgical, radiation therapy, and chemotherapy paradigms that limit risks. Further, prospective clinical assessments before and after treatment should be employed to diagnose subclinical disease. In those patients who require aggressive locoregional management, prophylactic therapies and the use of CDP can help reduce the long-term sequelae of BCRL.

  19. What is the best term in Spanish to express the concept of cancer-related fatigue?

    Science.gov (United States)

    Centeno, Carlos; Portela Tejedor, María Angustias; Carvajal, Ana; San Miguel, Maria Teresa; Urdiroz, Julia; Ramos, Luis; De Santiago, Ana

    2009-05-01

    Fatigue is one of the most frequent symptoms in patients with cancer. No adequate term in Spanish has been defined to describe the English concept of fatigue. To identify the most suitable Spanish words that define the concept of fatigue and to check psychometric characteristics. Consensus with professional experts on Spanish words that best suit the English concept of fatigue. A prospective study on oncologic patients was also undertaken, which included an evaluation of the intensity of fatigue through visual numeric scales (VNS) where the words had been previously selected. The fatigue subscale of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire was taken as a reference. The experts highlighted the words cansancio, agotamiento, and debilidad (tiredness, exhaustion, and weakness) as the terms that best defined the concept of fatigue. In the psychometric assessment study, 100 patients were included, of which 61 (61%) presented diagnostic values for cancer-related fatigue in the FACT-F fatigue subscale (score 34/52 or lower). The VNS for the chosen terms obtained a high correlation with the FACT-F fatigue subscale results: cansancio (tiredness) r = -0.71, agotamiento (exhaustion) r = -0.74, debilidad (weakness) r = -0.74, with no statistical differences between them. For the detection of fatigue by means of the VNS, tiredness (cutoff point > or =4/10) gave sensitivity (S) 0.90 and specificity (E) 0.72; exhaustion (cutoff point > or =3/10) S 0.95 and E 0.90 and weakness (cutoff point > or =4/10) S 0.92 and E 0.72. The ROC curve was 0.88 for tiredness, 0.94 for exhaustion, and 0.92 for weakness, with no significant difference between the areas mentioned. The terms cansancio, agotamiento, and debilidad (tiredness, exhaustion, and weakness) are suitable for defining the English concept of fatigue in Spanish, and should be the preferred option for inclusion in evaluation tools.

  20. Efficacy and safety of transdermal buprenorphine in the management of children with cancer-related pain.

    Science.gov (United States)

    Ruggiero, Antonio; Coccia, Paola; Arena, Roberta; Maurizi, Palma; Battista, Andrea; Ridola, Vita; Attinà, Giorgio; Riccardi, Riccardo

    2013-03-01

    The current study investigated the efficacy, safety, tolerability, and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population. Sixteen pediatric patients with moderate to severe cancer-related pain not satisfactorily controlled with previous non-opioid therapies were enrolled. Transdermal buprenorphine was administered following a 72 hour schedule and rescue medication (tramadol) was allowed for breakthrough pain. Pain intensity was assessed using the Wong-Baker faces pain rating scale (WBS) and other parameters related to the global quality of life were evaluated. Children's evaluations of efficacy, compliance, and tolerability were recorded using numerical scales. Adverse events were monitored during the study and the medications needed to control opioid-related nausea and constipation were recorded. Eleven patients (68.75%) responded to transdermal buprenorphine after 2 weeks of treatment. Pain intensity measured with WBS decreased from 6.25 at baseline to 1.38 at Day +60 (P alimentation, play and activity, speech, and crying) significantly improved over the 60-day study period. Children's evaluations of compliance and tolerability of the drug were always positive over the entire period of treatment. No severe adverse events were recorded. Opioid-related nausea was well controlled with medication on request, and the need for laxative therapy was greater at the end of the second month of treatment. Transdermal buprenorphine was found to represent an efficient, safe and well tolerated approach to the management of children's chronic cancer pain. Copyright © 2012 Wiley Periodicals, Inc.

  1. Patients' and physiotherapists' belief in and use of acupuncture for cancer-related symptoms.

    Science.gov (United States)

    Enblom, Anna

    2017-08-01

    It is important to investigate attitudes to acupuncture, because therapists' and patients' expectations may affect the treatment outcome. To explore the use of and belief in acupuncture among oncological physiotherapists and to explore patients' interest in receiving acupuncture during cancer therapy and their belief in its effectiveness. 522 patients (80% female, mean age 67 years) reported on their interest in receiving acupuncture for nausea during radiotherapy treatment; a subgroup (n=198) additionally disclosed their belief in the effectiveness of acupuncture. 117 Swedish oncological physiotherapists (96% female, mean age 48 years) answered a questionnaire regarding their use of and belief in acupuncture. Of the patients initiating cancer therapy, 359 (69%) were interested in receiving acupuncture. The patients believed acupuncture to be effective for pain (79%), nausea (79%) and vasomotor symptoms (48%). Of the 117 physiotherapists, 66 (56%) practised acupuncture. Physiotherapists generally believed in the effectiveness of acupuncture. For pain, 89% believed that acupuncture was effective and 42% of them practised it. Similar responses were noted for chemotherapy-induced nausea (86% and 38%, respectively) and vasomotor symptoms (80% and 28%, respectively). Younger physiotherapists and patients were more likely to believe in the effectiveness of acupuncture compared with older ones. More than two thirds of patients with cancer were interested in receiving acupuncture during therapy. Patients and oncological physiotherapists believed that acupuncture was effective for cancer pain, nausea and vasomotor symptoms. Further studies of acupuncture for cancer-related symptoms and of the effect of patients' and clinicians' therapeutic relationships, including treatment expectations, would be welcome. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  2. Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury.

    Directory of Open Access Journals (Sweden)

    Sonia Podvin

    Full Text Available By virtue of its ability to regulate the composition of cerebrospinal fluid (CSF, the choroid plexus (CP is ideally suited to instigate a rapid response to traumatic brain injury (TBI by producing growth regulatory proteins. For example, Esophageal Cancer Related Gene-4 (Ecrg4 is a tumor suppressor gene that encodes a hormone-like peptide called augurin that is present in large concentrations in CP epithelia (CPe. Because augurin is thought to regulate senescence, neuroprogenitor cell growth and differentiation in the CNS, we evaluated the kinetics of Ecrg4 expression and augurin immunoreactivity in CPe after CNS injury. Adult rats were injured with a penetrating cortical lesion and alterations in augurin immunoreactivity were examined by immunohistochemistry. Ecrg4 gene expression was characterized by in situ hybridization. Cell surface augurin was identified histologically by confocal microscopy and biochemically by sub-cellular fractionation. Both Ecrg4 gene expression and augurin protein levels were decreased 24-72 hrs post-injury but restored to uninjured levels by day 7 post-injury. Protein staining in the supraoptic nucleus of the hypothalamus, used as a control brain region, did not show a decrease of auguin immunoreactivity. Ecrg4 gene expression localized to CPe cells, and augurin protein to the CPe ventricular face. Extracellular cell surface tethering of 14 kDa augurin was confirmed by cell surface fractionation of primary human CPe cells in vitro while a 6-8 kDa fragment of augurin was detected in conditioned media, indicating release from the cell surface by proteolytic processing. In rat CSF however, 14 kDa augurin was detected. We hypothesize the initial release and proteolytic processing of augurin participates in the activation phase of injury while sustained Ecrg4 down-regulation is dysinhibitory during the proliferative phase. Accordingly, augurin would play a constitutive inhibitory function in normal CNS while down

  3. Do videos improve website satisfaction and recall of online cancer-related information in older lung cancer patients?

    Science.gov (United States)

    Bol, Nadine; Smets, Ellen M A; Rutgers, M Mattijs; Burgers, Jacobus A; de Haes, Hanneke C J M; Loos, Eugène F; van Weert, Julia C M

    2013-09-01

    This study investigated the effects of personalized audiovisual information in addition to text on website satisfaction and recall of cancer-related online information in older lung cancer patients. An experiment using a 3 (condition: text only vs. text with nonpersonalized video vs. text with personalized video) by 2 (age patient: younger [video compared to text only. Text with personalized video also outperformed text with nonpersonalized video regarding emotional support from the website. Furthermore, text with video improved patients' recall of cancer-related information as compared to text only. Older patients recalled less information correctly than younger patients, except when we controlled for Internet use. Text with personalized audiovisual information can enhance website satisfaction and information recall. Internet use plays an important role in explaining recall of information. The results of this study can be used to develop effective health communication materials for cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Dyadic Associations Between Cancer-Related Stress and Fruit and Vegetable Consumption Among Colorectal Cancer Patients and Their Family Caregivers

    OpenAIRE

    Shaffer, Kelly M.; Kim, Youngmee; Llabre, Maria M.; Carver, Charles S.

    2015-01-01

    This study examined how stress from cancer affects fruit and vegetable consumption (FVC) in cancer patients and their family caregivers during the year following diagnosis. Colorectal cancer patients and their caregivers (92 dyads) completed questionnaires at two (T1), six (T2), and 12 months post-diagnosis (T3). Individuals reported perceived cancer-related stress (CRS) at T1 and days of adequate FVC at T1 through T3. Both patients and caregivers reported inadequate FVC during the first year...

  5. Measuring the societal burden of cancer: the cost of lost productivity due to premature cancer-related mortality in Europe.

    Science.gov (United States)

    Hanly, Paul; Soerjomataram, Isabelle; Sharp, Linda

    2015-02-15

    Every cancer-related death in someone of working age represents an economic loss to society. To inform priorities for cancer control, we estimated costs of lost productivity due to premature cancer-related mortality across Europe, for all cancers and by site, gender, region and country. Cancer deaths in 2008 were obtained from GLOBOCAN for 30 European countries across four regions. Costs were valued using the human capital approach. Years of productive life lost (YPLL) were computed by multiplying deaths between 15 and 64 years by working-life expectancy, then by country-, age- and gender-specific annual wages, corrected for workforce participation and unemployment. Lost productivity costs due to premature cancer-related mortality in Europe in 2008 were €75 billion. Male costs (€49 billion) were almost twice female costs (€26 billion). The most costly sites were lung (€17 billion; 23% of total costs), breast (€7 billion; 9%) and colorectum (€6 billion; 8%). Stomach cancer (in Southern and Central-Eastern Europe) and pancreatic cancer (in Northern and Western Europe) were also among the most costly sites. The average lost productivity cost per cancer death was €219,241. Melanoma had the highest cost per death (€312,798), followed by Hodgkin disease (€306,628) and brain and CNS cancer (€288,850). Premature mortality costs were 0.58% of 2008 European gross domestic product, highest in Central-Eastern Europe (0.81%) and lowest in Northern Europe (0.51%). Premature cancer-related mortality costs in Europe are significant. These results provide a novel perspective on the societal cancer burden and may be used to inform priority setting for cancer control. © 2014 UICC.

  6. Weight lifting for women at risk for breast cancer-related lymphedema: a randomized trial.

    Science.gov (United States)

    Schmitz, Kathryn H; Ahmed, Rehana L; Troxel, Andrea B; Cheville, Andrea; Lewis-Grant, Lorita; Smith, Rebecca; Bryan, Cathy J; Williams-Smith, Catherine T; Chittams, Jesse

    2010-12-22

    Clinical guidelines for breast cancer survivors without lymphedema advise against upper body exercise, preventing them from obtaining established health benefits of weight lifting. To evaluate lymphedema onset after a 1-year weight lifting intervention vs no exercise (control) among survivors at risk for breast cancer-related lymphedema (BCRL). A randomized controlled equivalence trial (Physical Activity and Lymphedema trial) in the Philadelphia metropolitan area of 154 breast cancer survivors 1 to 5 years postunilateral breast cancer, with at least 2 lymph nodes removed and without clinical signs of BCRL at study entry. Participants were recruited between October 1, 2005, and February 2007, with data collection ending in August 2008. Weight lifting intervention included a gym membership and 13 weeks of supervised instruction, with the remaining 9 months unsupervised, vs no exercise. Incident BCRL determined by increased arm swelling during 12 months (≥5% increase in interlimb difference). Clinician-defined BCRL onset was also evaluated. Equivalence margin was defined as doubling of lymphedema incidence. A total of 134 participants completed follow-up measures at 1 year. The proportion of women who experienced incident BCRL onset was 11% (8 of 72) in the weight lifting intervention group and 17% (13 of 75) in the control group (cumulative incidence difference [CID], -6.0%; 95% confidence interval [CI], -17.2% to 5.2%; P for equivalence = .04). Among women with 5 or more lymph nodes removed, the proportion who experienced incident BCRL onset was 7% (3 of 45) in the weight lifting intervention group and 22% (11 of 49) in the control group (CID, -15.0%; 95% CI, -18.6% to -11.4%; P for equivalence = .003). Clinician-defined BCRL onset occurred in 1 woman in the weight lifting intervention group and 3 women in the control group (1.5% vs 4.4%, P for equivalence = .12). In breast cancer survivors at risk for lymphedema, a program of slowly progressive weight lifting

  7. Self-administered Acupressure for Persistent Cancer-related Fatigue: Fidelity Considerations.

    Science.gov (United States)

    Wyatt, Gwen Karilyn; Frambes, Dawn Annette; Harris, Richard E; Arnedt, John Todd; Murphy, Susan L; Zick, Suzanna M

    2015-01-01

    Complementary therapies are frequently used by breast cancer patients for symptom management; however, documentation of the components of intervention fidelity for studies is not widely available. This report examines the components of intervention fidelity, as put forth by the Treatment Fidelity Workgroup of the Behavior Change Consortium at the National Institutes for Health (NIH-BCC Workgroup), within an ongoing acupressure study of breast cancer survivors with persistent cancer-related fatigue (PCRF). For the acupressure study, the research team designed a randomized, controlled trial (RCT) with 3 parallel groups: (1) stimulating acupressure (intervention group); (2) relaxing acupressure (intervention group); and (3) standard care (control group). At baseline and at wk 3 and wk 6 of the study, women in the acupressure study attended sessions for training and data collection at clinics in the counties of Michigan where they lived. The self-administration of acupressure occurred in participants' homes. Targeted enrollment for the acupressure study is 300 breast cancer survivors who had experienced moderate-to-severe PCRF lasting longer than 1 y beyond treatment. The women are being recruited from 5 counties in Michigan, using the Michigan Tumor Registry to identify potential participants. The subsample report includes 183 participants who have completed all 10 wk of the acupressure study. Most participants in the acupressure study are Caucasian, are married, and have some college education. The acupressure study's educators teach participants in the intervention groups to self-administer either relaxing or stimulating acupressure for a 30-min period on a daily basis for 6 wk. All 3 groups receive the usual care for breast cancer survivors. For the acupressure study, the participants log the frequency of the self-administered acupressure sessions and their fatigue levels. Symptom assessments are made for all groups by telephone in the acupressure study at wk 2

  8. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema.

    Science.gov (United States)

    Kaufman, David I; Shah, Chirag; Vicini, Frank A; Rizzi, Marisa

    2017-12-01

    This analysis was performed to assess the impact of early intervention following prospective surveillance using bioimpedance spectroscopy (BIS) to detect and manage breast cancer-related lymphedema (BCRL). From 8/2010 to 12/2016, 206 consecutive patients were evaluated with BIS. The protocol included pre-operative assessment with L-Dex as well as post-operative assessments at regular intervals. Patients with L-Dex scores >10 from baseline were considered to have subclinical BCRL and were treated with over-the-counter (OTC) compression sleeve for 4 weeks. High-risk patients were defined as undergoing axillary lymph node dissection (ALND), receiving regional nodal irradiation (RNI), or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP). Median follow-up was 25.9 months. Overall, 17% of patients had one high-risk feature, 8% two, and 7% had three. 9.8% of patients were diagnosed with subclinical BCRL with highest rates seen following ALND (23 vs. 7%, p = 0.01). Development of subclinical BCRL was associated with ALND and receipt of RNI. At last follow-up, no patients (0%) developed chronic, clinically detectable, BCRL. Subset analysis was performed of the 30 patients undergoing ALND. Median number of nodes removed was 18 and median number of positive nodes was 2. 77% received taxane chemotherapy, 62% axillary RT, and 48% had elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three. Seven patients (23%) had abnormally elevated L-Dex scores at some point during follow-up. To date, none has required CDP. The results of this study support prospective surveillance utilizing BIS initiated pre-operatively with subsequent post-operative follow-up measurements for the detection of subclinical BCRL. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with no cases progressing to chronic, clinically detectable

  9. [Mental Health Determines the Quality of Life in Patients With Cancer-Related Neuropathic Pain in Quito, Ecuador].

    Science.gov (United States)

    Gordillo Altamirano, Fernando; Fierro Torres, María José; Cevallos Salas, Nelson; Cervantes Vélez, María Cristina

    To identify the main factors determining the health related quality of life (HRQL) in patients with cancer-related neuropathic pain in a tertiary care hospital. A cross-sectional analytical study was performed on a sample of 237 patients meeting criteria for cancer-related neuropathic pain. Clinical and demographic variables were recorded including, cancer type, stage, time since diagnosis, pain intensity, physical functionality with the Palliative Performance Scale (PPS), and anxiety and depression with the Hospital Anxiety and Depression Scale (HADS). Their respective correlation coefficients (r) with HRQL assessed with the SF-36v2 Questionnaire were then calculated. Linear regression equations were then constructed with the variables that showed an r≥.5 with the HRQL. The HRQL scores of the sample were 39.3±9.1 (Physical Component) and 45.5±13.8 (Mental Component). Anxiety and depression strongly correlated with the mental component (r=-.641 and r=-.741, respectively) while PPS score correlated with the physical component (r=.617). The linear regression model that better explained the variance of the mental component was designed combining the Anxiety and Depression variables (R=77.3%; P<.001). The strong influence of psychiatric comorbidity on the HRQL of patients with cancer-related neuropathic pain makes an integral management plan essential for these patients to include interventions for its timely diagnosis and treatment. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  10. A humanised tissue-engineered bone model allows species-specific breast cancer-related bone metastasis in vivo.

    Science.gov (United States)

    Quent, Vmc; Taubenberger, A V; Reichert, J C; Martine, L C; Clements, J A; Hutmacher, D W; Loessner, D

    2018-02-01

    Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer-related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell-bone interactions. In this study, two established tissue-engineered bone constructs (TEBCs) were applied to a breast cancer-related metastasis model. A cylindrical medical-grade polycaprolactone-tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate-coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA-MB-231, SUM1315, and MDA-MB-231BO breast cancer cells were cultured in polyethylene glycol-based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer-related bone metastasis seen in patients. Copyright © 2017 John Wiley & Sons, Ltd.

  11. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review.

    Science.gov (United States)

    Baguley, Brenton J; Bolam, Kate A; Wright, Olivia R L; Skinner, Tina L

    2017-09-12

    Improvements in diet and/or exercise are often advocated during prostate cancer treatment, yet the efficacy of, and optimal nutrition and exercise prescription for managing cancer-related fatigue and quality of life remains elusive. The aim of this study is to systematically review the effects of nutrition and/or exercise on cancer-related fatigue and/or quality of life. A literature search was conducted in six electronic databases. The Delphi quality assessment list was used to evaluate the methodological quality of the literature. The study characteristics and results were summarized in accordance with the review's Population, Intervention, Control, Outcome (PICO) criteria. A total of 20 articles (one diet only, two combined diet and exercise, and seventeen exercise only studies) were included in the review. Soy supplementation improved quality of life, but resulted in several adverse effects. Prescribing healthy eating guidelines with combined resistance training and aerobic exercise improved cancer-related fatigue, yet its effect on quality of life was inconclusive. Combined resistance training with aerobic exercise showed improvements in cancer-related fatigue and quality of life. In isolation, resistance training appears to be more effective in improving cancer-related fatigue and quality of life than aerobic exercise. Studies that utilised an exercise professional to supervise the exercise sessions were more likely to report improvements in both cancer-related fatigue and quality of life than those prescribing unsupervised or partially supervised sessions. Neither exercise frequency nor duration appeared to influence cancer-related fatigue or quality of life, with further research required to explore the potential dose-response effect of exercise intensity. Supervised moderate-hard resistance training with or without moderate-vigorous aerobic exercise appears to improve cancer-related fatigue and quality of life. Targeted physiological pathways suggest

  12. Pre-diagnosis employment status and financial circumstances predict cancer-related financial stress and strain among breast and prostate cancer survivors.

    Science.gov (United States)

    Sharp, Linda; Timmons, Aileen

    2016-02-01

    Cancer may have a significant financial impact on patients, but the characteristics that predispose patients to cancer-related financial hardship are poorly understood. We investigated factors associated with cancer-related financial stress and strain in breast and prostate cancer survivors in Ireland, which has a complex mixed public-private healthcare system. Postal questionnaires were distributed to 1373 people diagnosed with cancer 3-24 months previously identified from the National Cancer Registry Ireland. Outcomes were cancer-related financial stress (impact of cancer diagnosis on household ability to make ends meet) and financial strain (concerns about household financial situation since cancer diagnosis). Modified Poisson regression was used to estimate relative risks (RR) for factors associated with cancer-related financial stress and strain. Seven hundred forty survivors participated (response rate = 54 %). Of the respondents, 48 % reported cancer-related financial stress and 32 % cancer-related financial strain. Compared to those employed at diagnosis, risk of cancer-related financial stress was significantly lower in those not working (RR = 0.71, 95 % CI 0.58-0.86) or retired (RR = 0.48, 95 % CI 0.34-0.68). It was significantly higher in those who had dependents; experienced financial stress pre-diagnosis; had a mortgage/personal loans; had higher direct medical out-of-pocket costs; and had increased household bills post-diagnosis. For cancer-related financial strain, significant associations were found with dependents, pre-diagnosis employment status and pre-diagnosis financial stress; risk was lower in those with higher direct medical out-of-pocket costs. Cancer-related financial stress and strain are common. Pre-diagnosis employment status and financial circumstances are important predictors of post-diagnosis financial wellbeing. These findings could inform development of tools to identify patients/survivors most in need of financial

  13. Are Survivors Who Report Cancer-Related Financial Problems More Likely to Forgo or Delay Medical Care?

    Science.gov (United States)

    Kent, Erin E.; Forsythe, Laura P.; Yabroff, K. Robin; Weaver, Kathryn E.; de Moor, Janet S.; Rodriguez, Juan L.; Rowland, Julia H.

    2015-01-01

    BACKGROUND Financial problems caused by cancer and its treatment can substantially affect survivors and their families and create barriers to seeking health care. METHODS The authors identified cancer survivors diagnosed as adults (n = 1556) from the nationally representative 2010 National Health Interview Survey. Using multivariable logistic regression analyses, the authors report sociodemographic, clinical, and treatment-related factors associated with perceived cancer-related financial problems and the association between financial problems and forgoing or delaying health care because of cost. Adjusted percentages using the predictive marginals method are presented. RESULTS Cancer-related financial problems were reported by 31.8% (95% confidence interval, 29.3%–34.5%) of survivors. Factors found to be significantly associated with cancer-related financial problems in survivors included younger age at diagnosis, minority race/ethnicity, history of chemotherapy or radiation treatment, recurrence or multiple cancers, and shorter time from diagnosis. After adjustment for covariates, respondents who reported financial problems were more likely to report delaying (18.3% vs 7.4%) or forgoing overall medical care (13.8% vs 5.0%), prescription medications (14.2% vs 7.6%), dental care (19.8% vs 8.3%), eyeglasses (13.9% vs 5.8%), and mental health care (3.9% vs 1.6%) than their counterparts without financial problems (all Pfinancial problems are not only disproportionately represented in survivors who are younger, members of a minority group, and have a higher treatment burden, but may also contribute to survivors forgoing or delaying medical care after cancer. PMID:23907958

  14. Cancer-related channel selection: an extension for a sample of women who have had a mammogram.

    Science.gov (United States)

    Johnson, J D; Meischke, H

    1993-01-01

    This study examines the impact of three major classes of factors, triggers, impediments, and demographics, on the use of four different communication channels: doctors, friends/family, organizations, and media. A sample of women over forty (n = 209) who had a mammography were asked which channels they had turned to within the last year for cancer-related information. The most important variable in the significant discriminant functions was the degree of interpersonal influence within one's social network. These results are discussed in terms of their theoretic and pragmatic implications for the development of communication campaigns related to mammography screening.

  15. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review

    OpenAIRE

    Brenton J. Baguley; Kate A. Bolam; Olivia R. L. Wright; Tina L. Skinner

    2017-01-01

    Background: Improvements in diet and/or exercise are often advocated during prostate cancer treatment, yet the efficacy of, and optimal nutrition and exercise prescription for managing cancer-related fatigue and quality of life remains elusive. The aim of this study is to systematically review the effects of nutrition and/or exercise on cancer-related fatigue and/or quality of life. Methods: A literature search was conducted in six electronic databases. The Delphi quality assessment list was ...

  16. Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol

    OpenAIRE

    Baguley, Brenton J.; Skinner, Tina L.; Leveritt, Michael D.; Wright, Olivia R. L.

    2017-01-01

    Background Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse ...

  17. Cancer-Related Causes of Death among HIV-Infected Patients in France in 2010: Evolution since 2000.

    Science.gov (United States)

    Vandenhende, Marie-Anne; Roussillon, Caroline; Henard, Sandrine; Morlat, Philippe; Oksenhendler, Eric; Aumaitre, Hugues; Georget, Aurore; May, Thierry; Rosenthal, Eric; Salmon, Dominique; Cacoub, Patrice; Costagliola, Dominique; Chêne, Geneviève; Bonnet, Fabrice

    2015-01-01

    The current study aimed at describing the distribution and characteristics of malignancy related deaths in human immunodeficiency virus (HIV) infected patients in 2010 and at comparing them to those obtained in 2000 and 2005. Data were obtained from three national surveys conducted in France in 2010, 2005 and 2000. The underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards involved in the management of HIV infection. Among the 728 deaths reported in 2010, 262 were cancer-related (36%). After a significant increase from 28% in 2000 to 33% in 2005 and 36% in 2010, cancers represent the leading cause of mortality in HIV infected patients. The proportion of deaths attributed to non-AIDS/non-hepatitis-related cancers significantly increased from 2000 to 2010 (11% of the deaths in 2000, 17% in 2005 and 22% in 2010, p2000, 13% in 2005 and 9% in 2010, p = 0.024). Particularly, the proportion of respiratory cancers significantly increased from 5% in 2000 to 6% in 2005 and 11% in 2010 (p = 0.004). Lung cancer was the most common cancer-related cause of death in 2010 (instead of non-Hodgkin lymphoma so far) and represented the leading cause of death in people living with HIV overall. Cancer prevention (especially smoking cessation), screening strategies and therapeutic management need to be optimized in HIV-infected patients in order to reduce mortality, particularly in the field of respiratory cancers.

  18. A Chinese Decoction, Kuan-Sin-Yin, Improves Autonomic Function and Cancer-Related Symptoms of Metastatic Colon Cancer.

    Science.gov (United States)

    Chien, Tsai-Ju; Liu, Chia-Yu; Ko, Pin-Hao; Hsu, Chung-Hua

    2016-03-01

    Kuan-Sin-Yin (KSY) is a traditional Chinese medicine (TCM) decoction, which has been shown to have cytostatic effects on cancer cells and involved in the TCM theory of promoting yin-yang balance.Sonce many cancer patients suffer from autonomic dysfunction (AD), which correspond to yin-yang imbalance in TCM. The aim of this study is to evaluate the possible effect of KSY in metastatic colon cancer (mCRC) patients with AD. We conducted a single-group experiment. Total 52 qualified patients were enrolled. Participants took the KSY daily for 2 weeks. The primary outcome was KSY efficacy as reflected in the heart rate variability (HRV) and electrical conductivity (µA) over 12 meridian points. Autonomic function was examined before and after the KSY intervention. The vagal and sympathetic tone were recorded by HRV; 12 meridian energies were measured using a meridian energy analysis device. Secondary outcomes were cancer-related symptoms and patient quality of life (QoL). The results showed that the KSY intervention improved AD via increasing the vagal tone (HF: P = .041), but not the sympathetic tone (LF: P = .154); total autonomic activity was significantly enhanced (HRV activity: P = .013). Intriguingly, energy increased more over the yin meridian (P = .010) than over the yang meridian (P = .015). Cancer-related symptoms and QoL were significantly improved (P yin-yang concept of energy. © The Author(s) 2015.

  19. Effects of aerobic exercise on cancer-related fatigue: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Tian, Li; Lu, Hui J; Lin, Lu; Hu, Yan

    2016-02-01

    Cancer-related fatigue (CRF) is the most commonly reported and most distressing symptom in cancer patients. Currently, there are no effective strategies for managing this condition. The purpose of this study is to compare the effects of aerobic exercise on CRF with the standard of care. A systematic search for randomized controlled trials (RCTs) was performed using the Cochrane Library, JBI Library, Embase, MEDLINE, Web of Science, China Biology Medicine (CBM), and China National Knowledge Infrastructure (CNKI). The risk of bias was critically evaluated, and data were independently extracted by two reviewers. All of the analyses were performed using Review Manager 5. A total of 26 qualified studies that included 2830 participants (aerobic exercise, 1426; control, 1404) were included in the meta-analysis. Cancer patients who completed adjuvant therapy in the aerobic exercise group reported reduced CRF levels relative to patients undergoing the standard of care. Aerobic exercise had a moderate effect on CRF for patients not currently undergoing anticancer treatment. Supervised aerobic exercise, exercise for 20–30 min/session, or exercise three times/week had a small effect on CRF. Exercise for 50 min/session or exercise two sessions/week had a significant effect on patient CRF, whereas 8 weeks of exercise had a moderate effect. Aerobic exercise is effective for the management of CRF, especially for patients who have completed adjuvant therapy. Cancer patients can make more informed choices regarding their cancer-related fatigue management based on the best available evidence.

  20. Financial Impact of Colorectal Cancer and Its Consequences: Associations Between Cancer-Related Financial Stress and Strain and Health-Related Quality of Life.

    Science.gov (United States)

    Sharp, Linda; O'Leary, Eamonn; O'Ceilleachair, Alan; Skally, Mairead; Hanly, Paul

    2018-01-01

    The financial impact and consequences of cancer on the lives of survivors remain poorly understood. This is especially true for colorectal cancer. We investigated objective cancer-related financial stress, subjective cancer-related financial strain, and their association with health-related quality of life in colorectal cancer survivors. This was a cross-sectional postal survey. The study was conducted in Ireland, which has a mixed public-private healthcare system. Colorectal cancer survivors, diagnosed 6 to 37 months prior, were identified from the population-based National Cancer Registry. Cancer-related financial stress was assessed as impact of cancer on household ability to make ends meet and cancer-related financial strain by feelings about household financial situation since cancer diagnosis. Health-related quality of life was based on European Organisation for Research and Treatment of Cancer QLQ-C30 global health status. Logistic regression was used to identify associations between financial stress and strain and low health-related quality of life (lowest quartile, score ≤50). A total of 493 survivors participated. Overall, 41% reported cancer-related financial stress and 39% cancer-related financial strain; 32% reported both financial stress and financial strain. After adjustment for sociodemographic and clinical variables, the odds of low health-related quality of life were significantly higher in those who reported cancer-related financial stress postdiagnosis compared with those who reported no change in financial stress postcancer (OR = 2.54 (95% CI, 1.62-3.99)). The odds of low health-related quality of life were also significantly higher in those with worse financial strain postdiagnosis (OR =1.73 (95% CI, 1.09-2.72)). The OR for those with both cancer-related financial stress and financial strain was 2.59 (95% CI, 1.59-4.22). Survey responders were younger, on average, than nonresponders. Responders and nonresponders may have differed in cancer-related

  1. A high-throughput quantitative expression analysis of cancer-related genes in human HepG2 cells in response to limonene, a potential anticancer agent.

    Science.gov (United States)

    Hafidh, Rand R; Hussein, Saba Z; MalAllah, Mohammed Q; Abdulamir, Ahmed S; Abu Bakar, Fatimah

    2017-11-14

    Citrus bioactive compounds, as active anticancer agent, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted. The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene. The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity. The apoptotic induction was detected by flow cytometry and confocal fluorescence microscope. Two of pro-apoptotic events, caspase-3 activation and phosphatidylserine translocation were manifested by confocal fluorescence microscopy. High-throughput real-time PCR was used to profile 1023 cancer-related genes in 16 different gene families related to the cancer development. In comparison to untreated cells, limonene increased the percentage of apoptotic cells up to 89.61%, by flow cytometry, and 48.2% by fluorescence microscopy. There was a significant limonene-driven differential gene expression of HepG2 cells in 15 different gene families. Limonene was shown to significantly (>2log) up-regulate and down-regulate 14 and 59 genes, respectively. The affected gene families, from most to least affected, were apoptosis induction, signal transduction, cancer genes augmentation, alteration in kinases expression, inflammation, DNA damage repair, and cell cycle proteins. The current study reveals that limonene could be a promising, cheap, and effective anticancer compound. The broad spectrum of limonene anticancer activity is interesting for anticancer drug development. Further research is needed to confirm the current findings and to examine the anticancer potential of limonene along with underlying mechanisms on different cell lines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review

    Science.gov (United States)

    Baguley, Brenton J.; Bolam, Kate A.; Wright, Olivia R. L.

    2017-01-01

    Background: Improvements in diet and/or exercise are often advocated during prostate cancer treatment, yet the efficacy of, and optimal nutrition and exercise prescription for managing cancer-related fatigue and quality of life remains elusive. The aim of this study is to systematically review the effects of nutrition and/or exercise on cancer-related fatigue and/or quality of life. Methods: A literature search was conducted in six electronic databases. The Delphi quality assessment list was used to evaluate the methodological quality of the literature. The study characteristics and results were summarized in accordance with the review’s Population, Intervention, Control, Outcome (PICO) criteria. Results: A total of 20 articles (one diet only, two combined diet and exercise, and seventeen exercise only studies) were included in the review. Soy supplementation improved quality of life, but resulted in several adverse effects. Prescribing healthy eating guidelines with combined resistance training and aerobic exercise improved cancer-related fatigue, yet its effect on quality of life was inconclusive. Combined resistance training with aerobic exercise showed improvements in cancer-related fatigue and quality of life. In isolation, resistance training appears to be more effective in improving cancer-related fatigue and quality of life than aerobic exercise. Studies that utilised an exercise professional to supervise the exercise sessions were more likely to report improvements in both cancer-related fatigue and quality of life than those prescribing unsupervised or partially supervised sessions. Neither exercise frequency nor duration appeared to influence cancer-related fatigue or quality of life, with further research required to explore the potential dose-response effect of exercise intensity. Conclusion: Supervised moderate-hard resistance training with or without moderate-vigorous aerobic exercise appears to improve cancer-related fatigue and quality of life

  3. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Brenton J. Baguley

    2017-09-01

    Full Text Available Background: Improvements in diet and/or exercise are often advocated during prostate cancer treatment, yet the efficacy of, and optimal nutrition and exercise prescription for managing cancer-related fatigue and quality of life remains elusive. The aim of this study is to systematically review the effects of nutrition and/or exercise on cancer-related fatigue and/or quality of life. Methods: A literature search was conducted in six electronic databases. The Delphi quality assessment list was used to evaluate the methodological quality of the literature. The study characteristics and results were summarized in accordance with the review’s Population, Intervention, Control, Outcome (PICO criteria. Results: A total of 20 articles (one diet only, two combined diet and exercise, and seventeen exercise only studies were included in the review. Soy supplementation improved quality of life, but resulted in several adverse effects. Prescribing healthy eating guidelines with combined resistance training and aerobic exercise improved cancer-related fatigue, yet its effect on quality of life was inconclusive. Combined resistance training with aerobic exercise showed improvements in cancer-related fatigue and quality of life. In isolation, resistance training appears to be more effective in improving cancer-related fatigue and quality of life than aerobic exercise. Studies that utilised an exercise professional to supervise the exercise sessions were more likely to report improvements in both cancer-related fatigue and quality of life than those prescribing unsupervised or partially supervised sessions. Neither exercise frequency nor duration appeared to influence cancer-related fatigue or quality of life, with further research required to explore the potential dose-response effect of exercise intensity. Conclusion: Supervised moderate-hard resistance training with or without moderate-vigorous aerobic exercise appears to improve cancer-related fatigue and

  4. Bioinformatics Study of Cancer-Related Mutations within p53 Phosphorylation Site Motifs

    Directory of Open Access Journals (Sweden)

    Xiaona Ji

    2014-07-01

    Full Text Available p53 protein has about thirty phosphorylation sites located at the N- and C-termini and in the core domain. The phosphorylation sites are relatively less mutated than other residues in p53. To understand why and how p53 phosphorylation sites are rarely mutated in human cancer, using a bioinformatics approaches, we examined the phosphorylation site and its nearby flanking residues, focusing on the consensus phosphorylation motif pattern, amino-acid correlations within the phosphorylation motifs, the propensity of structural disorder of the phosphorylation motifs, and cancer mutations observed within the phosphorylation motifs. Many p53 phosphorylation sites are targets for several kinases. The phosphorylation sites match 17 consensus sequence motifs out of the 29 classified. In addition to proline, which is common in kinase specificity-determining sites, we found high propensity of acidic residues to be adjacent to phosphorylation sites. Analysis of human cancer mutations in the phosphorylation motifs revealed that motifs with adjacent acidic residues generally have fewer mutations, in contrast to phosphorylation sites near proline residues. p53 phosphorylation motifs are mostly disordered. However, human cancer mutations within phosphorylation motifs tend to decrease the disorder propensity. Our results suggest that combination of acidic residues Asp and Glu with phosphorylation sites provide charge redundancy which may safe guard against loss-of-function mutations, and that the natively disordered nature of p53 phosphorylation motifs may help reduce mutational damage. Our results further suggest that engineering acidic amino acids adjacent to potential phosphorylation sites could be a p53 gene therapy strategy.

  5. Efficacy of Compound Kushen Injection in Relieving Cancer-Related Pain: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yu-ming Guo

    2015-01-01

    Full Text Available Despite widespread popular use of complementary and alternative medicine (CAM therapies, a rigorous evidence based on the efficacy of compound kushen injection (CKI for cancer-related pain is lacking. In this study, we evaluated the efficacy and safety of compound kushen injection and provided information for current or future research and clinical application. Sixteen trials were identified with a total of 1564 patients. The total pain relief rate of CKI plus chemotherapy is better than chemotherapy except for colorectal cancer. The treatment groups achieved a reduction in the incidences of leukopenia and gastrointestinal, hepatic, and renal functional lesion. However, there is paucity of multi-institutional RCTs evaluating compound kushen injection for cancer pain with adequate power, duration, and sham control. The quantity and quality of RCTs are lower so that we still have to boost the research level through scientific design and normative report.

  6. A stepped care stress management intervention on cancer-related traumatic stress symptoms among breast cancer patients—a randomized study in group vs. individual setting.

    Science.gov (United States)

    Rissanen, Ritva; Nordin, Karin; Ahlgren, Johan; Arving, Cecilia

    2015-09-01

    To evaluate the mode of delivery of a stress management intervention, in a group or individual setting, on self-reported cancer-related traumatic stress symptoms. A secondary aim was to evaluate a stepped care approach. All study participants (n = 425), who were female, newly diagnosed with breast cancer and receiving standard oncological care were offered Step I of the stepped care approach, a stress management education (SME). Thereafter, they were screened for cancer-related traumatic stress symptoms, and, if present (n = 304), were invited to join Step II, a more intense intervention, derived from cognitive behavioral therapy, to which they were randomized to either a group (n = 77) or individual (n = 78) setting. To assess cancer-related traumatic stress symptoms, participants completed the Impact of Event Scale and the Hospital Anxiety and Depression Scale at the time of inclusion, three-months post-inclusion and approximately 12-months post-inclusion. The SME did not significantly decrease any of the cancer-related traumatic stress symptoms. No statistically significant differences were found between the group and the individual setting interventions. However, only 54% of the participants attended the group setting compared to 91% for the individual setting. The mode of delivery had no effect on the cancer-related traumatic stress symptoms; however, the individual setting was preferred. In future studies, a preference-based RCT design will be recommended for evaluating the different treatment effects. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Could Kinesio tape replace the bandage in decongestive lymphatic therapy for breast-cancer-related lymphedema? A pilot study.

    Science.gov (United States)

    Tsai, Han-Ju; Hung, Hsiu-Chuan; Yang, Jing-Lan; Huang, Chiun-Sheng; Tsauo, Jau-Yih

    2009-11-01

    The purpose of this study is to compare the treatment and retention effects between standard decongestive lymphatic therapy (DLT) combined with pneumatic compression (PC) and modified DLT, in which the use of a short-stretch bandage is replaced with the use of Kinesio tape (K-tape) combined with PC. Forty-one patients with unilateral breast-cancer-related lymphedema for at least 3 months were randomly grouped into the DLT group (bandage group, N = 21) or the modified DLT group (K-tape group, N = 20). Skin care, 30-min manual lymphatic drainage, 1-h pneumatic compression therapy, application of a short-stretch bandage or K-tape for each group, and a 20-min physical therapy exercise were given during every treatment session. Patient evaluation items included physical therapy assessment, limb size, water composition of the upper extremity, lymphedema-related symptoms, quality of life, and patients' acceptance to the bandage or tape. There was no significant difference between groups in all outcome variables (P > 0.05) through the whole study period. Excess limb size (circumference and water displacement) and excess water composition were reduced significantly in the bandage group; excess circumference and excess water composition were reduced significantly in the tape group. The acceptance of K-tape was better than the bandage, and benefits included longer wearing time, less difficulty in usage, and increased comfort and convenience (P tape could replace the bandage in DLT, and it could be an alternative choice for the breast-cancer-related lymphedema patient with poor short-stretch bandage compliance after 1-month intervention. If the intervention period was prolonged, we might get different conclusion. Moreover, these two treatment protocols are inefficient and cost time in application. More efficient treatment protocol is needed for clinical practice.

  8. Non-steroidal anti-inflammatory drugs (NSAIDs) for cancer-related pain in children and adolescents.

    Science.gov (United States)

    Cooper, Tess E; Heathcote, Lauren C; Anderson, Brian; Grégoire, Marie-Claude; Ljungman, Gustaf; Eccleston, Christopher

    2017-07-24

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for persisting pain in children acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences.We designed a suite of seven reviews in chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) to review the evidence for children's pain using pharmacological interventions.As one of the leading causes of mortality and morbidity for children and adolescents in the world today, childhood cancer (and its associated pain) is a major health concern. Specific mortality and morbidity data relating to children are not currently identified. All childhood cancer rates are on the rise; for example, in the USA approximately 10,380 children aged under 15 years were expected to be diagnosed with cancer by the end of 2016. However, with survival rates also increasing, over 80% of paediatric cancer patients are expected to survive for five years or more, thus identifying the need to address pain management in this population.Cancer pain in infants, children, and adolescents is primarily nociceptive pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs. Cancer-related pain generally occurs as a result of perioperative procedures, nerve damage caused by radiation or chemotherapy treatments, or mucositis. However, this review focused on pain caused directly by the tumour

  9. The effects of complex exercise on shoulder range of motion and pain for women with breast cancer-related lymphedema: a single-blind, randomized controlled trial.

    Science.gov (United States)

    Park, Jin-Hyuck

    2017-07-01

    This study was to investigate the effects of complex exercise on shoulder range of motion and pain for women with breast cancer-related lymphedema. 69 women participated in this study and then they were randomly allocated to complex exercise group (n = 35) or the conventional decongestive therapy group (n = 34). All subjects received 8 sessions for 4 weeks. To identify the effects on shoulder range of motion and pain, goniometer and visual analog scale were used, respectively. The outcome measurements were performed before and after the 4 week intervention. After 4 weeks, complex exercise group had greater improvements in shoulder range of motion and pain compared with the conventional decongestive therapy group (p women with breast cancer-related lymphedema. Complex exercise would be useful to improve shoulder range of motion and pain of the women with breast cancer-related lymphedema.

  10. Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate ceramics.

    Science.gov (United States)

    Tang, Zhurong; Wang, Zhe; Qing, Fangzhu; Ni, Yilu; Fan, Yujiang; Tan, Yanfei; Zhang, Xingdong

    2015-03-01

    Porous calcium phosphate ceramics (CaP ceramics) could induce ectopic bone formation which was regulated by various signal molecules. In this work, bone marrow mesenchymal stem cells (MSCs) were cultured on the surface of osteoinductive hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramics in comparison with control (culture plate) for up to 14 days to detect the signal molecules which might be affected by the CaP ceramics. Without adding osteogenic factors, MSCs cultured on HA and BCP both expressed higher Runx2, Osterix, collagen type I, osteopontin, bone sialoprotein, and osteocalcin at various stages compared with control, thus confirmed the osteoblastic differentiation of MSCs. Later study demonstrated the messenger RNA level of bone morphogenetic protein 2 (BMP2) and BMP4 were also significantly enhanced by HA and BCP. Furthermore, Smad1, 4, 5, and Dlx5, the main molecules in the BMP/Smads signaling pathway, were upregulated by HA and BCP. Moreover, the higher expression of Smads and BMP2, 4 in BCP over HA, corresponded to the better performance of BCP in stimulating in vitro osteoblastic differentiation of MSCs. This was in accordance with the better osteoinductivity of BCP over HA in vivo. Altogether, these results implied that the CaP ceramics may initiate the osteoblastic differentiation of MSCs by influencing the expression of molecules in BMP/Smads pathway. © 2014 Wiley Periodicals, Inc.

  11. Far infrared ray (FIR) therapy: An effective and oncological safe treatment modality for breast cancer related lymphedema.

    Science.gov (United States)

    Li, Ke; Xia, Liang; Liu, Ning Fei; Nicoli, Fabio; Constantinides, Joannis; D'Ambrosia, Christopher; Lazzeri, Davide; Tremp, Mathias; Zhang, Ju Fang; Zhang, Yi Xin

    2017-07-01

    The incidence of breast cancer related lymphedema is approximately 5%. Far infrared ray (FIR) treatment can potentially reduce fluid volume and extremity circumference as well as the frequency of dermato-lymphangitis (DLA). However, there is no published data on the oncological safety of FIR and the potential for activation of any residual breast cancer cells. The aim of this study is to investigate the safety of far infrared ray (FIR) treatment of postmastectomy lymphedema, clinically and in vitro. Patients who underwent mastectomy more than 5years ago complicated by upper extremity lymphedema for more than 1year were included. The enrolled patients were divided into an FIR treatment group and a control group (conservative treatment using bandage compression). Outcome measures included tumor markers (CA153, CA125), ultrasonography of relevant structures and monitoring for adverse reactions 1year after treatment. For the in vitro part of the study, the effects of FIR on human breast adenocarcinoma cell lines (MCF7, MDA-MB231) compared to the effects of FIR on human dermal fibroblasts as a control were considered. The viability, proliferation, cell cycle and apoptotic statistics of the adenocarcinoma and human dermal fibroblast cell lines were analyzed and compared. Results demonstrated that after treatment with FIR, tumor marker (CA153, CA125) concentrations in both the FIR and control groups were not elevated. There was no statistically significant difference between FIR and control group marker expression (p>0.05). Furthermore, no patients were diagnosed with lymphadenectasis or newly enlarged lymph nodes in these two groups. Importantly, there were no adverse events in either group. The in vitro experiment indicated that FIR radiation does not affect viability, proliferation, cell cycle and apoptosis of fibroblasts, MCF-7 and MDA-MB-231 cells. FIR should be considered as feasible and safe for the treatment of breast cancer related lymphedema patients 5years

  12. International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

    Science.gov (United States)

    Weis, Joachim; Tomaszewski, Krzysztof A; Hammerlid, Eva; Ignacio Arraras, Juan; Conroy, Thierry; Lanceley, Anne; Schmidt, Heike; Wirtz, Markus; Singer, Susanne; Pinto, Monica; Alm El-Din, Mohamed; Compter, Inge; Holzner, Bernhard; Hofmeister, Dirk; Chie, Wei-Chu; Czeladzki, Marek; Harle, Amelie; Jones, Louise; Ritter, Sabrina; Flechtner, Hans-Henning; Bottomley, Andrew

    2017-05-01

    The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. An examination of cancer-related fatigue through proposed diagnostic criteria in a sample of cancer patients in Taiwan

    Directory of Open Access Journals (Sweden)

    Su Wei-Ju

    2011-09-01

    Full Text Available Abstract Background Fatigue among cancer patients has often been reported in the literature; however, great variations have been documented, ranging from 15% to 90%, probably due to the lack of a widely accepted definition and established diagnostic criteria for cancer-related fatigue. The objective of this study was to evaluate the proposed International Statistical Classification of Diseases and Related Health Problems (10th revision (ICD-10 criteria in a sample of cancer patients from a medical center and a regional teaching hospital in northern Taiwan. More accurate prevalence estimates of CRF may result in improved diagnoses and management of one of the most common symptoms associated with cancer and its treatment. Methods Since self-reporting from patients is the most effective and efficient method to measure fatigue, the ICD-10 criteria for fatigue were used. The ICD-10 criteria questionnaire was translated into Chinese and was approved by experts. Patients were recruited from outpatient palliative and oncology clinics and from palliative and oncology inpatient units. Results Of the 265 cancer patients that were interviewed between 21 October 2008 and 28 October 2009, 228 (86% reported having at least 2 weeks of fatigue in the past month, and further evaluation with the ICD-10 criteria showed that 132 (49.8% had cancer-related fatigue. Internal consistency was very good, which was indicated by a Cronbach alpha of 0.843. Conclusion The prevalence of diagnosable CRF in the patients in this sample, of whom most were under palliative treatment, was 49.8%, which was probably somewhat lower than in some of the previous reports that have used less-strict criteria. In addition, among the various criteria of the proposed diagnostic criteria, the most frequently reported symptoms in our sample populations were regarding sleep disturbance and physical factors. Although they will require further replication in other samples, these formal diagnostic

  14. "Cancer-Related Fatigue: A Systematic and Meta-Analytic Review of Nonpharmacological Therapies for Cancer Patients:" Correction to Kangas, Bovbjerg, and Montgomery (2008)

    Science.gov (United States)

    Kangas, Maria; Bovbjerg, Dana H.; Montgomery, Guy H.

    2009-01-01

    Reports an error in "Cancer-related fatigue: A systematic and meta-analytic review of non-pharmacological therapies for cancer patients" by Maria Kangas, Dana H. Bovbjerg and Guy H. Montgomery (Psychological Bulletin, 2008[Sep], Vol 134[5], 700-741). The URL to the Supplemental Materials for the article is listed incorrectly in two places in the…

  15. Cancer-Related Fatigue and Rehabilitation : A Randomized Controlled Multicenter Trial Comparing Physical Training Combined With Cognitive-Behavioral Therapy With Physical Training Only and With No Intervention

    NARCIS (Netherlands)

    van Weert, E.; May, A.M.; Korstjens, I.; Post, W.J.; van der Schans, C.P.; van den Borne, B.; Mesters, I.; Ros, W.J.G.; Hoekstra-Weebers, J.E.H.M.

    2010-01-01

    Background. Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. Objective. This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with

  16. Assessment of Volume Measurement of Breast Cancer-Related Lymphedema by Three Methods: Circumference Measurement, Water Displacement, and Dual Energy X-Ray Absorptiometry

    DEFF Research Database (Denmark)

    Gjørup, Caroline; Zerahn, B.; Hendel, Helle Westergren

    2010-01-01

    Background: Following treatment for breast cancer 12%-60% develop breast cancer-related lymphedema (BCRL). There are several ways of assessing BCRL. Circumference measurement (CM) and water displacement (WD) for volume measurements (VM) are frequently used methods in practice and research...

  17. Global Variations in the Level of Cancer-Related Research Activity and Correlation to Cancer-Specific Mortality: Proposal for a Global Curriculum.

    Science.gov (United States)

    Are, C; Caniglia, A; Mohammed, Malik; Smith, L; Cummings, Charmaine; Lecoq, Carine; Berman, R; Audisio, R; Wyld, L

    2018-03-01

    The aim of this study was to analyze global variations in the level of cancer-related research activity and correlate this with cancer-specific mortality. The SCOPUS database was explored to obtain data relating to the number of cancer-related publications per country. Cancer-specific mortality rates were obtained from the World Health Organization. Global variations in the level of scholarly activity were analyzed and correlated with variations in cancer-specific mortality. Data for 142 countries were obtained and significant variations in the level of research activity was noted. The level of research activity increased with rising socio-economic status. The United States was the most prolific country with 222,300 publications followed by Japan and Germany. Several countries in different regions of the world had a low level of research activity. An inverse relationship between the level of research activity and cancer-specific mortality was noted. This relationship persisted even in countries with a low level of research activity. The socioeconomic status of a nation and geographic location (continent) had a mixed influence with an overall apparent correlation with cancer-related research activity. This study demonstrates significant global variation in the level of cancer-related research activity and a correlation with cancer-specific mortality. The presence of a minimum set of standards for research literacy, as proposed by the European Society of Surgical Oncology and the Society of Surgical Oncology may contribute to enhanced research activity and improve outcomes for cancer patients worldwide.

  18. Association between lymphedema self-care adherence and lymphedema outcomes among women with breast cancer-related lymphedema.

    Science.gov (United States)

    Brown, Justin C; Kumar, Anagha; Cheville, Andrea L; Tchou, Julia C; Troxel, Andrea B; Harris, Susan R; Schmitz, Kathryn H

    2015-04-01

    The aim of this study was to determine whether adherence to self-care modalities for breast cancer-related lymphedema (BCRL) predicts BCRL outcomes among 128 breast cancer survivors who participated in the 12-mo physical activity and lymphedema trial. This was a prospective cohort study. Adherence to ten BCRL self-care modalities, as recommended in the clinical practice guidelines for the management of BCRL, was assessed by a questionnaire at baseline. BCRL outcomes assessed at baseline and 12 mos included volumetry, circumferences, bioimpedence spectroscopy, the Norman lymphedema survey, and therapist-defined lymphedema exacerbations requiring treatment. Generalized linear models were used to estimate the relationship between adherence to BCRL self-care modalities and the likelihood of experiencing a BCRL outcome. Adherence to BCRL self-care activities did not predict experiencing any BCRL outcomes at 12 mos. Levels of adherence to BCRL self-care modalities did not predict a 5% or greater decrease in interlimb volume (Ptrend = 0.79), 5% or greater decrease in the sum of interlimb arm circumferences (Ptrend = 0.47), 10% or greater decrease in bioimpedence spectroscopy (Ptrend = 0.83), 1 or greater decrease in self-reported lymphedema symptoms (Ptrend = 0.91), or therapist-defined lymphedema exacerbation requiring treatment (Ptrend = 0.84). Our findings suggest that levels of BCRL self-care adherence do not predict BCRL outcomes among breast cancer survivors with stable lymphedema who were followed for 12 mos.

  19. Dyadic associations between cancer-related stress and fruit and vegetable consumption among colorectal cancer patients and their family caregivers.

    Science.gov (United States)

    Shaffer, Kelly M; Kim, Youngmee; Llabre, Maria M; Carver, Charles S

    2016-02-01

    This study examined how stress from cancer affects fruit and vegetable consumption (FVC) in cancer patients and their family caregivers during the year following diagnosis. Colorectal cancer patients and their caregivers (92 dyads) completed questionnaires at two (T1), six (T2), and 12 months post-diagnosis (T3). Individuals reported perceived cancer-related stress (CRS) at T1 and days of adequate FVC at T1 through T3. Both patients and caregivers reported inadequate FVC during the first year post-diagnosis. Latent growth modeling with actor-partner interdependence modeling revealed that, at T1, one's own greater CRS was associated with one's partner having fewer concurrent days of adequate FVC (ps = .01). Patients' greater CRS predicted their own more pronounced rebound pattern in FVC (p = .01); both patients' and caregivers' CRS marginally predicted their partners' change in FVC (p = .09). Findings suggest that perceived stress from cancer hinders FVC around the diagnosis, but motivates positive dietary changes by the end of the first year.

  20. Lymphatico-venous anastomosis as treatment for breast cancer-related lymphedema: a prospective study on quality of life.

    Science.gov (United States)

    Cornelissen, Anouk J M; Kool, Melissa; Lopez Penha, Tiara R; Keuter, Xavier H A; Piatkowski, Andrzej A; Heuts, E; van der Hulst, René R W J; Qiu, Shan Shan

    2017-06-01

    Lymphedema is a chronic and disabling sequel of breast cancer treatment that can be treated by lymphatico-venous anastomosis (LVA). Artificial connections between the venous and lymphatic system are performed supermicrosurgically. This prospective study analyses the effect of LVA on quality of life. A prospective study was performed between November 2015 and July 2016 on consecutive patients in the Maastricht University Medical Centre. Quality of life was considered as the primary outcome, and the Lymphedema International Classification of Functioning (Lymph-ICF) questionnaire was used. Discontinuation of compressive stockings and arm volume, using the Upper Extremity Lymphedema index (UEL-index), were the secondary outcomes. Twenty women with early-stage breast cancer-related lymphedema (BCRL) were included. The mean age was 55.9 ± 4 years and the median BMI was 25.1 [21-30] kg/m 2 . The mean follow-up was 7.8 ± 1.5 months. Statistically significant improvement in quality of life was achieved in the total score and for all the quality of life domains after one year of follow-up (p < 0.05). The discontinuation rate in compressive stockings use was 85%. The difference in mean relative volume did not show a statistically significant decrease. LVA for early-stage BCRL resulted in a significant improvement in quality of life and a high rate in stocking discontinuation.

  1. Cancer-related fatigue in breast cancer patients after surgery: a multicomponent model using partial least squares-path modeling.

    Science.gov (United States)

    Bortolon, Catherine; Krikorian, Alicia; Carayol, Marion; Brouillet, Denis; Romieu, Gilles; Ninot, Gregory

    2014-04-01

    The aim of this study is to examine factors contributing to cancer-related fatigue (CRF) in breast cancer patients who have undergone surgery. Sixty women (mean age: 50.0) completed self-rated questionnaires assessing components of CRF, muscular and cognitive functions. Also, physiological and subjective data were gathered. Data were analyzed using partial least squares variance-based structural equation modeling in order to examine factors contributing to CRF after breast surgery. The tested model was robust in terms of its measurement quality (reliability and validity). According to the structural model results, emotional distress (β = 0.59; p accounting for 61% of the explained variance. Also, emotional distress (β = 0.41; p accounted for 41% of the explained variance. However, the relationship between low physical function and CRF was weak and nonsignificant (β = 0.01; p > 0.05). Emotional distress, altered vigilance capacity, and pain are associated with CRF in postsurgical breast cancer. In addition, emotional distress and pain are related to diminished physical function, which, in turn, has no significant impact on CRF. The current model should be examined in subsequent phases of the treatment (chemotherapy and/or radiotherapy) when side effects are more pronounced and may lead to increased intensity of CRF and low physical function. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Body image mediates the effect of cancer-related stigmatization on depression: A new target for intervention.

    Science.gov (United States)

    Esser, Peter; Mehnert, Anja; Johansen, Christoffer; Hornemann, Beate; Dietz, Andreas; Ernst, Jochen

    2018-01-01

    Because cancer-related stigmatization is prevalent but difficult to change, research on its impact on psychological burden and respective intervening variables is needed. Therefore, we investigated the effect of stigmatization on depressive symptomatology and whether body image mediates this relationship. This bicentric study assessed patients of 4 major tumor entities. We measured stigmatization (SIS-D), depressive symptomatology (PHQ-9), and body image (FKB-20). Applying multiple mediator analyses, we calculated the total effect of stigmatization on depressive symptomatology and the indirect effects exerted via the 2 body image scales rejecting body evaluation and vital body dynamics. Among the 858 cancer patients recruited (breast: n = 297; prostate: n = 268; colorectal: n = 168; lung: n = 125), stigmatization showed total effects on depressive symptomatology across all stigma dimensions (all p total sample  Body image as a whole was shown to mediate the effect across all samples (γ total sample  = .04, 95%-CI: 0.03-0.06). Among the total sample and prostate cancer patients, the mediating effect of rejecting body evaluation was significantly larger than the effect of vital body dynamics (d total sample  = .02, 95%-CI: 0.01-0.04). Perceived stigmatization is an important and generalizable risk factor for depressive symptomatology among cancer patients. Apart from interventions addressing stigmatization, improving body image could additionally help to reduce the psychological burden in stigmatized patients. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Physical Exercise and Cancer-Related Fatigue in Hospitalized Patients: Role of the Clinical Nurse Leader in Implementation of Interventions.

    Science.gov (United States)

    McGowan, Katrina

    2016-02-01

    Guidelines suggest that aerobic endurance training and moderate resistance training lessen the effects of cancer-related fatigue (CRF). However, specifics regarding frequency, intensity, and type of physical activity required to alleviate fatigue are less specific. In addition, outcomes of these interventions during the initial stages of active treatment are not well documented. The purpose of this article is to review the current evidence-based literature regarding the effects of physical exercise on CRF and the role that the clinical nurse leader (CNL) can play in implementing interventions to address CRF and promote physical exercise to improve patient outcomes. A literature review of the effect of physical exercise on CRF was conducted using the CINAHL®, PubMed, and Google Scholar databases. As leaders in health care, CNLs have the knowledge and skill to take an active role in managing CRF and to develop evidence-based interventions to address fatigue in this patient population. Interventions may include creating and evaluating individualized exercise plans for inpatients with cancer and/or developing educational programs for the inpatient setting that may be continued after discharge and during outpatient treatment.

  4. The effect of marital status on breast cancer-related outcomes in women under 65: A SEER database analysis.

    Science.gov (United States)

    Hinyard, Leslie; Wirth, Lorinette Saphire; Clancy, Jennifer M; Schwartz, Theresa

    2017-04-01

    Marital status is strongly associated with improved health and longevity. Being married has been shown to be positively associated with survival in patients with multiple different types of malignancy; however, little is known about the relationship between marital status and breast cancer in younger women. The purpose of this study is to investigate the effect of marital status on diagnosis, and survival of women under the age of 65 with breast cancer. The SEER 18 regions database was used to identify women between the ages of 25-64 diagnosed with invasive breast cancer in the years 2004-2009. Logistic regression was used to predict later stage diagnosis by marital status and Cox proportional hazards models were used to compare breast cancer-related and all-cause survival by marital status classification. Models were stratified by AJCC stage. After adjusting for age, race, and ER status, unmarried women were 1.18 times more likely to be diagnosed at a later stage than married women (95% CI 1.15, 1.20). In adjusted analysis unmarried women were more likely to die of breast cancer and more likely to die of all causes than married women across all AJCC stages. Younger unmarried women with breast cancer may benefit from additional counseling, psychosocial support and case management at the time of diagnosis to ensure their overall outcomes are optimized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Cancer-Related Fatigue in Women With Breast Cancer: Outcomes of a 5-Year Prospective Cohort Study.

    LENUS (Irish Health Repository)

    Goldstein, David

    2012-04-16

    PURPOSEProlonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear. PATIENTS AND METHODSA prospective cohort study of women receiving adjuvant treatment for early-stage breast cancer was conducted. Women (n = 218) were enrolled after surgery and observed at end treatment and at 1, 3, 6, 9, and 12 months as well as 5 years. Structured interviews and self-report questionnaires were used to record physical and psychologic health as well as disability and health care utilization. Patients with CRF persisting for 6 months were assessed to exclude alternative medical and psychiatric causes of fatigue. Predictors of persistent fatigue, mood disturbance, and health care utilization were sought by logistic regression.ResultsThe case rate for CRF was 24% (n = 51) postsurgery and 31% (n = 69) at end of treatment; it became persistent in 11% (n = 24) at 6 months and 6% (n = 12) at 12 months. At each time point, approximately one third of the patients had comorbid mood disturbance. Persistent CRF was predicted by tumor size but not demographic, psychologic, surgical, or hematologic parameters. CRF was associated with significant disability and health care utilization. CONCLUSIONCRF is common but generally runs a self-limiting course. Much of the previously reported high rates of persistent CRF may be attributable to factors unrelated to the cancer or its treatment.

  6. THE APPROACH OF CANCER RELATED FATIGUE IN RHEABILITATION MEDICINE: PART I – MECHANISMS, SYMPTOMS, CLINICAL EVALUATION AND SCREENING

    Directory of Open Access Journals (Sweden)

    SALCA Amalia

    2015-05-01

    Full Text Available Cancer related fatigue (CRF is the most disabling and distressing symptom in cancer, throughout the whole history of the illness, including successfully treated cases. Rehabilitation medicine could have a positive impact on these patients’ outcomes, if well targeted. With these purpose, the rehabilitation clinician needs to correctly assess fatigue using standard, reliable scales. This review of articles and trials synthesizes the epidemiology, mechanics (including causes and effects, clinical presentation and means of assessment in CRF. CRF causes and mechanisms are not well known. Understanding them would provide specific targets to fatigue management. Clinical presentation is very variable, a wide range of features being found in literature. Poorly medical reports in assessing fatigue offer variable percentages of prevalence, inconsistent with patients’ daily burden due to CRF. There are many tools used to assess fatigue in clinical research and on them depends the percentages reported as fatigue prevalence. The hereby gathered information are useful in the approach of a patient that addresses to a rehabilitation clinician for CRF management.

  7. Cancer-Related Fatigue in Post-Treatment Cancer Survivors: Theory-Based Development of a Web-Based Intervention.

    Science.gov (United States)

    Corbett, Teresa; Walsh, Jane C; Groarke, AnnMarie; Moss-Morris, Rona; Morrissey, Eimear; McGuire, Brian E

    2017-07-04

    Cancer-related fatigue (CrF) is the most common and disruptive symptom experienced by cancer survivors. We aimed to develop a theory-based, interactive Web-based intervention designed to facilitate self-management and enhance coping with CrF following cancer treatment. The aim of our study was to outline the rationale, decision-making processes, methods, and findings which led to the development of a Web-based intervention to be tested in a feasibility trial. This paper outlines the process and method of development of the intervention. An extensive review of the literature and qualitative research was conducted to establish a therapeutic approach for this intervention, based on theory. The psychological principles used in the development process are outlined, and we also clarify hypothesized causal mechanisms. We describe decision-making processes involved in the development of the content of the intervention, input from the target patient group and stakeholders, the design of the website features, and the initial user testing of the website. The cocreation of the intervention with the experts and service users allowed the design team to ensure that an acceptable intervention was developed. This evidence-based Web-based program is the first intervention of its kind based on self-regulation model theory, with the primary aim of targeting the representations of fatigue and enhancing self-management of CrF, specifically. This research sought to integrate psychological theory, existing evidence of effective interventions, empirically derived principles of Web design, and the views of potential users into the systematic planning and design of the intervention of an easy-to-use website for cancer survivors. ©Teresa Corbett, Jane C Walsh, AnnMarie Groarke, Rona Moss-Morris, Eimear Morrissey, Brian E McGuire. Originally published in JMIR Cancer (http://cancer.jmir.org), 04.07.2017.

  8. Changes in arm tissue composition with slowly progressive weight-lifting among women with breast cancer-related lymphedema.

    Science.gov (United States)

    Zhang, Xiaochen; Brown, Justin C; Paskett, Electra D; Zemel, Babette S; Cheville, Andrea L; Schmitz, Kathryn H

    2017-07-01

    Studies in breast cancer-related lymphedema (BRCL) have exclusively examined total arm volume, but not the specific tissue composition that contributes to total volume. We evaluated baseline differences in arm tissue composition [fat mass, lean mass, bone mineral content (BMC), and bone mineral density (BMD)] between the affected and unaffected arms in women with BRCL. We compared changes in arm tissue composition and self-reported lymphedema symptoms after 1 year of weight-lifting versus control. We utilized data from physical activity and lymphedema trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy X-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. At baseline, the affected arm had more fat (∆ = 89.7 g; P arm. After 12 months of weight-lifting, composition of the affected arm was improved: lean mass (71.2 g; P = 0.01) and BMD (14.0 mg/cm 2 ; P = 0.02) increased, arm fat percentage decreased (-1.5%; P = 0.003). Composition of the unaffected arm was only improved in lean mass (65.2 g; P = 0·04). Increases in lean mass were associated with less severe BCRL symptoms. Among women with BRCL, slowly progressive weight-lifting could improve arm tissue composition. Changes in arm tissue composition predict changes in symptom burden. Investigating the combined effects of exercise and weight loss on arm tissue composition and BCRL symptoms may provide additional insight into the benefits of lifestyle modification on lymphedema biology.

  9. Prescription and adherence to lymphedema self-care modalities among women with breast cancer-related lymphedema.

    Science.gov (United States)

    Brown, Justin C; Cheville, Andrea L; Tchou, Julia C; Harris, Susan R; Schmitz, Kathryn H

    2014-01-01

    To profile the prescription for and adherence to breast cancer-related lymphedema (BCRL) self-care modalities among breast cancer (BrCa) survivors with BCRL in a 12-month randomized weightlifting trial. We developed a questionnaire that assessed prescription for and adherence to 10 BCRL self-care modalities that included physical therapy exercise, pneumatic compression pump, medication, lymphedema bandaging, arm elevation, self-administered lymphatic drainage, therapist-administered lymphatic drainage, compression garments, skin care, and taping. We measured prescription for and adherence to BCRL self-care modalities at baseline, 3, 6, and 12 months. Longitudinal logistic regression was used to estimate the odds ratio (OR) and 95 % confidence interval (95 % CI) associated with prescription for and adherence to BCRL modalities over time. This study included 141 BrCa survivors with BCRL. Women were prescribed an average of 3.6 ± 2.1 BCRL self-care modalities during the study. The prescription for therapist-administered lymphatic drainage (OR = 0.92, 95 % CI 0.88-0.96), pneumatic compression pump use (OR = 0.94, 95 % CI 0.89-0.98), and bandaging (OR = 0.96, 95 % CI 0.93-0.99) decreased over 12 months of follow-up. No other prescribed BCRL self-care modalities changed during the study. Over 12 months, the average adherence to all BCRL self-care modalities varied with 13, 24, 32, and 31 % of women reporting variable. The average adherence to BCRL self-care was non-optimal. Future research is necessary to prepare BrCa survivors with the knowledge, skills, abilities, and resources necessary to care for this lifelong condition.

  10. Cancer-Related Fatigue in Patients With and Survivors of Hodgkin Lymphoma: The Impact on Treatment Outcome and Social Reintegration.

    Science.gov (United States)

    Behringer, Karolin; Goergen, Helen; Müller, Horst; Thielen, Indra; Brillant, Corinne; Kreissl, Stefanie; Halbsguth, Teresa Veronika; Meissner, Julia; Greil, Richard; Moosmann, Peter; Shonukan, Oluwatoyin; Rueffer, Jens Ulrich; Flechtner, Hans-Henning; Fuchs, Michael; Diehl, Volker; Engert, Andreas; Borchmann, Peter

    2016-12-20

    Purpose Cancer-related fatigue occurs frequently in patients with Hodgkin lymphoma (HL) and has a major impact on their quality of life. We hypothesized that severe fatigue (sFA) might have an impact on patients' treatment outcome and social reintegration. Methods Of 5,306 patients enrolled in the German Hodgkin Study Group's fifth generation of clinical trials in HL (HD13, HD14, and HD15; nonqualified and older [> 60 years] patients excluded), 4,529 provided data on health-related quality of life. We describe sFA (defined as a score ≥ 50 on the 0 to 100 scale from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) before and up to 9 years after therapy and analyze its impact on treatment outcome and social reintegration. Results The proportion of patients reporting sFA was 37% at baseline and ranged from 20% to 24% during follow-up. Baseline sFA was associated with significantly impaired progression-free survival and a trend to impaired overall survival, which can be overcome in patients receiving highly effective HL therapies as applied in our fifth-generation trials. Our analysis revealed a significant negative association of sFA and employment in survivors: 5 years after therapy, 51% and 63% of female and male survivors, respectively, with sFA were working or in professional education, compared with 78% and 90% without sFA, respectively ( P financial problems and the number of visits to a general practitioner and medical specialists. Conclusion sFA is an important factor preventing survivors from social reintegration during follow-up. This observation underscores the need to address fatigue as a significant diagnosis when treating patients with and survivors of cancer.

  11. Cancer-related fatigue and depression in breast cancer patients postchemotherapy: Different associations with optimism and stress appraisals.

    Science.gov (United States)

    Levkovich, Inbar; Cohen, Miri; Pollack, Shimon; Drumea, Karen; Fried, Georgeta

    2015-10-01

    Symptoms of depression and cancer-related fatigue (CRF) are common among breast cancer patients postchemotherapy and may seriously impair quality of life (QoL). This study aimed to assess the relationship between depression and CRF in breast cancer patients postchemotherapy and to examine their relationships to optimism and to threat and challenge appraisals. Participants included 95 breast cancer patients (stages 1-3) 1 to 6 months after completion of chemotherapy. Patients submitted personal and medical details and completed the following: physical symptom questionnaires (EORTC QLQ-C30, and QLQ-BR23), a symptoms of depression questionnaire (CES-D), the Fatigue Symptom Inventory (FSI), the Life Orientation Test (LOT-R), and a stress appraisals questionnaire. We found levels of depression, CRF, and appraisals of cancer as a threat to bemoderate and levels of optimism and appraisals of cancer as a challenge to be high. Depression and CRF were positively associated. A multivariate regression analysis revealed that 51% of the CRF variancewas explained; physical symptoms and threat appraisal were significantly associated with CRF. A 67% of the CRF variance of depression was explained; challenge and threat appraisals were significantly associated with depression [corrected]. Although CRF and depression were often experienced simultaneously and both were found to be higher among individuals who gave higher appraisals of cancer as a threat, only depression was related to optimism and challenge appraisals, while CRF was related mainly to intensity of physical symptoms. The different pattern of associations between optimism and appraisals warrants further clinical attention as well as future study.

  12. Psychosocial factors associated with adherence for self-management behaviors in women with breast cancer-related lymphedema.

    Science.gov (United States)

    Alcorso, Jessica; Sherman, Kerry A; Koelmeyer, Louise; Mackie, Helen; Boyages, John

    2016-01-01

    Cognitive and affective psychosocial factors have been found to underlie adherence to preventive behaviors in women at risk of developing lymphedema following treatment for breast cancer. The aim of this study was to determine if these factors are associated with adherence to self-management behaviors for women diagnosed with breast cancer-related lymphedema (BCRL). Women with BCRL were recruited through a community-based breast cancer organization and three Australian lymphedema treatment clinics. Participants completed an online questionnaire assessing demographics, medical history, adherence to self-management behaviors, psychosocial variables (personal control, treatment control, consequences, distress, and self-regulation of affect), and knowledge about lymphedema self-management. A total of 166 women participated in the study. Participants reported adhering to a mean of five out of seven behaviors, with 19.5% of participants adhering to all seven behaviors. Adherence to individual behaviors ranged from 65% (self-lymphatic drainage) to 98.2% (skin care). Greater knowledge about lymphedema was significantly correlated with higher adherence. Hierarchical multiple linear regression analysis indicated that only medical history factors (time since diagnosis and having undergone hormone replacement therapy) predicted a significant amount of the variance in adherence. These findings highlight the importance of patient knowledge for optimal adherence to a self-management regimen. In addition, medical history factors may identify if a patient is at risk of nonadherence. The lack of association of adherence with other psychosocial factors considered in this study indicates that factors underlying adherence in affected women differ considerably from those factors prompting preventive behavior adherence in the at-risk population.

  13. Evidence of significant central fatigue in patients with cancer-related fatigue during repetitive elbow flexions till perceived exhaustion.

    Directory of Open Access Journals (Sweden)

    Bin Cai

    Full Text Available To investigate whether fatigue induced by an intermittent motor task in patients with cancer-related fatigue (CRF is more central or peripheral.Ten patients with CRF who were off chemo and radiation therapies and 14 age-matched healthy controls were enrolled. Participants completed a Brief Fatigue Inventory (BFI and performed a fatigue task consisting of intermittent elbow-flexion contractions at submaximal (40% maximal voluntary contraction intensity till self-perceived exhaustion. Twitch force was elicited by an electrical stimulation applied to the biceps brachii muscle. The relative degree of peripheral (muscle vs. central contribution to fatigue induced by the intermittent motor task (IMT was assessed using twitch force ratio (TF ratio defined as post IMT twitch force to pre IMT twitch force. The total number of trials (intermittent contractions and total duration of all trials performed by each subject were also quantified.BFI scores were higher (p < 0.001 in CRF than controls, indicating greater feeling of fatigue in CRF patients than controls. A significantly smaller number of trials and shorter total duration of the trials (p < 0.05 were observed in CRF than control participants. The TF ratio (0.81 ± 0.05 in CRF was higher (p < 0.05 compared with that of controls (0.62 ± 0.05, suggesting CRF patients experienced a significantly lower degree of muscle (peripheral fatigue at the time of perceived exhaustion.Consistent with prior findings for fatigue under submaximal sustained contraction, our results indicate that motor fatigue in CRF is more of central than peripheral origin during IMT. Significant central fatigue in CRF patients limits their ability to prolong motor performance.

  14. HPV and cervical cancer related knowledge, awareness and testing behaviors in a community sample of female sex workers in China.

    Science.gov (United States)

    Hong, Yan; Zhang, Chen; Li, Xiaoming; Lin, Danhua; Liu, Yingjie

    2013-07-30

    Limited data suggested that the prevalence of Human Papillomavirus (HPV) among female sex workers (FSW) is much higher than in the general female population. The current study aimed to examine the HPV and cervical cancer related awareness, knowledge, and behaviors among FSW in China. A total of 360 FSW recruited from entertainment establishments in Beijing completed a self-administered survey including demographics, HPV related knowledge, and health-seeking and cervical cancer preventive behaviors. Approximately 70.8% of the participants ever heard of cervical cancer, and as few as 22.1% and 13.3% ever heard of HPV and HPV vaccine, respectively. The mean score on a 7-item knowledge scale was 2.2 (SD = 2.4). Less than 10% of FSW perceived any risk of cervical cancer, and only 15.3% ever had a Pap smear. About 40.8% of FSW would accept HPV vaccine if it is free, and 21.8% would accept it even with a charge. Multivariate regression suggested that women with better knowledge of cervical cancer were more likely to have a Pap smear (aOR = 1.35); women who had tested for HIV were 11 times more likely to have a Pap smear, and women who had worked longer in commercial sex (aOR = 1.01) and had regular health check-ups (aOR = 1.95) were more likely to accept HPV vaccine. Our study underscores the needs for effective cervical cancer prevention programs for FSW in China and other resource-limited countries. We specifically call for cervical cancer and HPV knowledge and awareness programs and regular screening as well as HPV risk-reduction programs for these vulnerable women.

  15. Systematic Review and Meta-Analysis of the Effects of Exercise for Those With Cancer-Related Lymphedema.

    Science.gov (United States)

    Singh, Ben; Disipio, Tracey; Peake, Jonathan; Hayes, Sandra C

    2016-02-01

    To evaluate the effects of exercise on cancer-related lymphedema and related symptoms, and to determine the need for those with lymphedema to wear compression during exercise. CINAHL, Cochrane, EBSCOhost, MEDLINE, PubMed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, ScienceDirect, and SPORTDiscus databases were searched for trials published before January 1, 2015. Randomized and nonrandomized controlled trials and single-group pre-post studies published in English were included. Twenty-one (exercise) and 4 (compression and exercise) studies met inclusion criteria. Data were extracted into tabular format using predefined data fields by 1 reviewer and assessed for accuracy by a second reviewer. Study quality was evaluated using the Effective Public Health Practice Project Quality Assessment Tool. Data were pooled using a random-effects model to assess the effects of acute and long-term exercise on lymphedema and lymphedema-associated symptoms, with subgroup analyses for exercise mode and intervention length. There was no effect of exercise (acute or intervention) on lymphedema or associated symptoms, with standardized mean differences from all analyses ranging between -0.2 and 0.1 (P values ≥.22). Findings from subgroup analyses for exercise mode (aerobic, resistance, mixed, other) and intervention duration (>12wk or ≤12wk) were consistent with these findings-that is, no effect on lymphedema or associated symptoms. There were too few studies evaluating the effect of compression during regular exercise to conduct a meta-analysis. Individuals with secondary lymphedema can safely participate in progressive, regular exercise without experiencing a worsening of lymphedema or related symptoms. However, there is insufficient evidence to support or refute the current clinical recommendation to wear compression garments during regular exercise. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc

  16. Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis.

    Science.gov (United States)

    Meneses-Echávez, José Francisco; González-Jiménez, Emilio; Ramírez-Vélez, Robinson

    2015-02-21

    Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors. Approximately 40% to 80% of cancer patients undergoing active treatment suffer from CRF. Exercise improves overall quality of life and CRF; however, the specific effects of the training modalities are not well understood. This study aimed to determine the pooled effects of supervised exercise interventions on CRF in breast cancer survivors. We searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL and CINAHL databases between December 2013 and January 2014 without language restrictions. Risk of bias and methodological quality were evaluated using the PEDro score. Pooled effects were calculated with a random-effects model according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I (2) test. Nine high-quality studies (n = 1156) were finally included. Supervised aerobic exercise was statistically more effective than conventional care in improving CRF among breast cancer survivors (SMD = -0.51, 95%CI -0.81 to -0.21), with high statistical heterogeneity (P = 0.001; I (2)  = 75%). Similar effects were found for resistance training on CRF (SMD = -0.41, 95%CI -0.76 to -0.05; P = 0.02; I(2) = 64%). Meta-regression analysis revealed that exercise volume parameters are closely related with the effect estimates on CRF. Egger's test suggested moderate evidence of publication bias (P = 0.04). Supervised exercise reduces CRF and must be implemented in breast cancer rehabilitation settings. High-volume exercises are safe and effective in improving CRF and overall quality of life in women with breast cancer. Further research is encouraged. CRD42014007223.

  17. Development and evaluation of a cancer-related fatigue patient education program: protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Görres Stefan

    2008-07-01

    Full Text Available Abstract Background Cancer-related fatigue (CRF and its impact on patients' quality of life has been an increasing subject of research. However, in Germany there is a lack of evidence-based interventions consistent with the multidimensional character of fatigue. The objective of this study is to develop and evaluate a self-management program for disease-free cancer patients to cope with CRF. Methods Based on evidence extracted from a literature review, a curriculum for the self-management program was elaborated. The curriculum was reviewed and validated by an interdisciplinary expert group and the training-modules will be pretested with a small number of participants and discussed in terms of feasibility and acceptance. To determine the efficacy of the program a randomised controlled trial will be carried out: 300 patients will be recruited from oncological practices in Bremen, Germany, and will be allocated to intervention or control group. The intervention group participates in the program, whereas the control group receives standard care and the opportunity to take part in the program after the end of the follow-up (waiting control group. Primary outcome measure is the level of fatigue, secondary outcome measures are quality of life, depression, anxiety, self-efficacy and physical activity. Data will be collected before randomisation, after intervention, and after a follow-up of 6 months. Discussion Because there are no comparable self-management programs for cancer survivors with fatigue, the development of the curriculum has been complex; therefore, the critical appraisal by the experts was an important step to validate the program and their contributions have been integrated into the curriculum. The experts appreciated the program as filling a gap in outpatient cancer care. If the results of the evaluation prove to be satisfactory, the outpatient care of cancer patients can be broadened and supplemented. Trial Registration Clinical

  18. The effects of a six-week supervised multimodal exercise intervention during chemotherapy on cancer-related fatigue.

    Science.gov (United States)

    Andersen, Christina; Rørth, Mikael; Ejlertsen, Bent; Stage, Maria; Møller, Tom; Midtgaard, Julie; Quist, Morten; Bloomquist, Kira; Adamsen, Lis

    2013-06-01

    Cancer related fatigue (CRF) is a common problem for cancer patients across diagnoses during chemotherapy and is associated with physical inactivity, lower functional level and lack of energy. Few RCT exercise intervention studies have included cancer patients undergoing chemotherapy. The objective of this study is to evaluate whether a six-week supervised multimodal exercise intervention, adjunct to chemotherapy and standard care, can reduce the patient's CRF level. Data is based on analyses of a prospective randomised controlled trial 'The Body & Cancer Trial'. 213 cancer patients with different diagnoses were randomised into an intervention group or wait-list control group. The primary outcome, Fatigue score (CRF), was evaluated by the Functional Assessment of Cancer Therapy-Anaemia Questionnaire (FACT-An-) (FACT-G score & FACT-An Anemia subscale). Supervised exercise, comprising high-intensity cardiovascular and heavy resistance training, relaxation- and body awareness training and massage, 9 h weekly for 6 weeks. CRF was significantly reduced in the intervention group, corresponding to a Fatigue score reduction of 3.04 (effect size of 0.44, 95% CI 0.17-0.72) (P = .002), the FACT-An score by 5.40 (P = .015), the FACT-An Toi score by 5.22 (P = .009) and the Anaemia-ANS by 3.76 (P = .002). There was no statistically significant effect on the General Quality of Life score (FACT-G) or on any of the individual wellbeing scores; Physical (P = .13), Emotional (P = .87), Social (P = .83) and Functional (P = .26). In summary, this six-week supervised multimodal exercise intervention can lead to significant reduction in self-reported CRF in cancer patients undergoing chemotherapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Association of coping style, cognitive errors and cancer-related variables with depression in women treated for breast cancer.

    Science.gov (United States)

    Alcalar, Nilufer; Ozkan, Sedat; Kucucuk, Seden; Aslay, Isik; Ozkan, Mine

    2012-10-01

    The purpose of this study was to examine the correlation between depression levels with coping styles and cognitive errors in women treated for breast cancer. A total of 110 breast cancer outpatients who had had surgery at least 6 months previously, had completed adjuvant cancer treatment and had not experienced metastasis or recurrent lesions were evaluated. The Automatic Thoughts Questionnaire, Cognitive Errors Questionnaire, Mental Adjustment to Cancer Scale and Beck Depression Inventory were administered to all patients. Semi-structured interview forms were used to obtain medical and demographic data. All patients were categorized into depression and non-depression groups according to their Beck Depression Inventory scores. The study protocol was approved by the Medical Ethics Committee of Istanbul University Oncology Institute. Higher cognitive errors and automatic thought scores were found in the depression group. Fighting spirit was found to be the primary coping style used in the non-depression group, while helplessness/hopelessness, anxious/preoccupation and fatalism were the coping styles used the most in the depression group. No association between depression and socio-demographic (except for educational level) and cancer-related variables was detected. However, it was found that automatic thoughts, cognitive errors, education level, fighting spirit and anxious/preoccupation are important indicators of depression in our sample. A causal relationship exists between depression and a patient's cognitive patterns and accompanying anxiety. The degree of depression is inversely related to both fighting spirit coping type and educational level. If clinicians take this into consideration, diagnosing and treating depression will be more effective.

  20. Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women.

    Science.gov (United States)

    Sieuwerts, Anieta M; De Napoli, Giuseppina; van Galen, Anne; Kloosterboer, Helenius J; de Weerd, Vanja; Zhang, Hong; Martens, John W M; Foekens, John A; De Geyter, Christian

    2011-12-01

    Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes, non-representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (pbreast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Cystatin D Locates in the Nucleus at Sites of Active Transcription and Modulates Gene and Protein Expression*

    Science.gov (United States)

    Ferrer-Mayorga, Gemma; Alvarez-Díaz, Silvia; Valle, Noelia; De Las Rivas, Javier; Mendes, Marta; Barderas, Rodrigo; Canals, Francesc; Tapia, Olga; Casal, J. Ignacio; Lafarga, Miguel; Muñoz, Alberto

    2015-01-01

    Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer. PMID:26364852

  2. Does the number of cancer patients’ close social ties affect cancer-related information seeking through communication efficacy? Testing a mediation model

    Science.gov (United States)

    Lewis, Nehama; Martinez, Lourdes S.

    2014-01-01

    This study addresses the question of whether having a broad social network of close friends equips cancer patients with increased efficacy to engage in communication about their cancer, which then leads to an increased likelihood of patients’ actively seeking cancer-related information. Guided by the theory of motivated information management (TMIM: Afifi & Weiner, 2006), the study also tests whether the effect of the number of close social ties on information seeking is mediated, in part, by communication efficacy. Results are based on data collected from a randomly drawn sample from the Pennsylvania Cancer Registry of 2,013 cancer patients who completed mail surveys in the Fall of 2006. Results are consistent with a cross-sectional mediation effect in which the number of close social ties in one’s social network is positively associated with communication efficacy (b = .17, p = .001), which, in turn, is positively associated with cancer-related information seeking (b = .13, p < .001). PMID:24673194

  3. Does the number of cancer patients' close social ties affect cancer-related information seeking through communication efficacy? Testing a mediation model.

    Science.gov (United States)

    Lewis, Nehama; Martinez, Lourdes S

    2014-09-01

    This study addresses whether having a broad social network of close friends equips cancer patients with increased efficacy to engage in communication about their cancer, which then leads to an increased likelihood of patients actively seeking cancer-related information. Guided by the theory of motivated information management, the study also tests whether the effect of the number of close social ties on information seeking is mediated, in part, by communication efficacy. Results are based on data collected from a randomly drawn sample from the Pennsylvania Cancer Registry of 2,013 cancer patients who completed mail surveys in the Fall of 2006. Results are consistent with a cross-sectional mediation effect in which the number of close social ties in one's social network is positively associated with communication efficacy (b = .17, p = .001), which, in turn, is positively associated with cancer-related information seeking (b = .13, p < .001).

  4. Potential spillover educational effects of cancer-related direct-to-consumer advertising on cancer patients' increased information seeking behaviors: results from a cohort study.

    Science.gov (United States)

    Tan, Andy S L

    2014-06-01

    Spillover effects of exposure to direct-to-consumer advertising (DTCA) of cancer treatments on patients' general inquiry about their treatments and managing their illness are not well understood. This study examines the effects of cancer patients' exposure to cancer-related DTCA on subsequent health information seeking behaviors from clinician and non-clinician sources (lay media and interpersonal contacts). Using a longitudinal survey design over 3 years, data was collected from cancer survivors diagnosed with colorectal, breast, or prostate cancer who were randomly sampled from the Pennsylvania Cancer Registry. Study outcome measures include patients' information engagement with their clinicians and information seeking from non-medical sources about cancer treatment and quality of life issues, measured in the second survey. The predictor variable is the frequency of exposure to cancer-related DTCA since diagnosis, measured at the round 1 survey. The analyses utilized lagged-weighted multivariate regressions and adjusted for round 1 levels of patient-clinician engagement, information seeking from nonmedical sources, and confounders. Exposure to cancer-related DTCA is associated with increased levels of subsequent patient-clinician information engagement (B = .023, 95% CI = .005-.040, p = .012), controlling for confounders. In comparison, exposure to DTCA is marginally significant in predicting health information seeking from non-clinician sources (B = .009, 95% CI = -.001-.018, p = .067). Cancer-related DTCA has potentially beneficial spillover effects on health information seeking behaviors among cancer patients. Exposure to DTCA predicts (a little) more patient engagement with their physicians.

  5. Perceptions of Cancer Risk/Efficacy and Cancer-Related Risk Behaviors: Results From the HCHS/SOL Sociocultural Ancillary Study.

    Science.gov (United States)

    Fox, Rina S; Mills, Sarah D; Roesch, Scott C; Sotres-Alvarez, Daniela; Gonzalez, Patricia; Bekteshi, Venera; Cai, Jianwen; Lounsbury, David W; Talavera, Gregory A; Penedo, Frank J; Malcarne, Vanessa L

    2017-12-01

    This study evaluated the associations among perceived risk, perceived efficacy, and engagement in six cancer-related risk behaviors in a population-based Hispanic/Latino sample. Interviews were conducted with 5,313 Hispanic/Latino adults as part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. Participants were recruited from the study's four field centers (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) between February 2010 and June 2011. Perceived risk and perceived efficacy were assessed with questions drawn from the Health Interview National Trends Survey. More than half of the sample endorsed perceived risk of cancer associated with the six evaluated behaviors, as well as general perceived efficacy for preventing cancer. Adjusted logistic regression analyses demonstrated significant differences across Hispanic/Latino background groups for perceived risk associated with high consumption of alcohol and saturated fat, low consumption of fruits and vegetables, and insufficient exercise but not with smoking or low consumption of fiber. Differences were also found for the belief, "It seems like everything causes cancer" but not for other perceived efficacy items. Perceived cancer risk and perceived efficacy for preventing cancer were neither independently nor interactively associated with engagement in cancer-related risk behaviors after controlling for sociodemographic covariates. Results suggest that perceptions of risk and efficacy with regard to cancer vary across Hispanic/Latino background groups, and therefore background group differences should be considered in prevention efforts. Perceived risk and perceived efficacy were not related to cancer-related risk behaviors among Hispanics/Latinos. Further work is needed to evaluate determinants of cancer-related risk in this population.

  6. Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors - results from a nationwide randomized clinical trial.

    Science.gov (United States)

    Jensen-Johansen, M B; Christensen, S; Valdimarsdottir, H; Zakowski, S; Jensen, A B; Bovbjerg, D H; Zachariae, R

    2013-07-01

    To examine the effects of an expressive writing intervention (EWI) on cancer-related distress, depressive symptoms, and mood in women treated for early stage breast cancer. A nationwide sample of 507 Danish women who had recently completed treatment for primary breast cancer were randomly assigned to three 20-min home-based writing exercises, one week apart, focusing on either emotional disclosure (EWI group) or a non-emotional topic (control group). Cancer-related distress [Impact of Event Scale (IES)], depressive symptoms (Beck Depression Inventory-Short Form), and negative (37-item Profile of Moods State) and positive mood (Passive Positive Mood Scale) were assessed at baseline and at 3 and 9 months post-intervention. Choice of writing topic (cancer versus other), alexithymia (20-item Toronto Alexithymia Scale), and social constraints (Social Constraints Scale) were included as possible moderators. Significant (ppsychological symptoms were seen in both groups (pwriting topic moderated effects on IES, with women writing about other themes showing greater reductions in cancer-related avoidance than women writing about their cancer. Fewer depressive symptoms and higher levels of positive mood were seen 3 months post-intervention in women writing about their cancer when compared with the control group. Difficulties describing feelings and externally oriented thinking (20-item Toronto Alexithymia Scale) moderated effects on positive mood and IES-total, while no moderating effects were found of social constraints. In concordance with the majority of previous results with cancer patients, no main effects of EWI were found for cancer-related distress, depressive symptoms, and mood. Moderator analyses suggested that choice of writing topic and ability to process emotional experiences should be studied further. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Prevalence of the use of cancer related self-tests by members of the public: a community survey

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    Marriott John

    2006-08-01

    Full Text Available Abstract Background Self-tests are those where an individual can obtain a result without recourse to a health professional, by getting a result immediately or by sending a sample to a laboratory that returns the result directly. Self-tests can be diagnostic, for disease monitoring, or both. There are currently tests for more than 20 different conditions available to the UK public, and self-testing is marketed as a way of alerting people to serious health problems so they can seek medical help. Almost nothing is known about the extent to which people self-test for cancer or why they do this. Self-tests for cancer could alter perceptions of risk and health behaviour, cause psychological morbidity and have a significant impact on the demand for healthcare. This study aims to gain an understanding of the frequency of self-testing for cancer and characteristics of users. Methods Cross-sectional survey. Adults registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that will collect socio-demographic information and basic data regarding previous and potential future use of self-test kits. The only exclusions will be people who the GP feels it would be inappropriate to send a questionnaire, for example because they are unable to give informed consent. Freepost envelopes will be included and non-responders will receive one reminder. Standardised prevalence rates will be estimated. Discussion Cancer related self-tests, currently available from pharmacies or over the Internet, include faecal occult blood tests (related to bowel cancer, prostate specific antigen tests (related to prostate cancer, breast cancer kits (self examination guide and haematuria tests (related to urinary tract cancers. The effect of an increase in self-testing for cancer is unknown but may be considerable: it may affect the delivery of population based screening programmes; empower patients or cause unnecessary anxiety

  8. Adequacy of cancer-related pain management and predictors of undertreatment at referral to a pain clinic

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    Reis-Pina P

    2017-08-01

    Full Text Available Paulo Reis-Pina,1,2 Peter G Lawlor,3–5 António Barbosa6,7 1Palliative Care Unit, Casa de Saúde da Idanha, Sintra, 2Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; 3Ottawa Hospital Research Institute, 4Bruyère Research Institute, Bruyère Continuing Care, 5Division of Palliative Care, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 6Department of Psychiatry, North Lisbon Hospital Centre, Lisbon, 7Centre of Bioethics and Palliative Care Studies Division, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal Background: Several guidelines have advocated the need for adequate cancer-related pain (CRP management. The pain management index (PMI has been proposed as an auditable measure of the appropriateness for analgesic therapy. Objectives: To determine the adequacy of CRP management based on the PMI status and its patient-related predictors at the point of referral to a pain clinic (PC. Methods: Consecutive patients referred to a PC had standardized initial assessments and status documentation on the Brief Pain Inventory (BPI ratings; pain mechanism, using a neuropathic pain diagnostic questionnaire (the Douleur Neuropathique 4 tool; episodic pain; oral morphine equivalent daily dose; the Hospital Anxiety Depression Scale and the Emotion Thermometer scores; and cancer diagnosis, metastases, treatment, and pain duration. Predictors of “negative PMI status” [PMI(−] were examined in logistic regression models. Variables with p<0.25 in an initial bivariable analysis were entered into a multivariable model. Results: Of 371 participants, 95 (25.6% had PMI(−, suggesting undertreatment of CRP. Both female sex and higher scores on the BPI’s “interference with general activity” more strongly predicted PMI(−. Patients who received either radiotherapy or one or more adjuvant analgesics prior to the initial consultation at the PC, those who had neuropathic pain, those who had a greater need

  9. Effects of qigong training on health-related quality of life, functioning, and cancer-related symptoms in survivors of nasopharyngeal cancer: a pilot study.

    Science.gov (United States)

    Fong, Shirley S M; Ng, Shamay S M; Luk, W S; Chung, Louisa M Y; Wong, Janet Y H; Chung, Joanne W Y

    2014-01-01

    This study aimed to investigate the effects of Qigong intervention on quality of life (QOL), health-related functioning, and cancer-related symptoms in survivors of nasopharyngeal cancer (NPC). Twenty-five survivors of NPC were included in the experimental group (mean age ± SD: 55.4 ± 7.5 years) and 27 in the control group (mean age ± SD: 58.7 ± 9.5 years). The experimental group underwent a weekly 1.5-hour Qigong training program and an identical home program (three times/week) for six months. The control group received no training. Global health status/QOL, functioning, and cancer-related symptoms were assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires before training began, after three months of Qigong training, at the end of the six-month Qigong intervention (i.e., posttest), and six months posttest. Intention-to-treat analysis revealed no statistically (P > 0.05) or clinically significant improvement in global health status/QOL, functioning, or symptoms in either group. The experimental group had 45.8% fewer sense-related (smell and taste) problems (P Qigong intervention. Qigong training resulted in no apparent improvement in health-related QOL, functionality, or cancer-related symptoms in cancer-free survivors of NPC, except for a possible reduction in smell- and taste-related problems.

  10. Spore Powder of Ganoderma lucidum Improves Cancer-Related Fatigue in Breast Cancer Patients Undergoing Endocrine Therapy: A Pilot Clinical Trial

    Directory of Open Access Journals (Sweden)

    Hong Zhao

    2012-01-01

    Full Text Available The fatigue prevalence in breast cancer survivors is high during the endocrine treatment. However, there are few evidence-based interventions to manage this symptom. The aim of this study was to investigate the effectiveness of spore powder of Ganoderma lucidum for cancer-related fatigue in breast cancer patients undergoing endocrine therapy. Spore powder of Ganoderma lucidum is a kind of Basidiomycete which is a widely used traditional medicine in China. 48 breast cancer patients with cancer-related fatigue undergoing endocrine therapy were randomized into the experimental or control group. FACT-F, HADS, and EORTC QLQ-C30 questionnaires data were collected at baseline and 4 weeks after treatment. The concentrations of TNF-α, IL-6, and liver-kidney functions were measured before and after intervention. The experimental group showed statistically significant improvements in the domains of physical well-being and fatigue subscale after intervention. These patients also reported less anxiety and depression and better quality of life. Immune markers of CRF were significantly lower and no serious adverse effects occurred during the study. This pilot study suggests that spore powder of Ganoderma lucidum may have beneficial effects on cancer-related fatigue and quality of life in breast cancer patients undergoing endocrine therapy without any significant adverse effect.

  11. Fadiga relacionada ao câncer: uma revisão Cancer-related fatigue: a review

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    Maira Paschoin de Oliveira Campos

    2011-04-01

    este sintoma tão importante e de grande impacto na qualidade de vida de pacientes com câncer.Cancer-related fatigue is the most prevalent cancer symptom, reported in 50%-90% of patients and severely impacts quality of life and functional capacity. The condition remains underreported and often goes untreated. Guidelines suggest screening for fatigue at the initial visit, when the diagnosis of advanced disease is made, and at each chemotherapy session, as well as the identification of treatable contributing factors such as anemia, hypothyroidism, depression and sleep disorders. Brief assessment tools such as the Brief Fatigue Inventory or the Visual Analog Scale may be appropriate in the initial scoring of fatigue severity, but the initial approach to treatment usually requires a more comprehensive assessment, education, and the determination of an individualized treatment plan. Patients with moderate or severe fatigue may benefit from both pharmacological and non-pharmacological interventions, whereas mild fatigue that does not interfere with quality of life can be treated with non-pharmacological measures alone. Non-pharmacological measures that have shown to be promising include cognitive-behavioral interventions such as energy conservation and activity management (ECAM, exercise and perhaps sleep therapy. Many other modalities may be beneficial and can be used on an individual basis, but there is insufficient evidence to promote any single treatment. Pharmacological therapies that have shown to be promising include the psycho-stimulants methylphenidate and dexmethylphenidate, modafinil (in severely fatigued patients only, and erythropoietin-stimulating agents in patients with chemotherapy-associated anemia and hemoglobin levels < 10 g/dL. Recently, our group reported impressive results with the use of the dry extract of Guarana (Paullinia cupana, with no significant side effects and at low cost, for the treatment of physical and mental cancer-related fatigue.

  12. Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol.

    Science.gov (United States)

    Baguley, Brenton J; Skinner, Tina L; Leveritt, Michael D; Wright, Olivia R L

    2017-01-03

    Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse side effects of treatment. The exercise literature has shown high intensity interval training can improve various aspects of health that are typically impaired with androgen deprivation therapy; however exercise at this intensity is yet to be conducted in men with prostate cancer. The purpose of this study is to examine the effects of nutrition therapy beyond the current healthy eating guidelines with high intensity interval training for managing cancer-related fatigue in men with prostate cancer treated with androgen deprivation therapy. This is a two-arm randomized control trial of 116 men with prostate cancer and survivors treated with androgen deprivation therapy. Participants will be randomized to either the intervention group i.e. nutrition therapy and high intensity interval training, or usual care. The intervention group will receive 20 weeks of individualized nutrition therapy from an Accredited Practising Dietitian, and high intensity interval training (from weeks 12-20 of the intervention) from an Accredited Exercise Physiologist. The usual care group will maintain their standard treatment regimen over the 20 weeks. Both groups will undertake primary and secondary outcome testing at baseline, week 8, 12, and 20; testing includes questionnaires of fatigue and quality of life, objective measures of body composition, muscular strength, cardiorespiratory fitness, biomarkers for disease progression, as well as dietary analysis. The primary outcomes for this trial are measures of

  13. Protein Foods

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Protein Foods Foods high in protein such as fish, ... for the vegetarian proteins, whether they have carbohydrate. Protein Choices Plant-Based Proteins Plant-based protein foods ...

  14. miR-203 and miR-320 Regulate Bone Morphogenetic Protein-2-Induced Osteoblast Differentiation by Targeting Distal-Less Homeobox 5 (Dlx5

    Directory of Open Access Journals (Sweden)

    Navya Laxman

    2016-12-01

    Full Text Available MicroRNAs (miRNAs are a family of small, non-coding RNAs (17–24 nucleotides, which regulate gene expression either by the degradation of the target mRNAs or inhibiting the translation of genes. Recent studies have indicated that miRNA plays an important role in regulating osteoblast differentiation. In this study, we identified miR-203 and miR-320b as important miRNAs modulating osteoblast differentiation. We identified Dlx5 as potential common target by prediction algorithms and confirmed this by knock-down and over expression of the miRNAs and assessing Dlx5 at mRNA and protein levels and specificity was verified by luciferase reporter assays. We examined the effect of miR-203 and miR-320b on osteoblast differentiation by transfecting with pre- and anti-miRs. Over-expression of miR-203 and miR-320b inhibited osteoblast differentiation, whereas inhibition of miR-203 and miR-320b stimulated alkaline phosphatase activity and matrix mineralization. We show that miR-203 and miR-320b negatively regulate BMP-2-induced osteoblast differentiation by suppressing Dlx5, which in turn suppresses the downstream osteogenic master transcription factor Runx2 and Osx and together they suppress osteoblast differentiation. Taken together, we propose a role for miR-203 and miR-320b in modulating bone metabolism.

  15. Effects of Qigong Training on Health-Related Quality of Life, Functioning, and Cancer-Related Symptoms in Survivors of Nasopharyngeal Cancer: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Shirley S. M. Fong

    2014-01-01

    Full Text Available This study aimed to investigate the effects of Qigong intervention on quality of life (QOL, health-related functioning, and cancer-related symptoms in survivors of nasopharyngeal cancer (NPC. Twenty-five survivors of NPC were included in the experimental group (mean age ± SD: 55.4 ± 7.5 years and 27 in the control group (mean age ± SD: 58.7 ± 9.5 years. The experimental group underwent a weekly 1.5-hour Qigong training program and an identical home program (three times/week for six months. The control group received no training. Global health status/QOL, functioning, and cancer-related symptoms were assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires before training began, after three months of Qigong training, at the end of the six-month Qigong intervention (i.e., posttest, and six months posttest. Intention-to-treat analysis revealed no statistically (P>0.05 or clinically significant improvement in global health status/QOL, functioning, or symptoms in either group. The experimental group had 45.8% fewer sense-related (smell and taste problems (P<0.05 but 98.6% more speech-related problems (P<0.05 than the control group after the Qigong intervention. Qigong training resulted in no apparent improvement in health-related QOL, functionality, or cancer-related symptoms in cancer-free survivors of NPC, except for a possible reduction in smell- and taste-related problems.

  16. Teenage and Young Adult Cancer-Related Fatigue Is Prevalent, Distressing, and Neglected: It Is Time to Intervene. A Systematic Literature Review and Narrative Synthesis.

    Science.gov (United States)

    Spathis, Anna; Booth, Sara; Grove, Sarah; Hatcher, Helen; Kuhn, Isla; Barclay, Stephen

    2015-03-01

    Cancer-related fatigue in adults has been the subject of considerable recent research, confirming its importance as a common and debilitating symptom, and establishing a number of evidence-based interventions. There has, however, been limited focus on the fatigue suffered by teenagers and young adults with cancer, a group recognized as having unique experiences and developmental needs. We have undertaken a systematic review of the literature to provide a comprehensive overview of studies evaluating fatigue in this younger patient group in order to guide clinical practice and future research. We searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for literature containing data relating to any aspect of fatigue in patients aged 13-24 at cancer diagnosis or treatment. Sixty articles were identified, of which five described interventional clinical trials. Cancer-related fatigue was consistently one of the most prevalent, severe, and distressing symptoms, and it persisted long-term in survivors. It was associated with a number of factors, including poor sleep, depression, and chemotherapy. There was little evidence for the effectiveness of any intervention, although exercise appears to be the most promising. Importantly, fatigue was itself a significant barrier to physical and social activities. Cancer-related fatigue is a major and disabling problem in young cancer patients. Effective management strategies are needed to avoid compounding the dependence and social isolation of this vulnerable patient group. Future research should focus on providing evidence for the effectiveness of interventions, of which activity promotion and management of concurrent symptoms are the most promising.

  17. Association of cancer-related mortality, age and gonadectomy in golden retriever dogs at a veterinary academic center (1989-2016.

    Directory of Open Access Journals (Sweden)

    Michael S Kent

    Full Text Available Golden retriever dogs have been reported to have an increased prevalence of cancer compared to other breeds. There is also controversy over the effect spay or neuter status might have on longevity and the risk for developing cancer. The electronic medical records system at an academic center was searched for all dogs who had a necropsy exam from 1989-2016. 9,677 canine necropsy examinations were completed of which 655 were golden retrievers. Age was known for 652 with a median age of death 9.15 years. 424 of the 652 (65.0% were determined to have died because of cancer. The median age for dying of a cause other than cancer was 6.93 years while those dying of cancer had a median age of 9.83 years (p<0.0001. There was no significant difference in the proportion of intact males and castrated males dying of cancer (p = 0.43 but a greater proportion of spayed females died of cancer compared to intact females (p = 0.001. Intact female dogs had shorter life spans than spayed female dogs (p<0.0001, but there were no differences between intact and castrated males. Intriguingly, being spayed or neutered did not affect the risk of a cancer related death but increasing age did. The most common histologic diagnosis found in golden retrievers dying of cancer was hemangiosarcoma (22.64% followed by lymphoid neoplasia (18.40%. Overall golden retriever dogs have a substantial risk of cancer related mortality in a referral population and age appears to have a larger effect on cancer related mortality than reproductive status.

  18. Tapentadol prolonged release for severe chronic cancer-related pain: effectiveness, tolerability, and influence on quality of life of the patients.

    Science.gov (United States)

    Schikowski, Artur; Krings, Doris; Schwenke, Karla

    2015-01-01

    Clinical trials have shown the efficacy and good tolerability of tapentadol prolonged release (PR) for severe chronic pain of different etiologies. This study investigated the influence of tapentadol PR on pain control and quality of life of patients with severe chronic cancer-related pain in routine clinical practice in Germany. During a 3-month observation period, 45 physicians (mainly palliative care specialists) documented dosage and tolerability of tapentadol PR, previous and concomitant analgesic treatment, pain intensity, pain-related restrictions of daily activities and quality of life, and general state of health of 123 patients with chronic cancer-related pain in the context of a prospective noninterventional study. All patients (mean age 63.9±13.2 years, 93.5% in constant pain) had received analgesic long-term treatment (42.3% strong opioids) prior to the start of tapentadol PR treatment. During the observation period, tapentadol PR significantly reduced the average pain intensity by 2.4 points (from a mean 6.1±1.7 to 3.7±2.0, P<0.001); half of the patients (52%) achieved a pain score ≤3 at the end of observation. At the same time, mental and emotional well-being, pain-related impairments of daily activities, sleep quality, and quality of life improved, while the overall intake of analgesic concomitant medication could be reduced. Improvements in general state of health were significant (P<0.001). Overall, tapentadol PR was well tolerated. Good pain control with tapentadol PR was accompanied by markedly reduced pain-related mental and physical burden and quality of life improved. Overall, the general state of health of these patients with chronic cancer-related pain improved significantly despite the underlying illness.

  19. PRELP (proline/arginine-rich end leucine-rich repeat protein) promotes osteoblastic differentiation of preosteoblastic MC3T3-E1 cells by regulating the β-catenin pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Haiying; Cui, Yazhou; Luan, Jing [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji' nan, Shandong (China); Zhang, Xiumei [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Li, Chengzhi; Zhou, Xiaoyan; Shi, Liang [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji' nan, Shandong (China); Wang, Huaxin [Shandong University of Traditional Chinese Medicine, Ji' an, Shandong (China); Han, Jinxiang, E-mail: jxhan9888@aliyun.com [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji' nan, Shandong (China)

    2016-02-12

    Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a collagen-binding proteoglycan highly expressed in the developing bones. Recent studies indicated that PRELP could inhibit osteoclastogenesis as a NF-κB inhibitor. However, its role during osteoblast differentiation is still unclear. In this study, we confirmed that the expression of PRELP increased with the osteogenesis induction of preosteoblastic MC3T3-E1 cells. Down-regulation of PRELP expression by shRNA reduced ALP activity, mineralization and expression of osteogenic marker gene Runx2. Our microarray analysis data suggested that β-catenin may act as a hub gene in the PRELP-mediated gene network. We validated furtherly that PRELP knockdown could inhibit the level of connexin43, a key regulator of osteoblast differentiation by affecting β-catenin protein expression, and its nuclear translocation in MC3T3-E1 preosteoblasts. Therefore, this study established a new role of PRELP in modulating β-catenin/connexin43 pathway and osteoblast differentiation.

  20. Tapentadol prolonged release for severe chronic cancer-related pain: effectiveness, tolerability, and influence on quality of life of the patients

    Directory of Open Access Journals (Sweden)

    Schikowski A

    2014-12-01

    Full Text Available Artur Schikowski,1 Doris Krings,2 Karla Schwenke2 1Neurology and Specialist Pain Therapy, Specialist Center Düsseldorf, Düsseldorf, 2Grünenthal GmbH, Aachen, Germany Background: Clinical trials have shown the efficacy and good tolerability of tapentadol prolonged release (PR for severe chronic pain of different etiologies. This study investigated the influence of tapentadol PR on pain control and quality of life of patients with severe chronic cancer-related pain in routine clinical practice in Germany. Patients and methods: During a 3-month observation period, 45 physicians (mainly palliative care specialists documented dosage and tolerability of tapentadol PR, previous and concomitant analgesic treatment, pain intensity, pain-related restrictions of daily activities and quality of life, and general state of health of 123 patients with chronic cancer-related pain in the context of a prospective noninterventional study. Results: All patients (mean age 63.9±13.2 years, 93.5% in constant pain had received analgesic long-term treatment (42.3% strong opioids prior to the start of tapentadol PR treatment. During the observation period, tapentadol PR significantly reduced the average pain intensity by 2.4 points (from a mean 6.1±1.7 to 3.7±2.0, P<0.001; half of the patients (52% achieved a pain score ≤3 at the end of observation. At the same time, mental and emotional well-being, pain-related impairments of daily activities, sleep quality, and quality of life improved, while the overall intake of analgesic concomitant medication could be reduced. Improvements in general state of health were significant (P<0.001. Overall, tapentadol PR was well tolerated. Conclusion: Good pain control with tapentadol PR was accompanied by markedly reduced pain-related mental and physical burden and quality of life improved. Overall, the general state of health of these patients with chronic cancer-related pain improved significantly despite the underlying

  1. Cancer-Related Worry and Physical Well-Being in the Context of Perceived Stress in Young Adults with Testicular Cancer.

    Science.gov (United States)

    Darabos, Katie; Hoyt, Michael A

    2017-06-01

    Uncertainty associated with cancer can foster future-focused worry and ultimately diminish physical well-being, especially among young adult survivors. Stress perceptions might exacerbate the association of worry and physical well-being. Young adults with testicular cancer (N = 171) completed measures of physical well-being, perceived stress, and future cancer-related worry. Perceived stress and future worry were both negatively associated with physical well-being. Perceived stress moderated the relationship; more perceived stress was related to lower physical well-being in those with high worry. Interventions aimed at worry reduction might benefit from reducing global stress perceptions.

  2. Association of perceived physician communication style with patient satisfaction, distress, cancer-related self-efficacy, and perceived control over the disease

    DEFF Research Database (Denmark)

    Zachariae, R; Pedersen, C G; Jensen, A B

    2003-01-01

    -efficacy, and perceived control were completed prior to and after the consultation by 454 patients attending an oncology outpatient clinic. After the consultation, the patients also rated the physicians' communicative behaviours by completing a patient-physician relationship inventory (PPRI), and the physicians were......The aim of the study was to investigate the association of physician communication behaviours as perceived by the patient with patient reported satisfaction, distress, cancer-related self-efficacy, and perceived control over the disease in cancer patients. Questionnaires measuring distress, self...

  3. Effectiveness of an individualized program of muscular strength and endurance with aerobic training for improving germ cell cancer-related fatigue in men undergoing chemotherapy: EFICATEST study protocol for a randomized controlled trial

    OpenAIRE

    Cuesta-Vargas, Antonio Ignacio; Carabantes, Francisco; Caracuel, Zaira; Conejo, Inmaculada; Alba, Emilio

    2016-01-01

    Background Patients with testicular germ cell cancer (GCC) have a high cure rate; however, cancer-related fatigue is the most common complication among patients with GCC undergoing treatment with chemotherapy. Although exercise is widely recommended, information about the physio-pathological effects of cancer therapy on skeletal muscle is very limited. Our aim is to evaluate the effects of an individualized program of muscular strength and endurance with aerobic training on cancer-related fat...

  4. Effects of Supervised Multimodal Exercise Interventions on Cancer-Related Fatigue: Systematic Review and Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    José Francisco Meneses-Echávez

    2015-01-01

    Full Text Available Objective. Cancer-related fatigue (CRF is the most common and devastating problem in cancer patients even after successful treatment. This study aimed to determine the effects of supervised multimodal exercise interventions on cancer-related fatigue through a systematic review and meta-analysis. Design. A systematic review was conducted to determine the effectiveness of multimodal exercise interventions on CRF. Databases of PubMed, CENTRAL, EMBASE, and OVID were searched between January and March 2014 to retrieve randomized controlled trials. Risk of bias was evaluated using the PEDro scale. Results. Nine studies n=772 were included in both systematic review and meta-analysis. Multimodal interventions including aerobic exercise, resistance training, and stretching improved CRF symptoms (SMD=-0.23; 95% CI: −0.37 to −0.09; P=0.001. These effects were also significant in patients undergoing chemotherapy P<0.0001. Nonsignificant differences were found for resistance training interventions P=0.30. Slight evidence of publication bias was observed P=0.04. The studies had a low risk of bias (PEDro scale mean score of 6.4 (standard deviation (SD ± 1.0. Conclusion. Supervised multimodal exercise interventions including aerobic, resistance, and stretching exercises are effective in controlling CRF. These findings suggest that these exercise protocols should be included as a crucial part of the rehabilitation programs for cancer survivors and patients during anticancer treatments.

  5. Effects of Supervised Multimodal Exercise Interventions on Cancer-Related Fatigue: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Meneses-Echávez, José Francisco; González-Jiménez, Emilio; Ramírez-Vélez, Robinson

    2015-01-01

    Cancer-related fatigue (CRF) is the most common and devastating problem in cancer patients even after successful treatment. This study aimed to determine the effects of supervised multimodal exercise interventions on cancer-related fatigue through a systematic review and meta-analysis. A systematic review was conducted to determine the effectiveness of multimodal exercise interventions on CRF. Databases of PubMed, CENTRAL, EMBASE, and OVID were searched between January and March 2014 to retrieve randomized controlled trials. Risk of bias was evaluated using the PEDro scale. Nine studies (n = 772) were included in both systematic review and meta-analysis. Multimodal interventions including aerobic exercise, resistance training, and stretching improved CRF symptoms (SMD = -0.23; 95% CI: -0.37 to -0.09; P = 0.001). These effects were also significant in patients undergoing chemotherapy (P training interventions (P = 0.30). Slight evidence of publication bias was observed (P = 0.04). The studies had a low risk of bias (PEDro scale mean score of 6.4 (standard deviation (SD) ± 1.0)). Supervised multimodal exercise interventions including aerobic, resistance, and stretching exercises are effective in controlling CRF. These findings suggest that these exercise protocols should be included as a crucial part of the rehabilitation programs for cancer survivors and patients during anticancer treatments.

  6. Mediation by peer violence victimization of sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors: pooled youth risk behavior surveys.

    Science.gov (United States)

    Rosario, Margaret; Corliss, Heather L; Everett, Bethany G; Russell, Stephen T; Buchting, Francisco O; Birkett, Michelle A

    2014-06-01

    We examined the role of adolescent peer violence victimization (PVV) in sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex sexual attraction, partners, or identity as sexual minority and the remainder as heterosexual. We had 4 indicators of tobacco and alcohol use and 4 of sexual risk and 2 PVV factors: victimization at school and carrying weapons. We stratified associations by gender and race/ethnicity. PVV was related to disparities in cancer-related risk behaviors of substance use and sexual risk, with odds ratios (ORs) of 1.3 (95% confidence interval [CI] = 1.03, 1.6) to 11.3 (95% CI = 6.2, 20.8), and to being a sexual minority, with ORs of 1.4 (95% CI = 1.1, 1.9) to 5.6 (95% CI = 3.5, 8.9). PVV mediated sexual orientation disparities in substance use and sexual risk behaviors. Findings were pronounced for adolescent girls and Asian/Pacific Islanders. Interventions are needed to reduce PVV in schools as a way to reduce sexual orientation disparities in cancer risk across the life span.

  7. Efficacy and Safety of the Traditional Herbal Medicine, Gamiguibi-tang, in Patients With Cancer-Related Sleep Disturbance: A Prospective, Randomized, Wait-List-Controlled, Pilot Study.

    Science.gov (United States)

    Lee, Jee Young; Oh, Hye Kyung; Ryu, Han Sung; Yoon, Sung Soo; Eo, Wankyu; Yoon, Seong Woo

    2017-10-01

    Sleep disturbance is the second most bothersome symptom in patients with cancer, and it can significantly impair their quality of life. The aim of this study was to investigate the efficacy and safety of the traditional herbal medicine Gamiguibi-tang (GGBT) in patients with cancer-related sleep disturbance. We conducted a prospective, randomized, wait-list-controlled, open-label pilot clinical trial on cancer-related sleep disturbance. Patients with cancer experiencing poor sleep quality with a Pittsburgh Sleep Quality Index of at least 6 were randomly assigned to the GGBT and wait-list groups to receive GGBT and conventional care, respectively, for 2 weeks. The primary endpoint was the Insomnia Severity Index (ISI) score. Fatigue, depression, and cognitive impairment were assessed as the secondary endpoints by using the Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), and Montreal Cognitive Assessment (MoCA). Thirty participants who met the eligibility criteria were enrolled. Sleep disturbance assessed using the ISI improved significantly more in the GGBT group than in the wait-list group (-5.5 ± 4.4 vs 0.1 ± 1.1, P sleep disturbance. Further research is needed to investigate the efficacy and safety of GGBT.

  8. In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell-Derived Osteoprogenitors

    Directory of Open Access Journals (Sweden)

    Intekhab Islam

    2016-01-01

    Full Text Available Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs are potentially an unlimited source of healthy and functional osteoprogenitors (OPs that could be utilized for bone regenerative applications. However, limited ability to track hESC-derived progenies in vivo greatly hinders translational studies. Hence, in this study, we aimed to establish hESC-derived OPs (hESC-OPs expressing green fluorescent protein (GFP and to investigate their osteogenic differentiation potential in vitro. We fluorescently labelled H9-hESCs using a plasmid vector encoding GFP. The GFP-expressing hESCs were differentiated into hESC-OPs. The hESC-OPsGFP+ stably expressed high levels of GFP, CD73, CD90, and CD105. They possessed osteogenic differentiation potential in vitro as demonstrated by increased expression of COL1A1, RUNX2, OSTERIX, and OPG transcripts and mineralized nodules positive for Alizarin Red and immunocytochemical expression of osteocalcin, alkaline phosphatase, and collagen-I. In conclusion, we have demonstrated that fluorescently labelled hESC-OPs can maintain their GFP expression for the long term and their potential for osteogenic differentiation in vitro. In future, these fluorescently labelled hESC-OPs could be used for noninvasive assessment of bone regeneration, safety, and therapeutic efficacy.

  9. Biomimetic Engineering of Nanofibrous Gelatin Scaffolds with Noncollagenous Proteins for Enhanced Bone Regeneration

    Science.gov (United States)

    Sun, Yao; Jiang, Yong; Liu, Qilin; Gao, Tian; Feng, Jian Q.; Dechow, Paul; D'Souza, Rena N.; Qin, Chunlin

    2013-01-01

    Biomimetic approaches are widely used in scaffolding designs to enhance tissue regeneration. In this study, we integrated noncollagenous proteins (NCPs) from bone extracellular matrix (ECM) with three-dimensional nanofibrous gelatin (NF-Gelatin) scaffolds to form an artificial matrix (NF-Gelatin-NCPs) mimicking both the nano-structured architecture and chemical composition of natural bone ECM. Through a chemical coupling process, the NCPs were evenly distributed over all the surfaces (inner and outer) of the NF-gelatin-NCPs. The in vitro study showed that the number of osteoblasts (MC3T3-E1) on the NF-Gelatin-NCPs was significantly higher than that on the NF-Gelatin after being cultured for 14 days. Both the alkaline phosphatase (ALP) activity and the expression of osteogenic genes (OPN, BSP, DMP1, CON, and Runx2) were significantly higher in the NF-Gelatin-NCPs than in the NF-Gelatin at 3 weeks. Von Kossa staining, backscattered scanning electron microscopy, and microcomputed tomography all revealed a higher amount of mineral deposition in the NF-Gelatin-NCPs than in the NF-Gelatin after in vitro culturing for 3 weeks. The in vivo calvarial defect study indicated that the NF-Gelatin-NCPs recruited more host cells to the defect and regenerated a higher amount of bone than the controls after implantation for 6 weeks. Immunohistochemical staining also showed high-level mineralization of the bone matrix in the NF-Gelatin-NCPs. Taken together, both the in vitro and in vivo results confirmed that the incorporation of NCPs onto the surfaces of the NF-Gelatin scaffold significantly enhanced osteogenesis and mineralization. Biomimetic engineering of the surfaces of the NF-Gelatin scaffold with NCPs, therefore, is a promising strategy to enhance bone regeneration. PMID:23469769

  10. Protein-protein interactions

    DEFF Research Database (Denmark)

    Byron, Olwyn; Vestergaard, Bente

    2015-01-01

    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers......, are reported. The aim is to depict how the elucidation of the interplay of structures requires the interplay of methods....

  11. Research on Skin Cancer-Related Behaviors and Outcomes in the NIH Grant Portfolio, 2000-2014: Skin Cancer Intervention Across the Cancer Control Continuum (SCI-3C).

    Science.gov (United States)

    Perna, Frank M; Dwyer, Laura A; Tesauro, Gina; Taber, Jennifer M; Norton, Wynne E; Hartman, Anne M; Geller, Alan C

    2017-05-01

    The Surgeon General's Call to Action to Prevent Skin Cancer broadly identified research gaps, but specific objectives are needed to further behavioral intervention research. To review National Institute of Health (NIH) grants targeting skin cancer-related behaviors and relevant outcomes. A portfolio analysis of the title, abstract, specific aims, and research plans of identified grant applications from 2000 to 2014 targeting skin cancer-related behaviors or testing behavioral intervention effects on cancer-relevant outcomes along the cancer continuum. Funding trends were compared along the cancer control continuum, with respect to investigator demographics and use of theory, technology, policy, and changes to environmental surroundings (built environment). A total of 112 submitted applications met inclusion criteria; of these, 40 (35.7%) were funded, and 31 of the 40 were interventions. Comparing the 40 funded grants with the 72 unfunded grants, the overall success rates did not differ significantly between male (33.3%) and female (37.3%) investigators, nor did the frequency of R01 awards (36.7% and 28.1%, respectively). Among intervention awards, most (24 of 31) addressed prevention. Fewer awards targeted detection alone or in conjunction with prevention (3) or cancer survivorship (4), and no grant addressed emotional sequelae or adherence behavior related to diagnosis or treatment. Fewer than half of funded grants aimed for clinically related targets (eg, sunburn reduction). Use of theory and technology occurred in more than 75% of grants. However, the full capability of proposed technology was infrequently used, and rarely did constructs of the proposed behavior change theory clearly and comprehensively drive the intervention approach. Policy or environmental manipulation was present in all dissemination grants but was rarely used elsewhere, and 19.4% included policy implementation and 25.8% proposed changes in built environment. Grant success rate in skin

  12. Essential role for cyclic-AMP responsive element binding protein 1 (CREB) in the survival of acute lymphoblastic leukemia

    NARCIS (Netherlands)

    van der Sligte, Naomi E.; Kampen, Kim R.; ter Elst, Arja; Scherpen, Frank J. G.; Meeuwsen-de Boer, Tiny G. J.; Guryev, Victor; van Leeuwen, Frank N.; Kornblau, Steven M.; de Bont, Eveline S. J. M.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) relapse remains a leading cause of cancer related death in children, therefore, new therapeutic options are needed. Recently, we showed that a peptide derived from Cyclic-AMP Responsive Element Binding Protein (CREB) was highly phosphorylated in pediatric

  13. Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers.

    Directory of Open Access Journals (Sweden)

    Maciej Zabel

    2006-06-01

    Full Text Available It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3, immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02. Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively, in G2 cases (P = 0.003 and P = 0.03 and in G3 cases (P = 0.01 and P = 0.03. Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis.

  14. Case report: Manual lymphatic drainage and kinesio taping in the secondary malignant breast cancer-related lymphedema in an arm with arteriovenous (A-V) fistula for hemodialysis.

    Science.gov (United States)

    Chou, Ya-Hui; Li, Shu-Hua; Liao, Su-Fen; Tang, Hao-Wei

    2013-08-01

    Lymphedema is a dreaded complication of breast cancer treatment. The standard care for lymphedema is complex decongestive physiotherapy, which includes manual lymphatic drainage (MLD), short stretch bandaging, exercise, and skin care. The Kinesio Taping could help to improve lymphatic uptake. We reported a patient with unilateral secondary malignant breast cancer-related lymphedema and arteriovenous (A-V) fistula for hemodialysis happened in the same arm, and used kinesio taping, MLD, and exercise to treat this patient because no pressure could be applied to the A-V fistula. The 12-session therapy created an excellent effect. We do not think the kinesio taping could replace short stretch bandaging, but it could be another choice for contraindicating pressure therapy patients, and we should pay attention to wounds induced by kinesio tape.

  15. Sexual orientation disparities in cancer-related risk behaviors of tobacco, alcohol, sexual behaviors, and diet and physical activity: pooled Youth Risk Behavior Surveys.

    Science.gov (United States)

    Rosario, Margaret; Corliss, Heather L; Everett, Bethany G; Reisner, Sari L; Austin, S Bryn; Buchting, Francisco O; Birkett, Michelle

    2014-02-01

    We examined sexual orientation disparities in cancer-related risk behaviors among adolescents. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex orientation as sexual minority and the remainder as heterosexual. We compared the groups on risk behaviors and stratified by gender, age ( 14 years), and race/ethnicity. Sexual minorities (7.6% of the sample) reported more risk behaviors than heterosexuals for all 12 behaviors (mean = 5.3 vs 3.8; P sexual orientation disparities in analyses by gender, followed by age, and then race/ethnicity; they persisted in analyses by gender, age, and race/ethnicity, although findings were nuanced. Data on cancer risk, morbidity, and mortality by sexual orientation are needed to track the potential but unknown burden of cancer among sexual minorities.

  16. Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health.

    Science.gov (United States)

    Mańas, Ana; Ciria, Juan Pablo; Fernández, María Carmen; Gonzálvez, María Luisa; Morillo, Virginia; Pérez, María; Masramon, Xavier; López-Gómez, Vanessa

    2011-09-01

    A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.

  17. Prognostic value of computed tomography pulmonary angiography indices in patients with cancer-related pulmonary embolism: Data from a multicenter cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Plasencia-Martínez, Juana María, E-mail: plasen79@gmail.com [Radiology Department, Hospital Universitario Morales Meseguer, Av Marqués de los Vélez, s/n, 30008, Murcia (Spain); Carmona-Bayonas, Alberto [Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, Av Marqués de los Vélez, s/n, 30008, Murcia (Spain); Calvo-Temprano, David [Radiology Department, Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo (Spain); Jiménez-Fonseca, Paula [Medical Oncology Department, Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo (Spain); Fenoy, Francisco [Department of Physiology, Faculty of Medicine, Campus Universitario de Espinardo, University of Murcia, s/n, 30100 Espinardo, Murcia (Spain); Benegas, Mariana; Sánchez, Marcelo [Radiology Department, Hospital Clínic de Barcelona (HCB), Villarroel, 170, 08036, Barcelona (Spain); Font, Carme [Medical Oncology Department, Hospital Clínic de Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors, IDIBAPS, Villarroel, 170, 08036, Barcelona (Spain); Varona, Diego [Radiology Department, Hospital Universitari Vall d’Hebron, Passeig de la Vall d' Hebron, 119-129, 08035, Barcelona (Spain); Martínez de la Haza, David [Radiology Department, Hospital Duran i Reynals, Institut Català d’Oncologia (ICO), Avinguda Granvia, 199-203, 08907, Hospitalet de Llobregat, Barcelona (Spain); and others

    2017-02-15

    Highlights: • CTPA can predict the prognosis of pulmonary embolism in cancer patients. • Right ventricular dysfunction (RVD) is predictive of complications at 15 days. • The Frank-Starling mechanism is the theoretical framework to interpret RVD signs. • Pulmonary artery obstruction plays a pathophysiological role only in subjects with RVD. • A proposal for an explanation of clinical-radiological dissociation is presented. - Abstract: Objective: To analyze the prognostic value of pulmonary artery obstruction versus right-ventricle (RV) dysfunction radiologic indices in cancer-related pulmonary embolism (PE). Methods: We enrolled 303 consecutive patients with paraneoplastic PE, evaluated by computed tomography pulmonary angiography (CTPA) between 2013 and 2014. The primary outcome measure was serious complications at 15 days. Multivariate analyses were conducted by using binary logistic and robust regressions. Radiological features such as the Qanadli index (QI) and RV dysfunction signs were analyzed with Spearman’s partial rank correlations. Results: RV diameter was the only radiological variable associated with an adverse outcome. Subjects with enlarged RV (diameter > 45 mm) had more 15-day complications (58% versus 40%, p = 0.001). The QI correlated with the RV diameter (r = 0.28, p < 0.001), left ventricle diameter (r = −0.19, p < 0.001), right ventricular-to-left ventricular diameter ratio (r = 0.39, p < 0.001), pulmonary artery diameter (r = 0.22, p < 0.001), and pulmonary artery/ascending aorta ratio (r = 0.27, p < 0.001). A QI ≥ 50% was only associated with 15-day complications in subjects with enlarged RV, inverted intraventricular septum, or chronic cardiopulmonary diseases. The central or peripheral PE location did not affect the correlations among radiological variables and was not associated with clinical outcomes. Conclusions: Right ventricular dysfunction signs in CTPA are more useful than QI in predicting cancer-related PE outcome.

  18. Efficacy of low-frequency low-intensity electrotherapy in the treatment of breast cancer-related lymphoedema: a cross-over randomized trial.

    Science.gov (United States)

    Belmonte, Roser; Tejero, Marta; Ferrer, Montse; Muniesa, Josep Maria; Duarte, Esther; Cunillera, Oriol; Escalada, Ferran

    2012-07-01

    To compare the efficacy of low-frequency low-intensity electrotherapy and manual lymphatic drainage in the treatment of chronic upper limb breast cancer-related lymphoedema. Cross-over single-blind random clinical trial. Rehabilitation service. Thirty-six women with chronic upper limb breast cancer-related lymphoedema. Patients were randomized to undergo 10 sessions of manual lymphatic drainage followed by 10 sessions of low-frequency low-intensity electrotherapy or to undergo first low-frequency low-intensity electrotherapy followed by manual lymphatic drainage. There was a month of washout time between treatments. Each patient was examined just before and after each treatment. Researchers and outcome assessors were blinded for assigned treatment. Outcomes were lymphoedema volume, pain, heaviness and tightness, and health-related quality of life measured with the Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer version 4 (FACT-B+4). Carry-over, period and treatment effects were analysed. Treatment effect was assessed using paired t-test. Thirty patients finalized treatment. Comparing the changes in low-frequency low-intensity electrotherapy with manual lymphatic drainage changes, there were no significant differences. Low-frequency low-intensity electrotherapy did not reduce lymphoedema volume (mean of change = 19.77 mL, P = 0.36), but significant reductions were observed in pain, heaviness and tightness (mean of change = 13.1, 16.2 and 6.4 mm, respectively), and FACT-B+4 summaries improved significantly (Trial Outcome Index mean of change = 5.4, P = 0.015). Manual lymphatic drainage showed no significant changes in any of the outcomes Although there are no significant differences between treatment changes, the observed trend towards a better health-related quality of life is remarkable in low-frequency low-intensity electrotherapy.

  19. The effectiveness of a deep water aquatic exercise program in cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

    Science.gov (United States)

    Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Cuesta-Vargas, Antonio I; Del Moral-Avila, Rosario; Fernández-de-Las-Peñas, César; Arroyo-Morales, Manuel

    2013-02-01

    To investigate the effectiveness of an 8-week aquatic program on cancer-related fatigue, as well as physical and psychological outcomes in breast cancer survivors. A randomized controlled trial. Outpatient clinic, urban, academic medical center, and a sport university swimming pool. Breast cancer survivors (N=68) were randomly assigned to either an experimental (aquatic exercise group in deep water pool) group or a control (usual care) group. The intervention group attended aquatic exercise sessions 3 times per week for 8 weeks in a heated deep swimming pool. Sessions lasted 60 minutes in duration: 10 minutes of warm-up, 40 minutes of aerobic and endurance exercises, and 10 minutes of cool-down exercises. Patients allocated to the usual care group followed the oncologist's recommendations in relation to a healthy lifestyle. Values for fatigue (Piper Fatigue Scale), mood state (Profile of Mood States), and abdominal (trunk curl static endurance test) and leg (multiple sit-to-stand test) strength were collected at baseline, after the last treatment session, and at a 6-month follow-up. Immediately after discharge, the aquatic exercise group showed a large effect size in total fatigue score (d=.87; 95% confidence interval, .48-1.26), trunk curl endurance (d=.92; 95% confidence interval, 1.97-3.83), and leg strength (d=1.10; .55-2.76), but negligible effects in vigor, confusion, and disturbance of mood (daquatic exercise group maintained large to small effect sizes in fatigue scores, multiple sit-to-stand test, and trunk curl static endurance (.25>d>.90) and negligible effects for the fatigue-severity dimension and different scales of the Profile of Mood States (daquatic exercise program conducted in deep water was effective for improving cancer-related fatigue and strength in breast cancer survivors. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  20. Efficacy of night-time compression for breast cancer related lymphedema (LYNC): protocol for a multi-centre, randomized controlled efficacy trial

    International Nuclear Information System (INIS)

    McNeely, Margaret L.; Campbell, Kristin L.; Webster, Marc; Kuusk, Urve; Tracey, Karen; Mackey, John

    2016-01-01

    Lymphedema is a prevalent long-term effect of breast cancer treatment that is associated with reduced quality of life. More recent observational data suggest that the addition of night-time compression to day-time use of a compression garment results in better long-term control of arm lymphedema. The primary objectives of the randomized controlled phase of the trial are to determine the efficacy of night-time compression on arm lymphedema volume maintenance and quality of life in breast cancer survivors who have completed intensive reduction treatment for their lymphedema. The study will be a parallel 3-arm, multi-centre randomized fast-track trial. A total of 120 women with breast cancer related lymphedema will be recruited from 3 centres in Canada and randomized to group 1: Day-time compression garment alone or Group 2: Day-time compression garment + night-time compression bandaging or Group 3: Day-time compression garment + use of a night-time compression system garment. The duration of the primary intervention period will be 12 weeks. The follow-up period after the intervention (weeks 13 to 24) will follow a longitudinal observational design. The primary outcome variables: differences from baseline to week 12 in arm volume and quality of life (Lymphoedema Functioning, Disability and Health Questionnaire: Lymph-ICF). Secondary outcomes include bioimpedance analysis, sleep disturbance and self-efficacy. All measurements are standardized and will be performed prior to randomization, and at weeks 6, 12, 18 and 24. The use of night-time compression as a self-management strategy for chronic breast cancer related lymphedema is seen as an innovative approach to improve long-term control over the condition. This trial aims to advance the knowledge on self-management strategies for lymphedema

  1. Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life.

    Science.gov (United States)

    Steindorf, K; Schmidt, M E; Klassen, O; Ulrich, C M; Oelmann, J; Habermann, N; Beckhove, P; Owen, R; Debus, J; Wiskemann, J; Potthoff, K

    2014-11-01

    Exercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer (BC) populations. However, studies investigating exercise during radiotherapy or resistance training are scarce. We conducted a randomized, controlled trial (BEST study) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention. One hundred sixty patients with BC stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (RC, 2 times/week). Both interventions were group-based. The primary end point fatigue was assessed with a 20-item multidimensional questionnaire, QoL with EORTC questionnaires. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. Adherence to the intervention program as well as the completion rate (97%) for the primary outcome variable fatigue was high. In intention-to-treat analyses for the N = 155 patients, significant between-group mean differences (MD) favoring the exercise group (EX) were observed for general fatigue (P = 0.044), especially for the subscale physical fatigue [MD = -0.8; 95% confidence interval -1.5 to -0.2, P = 0.013], but not for affective (P = 0.91) or cognitive fatigue (P = 0.65). For QoL, significantly larger improvements regarding the role function (P = 0.035) and pain (P = 0.040) were noted among exercisers compared with RCs. Future perspective improved significantly stronger in the RC group compared with the EX group (P = 0.047). The 12-week resistance training program was a safe, feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy. As exercise was compared with another group-based intervention, results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits, and that the

  2. Cancer-related fatigue and rehabilitation: a randomized controlled multicenter trial comparing physical training combined with cognitive-behavioral therapy with physical training only and with no intervention.

    Science.gov (United States)

    van Weert, Ellen; May, Anne M; Korstjens, Irene; Post, Wendy J; van der Schans, Cees P; van den Borne, Bart; Mesters, Ilse; Ros, Wynand J G; Hoekstra-Weebers, Josette E H M

    2010-10-01

    Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with cognitive behavioral therapy with physical training alone and with no intervention. In this multicenter randomized controlled trial, 147 survivors of cancer were randomly assigned to a group that received physical training combined with cognitive-behavioral therapy (PT+CBT group, n=76) or to a group that received physical training alone (PT group, n=71). In addition, a nonintervention control group (WLC group) consisting of 62 survivors of cancer who were on the waiting lists of rehabilitation centers elsewhere was included. The study was conducted at 4 rehabilitation centers in the Netherlands. All patients were survivors of cancer. Physical training consisting of 2 hours of individual training and group sports took place twice weekly, and cognitive-behavioral therapy took place once weekly for 2 hours. Fatigue was assessed with the Multidimensional Fatigue Inventory before and immediately after intervention (12 weeks after enrollment). The WLC group completed questionnaires at the same time points. Baseline fatigue did not differ significantly among the 3 groups. Over time, levels of fatigue significantly decreased in all domains in all groups, except in mental fatigue in the WLC group. Analyses of variance of postintervention fatigue showed statistically significant group effects on general fatigue, on physical and mental fatigue, and on reduced activation but not on reduced motivation. Compared with the WLC group, the PT group reported significantly greater decline in 4 domains of fatigue, whereas the PT+CBT group reported significantly greater decline in physical fatigue only. No significant differences in decline in fatigue were found between the PT+CBT and PT groups. Physical training combined

  3. Effectiveness of an individualized program of muscular strength and endurance with aerobic training for improving germ cell cancer-related fatigue in men undergoing chemotherapy: EFICATEST study protocol for a randomized controlled trial.

    Science.gov (United States)

    Cuesta-Vargas, Antonio Ignacio; Carabantes, Francisco; Caracuel, Zaira; Conejo, Inmaculada; Alba, Emilio

    2016-01-05

    Patients with testicular germ cell cancer (GCC) have a high cure rate; however, cancer-related fatigue is the most common complication among patients with GCC undergoing treatment with chemotherapy. Although exercise is widely recommended, information about the physio-pathological effects of cancer therapy on skeletal muscle is very limited. Our aim is to evaluate the effects of an individualized program of muscular strength and endurance with aerobic training on cancer-related fatigue. The present study is a randomized controlled trial comparing an individualized program of muscular strength and endurance with aerobic training compared to a control group. We will conduct this trial in patients undergoing chemotherapy, recruited by the Department of Oncology of Virgen de la Victoria Hospital (Málaga). Patients will be included and evaluated before the first cycle of chemotherapy and assigned randomly to the experimental or control group. Cancer-related fatigue, physical condition and biological samples will be measured at the beginning and at the end of an 8-week intervention by the same evaluator, who will be unaware of the allocation of participants to each group. Furthermore, there will be monitoring for 6 months (24 weeks) after training for all outcome variables. This study hopes to offer patients with GCC an individualized exercise program with aerobic training for cancer-related fatigue. Such a scheme, if beneficial, could be implemented successfully within public health. ClinicalTrials.gov Identifier: NCT02433197 . Date of registration: 13 April 2015.

  4. Examining the mediating role of cancer-related problems on spirituality and self-rated health among African American cancer survivors: a report from the American Cancer Society's Studies of Cancer Survivors-II.

    Science.gov (United States)

    Best, Alicia L; Alcaraz, Kassandra I; McQueen, Amy; Cooper, Dexter L; Warren, Rueben C; Stein, Kevin

    2015-09-01

    African American (AA) cancer survivors report poorer self-rated health (SRH) compared to other racial/ethnic groups. Spirituality is often linked to positive health outcomes, with AAs reporting greater levels of spirituality. This study examined the potential mediating role of cancer-related problems in the relationship between spirituality and SRH among AA cancer survivors compared to non-African American (non-AA) survivors. We analyzed data on 9006 adult cancer survivors from the American Cancer Society's Study of Cancer Survivors-II. Preliminary analyses compared characteristics of AAs and non-AAs and identified significant covariates of SRH. We tested a path model using multi-group structural equation modeling (SEM), and then examined race as a moderator. Of the three domains of spirituality assessed, AAs had higher levels of peace (p spirituality and cancer-related problems on SRH. Specifically, spirituality had significantly stronger associations with cancer-related problems among AAs than non-AAs. Spirituality was positively associated with all four domains of cancer-related problems, but only physical distress was associated with SRH among AAs. The negative effects of physical distress may attenuate the positive effects of spirituality on AA's SRH. Future studies should consider racial/ethnic differences in the determinants and conceptualization of SRH, which is a known predictor of survival. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Interfacial Protein-Protein Associations

    OpenAIRE

    Langdon, Blake B.; Kastantin, Mark; Walder, Robert; Schwartz, Daniel K.

    2013-01-01

    While traditional models of protein adsorption focus primarily on direct protein-surface interactions, recent findings suggest that protein-protein interactions may play a central role. Using high-throughput intermolecular resonance energy transfer (RET) tracking, we directly observed dynamic, protein-protein associations of bovine serum albumin on poly(ethylene glycol) modified surfaces. The associations were heterogeneous and reversible, and associating molecules resided on the surface for ...

  6. Deciphering the protein-protein interaction network regulating hepatocellular carcinoma metastasis.

    Science.gov (United States)

    Qin, Guoxuan; Dang, Mengjiao; Gao, Huajun; Wang, Hao; Luo, Fengting; Chen, Ruibing

    2017-09-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. To better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by quantitative proteomics and bioinformatics analysis. As a result, we identified 378 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that the metabolism and cytoskeleton biological processes are greatly involved with HCC metastasis. Furthermore, the integrative network analysis revealed a rich-club organization within the PPI network, indicating a hub center of connections. The rich-club nodes include several well-known cancer-related proteins, such as proto-oncogene non-receptor tyrosine kinase (SRC) and pyruvate kinase M2 (PKM2). Moreover, the differential expressions of two identified proteins, including PKM2 and actin-related protein 2/3 complex subunit 4 (ARPC4), were validated using Western blotting. These two proteins were revealed as potential prognostic markers for HCC as shown by survival rate analysis. Copyright © 2017. Published by Elsevier B.V.

  7. A comparison of cognitive function, sleep and activity levels in disease-free breast cancer patients with or without cancer-related fatigue syndrome.

    Science.gov (United States)

    Minton, Ollie; Stone, Patrick C

    2012-09-01

    Chronic fatigue is a feature in a subset of women successfully treated for breast cancer but is not well characterised. This study examines differences in objective cognitive function, activity levels and sleep in disease-free women who do and do not meet criteria for cancer-related fatigue syndrome (CRFS). Women between 3 months and 2 years after completion of any primary therapy were recruited from a cancer centre follow-up clinic. On the basis of a diagnostic semi-structured interview they were classified as being CRFS cases or non-fatigued controls. Participants underwent objective cognitive testing using a computerised battery, wore an activity monitor for 1 week and completed quality of life and fatigue questionnaires. 114 women were recruited (69 controls and 45 CRFS cases). There were significant differences between groups on fatigue, mood, sleep and quality of life scores, and in objective cognitive testing (tests of sustained attention, reaction time and verbal memory all psleep or in routine laboratory measures. Our preliminary results suggest that disease-free women with CRFS after successful breast cancer treatment have significantly lower subjective quality of life and mood. Additionally, objective cognitive impairment in certain domains may play an important role in the subjective manifestation of these symptoms. There is also objective evidence on actigraphy of differing levels of activity. The subjective sleep disturbance and higher prevalence of insomnia do not correlate with objective measures.

  8. Do we have predictors of therapy responsiveness for a multimodal therapy concept and aerobic training in breast cancer survivors with chronic cancer-related fatigue?

    Science.gov (United States)

    Kröz, M; Reif, M; Zerm, R; Winter, K; Schad, F; Gutenbrunner, C; Girke, M; Bartsch, C

    2015-09-01

    Cancer-related fatigue (CRF) is a burdensome symptom for breast cancer (BC) patients. In this pilot study, we tested several questionnaires as predictors for treatment responsiveness, along with the implementation of a multimodal therapy concept consisting of sleep, psycho-education, eurythmy, painting therapy and standard aerobic training. At the Community Hospital Havelhöhe and the Hannover Medical School, 31 BC patients suffering from CRF could be evaluated in a 10-week intervention study. CRF was assessed by the Cancer Fatigue Scale (CFS-D). Further questionnaires were the Pittsburgh Sleep Quality Index, the autonomic regulation scale, Self-Regulation Scale (SRS), the Internal Coherence Scale (ICS) and the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale. We estimated the regression coefficients of all scales on CFS-D by simple and multiple linear regression analyses and compared regression slopes and variances between the different questionnaires on CFS-D at the end of treatment. We found a significant impact of SRS and ICS at baseline on CFS-D at the end of the intervention [absolute standardised multiple regression coefficient values ranging from 0.319 (SRS) to 0.269 (ICS)] but not for the other questionnaires. In conclusion, this study supports the hypothesis that the SRS or ICS measuring adaptive capacities could be more appropriate as outcome predictors than classical questionnaire measures in complex interventions studies. © 2015 John Wiley & Sons Ltd.

  9. Cancer-related fatigue management: evaluation of a patient education program with a large-scale randomised controlled trial, the PEPs fatigue study.

    Science.gov (United States)

    Bourmaud, A; Anota, A; Moncharmont, C; Tinquaut, F; Oriol, M; Trillet-Lenoir, V; Bajard, A; Parnalland, S; Rotonda, C; Bonnetain, F; Pérol, D; Chauvin, F

    2017-03-28

    To assess the efficacy of a patient educational program built according to guidelines that aims at reducing cancer-related fatigue (CRF). Randomised controlled trial, multicentre, comparing a patient education program, vs the standard of care. Patients were adult cancer outpatients with any tumour site. The primary outcome was fatigue severity assessed with a visual analogical scale (VAS), between the day of randomisation and week 7. Secondary outcomes were fatigue assessed with other scales, health-related quality of life, anxiety and depression. The time to fatigue severity deterioration was assessed. Analyses were performed in a modified intent-to-treat way, that is, including all patients with at least one baseline and 1 week 7 score. A total of 212 patients were included. Fatigue severity assessment was made on 79 patients in the experimental group and 65 in the control group. Between randomisation and week 7, the fatigue (VAS) improved by 0.96 (2.85) points in the experimental group vs 1.63 (2.63) points in the control group (P=0.15). No differences with the secondary outcomes were highlighted between two groups. No other factors were found to be associated with fatigue severity deterioration. Despite rigorous methodology, this study failed to highlight the program efficacy in fatigue reduction for cancer patients. Other assessment tools should be developed to measure the effect of the program on CRF and behaviour. The implementation of the program should also be explored in order to identify its mechanisms and longer-term impact.

  10. The reliable assurance of detecting somatic mutations in cancer-related genes by next-generation sequencing: the results of external quality assessment in China.

    Science.gov (United States)

    Zhang, Rui; Ding, Jiansheng; Han, Yanxi; Yi, Lang; Xie, Jiehong; Yang, Xin; Fan, Gaowei; Wang, Guojing; Hao, Mingju; Zhang, Dong; Zhang, Kuo; Lin, Guigao; Li, Jinming

    2016-09-06

    To evaluate the proficiencies of laboratories utilizing next-generation sequencing (NGS) to detect somatic mutations in cancer-related genes, an external quality assessment (EQA) was implemented by the National Center for Clinical Laboratories of China in 2015. We prepared a panel of samples that comprised eight samples made by mixing synthetic mutated DNA fragments with normal human genomic DNA and one reference sample containing only genomic DNA. We validated our sample panel, and then distributed it to laboratories across China. We received complete results from 64 laboratories. The performances of 51.6 % (33/64) respondent labs were acceptable and 26.6 % (17/64) of the labs returned perfect results. In total, 449 mistakes were reported, including 201 false-negatives (201/449, 44.8 %) and 222 false-positives (222/449, 49.4 %) and 26 slightly discordant results (26/449, 5.8 %). We believe these unsatisfactory results and varied performances are mainly due to the enrichment methods used, the diverse sequencing chemistries of the different NGS platforms, and other errors within the sequencing process. The results indicate that our sample panel is suitable for use in EQA studies, and that further laboratory training in targeted NGS testing is urgently required. To address this, we propose a targeted NGS workflow with details on quality assurance procedures according to the current guidelines.

  11. A Retrospective Study on the Effectiveness of Switching to Oral Methadone for Relieving Severe Cancer-Related Neuropathic Pain and Limiting Adjuvant Analgesic Use in Japan.

    Science.gov (United States)

    Sugiyama, Yosuke; Sakamoto, Nobuhiro; Ohsawa, Masahiro; Onizuka, Mami; Ishida, Kyoko; Murata, Yuki; Iio, Ayaka; Sugano, Koji; Maeno, Ken; Takeyama, Hiromitsu; Akechi, Tatsuo; Kimura, Kazunori

    2016-10-01

    Cancer-related neuropathic pain is resistant to treatment with multiple medications and results in reduced patient quality of life. The aim was to find a new curative to treat neuropathic pain without using adjuvant analgesics. This was a retrospective study that used the FACES Pain Scale (FPS) to measure pain intensity and pain relief. Twenty-eight inpatients who were treated with other strong opioids and who consulted the palliative care team about their pain relief. In 22 (78.6%) out of 28 patients who successfully switched to methadone from other strong opioids, such as oxycodone and fentanyl, within two weeks, the mean FPS score was significantly reduced from 4.43 to 1.86, and methadone switching either reduced the number of prescriptions or stopped them entirely in 12 out of 17 (70.5%) patients who had used adjuvant analgesics before switching to methadone. These results suggest that opioid switching to oral methadone not only achieves pain relief but also curtails substantial adjuvant analgesic use.

  12. Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms.

    Science.gov (United States)

    D'Ascenzio, Melissa; Guglielmi, Paolo; Carradori, Simone; Secci, Daniela; Florio, Rosalba; Mollica, Adriano; Ceruso, Mariangela; Akdemir, Atilla; Sobolev, Anatoly P; Supuran, Claudiu T

    2017-12-01

    A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (K i s > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with K i s ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (K i s ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.

  13. Barriers in the management of cancer-related pain and strategies to overcome them: findings of a qualitative research involving physicians and nurses in Italy

    Directory of Open Access Journals (Sweden)

    Cesarina Prandi

    2015-03-01

    Full Text Available Introduction and aims. There are many barriers and obstacles that even today lead to an inadequate treatment of cancer-related pain. The aim is to describe the experiences of a group of Italian physicians and nurses as far as the nature of these barriers is concerned and the possible tools to be used to overcome them. Material and method. We run 5 focus groups with 42 healthcare professionals (11 physicians, 31 nurses working in 5 hospitals in Italy. The findings of the focus groups were analysed according to the “Content Analysis” method. Results. Five main items emerged: the importance of communication, the need for education regarding pain therapy, the ethnic/cultural/religious differences, the mutual trust and support within the working group, the daily challenges. Conclusion. In harmony with the most recent literature, physicians and nurses voice above all their need for an education more directly aimed at overcoming the prevailing barriers rooted in ignorance, prejudice and fears.

  14. Racial disparities in cancer-related survival in patients with squamous cell carcinoma of the esophagus in the US between 1973 and 2013.

    Directory of Open Access Journals (Sweden)

    Alice Kim

    Full Text Available Esophageal cancer makes up approximately 1% of all diagnosed cancers in the US. There is a persistent disparity in incidence and cancer-related mortality rates among different races for esophageal squamous cell carcinoma (SCC. Most previous studies investigated racial disparities between black and white patients, occasionally examining disparities for Hispanic patients. Studies including Asians/Pacific Islanders (API as a subgroup are rare. Our objective was to determine whether there is an association between race and cancer-related survival in patients with esophageal SCC.This was a retrospective cohort study using the National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER database. The SEER registry is a national database that collects information on all incident cancer cases in 13 states of the United States and covers nearly 26% of the US population Patients aged 18 and over of White, Black, or Asian/Pacific Islander (API race with diagnosed esophageal SCC from 1973 to 2013 were included (n = 13,857. To examine overall survival, Kaplan-Meier curves were estimated for each race and the log-rank test was used to compare survival distributions. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios with 95% confidence intervals. The final adjusted model controlled for sex, marital status, age at diagnosis, decade of diagnosis, ethnicity, stage at diagnosis, and form of treatment. Additional analyses stratified by decade of diagnosis were conducted to explore possible changes in survival disparities over time. After adjustment for potential confounders, black patients had a statistically significantly higher hazard ratio compared to white patients (HR 1.08; 95% confidence interval (CI 1.03-1.13. However, API patients did not show a statistically significant difference in survival compared with white patients (HR 1.00; 95% CI 0.93-1.07. Patients diagnosed between 1973 and 1979 had twice

  15. The Impact of L-Dex® Measurements in Assessing Breast Cancer Related Lymphedema (BCRL as Part of Routine Clinical Practice

    Directory of Open Access Journals (Sweden)

    Alison L. Laidley, MD

    2016-09-01

    Full Text Available Purpose: With improved survivorship, the prevalence of breast cancer related lymphedema (BCRL continues to increase, leading to impairment of a patients’ quality of life. While traditional diagnostic methods are limited by an inability to detect BCRL until clinically apparent, bioimpedance spectroscopy (BIS has been shown to detect subclinical BCRL. The purpose of this study is to evaluate the role of BIS in the early detection of BCRL as well as assessment of response to BCRL treatment. Methods: A retrospective review of 1,133 patients treated between November 2008 and July 2013 at two surgical practices was performed. Eligible patients (n=326 underwent pre-operative and post-operative L-Dex measurements. Patients were identified as having subclinical lymphedema if they were asymptomatic and the L-Dex score increased > 10 units above baseline and were monitored following treatment. Patients were stratified by lymph node dissection technique (SLNB vs. ALND and receipt of BCRL treatment.Results: The average age of the cohort was 56.2 years old and mean follow-up was 21.7 months. Of the 326 patients, 210 underwent SLNB and 116 underwent ALND. BCRL was identified by L-Dex in 40 patients (12.3%. The cumulative incidence rate of subclinical lymphedema was 4.3% for SLNB (n=9 and 26.7% for ALND (n=31. Of those diagnosed with BCRL, 50% resolved following treatment, 27.5% underwent treatment without resolution, and 22.5% had resolution without treatment. The prevalence of persistent, clinical BCRL was 0.5% for SLNB and 8.6% for ALND.Conclusions: This study demonstrates both the feasibility and clinical utility of implementing L-Dex measurements in routine breast cancer care. L-Dex identified patients with possible subclinical BCRL and allowed for assessment of response to therapy.

  16. A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: a study protocol of a quasi-experimental design.

    Science.gov (United States)

    Borglin, Gunilla; Gustafsson, Markus; Krona, Hans

    2011-09-23

    Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted. A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention. Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain

  17. Are compression corsets beneficial for the treatment of breast cancer-related lymphedema? New opportunities in physiotherapy treatment – a preliminary report

    Directory of Open Access Journals (Sweden)

    Hansdorfer-Korzon R

    2016-04-01

    Full Text Available Rita Hansdorfer-Korzon,1 Jacek Teodorczyk,2 Agnieszka Gruszecka,3 Piotr Lass2,4 1Department of Physiotherapy, 2Department of Nuclear Medicine, 3Department of Informatics and Statistics, 4Department of Molecular Spectroscopy, Institute of Experimental Physics, Gdansk, Poland Introduction: Treatment of secondary lymphedema still remains an important medical issue. Treatment response is characterized by periodic remission rather than complete recovery. Compression methods currently used as part of complete decongestive therapy vary considerably in efficacy. Manual drainage, bandaging, and compression pumps are ineffective in everyday practice. Positive results have increasingly been reported where compression garments have been used as part of the treatment. This pilot study demonstrates a beneficial effect following the use of compression corsets in the treatment of edema in breast cancer-related lymphedema (BCRL. Material: A total of 35 women with BCRL were enrolled. Of these, 29 patients completed the study. Methods: Ultrasound (B-mode was used to evaluate lymphedema in the side of the chest after mastectomy. This test was performed three times at a specific site on the operated side and symmetrically on the opposite side. Subsequently, patients were fit with an appropriate compression corset. The data were then statistically analyzed. Conclusion: After the surgical treatment of breast cancer, lymphatic fluid reservoirs may form at the side of the chest. The use of carefully selected compression corsets is an effective treatment for BCRL. Corsets are an important item, which we recommend should be included in compression clothing sets. We anticipate this finding will form the foundation for further work on the use of modern compression garments for the treatment of BCRL as well as contribute to the limited number of published reports that exist on the subject. Keywords: lymphedema, breast cancer, physical therapy

  18. Perceptions of Patient-Provider Communication in Breast and Cervical Cancer-Related Care: A Qualitative Study of Low-Income English- and Spanish-Speaking Women

    Science.gov (United States)

    Simon, Melissa A.; Ragas, Daiva M.; Nonzee, Narissa J.; Phisuthikul, Ava M.; Luu, Thanh Ha; Dong, XinQi

    2013-01-01

    To explore patient perceptions of patient-provider communication in breast and cervical cancer-related care among low-income English- and Spanish- speaking women, we examined communication barriers and facilitators reported by patients receiving care at safety net clinics. Participants were interviewed in English or Spanish after receiving an abnormal breast or cervical cancer screening test or cancer diagnosis. Following an inductive approach, interviews were coded and analyzed by the language spoken with providers and patient-provider language concordance status. Of 78 participants, 53% (n = 41) were English-speakers and 47% (n = 37) were Spanish-speakers. All English-speakers were language-concordant with providers. Of Spanish-speakers, 27% (n = 10) were Spanish-concordant; 38% (n = 14) were Spanish-discordant, requiring an interpreter; and 35% (n = 13) were Spanish mixed-concordant, experiencing both types of communication throughout the care continuum. English-speakers focused on communication barriers, and difficulty understanding jargon arose as a theme. Spanish-speakers emphasized communication facilitators related to Spanish language use. Themes among all Spanish-speaking sub-groups included appreciation for language support resources and preference for Spanish-speaking providers. Mixed-concordant participants accounted for the majority of Spanish-speakers who reported communication barriers. Our data suggest that, although perception of patient-provider communication may depend on the language spoken throughout the care continuum, jargon is lost when health information is communicated in Spanish. Further, the respective consistency of language concordance or interpretation may play a role in patient perception of patient-provider communication. PMID:23553683

  19. Supermicrosurgical deep lymphatic vessel-to-venous anastomosis for a breast cancer-related arm lymphedema with severe sclerosis of superficial lymphatic vessels.

    Science.gov (United States)

    Yamamoto, Takumi; Yamamoto, Nana; Hayashi, Akitatsu; Koshima, Isao

    2017-02-01

    Lymphatic supermicrosurgery or supermicrosurgical lymphaticovenular anastomosis (LVA) is becoming popular for the treatment of compression-refractory upper extremity lymphedema (UEL) with its effectiveness and minimally invasiveness. In conventional LVA, superficial lymphatic vessels are used for anastomosis, but its treatment efficacy would be minimum when superficial lymphatic vessels are severely sclerotic. Theoretically, deep lymphatic vessels can be used for LVA, but no clinical case has been reported regarding deep lymphatic vessel-to-venous anastomosis (D-LVA). We report a breast cancer-related UEL case treated with D-LVA, in which a less-sclerotic deep lymphatic vessel was useful for anastomosis but superficial lymphatic vessels were not due to severe sclerosis. A 62-year-old female suffered from an 18-year history of compression-refractory right UEL after right breast cancer treatments, and underwent LVA under local infiltration anesthesia. Because superficial lymphatic vessels found in surgical fields were all severely sclerotic, a deep lymphatic vessel was dissected at the cubital fossa. A 0.50-mm deep lymphatic vessel running along the brachial artery was supermicrosurgically anastomosed to a nearby 0.40-mm vein. At postoperative 12 months, her right UEL index decreased from 134 to 118, and she could reduce compression frequency from every day to 1-2 days per week to maintain the reduced lymphedematous volume. D-LVA may be a useful option for the treatment of compression-refractory UEL, when superficial lymphatic vessels are severely sclerotic. © 2015 Wiley Periodicals, Inc. Microsurgery 37:156-159, 2017. © 2015 Wiley Periodicals, Inc.

  20. A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: A study protocol of a quasi-experimental design

    Directory of Open Access Journals (Sweden)

    Gustafsson Markus

    2011-09-01

    Full Text Available Abstract Background Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted. Methods/design A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome, patient perception regarding pain (secondary outcome, together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention. Discussion Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that

  1. A randomized controlled trial of home-based exercise for cancer-related fatigue in women during and after chemotherapy with or without radiation therapy.

    Science.gov (United States)

    Dodd, Marylin J; Cho, Maria H; Miaskowski, Christine; Painter, Patricia L; Paul, Steven M; Cooper, Bruce A; Duda, John; Krasnoff, Joanne; Bank, Kayee A

    2010-01-01

    Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment. The purpose of this study was to evaluate the effectiveness of a home-based exercise training intervention, the Pro-self Fatigue Control Program on the management of cancer-related fatigue. Participants (N = 119) were randomized into 1 of 3 groups: group 1 received the exercise prescription throughout the study; group 2 received their exercise prescription after completing cancer treatment; and group 3 received usual care. Patients completed the Piper Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies-Depression Scale, and Worst Pain Intensity Scale. All groups reported mild fatigue levels, sleep disturbance, and mild pain, but not depression. Using multilevel regression analysis, significant linear and quadratic trends were found for change in fatigue and pain (ie, scores increased, then decreased over time). No group differences were found in the changing scores over time. A significant quadratic effect for the trajectory of sleep disturbance was found, but no group differences were detected over time. No significant time or group effects were found for depression. Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment. The optimal timing of exercise remains to be determined. Clinicians need to be aware that some physical activity is better than none, and there is no harm in exercise as tolerated during cancer treatment. Further analysis is needed to examine the adherence to exercise. More frequent assessments of fatigue, sleep disturbance, depression, and pain may capture the effect of exercise.

  2. Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Huang Xu

    2010-08-01

    Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

  3. Atrial fibrillation, CHA2DS2-VASc score, antithrombotics and risk of non-traffic-, non-cancer-related bone fractures: A population-based cohort study.

    Science.gov (United States)

    Lai, Hui-Chin; Chien, Wu-Chien; Chung, Chi-Hsiang; Lee, Wen-Lieng; Wu, Tsu-Juey; Wang, Kuo-Yang; Liu, Chia-Ning; Liu, Tsun-Jui

    2015-12-01

    Accidental bone fractures are a major cause of premature disabilities and death. Whether atrial fibrillation (AF) treated with or without antithrombotics correlates with occurrence of such events remains under-investigated. Patients ≥18 years with newly diagnosed AF between 2005 and 2009 without previous cancers or traffic injury were identified from the "Longitudinal Health Insurance Database 2005" (1 million beneficiaries) of Taiwan's National Health Research Institutes and served as the AF group. A fourfold number of age-, gender-, and comorbidity-matched patients but without AF served as the non-AF controls. Patients were followed, and cumulative incidence of hospitalization-requiring bone fractures was compared between groups. Predictors of accidental bone fractures were determined by Cox regression analysis. Within a mean follow-up of 3.6 years, bone fractures, especially those involving neck/trunk and lower limbs, were significantly more frequent in patients with AF (N=6925) than in those without (N=27,700) (7.0 vs. 3.8 per 1000 person-years, log-rank p=0.001, adjusted HR=1.85, 95% CI=1.50-2.30, pfractures in AF patients, whereas oral anticoagulants (HR=0.62, 95% CI=0.35-0.91, p=0.034), especially when used in patients with CHA2DS2-VASc score≧1 but not antiplatelet therapy (p=0.39) as negative predictors. Patients with AF are more vulnerable to non-traffic-, non-cancer-related bone fractures especially when with specified characteristics. For those with higher CHA2DS2-VASc scores, the use of anticoagulant but not antiplatelet agents could be associated with lower risk of such events. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. A Pragmatic Evaluation of the National Cancer Institute Physician Data Query (PDQ)®-Based Brief Counseling on Cancer-Related Fatigue among Patients Undergoing Radiation Therapy.

    Science.gov (United States)

    Bauml, Joshua; Xie, Sharon X; Penn, Courtney; Desai, Krupali; Dong, Kimberly W; Bruner, Deborah Watkins; Vapiwala, Neha; Mao, Jun James

    2012-01-01

    Cancer-Related Fatigue (CRF) negatively affects quality of life among cancer patients. This study seeks to evaluate the outcome and patient receptiveness of a brief counseling program based on National Cancer Institute (NCI) PDQ® information to manage CRF when integrated into Radiation Therapy (RT). We conducted a prospective cohort study among patients undergoing non-palliative RT. Patients with stage I-III tumors and with Karnofsky score 60 or better were given a ten-minute behavioral counseling session during the first two weeks of RT. The Brief Fatigue Inventory (BFI) was administered at baseline/end of RT. Of 93 patients enrolled, 89% found the counseling useful and practical. By the end of RT, 59% reported increased exercise, 41.6% sought nutrition counseling, 72.7% prioritized daily activities, 74.4% took daytime naps, and 70.5% talked with other cancer patients. Regarding counseling, patients who had received chemotherapy prior to RT had no change in fatigue (-0.2), those who received RT alone had mild increase in fatigue (0.7, p=0.02), and those who received concurrent chemotherapy experienced a substantial increase in fatigue (3.0 to 5.2, p=0.05). Higher baseline fatigue and receipt of chemotherapy were predictive of worsened fatigue in a multivariate model (both pbrief behavioral counseling based on NCI guidelines is well accepted by patients showing an uptake in many activities to cope with CRF. Those who receive concurrent chemotherapy and with higher baseline fatigue are at risk for worsening fatigue despite of guideline-based therapy.

  5. Proteins engineering

    International Nuclear Information System (INIS)

    2000-01-01

    At the - Departement d'Ingenierie et d'etudes de proteines (Deip) of the CEA more than seventy researchers are working hard to understand the function of proteins. For that they use the molecular labelling technique (F.M.)

  6. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  7. Osteogenic Stimulation of Human Adipose-Derived Mesenchymal Stem Cells Using a Fungal Metabolite That Suppresses the Polycomb Group Protein EZH2.

    Science.gov (United States)

    Samsonraj, Rebekah M; Dudakovic, Amel; Manzar, Bushra; Sen, Buer; Dietz, Allan B; Cool, Simon M; Rubin, Janet; van Wijnen, Andre J

    2018-02-01

    Strategies for musculoskeletal tissue regeneration apply adult mesenchymal stem/stromal cells (MSCs) that can be sourced from bone marrow- and lipo-aspirates. Adipose tissue-derived MSCs are more easily harvested in the large quantities required for skeletal tissue-engineering approaches, but are generally considered to be less osteogenic than bone marrow MSCs. Therefore, we tested a new molecular strategy to improve their osteogenic lineage-differentiation potential using the fungal metabolite cytochalasin D (CytoD). We show that CytoD, which may function by redistributing the intracellular location of β-actin (ACTB), is a potent osteogenic stimulant as reflected by significant increases in alkaline phosphatase activity, extracellular matrix mineralization, and osteoblast-related gene expression (e.g., RUNX2, ALPL, SPARC, and TGFB3). RNA sequencing analyses of MSCs revealed that acute CytoD treatment (24 hours) stimulates a broad program of osteogenic biomarkers and epigenetic regulators. CytoD decreases mRNA and protein levels of the Polycomb chromatin regulator Enhancer of Zeste Homolog 2 (EZH2), which controls heterochromatin formation by mediating trimethylation of histone 3 lysine 27 (H3K27me3). Reduced EZH2 expression decreases cellular H3K27me3 marks indicating a global reduction in heterochromatin. We conclude that CytoD is an effective osteogenic stimulant that mechanistically functions by blocking both cytoplasmic actin polymerization and gene-suppressive epigenetic mechanisms required for the acquisition of the osteogenic phenotype in adipose tissue-derived MSCs. This finding supports the use of CytoD in advancing the osteogenic potential of MSCs in skeletal regenerative strategies. Stem Cells Translational Medicine 2018;7:197-209. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  8. Osteogenic Stimulation of Human Adipose‐Derived Mesenchymal Stem Cells Using a Fungal Metabolite That Suppresses the Polycomb Group Protein EZH2

    Science.gov (United States)

    Samsonraj, Rebekah M.; Dudakovic, Amel; Manzar, Bushra; Sen, Buer; Dietz, Allan B.; Cool, Simon M.; Rubin, Janet

    2017-01-01

    Abstract Strategies for musculoskeletal tissue regeneration apply adult mesenchymal stem/stromal cells (MSCs) that can be sourced from bone marrow‐ and lipo‐aspirates. Adipose tissue‐derived MSCs are more easily harvested in the large quantities required for skeletal tissue‐engineering approaches, but are generally considered to be less osteogenic than bone marrow MSCs. Therefore, we tested a new molecular strategy to improve their osteogenic lineage‐differentiation potential using the fungal metabolite cytochalasin D (CytoD). We show that CytoD, which may function by redistributing the intracellular location of β‐actin (ACTB), is a potent osteogenic stimulant as reflected by significant increases in alkaline phosphatase activity, extracellular matrix mineralization, and osteoblast‐related gene expression (e.g., RUNX2, ALPL, SPARC, and TGFB3). RNA sequencing analyses of MSCs revealed that acute CytoD treatment (24 hours) stimulates a broad program of osteogenic biomarkers and epigenetic regulators. CytoD decreases mRNA and protein levels of the Polycomb chromatin regulator Enhancer of Zeste Homolog 2 (EZH2), which controls heterochromatin formation by mediating trimethylation of histone 3 lysine 27 (H3K27me3). Reduced EZH2 expression decreases cellular H3K27me3 marks indicating a global reduction in heterochromatin. We conclude that CytoD is an effective osteogenic stimulant that mechanistically functions by blocking both cytoplasmic actin polymerization and gene‐suppressive epigenetic mechanisms required for the acquisition of the osteogenic phenotype in adipose tissue‐derived MSCs. This finding supports the use of CytoD in advancing the osteogenic potential of MSCs in skeletal regenerative strategies. Stem Cells Translational Medicine 2018;7:197–209 PMID:29280310

  9. Transforming growth factor-β inhibits CCAAT/enhancer-binding protein expression and PPARγ activity in unloaded bone marrow stromal cells

    International Nuclear Information System (INIS)

    Ahdjoudj, S.; Kaabeche, K.; Holy, X.; Fromigue, O.; Modrowski, D.; Zerath, E.; Marie, P.J.

    2005-01-01

    The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-β2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP)α and C/EBPβ α at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor γ (PPARγ2) transcripts at 7 days. TGF-β2 administration in unloaded rats corrected the rise in C/EBPα and C/EBPβ transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPARγ2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBPα and C/EBPβ expression by TGF-β2 was associated with increased PPARγ serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARγ transactivating activity. The sequential inhibitory effect of TGF-β2 on C/EBPα, C/EBPβ, and PPARγ2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-β2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBPα, C/EBPβ, and PPARγ expression and activity, which provides a sequential mechanism by which TGF-β2 regulates adipogenic differentiation of bone marrow stromal cells in vivo

  10. The influence of cancer-related distress and sense of coherence on anxiety and depression in patients with hereditary cancer: a study of patients' sense of coherence 6 months after genetic counseling.

    Science.gov (United States)

    Siglen, Elen; Bjorvatn, Cathrine; Engebretsen, Lars Fredrik; Berglund, Gunilla; Natvig, Gerd Karin

    2007-10-01

    This study examines the association between Sense of Coherence and anxiety and depression amongst patients at risk of hereditary cancer receiving genetic counseling. When writing this article, 144 patients referred for genetic counseling due to a suspicion of hereditary cancer in the family were recruited for this multicentered longitudinal study on the psychosocial aspects of genetic counseling in Norway. A total of 96 (66%) patients responded to the follow-up survey distributed 6 months after genetic counseling. This survey included the Sense of Coherence-29 Scale, Impact of Event Scale, and Hospital Anxiety and Depression Scale. Multiple regression analyses were applied. Our results show association between cancer-related distress and symptoms of anxiety and depression. Sense of Coherence is significantly associated with both anxiety and depression. The hypothesis of Sense of Coherence buffering cancer-related distress and the possible impact of these findings for genetic counseling are discussed.

  11. Design of a randomized controlled trial of physical training and cancer (Phys-Can) - the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome

    OpenAIRE

    Berntsen, Sveinung; Aaronson, Neil K; Buffart, Laurien; Börjeson, Sussanne; Demmelmaier, Ingrid; Hellbom, Maria; Hojman, Pernille; Igelström, Helena; Johansson, Birgitta; Pingel, Ronnie; Raastad, Truls; Velikova, Galina; Åsenlöf, P.; Nordin, Karin

    2017-01-01

    Background: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviou...

  12. Epidural analgesia during open radical prostatectomy does not improve long-term cancer-related outcome: a retrospective study in patients with advanced prostate cancer.

    Directory of Open Access Journals (Sweden)

    Patrick Y Wuethrich

    Full Text Available BACKGROUND: A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. METHODS: In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP with general anesthesia combined with intra- and postoperative epidural analgesia (n=67 or with postoperative ketorolac-morphine analgesia (n=81 were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs. Biochemical recurrence (BCR-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. RESULTS: The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07. For both groups, higher preoperative PSA (hazard ratio (HR 1.02, 95% confidence interval (CI 1.01-1.02, P<0.0001, increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007 and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04 were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001. CONCLUSIONS: General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

  13. Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

    Science.gov (United States)

    Mandelker, Diana; Zhang, Liying; Kemel, Yelena; Stadler, Zsofia K; Joseph, Vijai; Zehir, Ahmet; Pradhan, Nisha; Arnold, Angela; Walsh, Michael F; Li, Yirong; Balakrishnan, Anoop R; Syed, Aijazuddin; Prasad, Meera; Nafa, Khedoudja; Carlo, Maria I; Cadoo, Karen A; Sheehan, Meg; Fleischut, Megan H; Salo-Mullen, Erin; Trottier, Magan; Lipkin, Steven M; Lincoln, Anne; Mukherjee, Semanti; Ravichandran, Vignesh; Cambria, Roy; Galle, Jesse; Abida, Wassim; Arcila, Marcia E; Benayed, Ryma; Shah, Ronak; Yu, Kenneth; Bajorin, Dean F; Coleman, Jonathan A; Leach, Steven D; Lowery, Maeve A; Garcia-Aguilar, Julio; Kantoff, Philip W; Sawyers, Charles L; Dickler, Maura N; Saltz, Leonard; Motzer, Robert J; O'Reilly, Eileen M; Scher, Howard I; Baselga, Jose; Klimstra, David S; Solit, David B; Hyman, David M; Berger, Michael F; Ladanyi, Marc; Robson, Mark E; Offit, Kenneth

    2017-09-05

    change to targeted therapy in 38 patients tested (3.7%) and predictive testing in the families of 13 individuals (1.3%), including 6 for whom genetic evaluation would not have been initiated by guideline-based testing. In this referral population with selected advanced cancers, universal sequencing of a broad panel of cancer-related genes in paired germline and tumor DNA samples was associated with increased detection of individuals with potentially clinically significant heritable mutations over the predicted yield of targeted germline testing based on current clinical guidelines. Knowledge of these additional mutations can help guide therapeutic and preventive interventions, but whether all of these interventions would improve outcomes for patients with cancer or their family members requires further study. clinicaltrials.gov Identifier: NCT01775072.

  14. Effectiveness, Mediators, and Effect Predictors of Internet Interventions for Chronic Cancer-Related Fatigue: The Design and an Analysis Plan of a 3-Armed Randomized Controlled Trial.

    Science.gov (United States)

    Wolvers, Marije Dj; Bruggeman-Everts, Fieke Z; Van der Lee, Marije L; Van de Schoot, Rens; Vollenbroek-Hutten, Miriam Mr

    2015-06-23

    curative-intent cancer treatment at least 3 months previously, and have been suffering from severe fatigue ever since. All cancer types are included. A detailed analysis plan is described to address the research questions, which allows for individual variation, and fully exploits the longitudinal design. Recruitment started in April 2013 and will proceed until April 2015. This paper describes a systematic trial design for studying 2 different interventions for chronic cancer-related fatigue in order to gain insight into the effectiveness and mediators of the interventions. This design will also be used to identify predictors for the interventions' effect on fatigue. By publishing our hypotheses and analysis plan before completion of data collection, this paper is a first step in reporting on this trial comprehensively. The Netherlands National Trial Register (NTR3483). (Archived by WebCite at http://www.webcitation.org/6NWZqon3o).

  15. Blood-based biomarkers of cancer-related cognitive impairment in non-central nervous system cancer: protocol for a scoping review.

    Science.gov (United States)

    Mayo, Samantha J; Kuruvilla, John; Laister, Rob C; Ayala, Ana Patricia; Alm, Mark; Byker, Will; Kelly, Debra Lynch; Saligan, Leorey

    2018-01-27

    Cancer-related cognitive impairment (CRCI) can have detrimental effects on quality of life, even among patients with non-central nervous system (CNS) cancers. Several studies have been conducted to explore different markers associated with CRCI to understand its pathobiology. It is proposed that the underlying mechanisms of CRCI are related to a cascade of physiological adaptive events in response to cancer and/or treatment. Hence, peripheral blood would be a logical source to observe and identify these physiological events. This paper outlines the protocol for a scoping review being conducted to summarise the extant literature regarding blood-based biomarkers of CRCI among patients with non-CNS cancer. Methods will be informed by the updated guidelines of Arksey and O'Malley. The systematic search for literature will include electronic databases, handsearching of key journals and reference lists, forward citation tracking and consultation with content experts. Study selection will be confirmed by duplicate review and calculation of inter-rater reliability. Data to be charted will include study design, sample size, cancer and treatment characteristics, demographic characteristics, cognitive variable/s and biomarkers assessed, associations between cognitive functioning and biomarkers (including statistics used), and rigour in biomarker sample collection and processing. Results will be presented through: (1) a descriptive numerical summary of studies, including a flow diagram based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, (2) a list of blood-based biomarkers associated with CRCI and (3) a narrative overview developed through collaboration among the research team and consultation with content experts. The findings of this review will highlight current directions and gaps in the current body of evidence that may lead to improved rigour in future CRCI investigations. The dissemination of this work will be facilitated through

  16. Yoga for improving health-related quality of life, mental health and cancer-related symptoms in women diagnosed with breast cancer.

    Science.gov (United States)

    Cramer, Holger; Lauche, Romy; Klose, Petra; Lange, Silke; Langhorst, Jost; Dobos, Gustav J

    2017-01-03

    Breast cancer is the cancer most frequently diagnosed in women worldwide. Even though survival rates are continually increasing, breast cancer is often associated with long-term psychological distress, chronic pain, fatigue and impaired quality of life. Yoga comprises advice for an ethical lifestyle, spiritual practice, physical activity, breathing exercises and meditation. It is a complementary therapy that is commonly recommended for breast cancer-related impairments and has been shown to improve physical and mental health in people with different cancer types. To assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment. We searched the Cochrane Breast Cancer Specialised Register, MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), Indexing of Indian Medical Journals (IndMED), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal and Clinicaltrials.gov on 29 January 2016. We also searched reference lists of identified relevant trials or reviews, as well as conference proceedings of the International Congress on Complementary Medicine Research (ICCMR), the European Congress for Integrative Medicine (ECIM) and the American Society of Clinical Oncology (ASCO). We applied no language restrictions. Randomised controlled trials were eligible when they (1) compared yoga interventions versus no therapy or versus any other active therapy in women with a diagnosis of non-metastatic or metastatic breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances. Two review authors independently collected data on methods and results. We expressed outcomes as standardised mean differences (SMDs

  17. Non-cancer-related mortality after cisplatin-based adjuvant chemotherapy for non-small cell lung cancer: a study-level meta-analysis of 16 randomized trials.

    Science.gov (United States)

    Petrelli, Fausto; Barni, Sandro

    2013-01-01

    Adjuvant chemotherapy is associated with increased overall survival in non-small cell lung cancer (NSCLC), but is associated with high-grade toxicity. The effect of cisplatin-based adjuvant chemotherapy on non-lung cancer-related mortality is not well investigated. We conducted a systematic review and a study-level meta-analysis of published randomized controlled trials (RCTs) in order to determine the overall risk of non-lung cancer-related mortality associated with adjuvant cisplatin-based chemotherapy in NSCLC. PubMed was searched to identify relevant studies. Eligible publications included prospective RCTs in which cisplatin-based adjuvant chemotherapy plus local therapy was compared with local therapy alone in NSCLC. Summary incidence rates, relative risks (RRs), and 95 % confidence intervals (CIs) were calculated using fixed- or random-effects models. Primary endpoint was non-lung cancer-related mortality risk (due to cardiovascular, respiratory or second malignancy deaths for example), and secondary endpoints were chemotherapy-related, second primary tumor-related, cardiovascular-related, and unknown cause mortalities. A total of 6,430 patients with NSCLC from 16 RCTs were included in the analysis. Compared with no chemotherapy, the use of cisplatin-based adjuvant chemotherapy was associated with an increased risk of non-lung cancer-related death, with an RR of 1.30 (95 % CI 1.1-1.53; P = 0.002; incidence, 9.3 vs. 7.2 %; absolute difference 2 %). Cisplatin-based adjuvant chemotherapy was also associated with a greater risk of chemotherapy-related mortality (RR 2.16, 95 % CI 1.15-4.06; P = 0.02). Second primary tumor-related mortality and cardiovascular-related mortality were similar. In this meta-analysis of RCTs in NSCLC, cisplatin-based adjuvant chemotherapy was associated with a 30 % increase in non-lung cancer-related mortality compared with local therapy alone.

  18. Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Tong-ling Yuan

    2016-01-01

    Full Text Available Backgrounds. Heme oxygenase-1 (HO-1 has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2 in patients with rheumatoid arthritis (RA and ankylosing spondylitis (AS and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p<0.01. In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b (p<0.05, resp., BMP-7 was positively correlated with Runx2 and TRAP-5b (p<0.05, resp., and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID (p<0.05. In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

  19. Protein Extractability

    African Journals Online (AJOL)

    Results showed that protein extractability was dependent on pH, type of salt, salt concentrations and extraction time. Salts extracted more proteins from the moringa seed flour than water. Maximum extraction of protein was. 85.06% and 84.72% with 0.5 M CaCl and 0.75 M NaCl respectively. On varying the pH, maximum ...

  20. Protein politics

    NARCIS (Netherlands)

    Vijver, Marike

    2005-01-01

    This study is part of the program of the interdisciplinary research group Profetas (protein foods, environment, technology and society). Profetas consists of technological, environmental and socio-economic research projects on protein food systems which result in the development of scenarios and

  1. Whey Protein

    Science.gov (United States)

    ... Fraction de Lactosérum, Fraction de Petit-Lait, Goat Milk Whey, Goat Whey, Isolat de Protéine de Lactosérum, Isolat de Protéine de Petit-Lait, Lactosérum de Lait de Chèvre, MBP, Milk Protein, Milk Protein Isolate, Mineral Whey Concentrate, Proteínas ...

  2. Protein adhesives

    Science.gov (United States)

    Charles R. Frihart; Linda F. Lorenz

    2018-01-01

    Nature uses a wide variety of chemicals for providing adhesion internally (e.g., cell to cell) and externally (e.g., mussels to ships and piers). This adhesive bonding is chemically and mechanically complex, involving a variety of proteins, carbohydrates, and other compounds.Consequently,the effect of protein structures on adhesive properties is only partially...

  3. Tau protein

    DEFF Research Database (Denmark)

    Frederiksen, Jette Lautrup Battistini; Kristensen, Kim; Bahl, Jmc

    2011-01-01

    Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14......-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. Methods: A total of 66 patients with MS and/or ON from...... the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased concentration of tau...

  4. Protein-Protein Interaction Databases

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Jensen, Lars Juhl

    2015-01-01

    of research are explored. Here we present an overview of the most widely used protein-protein interaction databases and the methods they employ to gather, combine, and predict interactions. We also point out the trade-off between comprehensiveness and accuracy and the main pitfall scientists have to be aware...

  5. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    Science.gov (United States)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  6. A phase 3 randomized, placebo-controlled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: a University of Rochester Cancer Center Community Clinical Oncology Program Research base study.

    Science.gov (United States)

    Jean-Pierre, Pascal; Morrow, Gary R; Roscoe, Joseph A; Heckler, Charles; Mohile, Supriya; Janelsins, Michelle; Peppone, Luke; Hemstad, Amy; Esparaz, Benjamin T; Hopkins, Judith O

    2010-07-15

    Cancer-related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70% to 100% of cancer patients during and after treatment. The authors examined the effect of 200 mg of modafinil daily on the severity of cancer-related fatigue. The authors conducted a multicenter, randomized, double-blind, placebo-controlled, phase 3, clinical trial to examine the effect of modafinil on patient-reported fatigue in cancer patients undergoing chemotherapy. A sample of 877 cancer patients beginning chemotherapy at 23 geographically separate University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) affiliates were assessed for fatigue. Patients who reported fatigue (N=867) were randomly assigned to receive either 200 mg of oral modafinil (Provigil) daily or a placebo. Treatment began on Day 5 of Cycle 2 and ended after Day 7 of Cycle 4. Fatigue and depression were assessed during Cycles 2 to 4 by using psychometrically valid measures. Group differences (treatment vs control) in the worst level of fatigue during the previous week at Cycle 4 were examined by using an analysis of covariance (ANCOVA) adjusting for baseline fatigue (Cycle 2). There were 631 patients (315 modafinil, 316 placebo) who provided evaluable data. ANCOVA showed a significant interaction between treatment condition and baseline fatigue (P=.017), where patients with severe baseline fatigue (n=458) benefited from modafinil, whereas patients with mild or moderate fatigue did not. Modafinil had no statistically significant effect on depression (P>.05). Modafinil may be useful in controlling cancer-related fatigue in patients who present with severe fatigue but is not useful in patients with mild or moderate fatigue. Copyright (c) 2010 American Cancer Society.

  7. 
Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

    Science.gov (United States)

    Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

    2017-06-01

    The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
.

  8. Protein deamidation

    OpenAIRE

    Robinson, Noah E.

    2002-01-01

    A completely automatic computerized technique for the quantitative estimation of the deamidation rates of any protein for which the three-dimensional structure is known has been developed. Calculations of the specific deamidation rates of 170,014 asparaginyl residues in 13,335 proteins have been carried out. The calculated values have good quantitative reliability when compared with experimental measurements. These rates demonstrate that deamidation may be a biologically ...

  9. Cross-cultural adaptation and measurement properties of generic and cancer-related patient-reported outcome measures (PROMs) for use with cancer patients in Brazil: a systematic review.

    Science.gov (United States)

    Albach, Carlos Augusto; Wagland, Richard; Hunt, Katherine J

    2018-04-01

    This systematic review (1) identifies the current generic and cancer-related patient-reported outcome measures (PROMs) that have been cross-culturally adapted to Brazilian Portuguese and applied to cancer patients and (2) critically evaluates their cross-cultural adaptation (CCA) and measurement properties. Seven databases were searched for articles regarding the translation and evaluation of measurement properties of generic and cancer-related PROMs cross-culturally adapted to Brazilian Portuguese that are applied in adult (≥18 years old) cancer patients. The methodological quality of included studies was assessed using the COSMIN checklist. The bibliographic search retrieved 1674 hits, of which seven studies analysing eight instruments were included in this review. Data on the interpretability of scores were poorly reported. Overall, the quality of the CCA process was inconsistent throughout the studies. None of the included studies performed a cross-cultural validation. The evidence concerning the quality of measurement properties is limited by poor or fair methodological quality. Moreover, limited information regarding measurement properties was provided within the included papers. This review aids the selection process of Brazilian Portuguese PROMs for use in cancer patients. After acknowledging the methodological caveats and strengths of each tool, our opinion is that for quality of life and symptoms assessment the adapted FACT-G version and the ESAS could be recommended, respectively. Future research should rely on the already accepted standards of CCA and validation studies.

  10. Protein Crystallizability.

    Science.gov (United States)

    Smialowski, Pawel; Wong, Philip

    2016-01-01

    Obtaining diffracting quality crystals remains a major challenge in protein structure research. We summarize and compare methods for selecting the best protein targets for crystallization, construct optimization and crystallization condition design. Target selection methods are divided into algorithms predicting the chance of successful progression through all stages of structural determination (from cloning to solving the structure) and those focusing only on the crystallization step. We tried to highlight pros and cons of different approaches examining the following aspects: data size, redundancy and representativeness, overfitting during model construction, and results evaluation. In summary, although in recent years progress was made and several sequence properties were reported to be relevant for crystallization, the successful prediction of protein crystallization behavior and selection of corresponding crystallization conditions continue to challenge structural researchers.

  11. Alternative Splicing Regulation of Cancer-Related Pathways in Caenorhabditis elegans: An In Vivo Model System with a Powerful Reverse Genetics Toolbox

    Directory of Open Access Journals (Sweden)

    Sergio Barberán-Soler

    2013-01-01

    Full Text Available Alternative splicing allows for the generation of protein diversity and fine-tunes gene expression. Several model systems have been used for the in vivo study of alternative splicing. Here we review the use of the nematode Caenorhabditis elegans to study splicing regulation in vivo. Recent studies have shown that close to 25% of genes in the worm genome undergo alternative splicing. A big proportion of these events are functional, conserved, and under strict regulation either across development or other conditions. Several techniques like genome-wide RNAi screens and bichromatic reporters are available for the study of alternative splicing in worms. In this review, we focus, first, on the main studies that have been performed to dissect alternative splicing in this system and later on examples from genes that have human homologs that are implicated in cancer. The significant advancement towards understanding the regulation of alternative splicing and cancer that the C. elegans system has offered is discussed.

  12. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  13. Recombinant protein production technology

    Science.gov (United States)

    Recombinant protein production is an important technology for antibody production, biochemical activity study, and structural determination during the post-genomic era. Limiting factors in recombinant protein production include low-level protein expression, protein precipitation, and loss of protein...

  14. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

    Science.gov (United States)

    Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

    2013-08-01

    Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc

  15. Cancer-Related Triplets of mRNA-lncRNA-miRNA Revealed by Integrative Network in Uterine Corpus Endometrial Carcinoma

    Directory of Open Access Journals (Sweden)

    Chenglin Liu

    2017-01-01

    Full Text Available The regulation of transcriptome expression level is a complex process involving multiple-level interactions among molecules such as protein coding RNA (mRNA, long noncoding RNA (lncRNA, and microRNA (miRNA, which are essential for the transcriptome stability and maintenance and regulation of body homeostasis. The availability of multilevel expression data enables a comprehensive view of the regulatory network. In this study, we analyzed the coding and noncoding gene expression profiles of 301 patients with uterine corpus endometrial carcinoma (UCEC. A new method was proposed to construct a genome-wide integrative network based on variance inflation factor (VIF regression method. The cross-regulation relations of mRNA, lncRNA, and miRNA were then selected based on clique-searching algorithm from the network, when any two molecules of the three were shown as interacting according to the integrative network. Such relation, which we call the mRNA-lncRNA-miRNA triplet, demonstrated the complexity in transcriptome regulation process. Finally, six UCEC-related triplets were selected in which the mRNA participates in endometrial carcinoma pathway, such as CDH1 and TP53. The multi-type RNAs are proved to be cross-regulated as to each of the six triplets according to literature. All the triplets demonstrated the association with the initiation and progression of UCEC. Our method provides a comprehensive strategy for the investigation of transcriptome regulation mechanism.

  16. A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans.

    Science.gov (United States)

    Charron, Craig S; Dawson, Harry D; Albaugh, George P; Solverson, Patrick M; Vinyard, Bryan T; Solano-Aguilar, Gloria I; Molokin, Aleksey; Novotny, Janet A

    2015-11-01

    Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. We designed a study to probe the mechanisms of garlic action in humans. We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591. © 2015 American Society for Nutrition.

  17. A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans1234

    Science.gov (United States)

    Charron, Craig S; Dawson, Harry D; Albaugh, George P; Solverson, Patrick M; Vinyard, Bryan T; Solano-Aguilar, Gloria I; Molokin, Aleksey; Novotny, Janet A

    2015-01-01

    Background: Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. Objective: We designed a study to probe the mechanisms of garlic action in humans. Methods: We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. Results: The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. Conclusion: These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591. PMID:26423732

  18. p16INK4 expression in precursor lesions of squamous cell cervical cancer related to the presence of HPV-DNA

    Directory of Open Access Journals (Sweden)

    A.E.G. Godoy

    2008-07-01

    Full Text Available The purpose of the present study was to identify the expression of p16INK4 in cervical cancer precursor lesions by immunohistochemistry and to correlate it with lesion grade and presence of human papillomavirus (HPV infection. Cervical specimens from 144 women seen consecutively at the gynecology outpatient clinic of our institution from December 2003 to May 2005 were analyzed by cytopathology, histopathology, polymerase chain reaction for HPV-DNA, and p16INK4 immunostaining. Histologically normal biopsies, HPV-DNA negative by polymerase chain reaction, were used as control. HPV-DNA prevalence, including the control group, was 68.1% and the prevalence of p16INK4 expression was 55.0%. The percentage of cells stained by p16INK4 ranged from 10 to 100%, both in the group consisting of cervical intraepithelial neoplasia (CIN1/HPV specimens and in the group of CIN2/CIN3 specimens with P value of 0.0001. p16INK4 expression was 48.3% in the CIN1/HPV group, as opposed to 94.3% in the CIN2/CIN3 group (P = 0.001, showing a statistically significant difference between the two groups. The quantitative method used here is simple and less subjective than the different semiquantitative methods described in the literature. In view of the different definitions of a p16INK4-positive case, it is almost impossible to compare the findings reported by different investigators. This study confirms the association between p16INK4 and CIN2 and CIN3 lesions. Moreover, it shows that some low grade lesions expressed high levels of this protein. This may indicate that such low grade lesions may be predisposed to progress to high grade lesions. This means that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker.

  19. Human papillomavirus E6 and E7 oncoproteins affect the expression of cancer-related microRNAs: additional evidence in HPV-induced tumorigenesis.

    Science.gov (United States)

    Chiantore, Maria Vincenza; Mangino, Giorgio; Iuliano, Marco; Zangrillo, Maria Simona; De Lillis, Ilaria; Vaccari, Gabriele; Accardi, Rosita; Tommasino, Massimo; Columba Cabezas, Sandra; Federico, Maurizio; Fiorucci, Gianna; Romeo, Giovanna

    2016-08-01

    Human papillomaviruses (HPVs) are the causative agents of cervical cancer and are also associated with other types of cancers. HPVs can modulate microRNAs (miRNAs) expressed by infected cells. The production of extracellular vesicles is deregulated in cancer, and their cargo delivered to the microenvironment can promote tumorigenesis. The involvement of HPV oncoproteins on miRNA expression in cells and exosomes was analyzed in keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38). MiRNAs were investigated through the TaqMan Array Human MicroRNA Cards, followed by real-time RT-PCR assay for specific miRNAs. Selected miRNA targets were analyzed by Western blot and correlated to the HPV oncoproteins by specifically silencing E6 and E7 expression. Exosomes, isolated from K16 and K38 supernatants by differential centrifugations, were quantified through the vesicle-associated acetylcholinesterase activity. MiRNAs deregulated in K16 and K38 cells were identified. HPV-16 and/or HPV-38 E6 and E7 single proteins can modify the expression of selected miRNAs involved in the tumorigenesis, in particular miR-18a, -19a, -34a and -590-5p. The analysis of the content of exosomes isolated from HPV-positive cells revealed the presence of E6 and E7 mRNAs and few miRNAs. MiR-222, a key miRNA deregulated in many cancers, was identified in exosomes from K16 cells. HPV E6 and/or E7 oncoprotein expression can induce the deregulation of some miRNAs. Through the production and function of exosomes, HPV oncogenes as well as HPV-deregulated miRNAs can potentiate the virus oncogenic effects in the tumor cell microenvironment.

  20. The inflammatory/cancer-related IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts.

    Science.gov (United States)

    Hendrayani, Siti-Fauziah; Al-Harbi, Bothaina; Al-Ansari, Mysoon M; Silva, Gabriela; Aboussekhra, Abdelilah

    2016-07-05

    The IL-6/STAT3/NF-κB positive feedback loop links inflammation to cancer and maintains cells at a transformed state. Similarly, cancer-associated myofibroblats remains active even in absence of cancer cells. However, the molecular basis of this sustained active state remains elusive. We have shown here that breast cancer cells and IL-6 persistently activate breast stromal fibroblasts through the stimulation of the positive IL-6/STAT3/NF-κB feedback loop. Transient neutralization of IL-6 in culture inhibited this signaling circuit and reverted myofibrobalsts to a normalized state, suggesting the implication of the IL-6 autocrine feedback loop as well. Importantly, the IL-6/STAT3/NF-κB pro-inflammatory circuit was also active in cancer-associated fibroblasts isolated from breast cancer patients. Transient inhibition of STAT3 by specific siRNA in active fibroblasts persistently reduced the level of the RNA binding protein AUF1, blocked the loop and normalized these cells. Moreover, we present clear evidence that AUF1 is also part of this positive feedback loop. Interestingly, treatment of breast myofibroblasts with caffeine, which has been previously shown to persistently inhibit active breast stromal fibroblasts, blocked the positive feedback loop through potent and sustained inhibition of STAT3, AKT, lin28B and AUF1. These results indicate that the IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and is responsible for the sustained active status of cancer-associated fibroblasts. We have also shown that normalizing myofibroblasts, which could be of great therapeutic value, is possible through the inhibition of this procarcinogenic circuit.

  1. Design of a randomized controlled trial of physical training and cancer (Phys-Can) - the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome

    DEFF Research Database (Denmark)

    Berntsen, Sveinung; Aaronson, Neil K; Buffart, Laurien

    2017-01-01

    BACKGROUND: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies...... are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life...... on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. METHODS/DESIGN: Six hundred newly diagnosed...

  2. Mass spectrometry based biomarker discovery, verification, and validation--quality assurance and control of protein biomarker assays.

    Science.gov (United States)

    Parker, Carol E; Borchers, Christoph H

    2014-06-01

    In its early years, mass spectrometry (MS)-based proteomics focused on the cataloging of proteins found in different species or different tissues. By 2005, proteomics was being used for protein quantitation, typically based on "proteotypic" peptides which act as surrogates for the parent proteins. Biomarker discovery is usually done by non-targeted "shotgun" proteomics, using relative quantitation methods to determine protein expression changes that correlate with disease (output given as "up-or-down regulation" or "fold-increases"). MS-based techniques can also perform "absolute" quantitation which is required for clinical applications (output given as protein concentrations). Here we describe the differences between these methods, factors that affect the precision and accuracy of the results, and some examples of recent studies using MS-based proteomics to verify cancer-related biomarkers. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  3. Detection of Rare Variant of SS18-SSX1 Fusion Gene and Mutations of Important Cancer-Related Genes in Synovial Sarcoma of the Lip: Gene Analyses of a Case and Literature Review.

    Science.gov (United States)

    Mikami, Toshinari; Kurose, Akira; Javed, Fawad; Takeda, Yasunori

    2015-08-01

    Synovial sarcoma (SS) accounts for 5 to 10% of soft tissue sarcomas; however, intraoral SS is rare. Histopathologically, SS shows a biphasic pattern with epithelial and spindle cell components or a monophasic pattern with only spindle cells. The precise diagnosis of SS, especially at an unusual site, is often a challenge to pathologists and clinical oncologists, because the differential diagnosis of SS includes a broad range of tumors, such as soft tissue sarcomas and carcinomas. In the present case, the patient was a 50-year-old woman who presented with the chief complaint of swelling and a slowly enlarging mass of the lower lip in the mucolabial fold region. The mass was covered with intact mucosa and intraoral examination showed no malignant findings. The clinical diagnosis was a benign tumor and a probable salivary gland tumor. Macroscopically, the excised mass also indicated a benign tumor; however, histopathologic findings suggested the diagnosis of SS. For definitive diagnosis, genetic analyses were performed with conventional polymerase chain reaction and next-generation sequencing. As a result, a rare variant of the SS18-SSX1 fusion transcript, which could not be identified by routine procedures for genetic diagnosis, was detected. In addition, 8 missense mutations of cancer-related genes were confirmed. Detection of the fusion transcript is widely used in the diagnosis of SS; however, reported cases of transcript variants of each fusion gene type are limited. Reports of mutational analysis of cancer-related genes on SS also are rare. The accumulation of rare transcript variants and the cytogenetic characters of SS are suggested to be necessary for assuming a genetic diagnosis of SS. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Aquaporin Protein-Protein Interactions

    Directory of Open Access Journals (Sweden)

    Jennifer Virginia Roche

    2017-10-01

    Full Text Available Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein–protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein–protein interactions; dividing the interactions into three types: (1 interactions between aquaporin tetramers; (2 interactions between aquaporin monomers within a tetramer (hetero-tetramerization; and (3 transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.

  5. Protein immobilization strategies for protein biochips

    NARCIS (Netherlands)

    Rusmini, F.; Rusmini, Federica; Zhong, Zhiyuan; Feijen, Jan

    2007-01-01

    In the past few years, protein biochips have emerged as promising proteomic and diagnostic tools for obtaining information about protein functions and interactions. Important technological innovations have been made. However, considerable development is still required, especially regarding protein

  6. In silico modelling and validation of differential expressed proteins in lung cancer

    Directory of Open Access Journals (Sweden)

    Bhagavathi S

    2012-05-01

    Full Text Available Objective: The present study aims predict the three dimensional structure of three major proteins responsible for causing Lung cancer. Methods: These are the differentially expressed proteins in lung cancer dataset. Initially, the structural template for these proteins is identified from structural database using homology search and perform homology modelling approach to predict its native 3D structure. Three-dimensional model obtained was validated using Ramachandran plot analysis to find the reliability of the model. Results: Four proteins were differentially expressed and were significant proteins in causing lung cancer. Among the four proteins, Matrixmetallo proteinase (P39900 had a known 3D structure and hence was not considered for modelling. The remaining proteins Polo like kinase I Q58A51, Trophinin B1AKF1, Thrombomodulin P07204 were modelled and validated. Conclusions: The three dimensional structure of proteins provides insights about the functional aspect and regulatory aspect of the protein. Thus, this study will be a breakthrough for further lung cancer related studies.

  7. Learning about Proteins

    Science.gov (United States)

    ... Videos for Educators Search English Español Learning About Proteins KidsHealth / For Kids / Learning About Proteins What's in ... from the foods you eat. Different Kinds of Protein Protein from animal sources, such as meat and ...

  8. Bioactive glass induced osteogenic differentiation of human adipose stem cells is dependent on cell attachment mechanism and mitogen-activated protein kinases.

    Science.gov (United States)

    Ojansivu, M; Hyväri, L; Kellomäki, M; Hupa, L; Vanhatupa, S; Miettinen, S

    2018-01-30

    Bioactive glasses (BaGs) are widely utilised in bone tissue engineering (TE) but the molecular response of cells to BaGs is poorly understood. To elucidate the mechanisms of cell attachment to BaGs and BaG-induced early osteogenic differentiation, we cultured human adipose stem cells (hASCs) on discs of two silica-based BaGs S53P4 (23.0 Na2O - 20.0 CaO - 4.0 P2O5 - 53.0 SiO2 (wt-%)) and 1-06 (5.9 Na2O - 12.0 K2O - 5.3 MgO - 22.6 CaO - 4.0 P2O5 - 0.2 B2O3 - 50.0 SiO2) in the absence of osteogenic supplements. Both BaGs induced early osteogenic differentiation by increasing alkaline phosphatase activity (ALP) and the expression of osteogenic marker genes RUNX2a and OSTERIX. Based on ALP activity, the slower reacting 1-06 glass was a stronger osteoinducer. Regarding the cell attachment, cells cultured on BaGs had enhanced integrinβ1 and vinculin production, and mature focal adhesions were smaller but more dispersed than on cell culture plastic (polystyrene). Focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK)-induced c-Jun phosphorylations were upregulated by glass contact. Moreover, the BaG-stimulated osteoinduction was significantly reduced by FAK and mitogen-activated protein kinase (MAPK) inhibitors, indicating an important role for FAK and MAPKs in the BaG-induced early osteogenic commitment of hASCs. Upon indirect insert culture, the ions released from the BaG discs could not reproduce the observed cellular changes, which highlighted the role of direct cell-BaG interactions in the osteopotential of BaGs. These findings gave valuable insight into the mechanism of BaG-induced osteogenic differentiation and therefore provided knowledge to aid the future design of new functional biomaterials to meet the increasing demand for clinical bone TE treatments.

  9. Scaffold preferences of mesenchymal stromal cells and adipose-derived stem cells from green fluorescent protein transgenic mice influence the tissue engineering of bone.

    Science.gov (United States)

    Wittenburg, Gretel; Flade, Viktoria; Garbe, Annette I; Lauer, Günter; Labudde, Dirk

    2014-05-01

    We have analysed the growth and differentiation of mesenchymal stromal cells (MSC) from bone marrow, and of adipose derived stem cells (ASC) from murine abdominal fat tissue, of green fluorescent protein (GFP) transgenic animals grown directly on two types of hydroxyapatite ceramic bone substitutes. BONITmatrix® and NanoBone® have specific mechanical and physiochemical properties such as porosity and an inner surface that influence cellular growth. Both MSC and ASC were separately seeded on 200mg of each biomaterial and cultured for 3 weeks under osteogenic differentiation conditions. The degree of mineralisation was assessed by alizarin red dye and the specific alkaline phosphatase activity of the differentiated cells. The morphology of the cells was examined by scanning electron microscopy and confocal microscopy. The osteoblastic phenotype of the cells was confirmed by analysing the expression of bone-specific genes (Runx2, osteocalcin, osteopontin, and osteonectin) by semiquantitative reverse transcriptase polymerase chain reaction (PCR). Comparison of BONITmatrix® and NanoBone® showed cell type-specific preferences in terms of osteogenic differentiation. MSC-derived osteoblast-like cells spread optimally on the surface of NanoBone® but not BONITmatrix® granules. In contrast BONITmatrix® granules conditioned the growth of osteoblast-like cells derived from ASC. The osteoblastic phenotype of the cultured cells on all matrices was confirmed by specific gene expression. Our results show that the in vitro growth and osteogenic differentiation of murine MSC or ASC of GFP transgenic mice are distinctly influenced by the ceramic substratum. While NanoBone® granules support the proliferation and differentiation of murine MSC isolated from bone marrow, the growth of murine ASC is supported by BONITmatrix® granules. NanoBone® is therefore recommended for use as scaffold in tissue engineering that requires MSC, whereas ASC can be combined with BONITmatrix® for

  10. Effect of polygonimitin C on bone formation and resorption in human ...

    African Journals Online (AJOL)

    Western blot assay was used to evaluate the effect of PC on the expressions of osterix (OSX), bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX-2), osteocalcin (OC), fibronectin (FN), type I collagen (COL I), osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) proteins in ...

  11. Fusion-protein-assisted protein crystallization.

    Science.gov (United States)

    Kobe, Bostjan; Ve, Thomas; Williams, Simon J

    2015-07-01

    Fusion proteins can be used directly in protein crystallization to assist crystallization in at least two different ways. In one approach, the `heterologous fusion-protein approach', the fusion partner can provide additional surface area to promote crystal contact formation. In another approach, the `fusion of interacting proteins approach', protein assemblies can be stabilized by covalently linking the interacting partners. The linker connecting the proteins plays different roles in the two applications: in the first approach a rigid linker is required to reduce conformational heterogeneity; in the second, conversely, a flexible linker is required that allows the native interaction between the fused proteins. The two approaches can also be combined. The recent applications of fusion-protein technology in protein crystallization from the work of our own and other laboratories are briefly reviewed.

  12. Membrane bending by protein-protein crowding.

    Science.gov (United States)

    Stachowiak, Jeanne C; Schmid, Eva M; Ryan, Christopher J; Ann, Hyoung Sook; Sasaki, Darryl Y; Sherman, Michael B; Geissler, Phillip L; Fletcher, Daniel A; Hayden, Carl C

    2012-09-01

    Curved membranes are an essential feature of dynamic cellular structures, including endocytic pits, filopodia protrusions and most organelles. It has been proposed that specialized proteins induce curvature by binding to membranes through two primary mechanisms: membrane scaffolding by curved proteins or complexes; and insertion of wedge-like amphipathic helices into the membrane. Recent computational studies have raised questions about the efficiency of the helix-insertion mechanism, predicting that proteins must cover nearly 100% of the membrane surface to generate high curvature, an improbable physiological situation. Thus, at present, we lack a sufficient physical explanation of how protein attachment bends membranes efficiently. On the basis of studies of epsin1 and AP180, proteins involved in clathrin-mediated endocytosis, we propose a third general mechanism for bending fluid cellular membranes: protein-protein crowding. By correlating membrane tubulation with measurements of protein densities on membrane surfaces, we demonstrate that lateral pressure generated by collisions between bound proteins drives bending. Whether proteins attach by inserting a helix or by binding lipid heads with an engineered tag, protein coverage above ~20% is sufficient to bend membranes. Consistent with this crowding mechanism, we find that even proteins unrelated to membrane curvature, such as green fluorescent protein (GFP), can bend membranes when sufficiently concentrated. These findings demonstrate a highly efficient mechanism by which the crowded protein environment on the surface of cellular membranes can contribute to membrane shape change.

  13. EDITORIAL: Precision proteins Precision proteins

    Science.gov (United States)

    Demming, Anna

    2010-06-01

    Since the birth of modern day medicine, during the times of Hippocrates in ancient Greece, the profession has developed from the rudimentary classification of disease into a rigorous science with an inspiring capability to treat and cure. Scientific methodology has distilled clinical diagnostic tools from the early arts of prognosis, which used to rely as much on revelation and prophecy, as intuition and judgement [1]. Over the past decade, research into the interactions between proteins and nanosystems has provided some ingenious and apt techniques for delving into the intricacies of anatomical systems. In vivo biosensing has emerged as a vibrant field of research, as much of medical diagnosis relies on the detection of substances or an imbalance in the chemicals in the body. The inherent properties of nanoscale structures, such as cantilevers, make them well suited to biosensing applications that demand the detection of molecules at very low concentrations. Measurable deflections in cantilevers functionalised with antibodies provide quantitative indicators of the presence of specific antigens when the two react. Such developments have roused mounting interest in the interactions of proteins with nanostructures, such as carbon nanotubes [3], which have demonstrated great potential as generic biomarkers. Plasmonic properties are also being exploited in sensing applications, such as the molecular sentinel recently devised by researchers in the US. The device uses the plasmonic properties of a silver nanoparticle linked to a Raman labelled hairpin DNA probe to signal changes in the probe geometry resulting from interactions with substances in the environment. Success stories so far include the detection of two specific genes associated with breast cancer [4]. A greater understanding of how RNA interference regulates gene expression has highlighted the potential of using this natural process as another agent for combating disease in personalized medicine. However, the

  14. A novel role for Twist-1 in pulp homeostasis.

    Science.gov (United States)

    Galler, K M; Yasue, A; Cavender, A C; Bialek, P; Karsenty, G; D'Souza, R N

    2007-10-01

    The molecular mechanisms that maintain the equilibrium of odontoblast progenitor cells in dental pulp are unknown. Here we tested whether homeostasis in dental pulp is modulated by Twist-1, a nuclear protein that partners with Runx2 during osteoblast differentiation. Our analysis of Twist-1(+/-) mice revealed phenotypic changes that involved an earlier onset of dentin matrix formation, increased alkaline phosphatase activity, and pulp stones within the pulp. RT-PCR analyses revealed Twist-1 expression in several adult organs, including pulp. Decreased levels of Twist-1 led to higher levels of type I collagen and Dspp gene expression in perivascular cells associated with the pulp stones. In mice heterozygous for both Twist-1 and Runx2 inactivation, the phenotype of pulp stones appeared completely rescued. These findings suggest that Twist-1 plays a key role in restraining odontoblast differentiation, thus maintaining homeostasis in dental pulp. Furthermore, Twist-1 functions in dental pulp are dependent on its interaction with Runx2.

  15. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

    Science.gov (United States)

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase. PMID:27019663

  16. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I-III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue.

    Science.gov (United States)

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase.

  17. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neoadjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

    Directory of Open Access Journals (Sweden)

    Désirée Lötzke

    2016-01-01

    Full Text Available This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neoadjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI (n=45 or for a physical exercise intervention (PEI (n=47. Measurements were obtained before (t0 and after the intervention (t1 as well as 3 months after finishing intervention (t2 using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p<0.05 but not under YI (t0 to t2. Regarding quality of life (EORTC QLQ-C30 a direct effect (t0 to t1; p<0.001 of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p<0.001 were observed at both t1 and t2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t1 nor for t2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase.

  18. Cancers related to immunodeficiencies : Update and perspectives

    NARCIS (Netherlands)

    Mortaz, Esmaeil; Tabarsi, Payam; Mansouri, Davod; Khosravi, Adnan; Garssen, Johan; Velayati, Aliakbar; Adcock, Ian M.

    2016-01-01

    The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with

  19. Immunotherapy against cancer-related viruses

    Science.gov (United States)

    Tashiro, Haruko; Brenner, Malcolm K

    2017-01-01

    Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects. PMID:28008927

  20. Cancer Related-Knowledge - Small Area Estimates

    Science.gov (United States)

    These model-based estimates are produced using statistical models that combine data from the Health Information National Trends Survey, and auxiliary variables obtained from relevant sources and borrow strength from other areas with similar characteristics.

  1. Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

    Science.gov (United States)

    Yuan, Tong-Ling; Chen, Jin; Tong, Yan-Li; Zhang, Yan; Liu, Yuan-Yuan; Wei, James Cheng-Chung; Liu, Yi; Zhao, Yi; Herrmann, Martin

    2016-01-01

    Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p pathways in the two types of arthritis.

  2. Protein docking prediction using predicted protein-protein interface

    Directory of Open Access Journals (Sweden)

    Li Bin

    2012-01-01

    Full Text Available Abstract Background Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. Results We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm, is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. Conclusion We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  3. Shotgun protein sequencing.

    Energy Technology Data Exchange (ETDEWEB)

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.

    2009-06-01

    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  4. Our interests in protein-protein interactions

    Indian Academy of Sciences (India)

    protein interactions. Evolution of P-P partnerships. Evolution of P-P structures. Evolutionary dynamics of P-P interactions. Dynamics of P-P interaction network. Host-pathogen interactions. CryoEM mapping of gigantic protein assemblies.

  5. Evolution of protein-protein interactions

    Indian Academy of Sciences (India)

    Evolution of protein-protein interactions · Our interests in protein-protein interactions · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20.

  6. Ontological visualization of protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Hill David P

    2005-02-01

    Full Text Available Abstract Background Cellular processes require the interaction of many proteins across several cellular compartments. Determining the collective network of such interactions is an important aspect of understanding the role and regulation of individual proteins. The Gene Ontology (GO is used by model organism databases and other bioinformatics resources to provide functional annotation of proteins. The annotation process provides a mechanism to document the binding of one protein with another. We have constructed protein interaction networks for mouse proteins utilizing the information encoded in the GO annotations. The work reported here presents a methodology for integrating and visualizing information on protein-protein interactions. Results GO annotation at Mouse Genome Informatics (MGI captures 1318 curated, documented interactions. These include 129 binary interactions and 125 interaction involving three or more gene products. Three networks involve over 30 partners, the largest involving 109 proteins. Several tools are available at MGI to visualize and analyze these data. Conclusions Curators at the MGI database annotate protein-protein interaction data from experimental reports from the literature. Integration of these data with the other types of data curated at MGI places protein binding data into the larger context of mouse biology and facilitates the generation of new biological hypotheses based on physical interactions among gene products.

  7. 24-hour urine protein

    Science.gov (United States)

    Urine protein - 24 hour; Chronic kidney disease - urine protein; Kidney failure - urine protein ... Heart failure High blood pressure during pregnancy ( preeclampsia ) Kidney disease caused by diabetes, high blood pressure, autoimmune disorders, ...

  8. Protein-losing enteropathy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007338.htm Protein-losing enteropathy To use the sharing features on this page, please enable JavaScript. Protein-losing enteropathy is an abnormal loss of protein ...

  9. Protein in diet

    Science.gov (United States)

    Diet - protein ... Protein foods are broken down into parts called amino acids during digestion. The human body needs a ... to eat animal products to get all the protein you need in your diet. Amino acids are ...

  10. Oligomeric protein structure networks: insights into protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Brinda KV

    2005-12-01

    Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

  11. Protein surface shielding agents in protein crystallization

    International Nuclear Information System (INIS)

    Hašek, J.

    2011-01-01

    The crystallization process can be controlled by protein surface shielding agents blocking undesirable competitive adhesion modes during non-equilibrium processes of deposition of protein molecules on the surface of growing crystalline blocks. The hypothesis is based on a number of experimental proofs from diffraction experiments and also retrieved from the Protein Data Bank. The molecules adhering temporarily on the surface of protein molecules change the propensity of protein molecules to deposit on the crystal surface in a definite position and orientation. The concepts of competitive adhesion modes and protein surface shielding agents acting on the surface of molecules in a non-equilibrium process of protein crystallization provide a useful platform for the control of crystallization. The desirable goal, i.e. a transient preference of a single dominating adhesion mode between protein molecules during crystallization, leads to uniform deposition of proteins in a crystal. This condition is the most important factor for diffraction quality and thus also for the accuracy of protein structure determination. The presented hypothesis is a generalization of the experimentally well proven behaviour of hydrophilic polymers on the surface of protein molecules of other compounds

  12. Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue.

    Science.gov (United States)

    Kisiel-Sajewicz, Katarzyna; Davis, Mellar P; Siemionow, Vlodek; Seyidova-Khoshknabi, Dilara; Wyant, Alexandria; Walsh, Declan; Hou, Juliet; Yue, Guang H

    2012-09-01

    Fatigue is one of the most common symptoms reported by cancer survivors, and fatigue worsens when patients are engaged in muscle exertion, which results in early motor task failure. Central fatigue plays a significant role, more than muscle (peripheral) fatigue, in contributing to early task failure in cancer-related fatigue (CRF). The purpose of this study was to determine if muscle contractile property alterations (reflecting muscle fatigue) occurred at the end of a low-intensity muscle contraction to exhaustion and if these properties differed between those with CRF and healthy controls. Ten patients (aged 59.9±10.6 years, seven women) with advanced solid cancer and CRF and 12 age- and gender-matched healthy controls (aged 46.6±12.8 years, nine women) performed a sustained contraction of the right arm elbow flexion at 30% maximal level until exhaustion. Peak twitch force, time to peak twitch force, rate of peak twitch force development, and half relaxation time derived from electrical stimulation-evoked twitches were analyzed pre- and post-sustained contraction. CRF patients reported significantly greater fatigue as measured by the Brief Fatigue Inventory and failed the motor task earlier, 340±140 vs. 503±155 seconds in controls. All contractile property parameters did not change significantly in CRF but did change significantly in controls. CRF patients perceive physical exhaustion sooner during a motor fatigue task with minimal muscular fatigue. The observation supports that central fatigue is a more significant factor than peripheral fatigue in causing fatigue feelings and limits motor function in cancer survivors with fatigue symptoms. Copyright © 2012. Published by Elsevier Inc.

  13. Impact of aerobic exercise training during chemotherapy on cancer related cognitive impairments in patients suffering from acute myeloid leukemia or myelodysplastic syndrome - Study protocol of a randomized placebo-controlled trial.

    Science.gov (United States)

    Zimmer, P; Oberste, M; Bloch, W; Schenk, A; Joisten, N; Hartig, P; Wolf, F; Baumann, F T; Garthe, A; Hallek, M; Elter, T

    2016-07-01

    Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cancer Health Empowerment for Living without Pain (Ca-HELP: study design and rationale for a tailored education and coaching intervention to enhance care of cancer-related pain

    Directory of Open Access Journals (Sweden)

    Slee Christina

    2009-09-01

    Full Text Available Abstract Background Cancer-related pain is common and under-treated. This article describes a study designed to test the effectiveness of a theory-driven, patient-centered coaching intervention to improve cancer pain processes and outcomes. Methods/Design The Cancer Health Empowerment for Living without Pain (Ca-HELP Study is an American Cancer Society sponsored randomized trial conducted in Sacramento, California. A total of 265 cancer patients with at least moderate pain severity (Worst Pain Numerical Analog Score >=4 out of 10 or pain-related impairment (Likert score >= 3 out of 5 were randomly assigned to receive tailored education and coaching (TEC or educationally-enhanced usual care (EUC; 258 received at least one follow-up assessment. The TEC intervention is based on social-cognitive theory and consists of 6 components (assess, correct, teach, prepare, rehearse, portray. Both interventions were delivered over approximately 30 minutes just prior to a scheduled oncology visit. The majority of visits (56% were audio-recorded for later communication coding. Follow-up data including outcomes related to pain severity and impairment, self-efficacy for pain control and for patient-physician communication, functional status and well-being, and anxiety were collected at 2, 6, and 12 weeks. Discussion Building on social cognitive theory and pilot work, this study aims to test the hypothesis that a brief, tailored patient activation intervention will promote better cancer pain care and outcomes. Analyses will focus on the effects of the experimental intervention on pain severity and impairment (primary outcomes; self-efficacy and quality of life (secondary outcomes; and relationships among processes and outcomes of cancer pain care. If this model of coaching by lay health educators proves successful, it could potentially be implemented widely at modest cost. Trial Registration [Clinical Trials Identifier: NCT00283166

  15. Nanotechnologies in protein microarrays.

    Science.gov (United States)

    Krizkova, Sona; Heger, Zbynek; Zalewska, Marta; Moulick, Amitava; Adam, Vojtech; Kizek, Rene

    2015-01-01

    Protein microarray technology became an important research tool for study and detection of proteins, protein-protein interactions and a number of other applications. The utilization of nanoparticle-based materials and nanotechnology-based techniques for immobilization allows us not only to extend the surface for biomolecule immobilization resulting in enhanced substrate binding properties, decreased background signals and enhanced reporter systems for more sensitive assays. Generally in contemporarily developed microarray systems, multiple nanotechnology-based techniques are combined. In this review, applications of nanoparticles and nanotechnologies in creating protein microarrays, proteins immobilization and detection are summarized. We anticipate that advanced nanotechnologies can be exploited to expand promising fields of proteins identification, monitoring of protein-protein or drug-protein interactions, or proteins structures.

  16. Protein sequence comparison and protein evolution

    Energy Technology Data Exchange (ETDEWEB)

    Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

  17. Protein digestion in ruminants

    African Journals Online (AJOL)

    digestibility, or the contribution of endogenous protein to the indigestible feed .... endogenous protein fractions. Alternatively, Stern & Satter (1984) suggested a method whereby the increased protein outflow to the small intestine, resulting from the incremental addition of ..... definition of the various protein fractions. Finally ...

  18. Expansion of polyalanine tracts in the QA domain may play a critical ...

    Indian Academy of Sciences (India)

    2015-09-03

    Sep 3, 2015 ... According to the analysis of the protein structure, RUNX2 has several functional domains: QA domain, runt domain, nuclear localization signal (NSL),. PST domain, VWRPY and nuclear matrix targeting sequence. (NMTS). The QA domain, a stretch of 23 polyglutamine and 17 polyalanine tracts, is located in ...

  19. Homeostatic interplay between FoxO proteins and ER proteostasis in cancer and other diseases.

    Science.gov (United States)

    González-Quiroz, Matías; Urra, Hery; Limia, Celia María; Hetz, Claudio

    2018-01-31

    Cancer cells are exposed to adverse conditions within the tumor microenvironment that challenge cells to adapt and survive. Several of these homeostatic perturbations insults alter the normal function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a conserved signaling pathway known as the unfolded protein response (UPR) to cope with the stress or trigger apoptosis of damaged cells. The UPR has been described as a major driver in the acquisition of malignant characteristics that ultimately lead to cancer progression. Although, several reports describe the relevance of the UPR in tumor growth, the possible crosstalk with other cancer-related pathways is starting to be elucidated. The Forkhead Box O (FoxO) subfamily of proteins has a major role in cancer progression, where chromosomal translocations and deregulated signaling lead to loss-of-function of FoxO proteins, contributing to tumor progression. Here we discuss the homeostatic connection between the UPR and FoxO proteins and its possible implications to tumor progression and the acquisition of several hallmarks of cancer. In addition, studies linking a crosstalk between the UPR and FoxO proteins in other diseases, including neurodegeneration and metabolic disorders is provided. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. The Protein Model Portal

    OpenAIRE

    Arnold, Konstantin; Kiefer, Florian; Kopp, J?rgen; Battey, James N. D.; Podvinec, Michael; Westbrook, John D.; Berman, Helen M.; Bordoli, Lorenza; Schwede, Torsten

    2008-01-01

    Structural Genomics has been successful in determining the structures of many unique proteins in a high throughput manner. Still, the number of known protein sequences is much larger than the number of experimentally solved protein structures. Homology (or comparative) modeling methods make use of experimental protein structures to build models for evolutionary related proteins. Thereby, experimental structure determination efforts and homology modeling complement each other in the exploratio...

  1. Photoswitchable cyan fluorescent protein for protein tracking.

    Science.gov (United States)

    Chudakov, Dmitriy M; Verkhusha, Vladislav V; Staroverov, Dmitry B; Souslova, Ekaterina A; Lukyanov, Sergey; Lukyanov, Konstantin A

    2004-11-01

    In recent years diverse photolabeling techniques using green fluorescent protein (GFP)-like proteins have been reported, including photoactivatable PA-GFP, photoactivatable protein Kaede, the DsRed 'greening' technique and kindling fluorescent proteins. So far, only PA-GFP, which is monomeric and gives 100-fold fluorescence contrast, could be applied for protein tracking. Here we describe a dual-color monomeric protein, photoswitchable cyan fluorescent protein (PS-CFP). PS-CFP is capable of efficient photoconversion from cyan to green, changing both its excitation and emission spectra in response to 405-nm light irradiation. Complete photoactivation of PS-CFP results in a 1,500-fold increase in the green-to-cyan fluorescence ratio, making it the highest-contrast monomeric photoactivatable fluorescent protein described to date. We used PS-CFP as a photoswitchable tag to study trafficking of human dopamine transporter in living cells. At moderate excitation intensities, PS-CFP can be used as a pH-stable cyan label for protein tagging and fluorescence resonance energy transfer applications.

  2. Protein- protein interaction detection system using fluorescent protein microdomains

    Science.gov (United States)

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2010-02-23

    The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

  3. Comparing side chain packing in soluble proteins, protein-protein interfaces, and transmembrane proteins.

    Science.gov (United States)

    Gaines, J C; Acebes, S; Virrueta, A; Butler, M; Regan, L; O'Hern, C S

    2018-05-01

    We compare side chain prediction and packing of core and non-core regions of soluble proteins, protein-protein interfaces, and transmembrane proteins. We first identified or created comparable databases of high-resolution crystal structures of these 3 protein classes. We show that the solvent-inaccessible cores of the 3 classes of proteins are equally densely packed. As a result, the side chains of core residues at protein-protein interfaces and in the membrane-exposed regions of transmembrane proteins can be predicted by the hard-sphere plus stereochemical constraint model with the same high prediction accuracies (>90%) as core residues in soluble proteins. We also find that for all 3 classes of proteins, as one moves away from the solvent-inaccessible core, the packing fraction decreases as the solvent accessibility increases. However, the side chain predictability remains high (80% within 30°) up to a relative solvent accessibility, rSASA≲0.3, for all 3 protein classes. Our results show that ≈40% of the interface regions in protein complexes are "core", that is, densely packed with side chain conformations that can be accurately predicted using the hard-sphere model. We propose packing fraction as a metric that can be used to distinguish real protein-protein interactions from designed, non-binding, decoys. Our results also show that cores of membrane proteins are the same as cores of soluble proteins. Thus, the computational methods we are developing for the analysis of the effect of hydrophobic core mutations in soluble proteins will be equally applicable to analyses of mutations in membrane proteins. © 2018 Wiley Periodicals, Inc.

  4. Critical protein GAPDH and its regulatory mechanisms in cancer cells

    International Nuclear Information System (INIS)

    Zhang, Jin-Ying; Zhang, Fan; Hong, Chao-Qun; Giuliano, Armando E.; Cui, Xiao-Jiang; Zhou, Guang-Ji; Zhang, Guo-Jun; Cui, Yu-Kun

    2015-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and posttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 (HIF-1), p53, nitric oxide (NO), and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications (PTMs) occurring in GAPDH in cancer cells result in new activities unrelated to the original glycolytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described

  5. A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress.

    Science.gov (United States)

    Mantovani, Giovanni; Macciò, Antonio; Madeddu, Clelia; Gramignano, Giulia; Lusso, Maria Rita; Serpe, Roberto; Massa, Elena; Astara, Giorgio; Deiana, Laura

    2006-05-01

    To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress. An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF). From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the

  6. Design of a randomized controlled trial of physical training and cancer (Phys-Can) - the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome.

    Science.gov (United States)

    Berntsen, Sveinung; Aaronson, Neil K; Buffart, Laurien; Börjeson, Sussanne; Demmelmaier, Ingrid; Hellbom, Maria; Hojman, Pernille; Igelström, Helena; Johansson, Birgitta; Pingel, Ronnie; Raastad, Truls; Velikova, Galina; Åsenlöf, Pernilla; Nordin, Karin

    2017-03-27

    Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 × 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene

  7. Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

    Science.gov (United States)

    Kröz, Matthias; Reif, Marcus; Glinz, Augustina; Berger, Bettina; Nikolaou, Andreas; Zerm, Roland; Brinkhaus, Benno; Girke, Matthias; Büssing, Arndt; Gutenbrunner, Christoph

    2017-03-02

    Cancer-related fatigue (CRF) and insomnia are major complaints in breast cancer survivors (BC). Aerobic training (AT), the standard therapy for CRF in BC, shows only minor to moderate treatment effects. Other evidence-based treatments include cognitive behavioral therapy, e.g., sleep education/restriction (SE) and mindfulness-based therapies. We investigated the effectiveness of a 10-week multimodal program (MT) consisting of SE, psycho-education, eurythmy- and painting-therapy, administered separately or in combination with AT (CT) and compared both arms to AT alone. In a pragmatic comprehensive cohort study BC with chronic CRF were allocated randomly or by patient preference to (a) MT, (b) CT (MT + AT) or (c) AT alone. Primary endpoint was a composite score of the Pittsburgh Sleep Quality Index and the Cancer Fatigue Scale after 10 weeks of intervention (T1); a second endpoint was a follow-up assessment 6 months later (T2). The primary hypothesis stated superiority of CT and non-inferiority of MT vs. AT at T1. A closed testing procedure preserved the global α-level. The intention-to-treat analysis included propensity scores for the mode of allocation and for the preferred treatment, respectively. Altogether 126 BC were recruited: 65 were randomized and 61 allocated by preference; 105 started the intervention. Socio-demographic parameters were generally balanced at baseline. Non-inferiority of MT to AT at T1 was confirmed (p < 0.05), yet the confirmative analysis stopped as it was not possible to confirm superiority of CT vs. AT (p = 0.119). In consecutive exploratory analyses MT and CT were superior to AT at T1 and T2 (MT) or T2 alone (CT), respectively. The multimodal CRF-therapy was found to be confirmatively non-inferior to standard therapy and even yielded exploratively sustained superiority. A randomized controlled trial including a larger sample size and a longer follow-up to evaluate multimodal CRF-therapy is highly warranted. DRKS-ID: DRKS

  8. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, whereas vertebrates contain two to four genes. In cnidarians, the gene appears to encode a secreted protein, but transmembrane isoforms of the protein have also evolved, and in many species, alternative splicing facilitates the expression of both transmembrane and secreted isoforms. In most species......, the longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...

  9. Prediction of Protein-Protein Interactions Related to Protein Complexes Based on Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Peng Liu

    2015-01-01

    Full Text Available A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptive k-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction network. Based on different complex sets detected by various algorithms, we can obtain different prediction sets of protein-protein interactions. The reliability of the predicted interaction sets is proved by using estimations with statistical tests and direct confirmation of the biological data. In comparison with the approaches which predict the interactions based on the cliques, the overlap of the predictions is small. Similarly, the overlaps among the predicted sets of interactions derived from various complex sets are also small. Thus, every predicted set of interactions may complement and improve the quality of the original network data. Meanwhile, the predictions from the proposed method replenish protein-protein interactions associated with protein complexes using only the network topology.

  10. Personalizing Protein Nourishment

    Science.gov (United States)

    DALLAS, DAVID C.; SANCTUARY, MEGAN R.; QU, YUNYAO; KHAJAVI, SHABNAM HAGHIGHAT; VAN ZANDT, ALEXANDRIA E.; DYANDRA, MELISSA; FRESE, STEVEN A.; BARILE, DANIELA; GERMAN, J. BRUCE

    2016-01-01

    Proteins are not equally digestible—their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermentation (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been associated with inflammation in vivo. Individual humans differ in protein digestive capacity based on phenotypes, particularly disease states. To avoid putrefaction-induced intestinal inflammation, protein sources and processing methods must be tailored to the consumer’s digestive capacity. This review explores how food processing techniques alter protein digestibility and examines how physiological conditions alter digestive capacity. Possible solutions to improving digestive function or matching low digestive capacity with more digestible protein sources are explored. Beyond the ileal digestibility measurements of protein digestibility, less invasive, quicker and cheaper techniques for monitoring the extent of protein digestion and fermentation are needed to personalize protein nourishment. Biomarkers of protein digestive capacity and efficiency can be identified with the toolsets of peptidomics, metabolomics, microbial sequencing and multiplexed protein analysis of fecal and urine samples. By monitoring individual protein digestive function, the protein component of diets can be tailored via protein source and processing selection to match individual needs to minimize colonic putrefaction and, thus, optimize gut health. PMID:26713355

  11. Polymer Directed Protein Assemblies

    Directory of Open Access Journals (Sweden)

    Patrick van Rijn

    2013-05-01

    Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

  12. Protein Data Bank (PDB)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Protein Data Bank (PDB) archive is the single worldwide repository of information about the 3D structures of large biological molecules, including proteins and...

  13. Protein electrophoresis - urine

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003589.htm Urine protein electrophoresis test To use the sharing features on this page, please enable JavaScript. The urine protein electrophoresis (UPEP) test is used to estimate how much ...

  14. Protein electrophoresis - serum

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003540.htm Protein electrophoresis - serum To use the sharing features on ... JavaScript. This lab test measures the types of protein in the fluid (serum) part of a blood ...

  15. A protein prioritization approach tailored for the FA/BRCA pathway.

    Directory of Open Access Journals (Sweden)

    Anneke Haitjema

    Full Text Available Fanconi anemia (FA is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which predispose heterozygous mutation carriers to breast cancer. The FA proteins work together in a genome maintenance pathway, the so-called FA/BRCA pathway which is important during the S phase of the cell cycle. Since not all FA patients can be linked to (one of the sixteen known complementation groups, new FA genes remain to be identified. In addition the complex FA network remains to be further unravelled. One of the FA genes, FANCI, has been identified via a combination of bioinformatic techniques exploiting FA protein properties and genetic linkage. The aim of this study was to develop a prioritization approach for proteins of the entire human proteome that potentially interact with the FA/BRCA pathway or are novel candidate FA genes. To this end, we combined the original bioinformatics approach based on the properties of the first thirteen FA proteins identified with publicly available tools for protein-protein interactions, literature mining (Nermal and a protein function prediction tool (FuncNet. Importantly, the three newest FA proteins FANCO/RAD51C, FANCP/SLX4, and XRCC2 displayed scores in the range of the already known FA proteins. Likewise, a prime candidate FA gene based on next generation sequencing and having a very low score was subsequently disproven by functional studies for the FA phenotype. Furthermore, the approach strongly enriches for GO terms such as DNA repair, response to DNA damage stimulus, and cell cycle-regulated genes. Additionally, overlaying the top 150 with a haploinsufficiency probability score, renders the approach more tailored for identifying breast cancer related genes. This approach may be useful for prioritization of putative novel FA or breast cancer genes from next generation sequencing efforts.

  16. Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer

    OpenAIRE

    Łukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

    2010-01-01

    Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers—carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 ...

  17. CSF total protein

    Science.gov (United States)

    CSF total protein is a test to determine the amount of protein in your spinal fluid, also called cerebrospinal fluid (CSF). ... The normal protein range varies from lab to lab, but is typically about 15 to 60 milligrams per deciliter (mg/dL) ...

  18. Protein sequence databases.

    Science.gov (United States)

    Apweiler, Rolf; Bairoch, Amos; Wu, Cathy H

    2004-02-01

    A variety of protein sequence databases exist, ranging from simple sequence repositories, which store data with little or no manual intervention in the creation of the records, to expertly curated universal databases that cover all species and in which the original sequence data are enhanced by the manual addition of further information in each sequence record. As the focus of researchers moves from the genome to the proteins encoded by it, these databases will play an even more important role as central comprehensive resources of protein information. Several the leading protein sequence databases are discussed here, with special emphasis on the databases now provided by the Universal Protein Knowledgebase (UniProt) consortium.

  19. Protein hydration and dynamics

    International Nuclear Information System (INIS)

    Nakagawa, Hiroshi; Kataoka, Mikio

    2015-01-01

    Inelastic neutron scattering can measure the protein thermal fluctuations under the physiological aqueous environment, especially it is powerful to observe the low-energy protein dynamics in THz region, which are revealed theoretically to be coupled with solvations. Neutron enables the selective observation of protein and hydration water by deuteration. The complementary analysis with molecular dynamics simulation is also effective for the study of protein hydration. Some examples of the application toward the understanding of molecular basis of protein functions will be introduced. (author)

  20. Highly thermostable fluorescent proteins

    Science.gov (United States)

    Bradbury, Andrew M [Santa Fe, NM; Waldo, Geoffrey S [Santa Fe, NM; Kiss, Csaba [Los Alamos, NM

    2011-03-22

    Thermostable fluorescent proteins (TSFPs), methods for generating these and other stability-enhanced proteins, polynucleotides encoding such proteins, and assays and method for using the TSFPs and TSFP-encoding nucleic acid molecules are provided. The TSFPs of the invention show extremely enhanced levels of stability and thermotolerance. In one case, for example, a TSFP of the invention is so stable it can be heated to 99.degree. C. for short periods of time without denaturing, and retains 85% of its fluorescence when heated to 80.degree. C. for several minutes. The invention also provides a method for generating stability-enhanced variants of a protein, including but not limited to fluorescent proteins.

  1. Targeting proteins for degradation.

    Science.gov (United States)

    Schrader, Erin K; Harstad, Kristine G; Matouschek, Andreas

    2009-11-01

    Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cell to avoid toxicity. The concentrations of regulatory proteins are adjusted by degradation at the appropriate time. Both foreign and native proteins are digested into small peptides as part of the adaptive immune response. In eukaryotic cells, an ATP-dependent protease called the proteasome is responsible for much of this proteolysis. Proteins are targeted for proteasomal degradation by a two-part degron, which consists of a proteasome binding signal and a degradation initiation site. Here we describe how both components contribute to the specificity of degradation.

  2. Protein supplementation with aging.

    Science.gov (United States)

    Bauer, Juergen M; Diekmann, Rebecca

    2015-01-01

    To highlight the recent evicence for optimal protein intake and protein supplementation in older adults. A special focus has been placed on the effects on muscle protein synthesis, strength and overall performance in this population. Although for older adults, some additional evidence on the benefits of a higher protein intake than 0.8 g/kg body weight per day has been provided, the results of studies focusing on the timing of protein intake over the day have been contradictory. Supplementation with so-called 'fast' proteins, which are also rich in leucine, for example whey protein, proved superior with regard to muscle protein synthesis. First studies in frail older persons showed increased strength after supplementation with milk protein, whereas the combination with physical exercise increased muscle mass without additional benefit for strength or functionality. Recent evidence suggests positive effects of protein supplementation on muscle protein synthesis, muscle mass and muscle strength. However, as most studies included only small numbers of participants for short treatment periods, larger studies with longer duration are necessary to support the clinical relevance of these observations.

  3. Racemic protein crystallography.

    Science.gov (United States)

    Yeates, Todd O; Kent, Stephen B H

    2012-01-01

    Although natural proteins are chiral and are all of one "handedness," their mirror image forms can be prepared by chemical synthesis. This opens up new opportunities for protein crystallography. A racemic mixture of the enantiomeric forms of a protein molecule can crystallize in ways that natural proteins cannot. Recent experimental data support a theoretical prediction that this should make racemic protein mixtures highly amenable to crystallization. Crystals obtained from racemic mixtures also offer advantages in structure determination strategies. The relevance of these potential advantages is heightened by advances in synthetic methods, which are extending the size limit for proteins that can be prepared by chemical synthesis. Recent ideas and results in the area of racemic protein crystallography are reviewed.

  4. Intracellular protein breakdown. 8

    International Nuclear Information System (INIS)

    Bohley, P.; Kirschke, H.; Langner, J.; Wiederanders, B.; Ansorge, S.

    1976-01-01

    Double-labelled proteins from rat liver cytosol ( 14 C in long-lived, 3 H in short-lived proteins after in-vivo-labelling) are used as substrates for unlabelled proteinases in vitro. Differences in the degradation rates of short-lived and long-lived proteins in vitro by different proteinases and after addition of different effectors allow conclusions concerning their importance for the in-vivo-turnover of substrate proteins. The main activity (>90%) of soluble lysosomal proteinases at pH 6.1 and pH 6.9 is caused by thiolproteinases, which degrade preferentially short-lived cytosol proteins. These proteinases are inhibited by leupeptin. Autolysis of double-labelled cell fractions shows a remarkably faster breakdown of short-lived substrate proteins only in the soluble part of lysosomes. Microsomal fractions degrade in vitro preferentially long-lived substrate proteins. (author)

  5. Protein solubility modeling

    Science.gov (United States)

    Agena, S. M.; Pusey, M. L.; Bogle, I. D.

    1999-01-01

    A thermodynamic framework (UNIQUAC model with temperature dependent parameters) is applied to model the salt-induced protein crystallization equilibrium, i.e., protein solubility. The framework introduces a term for the solubility product describing protein transfer between the liquid and solid phase and a term for the solution behavior describing deviation from ideal solution. Protein solubility is modeled as a function of salt concentration and temperature for a four-component system consisting of a protein, pseudo solvent (water and buffer), cation, and anion (salt). Two different systems, lysozyme with sodium chloride and concanavalin A with ammonium sulfate, are investigated. Comparison of the modeled and experimental protein solubility data results in an average root mean square deviation of 5.8%, demonstrating that the model closely follows the experimental behavior. Model calculations and model parameters are reviewed to examine the model and protein crystallization process. Copyright 1999 John Wiley & Sons, Inc.

  6. Annotating gene sets by mining large literature collections with protein networks.

    Science.gov (United States)

    Wang, Sheng; Ma, Jianzhu; Yu, Michael Ku; Zheng, Fan; Huang, Edward W; Han, Jiawei; Peng, Jian; Ideker, Trey

    2018-01-01

    Analysis of patient genomes and transcriptomes routinely recognizes new gene sets associated with human disease. Here we present an integrative natural language processing system which infers common functions for a gene set through automatic mining of the scientific literature with biological networks. This system links genes with associated literature phrases and combines these links with protein interactions in a single heterogeneous network. Multiscale functional annotations are inferred based on network distances between phrases and genes and then visualized as an ontology of biological concepts. To evaluate this system, we predict functions for gene sets representing known pathways and find that our approach achieves substantial improvement over the conventional text-mining baseline method. Moreover, our system discovers novel annotations for gene sets or pathways without previously known functions. Two case studies demonstrate how the system is used in discovery of new cancer-related pathways with ontological annotations.

  7. Protein kinesis: The dynamics of protein trafficking and stability

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The purpose of this conference is to provide a multidisciplinary forum for exchange of state-of-the-art information on protein kinesis. This volume contains abstracts of papers in the following areas: protein folding and modification in the endoplasmic reticulum; protein trafficking; protein translocation and folding; protein degradation; polarity; nuclear trafficking; membrane dynamics; and protein import into organelles.

  8. PROTEIN - WHICH IS BEST?

    Directory of Open Access Journals (Sweden)

    Michael J. Falvo

    2004-09-01

    Full Text Available Protein intake that exceeds the recommended daily allowance is widely accepted for both endurance and power athletes. However, considering the variety of proteins that are available much less is known concerning the benefits of consuming one protein versus another. The purpose of this paper is to identify and analyze key factors in order to make responsible recommendations to both the general and athletic populations. Evaluation of a protein is fundamental in determining its appropriateness in the human diet. Proteins that are of inferior content and digestibility are important to recognize and restrict or limit in the diet. Similarly, such knowledge will provide an ability to identify proteins that provide the greatest benefit and should be consumed. The various techniques utilized to rate protein will be discussed. Traditionally, sources of dietary protein are seen as either being of animal or vegetable origin. Animal sources provide a complete source of protein (i.e. containing all essential amino acids, whereas vegetable sources generally lack one or more of the essential amino acids. Animal sources of dietary protein, despite providing a complete protein and numerous vitamins and minerals, have some health professionals concerned about the amount of saturated fat common in these foods compared to vegetable sources. The advent of processing techniques has shifted some of this attention and ignited the sports supplement marketplace with derivative products such as whey, casein and soy. Individually, these products vary in quality and applicability to certain populations. The benefits that these particular proteins possess are discussed. In addition, the impact that elevated protein consumption has on health and safety issues (i.e. bone health, renal function are also reviewed

  9. Decreased Levels of Circulating Cancer-Associated Protein Biomarkers Following Bariatric Surgery.

    Science.gov (United States)

    Farey, John Edward; Fisher, Oliver M; Levert-Mignon, Angelique J; Forner, Patrice M; Lord, Reginald V

    2017-03-01

    Epidemiological studies have identified obesity as a major risk factor for cancer in humans, and trials have demonstrated a significant reduction in the incidence of cancer after bariatric surgery. The rapidity of weight loss after bariatric surgery provides an opportunity to identify the molecular changes associated with effective obesity treatment. Indirectly, this may provide some insights into the mechanisms that drive the association between obesity and cancer. We sought to measure circulating cancer-associated proteins before and after laparoscopic sleeve gastrectomy (LSG). We prospectively enrolled 15 patients undergoing LSG. Thirty-four plasma protein biomarkers thought to be associated with cancer processes were analyzed at baseline and following successful weight loss at 12 weeks using a multiplex bead-based assay. Mean excess body weight loss was 44 % at 12-week follow-up. After LSG, a significant reduction in circulating plasma levels was observed for half (17/34) of the proteins assessed: VEGF-A, VEGF-C, VEGF-D, endoglin, PLGF, sFASL, IGFBP-1, IL-18, prolactin, EGF, TGFα, sCD40L, IL-18, TNFα, IL-6, HB-EGF, and PAI-1. Nonsignificant decreases were found for the remaining proteins. Circulating cancer-related biomarker levels were reduced by surgical weight loss, and this benefit was achieved as early as 3 months after operation. The observed reduction in cancer biomarkers may be related to the reported decrease in cancer incidence following bariatric surgery.

  10. Protein oxidation and peroxidation

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan

    2016-01-01

    Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard...... and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals...... and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function...

  11. Protein Misfolding Diseases.

    Science.gov (United States)

    Hartl, F Ulrich

    2017-06-20

    The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies. To prevent or regulate protein aggregation, all cells contain an extensive protein homeostasis (or proteostasis) network comprising molecular chaperones and other factors. These defense systems tend to decline during aging, facilitating the manifestation of aggregate deposition diseases. This volume of the Annual Review of Biochemistry contains a set of three articles addressing our current understanding of the structures of pathological protein aggregates and their associated disease mechanisms. These articles also discuss recent insights into the strategies cells have evolved to neutralize toxic aggregates by sequestering them in specific cellular locations.

  12. Computational Protein Design

    DEFF Research Database (Denmark)

    Johansson, Kristoffer Enøe

    with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part......Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together...

  13. Computational Protein Design

    DEFF Research Database (Denmark)

    Johansson, Kristoffer Enøe

    Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together...... with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part...

  14. Specificity and affinity quantification of protein-protein interactions.

    Science.gov (United States)

    Yan, Zhiqiang; Guo, Liyong; Hu, Liang; Wang, Jin

    2013-05-01

    Most biological processes are mediated by the protein-protein interactions. Determination of the protein-protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein-protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein-protein complexes. The scoring function of protein-protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein-protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein-protein complex against competitive ones. We developed a scoring function (named as SPA-PP, specificity and affinity of the protein-protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein-protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein-protein structure and affinity. The algorithm is implemented in C language, and the code can be downloaded from http://dl.dropbox.com/u/1865642/Optimization.cpp.

  15. Successful Protein Production

    OpenAIRE

    Culp, J.

    2011-01-01

    Successful production of functional proteins is more than an immunoreactive band on a Western blot. Availability of multiple expression vectors make accessible a variety of expression systems and parallel expression approaches can speed results and increase chance of success. The next hurdle is isolation of the protein target in sufficient amounts and with sufficient purity to support subsequent experimental work. Occasionally, protein refolding is the only method available to achieve the des...

  16. Pressure cryocooling protein crystals

    Science.gov (United States)

    Kim, Chae Un [Ithaca, NY; Gruner, Sol M [Ithaca, NY

    2011-10-04

    Preparation of cryocooled protein crystal is provided by use of helium pressurizing and cryocooling to obtain cryocooled protein crystal allowing collection of high resolution data and by heavier noble gas (krypton or xenon) binding followed by helium pressurizing and cryocooling to obtain cryocooled protein crystal for collection of high resolution data and SAD phasing simultaneously. The helium pressurizing is carried out on crystal coated to prevent dehydration or on crystal grown in aqueous solution in a capillary.

  17. Protein intakes in India.

    Science.gov (United States)

    Swaminathan, Sumathi; Vaz, Mario; Kurpad, Anura V

    2012-08-01

    Indian diets derive almost 60 % of their protein from cereals with relatively low digestibility and quality. There have been several surveys of diets and protein intakes in India by the National Nutrition Monitoring Board (NNMB) over the last 25 years, in urban and rural, as well as in slum dwellers and tribal populations. Data of disadvantaged populations from slums, tribals and sedentary rural Indian populations show that the protein intake (mainly from cereals) is about 1 gm/kg/day. However, the protein intake looks less promising in terms of the protein digestibility corrected amino acid score (PDCAAS), using lysine as the first limiting amino acid, where all populations, particularly rural and tribal, appear to have an inadequate quality to their protein intake. The protein: energy (PE) ratio is a measure of dietary quality, and has been used in the 2007 WHO/FAO/UNU report to define reference requirement values with which the adequacy of diets can be evaluated in terms of a protein quality corrected PE ratio. It is likely that about one third of this sedentary rural population is at risk of not meeting their requirements. These levels of risk of deficiency are in a population with relatively low BMI populations, whose diets are also inadequate in fruits and vegetables. Therefore, while the burden of enhancing the quality of protein intake in rural India exists, the quality of the diet, in general, represents a challenge that must be met.

  18. Protein carbonylation in plants

    DEFF Research Database (Denmark)

    Møller, Ian Max; Havelund, Jesper; Rogowska-Wrzesinska, Adelina

    2017-01-01

    This chapter provides an overview of the current knowledge on protein carbonylation in plants and its role in plant physiology. It starts with a brief outline of the turnover and production sites of reactive oxygen species (ROS) in plants and the causes of protein carbonylation. This is followed...... by a description of the methods used to study protein carbonylation in plants, which is also very brief as the methods are similar to those used in studies on animals. The chapter also focuses on protein carbonylation in plants in general and in mitochondria and in seeds in particular, as case stories where...

  19. MicroProteins

    DEFF Research Database (Denmark)

    Eguen, Teinai Ebimienere; Straub, Daniel; Graeff, Moritz

    2015-01-01

    MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining characterist......MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining...

  20. Acanthamoeba castellanii STAT protein.

    Science.gov (United States)

    Kicinska, Anna; Leluk, Jacek; Jarmuszkiewicz, Wieslawa

    2014-01-01

    STAT (signal transducers and activators of transcription) proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil), a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds) or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

  1. Acanthamoeba castellanii STAT protein.

    Directory of Open Access Journals (Sweden)

    Anna Kicinska

    Full Text Available STAT (signal transducers and activators of transcription proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil, a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

  2. What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae?

    OpenAIRE

    Ekman, Diana; Light, Sara; Bj?rklund, ?sa K; Elofsson, Arne

    2006-01-01

    Background Most proteins interact with only a few other proteins while a small number of proteins (hubs) have many interaction partners. Hub proteins and non-hub proteins differ in several respects; however, understanding is not complete about what properties characterize the hubs and set them apart from proteins of low connectivity. Therefore, we have investigated what differentiates hubs from non-hubs and static hubs (party hubs) from dynamic hubs (date hubs) in the protein-protein interact...

  3. Allosteric Regulation of Proteins

    Indian Academy of Sciences (India)

    For example, the structural changes that allowed for allosteric regulation of haemoglobin were re- vealed through structural elucidation of the protein in free and oxygen-bound forms by X-ray crystallography. Following this,. X-ray crystallography has been utilized to study a variety of al- losteric proteins including ATCase. 2.

  4. Modular protein domains

    National Research Council Canada - National Science Library

    Cesareni, Giovanni

    2005-01-01

    ... encodes not only sequence, but somehow explicitly specifies folding, structure, and biological function as well. How, then, can one learn to read this 'language of proteins'? One of the most powerful approaches to 'cracking the protein code' has involved sequence comparisons between and within species, a task now greatly simplified by the ever...

  5. Amino acids and proteins

    NARCIS (Netherlands)

    van Goudoever, Johannes B.; Vlaardingerbroek, Hester; van den Akker, Chris H.; de Groof, Femke; van der Schoor, Sophie R. D.

    2014-01-01

    Amino acids and protein are key factors for growth. The neonatal period requires the highest intake in life to meet the demands. Those demands include amino acids for growth, but proteins and amino acids also function as signalling molecules and function as neurotransmitters. Often the nutritional

  6. MODELS OF PROTEIN FOLDING

    Directory of Open Access Journals (Sweden)

    Unnati Ahluwalia

    2012-12-01

    Full Text Available In an attempt to explore the understanding of protein folding mechanism, various models have been proposed in the literature. Advances in recent experimental and computational techniques rationalized our understanding on some of the fundamental features of the protein folding pathways. The goal of this review is to revisit the various models and outline the essential aspects of the folding reaction.

  7. Green fluorescent protein.

    Science.gov (United States)

    Chalfie, M

    1995-10-01

    Several bioluminescent coelenterates use a secondary fluorescent protein, the green fluorescent protein (GFP), in an energy transfer reaction to produce green light. The most studied of these proteins have been the GFPs from the jellyfish Aequorea victoria and the sea pansy Renilla reniformis. Although the proteins from these organisms are not identical, they are thought to have the same chromophore, which is derived from the primary amino acid sequence of GFP. The differences are thought to be due to changes in the protein environment of the chromophore. Recent interest in these molecules has arisen from the cloning of the Aequorea gfp cDNA and the demonstration that its expression in the absence of other Aequorea proteins results in a fluorescent product. This demonstration indicated that GFP could be used as a marker of gene expression and protein localization in living and fixed tissues. Bacterial, plant and animal (including mammalian) cells all express GFP. The heterologous expression of the gfp cDNA has also meant that it could be mutated to produce proteins with different fluorescent properties. Variants with more intense fluorescence or alterations in the excitation and emission spectra have been produced.

  8. Proteins at surfaces

    NARCIS (Netherlands)

    Efimova, Y.M.

    2006-01-01

    Understanding protein adsorption is of vital importance in many fields of medicine and industry that can be divided into two categories: those in which it is desired to minimize adsorption, and those in which protein adsorption is desired. The first category covers materials for kidney dialysis

  9. Protein Attachment on Nanodiamonds.

    Science.gov (United States)

    Lin, Chung-Lun; Lin, Cheng-Huang; Chang, Huan-Cheng; Su, Meng-Chih

    2015-07-16

    A recent advance in nanotechnology is the scale-up production of small and nonaggregated diamond nanoparticles suitable for biological applications. Using detonation nanodiamonds (NDs) with an average diameter of ∼4 nm as the adsorbents, we have studied the static attachment of three proteins (myoglobin, bovine serum albumin, and insulin) onto the nanoparticles by optical spectroscopy, mass spectrometry, and dynamic light scattering, and electrophoretic zeta potential measurements. Results show that the protein surface coverage is predominantly determined by the competition between protein-protein and protein-ND interactions, giving each protein a unique and characteristic structural configuration in its own complex. Specifically, both myoglobin and bovine serum albumin show a Langmuir-type adsorption behavior, forming 1:1 complexes at saturation, whereas insulin folds into a tightly bound multimer before adsorption. The markedly different adsorption patterns appear to be independent of the protein concentration and are closely related to the affinity of the individual proteins for the NDs. The present study provides a fundamental understanding for the use of NDs as a platform for nanomedical drug delivery.

  10. Poxviral Ankyrin Proteins

    Directory of Open Access Journals (Sweden)

    Michael H. Herbert

    2015-02-01

    Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

  11. Advances in Protein Precipitation

    NARCIS (Netherlands)

    Golubovic, M.

    2009-01-01

    Proteins are biological macromolecules, which are among the key components of all living organisms. Proteins are nowadays present in all fields of biotech industry, such as food and feed, synthetic and pharmaceutical industry. They are isolated from their natural sources or produced in different

  12. NMR of unfolded proteins

    Indian Academy of Sciences (India)

    Unknown

    2005-01-03

    Jan 3, 2005 ... emerged as the sole, most powerful technique to help characterize these disordered protein systems. In ... tion of a protein is related to its significant and ...... This is likely to allow a number of both charged and hydrophobic groups to be presented to fibronectin for highly spe- cific binding.76. 5.3 Lysozyme.

  13. NMR of unfolded proteins

    Indian Academy of Sciences (India)

    In the post-genomic era, as more and more genome sequences are becoming known and hectic efforts are underway to decode the information content in them, it is becoming increasingly evident that flexibility in proteins plays a crucial role in many of the biological functions. Many proteins have intrinsic disorder either ...

  14. Brushes and proteins

    NARCIS (Netherlands)

    Bosker, W.T.E.

    2011-01-01

      Brushes and Proteins   Wouter T. E. Bosker         Protein adsorption at solid surfaces can be prevented by applying a polymer brush at the surface. A polymer brush consists of polymer chains end-grafted to the surface at such a grafting density that

  15. Artificially Engineered Protein Polymers.

    Science.gov (United States)

    Yang, Yun Jung; Holmberg, Angela L; Olsen, Bradley D

    2017-06-07

    Modern polymer science increasingly requires precise control over macromolecular structure and properties for engineering advanced materials and biomedical systems. The application of biological processes to design and synthesize artificial protein polymers offers a means for furthering macromolecular tunability, enabling polymers with dispersities of ∼1.0 and monomer-level sequence control. Taking inspiration from materials evolved in nature, scientists have created modular building blocks with simplified monomer sequences that replicate the function of natural systems. The corresponding protein engineering toolbox has enabled the systematic development of complex functional polymeric materials across areas as diverse as adhesives, responsive polymers, and medical materials. This review discusses the natural proteins that have inspired the development of key building blocks for protein polymer engineering and the function of these elements in material design. The prospects and progress for scalable commercialization of protein polymers are reviewed, discussing both technology needs and opportunities.

  16. Protein restriction and cancer.

    Science.gov (United States)

    Yin, Jie; Ren, Wenkai; Huang, Xingguo; Li, Tiejun; Yin, Yulong

    2018-03-26

    Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Sensitizing properties of proteins

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott

    2014-01-01

    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding...... the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary...

  18. The Protein Model Portal.

    Science.gov (United States)

    Arnold, Konstantin; Kiefer, Florian; Kopp, Jürgen; Battey, James N D; Podvinec, Michael; Westbrook, John D; Berman, Helen M; Bordoli, Lorenza; Schwede, Torsten

    2009-03-01

    Structural Genomics has been successful in determining the structures of many unique proteins in a high throughput manner. Still, the number of known protein sequences is much larger than the number of experimentally solved protein structures. Homology (or comparative) modeling methods make use of experimental protein structures to build models for evolutionary related proteins. Thereby, experimental structure determination efforts and homology modeling complement each other in the exploration of the protein structure space. One of the challenges in using model information effectively has been to access all models available for a specific protein in heterogeneous formats at different sites using various incompatible accession code systems. Often, structure models for hundreds of proteins can be derived from a given experimentally determined structure, using a variety of established methods. This has been done by all of the PSI centers, and by various independent modeling groups. The goal of the Protein Model Portal (PMP) is to provide a single portal which gives access to the various models that can be leveraged from PSI targets and other experimental protein structures. A single interface allows all existing pre-computed models across these various sites to be queried simultaneously, and provides links to interactive services for template selection, target-template alignment, model building, and quality assessment. The current release of the portal consists of 7.6 million model structures provided by different partner resources (CSMP, JCSG, MCSG, NESG, NYSGXRC, JCMM, ModBase, SWISS-MODEL Repository). The PMP is available at http://www.proteinmodelportal.org and from the PSI Structural Genomics Knowledgebase.

  19. Protein trapping of nanoparticles

    International Nuclear Information System (INIS)

    Ang, Joo C.; Lin, Jack M.; Yaron, Peter N.; White, John W.

    2009-01-01

    Full text: We have observed the formation of protein-nanoparticle complexes at the air-water interfaces from three different methods of presenting the nanoparticles to proteins. The structures formed resemble the 'protein-nanoparticle corona' proposed by Lynch et al. [1-3) in relation to a possible route for nanoparticle entry into living cells. To do this, the methods of x-ray and neutron reflectivity (with isotopic contrast variation between the protein and nanoparticles) have been used to study the structures formed at the air-water interface of l 3 - casein presented to silica nanoparticle dispersions. Whilst the silica dispersions showed no observable reflectivity, strong signals appear in the reflectivity when protein is present. Drop-wise spreading of a small amount of protein at the air-silica sol interface and presentation of the silica sol to an isolated monomolecular protein film (made by the 'flow-trough' method [4]) gave an immediate signal. Mixing the components in solution only produces a slow response but in all cases a similar structure is formed. The different responses are interpreted in structural and stoichiometric ways.

  20. Anchored design of protein-protein interfaces.

    Directory of Open Access Journals (Sweden)

    Steven M Lewis

    Full Text Available Few existing protein-protein interface design methods allow for extensive backbone rearrangements during the design process. There is also a dichotomy between redesign methods, which take advantage of the native interface, and de novo methods, which produce novel binders.Here, we propose a new method for designing novel protein reagents that combines advantages of redesign and de novo methods and allows for extensive backbone motion. This method requires a bound structure of a target and one of its natural binding partners. A key interaction in this interface, the anchor, is computationally grafted out of the partner and into a surface loop on the design scaffold. The design scaffold's surface is then redesigned with backbone flexibility to create a new binding partner for the target. Careful choice of a scaffold will bring experimentally desirable characteristics into the new complex. The use of an anchor both expedites the design process and ensures that binding proceeds against a known location on the target. The use of surface loops on the scaffold allows for flexible-backbone redesign to properly search conformational space.This protocol was implemented within the Rosetta3 software suite. To demonstrate and evaluate this protocol, we have developed a benchmarking set of structures from the PDB with loop-mediated interfaces. This protocol can recover the correct loop-mediated interface in 15 out of 16 tested structures, using only a single residue as an anchor.

  1. Intercellular protein-protein interactions at synapses.

    Science.gov (United States)

    Yang, Xiaofei; Hou, Dongmei; Jiang, Wei; Zhang, Chen

    2014-06-01

    Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer's disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.

  2. Protein oxidation in aquatic foods

    DEFF Research Database (Denmark)

    Baron, Caroline P.

    2014-01-01

    The chapter discusses general considerations about protein oxidation and reviews the mechanisms involved in protein oxidation and consequences of protein oxidation on fish proteins. It presents two case studies, the first deals with protein and lipid oxidation in frozen rainbow trout......, and the second with oxidation in salted herring. The mechanisms responsible for initiation of protein oxidation are unclear, but it is generally accepted that free radical species initiating lipid oxidation can also initiate protein oxidation. The chapter focuses on interaction between protein and lipid...... oxidation. The protein carbonyl group measurement is the widely used method for estimating protein oxidation in foods and has been used in fish muscle. The chapter also talks about the impact of protein oxidation on protein functionality, fish muscle texture, and food nutritional value. Protein oxidation...

  3. The transcription factor protein Sox11 enhances early osteoblast differentiation by facilitating proliferation and the survival of mesenchymal and osteoblast progenitors.

    Science.gov (United States)

    Gadi, Jogeswar; Jung, Seung-Hyun; Lee, Min-Jung; Jami, Ajita; Ruthala, Kalyani; Kim, Kyoung-Min; Cho, Nam-Hoon; Jung, Han-Sung; Kim, Cheol-Hee; Lim, Sung-Kil

    2013-08-30

    Sox11 deletion mice are known to exhibit developmental defects of craniofacial skeletal malformations, asplenia, and hypoplasia of the lung, stomach, and pancreas. Despite the importance of Sox11 in the developing skeleton, the role of Sox11 in osteogenesis has not been studied yet. In this study, we identified that Sox11 is an important transcription factor for regulating the proliferation and survival of osteoblast precursor cells as well as the self-renewal potency of mesenchymal progenitor cells via up-regulation of Tead2. Furthermore, Sox11 also plays an important role in the segregation of functional osteoblast lineage progenitors from osteochondrogenic progenitors. Facilitation of osteoblast differentiation from mesenchymal cells was achieved by enhanced expression of the osteoblast lineage specific transcription factors Runx2 and Osterix. Morpholino-targeted disruption of Sox11 in zebrafish impaired organogenesis, including the bones, which were under mineralized. These results indicated that Sox11 plays a crucial role in the proliferation and survival of mesenchymal and osteoblast precursors by Tead2, and osteogenic differentiation by regulating Runx2 and Osterix.

  4. Protein oxidation and ageing

    DEFF Research Database (Denmark)

    Linton, S; Davies, Michael Jonathan; Dean, R T

    2001-01-01

    of redox-active metal ions that could catalyse oxidant formation. As a result of this decrease in antioxidant defences, and increased rate of ROS formation, it is possible that the impact of ROS increases with age. ROS are known to oxidise biological macromolecules, with proteins an important target....... If the argument that the impact of ROS increases with age is true, then proteins would be expected to accumulate oxidised materials with age, and the rate of such accumulation should increase with time, reflecting impaired inefficiency of homeostasis. Here we review the evidence for the accumulation of oxidised......, or modified, extra- and intra-cellular proteins in vivo....

  5. Protein crystallography prescreen kit

    Science.gov (United States)

    Segelke, Brent W.; Krupka, Heike I.; Rupp, Bernhard

    2005-07-12

    A kit for prescreening protein concentration for crystallization includes a multiplicity of vials, a multiplicity of pre-selected reagents, and a multiplicity of sample plates. The reagents and a corresponding multiplicity of samples of the protein in solutions of varying concentrations are placed on sample plates. The sample plates containing the reagents and samples are incubated. After incubation the sample plates are examined to determine which of the sample concentrations are too low and which the sample concentrations are too high. The sample concentrations that are optimal for protein crystallization are selected and used.

  6. Sound of proteins

    DEFF Research Database (Denmark)

    2007-01-01

    In my group we work with Molecular Dynamics to model several different proteins and protein systems. We submit our modelled molecules to changes in temperature, changes in solvent composition and even external pulling forces. To analyze our simulation results we have so far used visual inspection...... and statistical analysis of the resulting molecular trajectories (as everybody else!). However, recently I started assigning a particular sound frequency to each amino acid in the protein, and by setting the amplitude of each frequency according to the movement amplitude we can "hear" whenever two aminoacids...

  7. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    2009-01-01

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  8. Protein Crystal Malic Enzyme

    Science.gov (United States)

    1992-01-01

    Malic Enzyme is a target protein for drug design because it is a key protein in the life cycle of intestinal parasites. After 2 years of effort on Earth, investigators were unable to produce any crystals that were of high enough quality and for this reason the structure of this important protein could not be determined. Crystals obtained from one STS-50 were of superior quality allowing the structure to be determined. This is just one example why access to space is so vital for these studies. Principal Investigator is Larry DeLucas.

  9. Designing microcapsules based on protein fibrils and protein - polysaccharide complexes

    NARCIS (Netherlands)

    Hua, K.N.P.

    2012-01-01

    Keywords: encapsulation, microcapsule, protein, fibril, protein-polysaccharide complex, controlled release, interfacial rheology, lysozyme, ovalbumin This thesis describes the design of encapsulation systems using mesostructures from proteins and polysaccharides. The approach was to first

  10. Designing microcapsules based on protein fibrils and protein - polysaccharide complexes

    NARCIS (Netherlands)

    Hua, K.N.P.

    2012-01-01

    Keywords: encapsulation, microcapsule, protein, fibril, protein-polysaccharide complex, controlled release, interfacial rheology, lysozyme, ovalbumin

    This thesis describes the design of encapsulation systems using mesostructures from proteins and polysaccharides. The approach

  11. Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west African populations.

    Directory of Open Access Journals (Sweden)

    Haddy K S Fye

    Full Text Available Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC.Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis.Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages.The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose

  12. Integral UBL domain proteins: a family of proteasome interacting proteins

    DEFF Research Database (Denmark)

    Hartmann-Petersen, Rasmus; Gordon, Colin

    2004-01-01

    The family of ubiquitin-like (UBL) domain proteins (UDPs) comprises a conserved group of proteins involved in a multitude of different cellular activities. However, recent studies on UBL-domain proteins indicate that these proteins appear to share a common property in their ability to interact......-domain proteins catalyse the formation of ubiquitin-protein conjugates, whereas others appear to target ubiquitinated proteins for degradation and interact with chaperones. Hence, by binding to the 26S proteasome the UBL-domain proteins seem to tailor and direct the basic proteolytic functions of the particle...

  13. Interactive protein manipulation

    Energy Technology Data Exchange (ETDEWEB)

    SNCrivelli@lbl.gov

    2003-07-01

    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures.

  14. Retinoblastoma protein partners.

    Science.gov (United States)

    Morris, E J; Dyson, N J

    2001-01-01

    Studies of the retinoblastoma gene (Rb) have shown that its protein product (pRb) acts to restrict cell proliferation, inhibit apoptosis, and promote cell differentiation. The frequent mutation of the Rb gene, and the functional inactivation of pRb in tumor cells, have spurred interest in the mechanism of pRb action. Recently, much attention has focused on pRb's role in the regulation of the E2F transcription factor. However, biochemical studies have suggested that E2F is only one of many pRb-targets and, to date, at least 110 cellular proteins have been reported to associate with pRb. The plethora of pRb-binding proteins raises several important questions. How many functions does pRb possess, which of these functions are important for development, and which contribute to tumor suppression? The goal of this review is to summarize the current literature of pRb-associated proteins.

  15. Interactive protein manipulation

    International Nuclear Information System (INIS)

    2003-01-01

    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures

  16. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  17. Protein Colloidal Aggregation Project

    Science.gov (United States)

    Oliva-Buisson, Yvette J. (Compiler)

    2014-01-01

    To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

  18. The protein protocols handbook

    National Research Council Canada - National Science Library

    Walker, John M

    2002-01-01

    .... The new chapters cover with many rapidly developing areas, particularly the application of mass spectrometry in protein characterization, as well as the now well-established 2-D PAGE technique in proteomics...

  19. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  20. Recombinant Collagenlike Proteins

    Science.gov (United States)

    Fertala, Andzej

    2007-01-01

    A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

  1. Protein targeting protocols

    National Research Council Canada - National Science Library

    Clegg, Roger A

    1998-01-01

    ... of intracellular environment. Because the concept of protein targeting is intuitive rather than explicitly defined, it has been variously used by different groups of researchers in cell biology, biochemistry, and molecular biology. For those working in the field of intracellular signaling, an influential introduction to the topic was the seminal article by Hubbard & Cohen (TIBS [1993] 18, 172- 177), which was based on the work of Cohen's laboratory on protein phosphatases. Subsequently, the ideas that t...

  2. Protein conducting nanopores

    International Nuclear Information System (INIS)

    Harsman, Anke; Krueger, Vivien; Bartsch, Philipp; Honigmann, Alf; Wagner, Richard; Schmidt, Oliver; Rao, Sanjana; Meisinger, Christof

    2010-01-01

    About 50% of the cellular proteins have to be transported into or across cellular membranes. This transport is an essential step in the protein biosynthesis. In eukaryotic cells secretory proteins are transported into the endoplasmic reticulum before they are transported in vesicles to the plasma membrane. Almost all proteins of the endosymbiotic organelles chloroplasts and mitochondria are synthesized on cytosolic ribosomes and posttranslationally imported. Genetic, biochemical and biophysical approaches led to rather detailed knowledge on the composition of the translocon-complexes which catalyze the membrane transport of the preproteins. Comprehensive concepts on the targeting and membrane transport of polypeptides emerged, however little detail on the molecular nature and mechanisms of the protein translocation channels comprising nanopores has been achieved. In this paper we will highlight recent developments of the diverse protein translocation systems and focus particularly on the common biophysical properties and functions of the protein conducting nanopores. We also provide a first analysis of the interaction between the genuine protein conducting nanopore Tom40 SC as well as a mutant Tom40 SC (S 54 →E) containing an additional negative charge at the channel vestibule and one of its native substrates, CoxIV, a mitochondrial targeting peptide. The polypeptide induced a voltage-dependent increase in the frequency of channel closure of Tom40 SC corresponding to a voltage-dependent association rate, which was even more pronounced for the Tom40 SC S54E mutant. The corresponding dwelltime reflecting association/transport of the peptide could be determined with t-bar off ≅1.1 ms for the wildtype, whereas the mutant Tom40 SC S54E displayed a biphasic dwelltime distribution ( t-bar off 1 ≅0.4 ms; t-bar off 2 ≅4.6 ms).

  3. The effect of protein-protein and protein-membrane interactions on membrane fouling in ultrafiltration

    NARCIS (Netherlands)

    Huisman, I.H.; Prádanos, P.; Hernández, A.

    2000-01-01

    It was studied how protein-protein and protein-membrane interactions influence the filtration performance during the ultrafiltration of protein solutions over polymeric membranes. This was done by measuring flux, streaming potential, and protein transmission during filtration of bovine serum albumin

  4. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformatio...

  5. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations...

  6. Protein: MPA1 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available MPA1 TLR signaling molecules RSAD2 CIG5 Radical S-adenosyl methionine domain-containing protein 2 Cytomegalo...virus-induced gene 5 protein, Viperin, Virus inhibitory protein, endoplasmic reticu

  7. More protein in cereals?

    International Nuclear Information System (INIS)

    1969-01-01

    Ways in which the protein content of plant crops may be raised by the use of nuclear radiation are to be discussed at a symposium in Vienna in June next year, organized by the joint Food and Agriculture Organization/Agency Division of Atomic Energy in Food and Agriculture. Plant crops - especially cereal grains - are the basic food and protein source of most of the world's population, particularly in less-developed countries. But their natural protein content is low; increasing the quantity and nutritional quality of plant protein is potentially the most feasible way to combat widespread protein malnutrition. This improvement in seed stock can be achieved by plant breeding methods in which nuclear irradiation techniques are used to induce mutations in grain, and other isotopic techniques can be used to select only those mutants which have the desired properties. The scientists who attend the symposium will have an opportunity to review what mutation plant breeders have achieved, the application of nuclear techniques to screening for protein and amino-acid content and nutritional value, and isotopic methods which contribute to research in plant nutrition and physiology. (author)

  8. Disease specific protein corona

    Science.gov (United States)

    Rahman, M.; Mahmoudi, M.

    2015-03-01

    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  9. Electrophoretic transfer protein zymography.

    Science.gov (United States)

    Pan, Daniel; Hill, Adam P; Kashou, Anthony; Wilson, Karl A; Tan-Wilson, Anna

    2011-04-15

    Zymography detects and characterizes proteolytic enzymes by electrophoresis of protease-containing samples into a nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel containing a copolymerized protein substrate. The usefulness of zymography for molecular weight determination and proteomic analysis is hampered by the fact that some proteases exhibit slower migration through a gel that contains substrate protein. This article introduces electrophoretic transfer protein zymography as one solution to this problem. In this technique, samples containing proteolytic enzymes are first resolved in nonreducing SDS-PAGE on a gel without protein substrate. The proteins in the resolving gel are then electrophoretically transferred to a receiving gel previously prepared with a copolymerized protein substrate. The receiving gel is then developed as a zymogram to visualize clear or lightly stained bands in a dark background. Band intensities are linearly related to the amount of protease, extending the usefulness of the technique so long as conditions for transfer and development of the zymogram are kept constant. Conditions of transfer, such as the pore sizes of resolving and receiving gels and the transfer time relative to the molecular weight of the protease, are explored. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Modelling of proteins in membranes

    DEFF Research Database (Denmark)

    Sperotto, Maria Maddalena; May, S.; Baumgaertner, A.

    2006-01-01

    This review describes some recent theories and simulations of mesoscopic and microscopic models of lipid membranes with embedded or attached proteins. We summarize results supporting our understanding of phenomena for which the activities of proteins in membranes are expected to be significantly...... oppositely charged lipid membranes, lipid-induced tilting of proteins embedded in lipid bilayers, protein-induced bilayer deformations, protein insertion and assembly, and lipid-controlled functioning of membrane proteins....

  11. Peptide Signals Encode Protein Localization▿

    OpenAIRE

    Russell, Jay H.; Keiler, Kenneth C.

    2007-01-01

    Many bacterial proteins are localized to precise intracellular locations, but in most cases the mechanism for encoding localization information is not known. Screening libraries of peptides fused to green fluorescent protein identified sequences that directed the protein to helical structures or to midcell. These peptides indicate that protein localization can be encoded in 20-amino-acid peptides instead of complex protein-protein interactions and raise the possibility that the location of a ...

  12. Protein hydrolysates in sports nutrition

    Directory of Open Access Journals (Sweden)

    Manninen Anssi H

    2009-09-01

    Full Text Available Abstract It has been suggested that protein hydrolysates providing mainly di- and tripeptides are superior to intact (whole proteins and free amino acids in terms of skeletal muscle protein anabolism. This review provides a critical examination of protein hydrolysate studies conducted in healthy humans with special reference to sports nutrition. The effects of protein hydrolysate ingestion on blood amino acid levels, muscle protein anabolism, body composition, exercise performance and muscle glycogen resynthesis are discussed.

  13. Transcriptome-wide analysis of UTRs in non-small cell lung cancer reveals cancer-related genes with SNV-induced changes on RNA secondary structure and miRNA target sites.

    Science.gov (United States)

    Sabarinathan, Radhakrishnan; Wenzel, Anne; Novotny, Peter; Tang, Xiaojia; Kalari, Krishna R; Gorodkin, Jan

    2014-01-01

    Traditional mutation assessment methods generally focus on predicting disruptive changes in protein-coding regions rather than non-coding regulatory regions like untranslated regions (UTRs) of mRNAs. The UTRs, however, are known to have many sequence and structural motifs that can regulate translational and transcriptional efficiency and stability of mRNAs through interaction with RNA-binding proteins and other non-coding RNAs like microRNAs (miRNAs). In a recent study, transcriptomes of tumor cells harboring mutant and wild-type KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) genes in patients with non-small cell lung cancer (NSCLC) have been sequenced to identify single nucleotide variations (SNVs). About 40% of the total SNVs (73,717) identified were mapped to UTRs, but omitted in the previous analysis. To meet this obvious demand for analysis of the UTRs, we designed a comprehensive pipeline to predict the effect of SNVs on two major regulatory elements, secondary structure and miRNA target sites. Out of 29,290 SNVs in 6462 genes, we predict 472 SNVs (in 408 genes) affecting local RNA secondary structure, 490 SNVs (in 447 genes) affecting miRNA target sites and 48 that do both. Together these disruptive SNVs were present in 803 different genes, out of which 188 (23.4%) were previously known to be cancer-associated. Notably, this ratio is significantly higher (one-sided Fisher's exact test p-value = 0.032) than the ratio (20.8%) of known cancer-associated genes (n = 1347) in our initial data set (n = 6462). Network analysis shows that the genes harboring disruptive SNVs were involved in molecular mechanisms of cancer, and the signaling pathways of LPS-stimulated MAPK, IL-6, iNOS, EIF2 and mTOR. In conclusion, we have found hundreds of SNVs which are highly disruptive with respect to changes in the secondary structure and miRNA target sites within UTRs. These changes hold the potential to alter the expression of known cancer genes or genes

  14. Transcriptome-wide analysis of UTRs in non-small cell lung cancer reveals cancer-related genes with SNV-induced changes on RNA secondary structure and miRNA target sites.

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Sabarinathan

    Full Text Available Traditional mutation assessment methods generally focus on predicting disruptive changes in protein-coding regions rather than non-coding regulatory regions like untranslated regions (UTRs of mRNAs. The UTRs, however, are known to have many sequence and structural motifs that can regulate translational and transcriptional efficiency and stability of mRNAs through interaction with RNA-binding proteins and other non-coding RNAs like microRNAs (miRNAs. In a recent study, transcriptomes of tumor cells harboring mutant and wild-type KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes in patients with non-small cell lung cancer (NSCLC have been sequenced to identify single nucleotide variations (SNVs. About 40% of the total SNVs (73,717 identified were mapped to UTRs, but omitted in the previous analysis. To meet this obvious demand for analysis of the UTRs, we designed a comprehensive pipeline to predict the effect of SNVs on two major regulatory elements, secondary structure and miRNA target sites. Out of 29,290 SNVs in 6462 genes, we predict 472 SNVs (in 408 genes affecting local RNA secondary structure, 490 SNVs (in 447 genes affecting miRNA target sites and 48 that do both. Together these disruptive SNVs were present in 803 different genes, out of which 188 (23.4% were previously known to be cancer-associated. Notably, this ratio is significantly higher (one-sided Fisher's exact test p-value = 0.032 than the ratio (20.8% of known cancer-associated genes (n = 1347 in our initial data set (n = 6462. Network analysis shows that the genes harboring disruptive SNVs were involved in molecular mechanisms of cancer, and the signaling pathways of LPS-stimulated MAPK, IL-6, iNOS, EIF2 and mTOR. In conclusion, we have found hundreds of SNVs which are highly disruptive with respect to changes in the secondary structure and miRNA target sites within UTRs. These changes hold the potential to alter the expression of known cancer genes

  15. Modeling Mercury in Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeremy C [ORNL; Parks, Jerry M [ORNL

    2016-01-01

    Mercury (Hg) is a naturally occurring element that is released into the biosphere both by natural processes and anthropogenic activities. Although its reduced, elemental form Hg(0) is relatively non-toxic, other forms such as Hg2+ and, in particular, its methylated form, methylmercury, are toxic, with deleterious effects on both ecosystems and humans. Microorganisms play important roles in the transformation of mercury in the environment. Inorganic Hg2+ can be methylated by certain bacteria and archaea to form methylmercury. Conversely, bacteria also demethylate methylmercury and reduce Hg2+ to relatively inert Hg(0). Transformations and toxicity occur as a result of mercury interacting with various proteins. Clearly, then, understanding the toxic effects of mercury and its cycling in the environment requires characterization of these interactions. Computational approaches are ideally suited to studies of mercury in proteins because they can provide a detailed picture and circumvent issues associated with toxicity. Here we describe computational methods for investigating and characterizing how mercury binds to proteins, how inter- and intra-protein transfer of mercury is orchestrated in biological systems, and how chemical reactions in proteins transform the metal. We describe quantum chemical analyses of aqueous Hg(II), which reveal critical factors that determine ligand binding propensities. We then provide a perspective on how we used chemical reasoning to discover how microorganisms methylate mercury. We also highlight our combined computational and experimental studies of the proteins and enzymes of the mer operon, a suite of genes that confers mercury resistance in many bacteria. Lastly, we place work on mercury in proteins in the context of what is needed for a comprehensive multi-scale model of environmental mercury cycling.

  16. Dynamic protein interaction modules in human hepatocellular carcinoma progression.

    Science.gov (United States)

    Yu, Hui; Lin, Chen-Ching; Li, Yuan-Yuan; Zhao, Zhongming

    2013-01-01

    Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms. Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development. We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases

  17. Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.

    Directory of Open Access Journals (Sweden)

    Makio Saeki

    Full Text Available Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in M