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Sample records for cancer decreased lak

  1. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer: Decreased LAK cytotoxicity caused by a low incidence of CD56+ and CD57+ mononuclear blood cells

    International Nuclear Information System (INIS)

    Hermann, G.G.; Petersen, K.R.; Steven, K.; Zeuthen, J.

    1990-01-01

    The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51 Cr-release assays. The PBMC subsets were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P less than 0.05). The percentages of PBMC positive for the NK-cell markers CD56 and CD57 were lowest in the patients and were correlated to the decrease in cytotoxicity. Depletion of CD56+ or CD57+ cells from PBMC prior to or after 2 days stimulation with IL-2 demonstrated that these cells are the major source of LAK-cell cytotoxicity and showed that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients

  2. Immunotherapy of human cancer with lak cells and IL-2

    International Nuclear Information System (INIS)

    Choi, Kyu Chul; Nam, Sang Yun; Ha, Youn Mun; Choi, Yong Mook

    1988-01-01

    The effects of adoptive immunotherapy with LAK cells and/or IL-2 were evaluated in 18 patients with advanced cancer for whom standard therapy had proved ineffective, from Jul. 1985 to Jan. 1988. Six patients were treated with LAK cells only, 4 patients treated with continuous IV infusion of IL-2 alone, and 8 patients treated with LAK cells plus IL-2. In a patient with hepatoma LAK cells and IL-2 were infused by selective catheterization to a branch of hepatic artery, in a patient with gastric cancer complicated by cancer peritonities LAK cells and IL-2 were infused to peritoneal cavity, and in a patient with renal cell carcinoma HLA-matched allogeneic LAK cells from 2 siblings were infused intravenously(8 times, total 2.49 X 10 10 cells). In the patient with gastric cancer who was treated by peritoneal infusion, LAK cells were induced from mononuclear cells obtained from ascites. Of 17 evaluable patients, 1(5.9%) had complete response(CR), 1(5.9%) had partial response (PR), 4(23.5%) had minimal responses(Min R), and 2(11.8%) had mixed responses(Mix R). Especially, of 7 evaluable patients treated with LAK cells plus IL-2, 1(14.3%) had CR, 1(14.3%) had PR, and 3(42.9%) had Min R. CR with relapse-free survival for 19 months was observed in a lung cancer (squamous cell carcinoma). PR was observed in a lung cancer, and Min R were observed in 2 hepatomas, 1 gastric cancer and 1 neuroblastoma. In 3 pediatric patients (3 to 7 years old) continuous infusion of IL-2 in dose-escalation mode were studied. They were able to tolerate 4,000,000 KH u/M 2 /day for 7 days of IL-2(1 KH u=1.1 BRMP u). Most of adult patients well tolerated 2,000,000 KH u/M 2 /day for 5 days of IL-2 in mode of continuous IV infusion. Most common side effects were chills and fever which could be prevented or minimized by premedication of antihistamine, indomethacin and acetaminophen, and IV infusion of demerol. Serious side effects were complicated by capillary leak syndrome which showed hypotension

  3. Influence of low dose ionizing radiation on amplification and antitumor activity of LAK/TIL cells

    International Nuclear Information System (INIS)

    Liu Wei; Hou Dianjun; Qiao Jianwei; Shang Ximei; Li Jieqing

    2000-01-01

    Objective: To study the influence of low dose ionization on amplification and antitumor activity of LAK/TIL cells. Methods: TIL cells isolated from Lewis lung cancer tissues and LAK cells from spleen of tumor-bearing mouse were irradiated with different low doses of X-rays and were cultured after irradiation. Results: Low dose ionizing radiation improved the amplification volume of LAK/TIL cells, decreased the cell death ratio in amplification process, and increased the toxicity of LAK/TIL cells, Conclusions: Low dose ionizing radiation can result in amplification of biologically activated lymphocytes, and decreases the death ratio of the cells in amplification process

  4. DesignLAK17

    DEFF Research Database (Denmark)

    Ringtved, Ulla; Milligan, Sandra; Corrin, Linda

    2017-01-01

    Notions of what constitutes quality in design in traditional on-campus or online teaching and learning may not always translate into scaled digital environments. The DesignLAK17 workshop builds on the DesignLAK16 workshop to explore one aspect of this theme, namely the opportunities arising from...

  5. The rd LAK data competition

    NARCIS (Netherlands)

    Drachsler, Hendrik; Dietze, Stefan; Herder, Eelco; d'Aquin, Mathieu; Taibi, Davide; Scheffel, Maren

    2017-01-01

    The LAK Data Challenge 2015 continues the research efforts of the previous data competitions in 2013 and 2014 by stimulating research on the evolving fields Learning Analytics (LA) and Educational Data Mining (EDM). Building on a series of activities of the LinkedUp project, the challenge aims to

  6. Autologous bone marrow purging with LAK cells.

    Science.gov (United States)

    Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

    1993-12-01

    In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

  7. Østersølaks bedst til at afvise snyltere

    DEFF Research Database (Denmark)

    Buchmann, Kurt

    2006-01-01

    Danske forskere fra KVL har påvist at østersølaks er langt bedre end skotske laks til at bekæmpe de patogene parasitter ved navn Gyrodactylus salaris. Laks fra Skotland og Norge reagerer uhen sigtmæssigt, medens østersølaksen producerer relevante immunfaktorer.......Danske forskere fra KVL har påvist at østersølaks er langt bedre end skotske laks til at bekæmpe de patogene parasitter ved navn Gyrodactylus salaris. Laks fra Skotland og Norge reagerer uhen sigtmæssigt, medens østersølaksen producerer relevante immunfaktorer....

  8. Proceedings of the 1st LAK Data Challenge

    NARCIS (Netherlands)

    d'Aquin, Mathieu; Dietze, Stefan; Drachsler, Hendrik; Herder, Eelco; Taibi, Davide

    2013-01-01

    d'Aquin, M., Dietze, S., Drachsler, H., Herder, E., & Taibi, D. (Eds.) (2013, April). Proceedings of the 1st LAK Data Challenge, held at LAK 2013, the Third Conference on Learning Analytics and Knowledge. Published by CEUR Workshop Proceedings, 2013, Vol. 974.

  9. Ionizing radiation decreases human cancer mortality rates

    International Nuclear Information System (INIS)

    Luckey, T.D.

    1997-01-01

    Information from nine studies with exposed nuclear workers and military observers of atmospheric bomb explosions confirms the results from animal studies which showed that low doses of ionizing radiation are beneficial. The usual ''healthy worker effect'' was eliminated by using carefully selected control populations. The results from 13 million person-years show the cancer mortality rate of exposed persons is only 65.6% that of carefully selected unexposed controls. This overwhelming evidence makes it politically untenable and morally wrong to withhold public health benefits of low dose irradiation. Safe supplementation of ionizing radiation should become a public health service. (author)

  10. Analysis and Reflections on the Third Learning Analytics and Knowledge Conference (LAK 2013)

    Science.gov (United States)

    Ochoa, Xavier; Suthers, Dan; Verbert, Katrien; Duval, Erik

    2014-01-01

    Analyzing a conference, especially one as young and focused as LAK, provides the opportunity to observe the structure and contributions of the scientific community around it. This work will perform a Scientometric analysis, coupled with a more in-depth manual content analysis, to extract this insight from the proceedings and program of LAK 2013.…

  11. Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

    Science.gov (United States)

    Liss, Michael A; White, Martha; Natarajan, Loki; Parsons, J Kellogg

    2017-06-01

    The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as "did no exercise" vs. "light, moderate, or vigorous exercise in ≥ 10-minute bouts"), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than "no exercise". Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. Published by Elsevier Inc.

  12. CURCUMIN DECREASES SPECIFICITY PROTEIN (Sp) EXPRESSION IN BLADDER CANCER CELLS

    OpenAIRE

    Chadalapaka, Gayathri; Jutooru, Indira; Chintharlapalli, Sudhakar; Papineni, Sabitha; Smith, Roger; Li, Xiangrong; Safe, Stephen

    2008-01-01

    Curcumin is the active component of tumeric, and this polyphenolic compound has been extensively investigated as an anticancer drug that modulates multiple pathways and genes. In this study, 10 – 25 µM curcumin inhibited 253JB-V and KU7 bladder cancer cell growth, and this was accompanied by induction of apoptosis and decreased expression of the proapoptotic protein survivin and the angiogenic proteins vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1). Since expression of...

  13. Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells

    International Nuclear Information System (INIS)

    Ettinghausen, S.E.; Lipford, E.H. III; Mule, J.J.; Rosenberg, S.A.

    1985-01-01

    The authors previously reported that the adoptive transfer of lymphokine-activated killer (LAK) cells plus repetitive injections of recombinant interleukin 2 (IL 2) produced a marked reduction in established pulmonary metastases from a variety of murine sarcomas. The requirement for the exogenous administration of IL 2 prompted a subsequent examination of the role of IL 2 in the in vivo function of transferred LAK cells. The in vivo proliferation and migration patterns of lymphoid cells in C57BL/6 mice were examined after i.v. transfer of LAK cells alone, i.p. injection of IL 2 alone, or the combination of LAK cells and IL 2. A model for in vivo labeling of the DNA of dividing cells was used in which mice were injected with 5-[ 125 I]-iodo-2'-deoxyuridine ( 125 IUdR) and, 20 hr later, their tissues were removed and were counted in a gamma analyzer. A proliferation index (PI) was calculated by dividing the mean cpm of organs of experimentally treated mice by the mean cpm of organs of control mice. In animals given LAK cells alone, the lungs and liver demonstrated little if any uptake of 125 IUdR above saline-treated controls, whereas the same organs of mice receiving 6000 U of IL 2 alone displayed higher radiolabel incorporation. When mice were given LAK cells plus 6000 U of IL 2, their tissues showed an additional increase in 125 IUdR uptake

  14. HIV tropism and decreased risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Nancy A Hessol

    2010-12-01

    Full Text Available During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked

  15. Resistance of some leukemic blasts to lysis by lymphokine activated killer (LAK) cells

    Energy Technology Data Exchange (ETDEWEB)

    Panayotides, P; Sjoegren, A -M; Reizenstein, P; Porwit, A. Immunopathology Lab., Dept. of Pathology, Karolinska Hospital, Stockholm; Wasserman, J

    1988-01-01

    Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant interleukin-2 (IL-2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by /sup 3/H-Thymidine uptake. A synergistic effect of PHA and IL-2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the /sup 51/Cr release assay. LAK cells showed a cytotoxicity (over 10% specific /sup 51/Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) /sup 51/Cr release were obtained in 4- and 18-hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut-agglutinin receptor expression. LAK cells were more cytotoxic towards the K-562 cell line (natural killer activity) than unstimulated PBMC.

  16. Atorvastatin correlates with decreased risk of esophageal cancer: A ...

    African Journals Online (AJOL)

    Objectives: The aim of this study was to explore the association between the use of statins and esophageal cancer in Taiwan. Methods: We designed a casecontrol study using database from the Taiwan National Health Insurance program. In all, 549 patients (cases) aged 20 years or older diagnosed recently with ...

  17. Endogenous glutamine decrease is associated with pancreatic cancer progression.

    Science.gov (United States)

    Roux, Cecilia; Riganti, Chiara; Borgogno, Sammy Ferri; Curto, Roberta; Curcio, Claudia; Catanzaro, Valeria; Digilio, Giuseppe; Padovan, Sergio; Puccinelli, Maria Paola; Isabello, Monica; Aime, Silvio; Cappello, Paola; Novelli, Francesco

    2017-11-10

    Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and spontaneous mouse models of PDAC and other pancreatic-related disorders by High-Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a reduction of blood glutamine as much as the tumor progressed from pancreatic intraepithelial lesions to invasive PDAC, but was not related to chronic pancreatitis-associated inflammation or diabetes. In parallel the increased levels of branched-chain amino acids (BCAA) were observed. By contrast blood glutamine levels were stable in non-tumor bearing mice. These findings demonstrated that glutamine uptake is measurable both in vitro and in vivo . The higher in vitro avidity of PDAC cells corresponded to a lower blood glutamine level as soon as the tumor mass grew. The reduction in circulating glutamine represents a novel tool exploitable to implement other diagnostic or prognostic PDAC biomarkers.

  18. Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

    Science.gov (United States)

    Lyons, John D; Mittal, Rohit; Fay, Katherine T; Chen, Ching-Wen; Liang, Zhe; Margoles, Lindsay M; Burd, Eileen M; Farris, Alton B; Ford, Mandy L; Coopersmith, Craig M

    2016-01-01

    Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered. C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival. Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003). Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury. Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on the models used.

  19. Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

    Directory of Open Access Journals (Sweden)

    John D Lyons

    Full Text Available Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered.C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival.Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003. Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury.Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on

  20. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.

    Science.gov (United States)

    Ide, Hisamitsu; Lu, Yan; Noguchi, Takahiro; Muto, Satoru; Okada, Hiroshi; Kawato, Suguru; Horie, Shigeo

    2018-04-01

    Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1-month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose-dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1-month oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  1. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, B. M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G. S.; Ahn, B.; Ferreira, L. F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

    2013-06-07

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  2. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    International Nuclear Information System (INIS)

    Roberts, B.M.; Frye, G.S.; Ahn, B.; Ferreira, L.F.; Judge, A.R.

    2013-01-01

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  3. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  4. Lung cancer death rates fall, helping drive decrease in overall cancer death rates

    Science.gov (United States)

    The Annual Report to the Nation on the Status of Cancer, covering the period 1975–2010, showed death rates for lung cancer, which accounts for more than one in four cancer deaths, dropping at a faster pace than in previous years.

  5. Correlates and geographic patterns of knowledge that physical activity decreases cancer risk.

    Science.gov (United States)

    Ramírez, A Susana; Finney Rutten, Lila J; Vanderpool, Robin C; Moser, Richard P; Hesse, Bradford W

    2013-04-01

    While many lifestyle-related cancer risk factors including tobacco use, poor diet, and sun exposure are well recognized by the general public, the role of physical activity in decreasing cancer risk is less recognized. Studies have demonstrated gender-, race/ethnicity-, and age-based disparities in cancer risk factor knowledge; however, beliefs and geographic factors that may be related to knowledge are under-examined. In this study, we analyzed data from the 2008 Health Information National Trends Survey to determine correlates of knowledge of the relationship between physical activity and reduced cancer risk in the adult US population. We generated geographic information system maps to examine the geographic distribution of this knowledge. Results revealed that there is confusion among US adults about the relationship between physical activity and cancer risk: Respondents who believed that cancer is not preventable had significantly lower odds of knowing that physical activity reduces cancer risk (p physical activity reduces cancer risk (p physical activity guidelines were also significantly more likely to know that physical activity reduces cancer risk (p physical inactivity. Correlates of cancer risk factor knowledge point to opportunities for targeted interventions.

  6. Butyrate decreases its own oxidation in colorectal cancer cells through inhibition of histone deacetylases.

    Science.gov (United States)

    Han, Anna; Bennett, Natalie; Ahmed, Bettaieb; Whelan, Jay; Donohoe, Dallas R

    2018-06-05

    Colorectal cancer is characterized by an increase in the utilization of glucose and a diminishment in the oxidation of butyrate, which is a short chain fatty acid. In colorectal cancer cells, butyrate inhibits histone deacetylases to increase the expression of genes that slow the cell cycle and induce apoptosis. Understanding the mechanisms that contribute to the metabolic shift away from butyrate oxidation in cancer cells is important in in understanding the beneficial effects of the molecule toward colorectal cancer. Here, we demonstrate that butyrate decreased its own oxidation in cancerous colonocytes. Butyrate lowered the expression of short chain acyl-CoA dehydrogenase, an enzyme that mediates the oxidation of short-chain fatty acids. Butyrate does not alter short chain acyl-CoA dehydrogenase levels in non-cancerous colonocytes. Trichostatin A, a structurally unrelated inhibitor of histone deacetylases, and propionate also decreased the level of short chain acyl-CoA dehydrogenase, which alluded to inhibition of histone deacetylases as a part of the mechanism. Knockdown of histone deacetylase isoform 1, but not isoform 2 or 3, inhibited the ability of butyrate to decrease short chain acyl-CoA dehydrogenase expression. This work identifies a mechanism by which butyrate selective targets colorectal cancer cells to reduce its own metabolism.

  7. Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2002-04-01

    To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ({sup 18}F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

  8. Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

    International Nuclear Information System (INIS)

    Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

    2002-01-01

    To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ( 18 F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes

  9. Strategies for Appropriate Patient-centered Care to Decrease the Nationwide Cost of Cancers in Korea

    Directory of Open Access Journals (Sweden)

    Jong-Myon Bae

    2017-07-01

    Full Text Available In terms of years of life lost to premature mortality, cancer imposes the highest burden in Korea. In order to reduce the burden of cancer, the Korean government has implemented cancer control programs aiming to reduce cancer incidence, to increase survival rates, and to decrease cancer mortality. However, these programs may paradoxically increase the cost burden. For examples, a cancer screening program for early detection could bring about over-diagnosis and over-treatment, and supplying medical services in a paternalistic manner could lead to defensive medicine or futile care. As a practical measure to reduce the cost burden of cancer, appropriate cancer care should be established. Ensuring appropriateness requires patient-doctor communication to ensure that utility values are shared and that autonomous decisions are made regarding medical services. Thus, strategies for reducing the cost burden of cancer through ensuring appropriate patient-centered care include introducing value-based medicine, conducting cost-utility studies, and developing patient decision aids.

  10. Tiamulin inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of CD73.

    Science.gov (United States)

    Yang, Xu; Pei, Shimin; Wang, Huanan; Jin, Yipeng; Yu, Fang; Zhou, Bin; Zhang, Hong; Zhang, Di; Lin, Degui

    2017-04-11

    Metastasis is the leading cause of death in breast cancer patients. CD73, also known as ecto-5'-nucleotidase, plays a critical role in cancer development including metastasis. The existing researches indicate that overexpression of CD73 promotes growth and metastasis of breast cancer. Therefore, CD73 inhibitor can offer a promising treatment for breast cancer. Here, we determined whether tiamulin, which was found to inhibit CD73, was able to suppress breast cancer development and explored the related mechanisms. We firstly measured the effect of tiamulin hydrogen fumarate (THF) on CD73 using high performance liquid chromatography (HPLC). Then, we investigated cell proliferation, migration and invasion in MDA-MB-231 human breast cancer cell line and 4 T1 mouse breast cancer cell line treated with THF by migration assay, invasion assay and activity assay. Besides, we examined the effect of THF on syngeneic mammary tumors of mice by immunohistochemistry. Our data demonstrated that THF inhibited CD73 by decreasing the activity instead of the expression of CD73. In vitro, THF inhibited the proliferation, migration and invasion of MDA-MB-231 and 4 T1 cells by suppressing CD73 activity. In vivo, animal experiments showed that THF treatment resulted in significant reduction in syngeneic tumor growth, microvascular density and lung metastasis rate. Our results indicate that THF inhibits growth and metastasis of breast cancer by blocking the activity of CD73, which may offer a promising treatment for breast cancer therapy.

  11. Decrease in specific micronutrient intake in colorectal cancer patients with tumors presenting Ki-ras mutation

    OpenAIRE

    JORDI SALAS; NURIA LASO; SERGI MAS; M. JOSE LAFUENTE; XAVIER CASTERAD; MANUEL TRIAS; ANTONIO BALLESTA; RAFAEL MOLINA; CARLOS ASCASO; SHICHUN ZHENG; JOHN K. WIENCKE; AMALIA LAFUENTE

    2004-01-01

    Decrease in specific micronutrient intake in colorectal cancer patients with tumors presenting Ki-ras mutation BACKGROUND: The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and mutations, such as Ki-ras mutations, in genes implicated in the pathogenesis of these neoplasms. PATIENTS AND METHODS: The study was based on 246 cases and 296 controls. For th...

  12. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    Science.gov (United States)

    Mahmood, M.; Xu, Y.; Dantuluri, V.; Mustafa, T.; Zhang, Y.; Karmakar, A.; Casciano, D.; Ali, S.; Biris, A.

    2013-02-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

  13. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    International Nuclear Information System (INIS)

    Mahmood, M; Xu, Y; Dantuluri, V; Mustafa, T; Karmakar, A; Casciano, D; Biris, A; Zhang, Y; Ali, S

    2013-01-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells. (paper)

  14. Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers

    NARCIS (Netherlands)

    Lobbes, Marc B.I.; Vriens, Ingeborg J.H.; van Bommel, Annelotte C.M.; Nieuwenhuijzen, Grard A.P.; Smidt, Marjolein L.; Boersma, Liesbeth J.; van Dalen, Thijs; Smorenburg, Carolien; Struikmans, Henk; Siesling, Sabine; Voogd, Adri C.; Tjan-Heijnen, Vivianne C.G.

    2017-01-01

    Purpose In this retrospective population-based cohort study, we analyzed breast MRI use and its impact on type of surgery, surgical margin involvement, and the diagnosis of contralateral breast cancer. Methods All Dutch patients with cT1–4N0–3M0 breast cancer diagnosed in 2011–2013 and treated with

  15. Analysis of Characteristics of Lateral Stability of Sailplane Lak 17a by Computational Method

    Directory of Open Access Journals (Sweden)

    Paulius Gildutis

    2011-04-01

    Full Text Available A computer-based geometrical model of the Lak-17a sailplane was generated with the program AVL (Athena Vortex Lattice, which is designed to analyse the characteristics of flight and to provide a rapid analysis of the configuration of an aircraft. Various characteristics of stability and control were calculated by simulating a real flight with the program. According to the results, a conclusion was formulated and suggestions about how to improve the stability and control of the aircraft were offered. Article in Lithuanian

  16. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  17. Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

    Science.gov (United States)

    Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

    2015-12-01

    Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

  18. Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression

    Directory of Open Access Journals (Sweden)

    Byler Timothy K

    2012-08-01

    Full Text Available Abstract Background Prevention of bladder cancer recurrence is a central challenge in the management of this highly prevalent disease. The histone deacetylase inhibitor valproic acid (sodium valproate has anti-angiogenic properties and has been shown to decrease bladder cancer growth in model systems. We have previously shown reduced expression of thrombospondin-1 in a mouse model and in human bladder cancer relative to normal urothelium. We speculated that inhibition of angiogenesis by valproate might be mediated by this anti-angiogenic protein. Methods Bladder cancer cell lines UMUC3 and T24 were treated with valproate or another histone deacetylase inhibitor, vorinostat, in culture for a period of three days. Proliferation was assessed by alamar blue reduction. Gene expression was evaluated by reverse transcription of RNA and quantitative PCR. Results Proliferation assays showed treatment with valproate or vorinostat decreased proliferation in both cell lines. Histone deacetylase inhibition also increased relative expression of thrombospondin-1 up to 8 fold at 5 mM valproate. Conclusions Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.

  19. Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner.

    Science.gov (United States)

    Tsai, Ming-Ju; Yang, Chih-Jen; Kung, Ya-Ting; Sheu, Chau-Chyun; Shen, Yu-Ting; Chang, Pi-Yu; Huang, Ming-Shyan; Chiu, Herng-Chia

    2014-11-01

    Higher risk of lung cancer has been noted in patients with type 2 diabetes mellitus (DM). Some observational studies have shown a reduced risk of lung cancer in DM patients taking metformin, but a dose-response relationship has never been reported. The aim of this study is to exam the association between the dose of metformin and the incidence of lung cancer in a Chinese population. The dataset used for this nationwide population-based study is a cohort of 1 million subjects randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. We enrolled all subjects with newly diagnosed type 2 DM between 1997 and 2007. Subjects with a diagnosis of neoplasm before DM diagnosis, those using metformin before DM diagnosis, those with polycystic ovary syndrome, and those with a DM diagnosis before their 15 years of age were excluded. The demographic data and duration, cumulative dose and intensity of metformin use were compared between patients developing lung cancer and those without lung cancer. Totally, 47,356 subjects were identified. After adjusting for age, gender, and modified Charlson Comorbidity Index score, the utilization of metformin was an independent protecting factor, and the risk of developing lung cancer decreased progressively with either the higher cumulative dose or the higher intensity of metformin use. This study revealed that the use of metformin decreased the risk of lung cancer in a dose-dependent manner in patients with type 2 DM. The chemo-preventive effect of metformin deserves further study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Take Action to Decrease Your Cancer Risk - Obesity and Its Role in Cancer Health Disparities

    Science.gov (United States)

    In support of this year’s National Minority Health Month theme “Prevention is Power: Taking Action for Health Equity!”, CRCHD is highlighting the role of obesity in cancer health disparities among diverse population groups in the U.S.

  1. Decreased sexual capacity after external radiation therapy for prostate cancer impairs quality of life

    International Nuclear Information System (INIS)

    Helgason, Asgeir R.; Fredrikson, Mats; Adolfsson, Jan; Steineck, Gunnar

    1995-01-01

    Purpose: The aim of this study was to assess to what extent patients treated with radiation therapy for prostate cancer experience change in sexual functioning and to what extent this effects quality of life. Methods and Materials: Information was provided by 53 men treated with radiation therapy for localized prostate cancer. Assessment was made with the ''Radiumhemmets Scale of Sexual Functioning,'' which measures sexual desire, erectile capacity, orgasm, and to what extent a decrease in any of these aspects of sexual functioning affects quality of life. Function before treatment was assessed retrospectively. Results: Sexual desire diminished among 77% after treatment. The erection stiffness decreased in 77%. Before external radiation therapy, 66% had an erection usually sufficient for intercourse. Half of the men lost this ability after treatment. Of those retaining orgasm after treatment, 47% reported a decreased orgasmic pleasure and 91% a reduced ejaculation volume. Of all men, 50% reported that quality of life had decreased much or very much due to a decline in the erectile capacity following external radiation therapy. Conclusion: The results of the present study indicate that external radiation therapy for prostate cancer is associated with a reduction in sexual desire, erectile capacity, and orgasm functions. In a majority of patients this reduces quality of life. Previously, we may have underestimated the importance an intact sexual function has for the quality of life in this patient category of elderly men

  2. Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

    Science.gov (United States)

    2013-01-01

    Background Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Methods Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. Results In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using

  3. Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer

    International Nuclear Information System (INIS)

    Xia, Peng; An, Han-Xiang; Dang, Cheng-Xue; Radpour, Ramin; Kohler, Corina; Fokas, Emmanouil; Engenhart-Cabillic, Rita; Holzgreve, Wolfgang; Zhong, Xiao Yan

    2009-01-01

    Alterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA). We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters. Peripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu protein. The content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023). Reduced mtDNA was found often in post menopausal cancer group (P = 0.024). No difference in mtDNA content, in regards to age (p = 0.564), lymph node involvement (p = 0.673), ER (p = 0.877), PR (p = 0.763), and Her-2/neu expression (p = 0.335), was observed. Early detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer

  4. Interleukin-2 (rIL-2)-induced lymphokine-activated killer (LAK) cells and their precursors express the VGO1 antigen

    International Nuclear Information System (INIS)

    Denegri, J.F.; Peterson, J.; Tilley, P.

    1989-01-01

    Precursor and effector cells of recombinant interleukin-2 (r-IL-2)-induced lymphokine-activated killer (LAK) activity were investigated for their expression of VGO1. Peripheral blood lymphocytes (PBL) from normal donors were purified and separated in a FACS 420 into VGO1+- and VGO1- cell fractions before and after culture for 96 hr with 100 U/ml of r-IL-2. Their lytic activity against K 562 and Daudi cells was measured in a 51Cr release assay. The majority, if not all, of the LAK effector and precursor cells was VGO1+ lymphocytes. The expression of VGO1 by LAK precursor cells remained stable under the culture conditions used in our experiments. VGO1- lymphocytes cultured with r-IL-2 demonstrated neither LAK-induced activity nor expression of VGO1 antigen

  5. The decrease of mineralcorticoid receptor drives angiogenic pathways in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Laura Tiberio

    Full Text Available Angiogenesis plays a crucial role in tumor growth and progression. Low expression of mineralocorticoid receptor (MR in several malignant tumors correlates with disease recurrence and overall survival. Previous studies have shown that MR expression is decreased in colorectal cancer (CRC. Here we hypothesize that decreased MR expression can contribute to angiogenesis and poor patient survival in colorectal malignancies. In a cohort of CRC patients, we analyzed tumor MR expression, its correlation with tumor microvascular density and its impact on survival. Subsequently, we interrogated the role of MR in angiogenesis in an in vitro model, based on the colon cancer cell line HCT116, ingenierized to re-express a physiologically controlled MR. In CRC, decreased MR expression was associated with increased microvascular density and poor patient survival. In pchMR transfected HCT116, aldosterone or natural serum steroids largely inhibited mRNA expression levels of both VEGFA and its receptor 2/KDR. In CRC, MR activation may significantly decrease angiogenesis by directly inhibiting dysregulated VEGFA and hypoxia-induced VEGFA mRNA expression. In addition, MR activation attenuates the expression of the VEGF receptor 2/KDR, possibly dampening the activation of a VEGFA/KDR dependent signaling pathway important for the survival of tumor cells under hypoxic conditions.

  6. Phenobarbital at Low Dose in the presence of Curcumin Decreases Progress of Cancer in Rats

    International Nuclear Information System (INIS)

    Mazen, G.M.A.

    2011-01-01

    This current investigation was conducted on male albino rats to elucidate the effects of curcumin alone or in the presence of phenobarbital at low dose to decrease the progress of hepato-gastrointestinal carcinogenesis induced by N-diethylnitrosoamine (DEN) in rats. As a result of cancer induction, the levels of serum tumour markers [carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA19.9)] were significantly elevated. On the other hand, glutathione (GSH) and glutathione peroxidase (GPx) were decreased significantly in blood, liver, stomach and intestine whereas the levels of malondialdehyde (MAD) in liver, stomach and intestine were significantly elevated in the cancer group of rats in comparison to their corresponding control group. The administration of curcumin alone or together with phenobarbital ameliorated all these alterations depending on the time of administration. The data of this study suggested that low dose of phenobarbital in the presence of curcumin may inhibit the development of hepato-gastrointestinal carcinogenesis initiated with DEN.

  7. The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Christine Henri

    2016-01-01

    Full Text Available With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab, and multikinase inhibitors (sunitinib. The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

  8. Epidemiologic Evidence That Excess Body Weight Increases Risk of Cervical Cancer by Decreased Detection of Precancer.

    Science.gov (United States)

    Clarke, Megan A; Fetterman, Barbara; Cheung, Li C; Wentzensen, Nicolas; Gage, Julia C; Katki, Hormuzd A; Befano, Brian; Demarco, Maria; Schussler, John; Kinney, Walter K; Raine-Bennett, Tina R; Lorey, Thomas S; Poitras, Nancy E; Castle, Philip E; Schiffman, Mark

    2018-04-20

    Purpose Obesity has been inconsistently linked to increased cervical cancer incidence and mortality; however, the effect of obesity on cervical screening has not been explored. We investigated the hypothesis that increased body mass might decrease detection of cervical precancer and increase risk of cervical cancer even in women undergoing state-of-the-art screening. Methods We conducted a retrospective cohort study of 944,227 women age 30 to 64 years who underwent cytology and human papillomavirus DNA testing (ie, cotesting) at Kaiser Permanente Northern California (January 2003 to December 2015). Body mass index was categorized as normal/underweight (< 25 kg/m 2 ), overweight (25 to < 30 kg/m 2 ), or obese (≥ 30 kg/m 2 ). We estimated 5-year cumulative risks of cervical precancer and cancer by category of body mass index using logistic Weibull survival models. Results We observed lower risk of cervical precancer (n = 4,489) and higher risk of cervical cancer (n = 490) with increasing body mass index. Specifically, obese women had the lowest 5-year risk of precancer (0.51%; 95% CI, 0.48% to 0.54% v 0.73%; 95% CI, 0.70% to 0.76% in normal/underweight women; P trend < .001). In contrast, obese women had the highest 5-year risk of cancer (0.083%; 95% CI, 0.072% to 0.096% v 0.056%; 95% CI, 0.048% to 0.066% in normal/underweight women; P trend < .001). Results were consistent in subgroups defined by age (30 to 49 v 50 to 64 years), human papillomavirus status (positive v negative), and histologic subtype (glandular v squamous). Approximately 20% of cervical cancers could be attributed to overweight or obesity in the women in our study who underwent routine cervical screening. Conclusion In this large, screened population, overweight and obese women had an increased risk of cervical cancer, likely because of underdiagnosis of cervical precancer. Improvements in equipment and/or technique to assure adequate sampling and visualization of women with elevated body mass

  9. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  10. Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

    Science.gov (United States)

    Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

    2017-08-03

    The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

  11. Decrease of anxio-depressive disorders in cancer with non drug psychotherapies

    Directory of Open Access Journals (Sweden)

    Marie-Frédérique Bacqué

    2015-12-01

    Full Text Available Background/Purpose: Cancer is well known for its psychological and psychiatric aftermath. About 40% of cancer patients present psychological or psychiatric troubles. First in contrast with the survival stakes, the psychopathological symptoms have been then ignored because they were confounding factors with the illness effect such as sadness, psychomotor slowing down or cognitive impairment. These troubles are now well known in international classifications (ICD, DSM-5 : from miss adaptation to delusion and especially anxio-depressive troubles.With its increasing worldwide frequency cancer has become a prominent figure of modern misfortune. Psycho-oncologyis the new branch of scientific knowledge that links cancer somatic consequences to their psychological expressions. Psycho-oncology opens a large area in psychopathology. But psycho-oncology is also interested in psychosociology. Cancer social representations interfere individually as with the group in cancer prevention and cancer detection.To decrease excessive anxiety in people cancer screening, countries must adapt their messages and work out a discourse that speaks to everybody. Furthermore, each gender, generation and personality has his specific prejudices. This reflexion introduces first  attempts of setting limits to psychotraumatism in cancer disclosure. Many symptoms could be avoided with a right training of doctors and caregivers. To begin a specific way to announce cancer will be exposed with authentic and empathic progressive approach of truth.Methods: Qualitative methods are preferentially used to expose somebody to what the majority consider as a death threat. With the humanization of healthcare, doctors can not announce cancer anymore in a corridor nor by phone neither with an email.  This first step of the « working alliance » between doctor and patient realizes the conditions of what Jimmie Holland calls the « patient total care » : a holistic approach of the patient in

  12. Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

    Science.gov (United States)

    Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

    2016-02-01

    Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

    Science.gov (United States)

    Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

    2009-08-01

    The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

  14. Effectiveness of Cepharanthin in decreasing interruptions during radiation therapy for oral cancer

    International Nuclear Information System (INIS)

    Uchiyama, Yuka; Murakami, Shumei; Kamimoto, Naoya; Nakatani, Atsutoshi; Furukawa, Souhei

    2005-01-01

    The objectives of this study was to examine the effectiveness of Cepharanthin (Kakensyoyaku, Tokyo, Japan) at decreasing side effects during radiation therapy for oral cancer and thereby allowing the completion of radiation therapy without interruption. Two hundred fifteen patients diagnosed with oral cancers were assigned to either Cepharanthin or control groups and underwent external beam irradiation. The completion of the course of radiation therapy and the occurrence of side effects such as mucositis, dysgeusia, and xerostomia during the radiation therapy were evaluated and compared. The completion rate was 87.4% for the Cepharanthin group versus 67.0% for the control group, and the difference was statistically significant (P<0.01). Mucositis did not appear in 58 of 127 cases (45.7%) in the Cepharanthin group or in 21 of 88 cases (23.9%) in the control group. Mucositis developed in 24.6% of the Cepharanthin group and 53.7% of the control group within 2 weeks of irradiation. There were significant relationships between the use of Cepharanthin and the development and timing of mucositis (both P<0.01). Cepharanthin improved the completion of radiation therapy without interruption and reduced or delayed the development of mucositis during radiation therapy for oral cancer. (author)

  15. UNBS5162, a Novel Naphthalimide That Decreases CXCL Chemokine Expression in Experimental Prostate Cancers

    Directory of Open Access Journals (Sweden)

    Tatjana Mijatovic

    2008-06-01

    Full Text Available Several naphthalimides have been evaluated clinically as potential anticancer agents. UNBS3157, a naphthalimide that belongs to the same class as amonafide, was designed to avoid the specific activating metabolism that induces amonafide’s hematotoxicity. The current study shows that UNBS3157 rapidly and irreversibly hydrolyzes to UNBS5162 without generating amonafide. In vivo UNBS5162 after repeat administration significantly increased survival in orthotopic human prostate cancer models. Results obtained by the National Cancer Institute (NCI using UNBS3157 and UNBS5162 against the NCI 60 cell line panel did not show a correlation with any other compound present in the NCI database, including amonafide, thereby suggesting a unique mechanism of action for these two novel naphthalimides. Affymetrix genome-wide microarray analysis and enzyme-linked immunosorbent assay revealed that in vitro exposure of PC-3 cells to UNBS5162 (1 μM for 5 successive days dramatically decreased the expression of the proangiogenic CXCL chemokines. Histopathology additionally revealed antiangiogenic properties in vivo for UNBS5162 in the orthotopic PC-3 model. In conclusion, the present study reveals UNBS5162 to be a pan-antagonist of CXCL chemokine expression, with the compound displaying antitumor effects in experimental models of human refractory prostate cancer when administered alone and found to enhance the activity of taxol when coadministered with the taxoid.

  16. Does cognitive decline decrease health utility value in older adult patients with cancer?

    Science.gov (United States)

    Akechi, Tatsuo; Aiki, Sayo; Sugano, Koji; Uchida, Megumi; Yamada, Atsuro; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Iida, Shinsuke; Okuyama, Toru

    2017-05-01

    Cognitive decline is common among older adults with cancer. The present study aimed to investigate the impact of cognitive decline on health utility value in older adults suffering from cancer. Consecutive patients aged 65 years or older with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Patients were asked to complete the EuroQoL-5 (EQ-5D) scale to measure health utility and the Mini-Mental State Examination to assess cognitive decline. The potential impact of cognitive decline was investigated with univariate analysis. A multivariate regression analysis was conducted to control for potential confounding factors. Complete data were obtained from 87 patients, 29% of whom had cognitive decline. The mean ± SE EQ-5D score for patients with cognitive decline was significantly lower than that for those without cognitive decline (0.67 ± 0.04 vs 0.79 ± 0.03, t = 2.38, P = 0.02). However, multiple regression analysis showed that cognitive decline was not significantly associated with EQ-5D scores. Female sex and lower performance scores (worse physical condition) were significantly associated with EQ-5D scores. Cognitive decline may be involved in decreased health utility value in older adult patients with cancer. However, this effect does not seem to be independent, and the patient's physical condition may be a relevant confounding factor. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

  17. Decrease in Prostate Cancer Testing Following the US Preventive Services Task Force (USPSTF) Recommendations.

    Science.gov (United States)

    Li, Jun; Berkowitz, Zahava; Hall, Ingrid J

    2015-01-01

    To assess changes of prostate-specific antigen (PSA) testing following recent US Preventive Services Task Force (USPSTF) prostate cancer screening recommendations using 2005 to 2013 National Health Interview Survey data. We calculated the percentage of PSA testing among men ≥40 years by age group and age-adjusted race for each survey year. Differences between years were assessed with linear contrasts after combining all years' data. The overall percentage of PSA testing was highest in 2008 and decreased significantly in 2013. Compared with 2008, each age group had significantly lower screening percentages in 2013, especially men ≥75 years old (-14.0% points; P testing percentages were highest in 2008 and decreased significantly in 2013. Only white men had a significantly lower percentage in 2013 than in 2010. Significant declines in PSA testing from 2008 to 2013 in men ≥75 years old may reflect the impact of the 2008 USPSTF recommendations. While the cause of the decreases in PSA testing between 2010 and 2013 among men aged 50 to 74 years old and white men is unknown, the decreases may suggest the early effects of the 2012 recommendations. © Copyright 2015 by the American Board of Family Medicine.

  18. Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

    Science.gov (United States)

    Rava, Marta; Czachorowski, Maciej J; Silverman, Debra; Márquez, Mirari; Kishore, Sirish; Tardón, Adonina; Serra, Consol; García-Closas, Montse; Garcia-Closas, Reina; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Kogevinas, Manolis; Malats, Núria

    2018-02-01

    Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis. © 2017 UICC.

  19. Decreases in Smoking-Related Cancer Mortality Rates Are Associated with Birth Cohort Effects in Korean Men.

    Science.gov (United States)

    Jee, Yon Ho; Shin, Aesun; Lee, Jong-Keun; Oh, Chang-Mo

    2016-12-05

    Background: This study aimed to examine trends in smoking-related cancer mortality rates and to investigate the effect birth cohort on smoking-related cancer mortality in Korean men. Methods: The number of smoking-related cancer deaths and corresponding population numbers were obtained from Statistics Korea for the period 1984-2013. Joinpoint regression analysis was used to detect changes in trends in age-standardized mortality rates. Birth-cohort specific mortality rates were illustrated by 5 year age groups. Results: The age-standardized mortality rates for oropharyngeal decreased from 2003 to 2013 (annual percent change (APC): -3.1 (95% CI, -4.6 to -1.6)) and lung cancers decreased from 2002 to 2013 (APC -2.4 (95% CI -2.7 to -2.2)). The mortality rates for esophageal declined from 1994 to 2002 (APC -2.5 (95% CI -4.1 to -0.8)) and from 2002 to 2013 (APC -5.2 (95% CI -5.7 to -4.7)) and laryngeal cancer declined from 1995 to 2013 (average annual percent change (AAPC): -3.3 (95% CI -4.7 to -1.8)). By the age group, the trends for the smoking-related cancer mortality except for oropharyngeal cancer have changed earlier to decrease in the younger age group. The birth-cohort specific mortality rates and age-period-cohort analysis consistently showed that all birth cohorts born after 1930 showed reduced mortality of smoking-related cancers. Conclusions: In Korean men, smoking-related cancer mortality rates have decreased. Our findings also indicate that current decreases in smoking-related cancer mortality rates have mainly been due to a decrease in the birth cohort effect, which suggest that decrease in smoking rates.

  20. Decreases in Smoking-Related Cancer Mortality Rates Are Associated with Birth Cohort Effects in Korean Men

    Directory of Open Access Journals (Sweden)

    Yon Ho Jee

    2016-12-01

    Full Text Available Background: This study aimed to examine trends in smoking-related cancer mortality rates and to investigate the effect birth cohort on smoking-related cancer mortality in Korean men. Methods: The number of smoking-related cancer deaths and corresponding population numbers were obtained from Statistics Korea for the period 1984–2013. Joinpoint regression analysis was used to detect changes in trends in age-standardized mortality rates. Birth-cohort specific mortality rates were illustrated by 5 year age groups. Results: The age-standardized mortality rates for oropharyngeal decreased from 2003 to 2013 (annual percent change (APC: −3.1 (95% CI, −4.6 to −1.6 and lung cancers decreased from 2002 to 2013 (APC −2.4 (95% CI −2.7 to −2.2. The mortality rates for esophageal declined from 1994 to 2002 (APC −2.5 (95% CI −4.1 to −0.8 and from 2002 to 2013 (APC −5.2 (95% CI −5.7 to −4.7 and laryngeal cancer declined from 1995 to 2013 (average annual percent change (AAPC: −3.3 (95% CI −4.7 to −1.8. By the age group, the trends for the smoking-related cancer mortality except for oropharyngeal cancer have changed earlier to decrease in the younger age group. The birth-cohort specific mortality rates and age-period-cohort analysis consistently showed that all birth cohorts born after 1930 showed reduced mortality of smoking-related cancers. Conclusions: In Korean men, smoking-related cancer mortality rates have decreased. Our findings also indicate that current decreases in smoking-related cancer mortality rates have mainly been due to a decrease in the birth cohort effect, which suggest that decrease in smoking rates.

  1. The Effectiveness of Parent-Child Play Therapy on Decreasing Depression Symptoms in Children with Cancer, Decreasing Perceived Stress on Their Mothers and Improving Parent-Child Relationship

    Directory of Open Access Journals (Sweden)

    رویا سادات علویان

    2017-01-01

    Full Text Available Present study, aimed to assess the effect of parent-child play therapy on decreasing depression symptoms in children with cancer, decreasing perceived stress of their mothers and improving the parent-child relationship. A total of 14 children diagnosed with cancer were selected, among the patients of Dr. Sheikh Hospital in the city of Mashhad, and randomly assigned into two groups of intervention and control. Mothers completed the Perceived Stress Scale (PSS and the Parent-Child Relationship Scale (PCRS, the children completed the Child Depression Inventory (CDI, both in pre-test and post-test. Eight sessions of parent-child play therapy were adminstered separately for every pair of mother-child from intervention group. Data were analyzed by using analysis of covariance. Compared to the control group, CDI scores of intervention group reduced significantly from pre to post test. Also scores of PCRS increased significantly for the intervention group. PSS Scores of intervention groups was not significantly different from control group. As a result, parent-child play therapy can be effective in reducing depression symptoms of children with cancer, and improving the parent-child relationship; while, it was not effective for reducing mothers' level of perceived stress.

  2. MiR-133b is frequently decreased in gastric cancer and its overexpression reduces the metastatic potential of gastric cancer cells

    International Nuclear Information System (INIS)

    Zhao, Yu; Zhu, Zhenggang; Huang, Jie; Zhang, Li; Qu, Ying; Li, Jianfang; Yu, Beiqin; Yan, Min; Yu, Yingyan; Liu, Bingya

    2014-01-01

    Emerging evidence has shown that microRNAs are involved in gastric cancer development and progression. Here we examine the role of miR-133b in gastric cancer. Quantitative real-time PCR analysis was performed in 140 patient gastric cancer tissues and 8 gastric cancer cell lines. The effects of miR-133b in gastric cancer cells metastasis were examined by scratch assay, transwell migration and matrigel invasion. In vivo effects of miR-133b were examined in an intraperitoneal mouse tumor model. Targets of miR-133b were predicted by bioinformatics tools and validated by luciferase reporter analyses, western blot, and quantitative real-time PCR. MiR-133b was significantly downregulated in 70% (98/140) of gastric cancer patients. Expression of miR-133b was negatively correlated with lymph node metastasis of gastric cancer in patients. Similarly, the expression of miR-133b was significantly lower in seven tested gastric cancer cell lines than in the immortalized non-cancerous GES-1 gastric epithelial cells. Overexpression of miR-133b markedly inhibited metastasis of gastric cancer cells in vitro and in vivo. Moreover, the transcriptional factor Gli1 was identified as a direct target for miR-133b. Level of Gli1 protein but not mRNA was decreased by miR-133b. Activity of luciferase with Gli1 3′-untranslated region was markedly decreased by miR-133b in gastric cancer cells. Gli1 target genes, OPN and Zeb2, were also inhibited by miR133b. MiR-133b is frequently decreased in gastric cancer. Overexpression of miR-133b inhibits cell metastasis in vitro and in vivo partly by directly suppressing expression of Gli1 protein. These results suggested that miR-133b plays an important role in gastric cancer metastasis

  3. Some low homogenization pressures improve certain probiotic characteristics of yogurt culture bacteria and Lactobacillus acidophilus LA-K.

    Science.gov (United States)

    Muramalla, T; Aryana, K J

    2011-08-01

    Lactobacillus delbrueckii ssp. bulgaricus, Streptococcus salivarius ssp. thermophilus, and Lactobacillus acidophilus are dairy cultures widely used in the manufacture of cultured dairy products. Commonly used homogenization pressures in the dairy industry are 13.80 MPa or less. It is not known whether low homogenization pressures can stimulate bacteria to improve their probiotic characteristics. Objectives were to determine the effect of homogenization at 0, 3.45, 6.90, 10.34, and 13.80 MPa on acid tolerance, bile tolerance, protease activity, and growth of L. delbrueckii ssp. bulgaricus LB-12, S. salivarius ssp. thermophilus ST-M5, and L. acidophilus LA-K. The cultures were individually inoculated in cool autoclaved skim milk (4°C) and homogenized for 5 continuous passes. Growth and bile tolerance of samples were determined hourly for 10h of incubation. Acid tolerance was determined every 20 min for 120 min of incubation. Protease activity was determined at 0, 12, and 24h of incubation. All homogenization pressures studied improved acid tolerance of L. delbrueckii ssp. bulgaricus LB-12 but had no beneficial effect on protease activity and had negative effects on growth and bile tolerance. A pressure of 6.90 MPa improved acid tolerance, bile tolerance, and protease activity of S. salivarius ssp. thermophilus ST-M5, but none of the homogenization pressures studied had an effect on its growth. Homogenization pressures of 13.80 and 6.90 MPa improved acid tolerance and bile tolerance, respectively, of L. acidophilus LA-K but had no effect on protease activity and its growth. Some low homogenization pressures positively influenced some characteristics of yogurt culture bacteria and L. acidophilus LA-K. Culture pretreatment with some low homogenization pressures can be recommended for improvement of certain probiotic characteristics. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Intraoperative Radiation for Breast Cancer with Intrabeam™: Factors Associated with Decreased Operative Times in Patients Having IORT for Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephanie A. Valente

    2017-10-01

    Full Text Available IntroductionIntraoperative radiation with Intrabeam™ (IORT for breast cancer is a newer technology recently implemented into the operating room (OR. This procedure requires time and coordination between the surgeon and radiation oncologist, who both perform their treatments in a single operative setting. We evaluated the surgeons at our center, who perform IORT and their OR times to examine changes in OR times following implementation of this new surgical procedure. We hypothesized that IORT is a technique for which timing could be improved with the increasing number of cases performed.MethodsA prospectively maintained IRB approved database was queried for OR times (incision and close in patients who underwent breast conserving surgery (BCS, sentinel lymph node biopsy with and without IORT using the Intrabeam™ system at our institution from 2011 to 2015. The total OR times were compared for each surgeon individually and over time. Next, the OR times of each surgeon were compared to each other. Continuous variables were summarized and then a prediction model was created using IORT time, OR time, surgeon, and number of cases performed.ResultsThere were five surgeons performing IORT at our institution during this time period with a total of 96 cases performed. There was a significant difference observed in baseline surgeon-specific OR time for BSC (p = 0.03 as well as for BCS with IORT (p < 0.05, attributable to surgeon experience. The average BCS times were faster than the BCS plus IORT procedure times for all surgeons. The overall mean OR time for the entire combined surgical and radiation procedure was 135.5 min. The most common applicator sizes used were the 3.5 and 4 cm, yielding an average 21 min IORT time. Applicator choice did not differ over time (p = 0.189. After adjusting for IORT time and surgeon, the prediction model estimated that surgeons decreased the total BCS plus IORT OR time at a rate of −4.5 min per

  5. GC protein-derived macrophage-activating factor decreases ?-N-acetylgalactosaminidase levels in advanced cancer patients

    OpenAIRE

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    ?-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort ...

  6. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

    Science.gov (United States)

    Advani, Shailesh; Tsilidis, Konstantinos K.; Wang, Run; Canfield, Steven

    2017-01-01

    For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990–2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

  7. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

    Science.gov (United States)

    Lopez, David S; Advani, Shailesh; Tsilidis, Konstantinos K; Wang, Run; Canfield, Steven

    2017-06-01

    For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990-2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

  8. SPIRITUAL EMOTIONAL FREEDOM TECHNIQUE DECREASING STRESS ON PATIENTS WITH CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Desmaniarti Z,

    2017-01-01

    Full Text Available Introduction: Cervical cancer is known as one of deadly disease. The global incidence of cervical cancer is the second largest in the entire world, including in Indonesia. RSUP Dr. Hasan Sadikin Bandung, cervical cancer ranked fi rst (62.27% compared with other fi ve types of obstetry and gynecology malignancies (suspected malignant ovarian tumors 16.12%, ovarian cancer 11.76%, vulva cancer 8.65% and endometrial cancer 1.19% (Destiana, 2012. Chemotherapy as one of cancer treatment causes various side effects include hair loss, nails blackened, nausea and vomiting, that could makes patient stressful. SEFT ( Spiritual Emotional Freedom Technique is useful to overcome negative emotions through a combination technique that uses psychological energy, spiritual strength, and praying. SEFT is an effective intervention in manage stress, there are some techniques that practiced simply such as praying, NLP (Neuro Linguistic Programming, hypnotherapy, visualisation, meditation, relaxation, imagery and desensitisasi (Zainuddin, 2008. The purpose of this study was to explain reducing stress on patiens with cervical cancer through Spiritual Emotional Freedom Technique (SEFT at RSUP Dr. Hasan Sadikin Bandung. Improvements on patient’s stress will lead to a better result on cervical cancer therapy. Methods: This study was used quasy experiment pre-post test randomize control group design. Patient with cervical cancer at stadium I to III that taking chemotherapy was selected by using purposive sampling and divided into two groups. Each group contains 34 patients. Intervention group was given SEFT in three round. Each round took 30 minutes. Before and after intervention patients was given Questionnaire. The data were analyzed using paired t-test and independent t-test. Result: The result of this research showed that patient’s stress getting lower signifi cantly after intervention. Discussion: SEFT could reduced stress on patients with cervical cancer that

  9. Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

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    Chong-Yu Zhang

    2015-02-01

    Full Text Available Recent evidence suggests that the human kallikrein 7 (KLK7 is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa and 92 with benign prostate hyperplasia (BPH were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57% benign cases showed positive staining for KLK7 and 23 of 116 (19.83% malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001. The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

  10. Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

    NARCIS (Netherlands)

    Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Sweep, Fred C. G. J.; Geurts-Moespot, Anneke; Engelhardt, Mallory S.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; van Laarhoven, Hanneke W. M.

    2014-01-01

    Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of

  11. Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

    Science.gov (United States)

    Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

    2013-03-01

    Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  12. Tsunami survivors' perspectives on vulnerability and vulnerability reduction: evidence from Koh Phi Phi Don and Khao Lak, Thailand.

    Science.gov (United States)

    Steckley, Marylynn; Doberstein, Brent

    2011-07-01

    This paper presents the results of primary research with 40 survivors of the 2004 Indian Ocean tsunami in two communities: Khao Lak (n=20) and Koh Phi Phi Don (n=20), Thailand. It traces tsunami survivors' perceptions of vulnerability, determines whether residents felt that the tsunami affected different communities differently, identifies the populations and sub-community groups that survivors distinguished as being more vulnerable than others, highlights community-generated ideas about vulnerability reduction, and pinpoints a range of additional vulnerability reduction actions. Tsunami survivors most consistently identified the 'most vulnerable' community sub-populations as women, children, the elderly, foreigners, and the poor. In Khao Lak, however, respondents added 'Burmese migrants' to this list, whereas in Koh Phi Phi Don, they added 'Thai Muslims'. Results suggest that the two case study communities, both small, coastal, tourism-dominated communities no more than 100 kilometres apart, have differing vulnerable sub-groups and environmental vulnerabilities, requiring different post-disaster vulnerability reduction efforts. © 2011 The Author(s). Disasters © Overseas Development Institute, 2011.

  13. TOX3 (TNRC9) overexpression in bladder cancer cells decreases cellular proliferation and triggers an interferon-like response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Mansilla, Francisco; Andersen, Lars Dyrskjøt

    2013-01-01

    Background Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+-dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells overexpressing TOX3 followed by Pathway analysis showed that TOX3 overexpression mainly affected the Interferon Signaling Pathway. TOX3 upregulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 overexpressing...

  14. TOX3 (TNRC9) Over Expression in Bladder Cancer Cells Decreases Cellular Proliferation and Triggers an Interferon-Like Response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Mansilla Castaño, Francisco; Dyrskjøt, Lars

    2013-01-01

    Background: Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+ dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells over expressing TOX3 followed by Pathway analysis showed that TOX3 Overexpression mainly affected the Interferon Signaling Pathway. TOX3 up regulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 over...

  15. Various functions of PBMC from colon cancer patients are not decreased compared to healthy blood donors

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, Hans Jørgen

    1997-01-01

    The immune surveillance hypothesis suggests impaired immune responses to participate in development of cancer. This may partly be due to increased amounts of PGE2 and histamine, which inhibit cellular immunity. These effects are mediated by cAMP, which is increased and thereby may down-regulate I...... no difference in levels of intracellular cAMP, IL-2 mRNA expression, IL-2R mRNA expression, or proliferative responses of PBMC from colon cancer patients compared to healthy blood donors. There was no effect of the immune modulating agents on PBMC from colon cancer patients....

  16. A genomic study on distribution of human leukocyte antigen (HLA-A and HLA-B alleles in Lak population of Iran

    Directory of Open Access Journals (Sweden)

    Farhad Shahsavar

    2017-03-01

    Full Text Available Anthropological studies based on the highly polymorphic gene, human leukocyte antigen (HLA, provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as infertility treatment, designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine HLA-A and HLA-B allele frequencies in 100 unrelated Lak/lᴂk/individuals from Lorestan province of Iran. Finally, we compared the results with that previously described in Iranian population. Commercial HLA-Type kits from BAG (Lich, Germany company were used for determination of the HLA-A and HLA-B allele frequencies in genomic DNA, based on polymerase chain reaction with sequence specific primer (PCR-SSP assay. The differences between the populations in distribution of HLA-A and HLA-B alleles were estimated by chi-squared test with Yate's correction. The most frequent HLA-A alleles were *24 (20%, *02 (18%, *03 (12% and *11 (10%, and the most frequent HLA-B alleles were *35 (24%, *51 (16%, *18 (6% and *38 (6% in Lak population. HLA-A*66 (1%, *74(1% and HLA-B*48 (1%, *55(1% were the least observed frequencies in Lak population. Our results based on HLA-A and HLA-B allele frequencies showed that Lak population possesses the previously reported general features of Iranians but still with unique.

  17. Obesity Contributes to Ovarian Cancer Metastatic Success Through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages

    Science.gov (United States)

    Liu, Yueying; Metzinger, Matthew N.; Lewellen, Kyle A.; Cripps, Stephanie N.; Carey, Kyle D.; Harper, Elizabeth I.; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A.; Conley, Kaitlyn; Johnson, Jeff J.; Klymenko, Yuliya; Bruney, Lana; Liang, Zhong; Dovichi, Norman J.; Cheatham, Bentley; Leevy, W. Matthew; Stack, M. Sharon

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intra-peritoneal (i.p.) metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional meso-mimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced i.p. tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histological analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently impacts ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival. PMID:26573796

  18. Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer

    DEFF Research Database (Denmark)

    Bundgaard, N S; Bendtsen, V O; Ingeholm, P

    2017-01-01

    BACKGROUND: It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. AIM: The aim of this study was to assess the effect of unintended intraoperative tumor perforation...... on postoperative mortality and long-term survival. MATERIAL AND METHODS: This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. RESULTS: Intraoperative...... tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative...

  19. Cancer prehabilitation: an opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes.

    Science.gov (United States)

    Silver, Julie K; Baima, Jennifer

    2013-08-01

    Cancer prehabilitation, a process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment, includes physical and psychological assessments that establish a baseline functional level, identifies impairments, and provides targeted interventions that improve a patient's health to reduce the incidence and the severity of current and future impairments. There is a growing body of scientific evidence that supports preparing newly diagnosed cancer patients for and optimizing their health before starting acute treatments. This is the first review of cancer prehabilitation, and the purpose was to describe early studies in the noncancer population and then the historical focus in cancer patients on aerobic conditioning and building strength and stamina through an appropriate exercise regimen. More recent research shows that opportunities exist to use other unimodal or multimodal prehabilitation interventions to decrease morbidity, improve physical and psychological health outcomes, increase the number of potential treatment options, decrease hospital readmissions, and reduce both direct and indirect healthcare costs attributed to cancer. Future research may demonstrate increased compliance with acute cancer treatment protocols and, therefore, improved survival outcomes. New studies suggest that a multimodal approach that incorporates both physical and psychological prehabilitation interventions may be more effective than a unimodal approach that addresses just one or the other. In an impairment-driven cancer rehabilitation model, identifying current and anticipating future impairments are the critical first steps in improving healthcare outcomes and decreasing costs. More research is urgently needed to evaluate the most effective prehabilitation interventions, and combinations thereof, for survivors of all types of cancer.

  20. Curcumin-mediated decrease in the expression of nucleolar organizer regions in cervical cancer (HeLa) cells.

    Science.gov (United States)

    Lewinska, Anna; Adamczyk, Jagoda; Pajak, Justyna; Stoklosa, Sylwia; Kubis, Barbara; Pastuszek, Paulina; Slota, Ewa; Wnuk, Maciej

    2014-09-01

    Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1 μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

    Science.gov (United States)

    Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

    2017-08-01

    To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

  2. Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer

    International Nuclear Information System (INIS)

    Adell, Gunnar; Zhang Hong; Jansson, Agneta; Sun Xiaofeng; Staal, Olle; Nordenskjoeld, Bo

    2001-01-01

    Background: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival. Purpose: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy. Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen. Materials: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990. Results: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p=0.03), with a trend toward improved disease-free survival (p=0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates. Conclusion: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer

  3. Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study.

    Science.gov (United States)

    Shih, H-J; Kao, M-C; Tsai, P-S; Fan, Y-C; Huang, C-J

    2017-09-01

    Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients. We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders. A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019). Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

  4. Lipoic Acid Decreases the Viability of Breast Cancer Cells and Activity of PTP1B and SHP2.

    Science.gov (United States)

    Kuban-Jankowska, Alicja; Gorska-Ponikowska, Magdalena; Wozniak, Michal

    2017-06-01

    Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases. ALA and DHLA decrease the activity of PTP1B and SHP2, and have inhibitory effects on the viability and proliferation of breast cancer cells. ALA and DHLA can be considered as potential agents for the adjunctive treatment of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer.

    Science.gov (United States)

    Takayama, Hitoshi; Nonomura, Norio; Nishimura, Kazuo; Oka, Daizo; Shiba, Masahiro; Nakai, Yasutomo; Nakayama, Masashi; Tsujimura, Akira; Aozasa, Katsuyuki; Okuyama, Akihiko

    2009-02-01

    The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR-positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene. MSR was evaluated by immunostaining in needle biopsies of the prostate from 135 patients who were confirmed to have prostate cancer. Among these men, 70 were treated by radical prostatectomy or by radiotherapy as definitive therapy; the other 65 were treated by hormonal therapy because of advanced disease or age. Needle-biopsy specimens were sectioned at 5 microm and immunostained with a monoclonal antibody against MSR. Six microscopic (x400) fields around the cancer foci were selected in each case for analysis. The median number of MSR-positive cells (MSR count) in each case was 24. There was an inverse correlation between the MSR count and Gleason score and clinical stage. The MSR count was lower in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (P or =24) than that in those with low MSR count (<24, P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with a higher MSR count were higher than in those with a lower MSR count (P < 0.001 and 0.014, respectively). Cox multivariate analysis showed that the MSR count was a prognostic factor for prostate cancer in addition to extraprostatic extension and Gleason score (P = 0.002, 0.038 and 0.011, respectively). The results of immunostaining of MSR in needle-biopsy specimens is a prognostic factor for prostate cancer.

  6. P53 Is Involved in a Three-Dimensional Architecture-Mediated Decrease in Chemosensitivity in Colon Cancer.

    Science.gov (United States)

    He, Jianming; Liang, Xi; Luo, Fen; Chen, Xuedan; Xu, Xueqing; Wang, Fengchao; Zhang, Zhenping

    2016-01-01

    Three-dimensional (3D) culture models represent a better approximation of solid tumor tissue architecture, especially cell adhesion, in vivo than two-dimensional (2D) cultures do. Here, we explored the role of architecture in chemosensitivity to platinum in colon cancer. Under the 3D culture condition, colon cancer cells formed multicellular spheroids, consisting of layers of cells. 3D cultures displayed significantly decreased sensitivity to platinum compared with 2D cultures. Platinum increased p53 in a dose-dependent and time-dependent manner. There was no detectable difference in basal p53 levels between 3D cultures and 2D cultures but cisplatin induced less p53 in both HCT116 3D cultures and LoVo 3D cultures. It was not due to cisplatin concentration because cisplatin induced similar γ-H2AX in 3D vs 2D. Knockdown of p53 significantly decreased sensitivity to platinum in 3D cultures. Knockdown of p53 decreased cleaved caspase 3 and apoptosis induced by cisplatin. These findings indicate that 3D architecture confers decreased chemosensitivity to platinum and p53 is involved in the mechanism. Knockdown of p53 decreased cisplatin's induction of c-Jun N-terminal kinase 1/2 (JNK1/2) activation, whereas inhibition of JNK1/2 activation increased chemosensitivity. Inhibition of p38 activation decreased cisplatin's induction of p53, but no difference in p38 activation by cisplatin was observed between 2D cultures and 3D cultures. Taken together, our results suggest that p53 is involved in a 3D architecture-mediated decrease in chemosensitivity to platinum in colon cancer. Mitogen-activated protein kinases (JNK1/2 and p38) do not play a dominant role in the mechanism.

  7. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori; Horyozaki, Akiko; Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp

    2016-09-09

    Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses the growth of spheroids of DLD-1, and enhances the effect of 5-FU.

  8. Decreased risk of stroke among 10-year survivors of breast cancer.

    NARCIS (Netherlands)

    Hooning, M.J.; Dorresteijn, L.D.A.; Aleman, B.; Kappelle, A.C.; Klijn, J.G.M.; Boogerd, W.; Leeuwen, F.E. van

    2006-01-01

    PURPOSE: To assess treatment-specific risk of cerebrovascular events in early breast cancer (BC) patients, accounting for cerebrovascular risk factors. PATIENTS AND METHODS: We studied the incidence of cerebrovascular accidents (CVA; stroke and transient ischemic attack [TIA]) in 10-year survivors

  9. AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

    DEFF Research Database (Denmark)

    Rodriguez-Teja, Mercedes; Gronau, Julian H; Breit, Claudia

    2015-01-01

    Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways...... in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major......(Δ) (Ex2-6/) (Δ) (Ex2-6) mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour...

  10. Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants.

    Science.gov (United States)

    Isharwal, Sumit; Modi, Shrey; Arora, Nivedita; Uhlrich, Charles; Giri, Bhuwan; Barlass, Usman; Soubra, Ayman; Chugh, Rohit; Dehm, Scott M; Dudeja, Vikas; Saluja, Ashok; Banerjee, Sulagna; Konety, Badrinath

    2017-05-01

    With almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo. Cell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide. Our study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal

  11. Healthy dietary patterns decrease the risk of colorectal cancer in the Mecca Region, Saudi Arabia: a case-control study.

    Science.gov (United States)

    Azzeh, Firas S; Alshammari, Eyad M; Alazzeh, Awfa Y; Jazar, Abdelelah S; Dabbour, Ibrahim R; El-Taani, Hani A; Obeidat, Ahmed A; Kattan, Fayrooz A; Tashtoush, Sufyan H

    2017-06-29

    Colorectal cancer (CRC) is the first most common cancer in males and the third most common cancer in females in Saudi Arabia. Dietary habits are strongly associated with the inhibition or proliferation of malignancy. Therefore, this study is aiming to investigate the risks and protective benefits of dietary factors affecting CRC in the Mecca region of Saudi Arabia. A case-control study was conducted from June 2014 to March 2015. One hundred thirty-seven patients with colon and/or rectal cancer were recruited in the case group, while 164 healthy participants were recruited in the control group. A questionnaire was completed with the help of trained dietitians to study the effects of several dietary patterns on the risk of CRC. Dairy product intake of 1-5 servings/day, legume intake of 3-5 servings/week, leafy vegetables intake of 1-5 servings/week, olive oil intake of 1-5 servings/week, black tea intake of three or more cups/day, and coffee intake of one or more cups/day was found to decrease the risk of CRC in participants. This study highlights the importance of changing dietary habits to decrease CRC incidence in the Mecca region.

  12. Healthy dietary patterns decrease the risk of colorectal cancer in the Mecca Region, Saudi Arabia: a case-control study

    Directory of Open Access Journals (Sweden)

    Firas S. Azzeh

    2017-06-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the first most common cancer in males and the third most common cancer in females in Saudi Arabia. Dietary habits are strongly associated with the inhibition or proliferation of malignancy. Therefore, this study is aiming to investigate the risks and protective benefits of dietary factors affecting CRC in the Mecca region of Saudi Arabia. Methods A case-control study was conducted from June 2014 to March 2015. One hundred thirty-seven patients with colon and/or rectal cancer were recruited in the case group, while 164 healthy participants were recruited in the control group. A questionnaire was completed with the help of trained dietitians to study the effects of several dietary patterns on the risk of CRC. Results Dairy product intake of 1–5 servings/day, legume intake of 3–5 servings/week, leafy vegetables intake of 1–5 servings/week, olive oil intake of 1–5 servings/week, black tea intake of three or more cups/day, and coffee intake of one or more cups/day was found to decrease the risk of CRC in participants. Conclusion This study highlights the importance of changing dietary habits to decrease CRC incidence in the Mecca region.

  13. Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.

    Science.gov (United States)

    Završnik, Janja; Butinar, Miha; Prebanda, Mojca Trstenjak; Krajnc, Aleksander; Vidmar, Robert; Fonović, Marko; Grubb, Anders; Turk, Vito; Turk, Boris; Vasiljeva, Olga

    2017-09-26

    Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth. Notably, a decrease in the proliferation of CstC knockout PyMT tumor cells was demonstrated ex vivo and in vitro , indicating a role for this protease inhibitor in signaling pathways that control cell proliferation. An increase in phosphorylated p-38 was observed in CstC knockout tumors, suggesting a novel function for cystatin C in cancer development, independent of the TGF-β pathway. Moreover, proteomic analysis of the CstC wild-type and knockout PyMT primary cell secretomes revealed a decrease in the levels of 14-3-3 proteins in the secretome of knock-out cells, suggesting a novel link between cysteine cathepsins, cystatin C and 14-3-3 proteins in tumorigenesis, calling for further investigations.

  14. MiR-371-5p facilitates pancreatic cancer cell proliferation and decreases patient survival.

    Directory of Open Access Journals (Sweden)

    De He

    Full Text Available microRNAs (miRNAs play a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. To date, scientists have obtained a substantial amount of knowledge with regard to miRNAs in pancreatic cancer. However, the expression and function of miR-371-5p in pancreatic cancer has not been clearly elucidated. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer.The expression of miR-371-5p was examined in pancreatic duct adenocarcinoma (PDAC and their adjacent normal pancreatic tissues (ANPT or in pancreatic cancer cell lines by qRT-PCR. The association of miR-371-5p expression with overall survival was determined. The proliferation and apoptosis of SW-1990 and Panc-1 cells, transfected with miR-371-5p mimics or inhibitor, were assessed using MTT assay and flow cytometry, respectively. The tumorigenicity was evaluated via mice xenograft experiments. miR-371-5p promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP. Protein expression was analyzed by Western blot.The expression level of miR-371-5p was dramatically upregulated in clinical PDAC tissues compared with ANPT. Patients with high miR-371-5p expression had a significantly shorter survival than those with low miR-371-5p expression. The in vitro and in vivo assays showed that overexpression of miR-371-5p resulted in cell proliferation and increased tumor growth, which was associated with inhibitor of growth 1 (ING1 downregulation. Interestingly, we also found that ING1, in turn, inhibited expression of miR-371-5p in the promoter region.our study demonstrates a novel ING1-miR-371-5p regulatory feedback loop, which may have a critical role in PDAC. Thus miR-371-5p can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.

  15. Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line.

    Science.gov (United States)

    Freiburghaus, C; Janicke, B; Lindmark-Månsson, H; Oredsson, S M; Paulsson, M A

    2009-06-01

    Food components modify the risk of cancer at a large number of sites but the mechanism of action is unknown. In the present investigation, we studied the effect of the peptide lactoferricin derived from bovine milk lactoferrin on human colon cancer CaCo-2 cells. The cells were either untreated or treated with 2.0, 0.2, or 0.02 microM lactoferricin. Cell cycle kinetics were investigated with a bromodeoxyuridine DNA flow cytometric method. The results show that lactoferricin treatment slightly but significantly prolonged the S phase of the cell cycle. Lactoferricin treatment lowered the level of cyclin E1, a protein involved in the regulation of genes required for G(1)/S transition and consequently for efficient S phase progression. The slight prolongation of the S phase resulted in a reduction of cell proliferation, which became more apparent after a long treatment time.

  16. Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes

    Science.gov (United States)

    2008-03-01

    A composite image of two separate Western blots. Whole-cell lysate from the MCF10A IHMEC line was used as a control on both blots in the composite ...which the nucleolus is depicted as a dark spot within the nucleus. Parental (far left ) and scramble shRNA controls (middle ) normally contain one or... Chemistry of Life Processes” Cumulative GPA: 3.97/4.0 Honors and Awards: University of Michigan Department of Defense Breast Cancer

  17. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    International Nuclear Information System (INIS)

    Li, Fang-qiu; Han, Yan-ling; Liu, Qun; Wu, Bo; Huang, Wen-bin; Zeng, Su-yun

    2009-01-01

    Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

  18. Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

    Science.gov (United States)

    Lefringhouse, Jason; Pavlik, Edward; Miller, Rachel; DeSimone, Christopher; Ueland, Frederick; Kryscio, Richard; van Nagell, J. R.

    2014-01-01

    Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. PMID:25254047

  19. Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.

    Science.gov (United States)

    Yan, Chen; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng

    2018-04-01

    Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Decreased expression of RNA interference machinery, Dicer and Drosha, is associated with poor outcome in ovarian cancer patients

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    Merritt, William M.; Lin, Yvonne G.; Han, Liz Y.; Kamat, Aparna A.; Spannuth, Whitney A.; Schmandt, Rosemarie; Urbauer, Diana; Pennacchio, Len A.; Cheng, Jan-Fang; Zeidan, Alexandra; Wang, Hua; Mueller, Peter; Lenburg, Marc E.; Gray, Joe W.; Mok, Samuel; Birrer, Michael J.; Lopez-Berestein, Gabriel; Coleman, Robert L.; Bar-Eli, Menashe; Sood, Anil K.

    2008-05-06

    The clinical and functional significance of RNA interference (RNAi) machinery, Dicer and Drosha, in ovarian cancer is not known and was examined. Dicer and Drosha expression was measured in ovarian cancer cell lines (n=8) and invasive epithelial ovarian cancer specimens (n=111) and correlated with clinical outcome. Validation was performed with previously published cohorts of ovarian, breast, and lung cancer patients. Anti-Galectin-3 siRNA and shRNA transfections were used for in vitro functional studies. Dicer and Drosha mRNA and protein levels were decreased in 37% to 63% of ovarian cancer cell lines and in 60% and 51% of human ovarian cancer specimens, respectively. Low Dicer was significantly associated with advanced tumor stage (p=0.007), and low Drosha with suboptimal surgical cytoreduction (p=0.02). Tumors with both high Dicer and Drosha were associated with increased median patient survival (>11 years vs. 2.66 years for other groups; p<0.001). In multivariate analysis, high Dicer (HR=0.48; p=0.02), high-grade histology (HR=2.46; p=0.03), and poor chemoresponse (HR=3.95; p<0.001) were identified as independent predictors of disease-specific survival. Findings of poor clinical outcome with low Dicer expression were validated in separate cohorts of cancer patients. Galectin-3 silencing with siRNA transfection was superior to shRNA in cell lines with low Dicer (78-95% vs. 4-8% compared to non-targeting sequences), and similar in cell lines with high Dicer. Our findings demonstrate the clinical and functional impact of RNAi machinery alterations in ovarian carcinoma and support the use of siRNA constructs that do not require endogenous Dicer and Drosha for therapeutic applications.

  1. Decreased expression of the ARID1A gene is associated with poor prognosis in primary gastric cancer.

    Directory of Open Access Journals (Sweden)

    Dan-dan Wang

    Full Text Available BACKGROUND: The ARID1A gene encodes adenine-thymine (AT-rich interactive domain-containing protein 1A, which participates in chromatin remodeling. ARID1A has been showed to function as a tumor suppressor in various cancer types. In the current study, we investigated the expression and prognosis value of ARID1A in primary gastric cancer. Meanwhile, the biological role of ARID1A was further investigated using cell model in vitro. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of ARID1A gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were used to examine the ARID1A expression in paired cancerous and noncancerous tissues. Results revealed decreased ARID1A mRNA (P = 0.0029 and protein (P = 0.0015 expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues, and in gastric cancer cell lines. To further investigate the clinicopathological and prognostic roles of ARID1A expression, we performed immunohistochemical analyses of the 224 paraffin-embedded gastric cancer tissue blocks. Data revealed that the loss of ARID1A expression was significantly correlated with T stage (P = 0.001 and grade (P = 0.006. Consistent with these results, we found that loss of ARID1A expression was significantly correlated with poor survival in gastric cancer patients (P = 0.003. Cox regression analyses showed that ARID1A expression was an independent predictor of overall survival (P = 0.029. Furthermore, the functions of ARID1A in the proliferation and colony formation of gastric cell lines were analyzed by transfecting cells with full-length ARID1A expression vector or siRNA targeting ARID1A. Restoring ARID1A expression in gastric cancer cells significantly inhibited cell proliferation and colony formation. Silencing ARID1A expression in gastric epithelial cell line significantly enhanced cell growth rate. CONCLUSIONS/SIGNIFICANCE: Our data suggest that ARID1A may play an important role

  2. MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer

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    Wolfe, Adam R.; Bambhroliya, Arvind [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Huo, Lei [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Larson, Richard; Li, Li [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-06-01

    Purpose: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. Methods and Materials: MiR-33a expression was analyzed by reverse transcriptase–polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Results: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a–expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a–expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a–expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a–expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P

  3. MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer

    International Nuclear Information System (INIS)

    Wolfe, Adam R.; Bambhroliya, Arvind; Reddy, Jay P.; Debeb, Bisrat G.; Huo, Lei; Larson, Richard; Li, Li; Ueno, Naoto T.; Woodward, Wendy A.

    2016-01-01

    Purpose: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. Methods and Materials: MiR-33a expression was analyzed by reverse transcriptase–polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Results: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a–expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a–expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a–expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a–expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P

  4. Breast cancer in South-Eastern European countries since 2000: Rising incidence and decreasing mortality at young and middle ages.

    Science.gov (United States)

    Dimitrova, Nadya; Znaor, Ariana; Agius, Dominic; Eser, Sultan; Sekerija, Mario; Ryzhov, Anton; Primic-Žakelj, Maja; Coebergh, Jan Willem

    2017-09-01

    Marked variations exist in the incidence and mortality trends of major cancers in South-Eastern European (SEE) countries which have now been detailed by age for breast cancer (BC) to seek clues for improvement. We brought together and analysed data from 14 cancer registries (CRs), situated in SEE countries or directly adjacent. Age-standardised rate at world standard (ASRw) and truncated incidence and mortality rates during 2000-2010 by year, and for four age groups, were calculated. Average annual percentage change of rates was estimated using Joinpoint regression. Annual incidence rates increased significantly in countries and age groups, by 2-4% (15-39 years), 2-5% (40-49), 1-4% (50-69) and 1-6% (at 70+). Mortality rates decreased significantly in all age-groups in most countries, but increased up to 5% annually above age 55 in Ukraine, Serbia, Moldova and Cyprus. The BC data quality was evaluated by internationally agreed indicators which appeared suboptimal for Moldova, Bosnia and Herzegovina and Romania. The observed variations of incidence trends reflect the influence of risk factors, as well as levels of early detection activities (screening). While mortality rates were mostly decreasing, probably due to improved cancer care and introduction of more effective systemic treatment regimens, the worrying increasing mortality trends in the 55-plus age groups in some countries have to be addressed by health professionals and policymakers. In order to assess and monitor the effects of cancer control activities in the region, the CRs need substantial investments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

    Science.gov (United States)

    Borowczyk, M; Janicki, A; Dworacki, G; Szczepanek-Parulska, E; Danieluk, M; Barnett, J; Antonik, M; Kałużna, M; Bromińska, B; Czepczyński, R; Bączyk, M; Ziemnicka, K; Ruchała, M

    2018-04-04

    The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

  6. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

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    Leifheit Erica C

    2004-07-01

    Full Text Available Abstract Background The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF has previously been associated with various types of adenocarcinoma. Methods MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA, anti-MIF antibody or MIF anti-sense on cell growth and cytokine expression were analyzed. Results Human bladder cancer cells (HT-1376 secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. Conclusions This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma.

  7. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

    International Nuclear Information System (INIS)

    Meyer-Siegler, Katherine L; Leifheit, Erica C; Vera, Pedro L

    2004-01-01

    The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

  8. Serum carcinoembryonic antigen tends to decrease in poorly-differentiated colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ester Morina Silalahi

    2015-12-01

    This was a cross-sectional study conducted on 40 CRC subjects from July 2012 until May 2013. Determination of serum CEA and CA 19-9 levels and histopathological (cellular differentiation grades in CRC biopsies was done in all subjects. RESULTS The study involved forty CRC patients, consisting of 22 males and 18 females, with mean age of 51.93 ± 11.63 years, CEA levels of 51.93 ± 84.07 ng/ml and CA 19-9 levels of 33.81 ± 62.39 U/ml. Carcino-embryonic antigen levels tended to decrease with decreasing CRC histopathological grade, while CA 19-9 levels increased in well-differentiated CRC. However, both relationships were statistically not significant (with p=0.314 and p=0.787, respectively. CONCLUSIONS Carcinoembryonic antigen (CEA levels tend to decrease with decreasing histopathological grade of CRC, and CA 19-9 levels tend to increase in well-differentiated CRC.

  9. IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence

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    Kelsey A. Finkel

    2016-05-01

    Full Text Available Head and neck squamous cell carcinomas (HNSCC exhibit a small population of uniquely tumorigenic cancer stem cells (CSC endowed with self-renewal and multipotency. We have recently shown that IL-6 enhances the survival and tumorigenic potential of head and neck cancer stem cells (i.e. ALDHhighCD44high cells. Here, we characterized the effect of therapeutic inhibition of IL-6 with a novel humanized anti-IL-6 antibody (MEDI5117 using three low-passage patient-derived xenograft (PDX models of HNSCC. We observed that single agent MEDI5117 inhibited the growth of PDX-SCC-M1 tumors (P < .05. This PDX model was generated from a previously untreated HNSCC. In contrast, MEDI5117 was not effective at reducing overall tumor volume for PDX models representing resistant disease (PDX-SCC-M0, PDX-SCC-M11. Low dose MEDI5117 (3 mg/kg consistently decreased the fraction of cancer stem cells in PDX models of HNSCC when compared to IgG-treated controls, as follows: PDX-SCC-M0 (P < .001, PDX-SCC-M1 (P < .001, PDX-SCC-M11 (P = .04. Interestingly, high dose MEDI5117 (30 mg/kg decreased the CSC fraction in the PDX-SCC-M11 model (P = .002, but not in PDX-SCC-M0 and PDX-SCC-M1. MEDI5117 mediated a dose-dependent decrease in the number of orospheres generated by ALDHhighCD44high cells cultured in ultra-low attachment plates (P < .05, supporting an inhibitory effect on head and neck cancer stem cells. Notably, single agent MEDI5117 reduced the overall recurrence rate of PDX-SCC-M0, a PDX generated from the local recurrence of human HNSCC. Collectively, these data demonstrate that therapeutic inhibition of IL-6 with low-dose MEDI5117 decreases the fraction of cancer stem cells, and that adjuvant MEDI5117 inhibits recurrence in preclinical models of HNSCC.

  10. Decrease in incidence of colorectal cancer among individuals 50 years or older following recommendations for population-based screening

    Science.gov (United States)

    Murphy, Caitlin C.; Sandler, Robert S.; Sanoff, Hanna K.; Yang, Y. Claire; Lund, Jennifer L.; Baron, John A.

    2016-01-01

    Background & Aims The incidence of colorectal cancer (CRC) in the U.S. is increasing among adults younger than age 50 years, but incidence has decreased among older populations after population-based screening was recommended in the late 1980s. Blacks have higher incidence than whites. These patterns have prompted suggestions to lower the screening age for average-risk populations or in blacks. At the same time, there has been controversy over whether reductions in CRC incidence can be attributed to screening. We examined age- and race-related differences in CRC incidence over a 40-year time period. Methods We determined the age-standardized incidence of CRC, from 1975 through 2013, using the population-based Surveillance, Epidemiology, and End Results (SEER) program of cancer registries. We calculated incidence for 5-year age categories (20—24 years through 80—84 years and 85 years or older) for different time periods (1975—1979, 1980—1984, 1985—1989, 1990—1994, 1995—1999, 2000—2004, 2005—2009, and 2010—2013), tumor subsite (proximal colon, descending colon, and rectum), and stages at diagnosis (localized, regional, and distant). Analyses were stratified by race (white vs. black). Results There were 450,682 incident cases of CRC reported to the SEER registries over the entire period (1975—2013). Overall incidence was 75.5/100,000 white persons and 83.6/100,000 black persons. CRC incidence peaked during 1980 through 1989 and began to decrease in 1990. In whites and blacks, the decreases in incidence between the time periods of 1980—1984 and 2010—2013 were limited to the screening-age population (ages 50 years or older). Between these time periods, there was a 40% decrease in incidence among whites compared with a 26% decrease in incidence among blacks. Decreases in incidence were greater for cancers of the distal colon and rectum, and reductions in these cancers were greater among whites than blacks. CRC incidence among persons younger

  11. Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes — A Meta-Analysis

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    Li-Shiun Chen

    2016-09-01

    Conclusion: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7 years for those who develop it. These results: 1 underscore the potential value of smoking cessation for all smokers, 2 suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3 have potential value for framing preventive interventions for those who smoke.

  12. Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs.

    Science.gov (United States)

    Mao, Ling; Li, Jian; Chen, Wei-Xian; Cai, Yan-Qin; Yu, Dan-Dan; Zhong, Shan-Liang; Zhao, Jian-Hua; Zhou, Jian-Wei; Tang, Jin-Hai

    2016-04-01

    While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr-resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co-culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes.

  13. Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage response of colon cancer cells

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Hahn, Stephan; Mansilla, Francisco

    2013-01-01

    correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed...... response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced......Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation...

  14. Keratin23 (KRT23 knockdown decreases proliferation and affects the DNA damage response of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Karin Birkenkamp-Demtröder

    Full Text Available Keratin 23 (KRT23 is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed that KRT23 depletion affected molecules of the cell cycle and DNA replication, recombination and repair. In vitro analyses confirmed that KRT23 depletion significantly decreased the cellular proliferation of SW948 and LS1034 cells and markedly decreased the expression of genes involved in DNA damage response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced proliferation of the KRT23 depleted cells compared to irradiated control cells.

  15. Decreased health-related quality of life in disease-free survivors of differentiated thyroid cancer in Korea

    Directory of Open Access Journals (Sweden)

    Kim Kwang-Won

    2010-09-01

    Full Text Available Abstract Background Concern regarding the health-related quality of life (HRQOL of long-term survivors of thyroid cancer has risen due to the rapid increase in the incidence of thyroid cancer, which generally has an excellent prognosis. The aim of this study was to evaluate the status of HRQOL in disease-free survivors of differentiated thyroid carcinoma (DTC and to evaluate the important determinants of HRQOL. Methods This was a cross-sectional study in which we interviewed consecutive disease-free survivors of DTC. Three different validated questionnaires ("EORTC QLQ-C30" for various functional domains, the "brief fatigue inventory (BFI" and the "hospital anxiety and depression scale" (HADS were used. Data from a large, population based survey of 1,000 people were used as a control. Results The response rate for the questionnaires was 78.9% (316/401. Disease-free survivors of DTC showed a decreased HRQOL in all five functional domains (physical, role, cognitive, emotional, and social on the EORTC QLQ-C30 compared with controls (P P Conclusions Although disease-free survivors of DTC are expected to have disease-specific survival comparable to the general population, they experience a significantly decreased HRQOL. Anxiety, depression, and fatigue were the major determinants of the decreased HRQOL. Supportive psychological care should be integrated into the management of long-term survivors of DTC.

  16. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    Science.gov (United States)

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α- N -acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

  17. Pattern of decrease of prostate specific antigen after radical radiotherapy for the prostate cancer

    International Nuclear Information System (INIS)

    Kim, Bo Kyoung; Park, Suk Won; Ha, Sung Whan

    1999-01-01

    Prostate specific antigen (PSA) is a useful tumor marker, which is widely used as a diagnostic index and predictor of both treatment and follow-up result in prostate cancer. A prospective analysis was carried out to obtain the period of PSA normalization and the half life of PSA and to analyze the factors influencing the period of PSA normalization. The PSA level was checked before and serially after radical radiotherapy. Twenty patients with clinically localized prostate cancer who underwent radical external beam radiotherapy were enrolled in this study. Accrual period was from April 1993 to May 1998. Median follow-up period was 26 months. Radiotherapy was given to whole pelvis followed by a boost to prostate. Dose range for the whole pelvis was from 45 Gy to 50 Gy and boost dose to prostate, from 14 Gy to 20 Gy. The post-irradiation PSA normal value was under 3.0 ng/ml. The physical examination and serum PSA level evaluation were performed at 3 month interval in the first on year, and then at every 4 to 6 months. PSA value was normalized in nineteen patients (95%) within 12 months. The mean period of PSA normalization was 5.3 (±2.7) months. The half life of PSA ofd the nonfailing patients was 2.1 (±0.9) month. The nadir PSA level of the nonfailing patients was 0.8 (±0.5) ng/ml. The period of PSA normalization had the positive correlation with pretreatment PSA level (R 2 =0.468). The nadir PSA level had no definite positive correlation with the pretreatment PSA level (R 2 =0.175). The half life of serum PSA level also had no definite correlation with pretreatment PSA level (R 2 =0.029). The PSA level was mostly normalized within 8 months (85%). If it has not normalized within 12 months, we should consider the residual disease in prostate or distant metastasis. In 2 patients, the PSA level increased 6 months or 20 months before clinical disease was detected. So the serum PSA level can be used as early diagnostic indicator of treatment failure

  18. A mild pulsed electric field condition that improves acid tolerance, growth, and protease activity of Lactobacillus acidophilus LA-K and Lactobacillus delbrueckii subspecies bulgaricus LB-12.

    Science.gov (United States)

    Najim, N; Aryana, Kayanush J

    2013-06-01

    Pulsed electric field (PEF) processing involves the application of pulses of voltage for less than 1 s to fluid products placed between 2 electrodes. The effect of mild PEF on beneficial characteristics of probiotic bacteria Lactobacillus acidophilus and Lactobacillus delbrueckii ssp. bulgaricus is not clearly understood. The objective of this study was to determine the influence of mild PEF conditions on acid tolerance, growth, and protease activity of Lb. acidophilus LA-K and Lactobacillus delbrueckii ssp. bulgaricus LB-12. A pilot plant PEF system (OSU-4M; The Ohio State University, Columbus) was used. The PEF treatments were positive square unipolar pulse width of 3 µs, pulse period of 0.5s, electric field strength of 1 kV/cm, delay time of 20 µs, flow rate of 60 mL/min, and 40.5°C PEF treatment temperature. Both Lb. acidophilus LA-K and Lb. bulgaricus LB-12 subjected to mild PEF conditions were acid tolerant until the end of the 120 min of incubation, unlike the Lb. bulgaricus control, which was not acid tolerant after 30 min. The mild PEF-treated Lb. acidophilus LA-K and Lb. bulgaricus LB-12 reached the logarithmic phase of growth an hour earlier than the control. Mild PEF conditions studied significantly improved acid tolerance, exponential growth, and protease activity of both Lb. acidophilus LA-K and Lb. bulgaricus LB-12 compared with the control. The mild PEF conditions studied can be recommended for pretreating cultures to enhance these desirable attributes. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

    Science.gov (United States)

    Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

    2014-03-01

    It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

  20. Decreased blood riboflavin levels are correlated with defective expression of RFT2 gene in gastric cancer

    Science.gov (United States)

    Eli, Maynur; Li, De-Sheng; Zhang, Wei-Wei; Kong, Bing; Du, Chen-Song; Wumar, Maimaitiaili; Mamtimin, Batur; Sheyhidin, Ilyar; Hasim, Ayshamgul

    2012-01-01

    AIM: To investigate the relationship between blood riboflavin levels and riboflavin transporter 2 (RFT2) gene expression in gastric carcinoma (GC) development. METHODS: High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC. Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue. RESULTS: A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane (0.398 ± 0.149 vs 1.479 ± 0.587; P = 0.040). Tumors exhibited low RFT2 protein expression (75%, 16.7%, 8.3% and 0% for no RFT2 staining, weak staining, medium staining and strong staining, respectively), which was significantly lower than that in the normal mucous membrane (10%, 16.7%, 26.7% and 46.7% for no RFT2 staining, weak staining, medium staining and strong staining, respectively; P riboflavin levels were reverse correlated with development of GC (1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients; P riboflavin levels with defective expression of RFT2 protein was found in GC patients (χ2 = 2.619; P = 0.019). CONCLUSION: Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC. PMID:22791947

  1. Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.

    Science.gov (United States)

    Mishra, Amrendra; Sriram, Harshini; Chandarana, Pinal; Tanavde, Vivek; Kumar, Rekha V; Gopinath, Ashok; Govindarajan, Raman; Ramaswamy, S; Sadasivam, Subhashini

    2018-05-01

    The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44 + Lin - and CD44 - Lin - subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44 + Lin - compared to CD44 - Lin - cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of

  2. Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

    Science.gov (United States)

    Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

    2015-11-01

    Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in

  3. The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

    DEFF Research Database (Denmark)

    Groizeleau, Julie; Rybtke, Morten; Andersen, Jens Bo

    2016-01-01

    Current antibiotic treatments are insufficient in eradicating bacterial biofilms, which represent the primary cause of chronic bacterial infections. Thus, there is an urgent need for new strategies to eradicate biofilm infections. The second messenger c-di-GMP is a positive regulator of biofilm...... formation in many clinically relevant bacteria. It is hypothesized that drugs lowering the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. To identify compounds capable of lowering c-di-GMP levels in Pseudomonas aeruginosa, we screened 5000 compounds...... for their potential c-di-GMP-lowering effect using a recently developed c-di-GMP biosensor strain. Our screen identified the anti-cancerous drug doxorubicin as a potent c-di-GMP inhibitor. In addition, the drug decreased the transcription of many biofilm-related genes. However, despite its effect on the c-di-GMP...

  4. A simple strategy to decrease fatal carotid blowout syndrome after stereotactic body reirradiaton for recurrent head and neck cancers

    International Nuclear Information System (INIS)

    Yazici, Gozde; Gurkaynak, Murat; Ozyigit, Gokhan; Sanlı, Tolga Yusuf; Cengiz, Mustafa; Yuce, Deniz; Gultekin, Melis; Hurmuz, Pervin; Yıldız, Ferah; Zorlu, Faruk; Akyol, Fadil

    2013-01-01

    This study aimed to compare the therapeutic outcomes and fatal carotid blow out syndrome (CBOS) incidence rates between two different stereotactic body radiotherapy (SBRT) protocols. The study included 75 patients with inoperable locally recurrent head and neck cancer treated with SBRT in our department between June 2007 and March 2011. The first 43 patients were treated sequentially (group I). Then our SBRT protocol was changed due to the high rate of CBOS, and the following 32 patients were treated every other day in a prospective institutional protocol (group II). Median overall survival in group I and group II was 11 months and 23 months, respectively (P = 0.006). We observed 11 cases of CBOS. Only 1 of 7 patients (14%) with CBOS survived in group I, whereas 2 of 4 patients (50%) in group II remain alive. CBOS free median overall survivals were 9 months, and 23 months in group I and group II respectively (P = 0.002). The median radiation dose received by the carotid artery in patients with CBOS was 36.5 Gy (range: 34–42.8 Gy), versus 34.7 Gy (range: 0–44 Gy) in the patients that didn’t have CBOS (P = 0.15). CBOS did not occur in any of the patients with a maximum carotid artery radiation dose <34 Gy. Every other day SBRT protocol for re-irradiation of recurrent head and neck cancer is promising in terms of decreasing the incidence of fatal CBOS

  5. Decreased survival of prostate cancer cells in vitro by combined treatment of heat and an antioxidant inhibitor diethyldithiocarbamate (DDC).

    Science.gov (United States)

    Moriyama-Gonda, Nobuko; Igawa, Mikio; Shiina, Hiroaki; Urakami, Shinji; Terashima, Masaharu

    2003-11-01

    The aim of this study was to examine a modulation of thermotolerance by treatment with combination of heat and the antioxidant inhibitor diethyldithiocarbamate (DDC) of the PC-3 prostate cancer cells. To determine thermotolerance, cells were heated once or twice. Two 1 h exposures at 43 degrees C, with a recovery period in between, revealed better survival/recovery of cells after the second exposure than after the first (fig. 1A + 1B). Additional experiments were performed, heating cells twice (fig. 1B + 1C). First, cells were heated at 43 degrees C for 1 h and, after various recovery times (intervals) at 37 degree C, subsequently reheated at 44 degrees C for 1 h. To ensure effective cell killing, efficiency of the combined treatments of 1 mM DDC and heating at 43 or 44 degrees C for 1 h was estimated by measuring cell survival, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and heat shock protein 70 (hsp 70) expression. To obtain a more effective method for subsequent heat exposure, cells were heated twice after a 24 h interval in the presence or absence of 1 mM DDC. ROS generation and SOD activity immediately increased correlating with duration of heating, but their levels gently decreased with time after discontinuation of heating. On the other hand, hsp 70 levels slowly increased, also correlating with duration of heating but continued to increase with time after discontinuation of heating for a certain period. DDC administration coupled with heating at 43 or 44 degrees C significantly decreased cell survival compared to heating alone (p DDC as compared to heat alone at 43 and 44 degrees C (p DDC could have potential benefits in the treatment of prostate cancer.

  6. Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

    Directory of Open Access Journals (Sweden)

    Francisco J Ortega

    Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  7. Decreased production of interleukin-12 and type 2 immune responses are marked in cachectic patients with colorectal and gastric cancer.

    Science.gov (United States)

    Shibata, Masahiko; Nezu, Takeshi; Kanou, Hisao; Abe, Hideo; Takekawa, Motoo; Fukuzawa, Masahiro

    2002-04-01

    Balance of the two types of T helper cells is one of the most important factors for regulation of the immune system. This study examines the production of interleukin (IL)-4, -6, -10, -12, and interferon-gamma by peripheral blood mononuclear cells stimulated with phytohemagglutinin or Staphylococcus aureus. Sixty-one patients, including 25 with gastric and 39 with colorectal cancer, and 39 normal volunteers were entered. The production of IL-12 decreased significantly with advancing disease and was lowest in the patients with distant metastases and cachexia. Compared with normal donors, the production of interferon-gamma decreased in all categories of patients, with no difference among patient groups. Levels of Th2 cytokines, such as IL-4, IL-6, and IL-10, also showed no difference among patient groups. However, production of all these cytokines had increased by 2.5 months after sequential testing in the same cachectic patients. The authors' findings indicate that the induction of Th1 cells seems to be suppressed at a relatively early stage of disease, whereas that of Th2 cells seems to increase in the terminal stage.

  8. A Decrease of Histone Deacetylase 6 Expression Caused by Helicobacter Pylori Infection is Associated with Oncogenic Transformation in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Qing He

    2017-07-01

    Full Text Available Background: Histone deacetylase 6 (HDAC6 plays a role in the progression of many tumors. However, the relationship between the level of HDAC6 expression and gastric tumorigenesis is still unclear. Here, we illustrate the potential correlation between Helicobacter pylori (HP infection and the variation of HDAC6 expression in different gastric lesions, as well as the clinical significance of HDAC6 expression in gastric cancer (GC patients. Materials and Methods: Between 2011 and 2016, 364 patients with different types of gastric lesions were enrolled in Baotou City Central Hospital. Immunostaining of HDAC6 expression and HP infection were performed in the following cohort including 21 normal tissues (Normal; 40 samples with chronic superficial gastritis (CSG; 106 with chronic atrophic gastritis (CAG; 94 with intestinal metaplasia (IM; 64 with dysplasia (DYS and 39 with gastric cancer (GC. Survival analysis was performed in another 80 GC patients using the Kaplan-Meier method and multivariate Cox regression analyses. The level of HDAC6 expression was determined by Real-time PCR, Western blotting and IHC staining in gastric cell lines and tissues. Furthermore, the correlation between HDAC6 expression and clinicopathological features and prognosis was analyzed in the GC cohort. HP strains were lavaged into Kunming mice to investigate the effects of HP infection on the expression of different HDAC members in this mouse model. Results: Higher levels of HDAC6 expression were detected in normal and premalignant lesions than in the GC tissues (p<0.01, and decreased HDAC6 expression was associated with HP infection and TNM stage (p<0.01 and p=0.048, respectively. Multivariate analysis revealed that HDAC6 expression was an independent predictor of the outcome of GC patients (p=0.04. HP mediated HDAC6 expression in the cell lines and KM mice. HP infection could promote HDAC1 and HDAC4 expression as determined by Western blotting. Conclusions: HDAC6 is a

  9. Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Blanca L Valle

    Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

  10. Decreased risk of surgery for small bowel obstruction after laparoscopic colon cancer surgery compared with open surgery

    DEFF Research Database (Denmark)

    Jensen, Kristian Kiim; Andersen, Peter; Erichsen, Rune

    2016-01-01

    cancer resection. METHODS: This was a nationwide cohort study of patients undergoing elective colonic cancer resection with primary anastomosis in Denmark between 2001 and 2008. All included patients were operated with curative intent. Patients were identified in the Danish Colorectal Cancer Group....... The HR for mortality after colonic resection was 2.54 (CI 1.91 to 3.38, P ... surgery. Further, subsequent SBO surgery was associated with increased mortality after colonic cancer resection....

  11. Decreased expression of the ATM gene linked to poor prognosis for gastric cancer of different nationalities in Xinjiang.

    Science.gov (United States)

    Han, Mei; Ma, Lanying; Qu, Yanli; Tang, Yong

    2017-08-01

    To explore the clinicopathological significance of ATM gene in the occurrence and prognosis of gastric cancer (GC) from different nationalities in Xinjiang. The expression of ATM in 385 patients with GC (including 98 Uygurs, 231 Hans and 56 Kazaks) and its corresponding adjacent tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay to, analyze its correlations with clinicopathological features and prognosis of GC. The ATM expression in GC tissues was significantly decreased when compared to that in adjacent normal tissues of Uygur, Han and Kazak patients in Xinjiang, while Uygurs and Kazaks were much lower than Hans in the ATM expression of GC tissues (all PATM-negative tumors had a markedly lower survival rate than patients in Hans (P=0.028), and GC patients with ATM negative expression presented more unfavorable overall survival rate than those with positive expression among the three different nationalities (all PATM expression, TNM staging, depth of invasion, and lymph node metastasis were independent factors affecting the prognosis of GC patients in Xinjiang (all PATM was downregulated in GC patients in Xinjiang, especially for Uygurs and Kazaks, which suggested ATM to be an independent indicator of prognosis for GC therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia

    International Nuclear Information System (INIS)

    Castelli, Joel; Simon, Antoine; Louvel, Guillaume; Henry, Olivier; Chajon, Enrique; Nassef, Mohamed; Haigron, Pascal; Cazoulat, Guillaume; Ospina, Juan David; Jegoux, Franck; Benezery, Karen; Crevoisier, Renaud de

    2015-01-01

    Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a “standard” IMRT (IMRT std ); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRT std ) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRT std and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Compared to the initial planning, a PG overdose was observed during IMRT std for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p < 0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p < 0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p < 0.001). During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk

  13. Investigation of Pitch and Jaw Width to Decrease Delivery Time of Helical Tomotherapy Treatments for Head and Neck Cancer

    International Nuclear Information System (INIS)

    Moldovan, Monica; Fontenot, Jonas D.; Gibbons, John P.; Lee, Tae Kyu; Rosen, Isaac I.; Fields, Robert S.; Hogstrom, Kenneth R.

    2011-01-01

    Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 ± 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 ± 0.6 min vs. 9.5 ± 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units.

  14. Interleukin-2 therapy for human cancer.

    Science.gov (United States)

    van Hoesel, Q G

    1990-01-01

    The concept of immunotherapy is evolving from nonspecific, haphazard stimulation of the immune apparatus to more specific and controlled manipulation of the immune system. IL-2 gives the opportunity to exert influence on the cellular immune system. Why LAK cells are able to lyse tumor cells and leave normal cells intact is not known. How LAK cells behave after reinfusion is not known; are they able to migrate to tumor sites? Can improvements be made in scheduling in order to decrease toxicity and to enhance efficacy? But first of all, the question arises whether the tremendous efforts required by adoptive transfer, in terms of toxicity, logistics, and money, are outweighed by the therapeutic results. For clinical practice inside the frontier of oncology, continuous infusion of IL-2 at an intermediate dose is a quite attractive option in finding a balance between efforts and results.

  15. Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Hao Tang

    2015-03-01

    Full Text Available Both BRCA1 and Beclin 1 (BECN1 are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA (n = 1067 and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC (n = 1992. In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly triple-negative breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1 was associated with poor prognosis, and BECN1 (but not BRCA1 expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.

  16. Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl- current associated with neuroendocrine differentiation of prostate cancer epithelial cells.

    NARCIS (Netherlands)

    Lemonnier, L.; Lazarenko, R.; Shuba, Y.; Thebault, S.C.; Roudbaraki, M.; Lepage, G.; Prevarskaya, N.; Skryma, R.

    2005-01-01

    Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. Here we report for the first time on alterations in regulatory volume decrease (RVD) and its key determinant,

  17. No decrease in the rate of early or missed colorectal cancers after colonoscopy with polypectomy over a 10-year period : A population-based analysis

    NARCIS (Netherlands)

    Pullens, Hendrikus J M; Leenders, Max; Schipper, Marguerite E I; van Oijen, Martijn G H; Siersema, Peter D.

    2015-01-01

    Background & Aims: It is not clear whether the incidence of missed or early colorectal cancers (CRCs) has decreased over time. We compared the rates of missed or early CRC after polypectomy between 1996 and 2006, and aimed to identify risk factors for these. Methods: We performed a population-based,

  18. No decrease in the rate of early or missed colorectal cancers after colonoscopy with polypectomy over a 10-year period: a population-based analysis

    NARCIS (Netherlands)

    Pullens, H.J.; Leenders, M.; Schipper, M.E.; Oijen, M.G. van; Siersema, P.D.

    2015-01-01

    BACKGROUND & AIMS: It is not clear whether the incidence of missed or early colorectal cancers (CRCs) has decreased over time. We compared the rates of missed or early CRC after polypectomy between 1996 and 2006, and aimed to identify risk factors for these. METHODS: We performed a population-based,

  19. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

    2017-04-01

    The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB = 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent

  20. It is out of my hands: how deferring control to God can decrease quality of life for breast cancer patients.

    Science.gov (United States)

    McLaughlin, Bryan; Yoo, Woohyun; D'Angelo, Jonathan; Tsang, Stephanie; Shaw, Bret; Shah, Dhavan; Baker, Timothy; Gustafson, David

    2013-12-01

    This paper seeks to contribute to the understanding of how and why religion affects psychosocial health outcomes. We propose a theoretical model predicting that when women with breast cancer defer control to God they will experience fewer breast cancer related concerns. Deferring control to God, however, should also reduce the likelihood that they take a proactive coping approach, which will be exacerbated by lowered breast cancer concerns. We therefore predict that this passive coping style will ultimately result in lower levels of quality of life. Data were collected as part of a randomized clinical trial funded by the National Cancer Institute. A total of 192 women with breast cancer participated in a computer-mediated social support group. Deferring control to God statements were captured by using computer-aided content analysis of discussion posts. Psychosocial outcomes were measured using longitudinal survey data. Analysis was performed using structural equation modeling. The results of our analysis largely confirm our mediation model for which we find significant model fit. As predicted, deferring control to God leads to lower levels of breast cancer concerns but also to more passive coping styles. Ultimately, deferring control to God can lead to lower levels of quality of life. Our study demonstrates how and why religious coping can lead to both positive and negative psychosocial health outcomes. Health care practitioners should encourage patients who are relying on religion to keep their end of the bargain and maintain an active coping style. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study

    Science.gov (United States)

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Mayo, Juan C.

    2017-01-01

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type. PMID:28933733

  2. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study.

    Science.gov (United States)

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Rodriguez-Gonzalez, Pablo; Garcia-Alonso, Jose I; Mayo, Juan C; Sainz, Rosa M

    2017-07-26

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/ SLC2A ) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13 C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13 C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13 C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13 C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.

  3. Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro.

    Science.gov (United States)

    Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

    2013-06-01

    Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P cancer may confer a growth advantage for neoplastic cells. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  4. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.

    Science.gov (United States)

    Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin

    2011-05-01

    Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.

  5. Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival

    Directory of Open Access Journals (Sweden)

    Gergana Metodieva

    2016-06-01

    Full Text Available SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies.

  6. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

    Science.gov (United States)

    Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

    2016-12-01

    Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. ClinicalTrials.gov identifier: NCT00465595. © The Author(s) 2016.

  7. Perioperative synbiotics administration decreases postoperative infections in patients with colorectal cancer: a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    ALINE TABORDA FLESCH

    Full Text Available ABSTRACT Objective: to evaluate the effect of perioperative administration of symbiotics on the incidence of surgical wound infection in patients undergoing surgery for colorectal cancer. Methods: We conducted a randomized clinical trial with colorectal cancer patients undergoing elective surgery, randomly assigned to receive symbiotics or placebo for five days prior to the surgical procedure and for 14 days after surgery. We studied 91 patients, 49 in the symbiotics group (Lactobacillus acidophilus 108 to 109 CFU, Lactobacillus rhamnosus 108 to 109 CFU, Lactobacillus casei 108 to 109 CFU, Bifi dobacterium 108 to 109 CFU and fructo-oligosaccharide (FOS 6g and 42 in the placebo group. Results: surgical site infection occurred in one (2% patient in the symbiotics group and in nine (21.4% patients in the control group (p=0.002. There were three cases of intraabdominal abscess and four cases of pneumonia in the control group, whereas we observed no infections in patients receiving symbiotics (p=0.001. Conclusion: the perioperative administration of symbiotics significantly reduced postoperative infection rates in patients with colorectal cancer. Additional studies are needed to confirm the role of symbiotics in the surgical treatment of colorectal cancer.

  8. Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype

    Directory of Open Access Journals (Sweden)

    Watanabe Mika

    2010-10-01

    Full Text Available Abstract Background Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding and further investigate combined antitumor effects of dasatinib with cytotoxic agents, a panel of breast cancer cell lines of various subtypes was treated with dasatinib and/or chemotherapeutic agents. Methods Seven human breast cancer cell lines were treated with dasatinib and/or seven chemotherapeutic agents. Effects of the treatments on c-Src activation, cell growth, cell cycle, apoptosis and the proportion of aldehyde dehydrogenase (ALDH 1-positive cells were examined. Results The 50%-growth inhibitory concentrations (IC50s of dasatinib were much lower in two basal B cell lines than those in the other cell lines. The IC50s of chemotherapeutic agents were not substantially different among the cell lines. Dasatinib enhanced antitumor activity of etoposide in the basal B cell lines. Dasatinib induced a G1-S blockade with a slight apoptosis, and a combined treatment of dasatinib with etoposide also induced a G1-S blockade in the basal B cell lines. Dasatinib decreased the expression levels of phosphorylated Src in all cell lines. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in the basal B cell lines but not in the other cell lines. Conclusions The present study indicates that dasatinib preferentially inhibits the growth of breast cancer cells of the basal B subtype associated with a significant loss of putative cancer stem cell population. A combined use of dasatinib with etoposide additively inhibits their growth. Further studies targeting breast cancers of the basal B subtype using dasatinib with cytotoxic agents are warranted.

  9. Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential.

    Science.gov (United States)

    Ni, Chien-Hang; Yu, Chun-Shu; Lu, Hsu-Feng; Yang, Jai-Sing; Huang, Hui-Ying; Chen, Po-Yuan; Wu, Shin-Hwar; Ip, Siu-Wan; Chiang, Su-Yin; Lin, Jaung-Geng; Chung, Jing-Gung

    2014-05-01

    Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone compounds, and it has been shown to induce cell death in different types of cancer cells. The effects of chrysophanol on human lung cancer cell death have not been well studied. The purpose of this study is to examine chrysophanol-induced cytotoxic effects and also to investigate such influences that involved apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results indicated that chrysophanol decreased the viable A549 cells in a dose- and time-dependent manner. Chrysophanol also promoted the release of reactive oxygen species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane potential (ΔΨm ) and adenosine triphosphate in A549 cells. Furthermore, chrysophanol triggered DNA damage by using Comet assay and DAPI staining. Importantly, chrysophanol only stimulated the cytocheome c release, but it did not activate other apoptosis-associated protein levels including caspase-3, caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 740-749, 2014. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  10. Publikuarmastus hotellitubades / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2011-01-01

    NU Performance Festival IV: Külalislahkusest / On Hospitality Tallinnas Viru hotellis 7.-10.11. 2011, kuraatorid Silke Bake ja Peter Stamer (Saksamaa). Heine Røsdal Avdali ja Yukiko Shinozaki lavastusest "Field Works - hotel". Kümne riigi kunstniku etendatavast performance'ist "The Love Piece"

  11. Plaadid / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2006-01-01

    Uutest heliplaatidest Arctic Monkeys "Whatever People Say I Am", Dreamphish "Happiness Happens", Viktoria Tolstoy "My Sweadish Heart", Ursula Rucker "Ma'at Mama", Sissel "Into Paradise", Blacky "See on me meeltele", "Alternating Current 2"

  12. Plaadid / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2007-01-01

    Uutest heliplaatidest The Shins "Wincing The Night Away", A Am Kloot "BBC Radio 1Peel Sessions", Tim Finn "Imaginary Kingdom", Kling Klang "The Esthetik of destruction", "25 Avenue le bar plaza Athenee Paris", Paul Weller "Hit Parade"

  13. Plaadid / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2008-01-01

    Uutest heliplaatidest Lightspeed Champion "Falling Off The Lavender Bridge", Sebastian Bach "Angel Down", Juanes "La Vida...", raadi Maria "Siin Tallinn", Erich Krieger "Live", Rock Hotel "Rock Hotel Rock Cafes"

  14. Plaadid / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2006-01-01

    Uutest plaatidest The Scaramangas "All Is Good Now", Jim Weider "Percolator", Think Of One "Tarfico", Primal Scream "Riot City Blues", Wochtzchee "Diktüoneemikalt", The Feeling "Tweöve Stops And Home", Sunblock "I'll Be Ready",

  15. TERT-CLPTM1L Rs401681 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Jun Yin

    Full Text Available BACKGROUND: Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis. METHODS: We conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR method. RESULTS: When the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.58-0.94, p = 0.012; the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.59-0.93, P = 0.009. The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (A polymorphism and ESCC risk was observed. CONCLUSION: TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.

  16. Naringenin decreases invasiveness and metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Changjie Lou

    Full Text Available Epithelial to mesenchymal transition (EMT promotes cellular motility, invasiveness and metastasis during embryonic development and tumorigenesis. Transforming growth factor-β (TGF-β signaling pathway is a key regulator of EMT. A lot of evidences suggest that this process is Smad3-dependent. Herein we showed that exposure of aspc-1 and panc-1 pancreatic cancer cells to TGF-β1 resulted in characteristic morphological alterations of EMT, and enhancement of cell motility and gemcitabine (Gem resistance along with an up-regulation of EMT markers genes such as vimentin, N-cadherin, MMP2 and MMP9. Naringenin (Nar down-regulated EMT markers expression in both mRNA and protein levels by inhibiting TGF-β1/Smad3 signal pathway in the pancreatic cancer cells. Consequently, Nar suppressed the cells migration and invasion and reversed their resistance to Gem.

  17. Decrease social inequalities return-to-work: development and design of a randomised controlled trial among women with breast cancer.

    Science.gov (United States)

    Vidor, Clémence; Leroyer, Ariane; Christophe, Véronique; Seillier, Mélanie; Foncel, Jérome; Van de Maële, Justine; Bonneterre, Jacques; Fantoni, Sophie

    2014-04-17

    Despite the improvement in the care management, women cancer patients who are still in employment find themselves for the most part obliged to stop working while they are having treatment. Their return-to-work probability is impacted by numerous psychosocial factors. The objective is to describe the development and the content of an intervention aimed to facilitate the return to work of female breast cancer patients and in particular the women in the most precarious situations through early active individualised psychosocial support (APAPI). The intervention proposed is made up of 4 interviews with a psychologist at the hospital, distributed over the year according to the diagnosis and conducted on the same day as a conventional follow-up consultation, then a consultation with a specialist job retention physician. We expect, in the first instance, that this intervention will reduce the social inequalities of the return-to-work rate at 12 months. The EPICES score will enable the population to be broken down according to the level of social precariousness. The other expected results are the reduction of the social inequalities in the quality of the return to work at 18 and 24 months and the disparities between the individual and collective resources of the patients. This intervention is assessed in the context of a controlled and randomised multi-centre study. The patients eligible are women aged between 18 and 55 years with a unilateral breast cancer with local extension exclusively, having received surgery followed by adjuvant chemotherapy, in employment at the time of the diagnosis and dealt with by one of the 2 investigating centres. It is essential to assess this type of intervention before envisaging its generalisation. The study set in place will enable us to measure the impact of this intervention aiming to facilitate the return to work of breast cancer patients, in particular for those who suffer from social fragility, compared with the standard care.

  18. Atlas-Based Segmentation Improves Consistency and Decreases Time Required for Contouring Postoperative Endometrial Cancer Nodal Volumes

    International Nuclear Information System (INIS)

    Young, Amy V.; Wortham, Angela; Wernick, Iddo; Evans, Andrew; Ennis, Ronald D.

    2011-01-01

    Purpose: Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized that atlas-based segmentation ('autocontouring') would lead to time savings and more consistent contours among physicians. Methods and Materials: A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical target volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient. Results: For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean ± standard deviation of 32 ± 9 vs. 23 ± 7 minutes, respectively (p = .000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30 ± 3 vs. 21 ± 5 min (p = .003), 39 ± 12 vs. 30 ± 5 min (p = .055), and 29 ± 5 vs. 20 ± 5 min (p = .0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p = .038). Conclusion: The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the target volume.

  19. Fatigue and gene expression in human leukocytes: Increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue

    Science.gov (United States)

    Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Arevalo, Jesusa M.G.; Cole, Steve W.

    2013-01-01

    Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n = 11) and non-fatigued controls (n = 10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p < .05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. PMID:20854893

  20. Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

    International Nuclear Information System (INIS)

    Oh, Somi; You, Eunae; Ko, Panseon; Jeong, Jangho; Keum, Seula; Rhee, Sangmyung

    2017-01-01

    Microtubules are required for diverse cellular processes, and abnormal regulation of microtubule dynamics is closely associated with severe diseases including malignant tumors. In this study, we report that α-tubulin N-acetyltransferase (αTAT1), a regulator of α-tubulin acetylation, is required for colon cancer proliferation and invasion via regulation of Wnt1 and its downstream genes expression. Public transcriptome analysis showed that expression of ATAT1 is specifically upregulated in colon cancer tissue. A knockout (KO) of ATAT1 in the HCT116 colon cancer cell line, using the CRISPR/Cas9 system showed profound inhibition of proliferative and invasive activities of these cancer cells. Overexpression of αTAT1 or the acetyl-mimic K40Q α-tubulin mutant in αTAT1 KO cells restored the invasiveness, indicating that microtubule acetylation induced by αTAT1 is critical for HCT116 cell invasion. Analysis of colon cancer-related gene expression in αTAT1 KO cells revealed that the loss of αTAT1 decreased the expression of WNT1. Mechanistically, abrogation of tubulin acetylation by αTAT1 knockout inhibited localization of β-catenin to the plasma membrane and nucleus, thereby resulting in the downregulation of Wnt1 and of its downstream genes including CCND1, MMP-2, and MMP-9. These results suggest that αTAT1-mediated Wnt1 expression via microtubule acetylation is important for colon cancer progression. - Highlights: • Ablation of αTAT1 inhibits HCT116 colon cancer cell invasion. • αTAT1/acetylated microtubules regulate expression of Wnt1/β-catenin target genes. • Acetylated microtubules regulate cellular localization of β-catenin. • Loss of αTAT1 prevents Wnt1 from inducing β-catenin-dependent and -independent pathways.

  1. Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

    Directory of Open Access Journals (Sweden)

    Junjie Chen

    2016-11-01

    Full Text Available Abstract Background The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC is not fully elucidated. Methods The expressions of miR-193a (miR-193a-5p in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively. Results The expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1-induced epithelial-to-mesenchymal transition (EMT in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice. Conclusion Collectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC.

  2. The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: Reduced cervical cancer risk and decreased yield of precancer per screen.

    Science.gov (United States)

    Silver, Michelle I; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Gage, Julia C; Wentzensen, Nicolas; Lorey, Thomas; Kinney, Walter K; Castle, Philip E

    2016-12-01

    The objective of cervical screening is to detect and treat precancer to prevent cervical cancer mortality and morbidity while minimizing overtreatment of benign human papillomavirus (HPV) infections and related minor abnormalities. HPV/cytology cotesting at extended 5-year intervals currently is a recommended screening strategy in the United States, but the interval extension is controversial. In the current study, the authors examined the impact of a decade of an alternative, 3-year cotesting, on rates of precancer and cancer at Kaiser Permanente Northern California. The effect on screening efficiency, defined as numbers of cotests/colposcopy visits needed to detect a precancer, also was considered. Two cohorts were defined. The "open cohort" included all women screened at least once during the study period; > 1 million cotests were performed. In a fixed "long-term screening cohort," the authors considered the cumulative impact of repeated screening at 3-year intervals by restricting the cohort to women first cotested in 2003 through 2004 (ie, no women entering screening later were added to this group). Detection of cervical intraepithelial neoplasia 3/adenocarcinoma in situ (CIN3/AIS) increased in the open cohort (2004-2006: 82.0/100,000 women screened; 2007-2009: 140.6/100,000 women screened; and 2010-2012: 126.0/100,000 women screened); cancer diagnoses were unchanged. In the long-term screening cohort, the detection of CIN3/AIS increased and then decreased to the original level (2004-2006: 80.5/100,000 women screened; 2007-2009: 118.6/100,000 women screened; and 2010-2012: 84.9./100,000 women screened). The number of cancer diagnoses was found to decrease. When viewed in terms of screening efficiency, the number of colposcopies performed to detect a single case of CIN3/AIS increased in the cohort with repeat screening. Repeated cotesting at a 3-year interval eventually lowers population rates of precancer and cancer. However, a greater number of

  3. Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1.

    Directory of Open Access Journals (Sweden)

    Hui Li

    2009-05-01

    Full Text Available Ovarian cancer G protein-coupled receptor 1 (OGR1 has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK activation and nitric oxide (NO production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases.

  4. Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers.

    Science.gov (United States)

    Drzewiecka, Hanna; Gałęcki, Bartłomiej; Jarmołowska-Jurczyszyn, Donata; Kluk, Andrzej; Dyszkiewicz, Wojciech; Jagodziński, Paweł P

    2016-09-01

    Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. We found significantly decreased levels of CTGF mRNA and protein (both p cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development.

  5. The population impact of HPV/cytology cervical cotesting at 3-year intervals: reduced cervical cancer risk and decreased yield of precancer per screen

    Science.gov (United States)

    Silver, Michelle I.; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy; Gage, Julia C.; Wentzensen, Nicolas; Lorey, Thomas; Kinney, Walter; Castle, Philip E.

    2016-01-01

    Background Cervical screening aims to detect and treat precancer to prevent cervical cancer mortality and morbidity, while minimizing overtreatment of benign human papillomavirus (HPV) infections and related minor abnormalities. HPV/cytology cotesting at extended 5-year intervals is now a recommended screening strategy in the US, but the interval extension is controversial. We studied the impact of a decade of an alternative, 3-year cotesting, on rates of precancer and cancer at Kaiser Permanente Northern California. We also considered the effect on screening efficiency, defined as numbers of cotests/colposcopy visits needed to detect a precancer. Methods Two cohorts were defined. The “open cohort” included all women screened at least once during the study period; >1 million cotests were performed. In a fixed “long-term screening cohort”, we considered the cumulative impact of repeated screening at 3-year intervals by restricting to women first cotested in 2003–4 (i.e., no women entering screening later were added to this group). Results Detection of CIN3/AIS increased in the open cohort (2004–6, 82.0/100,000 women screened; 2007–9, 140.6/100,000; and 2010–12, 126.0/100,000); cancer diagnoses were unchanged. In the long-term screening cohort, detection of CIN3/AIS increased then decreased to the original level (2004–6, 80.5/100,000; 2007–9, 118.6/100,000; and 2010–2, 84.9/100,000). Cancer diagnoses decreased. Seen in terms of screening efficiency, the number of colposcopies performed todetect a single CIN3/AIS increased in the cohort with repeat screening. Conclusion Repeated cotesting at a 3-year interval eventually lowers population rates of precancer and cancer; however, a greater number of colposcopies is required to detect a single precancer. PMID:27657992

  6. Brazilian Red Propolis Induces Apoptosis-Like Cell Death and Decreases Migration Potential in Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Karine Rech Begnini

    2014-01-01

    Full Text Available Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL. Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

  7. Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

    Science.gov (United States)

    Hendriks, B S; Griffiths, G J; Benson, R; Kenyon, D; Lazzara, M; Swinton, J; Beck, S; Hickinson, M; Beusmans, J M; Lauffenburger, D; de Graaf, D

    2006-11-01

    A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer have been found to carry mutations in ErbB1. Previously, it has been observed that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis. Using a computational model of ErbB1 trafficking and signalling, it is found that a deficiency in ErbB1 internalisation is sufficient to explain the observed signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with and without ErbB1 mutations exhibit markedly slower internalisation rates than gefitinib-insensitive cell lines. Moreover, the computational model demonstrates that reduced ErbB1 internalisation rates are mechanistically linked to upregulated AKT signalling. Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation.

  8. Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Kun

    2012-10-01

    Full Text Available Abstract Background MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC, and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction. Methods Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs, using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS was also investigated. Results Let-7i was significantly down-regulated in most tumor tissues (78/86: 91% compared with paired NATs (P P =0.024 independently of other clinicopathological factors, including tumor node metastasis (TNM stage (HR = 3.226, P = 0.013, depth of infiltration (HR = 4.167, P P = 0.037. Conclusions These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.

  9. Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells.

    Science.gov (United States)

    Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Toro, Lenka; Durinikova, Erika; Tyciakova, Silvia; Demkova, Lucia; Gursky, Jan; Kucerova, Lucia

    2016-01-12

    Cells of the tumor microenvironment are recognized as important determinants of the tumor biology. The adjacent non-malignant cells can regulate drug responses of the cancer cells by secreted paracrine factors and direct interactions with tumor cells. Human mesenchymal stromal cells (MSC) actively contribute to tumor microenvironment. Here we focused on their response to chemotherapy as during the treatment these cells become affected. We have shown that the secretory phenotype and behavior of mesenchymal stromal cells influenced by cisplatin differs from the naïve MSC. MSC were more resistant to the concentrations of cisplatin, which was cytotoxic for tumor cells. They did not undergo apoptosis, but a part of MSC population underwent senescence. However, MSC pretreatment with cisplatin led to changes in phosphorylation profiles of many kinases and also increased secretion of IL-6 and IL-8 cytokines. These changes in cytokine and phosphorylation profile of MSC led to increased chemoresistance and stemness of breast cancer cells. Taken together here we suggest that the exposure of the chemoresistant cells in the tumor microenvironment leads to substantial alterations and might lead to promotion of acquired microenvironment-mediated chemoresistance and stemness.

  10. Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells.

    Science.gov (United States)

    Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Martins Rodrigues, Fernanda; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Roesch-Ely, Mariana; Moura, Sidnei; Padilha, Francine F; Collares, Tiago; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

    2014-01-01

    Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

  11. Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population

    DEFF Research Database (Denmark)

    Johansen, J.S.; Bojesen, S.E.; Mylin, A.K.

    2009-01-01

    ,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according...... to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%. RESULTS: The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P ....0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P any cancer event and YKL-40 category 91% to 100% had...

  12. Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

    Science.gov (United States)

    Ho, Gwendolyn; Wun, Ted; Muffly, Lori; Li, Qian; Brunson, Ann; Rosenberg, Aaron S; Jonas, Brian A; Keegan, Theresa H M

    2018-05-01

    To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society. © 2018 American Cancer Society.

  13. [Impact of an educational program for parents of children with cancer on the increased knowledge of their children's disease and the decrease in anxiety].

    Science.gov (United States)

    de la Maza L, Verónica; Fernández C, Maria; Concha R, Lorena; Santolaya D, María Elena; Villarroel C, Milena; Castro C, Magdalena; Torres T, Juan Pablo

    2015-01-01

    To determine the impact of an educational program provided by a nurse to parents of children with cancer to improve the level of knowledge of the disease and to decrease the levels of anxiety. A prospective randomized study was conducted on parents of children recently diagnosed with cancer and treated in the Hospital Luis Calvo Mackenna. After informed consent, parents were randomized in two groups: one receiving the educational program and another without intervention. Both groups completed a questionnaire on social risk, and three tests to assess the levels of knowledge and anxiety. A total of 96 parents were enrolled (July 2010-November 2011). When comparing the number of correct responses on day 10, and day 90 after the intervention, a significant increase was observed in the level of parental knowledge in the group that received the educational program (P<.0001). No significant differences were observed in the levels of anxiety (P=.06) between both groups. An educational program provided by nurses to parents of children recently diagnosed with cancer, increased the knowledge of their children's disease. However there was no effect on the levels of anxiety. A feasible educational intervention is proposed that could be implemented at other cancer centers for children. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. GPR55 receptor antagonist decreases glycolytic activity in PANC-1 pancreatic cancer cell line and tumor xenografts.

    Science.gov (United States)

    Bernier, Michel; Catazaro, Jonathan; Singh, Nagendra S; Wnorowski, Artur; Boguszewska-Czubara, Anna; Jozwiak, Krzysztof; Powers, Robert; Wainer, Irving W

    2017-11-15

    The Warburg effect is a predominant metabolic pathway in cancer cells characterized by enhanced glucose uptake and its conversion to l-lactate and is associated with upregulated expression of HIF-1α and activation of the EGFR-MEK-ERK, Wnt-β-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1-naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55 receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and tumors. Global NMR metabolomics was used to elucidate differences in the metabolome between untreated and (R,R')-MNF-treated cells. LC/MS analysis was used to quantify intracellular concentrations of β-hydroxybutyrate, carnitine, and l-lactate. Changes in target protein expression were determined by Western blot analysis. Data was also obtained from mouse PANC-1 tumor xenografts after administration of (R,R')-MNF. Metabolomics data indicate that (R,R')-MNF altered fatty acid metabolism, energy metabolism, and amino acid metabolism and increased intracellular concentrations of β-hydroxybutyrate and carnitine while reducing l-lactate content. The cellular content of phosphoinositide-dependent kinase-1 and hexokinase 2 was reduced consistent with diminished PI3K-AKT signaling and glucose metabolism. The presence of the GLUT8 transporter was established and found to be attenuated by (R,R')-MNF. Mice treated with (R,R')-MNF had significant accumulation of l-lactate in tumor tissue relative to vehicle-treated mice, together with reduced levels of the selective l-lactate transporter MCT4. Lower intratumoral levels of EGFR, pyruvate kinase M2, β-catenin, hexokinase 2, and p-glycoprotein were also observed. The data suggest that (R,R')-MNF reduces glycolysis in PANC-1 cells and tumors through reduced expression and function at multiple controlling sites in the glycolytic pathway. © 2017 UICC.

  15. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  16. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    International Nuclear Information System (INIS)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

    2015-01-01

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  17. The 2-oxoglutarate analog 3-oxoglutarate decreases normoxic hypoxia-inducible factor-1α in cancer cells, induces cell death, and reduces tumor xenograft growth

    Directory of Open Access Journals (Sweden)

    Koivunen P

    2016-03-01

    Full Text Available Peppi Koivunen,1 Stuart M Fell,2,3 Wenyun Lu,4 Joshua D Rabinowitz,4 Andrew L Kung,5,6 Susanne Schlisio,2,7 1Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland; 2Ludwig Institute for Cancer Research Ltd, Stockholm, Sweden; 3Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; 4Department of Chemistry and Integrative Genomics, Princeton University, Princeton, NJ, 5Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 6Department of Pediatrics, Columbia University Medical Center, New York, NY, USA; 7Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden Abstract: The cellular response to hypoxia is primarily regulated by the hypoxia-inducible factors (HIFs. HIF-1α is also a major mediator of tumor physiology, and its abundance is correlated with therapeutic resistance in a broad range of cancers. Accumulation of HIF-1α under hypoxia is mainly controlled by the oxygen-sensing HIF prolyl 4-hydroxylases (EGLNs, also known as PHDs. Here, we identified a high level of normoxic HIF-1α protein in various cancer cell lines. EGLNs require oxygen and 2-oxoglutarate for enzymatic activity. We tested the ability of several cell-permeable 2-oxoglutarate analogs to regulate the abundance of HIF-1α protein. We identified 3-oxoglutarate as a potent regulator of HIF-1α in normoxic conditions. In contrast to 2-oxoglutarate, 3-oxoglutarate decreased the abundance of HIF-1α protein in several cancer cell lines in normoxia and diminished HIF-1α levels independent of EGLN enzymatic activity. Furthermore, we observed that 3-oxoglutarate was detrimental to cancer cell survival. We show that esterified 3-oxoglutarate, in combination with the cancer chemotherapeutic drug vincristine, induces apoptosis and inhibits tumor growth in vitro and in vivo. Our data

  18. p53 inactivation decreases dependence on estrogen/ERK signalling for proliferation but promotes EMT and susceptility to 3-bromopyruvate in ERα+ breast cancer MCF-7 cells.

    Science.gov (United States)

    Rieber, Manuel; Strasberg-Rieber, Mary

    2014-03-15

    Most breast cancers express the estrogen receptor alpha (ERα(+)), harbor wt TP53, depend on estrogen/ERK signalling for proliferation, and respond to anti-estrogens. However, concomittant activation of the epidermal growth factor receptor (EGFR)/MEK pathway promotes resistance by decreasing estrogen dependence. Previously, we showed that retroviral transduction of mutant p53 R175H into wt TP53 ERα(+) MCF-7 cells induces epidermal growth factor (EGF)-independent proliferation, activation of the EGF receptor (p-EGFR) and some characteristics of epithelial-mesenchymal transition (EMT). To investigate whether p53 inactivation augments ERα(+) cell proliferation in response to restrictive estradiol, chemical MEK inhibition or metabolic inhibitors. Introduction of mutant p53 R175H lowered expression of p53-dependent PUMA and p21WAF1, decreased E-cadherin and cytokeratin 18 associated with EMT, but increased the % of proliferating ERα(+)/Ki67 cells, diminishing estrogen dependence. These cells also exhibited higher proliferation in the presence of MEK-inhibitor UO126, reciprocally correlating with preferential susceptibility to the pyruvate analog 3-bromopyruvate (3-BrPA) without a comparable response to 2-deoxyglucose. p53 siRNA silencing by electroporation in wt TP53 MCF-7 cells also decreased estrogen dependence and response to MEK inhibition, while also conferring susceptibility to 3-BrPA. (a) ERα(+) breast cancer cells dysfunctional for TP53 which proliferate irrespective of low estrogen and chemical MEK inhibition are likely to increase metabolic consumption becoming increasingly susceptible to 3-BrPA; (b) targeting the pyruvate pathway may improve response to endocrine therapy in ERα(+) breast cancer with p53 dysfunction. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Appetite - decreased

    Science.gov (United States)

    Loss of appetite; Decreased appetite; Anorexia ... Any illness can reduce appetite. If the illness is treatable, the appetite should return when the condition is cured. Loss of appetite can cause weight ...

  20. Interleukin 1B rs16944 G>A polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population.

    Science.gov (United States)

    Zheng, Liang; Yin, Jun; Wang, Liming; Wang, Xu; Shi, Yijun; Shao, Aizhong; Tang, Weifeng; Ding, Guowen; Liu, Chao; Chen, Suocheng; Gu, Haiyong

    2013-10-01

    Esophageal cancer is the sixth leading cause of cancer-associated deaths worldwide and represents a particularly aggressive type of cancer. Genetic polymorphisms may partly explain individual differences in esophageal cancer susceptibility. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin 1 (IL1A and IL1B), IL1f7, IL3 and IL7Ra genes on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit. When the IL1B rs16944 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly decreased risk of ESCC (GA vs. GG: adjusted OR=0.69, 95% CI=0.49-0.99, p=0.041). However, there were no significant associations between the other five SNPs and ESCC risk. Stratified analyses indicated no significantly different risks of ESCC associated with the IL1B rs16944 G>A polymorphism according to sex, age, smoking status or alcohol consumption. IL3 rs2073506 G>A polymorphism was associated with an increased risk for ESCC higher tumor, nodal, and metastatic (TNM) stages. These findings indicated that the functional IL1B rs16944 G>A polymorphism might contribute to ESCC susceptibility. IL3 rs2073506 G>A polymorphism was associated with an increased risk for ESCC higher TNM stages. However, the results were based on a limited sample size and larger well-designed studies are warranted to confirm these initial findings. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  1. Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia.

    Science.gov (United States)

    Castelli, Joel; Simon, Antoine; Louvel, Guillaume; Henry, Olivier; Chajon, Enrique; Nassef, Mohamed; Haigron, Pascal; Cazoulat, Guillaume; Ospina, Juan David; Jegoux, Franck; Benezery, Karen; de Crevoisier, Renaud

    2015-01-09

    Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (pxerostomia by 11% (pxerostomia risk.

  2. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Hung, Chein-Hui [Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Puizi City, Chiayi 613, Taiwan, ROC (China); Chang, Nai Wen [Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, ROC (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China)

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  3. Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

    Science.gov (United States)

    De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

    2018-07-01

    To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P PSA returned to normal values (PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

  4. Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16.

    Science.gov (United States)

    Yang, Hua; Yao, Jun; Yin, Jiangpin; Wei, Xuan

    2016-05-01

    The leucine-rich repeats and immunoglobulin-like domains (LRIG) are used as tumor suppressors in clinical applications. Although the LRIG has been identified to manipulate the cell proliferation via various oncogenic receptor tyrosine kinases in diverse cancers, its role in multidrug resistance needs to be further elucidated, especially in human ovarian cancer. We herein established that the etoposide (VP16)-resistant SKOV3 human ovarian cancer cell clones (SKOV3/VP16 cells) and mRNA expression of LRIG1 were significantly reduced by the treatment of VP16 in a concentration-dependent manner. Moreover, downregulated LRIG1 in SKOV3 could enhance the colony formation and resist the inhibition of proliferation by VP16, leading to the elevated expression of Bcl-2 and decreased apoptosis of SKOV3. Interestingly, our results uncovered that the multidrug resistance-associated protein 1 (MRP-1) was upregulated for the chemoresistance of VP16. To overcome the chemoresistance of SKOV3, SKOV3/VP16 was ectopically expressed of LRIG1. We found that the inhibition of VP16 on colony formation and proliferation was remarkably enhanced with increased apoptosis in SKOV3/VP16. Furthermore, the expression of MRP-1 and Bcl-2 was also inhibited, suggesting that the LRIG1could negatively control MRP-1 and the apoptosis to improve the sensitivity of VP16-related chemotherapy.

  5. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    International Nuclear Information System (INIS)

    Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

    2014-01-01

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools

  6. Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes.

    Science.gov (United States)

    Clare, Susan E; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z; Kim, J Julie; Khan, Seema A

    2016-05-23

    The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then identified a set of genes that overlap with human breast luteal-phase expressed genes and signify progesterone activity in both normal breast cells and breast cancer cell lines. TPA administration to T47D cells results in a 30 % decrease in cell number at 24 h, which is maintained over 72 h only in the presence of estradiol. Blockade of progesterone signaling by TPA for 24 h results in fewer cells in G2/M, attributable to decreased expression of genes that facilitate the G2/M transition. Gene expression data suggest that TPA affects several mechanisms that progesterone utilizes to control gene expression, including specific post-translational modifications, and nucleosomal organization and higher order chromatin structure, which regulate access of PR to its DNA binding sites. By comparing genes induced by the progestin R5020 in T47D cells with those increased in the luteal-phase normal breast, we have identified a set of genes that predict functional progesterone signaling in tissue. These data will facilitate an understanding of the ways in which drugs such as TPA may be utilized for the prevention, and possibly the therapy, of human breast cancer.

  7. Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes

    International Nuclear Information System (INIS)

    Clare, Susan E.; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z.; Kim, J. Julie; Khan, Seema A.

    2016-01-01

    The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then identified a set of genes that overlap with human breast luteal-phase expressed genes and signify progesterone activity in both normal breast cells and breast cancer cell lines. TPA administration to T47D cells results in a 30 % decrease in cell number at 24 h, which is maintained over 72 h only in the presence of estradiol. Blockade of progesterone signaling by TPA for 24 h results in fewer cells in G2/M, attributable to decreased expression of genes that facilitate the G2/M transition. Gene expression data suggest that TPA affects several mechanisms that progesterone utilizes to control gene expression, including specific post-translational modifications, and nucleosomal organization and higher order chromatin structure, which regulate access of PR to its DNA binding sites. By comparing genes induced by the progestin R5020 in T47D cells with those increased in the luteal-phase normal breast, we have identified a set of genes that predict functional progesterone signaling in tissue. These data will facilitate an understanding of the ways in which drugs such as TPA may be utilized for the prevention, and possibly the therapy, of human breast cancer. The online version of this article (doi:10.1186/s12885-016-2355-5) contains supplementary material, which is available to authorized users

  8. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  9. Older Age Predicts Decreased Metastasis and Prostate Cancer-Specific Death for Men Treated With Radiation Therapy: Meta-Analysis of Radiation Therapy Oncology Group Trials

    Energy Technology Data Exchange (ETDEWEB)

    Hamstra, Daniel A., E-mail: dhamm@umich.edu [University of Michigan, Ann Arbor, Michigan (United States); Bae, Kyounghwa [Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States); Pilepich, Miljenko V. [UCLA Medical Center, Los Angeles, California (United States); Hanks, Gerald E. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Grignon, David J. [Indiana University-Purdue University Indianapolis, Indiana (United States); McGowan, David G. [Cross Cancer Institute, Edmonton, Alberta (Canada); Roach, Mack [UCSF, San Francisco, California (United States); Lawton, Colleen [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lee, R. Jeffrey [Intermountain Medical Center, Salt Lake City, Utah (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, California (United States)

    2011-12-01

    Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age ({<=}70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p < 0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p < 0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.

  10. Piperlongumine decreases cell proliferation and the expression of cell cycle-associated proteins by inhibiting Akt pathway in human lung cancer cells.

    Science.gov (United States)

    Seok, Jin Sil; Jeong, Chang Hee; Petriello, Michael C; Seo, Han Geuk; Yoo, Hyunjin; Hong, Kwonho; Han, Sung Gu

    2018-01-01

    Piperlongumine (PL) is an alkaloid of a pepper plant found in Southeast Asia. PL is known to induce selective toxicity towards a variety of cancer cell types. To explore the possible anti-lung cancer effects of PL, A549 cells were treated with PL (0-40 μM) for 24 h. Alterations in the expression of cell cycle-associated proteins (cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6 and retinoblastoma (Rb)) and intracellular signaling molecules (extracellular signal receptor-activated kinase 1/2 (ERK1/2), Akt, p38 and nuclear factor-κB (NF-κB)) were examined in cells following treatment of PL using Western blot analysis. Results showed that proliferation of cells were significantly decreased by PL in a dose-dependent manner. Flow cytometry results demonstrated increased number of cells in G1 phase in PL (40 μM)-treated group. Reactive oxygen species was significantly increased in cells treated with PL at 20-40 μM. The expression of cyclin D1, CDK4, CDK6 and p-Rb were markedly decreased in cells treated with PL at 40 μM. Treatment of cells with PL suppressed phosphorylation of Akt but increased ERK1/2 phosphorylation. Treatment of PL significantly decreased nuclear translocation of NF-κB p65 in cells. These results suggest that PL possesses antiproliferative properties in A549 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Influence of operation and irradiation on cell-mediated immunity in patients with oral cancer

    International Nuclear Information System (INIS)

    Tominaga, Kazuhiro; Tominaga, Naohiro; Tokuhisa, Michio

    1995-01-01

    To evaluate the influence of operation and irradiation on cell-mediated immunity in patients with primary oral squamous cell carcinoma, several parameters, including NK activity, LAK activity, and IL-2 production, were selected. Twenty-two patients who underwent operation and/or irradiation from 1989 to 1993 were evaluated. Perioperatively, no significant change of immunologic parameters was observed except increased number of peripheral leukocytes at two weeks after operation. Immediately and/or one month after irradiation, significantly decreased numbers of leukocytes and lymphocytes as well as significantly depressed levels of blastoid transformation of lymphocytes, LAK activity, and IL-2 production were observed. By three months after irradiation, values of immunologic parameters returned to preirradiation values. The number of monocytes and level of NK activity showed little change after irradiation. (author)

  12. A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

    Science.gov (United States)

    Hui, Susanta K; Arentsen, Luke; Sueblinvong, Thanasak; Brown, Keenan; Bolan, Pat; Ghebre, Rahel G; Downs, Levi; Shanley, Ryan; Hansen, Karen E; Minenko, Anne G; Takhashi, Yutaka; Yagi, Masashi; Zhang, Yan; Geller, Melissa; Reynolds, Margaret; Lee, Chung K; Blaes, Anne H; Allen, Sharon; Zobel, Bruno Beomonte; Le, Chap; Froelich, Jerry; Rosen, Clifford; Yee, Douglas

    2015-04-01

    Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and

  13. Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium

    DEFF Research Database (Denmark)

    Henriksen, Rudi; Sørensen, Flemming Brandt; Orntoft, Torben Falck

    2011-01-01

    to be followed by a strongly increased risk of ovarian cysts. We performed the present study to reveal how FKBP65 is expressed in the ovary and in ovarian tumors and to see if this expression might be related to ovarian tumor development, a relationship we have found in colorectal cancer. Biopsies from...... prospectively collected samples from ovaries and benign, borderline, and invasive ovarian tumors were analyzed for expression of FKBP65 by immunohistochemistry. The expression was compared to survival and several clinicopathological parameters. FKBP65 is strongly expressed in ovarian epithelium and in benign...... ovarian tumor cells. In the ovary, a positive staining was also found in endothelial cells of blood vessels. In non-invasive and in invasive malignant tumor cells, a decreased staining was observed, which was not correlated to stage, histology, or survival. A significant inversed correlation to expression...

  14. Decreased expression of miR‑490‑3p in colorectal cancer predicts poor prognosis and promotes cell proliferation and invasion by targeting RAB14.

    Science.gov (United States)

    Wang, Bo; Yin, Mujun; Cheng, Cheng; Jiang, Hongpeng; Jiang, Kewei; Shen, Zhanlong; Ye, Yingjiang; Wang, Shan

    2018-06-19

    Growing evidence indicates a potential role for miR‑490‑3p in tumorigenesis. However, its function in colorectal carcinoma (CRC) remains undefined. In this study, miR‑490‑3p was markedly downregulated in fifty colorectal cancer tissue samples compared with the corresponding adjacent non‑cancerous specimens, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of miR‑490‑3p were closely associated with tumor differentiation and distant metastasis. In addition, both Kaplan-Meier and multivariate analyses indicated CRC patients with elevated miR‑490‑3p amounts had prolonged overall survival. Overexpression of miR‑490‑3p markedly reduced proliferation, colony formation and invasion in CRC cells by enhancing apoptosis and promoting G2/M phase arrest. Furthermore, ectopic expression of miR‑490‑3p resulted in decreased expression of RAB14, which was directly targeted by miR‑490‑3p, as shown by the dual-luciferase reporter gene assay. Finally, in a nude mouse model, miR‑490‑3p overexpression significantly suppressed the growth of CRC cells. The above results indicated that miR‑490‑3p might constitute a prognostic indicator and a novel molecular target for miRNA-based CRC therapy.

  15. Feeling powerless: Locus of control as a potential target for supportive care interventions to increase quality of life and decrease anxiety in ovarian cancer patients.

    Science.gov (United States)

    Brown, Alaina J; Sun, Charlotte C; Urbauer, Diana L; Bodurka, Diane C; Thaker, Premal H; Ramondetta, Lois M

    2015-08-01

    To evaluate if an individual's locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients. Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal or fallopian tube cancer. Patients completed the following surveys: Locus of Control Scale (LOC), Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment score (ESAS), Hospital Anxiety Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site of care, race, and partnership status as potential confounders. This study enrolled 104 patients from three separate treatment facilities. After adjusting for site, race and partnership status, higher levels of external LOC predicted decreased QOL (FACT-O) (pcontrol over her situation may improve QOL and overall mental well-being. Copyright © 2015. Published by Elsevier Inc.

  16. Triterpenoid herbal saponins enhance beneficial bacteria, decrease sulfate-reducing bacteria, modulate inflammatory intestinal microenvironment and exert cancer preventive effects in ApcMin/+ mice

    Science.gov (United States)

    Chen, Lei; Brar, Manreetpal S.; Leung, Frederick C. C.; Hsiao, W. L. Wendy

    2016-01-01

    Saponins derived from medicinal plants have raised considerable interest for their preventive roles in various diseases. Here, we investigated the impacts of triterpenoid saponins isolated from Gynostemma pentaphyllum (GpS) on gut microbiome, mucosal environment, and the preventive effect on tumor growth. Six-week old ApcMin/+ mice and their wild-type littermates were fed either with vehicle or GpS daily for the duration of 8 weeks. The fecal microbiome was analyzed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and 16S rRNA gene pyrosequencing. Study showed that GpS treatment significantly reduced the number of intestinal polyps in a preventive mode. More importantly, GpS feeding strikingly reduced the sulfate-reducing bacteria lineage, which are known to produce hydrogen sulfide and contribute to damage the intestinal epithelium or even promote cancer progression. Meanwhile, GpS also boosted the beneficial microbes. In the gut barrier of the ApcMin/+ mice, GpS treatment increased Paneth and goblet cells, up-regulated E-cadherin and down-regulated N-cadherin. In addition, GpS decreased the pro-oncogenic β-catenin, p-Src and the p-STAT3. Furthermore, GpS might also improve the inflamed gut epithelium of the ApcMin/+ mice by upregulating the anti-inflammatory cytokine IL-4, while downregulating pro-inflammatory cytokines TNF-β, IL-1β and IL-18. Intriguingly, GpS markedly stimulated M2 and suppressed M1 macrophage markers, indicating that GpS altered mucosal cytokine profile in favor of the M1 to M2 macrophages switching, facilitating intestinal tissue repair. In conclusion, GpS might reverse the host's inflammatory phenotype by increasing beneficial bacteria, decreasing sulfate-reducing bacteria, and alleviating intestinal inflammatory gut environment, which might contribute to its cancer preventive effects. PMID:27121311

  17. Decreased background parenchymal enhancement of the contralateral breast after two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2-positive breast cancer.

    Science.gov (United States)

    You, Chao; Gu, Yajia; Peng, Wen; Li, Jianwei; Shen, Xuxia; Liu, Guangyu; Peng, Weijun

    2018-07-01

    Background Several recent studies have focused on the association between background parenchymal enhancement (BPE) and tumor response to neoadjuvant chemotherapy (NAC), but early prediction of tumor response based on BPE has yet not been investigated. Purpose To retrospectively investigate whether changes in the BPE of the contralateral breast following NAC could help predict tumor response in early stage HER2-positive breast cancer. Material and Methods Data from 71 patients who were diagnosed with unilateral HER2 positive breast cancer and then underwent NAC with trastuzumab before surgery were analyzed retrospectively. Two experienced radiologists independently categorized the patients' levels of BPE of the contralateral breast into four categories (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete response (pCR) and 37 patients had residual disease (non-pCR). The association between BPE and histopathologic tumor response was analyzed. Result The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P < 0.001) was observed after the second NAC cycle; however, a more obvious decrease in BPE was identified in premenopausal relative to post-menopausal women ( P = 0.041). No significant association was identified between pCR and baseline BPE ( P = 0.287). However, after the second NAC cycle, decreased BPE was significantly associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes in BPE may serve as an additional imaging biomarker of treatment response at an early stage.

  18. Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

    International Nuclear Information System (INIS)

    Meerson, Ari; Yehuda, Hila

    2016-01-01

    Obesity is a risk factor for colorectal cancer (CRC). Normal and tumor cells respond to metabolic hormones, such as leptin and insulin. Thus, obesity-associated resistance to these hormones likely leads to changes in gene expression and behavior of tumor cells. However, the mechanisms affected by leptin and insulin signaling in CRC cells remain mostly unknown. We hypothesized that microRNAs (miRNAs) are involved in the regulation of tumorigenesis-related gene expression in CRC cells by leptin and insulin. To test this hypothesis, miRNA levels in the CRC-derived cell lines HCT-116, HT-29 and DLD-1 were profiled, following leptin and insulin treatment. Candidate miRNAs were validated by RT-qPCR. Predicted miRNA targets with known roles in cancer, were validated by immunoblots and reporter assays in HCT-116 cells. Transfection of HCT-116 cells with candidate miRNA mimic was used to test in vitro effects on proliferation and invasion. Of ~800 miRNAs profiled, miR-4443 was consistently up-regulated by leptin and insulin in HCT-116 and HT-29, but not in DLD-1, which lacked normal leptin receptor expression. Dose response experiments showed that leptin at 100 ng/ml consistently up-regulated miR-4443 in HCT-116 cells, concomitantly with a significant decrease in cell invasion ability. Transfection with miR-4443 mimic decreased invasion and proliferation of HCT-116 cells. Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay. The up-regulation of miR-4443 by leptin or insulin was attenuated by the inhibition of MEK1/2. Our findings suggest that miR-4443 acts in a tumor-suppressive manner by down-regulating TRAF4 and NCOA1 downstream of MEK-C/EBP-mediated leptin and insulin signaling, and that insulin and/or leptin resistance (e.g. in obesity) may suppress this pathway

  19. Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Caroline eKuiper

    2014-02-01

    Full Text Available Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3 and VEGF. Patient survival was monitored for the first six years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p< 0.001 but overall levels varied considerably. HIF-1α, VEGF and BNIP3 were elevated in tumor samples (p< 0.01. There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p=0.002 and tumor size (p=0.018. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p=0.006, with 141 - 1,094 additional disease free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

  20. A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL.

    Science.gov (United States)

    Hwang, Jung Jin; Kim, Yong Sook; Kim, Taelim; Kim, Mi Joung; Jeong, In Gab; Lee, Je-Hwan; Choi, Jene; Jang, Sejin; Ro, Seonggu; Kim, Choung-Soo

    2012-08-01

    We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and -8 in LNCaP, DU145 and PC3 cells. These results indicate that CG200745 induces apoptosis. Next, we examined the effect of CG200745 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Compared to mono-treatment with each drug, pre-treatment of DU145 cells with docetaxel followed by CG200745 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation. Moreover, the combination treatment decreased Mcl-1 and Bcl-(XL). Docetaxel and CG200745 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that combination treatment with docetaxel and new HDACI, CG200745, potentiated anti-tumor effect in hormone-refractory prostate cancer (HRPC) cells via activation of apoptosis.

  1. Decreased expression of 17β-hydroxysteroid dehydrogenase type 1 is associated with DNA hypermethylation in colorectal cancer located in the proximal colon

    International Nuclear Information System (INIS)

    Rawłuszko, Agnieszka Anna; Horbacka, Karolina; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2011-01-01

    The importance of 17β-estradiol (E2) in the prevention of large bowel tumorigenesis has been shown in many epidemiological studies. Extragonadal E2 may form by the aromatase pathway from androstenedione or the sulfatase pathway from estrone (E1) sulfate followed by E1 reduction to E2 by 17-β-hydroxysteroid dehydrogenase (HSD17B1), so HSD17B1 gene expression may play an important role in the production of E2 in peripheral tissue, including the colon. HSD17B1 expression was analyzed in colorectal cancer cell lines (HT29, SW707) and primary colonic adenocarcinoma tissues collected from fifty two patients who underwent radical colon surgical resection. Histopathologically unchanged colonic mucosa located at least 10-20 cm away from the cancerous lesions was obtained from the same patients. Expression level of HSD17B1 using quantitative PCR and western blot were evaluated. DNA methylation level in the 5' flanking region of HSD17B1 CpG rich region was assessed using bisulfite DNA sequencing and HRM analysis. The influence of DNA methylation on HSD17B1 expression was further evaluated by ChIP analysis in HT29 and SW707 cell lines. The conversion of estrone (E1) in to E2 was determined by electrochemiluminescence method. We found a significant decrease in HSD17B1 transcript (p = 0.0016) and protein (p = 0.0028) levels in colorectal cancer (CRC) from the proximal but not distal colon and rectum. This reduced HSD17B1 expression was associated with significantly increased DNA methylation (p = 0.003) in the CpG rich region located in the 5' flanking sequence of the HSD17B1 gene in CRC in the proximal but not distal colon and rectum. We also showed that 5-dAzaC induced demethylation of the 5' flanking region of HSD17B1, leading to increased occupation of the promoter by Polymerase II, and increased transcript and protein levels in HT29 and SW707 CRC cells, which contributed to the increase in E2 formation. Our results showed that reduced HSD17B1 expression can

  2. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  3. Transperineal Injection of Hyaluronic Acid in Anterior Perirectal Fat to Decrease Rectal Toxicity From Radiation Delivered With Intensity Modulated Brachytherapy or EBRT for Prostate Cancer Patients

    International Nuclear Information System (INIS)

    Prada, Pedro J.; Fernandez, Jose; Martinez, Alvaro A.; Rua, Angeles de la; Gonzalez, Jose M.; Fernandez, Jose M.; Juan, German

    2007-01-01

    Purpose: Rectal toxicity remains a serious complication affecting quality of life for prostate cancer patients treated with radiotherapy. We began an investigational trial injecting hyaluronic acid (HA) in the perirectal fat to increase the distance between the prostate and the anterior rectal wall. This is the first report using HA injection in oncology. Methods and Materials: This is a trial of external beam radiation therapy with HDR brachytherapy boosts in prostate cancer. During the two high-dose-rate (HDR) fractions, thermoluminescent dosimeter dosimeters were placed in the urethra and in the rectum. Before the second HDR fraction, 3-7 mL (mean, 6 mL) of HA was injected under transrectal ultrasound guidance in the perirectal fat to systematically create a 1.5-cm space. Urethral and rectal HDR doses were calculated and measured. Computed tomography and magnetic resonance imaging were used to assess the stability of the new space. Results: Twenty-seven patients enrolled in the study. No toxicity was produced from the HA or the injection. In follow-up computed tomography and magnetic resonance imaging, the HA injection did not migrate or change in mass/shape for close to 1 year. The mean distance between rectum and prostate was 2.0 cm along the entire length of the prostate. The median measured rectal dose, when normalized to the median urethral dose, demonstrated a decrease in dose from 47.1% to 39.2% (p < 0.001) with or without injection. For an HDR boost dose of 1150 cGy, the rectum mean Dmax reduction was from 708 cGy to 507 cGy, p < 0.001, and the rectum mean Dmean drop was from 608 to 442 cGy, p < 0.001 post-HA injection. Conclusion: The new 2-cm distance derived from the HA injection significantly decreased rectal dose in HDR brachytherapy. Because of the several-month duration of stability, the same distance was maintained during the course of external beam radiation therapy

  4. DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer

    International Nuclear Information System (INIS)

    Kalmár, Alexandra; Péterfia, Bálint; Hollósi, Péter; Galamb, Orsolya; Spisák, Sándor; Wichmann, Barnabás; Bodor, András; Tóth, Kinga; Patai, Árpád V.; Valcz, Gábor; Nagy, Zsófia Brigitta; Kubák, Vivien; Tulassay, Zsolt; Kovalszky, Ilona; Molnár, Béla

    2015-01-01

    Colorectal cancer (CRC) development is accompanied by changes in expression for several genes; but the details of the underlying regulatory procesess remain unknown. Our aims were to assess the role of epigenetic processes in tumour formation and to identify characteristic DNA methylation and miRNA alterations in the colorectal adenoma-carcinoma sequence. Whole genome expression profiling was performed on colonic biopsy samples (49 healthy normal, 49 colorectal adenoma (AD), 49 CRC); on laser capture microdissected (LCM) epithelial and stromal cells from 6 CRC-normal adjacent tissue (NAT) samples pairs, and on demethylated human CRC cell lines using HGU133 Plus 2.0 microarrays (Affymetrix). Methylation status of genes with gradually altering expression along the AD-CRC sequence was further analysed on 10–10 macrodissected and 5–5 LCM samples from healthy colon, from adenoma and from CRC biopsy samples using bisulfite-sequencing PCR (BS-PCR) followed by pyrosequencing. In silico miRNA prediction for the selected genes was performed with miRWALK algorithm, miRNA expression was analysed on 3 CRC-NAT sample pairs and 3 adenoma tissue samples using the Human Panel I + II (Exiqon). SFRP1 immunohistochemistry experiments were performed. A set of transcripts (18 genes including MAL, SFRP1, SULT1A1, PRIMA1, PTGDR) showed decreasing expression (p < 0.01) in the biopsy samples along the adenoma-carcinoma sequence. Three of those (COL1A2, SFRP2, SOCS3) showed hypermethylation and THBS2 showed hypomethylation both in AD and in CRC samples compared to NAT, while BCL2, PRIMA1 and PTGDR showed hypermethylation only in the CRC group. miR-21 was found to be significantly (p < 0.01) upregulated in adenoma and tumour samples compared to the healthy colonic tissue controls and could explain the altered expression of genes for which DNA methylation changes do not appear to play role (e.g. BCL2, MAL, PTGS2). Demethylation treatment could upregulate gene expression of genes that were

  5. MO-E-17A-09: Has Cancer Risk for Pediatric CT Increased Or Decreased? An Analysis of Cohort Data From 2004-2013

    International Nuclear Information System (INIS)

    Brady, S; Kaufman, R

    2014-01-01

    Purpose: To analyze CT radiation dosimetry trends in a pediatric population imaged with modern (2004-2013) CT technology Methods: The institutional review board approved this retrospective review. Two cohorts of pediatric patients that received CT scans for treatment or surveillance for Wilms tumor (n=73) or Neuroblastoma (n=74) from 2004–2013 were included in this study. Patients were scanned during this time period on a GE Ultra (8 slice; 2004–2007), a GE VCT (2008–2011), or a GE VCT-XTe (2011–2013). Each patient's individual or combined chest, abdomen, and pelvic CT exams (n=4138) were loaded onto a PACS workstation (Intelerad, Canada) and measured to calculate their effective diameter and SSDE. Patient SSDE was used to estimate patient organ dosimetry based on previously published data. Patient's organ dosimetry were sorted by gender, weight, age, scan protocol (i.e., chest, abdomen, or pelvis), and CT scanner technology and averaged accordingly to calculate population averaged absolute and effective dose values. Results: Patient radiation dose burden calculated for all genders, weights, and ages decreased at a rate of 0.2 mSv/year (4.2 mGy/year; average organ dose) from 2004–2013; overall levels decreased by 50% from 3.0 mSv (60.0 mGy) to 1.5 mSv (25.9 mGy). Patient dose decreased at equal rates for both male and female, and for individual scan protocols. The greatest dose savings was found for patients between 0–4 years old (65%) followed by 5-9 years old (45%), 10–14 years old (30%), and > 14 years old (21%). Conclusion: Assuming a linear-nothreshold model, there always will be potential risk of cancer induction from CT. However, as demonstrated among these patient populations, effective and organ dose has decreased over the last decade; thus, potential risk of long-term side effects from pediatric CT examinations has also been reduced

  6. MO-E-17A-09: Has Cancer Risk for Pediatric CT Increased Or Decreased? An Analysis of Cohort Data From 2004-2013

    Energy Technology Data Exchange (ETDEWEB)

    Brady, S; Kaufman, R [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2014-06-15

    Purpose: To analyze CT radiation dosimetry trends in a pediatric population imaged with modern (2004-2013) CT technology Methods: The institutional review board approved this retrospective review. Two cohorts of pediatric patients that received CT scans for treatment or surveillance for Wilms tumor (n=73) or Neuroblastoma (n=74) from 2004–2013 were included in this study. Patients were scanned during this time period on a GE Ultra (8 slice; 2004–2007), a GE VCT (2008–2011), or a GE VCT-XTe (2011–2013). Each patient's individual or combined chest, abdomen, and pelvic CT exams (n=4138) were loaded onto a PACS workstation (Intelerad, Canada) and measured to calculate their effective diameter and SSDE. Patient SSDE was used to estimate patient organ dosimetry based on previously published data. Patient's organ dosimetry were sorted by gender, weight, age, scan protocol (i.e., chest, abdomen, or pelvis), and CT scanner technology and averaged accordingly to calculate population averaged absolute and effective dose values. Results: Patient radiation dose burden calculated for all genders, weights, and ages decreased at a rate of 0.2 mSv/year (4.2 mGy/year; average organ dose) from 2004–2013; overall levels decreased by 50% from 3.0 mSv (60.0 mGy) to 1.5 mSv (25.9 mGy). Patient dose decreased at equal rates for both male and female, and for individual scan protocols. The greatest dose savings was found for patients between 0–4 years old (65%) followed by 5-9 years old (45%), 10–14 years old (30%), and > 14 years old (21%). Conclusion: Assuming a linear-nothreshold model, there always will be potential risk of cancer induction from CT. However, as demonstrated among these patient populations, effective and organ dose has decreased over the last decade; thus, potential risk of long-term side effects from pediatric CT examinations has also been reduced.

  7. Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model

    International Nuclear Information System (INIS)

    Marincola, F.M.; Da Pozzo, L.F.; Drucker, B.J.; Holder, W.D. Jr.

    1990-01-01

    A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC)

  8. Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

    Science.gov (United States)

    Falcão, Daniela; Alexandrino, Henrique; Caetano Oliveira, Rui; Martins, João; Ferreira, Luís; Martins, Ricardo; Serôdio, Marco; Martins, Mónica; Tralhão, José Guilherme; Cipriano, Maria Augusta; Castro E Sousa, Francisco

    2018-04-11

    Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  9. A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer.

    Science.gov (United States)

    Nakayama, Michihiro; Okizaki, Atsutaka; Takahashi, Koji

    2016-01-01

    Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A ( P aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

  10. A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Michihiro Nakayama

    2016-01-01

    Full Text Available Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI therapy with differentiated thyroid cancer (DTC. Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n=35 and a control group (group B, n=36. We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P<0.05. In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P<0.05. Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

  11. Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

    OpenAIRE

    Cawthorn, Thomas R.; Moreno, Juan C.; Dharsee, Moyez; Tran-Thanh, Danh; Ackloo, Suzanne; Zhu, Pei Hong; Sardana, Girish; Chen, Jian; Kupchak, Peter; Jacks, Lindsay M.; Miller, Naomi A.; Youngson, Bruce J.; Iakovlev, Vladimir; Guidos, Cynthia J.; Vallis, Katherine A.

    2012-01-01

    BACKGROUND: Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample scree...

  12. Down-regulation of human endogenous retrovirus type K (HERV-K) viral env RNA in pancreatic cancer cells decreases cell proliferation and tumor growth

    Science.gov (United States)

    Li, Ming; Radvanyi, Laszlo; Yin, Bingnan; Li, Jia; Chivukula, Raghavender; Lin, Kevin; Lu, Yue; Shen, JianJun; Chang, David Z.; Li, Donghui; Johanning, Gary L.; Wang-Johanning, Feng

    2017-01-01

    Purpose We investigated the role of the human endogenous retrovirus type K (HERV-K) envelope (env) gene in pancreatic cancer (PC). Experimental Design shRNA was employed to knockdown (KD) the expression of HERV-K in PC cells. Results HERV-K env expression was detected in seven PC cell lines and in 80% of PC patient biopsies, but not in two normal pancreatic cell lines or uninvolved normal tissues. A new HERV-K splice variant was discovered in several PC cell lines. RT activity and virus-like particles were observed in culture media supernatant obtained from Panc-1 and Panc-2 cells. HERV-K viral RNA levels and anti-HERV-K antibody titers were significantly higher in PC patient sera (N=106) than in normal donor sera (N=40). Importantly, the in vitro and in vivo growth rates of three PC cell lines were significantly reduced after HERV-K KD by shRNA targeting HERV-K env, and there was reduced metastasis to lung after treatment. RNA-seq results revealed changes in gene expression after HERV-K env KD, including RAS and TP53. Furthermore, downregulation of HERV-K Env protein expression by shRNA also resulted in decreased expression of RAS, p-ERK, p-RSK, and p-AKT in several PC cells or tumors. Conclusion These results demonstrate that HERV-K influences signal transduction via the RAS-ERK-RSK pathway in PC. Our data highlight the potentially important role of HERV-K in tumorigenesis and progression of PC, and indicate that HERV-K viral proteins may be attractive biomarkers and/or tumor-associated antigens, as well as potentially useful targets for detection, diagnosis and immunotherapy of PC. PMID:28679769

  13. Expression of the Na+/l- symporter (NIS is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

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    Wapnir Irene L

    2007-01-01

    Full Text Available Abstract Background The sodium/iodide symporter (NIS is a plasma membrane glycoprotein that mediates iodide (I- transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. Methods Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. Results Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. Conclusion That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

  14. Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer.

    Science.gov (United States)

    Schroll, Monica M; Ludwig, Katelyn R; Bauer, Kerry M; Hummon, Amanda B

    2018-01-11

    Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side) colon is different from cancer of the descending (left side) colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

  15. Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer

    Directory of Open Access Journals (Sweden)

    Monica M. Schroll

    2018-01-01

    Full Text Available Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side colon is different from cancer of the descending (left side colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

  16. No Decreased Risk of Gastrointestinal Cancers in Users of Metformin in The Netherlands; A Time-Varying Analysis of Metformin Exposure

    NARCIS (Netherlands)

    de Jong, Roy G; Burden, Andrea M; de Kort, Sander; van Herk-Sukel, Myrthe P; Vissers, Pauline A; Janssen, Paddy K; Haak, Harm R; Masclee, Ad A; de Vries, Frank; Janssen-Heijnen, Maryska L

    2017-01-01

    Previous studies on metformin use and gastrointestinal (GI) cancer risk have yielded inconclusive results on metformin's chemoprotective effects. We aimed to evaluate GI cancer risk in users of metformin in The Netherlands using a time-varying approach in a large population-based database. A cohort

  17. MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial-mesenchymal transition, decreased ER alpha expression and AKT activation

    NARCIS (Netherlands)

    Liang, Yuan-Ke; Zeng, De; Xiao, Ying-Sheng; Wu, Yang; Ouyang, Yan-Xiu; Chen, Min; Li, Yao-Chen; Lin, Hao-Yu; Wei, Xiao-Long; Zhang, Yong-Qu; Kruyt, Frank A. E.; Zhang, Guo-Jun

    2017-01-01

    Tamoxifen resistance presents a prominent clinical challenge in endocrine therapy for hormone sensitive breast cancer. However, the underlying mechanisms that contribute to tamoxifen resistance are not fully understood. In this study, we established a tamoxifen resistant MCF-7 cell line

  18. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect).

    Science.gov (United States)

    El Sayed, Salah Mohamed; Mahmoud, Ahmed Alamir; El Sawy, Samer Ahmed; Abdelaal, Esam Abdelrahim; Fouad, Amira Murad; Yousif, Reda Salah; Hashim, Marwa Shaban; Hemdan, Shima Badawy; Kadry, Zainab Mahmoud; Abdelmoaty, Mohamed Ahmed; Gabr, Adel Gomaa; Omran, Faten M; Nabo, Manal Mohamed Helmy; Ahmed, Nagwa Sayed

    2013-11-01

    Cancer cells undergo an increased steady-state ROS condition compared to normal cells. Among the major metabolic differences between cancer cells and normal cells is the dependence of cancer cells on glycolysis as a major source of energy even in the presence of oxygen (Warburg effect). In Warburg effect, glucose is catabolized to lactate that is extruded through monocarboxylate transporters to the microenvironment of cancer cells, while in normal cells, glucose is metabolized into pyruvate that is not extruded. Pyruvate is a potent antioxidant, while lactate has no antioxidant effect. Pyruvate in normal cells may be further metabolized to acetyl CoA and then through Krebs cycle with production of antioxidant intermediates e.g. citrate, malate and oxaloacetate together with the reducing equivalents (NADH.H+). Through activity of mitochondrial transhydrogenase, NADH.H+ replenishes NADPH.H+, coenzyme of glutathione reductase which replenishes reduced form of glutathione (potent antioxidant). This enhances antioxidant capacities of normal cells, while cancer cells exhibiting Warburg effect may be deprived of all that antioxidant capabilities due to loss of extruded lactate (substrate for Krebs cycle). Although intrinsic oxidative stress in cancer cells is high, it may be prevented from reaching progressively increasing levels that are cytotoxic to cancer cells. This may be due to some antioxidant effects exerted by hexokinase II (HK II) and NADPH.H+ produced through HMP shunt. Glycolytic phenotype in cancer cells maintains a high non-toxic oxidative stress in cancer cells and may be responsible for their malignant behavior. Through HK II, glycolysis fuels the energetic arm of malignancy, the mitotic arm of malignancy (DNA synthesis through HMP shunt pathway) and the metastatic arm of malignancy (hyaluronan synthesis through uronic acid pathway) in addition to the role of phosphohexose isomerase (autocrine motility factor). All those critical three arms start with the

  19. Convergence of decreasing male and increasing female incidence rates in major tobacco-related cancers in Europe in 1988-2010.

    Science.gov (United States)

    Lortet-Tieulent, Joannie; Renteria, Elisenda; Sharp, Linda; Weiderpass, Elisabete; Comber, Harry; Baas, Paul; Bray, Freddie; Coebergh, Jan Willem; Soerjomataram, Isabelle

    2015-06-01

    Smoking prevalence has been declining in men all over Europe, while the trend varies in European regions among women. To study the impact of past smoking prevalence, we present a comprehensive overview of the most recent trends in incidence, during 1988-2010, in 26 countries, of four of the major cancers in the respiratory and upper gastro-intestinal tract associated with tobacco smoking. Data from 47 population-based cancer registries for lung, laryngeal, oral cavity and pharyngeal, and oesophageal cancer cases were obtained from the newly developed data repository within the European Cancer Observatory (http://eco.iarc.fr/). Truncated age-standardised incidence rates (35-74 years) by calendar year, average annual percentage change in incidence over 1998-2007 were calculated. Smoking prevalence in selected countries was extracted from the Organisation for Economic Co-operation and Development and the World Health Organization databases. There remained great but changing variation in the incidence rates of tobacco-related cancers by European region. Generally, the high rates among men have been declining, while the lower rates among women are increasing, resulting in convergence of the rates. Female lung cancer rates were above male rates in Denmark, Iceland and Sweden (35-64 years). In lung and laryngeal cancers, where smoking is the main risk factor, rates were highest in central and eastern Europe, southern Europe and the Baltic countries. Despite a lowering of female smoking prevalence, female incidence rates of lung, laryngeal and oral cavity cancers increased in most parts of Europe, but were stable in the Baltic countries. Mixed trends emerged in oesophageal cancer, probably explained by differing risk factors for the two main histological subtypes. This data repository offers the opportunity to show the variety of incidence trends by sex among European countries. The diverse patterns of trends reflect varied exposure to risk factors. Given the heavy cancer

  20. 4-IBP, a σ1 Receptor Agonist, Decreases the Migration of Human Cancer Cells, Including Glioblastoma Cells, In Vitro and Sensitizes Them In Vitro and In Vivo to Cytotoxic Insults of Proapoptotic and Proautophagic Drugs

    Directory of Open Access Journals (Sweden)

    Veronique Mégalizzi

    2007-05-01

    Full Text Available Although the molecular function of cr receptors has not been fully defined and the natural ligand(s is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-tibenzylpiperidin-4-yl-4iodobenzamide (4-IBP, a selective σ1, agonist, has been used to investigate whether this compound is able to modify: 1 in vitro the migration and proliferation of human cancer cells; 2 in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3 in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC models the survival of mice coadministered cytotoxic agents. 4-IBP has revealed weak anti proliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

  1. High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

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    Firdaus S Dhabhar

    Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

  2. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    International Nuclear Information System (INIS)

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel Ángel

    2014-01-01

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells

  3. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas, Casimiro [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); Research Support Central Services (SCAI) of the University of Málaga, E-29071 Málaga (Spain); Quesada, Ana R. [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain); Medina, Miguel Ángel, E-mail: medina@uma.es [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain)

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  4. A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    John F. Hernández

    Full Text Available Abstract Metabolic plasticity in cancer cells assures cell survival and cell proliferation under variable levels of oxygen and nutrients. Therefore, new anticancer treatments endeavor to target such plasticity by modifying main metabolic pathways as glycolysis or oxidative phosphorylation. In American traditional medicine Petiveria alliacea L., Phytolaccacea, leaf extracts have been used for leukemia and breast cancer treatments. Herein, we study cytotoxicity and antitumoral effects of P. alliacea extract in tumor/non-tumorigenic cell lines and murine breast cancer model. Breast cancer cells treated with P. alliacea dry extract showed reduction in β-F1-ATPase expression, glycolytic flux triggering diminished intracellular ATP levels, mitochondrial basal respiration and oxygen consumption. Consequently, a decline in cell proliferation was observed in conventional and three-dimension spheres breast cancer cells culture. Additionally, in vivo treatment of BALB/c mice transplanted with the murine breast cancer TS/A tumor showed that P. alliacea extract via i.p. decreases the primary tumor growth and increases survival in the TS/A model.

  5. Plasma 25-hydroxyvitamin D3 is associated with decreased risk of postmenopausal breast cancer in whites: a nested case–control study in the multiethnic cohort study

    International Nuclear Information System (INIS)

    Kim, Yeonju; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T; Franke, Adrian A; Shvetsov, Yurii B; Wilkens, Lynne R; Cooney, Robert V; Lurie, Galina; Maskarinec, Gertraud; Hernandez, Brenda Y; Le Marchand, Loïc

    2014-01-01

    Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies, but findings from prospective studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null. The objective of this study was to examine the relation between plasma levels of vitamin D and the risk of postmenopausal breast cancer. We conducted a nested case–control study within the Multiethnic Cohort Study of five race/ethnic groups (white, African-American, Native Hawaiian, Japanese, and Latino) from Hawaii and Los Angeles between 2001 and 2006. Pre-diagnostic plasma levels of 25-hydroxyvitamin D2 [25(OH)D 2 ], 25-hydroxyvitamin D3 [25(OH)D 3 ] and 25(OH)D (sum of 25(OH)D 2 and 25(OH)D 3 ) were examined among 707 postmenopausal breast cancer cases and matched controls. Using conditional logistic regression models, 20 ng/mL increases of plasma 25(OH)D 3 (odds ratio (OR) 0.28; 95% confidence interval (CI) 0.14-0.56) and 25(OH)D (OR 0.43; 95% CI 0.23-0.80) were inversely associated with breast cancer risk among white women, but not among women in other race/ethnic groups. Using two-segmented, piecewise-linear logistic regression models, the change-points of the ORs, either for 25(OH)D 3 or for 25(OH)D, were detected as 20 ng/mL among whites. Circulating 25(OH)D 3 and 25(OH)D were associated with a reduced risk of postmenopausal breast cancer among whites, but not in other ethnic groups, who reside in low latitude regions

  6. Decreased expression of MUC1 induces apoptosis and inhibits migration in pancreatic cancer PANC-1 cells via regulation of Slug pathway.

    Science.gov (United States)

    Zhao, Ping; Meng, Meng; Xu, Bin; Dong, Aiping; Ni, Guangzhen; Lu, Lianfang

    2017-12-06

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed in > 60% of human pancreatic cancers (PCs), and is associated with poor prognosis and enhanced metastasis. Here, we report the effect of silencing MUC1 expression on the growth, migration and invasive ability of pancreatic cancer cells, and explored its mechanisms. We observed that siRNA mediated suppression of the MUC1 expression significantly reduced invasive and migrative capability and induced apoptosis of the pancreatic cancer PANC-1 cells. We found that Slug was inhibited in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Expression of PUMA and E-cadherin was increased in the MUC1 siRNA/PANC-1 cells. PANC-1 cells overexpressing full long Slug gene (when transfected with Slug cDNA plasmid) significantly inhibited PUMA and E-cadherin expression in the MUC1 siRNA/PANC-1 cells. Silencing PUMA expression inhibited apoptosis in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Silencing E-cadherin expression restored the invasion and migration ability in the MUC1 siRNA/PANC-1 cells. We therefore concluded that silencing MUC1 expression inhibited migration and invasion, and induced apoptosis of PANC-1 cells via downregulation of Slug and upregulation of Slug dependent PUMA and E-cadherin expression. MUC1 could serve as a potential therapeutic target in pancreatic cancer.

  7. Decrease in Survival Rate of Colorectal Cancer Patients Due to Insertion of a Single Guanine Base in Promoter Sequences of Matrix Metalloproteinase-1 Gene (in Tehran Population

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    Z Hojati

    2009-01-01

    Full Text Available Introduction: Insertion or deletion of a guanine in -1607 at promoter region of matrix metalloproteinase-1 enzyme creates two allelic types for this gene in the population: 2G and 1G, respectively. 2G allele contains an extra binding site for ETS transcription factors that this may increase the level of gene expression. Therefore, aim of this study was investigation of the single Guanine insertion in the promoter gene and its association with colorectal cancer patient survival rate and tumor progression. Methods: Blood samples from 150 colorectal patients and 100 cases were extracted. The mean follow-up was 25 months (12-36 months. Cases and patients were genotyped using genomic DNA extraction and PCR-RFLP. Results: Colorectal cancer patients were divided in two groups; with activity of metastasis (M+ and without activity of metastasis (M-. 2G allele in metastasis group (55% showed more frequency rather than controls (23%. Survival analyses showed that 3 years survival patients rate in the patients without metastasis activity carrying 1G allele (homo and heterozygote was 81% and for 2G homozygote is 66% (p=0.04. The survival rate dependent to cancer was 90% and 71%, respectively (P=0.01. Conclusion: According to the results, it seems that patients carrying 1G allele show a better survival rate dependent on cancer as compared to patients who do not carry this allele.

  8. Decreased survival in patients with carcinoma of axillary tail versus upper outer quadrant breast cancers: a SEER population-based study

    Directory of Open Access Journals (Sweden)

    Gou ZC

    2018-05-01

    Full Text Available Zong-Chao Gou,1,2,* Xi-Yu Liu,1,2,* Yi Xiao,1,2 Shen Zhao,1,2 Yi-Zhou Jiang,1,2 Zhi-Ming Shao1–3 1Department of Breast Surgery, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Carcinoma of the axillary tail of Spence (CATS is a poorly studied type of breast cancer. The clinicopathological characteristics and prognostic features of CATS are unclear. Methods: Using the Surveillance, Epidemiology, and End Results database, we identified 149,026 patients diagnosed with upper outer quadrant breast cancer (UOBC (n=146,343 or CATS (n=2,683. The median follow-up was 88 months. The primary and secondary outcomes were breast cancer-specific survival (BCSS and overall survival. The survival outcomes of UOBC and CATS were compared using competing risks analysis, log-rank test, Cox proportional hazards regression model, and propensity score matching method. Multivariate logistic regression was utilized to present the relationship between CATS and lymph node (LN metastasis. Results: CATS presented a higher grade, higher negative hormone receptor rate, and more positive nodal metastasis. The 10-year BCSS rate was worse for CATS than for UOBC (85.1% vs 87.3%, P=0.001. The multivariate Cox analysis showed a higher hazard ratio (HR for CATS over UOBC (BCSS: HR =1.20, P=0.001; overall survival: HR =1.11, P=0.019. The difference in the BCSS was also observed in a 1:1 matched cohort (BCSS P=0.019. A subgroup analysis revealed the inferior outcomes of CATS in the metastatic LN subgroup and the hormone receptor-negative subgroup. The multivariate logistic regression indicated that CATS is an independent contributing factor to LN metastasis. Conclusion: CATS

  9. Luteolin decreases invasiveness, deactivates STAT3 signaling, and reverses interleukin-6 induced epithelial–mesenchymal transition and matrix metalloproteinase secretion of pancreatic cancer cells

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    Huang XC

    2015-10-01

    Full Text Available Xince Huang,1 Shengjie Dai,1 Juji Dai,1 Yuwu Xiao,1 Yongyu Bai,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Luteolin, a flavone, has been shown to exhibit anticancer properties. Here, we investigated whether luteolin affects epithelial–mesenchymal transition (EMT and invasiveness of pancreatic cancer cell lines and their underlying mechanism. Pancreatic cancer cell lines PANC-1 and SW1990 were used in our study, and their EMT characters, matrix metalloproteinase (MMP expression level, invasiveness, and signal transducer and activator of transcription 3 (STAT3 activity were determined after luteolin treatment. We also treated pancreatic cancer cells with interleukin-6 (IL-6 to see whether IL-6-induced activation of STAT3, EMT, and MMP secretion was affected by luteolin. We found that luteolin inhibits EMT and MMP2, MMP7, and MMP9 expression in a dose-dependent manner, similar to STAT3 signaling. Through Transwell assay, we found that invasiveness of pancreatic cancer cells was inhibited by luteolin. EMT characters and MMP secretion increase with STAT3 activity after IL-6 treatment and these effects, caused by IL-6, were inhibited by luteolin. We concluded that luteolin inhibits invasiveness of pancreatic cancer cells, and we speculated that luteolin inhibits EMT and MMP secretion likely through deactivation of STAT3 signaling. Luteolin has potential antitumor effects and merits further investigation. Keywords: epithelial–mesenchymal transition, matrix metalloproteinase, luteolin, STAT3

  10. Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells.

    Science.gov (United States)

    Maxwell, Thressi; Lee, Kyu Shik; Kim, Soyoung; Nam, Kyung-Soo

    2018-04-01

    Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer. First, we found that arctigenin inhibited the viability of the MCF-7 cells, and colony formation assay confirmed that this effect was cytotoxic rather than cytostatic. The cytotoxic effects were not mediated by cell cycle arrest, apoptosis, or necroptosis, despite DNA damage, as indicated by poly(ADP-ribose) polymerase (PARP) cleavage and phosphorylated H2A.X. An increase in lipidated LC3, a marker of autophagosome formation, was observed, indicating that autophagy was induced by arctigenin, which was found to be triggered by the inhibition of the mechanistic target of rapamycin (mTOR) pathway. We then examined the effects of arctigenin on ERα expression and determined whether it affects the sensitivity of the cells to tamoxifen, as tamoxifen is commonly used against hormone-responsive cancers and is known to act via the ERα. We found that treatment with arctigenin effectively downregulated ERα expression, which was found to be a consequence of the inhibition of the mTOR pathway. However, treatment with arctigenin in combination with tamoxifen did not affect the sensitivity of the cells to tamoxifen, but instead, exerted a synergistic effect. On the whole, our data indicate that the phytoestrogen, arctigenin, mainly targeted the mTOR pathway in ERα-positive MCF-7 human breast cancer cells, leading to autophagy-induced cell death and the downregulation of ERα expression. Furthermore, the synergistic effects

  11. Homodimers of Vanillin and Apocynin Decrease the Metastatic Potential of Human Cancer Cells by Inhibiting the FAK/PI3K/Akt Signaling Pathway.

    Science.gov (United States)

    Jantaree, Phatcharida; Lirdprapamongkol, Kriengsak; Kaewsri, Wilailak; Thongsornkleeb, Charnsak; Choowongkomon, Kiattawee; Atjanasuppat, Korakot; Ruchirawat, Somsak; Svasti, Jisnuson

    2017-03-22

    The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model. Here, we evaluated the antimetastatic potential of the food additive divanillin, the homodimer of vanillin, and their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells. The Transwell invasion assay showed that the dimeric forms exhibited a potency higher than those of vanillin and apocynin in inhibiting invasion, with IC 50 values of 23.3 ± 7.4 to 41.3 ± 4.2 μM for the dimers, which are 26-34-fold lower than IC 50 values of vanillin and apocynin (p vanillin and apocynin to the Y397 pocket of the FAK FERM domain. Thus, the food additive divanillin has antimetastatic potential greater than that of the flavoring agent vanillin.

  12. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  13. Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes

    OpenAIRE

    Clare, Susan E.; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z.; Kim, J. Julie; Khan, Seema A.

    2016-01-01

    Background The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. Methods We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then...

  14. Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.

    Science.gov (United States)

    Cui, Jiajun; Meng, Xianfeng; Gao, Xudong; Tan, Guangxuan

    2010-03-01

    Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger, anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour cells. To investigate whether curcumin can regulate the expression of Pokemon, a series of experiments were carried out. Transient transfection experiments demonstrated that curcumin could decrease the activity of the Pokemon promoter. Western blot analysis suggested that curcumin could significantly decrease the expression of the Pokemon. Overexpression of Sp1 could enhance the activity of the Pokemon promoter, whereas knockdown of Sp1 could decrease its activity. More important, we also found that curcumin could decrease the expression of the Pokemon by suppressing the stimulation of the Sp1 protein. Therefore, curcumin is a potential reagent for tumour therapy which may target Pokemon.

  15. Potential of Anti Breast Cancer Black Ethanol Rice Extract (Oryza sativa L. indica In Decreasing Levels of CA 15-3 Serum in the White Mice Sprague dawley in Induction 7.12-Dimethylbenz (α Antracene (DMBA and Estrogen

    Directory of Open Access Journals (Sweden)

    Zanuar Abidin

    2017-01-01

    Full Text Available Breast cancer is cancer that has the high incidence in Indonesia. Black rice (Oryza sativa L. indica is a plant that has an anticancer potency. This research aim is to prove black rice as a potential anticancer by using experimental animals, 20 Sprague Dawley female rats aged 7-8 weeks induced breast cancer by using the combination of 7,12-dimethylbenz (α anthracene (DMBA and estrogen. Rats were divided into two groups, namely the K-induced breast cancer and a group of P-induced cancer and treated with black rice. Black rice is given in the form of ethanol extract at a dose of 75 mg / kg / day for six weeks. Levels of CA 15-3 serum are used as a parameter. The result showed that the differences in levels of serum CA 15-3 are significant (p <0.05. Serum CA 15-3 level in P group is lower than in K group. This study proved that the ethanol extract of black rice (Oryza sativa L. indica has potential as an anticancer breast as indicated by decreased level of serum CA 15-3

  16. Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients

    Directory of Open Access Journals (Sweden)

    Xu Zhuwei

    2009-06-01

    Full Text Available Abstract Background As a cellular membrane triggering receptor, CD226 is involved in the NK cell- or CTL-mediated lysis of tumor cells of different origin, including freshly isolated tumor cells and tumor cell lines. Here, we evaluated soluble CD226 (sCD226 levels in sera, and membrane CD226 (mCD226 expression on peripheral blood mononuclear cells (PBMC from cancer patients as well as normal subjects, and demonstrated the possible function and origin of the altered sCD226, which may provide useful information for understanding the mechanisms of tumor escape and for immunodiagnosis and immunotherapy. Results Soluble CD226 levels in serum samples from cancer patients were significantly higher than those in healthy individuals (P P Conclusion These findings suggest that sCD226 might be shed from cell membranes by certain proteases, and, further, sCD226 may be used as a predictor for monitoring cancer, and more important, a possible immunotherapy target, which may be useful in clinical application.

  17. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  18. Does depression decrease the moderating effect of self-efficacy in the relationship between illness perception and fear of progression in breast cancer?

    Science.gov (United States)

    Shim, Eun-Jung; Lee, Jong Won; Min, Yul Ha

    2018-02-01

    Fear of progression (FOP) is a prevalent concern among breast cancer patients that affect their adjustment to disease. This study examined whether self-efficacy moderates the effect of illness perception (IP) on FOP and whether the moderating effect of self-efficacy depends on the level of depressive symptoms. A cross-sectional survey including brief illness perception questionnaire (BIPQ), FOP short form, general self-efficacy scale, and the center for epidemiologic studies depression scale were administered to 245 patients with breast cancer in Korea. Self-efficacy moderated the negative impact of the patients' perception of chronic timeline and a greater emotional impact of the illness on FOP. However, the moderating effect of self-efficacy of the BIPQ timeline and emotions on FOP depended on level of depressive symptoms. The findings underscore the importance of considering the IP as determinants of FOP, as well as of self-efficacy and depression as the moderating factors in the relationship between IP and FOP, suggesting the need to enhance self-efficacy and depressive symptoms in order to compensate the negative impact of IP on FOP in breast cancer patients. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Efficacy of DNA double-strand breaks repair in breast cancer is decreased in carriers of the variant allele of the UBC9 gene c.73G>A polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Synowiec, Ewelina [Department of Molecular Genetics, University of Lodz, Lodz (Poland); Krupa, Renata [Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, Banacha 12/16, Lodz (Poland); Morawiec, Zbigniew; Wasylecka, Maja [Department of Surgical Oncology, N. Copernicus Hospital, Lodz (Poland); Dziki, Lukasz; Morawiec, Jan [Department of General and Colorectal Surgery, Medical University of Lodz, Lodz (Poland); Blasiak, Janusz [Department of Molecular Genetics, University of Lodz, Lodz (Poland); Wozniak, Katarzyna, E-mail: wozniak@biol.uni.lodz.pl [Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, Banacha 12/16, Lodz (Poland)

    2010-12-10

    UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by {gamma}-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p < 0.05) difference in DRE related to the c.73G>A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.

  20. Efficacy of DNA double-strand breaks repair in breast cancer is decreased in carriers of the variant allele of the UBC9 gene c.73G>A polymorphism

    International Nuclear Information System (INIS)

    Synowiec, Ewelina; Krupa, Renata; Morawiec, Zbigniew; Wasylecka, Maja; Dziki, Lukasz; Morawiec, Jan; Blasiak, Janusz; Wozniak, Katarzyna

    2010-01-01

    UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by γ-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.

  1. EMERALD: Emergency visit audit of patients treated under medical oncology in a tertiary cancer center: Logical steps to decrease the burden.

    Science.gov (United States)

    Joshi, Amit; Patil, Vijay M; Noronha, Vanita; Ramaswamy, Anant; Gupta, Sudeep; Bhattacharjee, Atanu; Bonda, Avinash; Chandrakanth, M V; Ostwal, Vikas; Khattry, Navin; Banavali, Shripad; Prabhash, Kumar

    2017-01-01

    We are a tertiary care cancer center and have approximately 1000-1500 emergency visits by cancer patients undergoing treatment under the adult medical oncology unit each month. However, due to the lack of a systematic audit, we are unable to plan steps toward the improvement in quality of emergency services, and hence the audit was planned. All emergency visits under the adult medical oncology department in the month of July 2015 were audited. The cause of visit, the demographic details, cancer details, and chemotherapy status were obtained from the electronic medical records. The emergency visits were classified as avoidable or unavoidable. Descriptive statistics were performed. Reasons for avoidable emergency visits were sought. Out of 1199 visits, 1168 visits were classifiable. Six hundred and ninety-six visits were classified as unavoidable (59.6%, 95% CI: 56.7-62.4), 386 visits were classified as probably avoidable visit (33.0%, 95% CI: 30.4-35.8) whereas the remaining 86 (7.4%, 95% CI: 6.0-9.01) were classified as absolutely avoidable. Two hundred and ninety-seven visits happened on weekends (25.6%) and 138 visits converted into an inpatient admission (11.9%). The factors associated with avoidable visits were curative intention of treatment (odds ratio - 2.49), discontinued chemotherapy status (risk ratio [RR] - 8.28), and private category file status (RR - 1.89). A proportion of visits to emergency services can be curtailed. Approximately one-fourth of patients are seen on weekends, and only about one-tenth of patients get admitted.

  2. Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells

    OpenAIRE

    Moody, Terry W.; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A.; Berna, Marc; Thill, Michelle; Jensen, Robert T.; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D.; Giaccone, Giuseppe; Wink, David A.

    2009-01-01

    The effects of dithiolethione-modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 μg/ml concentrations significantly reduced prostaglandin (PG)E2 levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 μg/ml, respectively. Using the MTT assay, 10...

  3. Lung Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of lung cancer. Lung cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about lung cancer: Lung Cancer Prevention Non-Small Cell Lung Cancer Treatment ...

  4. Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

    Science.gov (United States)

    Seo, Kyung Hye; Ryu, Hyung Won; Park, Mi Jin; Park, Ki Hun; Kim, Jin Hyo; Lee, Mi-Ja; Kang, Hyeon Jung; Kim, Sun Lim; Lee, Jin Hwan; Seo, Woo Duck

    2015-11-01

    Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Decreased length of stay and earlier oral feeding associated with standardized postoperative clinical care for total gastrectomies at a cancer center.

    Science.gov (United States)

    Selby, Luke V; Rifkin, Marissa B; Yoon, Sam S; Ariyan, Charlotte E; Strong, Vivian E

    2016-09-01

    Standardization of postoperative care has been shown to decrease postoperative length of stay. In June 2009, we standardized postoperative care for all gastrectomies at our institution. Four years' worth of total gastrectomies (2 years prior to standardization and 2 years after standardization) were reviewed to determine the effect of standardization on postoperative care, length of stay, complications, and readmissions. Between June 2007 and July 2011, 99 patients underwent curative intent open total gastrectomy: 51 patients prior to standardization, and 48 patients poststandardization. Patients were predominantly male (70%); median age was 63; and median body mass index was 26. Standardization of postoperative care was associated with a decrease in median time to beginning both clear liquids and a postgastrectomy diet, earlier removal of epidural catheters, earlier use of oral pain medication, less time receiving intravenous fluids, and decreased length of stay (all P Care Center, or readmission. Institution of standardized postoperative orders for total gastrectomy was associated with a significantly decreased length of stay and earlier oral feeding without increasing postoperative complications, early postoperative outpatient visits, or readmissions. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Miller Andrew F

    2008-11-01

    Full Text Available Abstract Background Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2. In this study, we evaluate the use of CT-322, a novel biologic (Adnectin. This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2. Methods The efficacy of CT-322 was evaluated in vivo using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL, microvessel density (MECA-32, and VEGF-activated blood vessels (Gv39M. Results Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors

  7. Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Laetitia Huiart

    Full Text Available PURPOSE: Aromatase inhibitor therapy (AI significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. METHODS: We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. RESULTS: Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1 at 1 year, to 15.6% (95%CI: 12.2-19.8 at 2 years, 20.8% (95%CI: 16.7-25.6 at 3 years, and 24.7% (95%CI: 19.5-31.0 at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM (HR = 3.2; 95%CI: 1.5-6.9 or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8 were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91 were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. CONCLUSION: AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

  8. Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer.

    Science.gov (United States)

    Huiart, Laetitia; Bouhnik, Anne-Deborah; Rey, Dominique; Rousseau, Frédérique; Retornaz, Frédérique; Meresse, Mégane; Bendiane, Marc Karim; Viens, Patrice; Giorgi, Roch

    2013-01-01

    Aromatase inhibitor therapy (AI) significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women. We constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques. Overall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1) at 1 year, to 15.6% (95%CI: 12.2-19.8) at 2 years, 20.8% (95%CI: 16.7-25.6) at 3 years, and 24.7% (95%CI: 19.5-31.0) at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM) (HR = 3.2; 95%CI: 1.5-6.9) or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8) were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91) were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy. AI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

  9. Stable alterations of CD44 isoform expression in prostate cancer cells decrease invasion and growth and alter ligand binding and chemosensitivity

    International Nuclear Information System (INIS)

    Yang, Kui; Tang, Yaqiong; Habermehl, Gabriel K; Iczkowski, Kenneth A

    2010-01-01

    Dysregulated CD44 expression characterizes most human cancers, including prostate cancer (PCa). PCa loses expression of CD44 standard (CD44s) that is present in benign epithelium, and overexpresses the novel splice variant isoform, CD44v7-10. Using retroviral gene delivery to PC-3M PCa cells, we expressed luciferase-only, enforced CD44s re-expression as a fusion protein with luciferase at its C-terminus or as a protein separate from luciferase, or knocked down CD44v7-10 by RNAi. Invasion, migration, proliferation, soft agar colony formation, adhesion, Docetaxel sensitivity, and xenograft growth assays were carried out. Expression responses of merlin, a CD44 binding partner, and growth-permissive phospho-merlin, were assessed by western blot. Compared to luciferase-only PC-3M cells, all three treatments reduced invasion and migration. Growth and soft agar colony formation were reduced only by re-expression of CD44s as a separate or fusion protein but not CD44v7-10 RNAi. Hyaluronan and osteopontin binding were greatly strengthened by CD44s expression as a separate protein, but not a fusion protein. CD44v7-10 RNAi in PC-3M cells caused marked sensitization to Docetaxel; the two CD44s re-expression approaches caused minimal sensitization. In limited numbers of mouse subcutaneous xenografts, all three alterations produced only nonsignificant trends toward slower growth compared with luciferase-only controls. The expression of CD44s as a separate protein, but not a fusion protein, caused emergence of a strongly-expressed, hypophosphorylated species of phospho-merlin. Stable re-expression of CD44s reduces PCa growth and invasion in vitro, and possibly in vivo, suggesting CD44 alterations have potential as gene therapy. When the C-terminus of CD44s is fused to another protein, most phenotypic effects are lessened, particularly hyaluronan adhesion. Finally, CD44v7-10, although it was not functionally significant for growth, may be a target for chemosensitization

  10. Decreased stage migration rate of early gastric cancer with a new reconstruction algorithm using dual-energy CT images: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Cen [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); First Affiliated Hospital of Soochow University, Department of Radiology, Suzhou (China); Zhang, Huan; Du, Lianjun; Pan, Zilai; Yan, Fuhua [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Yan, Jing [Siemens Medical System, Shanghai (China); Wang, Baisong [Shanghai Jiao Tong University School of Medicine, Department of Biological Statistics, Shanghai (China)

    2017-02-15

    To evaluate the potential value of advanced monoenergetic images (AMEIs) on early gastric cancer (EGC) using dual-energy CT (DECT). 31 EGC patients (19 men, 12 women; age range, 38-81 years; mean age, 57.19 years) were retrospectively enrolled in this study. Conventionally reconstructed polyenergetic images (PEIs) at 120 kV and virtual monoenergetic images (MEIs) and AMEIs at six different kiloelectron volt (keV) levels (from 40 to 90 keV) were evaluated from the 100 and Sn 140 kV dual energy image data, respectively. The visibility and stage migration of EGC for all three image data sets were evaluated and statistically analyzed. The objective and subjective image qualities were also evaluated. AMEIs at 40 keV showed the best visibility (80.7 %) and the lowest stage migration (35.5 %) for EGC. The stage migration for AMEIs at 40 keV was significantly lower than that for PEIs (p = 0.026). AMEIs at 40 keV had statistically higher CNR in the arterial and portal phases, gastric-specific diagnostic performance and visual sharpness compared with other AMEIs, MEIs and PEIs (all p < 0.05). AMEIs at 40 keV with MPR increase the CNR of EGC and thus potentially lower the stage migration of EGC. (orig.)

  11. Music Therapy is Associated With Family Perception of More Spiritual Support and Decreased Breathing Problems in Cancer Patients Receiving Hospice Care.

    Science.gov (United States)

    Burns, Debra S; Perkins, Susan M; Tong, Yan; Hilliard, Russell E; Cripe, Larry D

    2015-08-01

    Music therapy is a common discretionary service offered within hospice; however, there are critical gaps in understanding the effects of music therapy on hospice quality indicators, such as family satisfaction with care. The purpose of this study was to examine whether music therapy affected family perception of patients' symptoms and family satisfaction with hospice care. This was a retrospective, cross-sectional analysis of electronic medical records from 10,534 cancer patients cared for between 2006 and 2010 by a large national hospice. Logistic regression was used to estimate the effect of music therapy using propensity scores to adjust for non-random assignment. Overall, those receiving music therapy had higher odds of being female, having longer lengths of stay, and receiving more services other than music therapy, and lower odds of being married/partnered or receiving home care. Family satisfaction data were available for 1495 (14%) and were more likely available if the patient received music therapy (16% vs. 12%, P music therapy vs. those not. Patients who received music therapy were more likely to report discussions about spirituality (odds ratio [OR] = 1.59, P = 0.01), had marginally less trouble breathing (OR = 0.77, P = 0.06), and were marginally more likely to receive the right amount of spiritual support (OR = 1.59, P = 0.06). Music therapy was associated with perceptions of meaningful spiritual support and less trouble breathing. The results provide preliminary data for a prospective trial to optimize music therapy interventions for integration into clinical practice. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  12. Can we decrease the skin reaction in breast cancer patients using hyaluronic acid during radiation therapy? Results of phase III randomised trial

    International Nuclear Information System (INIS)

    Kirova, Youlia M.; Fromantin, Isabelle; De Rycke, Yann; Fourquet, Alain; Morvan, Esra; Padiglione, Solene; Falcou, Marie-Christine; Campana, Francois; Bollet, Marc A.

    2011-01-01

    Purpose: Radio-induced early skin reactions still remain a clinical challenge. Preliminary results with Hyaluronic acid, one of the most recent topical products used in this indication are proving interesting. To evaluate the efficacy of Hyaluronic acid compared to placebo. Material and methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during postoperative radiotherapy were eligible. They were randomised to receive either hyaluronic acid (A) or a simple emollient (B). The primary endpoint was the clinical evaluation of the erythema (success versus failure). Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Results: Two-hundred patients were enroled (A = 99, B = 101). Ninety-five patients per treatment arm could be evaluated. Failures occurred in 23 patients (24%) in the hyaluronic acid arm, and 32 (34%) in the emollient arm (p = 0.15). Seventy-three patients (36.5%) prematurely stopped the treatment without any ensuing difference between the two arms. Body mass index and the size of the epithelitis were both independently associated with the failure of the local treatment. The relative reduction of colorimetric levels was 20% in the hyaluronic acid group, and 13% in the emollient group (p = 0.46). Concerning the quality of life assessment, there was a trend towards a lower level of pain in patients receiving hyaluronic acid (p = 0.053). Conclusions: The present study showed no significant difference between hyaluronic acid and simple emollient in the treatment of acute radio-induced dermatitis. There was however a trend towards an improvement in both pain level and skin colorimetry.

  13. Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells.

    Science.gov (United States)

    Moody, Terry W; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A; Berna, Marc; Thill, Michelle; Jensen, Robert T; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D; Giaccone, Giuseppe; Wink, David A

    2010-05-01

    The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 microg/ml concentrations significantly reduced prostaglandin (PG)E(2) levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 microg/ml, respectively. Using the MTT assay, 10 microg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE(2) levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC. Published by Elsevier Ireland Ltd.

  14. Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.

    Directory of Open Access Journals (Sweden)

    Stuart J Smith

    Full Text Available INTRODUCTION: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS. METHODS: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS: Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.

  15. Rapid decrease of circulating tumor DNA predicted the treatment effect of nivolumab in a lung cancer patient within only 5 days

    Directory of Open Access Journals (Sweden)

    Yuki Iijima

    2017-01-01

    Full Text Available A 77-year-old Japanese man presented to our hospital with a 1-month history of low back pain and was diagnosed as having stage IV EGFR mutation-positive lung adenocarcinoma. After treatment with EGFR tyrosine kinase inhibitor and cytotoxic chemotherapy, nivolumab was started as fourth-line therapy. Remarkable regression of the primary tumor was observed, suggesting high anti-tumor activity of nivolumab. We retrospectively investigated the change in circulating tumor DNA (ctDNA variant allele fractions in serial plasma samples before and after the nivolumab therapy. Targeted sequencing analysis showed tumor-derived TP53R249S and EGFRL858R mutations detectable in plasma, and the timing of decrease was only 5 days, much earlier than the appearance of radiological changes. Overall, these results suggest that ctDNA might reflect tumor burden and might be a surrogate marker of the therapeutic efficacy of immune checkpoint therapy.

  16. Fish oil decreases C-reactive protein/albumin ratio improving nutritional prognosis and plasma fatty acid profile in colorectal cancer patients.

    Science.gov (United States)

    Mocellin, Michel Carlos; Pastore e Silva, Juliana de Aguiar; Camargo, Carolina de Quadros; Fabre, Maria Emília de Souza; Gevaerd, Scheila; Naliwaiko, Katya; Moreno, Yara Maria Franco; Nunes, Everson Araújo; Trindade, Erasmo Benicio Santos de Moraes

    2013-09-01

    Previous studies have shown that n-3 polyunsaturated fatty acids n-3 (n-3 PUFA) have several anticancer effects, especially attributed to their ability to modulate a variety of genomic and immune responses. In this context, this randomized, prospective, controlled clinical trial was conducted in order to check whether supplementation of 2 g/day of fish oil for 9 weeks alters the production of inflammatory markers, the plasma fatty acid profile and the nutritional status in patients with colorectal cancer (CRC). Eleven adults with CRC in chemotherapy were randomized into two groups: (a) supplemented (SG) daily with 2 g/day of encapsulated fish oil [providing 600 mg/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] for 9 weeks (n = 6), and (b) control (CG) (n = 5). All outcomes were evaluated on the day before the first chemotherapy session and 9 weeks later. Plasma TNF-α, IL-1β, IL-10 and IL-17A, the pro/anti-inflammatory balance (ratio TNF-α/IL-10 and IL-1β/IL10) and serum albumin, showed no significant changes between times and study groups (p > 0.05). C-reactive protein (CRP) and the CRP/albumin ratio showed opposite behavior in groups, significantly reducing their values in SG (p < 0.05). Plasma proportions of EPA and DHA increased 1.8 and 1.4 times, respectively, while the ARA reduced approximately 0.6 times with the supplementation (9 weeks vs baseline, p < 0.05). Patients from SG gained 1.2 kg (median) while the CG lost -0.5 kg (median) during the 9 weeks of chemotherapy (p = 0.72). These results demonstrate that 2 g/day of fish oil for 9 weeks of chemotherapy improves CRP values, CRP/albumin status, plasma fatty acid profile and potentially prevents weight loss during treatment.

  17. HET0016, a selective inhibitor of 20-HETE synthesis, decreases pro-angiogenic factors and inhibits growth of triple negative breast cancer in mice.

    Directory of Open Access Journals (Sweden)

    Thaiz Ferraz Borin

    Full Text Available A selective inhibitor of 20-HETE synthesis, HET0016, has been reported to inhibit angiogenesis. 20-HETE has been known as a second mitogenic messenger of angiogenesis inducing growth factors. HET0016 effects were analyzed on MDA-MB-231 derived breast cancer in mouse and in vitro cell line. MDA-MB-231 tumor cells were implanted in animals' right flank and randomly assigned to early (1 and 2, starting treatments on day 0, or delayed groups (3 and 4 on day 8 after implantation of tumor. Animals received HET0016 (10 mg/kg treatment via intraperitoneal injection for 5 days/week for either 3 or 4 weeks. Control group received vehicle treatment. Tumor sizes were measured on days 7, 14, 21, and 28 and the animals were euthanized on day 22 and 29. Proteins were extracted from the whole tumor and from cells treated with 10 µM HET0016 for 4 and 24 hrs. Protein array kits of 20 different cytokines/factors were used. ELISA was performed to observe the HIF-1α and MMP-2 protein expression. Other markers were confirmed by IHC. HET0016 significantly inhibited tumor growth in all treatment groups at all-time points compared to control (p<0.05. Tumor growth was completely inhibited on three of ten animals on early treatment group. Treatment groups showed significantly lower expression of pro-angiogenic factors compared to control at 21 days; however, there was no significant difference in HIF-1α expression after treatments. Similar results were found in vitro at 24 hrs of HET0016 treatment. After 28 days, significant increase of angiogenin, angiopoietin-1/2, EGF-R and IGF-1 pro-angiogenic factors were found (p<0.05 compared to control, as well as an higher intensity of all factors were found when compared to that of 21 day's data, suggesting a treatment resistance. HET0016 inhibited tumor growth by reducing expression of different set of pro-angiogenic factors; however, a resistance to treatment seemed to happen after 21 days.

  18. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    Science.gov (United States)

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  19. The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo.

    Science.gov (United States)

    Susanto, Johana M; Colvin, Emily K; Pinese, Mark; Chang, David K; Pajic, Marina; Mawson, Amanda; Caldon, C Elizabeth; Musgrove, Elizabeth A; Henshall, Susan M; Sutherland, Robert L; Biankin, Andrew V; Scarlett, Christopher J

    2015-05-01

    Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.

  20. Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Yu D

    2017-09-01

    Full Text Available Dinglai Yu,1 Tingting Ye,1 Yukai Xiang,1 Zhehao Shi,1 Jie Zhang,1 Bin Lou,1 Fan Zhang,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Quercetin, a flavone, is multifaceted, having anti-oxidative, anti-inflammatory, and anticancer properties. In the present study, we explored the effects of quercetin on the epithelial–mesenchymal transition (EMT and invasion of pancreatic cancer cells and the underlying mechanisms. We noted that quercetin exerted pronounced inhibitory effects in PANC-1 and PATU-8988 cells. Moreover, quercetin inhibited EMT and decreased the secretion of matrix metalloproteinase (MMP. Meanwhile, we determined the activity of STAT3 after quercetin treatment. STAT3 phosphorylation decreased following treatment with quercetin. We also used activating agent of STAT3, IL-6, to induce an increase in cell malignancy and to observe the effects of treatment with quercetin. As expected, the EMT and MMP secretion increased with activation of the STAT3 signaling pathway, and quercetin reversed IL-6-induced EMT, invasion, and migration. Therefore, our results demonstrate that quercetin triggers inhibition of EMT, invasion, and metastasis by blocking the STAT3 signaling pathway, and thus, quercetin merits further investigation. Keywords: quercetin, EMT, MMPs, STAT3, pancreatic cancer

  1. Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T-cells and decrease of ''naive'' (CD4-CD45R) T lymphocytes

    International Nuclear Information System (INIS)

    De Ruysscher, D.; Aerts, R.; Vantongelen, K.; Schueren, E. van der; Waer, M.; Vandeputte, M.

    1992-01-01

    Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or ''memory'' T cells recovered completely, while the CD4-45R or ''naive'' T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells (''activated'' T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. The authors propose that recovery of the CD4 cells is limited to the CD4-w29 (''memory'') population because of thymic dysfunction in older humans. (Author)

  2. Risks of Skin Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of skin cancer. Skin cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about skin cancer: Skin Cancer Prevention Skin Cancer Treatment Melanoma Treatment Genetics ...

  3. The phytochemical 3,3'-diindolylmethane decreases expression of AR-controlled DNA damage repair genes through repressive chromatin modifications and is associated with DNA damage in prostate cancer cells.

    Science.gov (United States)

    Palomera-Sanchez, Zoraya; Watson, Gregory W; Wong, Carmen P; Beaver, Laura M; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2017-09-01

    Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK). Decreased expression of these genes was accompanied by an increase in repressive chromatin marks, loss of AR occupancy and EZH2 recruitment to their regulatory regions. Decreased DNA repair gene expression was associated with an increase in DNA damage (γH2Ax) and up-regulation of genomic repeat elements LINE1 and α-satellite. Our results suggest that DIM suppresses AR-dependent gene transcription through epigenetic modulation, leading to DNA damage and genome instability in PCa cells. Published by Elsevier Inc.

  4. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  5. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky......We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...

  6. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  7. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

  8. The early predictive value of a decrease of metabolic tumor volume in repeated 18F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    International Nuclear Information System (INIS)

    Huang, Wei; Liu, Bo; Fan, Min; Zhou, Tao; Fu, Zheng; Zhang, Zicheng; Li, Hongsheng; Li, Baosheng

    2015-01-01

    Highlights: •The patients underwent the second FDG PET during the early stage of concurrent chemoradiotherapy (CCRT). •To our knowledge, this could be the first study showing that the repeated FDG PET during the early stage of CCRT has added value by being a prognostic factor for recurrence of the locally advanced NSCLC patients. •This is a result of continuous research. •The decrease of MTV was the only significant risk factor for recurrence. -- Abstract: Purpose: The aim of this study is to investigate the value of [ 18 F] fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). Methods: A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan–Meier curves. Results: Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan–Meier curve successfully. Conclusion: The prospective study has reinforced the early predictive value of MTV in repeated 18 F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who underwent CCRT. A

  9. Oral Cancer Screening

    Science.gov (United States)

    ... decrease the risk of oral cavity and oropharyngeal cancer. Oral cavity, pharyngeal, and laryngeal cancer are diseases in ... and treatment of oral cavity, pharyngeal, and laryngeal cancer: Oral Cavity and Oropharyngeal Cancer Prevention Lip and Oral ...

  10. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...

  11. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  12. The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line

    Directory of Open Access Journals (Sweden)

    Jun Xie

    2015-11-01

    Full Text Available The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.

  13. Hispaanias auhinnati Eesti jalatsikunstnikke / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2006-01-01

    Eesti Kunstiakadeemia nahakunsti magistrandid Maris Pill ja Karen Milistver esinesid edukalt võistlusel "Lapiz de Oro 2006". Maris Pill võitis jalatsiprototüüpide kategoorias tööga "Two Faces" Kuldpliiatsi ja Karen Milistver tööga "Showy shoes" teise auhinna

  14. Plaadid / Veiko Pesur, Tiiu Laks, Mart Normet

    Index Scriptorium Estoniae

    Pesur, Veiko

    2008-01-01

    Uutest heliplaatidest Shower, Nice Try ja Jim Arrow & The Anachrones "Eesti Rock Antoloogia", Eskimo "Psst! pole sõnu sõnumiks tarvis", Tanel Padar & The Sun "Veidi valjem kui vaikus II", Liisi Koikson "Väikeste asjade võlu"

  15. Plaadid / Kaur Garshnek, Maris Meiesaar, Tiiu Laks

    Index Scriptorium Estoniae

    Garšnek, Kaur, 1983-

    2008-01-01

    Uutest heliplaatidest Holst Singers ja Stephen Layton, Stephen "Rockferry", Queens Of Stone Age "Era Vulgaris Tour Edition", "Crystal Castles", Operator Please "Yes Yes Vindictive", Morcheeba "Dive Deep"

  16. Nele Suisalu otsib aktiivset vaatajat / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2008-01-01

    Lõuna-Prantsusmaal Montpellier's koreograaf Xavier le Roi juures õppiv Nele Suisalu lavastab koos elukaaslase Florent Hamoniga Tallinnas Kanuti Gildi saalis Augusti tantsufestivali raames tantsuetenduse "Ball"

  17. Ajakirjanike blogid ilmusid raamatutes / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2007-01-01

    Petrone, Epp. Minu Ameerika : reportaaže ja pihtimusi 2003-2006. 1. osa. Tartu : Petrone Print, 2007 ; Petrone, Epp, Reintam, Dagmar. Õun ära süüa? : [SL Õhtulehe populaarne suvejutt koos epiloogide ja lisadega. Tallinn] : Pegasus, 2007 ; Reintam, Dagmar. daki.elab.siin. Tartu : Petrone Print, 2007

  18. Tantsuline vaade kodusele Eestimaale Aafrikast / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    9. dets. esietendub Tallinna Meistrite Hoovi teatrisaalis Eike Ülevainu, Jaak Sapase ning Eneli Meresmaa lavastus "Estonia Meets Africa ehk Vaade eemalt", mis kannab tinglikult dokumentaallavastuse nime ja esitatakse nüüdistantsu ja -teatri vormis

  19. Tampere Teatrisuve maiuspalaks olid soomlased / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2006-01-01

    38. Tampere teatrisuvest (Tamperen teatterikesä), vaatluse all on soomlaste menutükid - Anna Krogeruse "Armastusest minu vastu" (lav. Irene Aho, Soome Rahvusteater) ja William Shakespeare'i "Richard III" (lav. Juha Luukkonen, Vaasa Linnateater)

  20. Frisk laks fra Norge til Japan

    DEFF Research Database (Denmark)

    Petersen, Tina; Nielsen, Lise Drewes

    2006-01-01

    Denne case er gennemført som en del af projektet "Konsekvenser af infrastruktur og det indre marked for udvalgte forsyningskæder", der blev gennemført på Institut for Transportstudier og finansieret af Transportrådet. I henhold til projektbeskrivelsen har formålet med projektet været at gennemfør...

  1. Kuninglikud lapsed keset Mallorcat / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2007-01-01

    Kunstnike Yannick (s. 1942) ja Ben (s. 1930) Jakoberi eramuuseumist Hispaanias. Lisaks 16.-19. saj. pärit lasteportreedele sisaldab muuseum moodsa kunsti töid, sealhulgas kunstnike endi tehtud skulptuure ning Domenico Gnolli teoseid. Kodumaja kujundajaks on egiptuse arhitekt Hassan Fathy

  2. TGF-β1 downregulates COX-2 expression leading to decrease of PGE2 production in human lung cancer A549 cells, which is involved in fibrotic response to TGF-β1.

    Directory of Open Access Journals (Sweden)

    Erina Takai

    Full Text Available Transforming growth factor-ß1 (TGF-β1 is a multifunctional cytokine that is involved in various pathophysiological processes, including cancer progression and fibrotic disorders. Here, we show that treatment with TGF-β1 (5 ng/mL induced downregulation of cyclooxygenase-2 (COX-2, leading to reduced synthesis of prostaglandin E2 (PGE2, in human lung cancer A549 cells. Treatment of cells with specific inhibitors of COX-2 or PGE2 receptor resulted in growth inhibition, indicating that the COX-2/PGE2 pathway contributes to proliferation in an autocrine manner. TGF-β1 treatment induced growth inhibition, which was attenuated by exogenous PGE2. TGF-β1 is also a potent inducer of epithelial mesenchymal transition (EMT, a phenotype change in which epithelial cells differentiate into fibroblastoid cells. Supplementation with PGE2 or PGE2 receptor EP4 agonist PGE1-alcohol, as compared with EP1/3 agonist sulprostone, inhibited TGF-β1-induced expression of fibronectin and collagen I (extracellular matrix components. Exogenous PGE2 or PGE2 receptor agonists also suppressed actin remodeling induced by TGF-β1. These results suggest that PGE2 has an anti-fibrotic effect. We conclude that TGF-β1-induced downregulation of COX-2/PGE2 signaling is involved in facilitation of fibrotic EMT response in A549 cells.

  3. Do patients' information needs decrease over the course of radiotherapy?

    NARCIS (Netherlands)

    Douma, Kirsten F. L.; Koning, Caro C. E.; Zandbelt, Linda C.; de Haes, Hanneke C. J. M.; Smets, Ellen M. A.

    2012-01-01

    We aimed to investigate if cancer patients' information needs decrease during radiotherapy and if so, which patient, consultation and radiation oncologist characteristics are associated with a decrease in information needs over time. In this longitudinal study, patients (n = 104) completed a

  4. Nuclear translocation of β-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression?

    Science.gov (United States)

    Stenner, Markus; Yosef, Basima; Huebbers, Christian U; Preuss, Simon F; Dienes, Hans-Peter; Speel, Ernst-Jan M; Odenthal, Margarete; Klussmann, Jens P

    2011-06-01

    High-risk human papillomaviruses (HPVs) constitute an important risk factor for tonsillar cancer. This study describes changes in cell adhesion molecules during metastasis of HPV-related and HPV-unrelated tonsillar carcinomas. We examined 48 primary tonsillar carcinoma samples (25 HPV-16 DNA-positive, 23 HPV-16 DNA-negative) and their respective lymph node metastases for their HPV status and for the expression of p16, epithelial cadherin (E-cadherin), β-catenin, and vimentin. A positive HPV-specific polymerase chain reaction finding correlated significantly with p16 overexpression in both primary tumours and their metastases (P<0.0001 for both). In HPV-unrelated carcinomas, the expression of E-cadherin was significantly lower in metastases than in primary tumours (P<0.001). In contrast, the expression of nuclear β-catenin was significantly higher in metastases than in primary tumours (P=0.016). In HPV-related carcinomas, nuclear localization of β-catenin expression was already apparent in primary tumours (P=0.030). The expression of vimentin significantly correlated with the grading of the primary tumour (P=0.021). Our data indicate that the down-regulation of E-cadherin and the up-regulation of nuclear β-catenin expression might be crucial steps during tumour progression of tonsillar carcinomas, being already present in primary tumours in HPV-driven carcinomas, but becoming apparent in HPV-unrelated tumours later in the process of metastasis. © 2011 Blackwell Publishing Limited.

  5. SU-F-T-106: A Dosimetric Study of Intensity Modulated Radiation Therapy to Decrease Radiation Dose to the Thoracic Vertebral Bodies in Patients Receiving Concurrent Chemoradiation for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiCostanzo, Dominic; Barney, Christian L.; Bazan, Jose G. [The Ohio State University, Columbus, Ohio (United States)

    2016-06-15

    Purpose: Recent clinical studies have shown a correlation between radiation dose to the thoracic vertebral bodies (TVB) and the development of hematologic toxicity (HT) in patients receiving chemoradiation (CRT) for lung cancer (LuCa). The feasibility of a bone-marrow sparing (BMS) approach in this group of patients is unknown. We hypothesized that radiation dose to the TVB can be reduced with an intensity modulated radiation therapy(IMRT)/volumetric modulated arc radiotherapy(VMAT) without affecting plan quality. Methods: We identified LuCa cases treated with curative intent CRT using IMRT/VMAT from 4/2009 to 2/2015. The TVBs from T1–T10 were retrospectively contoured. No constraints were placed on the TVB structure initially. A subset were re-planned with BMS-IMRT/VMAT with an objective or reducing the mean TVB dose to <23 Gy. The following data were collected on the initial and BMS plans: mean dose to planning target volume (PTV), lungs-PTV, esophagus, heart; lung V20; cord max dose. Pairwise comparisons were performed using the signed rank test. Results: 94 cases received CRT with IMRT/VMAT. We selected 11 cases (7 IMRT, 4 VMAT) with a range of initial mean TVB doses (median 35.7 Gy, range 18.9–41.4 Gy). Median prescription dose was 60 Gy. BMS-IMRT/VMAT significantly reduced the mean TVB dose by a median of 10.2 Gy (range, 1.0–16.7 Gy, p=0.001) and reduced the cord max dose by 2.9 Gy (p=0.014). BMS-IMRT/VMAT had no impact on lung mean (median +17 cGy, p=0.700), lung V20 (median +0.5%, p=0.898), esophagus mean (median +13 cGy, p=1.000) or heart mean (median +16 cGy, p=0.365). PTV-mean dose was not affected by BMS-IMRT/VMAT (median +13 cGy, p=0.653). Conclusion: BMS-IMRT/VMAT was able to significantly reduce radiation dose to the TVB without compromising plan quality. Prospective evaluation of BMS-IMRT/VMAT in patients receiving CRT for LuCa is warranted to determine if this approach results in clinically significant reductions in HT.

  6. Airplane radiation dose decrease during a strong Forbush decrease

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2004-01-01

    Roč. 2, S05001 (2004), s. 1-4 ISSN 1542-7390 Grant - others:EC project(XE) FIGM-CT2000-00068 Institutional research plan: CEZ:AV0Z1048901 Keywords : airplane dose * Forbush decrease * cosmic rays Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  7. Risks of Lung Cancer Screening

    Science.gov (United States)

    ... in women. Different factors increase or decrease the risk of lung cancer. Anything that increases your chance ... been studied to see if they decrease the risk of dying from lung cancer. The following screening ...

  8. [Why is bread consumption decreasing?].

    Science.gov (United States)

    Rolland, M F; Chabert, C; Serville, Y

    1977-01-01

    In France bread plays a very special and ambivalent role among our foodstuffs because of the considerable drop in its consumption, its alleged harmful effects on our health and the respect in which it is traditionally held. More than half the 1 089 adults interviewed in this study say they have decreased their consumption of bread in the last 10 years. The reasons given vary according to age, body weight and urbanization level. The main reasons given for this restriction are the desire to prevent or reduce obesity, the decrease in physical activity, the general reduction in food consumption and the possibility of diversifying foods even further. Moreover, the decreasing appeal of bread in relation to other foods, as well as a modification in the structure of meals, in which bread becomes less useful to accompany other food, accentuate this loss of attraction. However, the respect for bread as part of the staple diet remains very acute as 95 p. 100 of those interviewed express a reluctance to throw bread away, more for cultural than economic reasons. Mechanization and urbanization having brought about a decrease in energy needs, the most common alimentary adaptation is general caloric restriction by which glucids, and especially bread, are curtailed.

  9. Magical thinking decreases across adulthood.

    Science.gov (United States)

    Brashier, Nadia M; Multhaup, Kristi S

    2017-12-01

    Magical thinking, or illogical causal reasoning such as superstitions, decreases across childhood, but almost no data speak to whether this developmental trajectory continues across the life span. In four experiments, magical thinking decreased across adulthood. This pattern replicated across two judgment domains and could not be explained by age-related differences in tolerance of ambiguity, domain-specific knowledge, or search for meaning. These data complement and extend findings that experience, accumulated over decades, guides older adults' judgments so that they match, or even exceed, young adults' performance. They also counter participants' expectations, and cultural sayings (e.g., "old wives' tales"), that suggest that older adults are especially superstitious. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Does fertility decrease household consumption?

    OpenAIRE

    Jungho Kim; Henriette Engelhardt; Alexia Fürnkranz-Prskawetz; Arnstein Aassve

    2009-01-01

    This paper presents an empirical analysis of the relationship between fertility and a direct measure of poverty for Indonesia, a country, which has experienced unprecedented economic growth and sharp fertility declines over recent decades. It focuses on illustrating the sensitivity of the effect of fertility on household consumption with respect to the equivalence scale by applying the propensity score matching method. The analysis suggests that a newborn child decreases household consumption...

  11. Chemotherapy decreases epiphyseal strength and increases bone fracture risk

    NARCIS (Netherlands)

    Van Leeuwen, BL; Verkerke, GJ; Hartel, RM; Sluiter, WJ; Kamps, WA; Jansen, HWB; Hoekstra, HJ

    To establish the effect of three frequently used chemotherapeutic agents in childhood cancer on the skeleton, growing male Wistar rats were studied. Treatment with doxorubicin, methotrexate, and cisplatin reduces the proximal tibial growth plate shear strength because of a decreased surface area and

  12. Decreasing Fires in Mediterranean Europe.

    Directory of Open Access Journals (Sweden)

    Marco Turco

    Full Text Available Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value. These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011 and a mixed trend in Portugal (1980-2011. Similar overall results were found for the annual number of fires (NF, which globally decreased by about 12600 in the study period (about -59%, except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  13. Decreasing Fires in Mediterranean Europe.

    Science.gov (United States)

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  14. Technologies for Decreasing Mining Losses

    Science.gov (United States)

    Valgma, Ingo; Väizene, Vivika; Kolats, Margit; Saarnak, Martin

    2013-12-01

    In case of stratified deposits like oil shale deposit in Estonia, mining losses depend on mining technologies. Current research focuses on extraction and separation possibilities of mineral resources. Selective mining, selective crushing and separation tests have been performed, showing possibilities of decreasing mining losses. Rock crushing and screening process simulations were used for optimizing rock fractions. In addition mine backfilling, fine separation, and optimized drilling and blasting have been analyzed. All tested methods show potential and depend on mineral usage. Usage in addition depends on the utilization technology. The questions like stability of the material flow and influences of the quality fluctuations to the final yield are raised.

  15. Decreasing incidence rates of bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G

    2014-01-01

    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS: The overall incidence rate was 215.7, including 99.0 for community......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p incidence rate of community-acquired bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p

  16. Price of forest chips decreasing

    International Nuclear Information System (INIS)

    Hakkila, P.

    2001-01-01

    Use of forest chips was studied in 1999 in the national Puuenergia (Wood Energy) research program. Wood combusting heating plants were questioned about are the main reasons restricting the increment of the use of forest chips. Heating plants, which did not use forest chips at all or which used less than 250 m 3 (625 bulk- m 3 ) in 1999 were excluded. The main restrictions for additional use of forest chips were: too high price of forest chips; lack of suppliers and/or uncertainty of deliveries; technical problems of reception and processing of forest chips; insufficiency of boiler output especially in winter; and unsatisfactory quality of chips. The price of forest chips becomes relatively high because wood biomass used for production of forest chips has to be collected from wide area. Heavy equipment has to be used even though small fragments of wood are processed, which increases the price of chips. It is essential for forest chips that the costs can be pressed down because competition with fossil fuels, peat and industrial wood residues is hard. Low market price leads to the situation in which forest owner gets no price of the raw material, the entrepreneurs operate at the limit of profitability and renovation of machinery is difficult, and forest chips suppliers have to sell the chips at prime costs. Price of forest chips has decreased significantly during the past decade. Nominal price of forest chips is now lower than two decades ago. The real price of chips has decreased even more than the nominal price, 35% during the past decade and 20% during the last five years. Chips, made of small diameter wood, are expensive because the price includes the felling costs and harvesting is carried out at thinning lots. Price is especially high if chips are made of delimbed small diameter wood due to increased the work and reduced amount of chips. The price of logging residue chips is most profitable because cutting does not cause additional costs. Recovery of chips is

  17. Nanoparticle augmented radiation treatment decreases cancer cell proliferation.

    Science.gov (United States)

    Townley, Helen E; Rapa, Elizabeth; Wakefield, Gareth; Dobson, Peter J

    2012-05-01

    We report significant and controlled cell death using novel x-ray-activatable titania nanoparticles (NPs) doped with lanthanides. Preferential incorporation of such materials into tumor tissue can enhance the effect of radiation therapy. Herein, the incorporation of gadolinium into the NPs is designed to optimize localized energy absorption from a conventional medical x-ray. This result is further optimized by the addition of other rare earth elements. Upon irradiation, energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species (ROS). The authors report significant and controlled cell death using x-ray-activated titania nanoparticles doped with lanthanides as enhancers. Upon irradiation X-ray energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Rigidity spectrum of Forbush decrease

    International Nuclear Information System (INIS)

    Sakakibara, S.; Munakata, K.; Nagashima, K.

    1985-01-01

    Using data from neutron monitors and muon telescopes at surface and underground stations, the average rigidity spectrum of Forbush decreases (Fds) during the period of 1978-1982 were obtained. Thirty eight Ed-events are classified into two groups, Hard Fd and Soft FD according to size of Fd at the Sakashita station. It is found that a spectral form of a fractional-power type (P to the-gamma sub 1 (P+P sub c) to the -gamma sub2) is more suitable than that of a power-exponential type or of a power type with an upper limiting rigidity. The best fitted spectrum of the fractional-power type is expressed by gamma sub1 = 0.37, gamma sub2 = 0.89 and P subc = 10 GV for Hard Fd and gamma sub1 = 0.77, gamma sub2 = 1.02 and P sub c - 14GV for Soft Fd

  19. Method of decreasing nuclear power

    International Nuclear Information System (INIS)

    Masuda, Hiromi

    1987-01-01

    Purpose: To easily attain the power decreasing in a HWLWR type reactor and improve the reactor safety. Method: The method is applied to a nuclear reactor in which the reactor reactivity is controlled by control rods and liquid posions dissolved in moderators. Means for forecasting the control rod operation amount required for the reactor power down and means for removing liquid poisons in the moderators are provided. The control rod operation amount required for the power down is forecast before the power down and the liquid poisons in the moderators are removed. Then, the control rods are inserted into a deep insertion position to reduce the reactor power. This invention can facilitate easy power down, as well as provide effects of improving the controllability in the usual operation and of avoiding abrupt power down which leads to an improved availability. (Kamimura, M.)

  20. Summer Student Breast Cancer Research Training Program

    National Research Council Canada - National Science Library

    Zaloga, Gary P

    2005-01-01

    ... projects addressed the effects of omega-3 lipids upon breast cancer cells. 0mega-3 lipids were found to decrease breast cancer-induced muscle cell proteolysis and to induce apoptosis in cancer cells...

  1. Breast cancer

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi

    1992-01-01

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  2. Breast Cancer in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Tessier Cloutier, B; Clarke, A E; Ramsey-Goldman, R

    2013-01-01

    Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.......Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries....

  3. Tumor-derived transforming growth factor-beta 1 and interleukin-6 are chemotactic for lymphokine-activated killer cells

    NARCIS (Netherlands)

    Delens, N.; Torreele, E.; Savelkoul, H.; Baetselier, de P.; Bouwens, L.

    1994-01-01

    Adherent lymphokine-activated killer (A-LAK) cells are purified IL-2 activated natural killer (NK) cells with potent anti-tumor cytotoxic activity. They have been used in the adoptive immunotherapy of metastatic cancers. However, it has been shown that intravenously transferred LAK cells have a poor

  4. Risks of Breast Cancer Screening

    Science.gov (United States)

    ... is small. Different factors increase or decrease the risk of breast cancer. Anything that increases your chance ... magnetic resonance imaging) in women with a high risk of breast cancer MRI is a procedure that ...

  5. Oral cancer

    Science.gov (United States)

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... National Cancer Institute. PDQ lip and oral cavity cancer ... September 25, 2015. www.cancer.gov/types/head-and-neck/hp/lip- ...

  6. Cancer Statistics

    Science.gov (United States)

    ... What Is Cancer? Cancer Statistics Cancer Disparities Cancer Statistics Cancer has a major impact on society in ... success of efforts to control and manage cancer. Statistics at a Glance: The Burden of Cancer in ...

  7. Progreso en el logro de los Objetivos de Desarrollo del Milenio: la mortalidad por cáncer de cérvix desciende en Colombia / Progress in the achievement of the millennium development goals: the rate of mortality by cervical cancer decreases in Colombia

    Directory of Open Access Journals (Sweden)

    Jancy A. Huertas Q.

    2015-09-01

    Full Text Available Resumen Colombia cumpliendo en 2015 la fecha establecida para el alcance de los Objetivos de Desarrollo del Milenio (odm, ha logrado un descenso progresivo en las tasas de incidencia y mortalidad por cáncer de cuello uterino durante el decenio 2000 - 2010. En este período, la tasa de mortalidad descendió significativamente para las mujeres de todas las edades (11,4% en 1998 – 6,9 en 2011, meta a 2015: 6,8% y aumentó la proporción de casos in situ detectados oportunamente (63,31% en 2012. Colombia asumió el cáncer como un problema de salud pública y logró posicionarlo en la agenda pública. De igual forma, el cambio en el conocimiento y el autocuidado de la población, dieron como resultado un aumento en el pronóstico de las pacientes. A pesar de estos avances, el país continúa concentrando esfuerzos en reducir tasas de incidencia y mortalidad, aumentar los niveles de tecnología y promover mayor desarrollo en las regiones, mejorar sustancialmente el derecho de las mujeres a ser protegidas contra esta enfermedad, a través de acceso sin barreras a los programas de tamización y tratamientos del cáncer de cuello uterino. Y finalmente, la inclusión más amplia de la vacuna contra el vph con intervalo de cada 5 años, y que tiene un mayor potencial, especialmente entre las mujeres más jóvenes. La pregunta clave hoy en día es cómo acelerar ese ritmo de progreso en los indicadores propuestos por la agenda para el desarrollo después del 2015: Objetivos de Desarrollo Sostenible (ods, y ofrecer suficientes ejemplos de estrategias eficaces y adecuadas, y proporcionar experiencias en un contexto latinoamericano./ Abstract Two years before the deadline set for the achievement of the Millennium Development Goals (MDG, Colombia is experiencing a steady decline in the incidence and mortality rates of cervical cancer during the 2000-2010 decade. During this time, the mortality rate decreased significantly for women of all ages (11,4% in

  8. Stomach cancer

    International Nuclear Information System (INIS)

    Ito, Chikako

    1992-01-01

    Malignant tumors have received much attention as delayed effects of A-bomb radiation. Above all, it is of a major concern to determine how the incidence of stomach cancer, commonly observed among Japanese, is influenced by A-bomb radiation. This article focusses on the relationship between A-bomb radiation and the incidence of stomach cancer, and its histological features with a brief review of the literature. Mass screening for stomach cancer has showed in 1973 that the incidence of stomach cancer is definitely high among the heavily exposed A-bomb survivors. Since then, data analyses using the T65DR have showed it to be higher in the 100 rad exposed group than the 0 rad exposed group. On the basis of death certificates, the incidence of stomach cancer is found to be increased around 1976. When using DS86, the calculated lowest dose that produces a significantly high mortality incidence from stomach cancer is 1 Gy at the sheilding kerma and 0.5 Gy at organ absorbed dose. Histopathologically, the incidence of poorly differentiated adenocarcinoma is increased with increasing radiation doses; it is significantly increased in the 1 rad exposed group. The incidence of medullary type is decreased and the incidence of scirrhous type is increased with increasing radiation doses. (N.K.)

  9. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

  10. Plaadid / Rein Vader, Heidi Purga, Tiiu Laks...[jt.

    Index Scriptorium Estoniae

    2008-01-01

    Uutest heliplaatidest Nick Cave & The Bad Seeds "Dig, Lazarus, Dig!", Erykah Badu "New Amerikah Part One", Leslie da Bass "Nights By Open Windows", Jack Johnson "Sleep Througth The Static", Janet Jackson "Discipline", "Rock & Roll City"

  11. VAT-teater vaatab 30 aastat tulevikku / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2010-01-01

    VAT Teater toob S. Becketti "Krappi viimase lindi" lavale ebatavalisel moel. Festivalil "Draama 2010" Tartus toimub 8. septembril esimene avalik lindistus "...viimane lint / Saare esimene lint". Kontseptsioon: Tanel Saar ja Co. Esitus: Tanel Saar ja Hanna Allsaar. Näitejuhid-konsultandid: Rait Avestik ja Aare Toikka. "Krappi viimane lint" esietendub VAT Teatri ja Tanel Saare esituses 2040. a. sügisel. Festivali "Draama 2010" kavast

  12. Baltoscandal näitas Euroopa absurdi / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2010-01-01

    Rakveres 10. juulil lõppenud 11. rahvusvahelisest teatrifestivalist Baltoscandal. Prantslase Gerald Kurdiani kontsertetendusest "This is the Hello Monster!". Riina Maidre ja Maike Londi kontsertetendusest "PostUganda". Philippe Quesne'i ja tema trupi Vivarium Studio lavastusest "Big Bang". Taani tantsija Mette Ingvartseni lavastusest "Giant City". Akhe inseneriteatri lavastusest "Faust. 2360 sõna". Hollandi trupi Dood Paard lavastusest "Answer Me"

  13. Joonas Hellerma otsib teed vastuste juurde / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu

    2006-01-01

    Vestlusest 21-aastase Joonas Hellermaga, kes on lõpetanud Tallinna Ülikooli filmi ja video eriala ja on 2006. aastast Eesti Humanitaarinstituudi filosoofia magistrant, toimetab ETV kultuurisaadet "OP!", on kirjutanud kultuurilehes Sirp ja koolipõlves töötanud ka raadios

  14. Plaadid / Liina Valdre, Erik Aru, Tiiu Laks...[jt.

    Index Scriptorium Estoniae

    2007-01-01

    Uutest heliplaatidest Dylan Donkin "Food For Thoughtlessness", Kreatiivmootor "Irratsionaalne", Coco Electrik "Army Behind The Sun", Marc Collin featuring Katrine Ottosen & Valente "Two For The Road", Korn "Untitled"

  15. Kaks vaadet narkoelule ja tõlkimisele / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2010-01-01

    Arvustus: Thompson, Hunter Stockton. Hirm ja jälestus Las Vegases : metsik rännak Ameerika unelma südamesse / inglise keelest tõlkinud [ja järelsõna autor] Mihkel Kaevats. [Tallinn] : Eesti Päevaleht, 2010 ; Welsh, Irvine. Trainspotting : romaan / tõlkinud Olavi Teppan. Tallinn : Koolibri, 2010

  16. "Vasha" on mitme lõpuga film / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    Hannu Saloneni uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksa ja Iiri koostööfilmist, kus kesksetes osades on türklane Mehmet Kurtulus, eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  17. Pean saama Eurovisioonile, muidu suren 2010 / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2010-01-01

    12. märtsil Nokia kontserdimajas toimunud konkursi Eesti laul 2010 finaalkontserdist, saatejuhtidest Ott Sepast ja Märt Avandist, Madis Aesma loodud Pean saama Eurovisioonile, muidu suren 2010 lugudest. Robin Juhkentali võidulaulust

  18. Kivirähk korraga kahel laval / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    31. jaan. Ugalas esietenduvast Andrus Kivirähki esimesest näidendist "Vanamehed seitsmendalt" Peeter Tammearu lavastuses ja VAT Teatris lavale jõudvast Kivirähki uusimast tükist "Ingel, ingel, vii mind taeva" Aare Toikka lavastuses

  19. Plaadid / Mari Rebane, Heidi Purga, Tiiu Laks...[jt.

    Index Scriptorium Estoniae

    2008-01-01

    Uutest heliplaatidest Sigur Ros "Heim/Hvart", Jay-Z "American Gangster", Bob Marley and The Wailers "Roots, Rock, Remixed", Ghostface killah "The Big doe Rehab", Backstreet Boys "Unbreakable", Matchbox Twenty "Exile on Mainstream", "Just" Hits 6"

  20. Rahvusteema nüüdistantsu laval / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    5. nov. Kanuti Gildi saalis esietenduvast tantsulavastusest "Tavaj", mille autoriteks ja esitajateks on Alissa Šnaider, Päär Pärenson ja Renzo van Steenbergen. Lavastus uurib eesti- ja venekeelsete elanike suhtlemist Eestis

  1. Lavaka lõpetajate pink on pikk / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    Kevadel lavakunstikooli lõpetavate tudengite lavastusest "Pikk pink" , mis koosneb kuuest lühiloost - Mait Jooritsa "Kantani padi", Kristjan Üksküla "Jääger" ja "Albioni tütar", Roland Laosi "Genees ja katastroof", Hendrik Toompere jun. jun. "Karupoeg Puhh" ja Kerttu Moppeli " Leib!". Etendused toimuvad Hobuveskis

  2. Kümme teatristarti alustas suureks kasvamisega / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu,1984-

    2010-01-01

    Tallinna Linnateater annab kümnele algajale võimaluse lavastada professionaalses teatris. 6. oktoobril esietendunud monotükist "Suur mees juba", millega jõudis lavale kolm professionaalset debüüti korraga - Kaarel B. Väljamäe esimene teatritekst, Diana Leesalu esimene lavastus ning Priit Piusi esimene suur roll

  3. Kuulsused võitlevad õiglase kaubanduse eest / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2006-01-01

    Arenenud riigid ekspordivad oma põllumajandusülejääke arengumaadesse, müües neid seal odavama hinnaga kui kohalikud põllumehed oma toodangut, nii jäävad kohalikud farmerid rahata. Mitmed maailmakuulsad näitlejad ja lauljad osalevad õiglase kaubanduse liikumises. Lisa: Make Trade Fair üritab ohjeldada heaoluriike

  4. Hämmingut, striptiisi ja naeru Baltoscandalilt / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2010-01-01

    Itaalia eksperimentaalse teatri lavastaja Romeo Castellucci lavastusest "Hey Girl" ning briti näitleja Ursula Martinezi lavastusest "My Stories Your E-mails" Rakveres 7.-10. juulini toimunud teatrifestivalil Baltiscandal

  5. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Research Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer ...

  6. Lysis of autologous human macrophages by lymphokine-activated killer cells: interaction of effector cell and target cell conjugates analyzed by scanning electron microscopy.

    Science.gov (United States)

    Streck, R J; Helinski, E H; Ovak, G M; Pauly, J L

    1990-09-01

    Lymphokine (i.e., interleukin 2; IL-2)-activated killer (LAK) cells derived from normal human blood are known to destroy human tumor target cells. Accordingly, immunotherapy modalities using IL-2, either alone or in combination with LAK cells, have been evaluated for eradicating metastatic cancer. In studies conducted to characterize receptors on LAK cell membrane ultrastructures, we observed that LAK cells kill autologous human monocyte-derived macrophages (M phi). In these experiments, peripheral blood mononuclear cells of a healthy adult donor were cultured to generate LAK cells and autologous non-adherent M phi. Thereafter, conjugates were prepared by incubating for 3 h autologous populations of LAK cells and M phi. Examination of the conjugates by scanning electron microscopy (SEM) identified LAK cell-mediated killing of M phi. Moreover, SEM analysis of the LAK cell membrane architecture identified microvilli-like ultrastructures that provided a physical bridge that joined together the LAK cell and M phi. The immunological mechanism(s) underling LAK cell killing of autologous M phi is not known; nevertheless, these conjugates will provide a useful model to study membrane receptors on ultrastructures that mediate the initial stages of cytolysis that include target cell recognition and cell-to-cell adhesion. The results of our observations and the findings of other investigators who have also demonstrated LAK cell killing of autologous normal human leukocytes are discussed in the context of the association of IL-2 and IL-2-activated killer cells with side effects observed in ongoing clinical trials and with autoimmune disorders.

  7. Spontaneous entropy decrease and its statistical formula

    OpenAIRE

    Xing, Xiu-San

    2007-01-01

    Why can the world resist the law of entropy increase and produce self-organizing structure? Does the entropy of an isolated system always only increase and never decrease? Can be thermodymamic degradation and self-organizing evolution united? How to unite? In this paper starting out from nonequilibrium entropy evolution equation we proved that a new entropy decrease could spontaneously emerge in nonequilibrium system with internal attractive interaction. This new entropy decrease coexists wit...

  8. Bogarting that joint might decrease oral HPV among cannabis users.

    Science.gov (United States)

    Zwenger, S R

    2009-12-01

    Human papilloma virus (HPV) has many known strains, two of the most well studied perhaps being the high-risk types 16 and 18. These strains have attracted more interest because they are known to disrupt tumour-suppressor genes that control the cell cycle, rendering those genes less effective at keeping cell division in check.Within the last decade, an increase in oral hpv-linked cancers of the throat and tongue has been attributed to exposure and contraction of hpv through oral sex, most notably in younger people. An understudied and arguably equal contributor to oral hpv infection might be indirect contact with an infected person. Presented here is a brief but important perspective on the relationship between cannabis use and oral cancer. The development of oral cancer is not a result of smoking cannabis per se; rather, it is hypothesized to be a result of contracting hpv through various forms of sharing and passing joints and other smoking apparatuses. Therefore, it is hypothesized that bogarting (and not passing) joints might decrease oral hpv among cannabis smokers. Future research should therefore investigate the prevalence of oral hpv in cannabis smokers to better understand its epidemiology.

  9. Use of biofuels in road transport decreases

    International Nuclear Information System (INIS)

    Segers, R.

    2011-01-01

    The use of biofuels decreased from 3.5 percent, for all gasoline and diesel used by road transport in 2009, to 2 percent in 2010. Particularly the use of biodiesel decreased, dropping from 3.5 to 1.5 percent. The use of biogasoline remained stable, catering for 3 percent of all gasoline use. [nl

  10. Mastery Learning and the Decreasing Variability Hypothesis.

    Science.gov (United States)

    Livingston, Jennifer A.; Gentile, J. Ronald

    1996-01-01

    This report results from studies that tested two variations of Bloom's decreasing variability hypothesis using performance on successive units of achievement in four graduate classrooms that used mastery learning procedures. Data do not support the decreasing variability hypothesis; rather, they show no change over time. (SM)

  11. Cancer incidence among waiters

    DEFF Research Database (Denmark)

    Reijula, Jere; Kjaerheim, Kristina; Lynge, Elsebeth

    2015-01-01

    AIMS: To study cancer risk patterns among waiters in the Nordic countries. METHODS: We identified a cohort of 16,134 male and 81,838 female waiters from Denmark, Finland, Iceland, Norway and Sweden. During the follow-up period from 1961 to 2005, we found that 19,388 incident cancer cases were...... diagnosed. Standardised incidence ratio (SIR) was defined as the observed number of cancer cases divided by the expected number, based on national age, time period and gender-specific cancer incidence rates in the general population. RESULTS: The SIR of all cancers in waiters, in the five countries combined...... INCIDENCE IN SOME CANCER SITES CAN LIKELY BE EXPLAINED BY HIGHER ALCOHOL CONSUMPTION, THE PREVALENCE OF SMOKING AND OCCUPATIONAL EXPOSURE TO TOBACCO SMOKE HOPEFULLY, THE INCIDENCE OF CANCER AMONG WAITERS WILL DECREASE IN THE FUTURE, DUE TO THE BANNING OF TOBACCO SMOKING IN RESTAURANTS AND BARS IN THE NORDIC...

  12. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer Treatment Research Cancer & ...

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer Treatment Research Cancer & Public Health ...

  15. Eyelid Cancer

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  16. Anal Cancer

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  17. Thyroid Cancer

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  18. Appendix Cancer

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  19. Testicular cancer

    Science.gov (United States)

    ... Germ cell tumor; Seminoma testicular cancer; Nonseminoma testicular cancer; Testicular neoplasm ... Philadelphia, PA: Elsevier Saunders; 2014:chap 86. National Cancer Institute. PDQ testicular cancer treatment. Updated February 17, 2016. www.cancer. ...

  20. Socioeconomic position and survival after cervical cancer

    DEFF Research Database (Denmark)

    Ibfelt, E H; Kjær, S K; Høgdall, C

    2013-01-01

    In an attempt to decrease social disparities in cancer survival, it is important to consider the mechanisms by which socioeconomic position influences cancer prognosis. We aimed to investigate whether any associations between socioeconomic factors and survival after cervical cancer could...... be explained by socioeconomic differences in cancer stage, comorbidity, lifestyle factors or treatment....

  1. Can Diuretics Decrease Your Potassium Level?

    Science.gov (United States)

    ... of low potassium? Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, ... your urine. This can lead to low potassium levels in your blood (hypokalemia). Signs and symptoms of ...

  2. Using a Nonaversive Procedure to Decrease Refusals.

    Science.gov (United States)

    Spooner, Fred; And Others

    1990-01-01

    A nonaversive technique was used to teach a severely handicapped woman to decrease her refusals. The technique employed precision teaching via precise daily measurement strategies, environmental analysis, and a focus on building appropriate behavior. (JDD)

  3. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.

  4. Guilt decreasing marketing communication: an unexplored appeal

    OpenAIRE

    B. BUSACCA; SOSCIA I; PITRELLI E

    2007-01-01

    The phenomenon of guilt is relevant to a variety of consumption situations and practitioners around the world have continued to use it as a communication appeal. Marketing literature demonstrated that guilt as a distinct emotion can be aroused by advertising. Nevertheless, the capacity of advertising to decrease guilt was neglected by marketing scholars and the aim of this research is to assess the role of the guilt decreasing appeal in reducing anticipated guilt. Findings demonstrate the eff...

  5. Cancer incidence and novel therapies developed in Japan

    Directory of Open Access Journals (Sweden)

    Masaru Iwasaki

    2012-01-01

    -injected into the body to exert their action against the cancer. There are different kinds of Immuno-cell therapies being practised in more than 25 private and public institutions in Japan using Natural Killer (NK cells, Cytotoxic T lymphocytes (CTLs, Tumour Infiltrating Lymphocytes (TIL, Lymphokine activated Killer (LAK cells, Dendritic cells and Gamma Delta T (γδ T cells. [7] Importantly most of the innovations in cell based therapies in the world have been made in Japan because immunotherapy is a part of the Japanese Health care system and routine therapies for cancer in Japan. There have been randomized clinical trials on Immuno-cell therapy for liver cancer, lung cancer, gastric cancer, ovarian cancer with the results suggesting statistically significant increase in survival rate and increase in disease free survival rate. [8, 9, 10, 11] There are more than 25 institutions in Japan performing such cell based immunotherapies. A comprehensive review by Egawa et al on 1401 patients showed that when Immuno-cell therapy was combined with the conventional therapies, the efficacy increased upto 20-30%. [7] Immuno-cell is the least toxic of all therapies and can be administered even to terminally ill cancer patients. [12] Contrast to drugs, as autologous cell based Immuno-therapies are from the patient’s own blood and as they are custom tailored to each patient, though expensive, the adverse effects are minimal. To conclude, cancer-Immunocell therapies are the future of cancer therapies and further research is needed to enhance its efficacy and validate the results. References: 1.Cancer Statistics in Japan 2011. http://ganjoho.jp/data/public/statistics/backnumber/2011/files/cancer_statistics_2011.pdf2.Japan Cancer Society. Statistics on dynamic trends in Population compiled by the Ministry of Health, Labour and welfare. http://www.jcancer.jp/english/cancerinjapan/3.Maehara Y. Current Status of Cancer Treatment in Japan, and Future Prospects for the Japan Society of Clinical

  6. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  7. 6 Common Cancers - Skin Cancer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of cancer ...

  8. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  9. Risks of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening

    Science.gov (United States)

    ... black women. Different factors increase or decrease the risk of getting ovarian, fallopian tube, and primary peritoneal ... decrease the number of deaths from ovarian cancer. Risks of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer ...

  10. Decreased uptake after fractionated ablative doses of iodine-131

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hurng-Sheng [Show Chwan Memorial Hospital, Department of Surgery, Changhua, Taiwan (Taiwan); Hseu, Huey-Herng [Taichung Veterans General Hospital, Department of Medical Education and Research, Taichung (Taiwan); Lin, Wan-Yu; Wang, Shyh-Jen [Taichung Veterans General Hospital, Department of Nuclear Medicine, Taichung, Taiwan (Taiwan); Liu, Yao-Chi [Department of Surgery, General Surgery, National Defense Medical Center, Taipe (Taiwan)

    2005-02-01

    In an attempt to obviate the necessity for hospitalisation, the ablative dose of {sup 131}I in the treatment of thyroid cancer is divided into two or three fractions at weekly intervals in some hospitals with no special bed for {sup 131}I treatment. Thyroid stunning has been observed in patients receiving a {sup 131}I dose between 74 and 370 MBq (2-10 mCi). However, the influence of {sup 131}I uptake after administration of a higher dose, such as 1,110-1,850 MBq of {sup 131}I, has never been reported. In this study, we evaluated the degree of reduction in {sup 131}I uptake after patients received 1,480 MBq of {sup 131}I and evaluated the clinical value of fractionated ablative doses of {sup 131}I. Thirty-five patients with functional thyroid cancer received a total of 4,440 MBq (120 mCi) of {sup 131}I which was divided into three fractions administered at weekly intervals. In all patients two {sup 131}I whole-body scans were performed. The first scan was performed directly prior to the second dose of {sup 131}I (7 days after the first administration of {sup 131}I), and the second scan was performed 7 days after the second administration of {sup 131}I and directly prior to the third administration. Regions of interest including the neck and lungs were drawn to calculate the uptake of {sup 131}I in the thyroid remnant and possible cervical lymph node and lung metastases. The mean uptake of {sup 131}I was 2.73% 7 days after the first administration, and decreased significantly to 0.26% 7 days after the second administration. The mean decrease was as high as 80.7%. The decrease in {sup 131}I uptake was significant in all patients except the two with lung metastases. In the two patients with lung metastases, no definite evidence of decreased uptake was noted; the uptake of {sup 131}I in the lung metastases even increased on the second {sup 131}I image in one of these patients. After administration of 1,480 MBq of {sup 131}I, the decreased uptake was significant in all

  11. Smart bomb for cancer

    International Nuclear Information System (INIS)

    Karagiannis, Tom

    2006-01-01

    Cancer is a common disease that directly affects approximately one in three men and one in four women. Conventional cancer therapies - surgery, chemotherapy and radiotherapy - have improved markedly over the years but this has translated to only a small improvement in the mortality rate for many cancers. Figures from the World Health Organisation show that approximately 50% of people diagnosed with cancer will still die from the disease in developed countries, and about 80% will die in the developing world. The most obvious way of improving the cancer survival rate is early diagnosis of the disease. There is a strong correlation between the stage of the cancer at diagnosis and mortality for most cancers. For example, according to data from the American Cancer Society the 5-year survival rate for women diagnosed with stage I breast cancer is about 98%, but this decreases to just 16% for women with stage IV cancer. Similarly, the 5-year survival for men diagnosed with stage I prostate cancer is 100%, decreasing to 31% if the cancer had spread to other parts of the body prior to diagnosis. However, one of the main problems related to early diagnosis of cancer is that in many instances there are minimal symptoms until the disease has progressed. As a result, in many cases the cancer is quite advanced at the time of diagnosis. The most life-threatening aspect of the cancer is when cancer cells have spread from the tissue in which the disease originated to other organs, which is known as metastasis. Unfortunately, conventional therapies are not ideal for curing advanced cancers that have undergone metastasis. Therefore, to improve cancer survival rates we require more sophisticated therapeutic approaches. One of these relatively new strategies involves the use of monoclonal antibodies, which are proteins that bind specifically to targets on cancer cells. These targets, known as receptors, are expressed on the surface of cells. The monoclonal antibodies used for therapy

  12. Distraction decreases prefrontal oxygenation: A NIRS study.

    Science.gov (United States)

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. IGF-Regulated Genes in Prostate Cancer

    National Research Council Canada - National Science Library

    Roberts, Charles

    2003-01-01

    We hypothesized that genes that are differentially expressed as a result of the decreased IGF-I receptor gene expression seen in metastatic prostate cancer contribute to prostate cancer progression...

  14. IGF-Regulated Genes in Prostate Cancer

    National Research Council Canada - National Science Library

    Roberts, Charles T., Jr

    2005-01-01

    We hypothesized that genes that are differentially expressed as a result of the decreased IGF-I receptor gene expression seen in metastatic prostate cancer contribute to prostate cancer progression...

  15. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Unusual Cancers of Childhood Treatment Childhood Cancer Genomics Study Findings Metastatic Cancer Metastatic Cancer Research Common Cancer Types Recurrent Cancer Common Cancer Types ...

  16. Maternal lung cancer and testicular cancer risk in the offspring.

    Science.gov (United States)

    Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

    2003-07-01

    It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

  17. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate ... Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer ...

  18. Lung Cancer Prevention

    Science.gov (United States)

    ... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... following PDQ summaries for more information about lung cancer: Lung Cancer Screening Non-Small Cell Lung Cancer Treatment ...

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer ...

  20. Cancer treatment: what's ahead?

    International Nuclear Information System (INIS)

    Parvez, T.

    2005-01-01

    Surgery, chemotherapy, and radiation therapy are standard modalities for cancer treatment. Biological therapy (immunotherapy, biotherapy, or biological response modifier therapy) is a comparatively novel addition to this armamentarium. Biological therapies use the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some cancer treatments. Biological therapeutic agents include interferons, interleukins, colony-simulating factors, monoclonal antibodies, vaccines, gene therapy, and nonspecific immunomodulating agents. A promising form of cancer treatment is immunotherapy. Immunotherapy for cancer is essentially the stimulation of the immune system through a variety of reagents such as vaccines, infusion of T-cells, or cytokines. These reagents act through one of several mechanisms including stimulating the anti-tumour response, decreasing suppressor mechanisms, altering tumour cells to increase their immunogenicity and making them more susceptible to immunologic defenses, and improving tolerance to cytotoxic agents or radiotherapy. This review describes some novel approaches in the immunotherapy in cancer. (author)

  1. Radiobiological characteristics of cervical cancer

    International Nuclear Information System (INIS)

    Kagabu, Teruo; Kobayashi, Takashi; Nanayama, Kunihiko

    1976-01-01

    In order to observe the radiobiological characteristics of cervical cancer, the author carried out irradiation of 60 Co in 16 cases of cervical cancer. The primary lesion of each case was exposed to radiation of 100 R once a day, 40 times in sequence, totaling 4,000 R. To evaluate this results, the vaginal smears were obtained everyday and examined for changes in cancerous cells caused by the irradiation. The results of our study showed that cervical cancer could be classified into three groups according to the radiosensitivity of its cancerous cells. In the group of low-radiosensitivity (11 cases of 16), the cancerous cells decreased gradually, and enlargement of the nuclei of the cancerous cells was observed from 2,000 R of irradiation, but the majority of the cancerous cells were those of nucleus after the irradiation of 4,000 R. In all of the 5 uterus removed, residual cancer lesion was noted. The radiocuability was unfavourable. In the group of high-radiosensitivity (4 cases of 16), the cancerous cells decreased remarkablly. Enlargement of nucleus was noted from 1,000 R of the irradiation, the cancerous cells of small-sized nucleus appeared with the irradiation of 3,000 R but the cancerous cells almost disappeared with the irradiation of 4,000 R. The radiocuability was favourable. In the group of combination of high-radiosensitivity and low-radiosensitivity portions (one case of 16), the cancerous cells decreased remarkablly until the exposure to the radiation of 2,000 R but thereafter did slowly. In a removed uterus, the cancer lesion was noted, but the prognosis was favourable. The foregoing results suggest that changes in the nuclear diameter of the cancerous cells in vaginal smears during irradiation can tell the radiosensitivity of the cancerous cells. (Kanao, N.)

  2. Aggregate Unemployment Decreases Individual Returns to Education

    Science.gov (United States)

    Ammermueller, Andreas; Kuckulenz, Anja; Zwick, Thomas

    2009-01-01

    Aggregate unemployment may affect individual returns to education through qualification-specific responses in participation and wage bargaining. This paper shows that an increase in regional unemployment by 1% decreases returns to education by 0.005 percentage points. This implies that higher skilled employees are better sheltered from labour…

  3. Italian cancer figures, report 2009: Cancer trend (1998-2005).

    Science.gov (United States)

    2009-01-01

    the aim of this collaborative project of the Italian Network of Cancer Registries (Airtum; www.registri-tumori.it) was to analyse cancer incidence and mortality trends in Italy with special reference to the period 1998-2005. the study was based on the Airtum database, which collects and checks data from all the Airtum registries. The present study was based on 20 general and 2 specific populationbased cancer registries. Overall, we analysed 818,017 incident cases and 342,444 cancer deaths for the time period 1998-2005. Seventy percent of the analysed population was from the North of Italy, 17% from the Centre, and 13% from the South. A joinpoint analysis was carried out to detect the point in time where the trend changed; trends are described by means of the estimated annual percent change (APC), with appropriate 95% confidence intervals. Crude and standardized incidence and mortality rates were computed for 36 cancer sites, for both sexes, three age-classes (0-49, 50-69 and 70+ years), and three geographic areas (North, Centre, and South of Italy). Specific chapters are devoted to long-term trends (1986-2005), differences among age-groups, and international comparisons. In 1998-2005, cancer mortality for all sites showed a statistically significant decrease among men (APC - 1.7) and women (- 0.8). Mortality significantly decreased in both sexes for stomach cancer, rectum cancer, liver cancer, and Hodgkin lymphoma. Mortality also decreased among men for cancers of the upper aerodigestive tract, oesophagus, lung, prostate, urinary bladder, and leukaemia. Among women mortality decreased for cancers of the colon, bone, breast, and uterus not otherwise specified. An increase in mortality was recorded for lung cancer among women (+1.5) and melanoma among men (+2.6). Incidence for all cancers together (except non-melanoma skin cancers) increased among men (APC +0.3) and remained stable among women. Cancer sites which showed increasing incidence were thyroid and melanoma

  4. Lifestyle changes for prevention of breast cancer

    OpenAIRE

    Hashemi, Seyed Hesam Bani; Karimi, Samieh; Mahboobi, Hamidreza

    2014-01-01

    Breast cancer is the second most common cause of death from cancer among women. Lifestyle changes are shown to be important in the prevention of breast cancer. Diet, physical activity, smoking, alcohol use, and vitamin and mineral use are key factors influencing the risk of breast cancer among women. Because these factors are related to each other, it is difficult to assess their individual roles in breast cancer. Some of these factors are alterable, meaning that women can decrease their risk...

  5. Did liberalising bar hours decrease traffic accidents?

    Science.gov (United States)

    Green, Colin P; Heywood, John S; Navarro, Maria

    2014-05-01

    Legal bar closing times in England and Wales have historically been early and uniform. Recent legislation liberalised closing times with the object of reducing social problems thought associated with drinking to "beat the clock." Indeed, using both difference in difference and synthetic control approaches we show that one consequence of this liberalisation was a decrease in traffic accidents. This decrease is heavily concentrated among younger drivers. Moreover, we provide evidence that the effect was most pronounced in the hours of the week directly affected by the liberalisation: late nights and early mornings on weekends. This evidence survives a series of robustness checks and suggests at least one socially positive consequence of extending bar hours. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Decreased decorin expression in the tumor microenvironment

    International Nuclear Information System (INIS)

    Bozoky, Benedek; Savchenko, Andrii; Guven, Hayrettin; Ponten, Fredrik; Klein, George; Szekely, Laszlo

    2014-01-01

    Decorin is a small leucine-rich proteoglycan, synthesized and deposited by fibroblasts in the stroma where it binds to collagen I. It sequesters several growth factors and antagonizes numerous members of the receptor tyrosine kinase family. In experimental murine systems, it acted as a potent tumor suppressor. Examining the Human Protein Atlas online database of immunostained tissue samples we have surveyed decorin expression in silico in several different tumor types, comparing them with corresponding normal tissues. We found that decorin is abundantly secreted and deposited in normal connective tissue but its expression is consistently decreased in the tumor microenvironment. We developed a software to quantitate the difference in expression. The presence of two closely related proteoglycans in the newly formed tumor stroma indicated that the decreased decorin expression was not caused by the delay in proteoglycan deposition in the newly formed connective tissue surrounding the tumor

  7. Calming Meditation Increases Altruism, Decreases Parochialism

    OpenAIRE

    Frost, Karl

    2017-01-01

    It has been proposed that cultivating calm will increase altruism and decrease parochialism, where altruism is defined as self-sacrifice in support of others, regardless of group affiliation or identity, and parochialism is defined as prosocial self-sacrifice restricted to fellow members of a group. Such could be the case with a calming meditation practice. An alternate hypothesis, coming from the study of ritual, proposes that shared practices lead to bonding, increasing parochialism, but no...

  8. INVENTORY DECISIONS WITH DECREASING PURCHASING COSTS

    OpenAIRE

    XIANGPEI HU; HUIMIN WANG; YUNZENG WANG

    2012-01-01

    Costs of many items drop systematically throughout their life-cycles, due to advances in technology and competition. Motivated by the management of service parts for some high-tech products, this paper studies inventory decisions for such items. In a periodic review setting with stochastic demand, we model the purchasing costs of successive periods as a stochastic and decreasing sequence. Unit selling price of the item is determined as some mark-up of the purchasing cost and, hence, will chan...

  9. Metastatic Cancer

    Science.gov (United States)

    Metastatic cancer is cancer that spreads from its site of origin to another part of the body. Learn how cancer spreads, possible symptoms, common sites where cancer spreads, and how to find out about treatment options.

  10. Prostate Cancer

    Science.gov (United States)

    ... breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Obesity. Obese men diagnosed with prostate cancer may be more likely ...

  11. Cervical Cancer

    Science.gov (United States)

    ... I find more information about cervical and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...

  12. Ovarian Cancer

    Science.gov (United States)

    ... I find more information about ovarian and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...

  13. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  14. Topical nutlin-3a does not decrease photocarcinogenesis induced by simulated solar radiation in hairless mice

    DEFF Research Database (Denmark)

    Lerche, Catharina Margrethe; Philipsen, Peter Alshede; Poulsen, Thomas

    2012-01-01

    Nutlin-3a increases p53 levels after UVB radiation, which could result in a decrease in DNA damage and thus lead to a lower risk of non-melanoma skin cancer. Especially, organ transplant recipients might derive benefit from such a topical formulation with an active ingredient to prevent DNA damage....

  15. Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin resistant mouse B16-BL6 melanoma.

    Science.gov (United States)

    Gautam, S C; Chikkala, N F; Lewis, I; Grabowski, D R; Finke, J H; Ganapathi, R

    1992-01-01

    Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM-resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM-resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype.

  16. Cancer following medical irradiation

    International Nuclear Information System (INIS)

    Boice, J.D.

    1981-01-01

    Several generalizations about radiation carcinogenesis can be made: (1) a single exposure is sufficient to elevate cancer incidence many years later; (2) radiation-induced cancer cannot be distinguished from naturally occurring cancer, i.e., there is no unique radiogenic cancer; (3) all cancers appear to be increased after irradiation with the exception of chronic lymphocytic leukemia, and possibly Hodgkin's disease, cervical cancer, and a few others; (4) the breast, thyroid, and bone marrow appear especially radiosensitive; (5) leukemia is the most prominent radiogenic tumor and shows a wave-like pattern of excess incidence over time, and the excess begins within two to four years, peaks about six to eight years, and decreases to normal levels about 25 years later; (6) solid tumors have a minimum latent period of about ten years, and for several cancers, the temporal pattern of incidence appears to follow the natural incidence, i.e., the cancers do not occur before the ages normally associated with increased incidence, implying that age-dependent factors influence the expression of disease; (7) age at exposure is perhaps the most important host factor influencing subsequent cancer risk; (8) the percentage increase in cancer incidence per rad is not the same for all cancers, i.e., some cancers of high natural incidence, e.g., colon, have low relative risks and some cancers of low natural incidence, e.g., thyroid, have high relative risks; (9) dose-effect curves are often linear, but curvilinearity is also observed and is possibly associated with the need for two ionizing events for transformation to occur at low doses, the influence of cell sterilization at moderate doses, the likelihood of wasted dose at high doses, and/or the influence of factors that effect the expression of disease

  17. Lung cancer

    International Nuclear Information System (INIS)

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer

  18. Breast cancer in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, S.; Ramsey-Goldman, R.; Petri, M.

    2017-01-01

    Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi......-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results...... There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug...

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Reports, Research, and Literature Cancers by Body Location/System Childhood Cancers Late Effects of Childhood Cancer ... to Z List of Cancers Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer ...

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Understanding Cancer What Is Cancer? Cancer Statistics Cancer Disparities Understanding Cancer What Is Cancer Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview ...

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Contact Dictionary Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer ... Is Cancer Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening Overview ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Directives Using Trusted Resources Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and Literature Cancers ... Cancers Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research NCI’s ...

  3. Tumor-cytolytic human macrophages cultured as nonadherent cells: potential for the adoptive immunotherapy of cancer.

    Science.gov (United States)

    Helinski, E H; Hurley, E L; Streck, R J; Bielat, K L; Pauly, J L

    1990-01-01

    Tumor-cytolytic lymphokine (e.g., interleukin-2; IL-2)-activated killer cells are currently being evaluated in IL-2/LAK cell adoptive immunotherapy regimens for the treatment of cancer. Monocyte-derived macrophages (M phi) are also known to be efficient tumor killer cells; accordingly, M phi that have been activated in vitro may also be of therapeutic merit. However, attempts to cultivate M phi for morphological and functional studies have often been compromised because M phi adhere rapidly and tenaciously to cultureware. Studies that we have conducted to address this problem have proven successful in developing procedures for the long-term cultivation of non-adherent immunocompetent M phi in serum-free medium using petri dishes containing a thin Teflon liner. The utility of this technology is documented by the results of studies presented herein in which light and scanning electron microscopy was used to analyze tumor-cytolytic human M phi. In these experiments, we demonstrated that nonadherent immunocompetent human M phi can be prepared for detailed examinations of their pleomorphic membrane architecture. Moreover, nonadherent human M phi could readily be collected for preparing conjugates of M phi and tumor cells. It is anticipated that this technology should prove useful for future structure-function studies defining the topographical location and spatial distribution of antigens and receptors on M phi membrane ultrastructures, particularly the microvilli-like projections that bridge together an immunocompetent effector M phi and target cell (e.g., tumor cells and microbial pathogens) and which provide the physical interaction required for the initial phases of a cellular immune response that includes antigen recognition and cell-to-cell adhesion.

  4. 6 Common Cancers - Lung Cancer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next three ...

  5. Music decreases aortic stiffness and wave reflections.

    Science.gov (United States)

    Vlachopoulos, Charalambos; Aggelakas, Angelos; Ioakeimidis, Nikolaos; Xaplanteris, Panagiotis; Terentes-Printzios, Dimitrios; Abdelrasoul, Mahmoud; Lazaros, George; Tousoulis, Dimitris

    2015-05-01

    Music has been related to cardiovascular health and used as adjunct therapy in patients with cardiovascular disease. Aortic stiffness and wave reflections are predictors of cardiovascular risk. We investigated the short-term effect of classical and rock music on arterial stiffness and wave reflections. Twenty healthy individuals (22.5±2.5 years) were studied on three different occasions and listened to a 30-min music track compilation (classical, rock, or no music for the sham procedure). Both classical and rock music resulted in a decrease of carotid-femoral pulse wave velocity (PWV) immediately after the end of music listening (all pclassical or rock music in a more sustained way (nadir by 6.0% and 5.8%, respectively, at time zero post-music listening, all pmusic preference was taken into consideration, both classical and rock music had a more potent effect on PWV in classical aficionados (by 0.20 m/s, p=0.003 and 0.13 m/s, p=0.015, respectively), whereas there was no effect in rock aficionados (all p=NS). Regarding wave reflections, classical music led to a more potent response in classical aficionados (AIx decrease by 9.45%), whereas rock led to a more potent response to rock aficionados (by 10.7%, all pMusic, both classical and rock, decreases aortic stiffness and wave reflections. Effect on aortic stiffness lasts for as long as music is listened to, while classical music has a sustained effect on wave reflections. These findings may have important implications, extending the spectrum of lifestyle modifications that can ameliorate arterial function. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. SPP will decrease price of transport

    International Nuclear Information System (INIS)

    Janoska, J.

    2003-01-01

    Starting next year gas utility Slovensky plynarensky priemysel, a.s., Bratislava (SPP) will decrease the fees for transport of gas to its client from third parties. This decision should have a positive effect mainly on large industrial customers. The fact that SPP decided not to apply the approved ruling to its full extent was the result of negotiations with the regulator and the Ministry of Economy. SPP is not afraid it might lose customers. This decision only gives them a competitive advantage. (Author)

  7. Decreasing Human Trafficking through Sex Work Decriminalization.

    Science.gov (United States)

    Albright, Erin; D'Adamo, Kate

    2017-01-01

    In order to decrease human trafficking, health care workers should support the full decriminalization of prostitution. Similar to trafficking in other forms of labor, preventing trafficking in the sex trade requires addressing the different forms of marginalization that create vulnerable communities. By removing punitive laws that prevent reporting of exploitation and abuse, decriminalization allows sex workers to work more safely, thereby reducing marginalization and vulnerability. Decriminalization can also help destigmatize sex work and help resist political, social, and cultural marginalization of sex workers. © 2017 American Medical Association. All Rights Reserved.

  8. Methodology of decreasing software complexity using ontology

    Science.gov (United States)

    DÄ browska-Kubik, Katarzyna

    2015-09-01

    In this paper a model of web application`s source code, based on the OSD ontology (Ontology for Software Development), is proposed. This model is applied to implementation and maintenance phase of software development process through the DevOntoCreator tool [5]. The aim of this solution is decreasing software complexity of that source code, using many different maintenance techniques, like creation of documentation, elimination dead code, cloned code or bugs, which were known before [1][2]. Due to this approach saving on software maintenance costs of web applications will be possible.

  9. Breastfeeding Is Associated with Decreased Childhood Maltreatment.

    Science.gov (United States)

    Kremer, Kristen P; Kremer, Theodore R

    Child maltreatment has serious implications for youth outcomes, yet its associations with early parenting practices are not fully understood. This study investigated whether breastfeeding practices are correlated with childhood maltreatment. Data were utilized from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative and longitudinal study of adolescents. The analytic sample comprised 4,159 adolescents. The outcome variables included four subtypes of childhood maltreatment (neglect, inadequate supervision, physical abuse, and sexual abuse). The primary independent variable was breastfeeding duration. Covariates of the child, mother, and household were included in analyses. Logistic regression models were employed to predict odds of maltreatment subtypes from breastfeeding duration and covariates. Compared with adolescents never breastfed, adolescents breastfed 9 months or longer had a reduced odds of having experienced neglect (odds ratio [OR] = 0.54; 95% confidence interval [CI] = 0.35-0.83) and sexual abuse (OR = 0.47; 95% CI = 0.24-0.93) after controlling for covariates. Breastfeeding duration is significantly associated with decreased childhood neglect and sexual abuse. Breastfeeding practices should be explored as a consideration among clinicians when assessing maltreatment risk. Further research should examine whether a causal relationship exists between breastfeeding and decreased maltreatment.

  10. Statins Decrease Oxidative Stress and ICD Therapies

    Directory of Open Access Journals (Sweden)

    Heather L. Bloom

    2010-01-01

    Full Text Available Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs and interleukin-6 (IL-6. Results. Subjects included 252 (83% men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r=0.12, P=.02. Subjects on statins had lower hsCRP (5.2 versus 6.3; P=.05 and DROM levels (373 versus 397; P=.03. Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation.

  11. Serum Soluble Corin is Decreased in Stroke.

    Science.gov (United States)

    Peng, Hao; Zhu, Fangfang; Shi, Jijun; Han, Xiujie; Zhou, Dan; Liu, Yan; Zhi, Zhongwen; Zhang, Fuding; Shen, Yun; Ma, Juanjuan; Song, Yulin; Hu, Weidong

    2015-07-01

    Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke. © 2015 American Heart Association, Inc.

  12. Lifestyle Decreases Risk Factors for Cardiovascular Diseases

    Science.gov (United States)

    Slavíček, Jaroslav; Kittnar, Otomar; Fraser, Gary E.; Medová, Eva; Konečná, Jana; Žižka, Robert; Dohnalová, Alena; Novák, Vladimír

    2009-01-01

    Summary The morbidity and mortality of the cardiovascular diseases is high in the developed countries. The lifestyle changes are capable to decrease it by 50%. The aim of the present study was to measure the parameters of some risk factors before and after a one-week NEW START rehabilitative retreat. 1,349 volunteers, 320 men, 1,029 woman, mean age 51±14.5 (SD) years participated in 30 rehabilitative retreats from 1999–2006 in the Czech Republic, using a low-fat, low-energy, lacto-ovo-vegetarian diet and exercise, in a stress-free environment. Body weight, height, BMI, blood pressure, heart rate, serum cholesterol and blood glucose were measured. Body weight decreased in 1,223 measured persons from 71.2±14.38 (SD) to 70.6±14.02 kg (pSeventh-day Adventists than in controls who never observed the diet and avail the lifestyle programs. The parameters were nonsignificantly changed one year after finishing the retreat in the sample of 68 persons showing the positive effect of retreats. Our results showed, that the intake of a low-fat, low-energy diet, over the course of one week in a stress-free environment, had positive impact on the risk factors of cardiovascular diseases. PMID:19256282

  13. Targeting cancer cells using 3-bromopyruvate for selective cancer treatment

    Directory of Open Access Journals (Sweden)

    Hussam H Baghdadi

    2017-01-01

    Full Text Available Cancer treatment deserves more research efforts despite intensive conventional treatment modalities for many types of malignancies. Metastasis and resistance to chemotherapy and radiotherapy receive a lot of global research efforts. The current advances in cancer biology may improve targeting the critical metabolic differences that distinguish cancer cells from normal cells. Cancer cells are highly glycolytic for energy production, exhibit the Warburg effect, establish aggressive acidic microenvironment, maintain cancer stem cells, exhibit resistance to chemotherapy, have low antioxidant systems but different ΔΨm (delta psi, mitochondrial transmembrane potential, express P-glycoprotein for multidrug resistance, upregulate glucose transporters and monocarboxylate transporters and are under high steady-state reactive oxygen species conditions. Normal cells differ in all these aspects. Lactate produced through the Warburg effect helps cancer metastasis. Targeting glycolysis reactions for energy production in cancer cells seems promising in decreasing the proliferation and metastasis of cancer cells. 3-bromopyruvate makes use of cancer biology in treating cancer cells, cancer stem cells and preventing metastasis in human cancer as discussed in this review. Updated advances are analyzed here, which include research analysis of background, experience, readings in the field of cancer biology, oncology and biochemistry.

  14. Radiation-induced cancers in man

    International Nuclear Information System (INIS)

    Hirose, Fumio

    1978-01-01

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer. (Ichikawa, K.)

  15. Radiation-induced cancers in man

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, F [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1978-07-01

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer.

  16. Palliative therapy of advanced breast cancer with targeted polymer-bound drug

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka; Strohalm, Jiří; Kubáčková, K.; Jelínková, Markéta; Rozprimová, L.; Šírová, Milada; Plocová, Daniela; Etrych, Tomáš; Mrkvan, Tomáš; Kovář, Marek; Ulbrich, Karel

    2003-01-01

    Roč. 12, č. 1 (2003), s. 375 ISSN 1107-3756. [World Congress on Advances in Oncology /8./. Crete, 16.10.2003-18.10.2003] Institutional research plan: CEZ:AV0Z4050913; CEZ:AV0Z5020903 Keywords : hpma * epr * lak Subject RIV: EE - Microbiology, Virology Impact factor: 1.940, year: 2003

  17. Meat, dairy, and cancer1234

    Science.gov (United States)

    Abid, Zaynah; Cross, Amanda J; Sinha, Rashmi

    2014-01-01

    In 2007 the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) report judged that the evidence for an association between red and processed meat consumption and colorectal cancer was convincing. In addition, the effect of other animal products on cancer risk has been studied, and the WCRF/AICR report concluded that milk probably decreases the risk of colorectal cancer but diets high in calcium probably increase the risk of prostate cancer, whereas there was limited evidence for an association between milk and bladder cancer and insufficient evidence for other cancers. There are several potential mechanisms relating meat to cancer, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Although the evidence in favor of a link between red and processed meat and colorectal cancer is convincing, the relations with other cancers are unclear. In this review, we summarize cohort studies conducted by the National Cancer Institute on meat and dairy intake in relation to cancer since the 2007 WCRF/AICR report. We also report the findings of meta-analyses published since 2007. PMID:24847855

  18. Breast cancer statistics, 2011.

    Science.gov (United States)

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. Copyright © 2011 American Cancer Society, Inc.

  19. Decreasing barriers for nurse practitioner social entrepreneurship.

    Science.gov (United States)

    Sharp, Dayle B; Monsivais, Diane

    2014-10-01

    To describe difficulties associated with the business-related aspects of practice in role transition of rural nurse practitioners (NPs), and to give practice implications. This focused ethnographic study derived data from semi-structured interviews. Participants provided information about rural NP practice ownership and barriers. The sample consisted of 24 rural NPs living throughout the United States. The majority were 51-60 years of age (45%) and females (93%) who had been in rural practice for 1 to over 20 years. NP social entrepreneurs experience difficulties related to scope of practice, business skills, and role conflict. To decrease barriers for NP clinic ownership and management, NPs need to receive education related to financing a rural practice, legal/regulatory practices, strategic planning, leadership, and clinic management. ©2014 American Association of Nurse Practitioners.

  20. Decreasing Ambiguity of the Safety Culture Concept

    International Nuclear Information System (INIS)

    Inoue, Shiichiro; Hosoda, Satoshi; Suganuma, Takashi; Monta, Kazuo; Kameda, Akiyuki

    2001-01-01

    The status of the concept of ''safety culture'' is reviewed. It has not sufficiently taken root. One cause for this is the abstract nature of the concept. Organizations must become aware of the necessity of improving safety and have sufficient power to promote this. The culture of safety must be instilled in each employee, so that each of them will feel responsible for identifying weak points in plant safety. The authors devised a tool for a self-assessment of the safety culture. The tool will bring to light information divides, communication gaps, etc. Recognizing the vulnerabilities of the organization by themselves and discussing these weak points among them is the first step to decrease the ambiguity of the safety culture. The next step is to make these gaps known along with agreed-upon countermeasures. The concept of safety culture will be greatly clarified in this way and lead to safer nuclear power plants

  1. Towards prevention of ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2018-01-01

    Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Troubleshooting at Reverse Osmosis performance decrease

    Energy Technology Data Exchange (ETDEWEB)

    Soons, Jan [KEMA (Netherlands)

    2011-07-01

    There are several causes for a decrease in Reverse Osmosis (RO) membrane performance each of which requiring actions to tackle the possible cause. Two of the main factors affecting the performance of the system are the feed quality (poor feed quality can lead to fouling of the membranes) and the operational conditions (including the maximum allowed pressure, minimum cleaning frequencies and types, recovery rate etc, which should be according to the design conditions). If necessary, pre-treatment will be applied in order to remove the fouling agents from the influent, reduce scaling (through the addition of anti-scalants) and for the protection of the membranes (for example, sodium metabisulphite addition for the removal of residual chlorine which can harm the membranes). Fouling is not strictly limited to the use of surface water as feed water, also relatively clean water sources will, over time, lead to organic and inorganic fouling when cleaning is not optimum. When fouling occurs, the TransMembrane Pressure (TMP) increases and more energy will be needed to produce the same amount of product water. Also, the cleaning rate will increase, reducing the production rate and increasing the chemical consumption and the produced waste streams. Furthermore, the quality of the effluent will decrease (lower rejection rates at higher pressures) and the lifetime of the membranes will decrease. Depending on the type of fouling different cleaning regimes will have to be applied: acidic treatment for inorganic fouling, the addition of bases against organic fouling. Therefore, it is very important to have a clear view of the type of fouling that is occurring, in order to apply the correct treatment methods. Another important aspect to be kept in mind is that the chemistry of the water - in the first place ruled by the feed water composition - can change during passage of the modules, in particular in cases where the RO system consists of two or more RO trains, and where the

  3. Sled Towing Acutely Decreases Acceleration Sprint Time.

    Science.gov (United States)

    Wong, Megan A; Dobbs, Ian J; Watkins, Casey M; Barillas, Saldiam R; Lin, Anne; Archer, David C; Lockie, Robert G; Coburn, Jared W; Brown, Lee E

    2017-11-01

    Wong, MA, Dobbs, IJ, Watkins, C, Barillas, SR, Lin, A, Archer, DC, Lockie, RG, Coburn, JW, and Brown, LE. Sled towing acutely decreases acceleration sprint time. J Strength Cond Res 31(11): 3046-3051, 2017-Sled towing is a common form of overload training in sports to develop muscular strength for sprinting. This type of training leads to acute and chronic outcomes. Acute training potentially leads to postactivation potentiation (PAP), which is when subsequent muscle performance is enhanced after a preload stimulus. The purpose of this study was to determine differences between rest intervals after sled towing on acute sprint speed. Twenty healthy recreationally trained men (age = 22.3 ± 2.4 years, height = 176.95 ± 5.46 cm, mass = 83.19 ± 11.31 kg) who were currently active in a field sport twice a week for the last 6 months volunteered to participate. A maximal 30-meter (m) baseline (BL) body mass (BM) sprint was performed (with splits at 5, 10, 20, and 30 m) followed by 5 visits where participants sprinted 30 m towing a sled at 30% BM then rested for 2, 4, 6, 8, or 12 minutes. They were instructed to stand still during rest times. After the rest interval, they performed a maximal 30-m post-test BM sprint. Analysis of variance (ANOVA) revealed that post sled tow BM sprint times (4.47 ± 0.21 seconds) were less than BL times (4.55 ± 0.18 seconds) on an individualized rest interval basis. A follow-up 2 × 4 ANOVA showed that this decrease occurred only in the acceleration phase over the first 5 m (BL = 1.13 ± 0.08 seconds vs. Best = 1.08 ± 0.08 seconds), which may be the result of PAP and the complex relationship between fatigue and potentiation relative to the intensity of the sled tow and the rest interval. Therefore, coaches should test their athletes on an individual basis to determine optimal rest time after a 30-m 30% BM sled tow to enhance acute sprint speed.

  4. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Esophageal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  12. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  13. Testicular Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  14. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Cancer incidence in Spain, 2015.

    Science.gov (United States)

    Galceran, J; Ameijide, A; Carulla, M; Mateos, A; Quirós, J R; Rojas, D; Alemán, A; Torrella, A; Chico, M; Vicente, M; Díaz, J M; Larrañaga, N; Marcos-Gragera, R; Sánchez, M J; Perucha, J; Franch, P; Navarro, C; Ardanaz, E; Bigorra, J; Rodrigo, P; Bonet, R Peris

    2017-07-01

    Periodic cancer incidence estimates of Spain from all existing population-based cancer registries at any given time are required. The objective of this study was to present the current situation of cancer incidence in Spain. The Spanish Network of Cancer Registries (REDECAN) estimated the numbers of new cancer cases occurred in Spain in 2015 by applying the incidence-mortality ratios method. In the calculus, incidence data from population-based cancer registries and mortality data of all Spain were used. In 2015, nearly a quarter of a million new invasive cancer cases were diagnosed in Spain, almost 149,000 in men (60.0%) and 99,000 in women. Globally, the five most common cancers were those of colon-rectum, prostate, lung, breast and urinary bladder. By gender, the four most common cancers in men were those of prostate (22.4%), colon-rectum (16.6%), lung (15.1%) and urinary bladder (11.7%). In women, the most common ones were those of breast (28.0%), colon-rectum (16.9%), corpus uteri (6.2%) and lung (6.0%). In recent years, cancer incidence in men seems to have stabilized due to the fact that the decrease in tobacco-related cancers compensates for the increase in other types of cancer like those of colon and prostate. In women, despite the stabilization of breast cancer incidence, increased incidence is due, above all, to the rise of colorectal and tobacco-related cancers. To reduce these incident cancer cases, improvement of smoking control policies and extension of colorectal cancer screening should be the two priorities in cancer prevention for the next years.

  16. Hyper-arousal decreases human visual thresholds.

    Directory of Open Access Journals (Sweden)

    Adam J Woods

    Full Text Available Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0-2° C water, a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1 and contrast thresholds (Experiment 2 were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

  17. Decreased lymphocyte dopamine transporter in romantic lovers.

    Science.gov (United States)

    Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Piccinni, Armando; Mucci, Federico; Catena-Dell'Osso, Mario; Rutigliano, Grazia; Massimetti, Gabriele; Dell'Osso, Liliana

    2017-06-01

    The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship. All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us. The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax). Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

  18. COGNITIVE THERAPY DECREASE THE LEVEL OF DEPRESSION

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Aging is a natural process in individuals. Most of the elderly have problems in dealing with this natural process. Lost of occupation, friends and loneliness may result in depression in this age group. Cognitive therapy changes pessimistic idea, unrealistic hopes and excessive self evaluation may result and justify depression. Cognitive therapy may help elderly to recognize the problem in life, to develop positive objective of life and to create more positive personality. The aimed of this study was to analyze the effect of cognitive therapy to reduce the level of depression. Method: This study was used a pre experimental pre post test design. Sample were 10 elderly people who met to the inclusion criteria. The independent variable was cognitive therapy and dependent variable was the level of depression in elderly. Data were collected by using Geriatric Depression Scale (GDS 15, then analyzed by using Wilcoxon Signed Rank Test with significance levelα≤0.05. Result: The result showed that cognitive therapy has an effect on reducing depression with significance level p=0.005. Discussion: It can be concluded that cognitive therapy was effective in reducing depression level in elderly. Further studies are recommended to analyze the effect of cognitive therapy on decreasing anxiety in elderly by measuring cathecolamin.

  19. Urological Cancers

    African Journals Online (AJOL)

    Results. A total of 8829 cancers were diagnosed over the 15 year study period, 749 (8.4%) were Urological malignancies. The male to female ratio of the. Urological cancers was 10.7 to 1. Cancer of the prostate was the most common urological malignancy (54.6%), followed by cancer of the bladder (21.1%) and cancer of ...

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View this ...

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View this ...

  3. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening ... What Is Cancer Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening ...

  4. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Contact Dictionary Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening ... Is Cancer Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening ...

  5. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid ... and where it is in your body The stage of the cancer, which refers to the size ...

  6. Cancer and Women

    Science.gov (United States)

    ... Materials Infographics Cancer and Alcohol Web Features Breast Cancer Awareness Breast Cancer in Young Women Cancer and Men ... in Childhood Cancer, the Flu, and You Cervical Cancer Awareness Colorectal Cancer Awareness Gynecologic Cancer Awareness Health Disparities ...

  7. CDC's Cervical Cancer Study

    Science.gov (United States)

    ... Materials Infographics Cancer and Alcohol Web Features Breast Cancer Awareness Breast Cancer in Young Women Cancer and Men ... in Childhood Cancer, the Flu, and You Cervical Cancer Awareness Colorectal Cancer Awareness Gynecologic Cancer Awareness Health Disparities ...

  8. Cancer and Men

    Science.gov (United States)

    ... Materials Infographics Cancer and Alcohol Web Features Breast Cancer Awareness Breast Cancer in Young Women Cancer and Men ... in Childhood Cancer, the Flu, and You Cervical Cancer Awareness Colorectal Cancer Awareness Gynecologic Cancer Awareness Health Disparities ...

  9. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Using Trusted Resources Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and Literature Cancers by ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research NCI’s Role ...

  10. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer Treatment Research Cancer & Public Health Cancer Health ... Genomics Causes of Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer Health Disparities Childhood ...

  11. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Research Screening & Early Detection Cancer Treatment Research Cancer & Public Health Cancer Health Disparities Childhood Cancers Clinical Trials Global ... Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer Health Disparities Childhood Cancer Clinical Trials Global ...

  12. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Coping with Your Feelings During Advanced Cancer Planning for Advanced Cancer Advanced Cancer and Caregivers Questions ... Talking About Advanced Cancer Coping With Your Feelings Planning for Advanced Cancer Advanced Cancer & Caregivers Managing Cancer ...

  13. Stages of Endometrial Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs , surgery, or radiation therapy is used to ...

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer Screening ... Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening Overview Screening ...

  15. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Information Advance Directives Using Trusted Resources Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and ... of Cancers Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Research Screening & Early Detection Cancer Treatment Research Cancer & Public Health Cancer Health Disparities Childhood Cancers Clinical Trials ... Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer Health Disparities Childhood Cancer Clinical Trials ...

  17. Decrease in artificial tanning by French teenagers: 2011-2016.

    Science.gov (United States)

    Say, Matthieu; Beauchet, Alain; Vouldoukis, Ioannis; Beauchet, Pascale; Boudet, Monique; Tella, Emilie; Mahé, Emmanuel

    2018-03-13

    The major risk factor for skin cancers is exposure to solar and artificial ultraviolet radiation, in particular during childhood and adolescence. In France, a law was restricted for tanning-bed access to adults (≥18 years) since 1997. To evaluate teenagers' artificial tanning behaviour in 2016 and to compare results with those obtained in a similar survey performed in 2011. The SOLADO 2011 and 2016 surveys were conducted in a general school in Antony and a technical school in Fontenay-aux-Roses (Paris suburb). In 2016, 630 teenagers (mean age: 14.2 ± 1.9 y: Males/Females: 301/329) completed the questionnaire, 1.3% of teenagers reported using tanning beds, 1.1% tanning pills and 8.9% tanning creams. Between 2011 and 2016, the use of tanning beds decreased from 1.4% to 0.7% in Antony (P = .26) and from 9.5% to 4.8% in Fontenay-aux-Roses (P = .01), and the use of tanning creams from 39.8% to 17.6% in Fontenay-aux-Rose (P = .0007). The incidence of sunburn decreased from 60.5% to 54.0% in Antony (P = .02) and from 55.4% to 42.4% in Fontenay-aux-Roses (P = .05). As compared to 2011, teenagers used artificial tanning methods less frequently in 2016. In particular, they used tanning beds less frequently, suggesting that the new stricter legislation has been effective. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Molecular biology of gastric cancer.

    Science.gov (United States)

    Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

    2007-04-01

    Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

  19. Role of Aspirin in Breast Cancer Survival.

    Science.gov (United States)

    Chen, Wendy Y; Holmes, Michelle D

    2017-07-01

    Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

  20. The Alpha value decrease when the annual individual effective dose decreases?

    International Nuclear Information System (INIS)

    Sordi, Gian M.; Marchiusi, Thiago; Sousa, Jefferson de J.

    2008-01-01

    A recent IAEA publication tells that a few entities took different alpha values for maxima individual doses. Beyond to disregard the international agencies, that recommend only one alpha value for each country, the alpha values decreases when the individual doses decreases and the practice happens exactly the conversely as we will show in this paper. We will prove that the alpha value increase when the maximum individual doses decreases in a four different manner. The first one we call the theoretical conception and it is linked to the emergent of the ALARA policy and to the purpose that led to the 3/10 of the annual limits, for to decrease the individual doses as a first resort and a 1/10 as a last resort. The second prove will be based in a small mine example used in the ICRP publication number 55 concerning to the optimization and the quantitative decision-aiding techniques in radiological protection where we will determine the alpha value ranges in which each radiological protection options becomes the analytical solution. The third prove will be based in the determination of the optimized thickness example of a plane shielding for a radiation source exposed in the ICRP publication number 37. We will use, also, the numerical example provided there. Eventually, as four prove we will show that the alpha value dos not only increases with the maximum individual dose decrease, but also, with the shielding geometry. (author)

  1. RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2011-07-28

    We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70\\/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

  2. Specific immunotherapy in renal cancer: a systematic review.

    Science.gov (United States)

    Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima

    2017-02-01

    Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy

  3. Decrease in pulmonary function and oxygenation after lung resection.

    Science.gov (United States)

    Brocki, Barbara Cristina; Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S R; Andreasen, Jan Jesper

    2018-01-01

    Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity -0.6±0.6 L and forced expiratory volume in 1 s -0.43±0.4 L; both p<0.0001), 6MWT (-37.6±74.8 m; p<0.0001) and oxygenation (-2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

  4. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

    Science.gov (United States)

    Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L.; Olenyuk, Bogdan Z.; Chen, Thomas C.; Hofman, Florence M.; Shih, Jean C.

    2016-01-01

    Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID:26871599

  5. Stomach Cancer

    Science.gov (United States)

    ... with stomach acid and helps digest protein. Stomach cancer mostly affects older people - two-thirds of people ... Smoke cigarettes Have a family history of stomach cancer It is hard to diagnose stomach cancer in ...

  6. Cancer Research

    Science.gov (United States)

    NCI is the nation's leader in cancer research. Learn more about NCI's cancer research areas, key initiatives, progress made in cancer research, and resources for researchers like research tools, specimens and data.

  7. Cancer Immunotherapy

    Science.gov (United States)

    Immunotherapy is a cancer treatment that helps your immune system fight cancer. It is a type of biological therapy. Biological therapy uses substances ... t yet use immunotherapy as often as other cancer treatments, such as surgery, chemotherapy, and radiation therapy. ...

  8. Uterine Cancer

    Science.gov (United States)

    ... is pregnant. There are different types of uterine cancer. The most common type starts in the endometrium, ... the uterus. This type is also called endometrial cancer. The symptoms of uterine cancer include Abnormal vaginal ...

  9. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  10. Thyroid Cancer

    Science.gov (United States)

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  11. Childhood Cancer

    Science.gov (United States)

    ... toxins. In children, a genetic condition, such as Down syndrome , can sometimes increase the risk of cancer. Kids who have had chemotherapy or radiation treatment for cancer are more likely to get cancer ...

  12. Stomach Cancer

    Science.gov (United States)

    ... familydoctor.org editorial staff Categories: Men, Seniors, WomenTags: cancer, gastric cancer, stomach cancer May 1, 1999 Copyright © American Academy ... Crisis Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans ...

  13. Eye Cancer

    Science.gov (United States)

    Cancer of the eye is uncommon. It can affect the outer parts of the eye, such as the eyelid, which are made up ... and nerves. If the cancer starts inside the eyeball it's called intraocular cancer. The most common intraocular ...

  14. Oral Cancer

    Science.gov (United States)

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  15. Skin Cancer

    Science.gov (United States)

    Skin cancer is the most common form of cancer in the United States. The two most common types ... face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ...

  16. Kidney Cancer

    Science.gov (United States)

    ... common cancers in the United States. Cancer Home Kidney Cancer Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Anatomy of the male urinary system (left panel) and ...

  17. Decreased active vasodilator sensitivity in aged skin.

    Science.gov (United States)

    Kenney, W L; Morgan, A L; Farquhar, W B; Brooks, E M; Pierzga, J M; Derr, J A

    1997-04-01

    Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with

  18. Outcome of breast cancer screening in Denmark

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Bak, Martin; von Euler-Chelpin, My

    2017-01-01

    were node negative and 40% ≤10 mm. False-positive rate was around 2%; higher for North Denmark Region than for the rest of Denmark. Three out of 10 breast cancers in screened women were diagnosed as interval cancers. Conclusions: High coverage by examination and low interval cancer rate are required...... for screening to decrease breast cancer mortality. Two pioneer local screening programs starting in the 1990s were followed by a decrease in breast cancer mortality of 22-25%. Coverage by examination and interval cancer rate of the national program were on the favorable side of values from the pioneer programs...... calculated coverage by examination; participation after invitation; detection-, interval cancer- and false-positive rates; cancer characteristics; sensitivity and specificity, for Denmark and for the five regions. Results: At the national level coverage by examination remained at 75-77%; lower in the Capital...

  19. Outcome of breast cancer screening in Denmark

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Bak, Martin; von Euler-Chelpin, My

    2017-01-01

    were node negative and 40% ≤10 mm. False-positive rate was around 2%; higher for North Denmark Region than for the rest of Denmark. Three out of 10 breast cancers in screened women were diagnosed as interval cancers. Conclusions: High coverage by examination and low interval cancer rate are required...... for screening to decrease breast cancer mortality. Two pioneer local screening programs starting in the 1990s were followed by a decrease in breast cancer mortality of 22-25%. Coverage by examination and interval cancer rate of the national program were on the favorable side of values from the pioneer programs...... Region than in the rest of Denmrk. Detection rate was slightly below 1% at first screen, 0.6% at subsequent screens, and one region had some fluctuation over time. Ductal carcinoma in situ (DCIS) constituted 13-14% of screen-detected cancers. In subsequent rounds, 80% of screen-detected invasive cancers...

  20. Lung Cancer Screening (PDQ®)—Health Professional Version

    Science.gov (United States)

    Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Screening with chest x-ray or sputum cytology does not reduce lung cancer mortality. Get detailed information about lung cancer screening in this clinician summary.

  1. Cervical Cancer Screening by Female Workers in South East Nigeria

    African Journals Online (AJOL)

    India, with approximately 71,600 new cases occurring ... cancer is the most common cancer among women and ... The poor utilization of the cervical ... known that pre-cancerous lesions are detectable for 10 ... of cervical cancer deaths decreased from 70% between .... screening should be 30 - 40 years, which is the age.

  2. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention

    Science.gov (United States)

    ... black women, but have decreased in both groups. Women who have a family history of ovarian cancer and/or certain inherited gene ... ovarian, fallopian tube, and primary peritoneal cancer: Personal history of breast cancer A woman who has had breast cancer has an increased ...

  3. General Information About Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

    Science.gov (United States)

    ... black women, but have decreased in both groups. Women who have a family history of ovarian cancer and/or certain inherited gene ... ovarian, fallopian tube, and primary peritoneal cancer: Personal history of breast cancer A woman who has had breast cancer has an increased ...

  4. Cancer prevention.

    Science.gov (United States)

    Tubiana, M

    1999-01-01

    Over 70% of human cancers are associated with lifestyle and about half of cancer deaths could be prevented by relatively simple individual actions: no smoking, moderate consumption of alcohol, increased consumption of fruit and vegetables, avoidance of sunbathing, obesity and a too high consumption of saturated lipids. Most of these efforts would also markedly decrease the incidence of cardiovascular and respiratory diseases. However, the concept of prevention is currently neither well accepted nor understood by the medical community and the general public. It is often felt that it restricts freedom, imposes a choice between pleasure and duty, and that passing judgement on lifestyle is a form of intolerance. The case of tobacco illustrates the difficulties encountered by prevention, notably among adolescents. The fight against smoking requires information, a societal approach (ban on advertising, increase in price), and a reduction of the example given by adult smoking (parents, peers, teachers, physicians, TV presenters, movie stars, have a great influence on adolescents), while tobacco cessation programs must be promoted. The various approaches should be integrated into a global program of health prevention, including health education at school from 5 to 12 years of age. The efficacy of each of the global program's components should be evaluated. Misconceptions such as overestimation of the impact of pollution on health should also be corrected. Health is created and experienced by people within the setting of their daily lives, in particular during childhood. Prevention is the responsibility of individual members of the community but also of the community as a whole.

  5. Stop signals decrease choices for palatable foods through decreased food evaluation

    Science.gov (United States)

    Veling, Harm; Aarts, Henk; Stroebe, Wolfgang

    2013-01-01

    The present study explores whether presenting specific palatable foods in close temporal proximity of stop signals in a go/no-go task decreases subsequent evaluations of such foods among participants with a relatively high appetite. Furthermore, we tested whether any decreased evaluations could mediate subsequent food choice. Participants first received a go/no-go task in which palatable foods were consistently linked to go cues or no-go cues within participants. Next, evaluation of the palatable foods was measured as well as food choice. Replicating previous work, results show that among participants with a relatively high appetite palatable foods associated with no-go cues are less often chosen as snacks compared to when these foods are associated with go cues, whereas this manipulation did not affect participants with a relatively low appetite. Moreover, this effect was completely mediated by decreased evaluation of the palatable foods that had been associated with the no-go cues, whereas evaluation of the foods associated with go cues did not mediate this effect. Results further showed that the devaluation effect of foods associated with no-go cues was independent of the amount of pairings (4 vs. 12 vs. 24) with the no-go cues. The current findings suggest that decreased food evaluation is a mechanism that explains effects of stop signals on food choice. PMID:24324451

  6. Cancer Disparities - Cancer Currents Blog

    Science.gov (United States)

    Blog posts on cancer health disparities research—including factors that influence disparities, disparities-related research efforts, and diversity in the cancer research workforce—from NCI Cancer Currents.

  7. Cancer Technology - Cancer Currents Blog

    Science.gov (United States)

    Blog posts on technologies that affect cancer research and care—including new technologies for detecting cancer, testing treatments, storing/analyzing data, and improving patient care—from NCI Cancer Currents.

  8. Mammography - importance, possibilities, current screening situation of the breast cancer and further expansion possibilities

    International Nuclear Information System (INIS)

    Bella, V.

    2006-01-01

    Breast cancer still remains the most frequent cancer in women population. Incidence of breast cancer is increasing, but mortality is decreasing. The most important for decreasing of breast cancer mortality is early diagnostic, especially screening. Screening is a form of secondary prevention. Although many screening studies have shown that mammography decreases of the breast cancer death, there are still many controversies. The published recommendations for the breast screening are sometimes very different. (author)

  9. Effects of irradiation for cervical cancer on subsequent breast cancer

    International Nuclear Information System (INIS)

    Harlan, L.C.M.

    1985-01-01

    Previous research suggests that cervical cancer patients have a lower risk of breast cancer than women in the general population. Possible explanations include opposing risk factors for cervical cancer and breast cancer, the effect of irradiation used to treat cervical cancer, or both. The purpose of this study was to explore the relationship between irradiation for cervical cancer and the subsequent development of breast cancer. There was no statistically significant relationship between radiation to the ovarian area and the risk of breast cancer in this study. However, the results were consistent with a 19% reduction in risk for women irradiated for cervical cancer when compared to nonirradiated women. In a dose-response analysis, there was a nonsignificant trend of decreased risk of breast cancer with increased radiation up to 1800 rad. There was no consistent pattern for higher doses. The trend, although nonsignificant, differed by age. Women <60 years of age at irradiation were generally at a lower risk of breast cancer than nonirradiated women. Women over 59 years were at an increased risk. There are some potentially important findings from this study which might influence medical care. These should be examined in the larger International Radiation Study

  10. Uterine Cancer: Cancer of the Uterus

    Science.gov (United States)

    ... Subscribe To receive Publications email updates Submit Uterine cancer Cancer of the uterus (uterine cancer) is cancer ... Institute . Expand all | Collapse all What is uterine cancer? Cancer is a disease in which certain body ...

  11. Martial arts intervention decreases pain scores in children with malignancy.

    Science.gov (United States)

    Bluth, Martin H; Thomas, Ronald; Cohen, Cindy; Bluth, Amanda C; Goldberg, Elimelech

    2016-01-01

    Martial arts intervention in disease has been mostly limited to adult inflammatory, musculoskeletal, or motor diseases, where a mechanical intervention effects positive change. However, the application and benefit to pain management in childhood malignancy are not well described. Here, we assess the effects of defined martial arts intervention in children with cancer with respect to their pain perception and management. Sixty-four children with childhood malignancies were enrolled in a martial arts program, which encompassed both meditation and movement modalities. Pain scores (0-10) were recorded pre- and post- 1-hour session intervention. Pain scores were crossed by total visits and tabulated by whether participant pain reduced at least 1 unit, stayed the same, or increased in intensity immediately after (post) participation session. Differences in pain scores were further compared by age and sex. Prepain and postpain scale data were measured for 64 participants, 43 males (67.2%) and 21 females (32.8%), ranging from 3 years to 19 years. Preintervention and postintervention data were obtained for 223 individual session visits. Mean number of patient participation visits was 1.8±1.6 (range one to nine visits). Of 116 individual measured sessions where the participants began with a pain score of at least 1, pain intensity reduced ≥1 unit in 85.3% (99/116) of visits, remained the same in 7.8% (9/116), and increased in 6.9% (8/116). For the majority (96.3%; 77/80) of sessions, participants began with a prepain intensity score of at least 5-10 with reduction in pain intensity following the session. The overall mean pain score presession visit was reduced bŷ40% (pre: 5.95±2.64 and post: 3.03±2.45 [95% CI: 2.34-3.50]; P ≤0.001). Median pain intensity scores had greater reductions with increased age of participants (3-6 years [-1], 7-10 years [-2], 11-14 years [-3], and 15-19 years [-4]). Martial arts intervention can provide a useful modality to decrease pain in

  12. Gastric cancer review

    Directory of Open Access Journals (Sweden)

    Lauren Peirce Carcas

    2014-01-01

    Full Text Available Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Despite an overall decline in incidence over the last several decades, gastric cancer remains the fourth most common type of cancer and is the second leading cause of cancer-related death worldwide. This review aims to discuss the global distribution of the disease and the trend of decreasing incidence of disease, delineate the different pathologic subtypes and their immunohistochemical (IHC staining patterns and molecular signatures and mutations, explore the role of the pathogen H. pylori in tumorgenesis, discuss the increasing incidence of the disease in the young, western populations and define the role of biologic agents in the treatment of the disease.

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer & Public Health Cancer Health Disparities Childhood Cancers Clinical Trials Global Cancer Research Key Initiatives The RAS Initiative Cancer Moonshot℠ Immunotherapy ...

  14. Bladder cancer and schistosomiasis

    International Nuclear Information System (INIS)

    Zaghloul, M.S.

    2012-01-01

    Schistosoma-associated bladder cancer was believed, for several decades, to be a completely unique entity of disease, different from urothelial cancer. This was probably due to its distinct clinico pathologic and demographic features that varied from those of urothelial entity. The carcinogenesis is an extremely complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation regulation process. In bladder cancer, many of these carcinogenic cascades were not fully documented or somewhat conflicting. In spite of the efforts performed, much is still needed to explore the presence or absence of the carcinogenic difference with a different etiology. The control of schistosomiasis in certain countries and the subsequent decrease in the intensity of infestation showed changing of features approaching that of urothelial tumors. However the schistosoma-associated bladder cancer presented in more advanced stages than schistosoma-non associated urothelial cancer. More recently, data are gathered that, upon applying the same treatment protocol and management care, stage by stage comparison of the treatment end-results were found to be similar in bladder cancer patients with a different etiology. All treatment options; including radical cystectomy with or without adjuvant or neoadjuvant chemo- or radiotherapy or tri modality bladder preserving treatment seem to lead to similar end-results regardless of etiologic factor(s) implicated in bladder cancer development.

  15. Nanotechnology in cancer treatment

    Science.gov (United States)

    Mironidou-Tzouveleki, Maria; Imprialos, Konstantinos; Kintsakis, Athanasios

    2011-10-01

    The purpose of this paper is to analyze the current evolutions on nanotechnology and its applications on cancer theragnostics.Rapid advances and emerging technologies in nanotechnology are having a profound impact on cancer treatment. Applications of nanotechnology, which include liposomes, nanoparticles, polymeric micelles, dendrimers, nanocantilever, carbon nanotubes and quantum dots have significantly revolutionized cancer theragnostics. From a pharmaceutical viewpoint, it is critical that the biodistribution of active agents has to be controlled as much as possible. This aspect is vital in order to assure the proper efficiency and safety of the anticancer agents. These biocompatible nanocomposites provide specific biochemical interactions with receptors expressed on the surface of cancer cells. With passive or active targeting strategies, an increased intracellular concentration of drugs can be achieved in cancer cells , while normal cells are being protected from the drug simultaneously. Thus, nanotechnology restricts the extent of the adverse effects of the anticancer therapy. Treatment for metastatic breast cancer, sarcoma in AIDS patients, ovarian and lung cancer is already on market or under final phases of many clinical trials, showing remarkable results. As nanotechnology is perfected, side effects due to normal cell damage will decrease, leading to better results and lengthening patient's survival.

  16. Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression.

    Science.gov (United States)

    Xue, Lingyu; Feng, Xiaoqing; Wang, Chuanhai; Zhang, Xuebin; Sun, Wenqiang; Yu, Kebo

    2017-10-04

    This study aimed to investigate the effects of benazepril hydrochloride (BH) on proteinuria and ANGPTL-4 expression in a diabetic nephropathy (DN) rat model. A total of 72 Wistar male rats were randomly divided into three groups: normal control (NC), DN group and BH treatment (BH) groups. The DN model was induced by streptozotocin (STZ). Weight, glucose, proteinuria, biochemical indicators and the kidney weight index were examined at 8, 12 and 16 weeks. In addition, ANGPTL-4 protein and mRNA expressions were assessed by immunohistochemistry and qRT-PCR, respectively. Relationships between ANGPTL-4 and biochemical indicators were investigated using Spearman analysis. Weight was significantly lower but glucose levels were significantly higher in both the DN and BH groups than in the NC group (P Benazepril hydrochloride improves DN and decreases proteinuria by decreasing ANGPTL-4 expression.

  17. Cancer molecular markers: A guide to cancer detection and management.

    Science.gov (United States)

    Nair, Meera; Sandhu, Sardul Singh; Sharma, Anil Kumar

    2018-02-08

    Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Recent advances in oncology have led to the discovery of cancer markers that has allowed early detection and targeted therapy of tumors. In this context, current review provides a detail outlook on various molecular markers for diagnosis, prognosis and management of therapeutic response in cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  19. Vaginal Cancer

    Science.gov (United States)

    Vaginal cancer is a rare type of cancer. It is more common in women 60 and older. You are also more likely to get it if you have had a human ... test can find abnormal cells that may be cancer. Vaginal cancer can often be cured in its ...

  20. Gastric cancer

    International Nuclear Information System (INIS)

    Douglass, H.O.

    1988-01-01

    This book contains 10 selections. Some of the titles are: Radiation therapy for gastric cancer; Experimental stomach cancer: Drug selection based on in vitro testing; Western surgical adjuvant trials in gastric cancers: Lessons from current trials to be applied in the future; and Chemotherapy of gastric cancer

  1. Diet and cancer

    Science.gov (United States)

    Fiber and cancer; Cancer and fiber; Nitrates and cancer; Cancer and nitrates ... DIET AND BREAST CANCER The link between nutrition and breast cancer has been well studied. To reduce risk of breast cancer the American ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic ... grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ...

  3. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... with Cancer Reports, Research, and Literature Cancers by Body Location/System Childhood Cancers Late Effects of Childhood ... A to Z List of Cancers Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic ...

  4. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

  5. Stages of Rectal Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  6. Stages of Colon Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  7. Obesity and Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... hormone therapy and for tumors that express hormone receptors . Obesity is also a risk factor for breast ...

  8. Testicular Cancer Screening

    Science.gov (United States)

    ... undescended testicle) is a risk factor for testicular cancer. Testicular cancer is a disease in which malignant (cancer) ... Testicular Cancer Treatment for more information about testicular cancer. Testicular cancer is the most common cancer in men ...

  9. Human papillomavirus associated oropharyngeal cancer

    International Nuclear Information System (INIS)

    Stefanicka, P.

    2015-01-01

    Recently, there is substantial epidemiological, molecular-pathological and experimental evidence indicating that some of the high-risk human papillomavirus (HR-HPV), especially HPV type 16, are etiologically related to a subset of head and neck squamous cell carcinomas, in particular, those arising from the oropharynx. Incidence of oropharyngeal cancer is increasing in direct opposition to a decreasing incidence of all other head and neck cancers. The prognosis of patients with HPV associated oropharyngeal cancer is significantly better compare to patients with non associated oropharyngeal cancers. Patients with HPV-positive oropharyngeal cancer respond better to radiotherapy, surgery, chemoradiotherapy. Therefore, the presence of HPV in tumor is the most important prognostic factor in patients with oropharyngeal cancers. These findings have prompted the need for change of treatment strategies in these patients. The goal is selective de-intensified treatment stratified for HPV status. (author)

  10. Decrease in pulmonary function and oxygenation after lung resection

    Directory of Open Access Journals (Sweden)

    Barbara Cristina Brocki

    2018-01-01

    Full Text Available Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure and 6-min walk test (6MWT were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years. Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001, 6MWT (−37.6±74.8 m; p<0.0001 and oxygenation (−2.9±4.7 units; p<0.001, while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001, whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

  11. Cigarette Smoke Decreases the Maturation of Lung Myeloid Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Elena Arellano-Orden

    Full Text Available Conflicting data exist on the role of pulmonary dendritic cells (DCs and their maturation in patients with chronic obstructive pulmonary disease (COPD. Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer.A total of 75 consecutive patients were included. Spirometry testing was used to identify COPD. Lung parenchyma sections anatomically distant from the primary lesion were examined. We used flow cytometry to identify different DCs subtypes-including BDCA1-positive myeloid DCs (mDCs, BDCA3-positive mDCs, and plasmacytoid DCs (pDCs-and determine their maturation markers (CD40, CD80, CD83, and CD86 in all participants. We also identified follicular DCs (fDCs, Langerhans DCs (LDCs, and pDCs in 42 patients by immunohistochemistry.COPD was diagnosed in 43 patients (16 current smokers and 27 former smokers, whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers. The number and maturation of DCs did not differ significantly between COPD and non-COPD patients. However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively. Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects.Cigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung.

  12. Occupational cancer

    International Nuclear Information System (INIS)

    Nelson, N.

    1987-01-01

    Cancer resulting from occupational exposure is now receiving major attention, focusing on identification, regulation, and control of cancer-causing agents. Such cancer can result from exposure to chemicals and ionizing and nonionizing radiation. Extended exposure (often years) and an extended latent period of perhaps decades may intervene before tumor appearance. Although the actual extent of occupational cancer is in debate, estimates have ranged from 4 to 15 per cent of all cancer

  13. Occupational cancer

    International Nuclear Information System (INIS)

    Alderson, M.

    1986-01-01

    This book aims to review the occurrence and causes of occupational cancer and is aimed at assisting medical and safety staff, management and health and safety representatives. It is presented in the following chapters: 1) Epidemiological method 2) Agents causing occupationally induced cancer, including radiation 3) Occupations associated with risk of cancer 4) Aetiology of cancer 5) Control of occupationally induced cancer, research, prevention, legislation, national and international bodies, control of specific occupational carcinogens, including irradiation. (U.K.)

  14. Cancer among farmers in central Italy.

    Science.gov (United States)

    Forastiere, F; Quercia, A; Miceli, M; Settimi, L; Terenzoni, B; Rapiti, E; Faustini, A; Borgia, P; Cavariani, F; Perucci, C A

    1993-12-01

    This case-referent study evaluated cancer risks among farmers in central Italy. Cancer cases (N = 1674, 17 sites) were selected from all deceased men aged 35-80 years; a random sample of 480 decedents formed the reference series. Farmers had a decreased risk of lung and bladder cancer and melanoma and nonsignificant excess risks for stomach, rectal, kidney, and nonmelanoma skin cancer. Stomach and kidney cancer were significantly increased among the farmers with > 10 years' experience, and stomach, rectal, and pancreatic cancer were increased among licensed pesticide users with > 10 years' experience. Possible relationships emerged between specific crops and cancer: fruit and colon and bladder cancer, wheat and prostate cancer, olives and kidney cancer, and potato and kidney cancer. The results regarding stomach, pancreatic, lung, bladder, and prostate cancer and melanoma congrue with earlier results. The kidney cancer excess, the association of colon and bladder cancer with orchard farming, and the excess of rectal cancer among licensed farmers are new and unexpected findings.

  15. Decreasing child mortality, spatial clustering and decreasing disparity in North-Western Burkina Faso.

    Science.gov (United States)

    Becher, Heiko; Müller, Olaf; Dambach, Peter; Gabrysch, Sabine; Niamba, Louis; Sankoh, Osman; Simboro, Seraphin; Schoeps, Anja; Stieglbauer, Gabriele; Yé, Yazoume; Sié, Ali

    2016-04-01

    Within relatively small areas, there exist high spatial variations of mortality between villages. In rural Burkina Faso, with data from 1993 to 1998, clusters of particularly high child mortality were identified in the population of the Nouna Health and Demographic Surveillance System (HDSS), a member of the INDEPTH Network. In this paper, we report child mortality with respect to temporal trends, spatial clustering and disparity in this HDSS from 1993 to 2012. Poisson regression was used to describe village-specific child mortality rates and time trends in mortality. The spatial scan statistic was used to identify villages or village clusters with higher child mortality. Clustering of mortality in the area is still present, but not as strong as before. The disparity of child mortality between villages has decreased. The decrease occurred in the context of an overall halving of child mortality in the rural area of Nouna HDSS between 1993 and 2012. Extrapolated to the Millennium Development Goals target period 1990-2015, this yields an estimated reduction of 54%, which is not too far off the aim of a two-thirds reduction. © 2016 John Wiley & Sons Ltd.

  16. Decreased EGFR mRNA expression in response to antipsoriatic ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Jul 20, 2009 ... pathogenesis of psoriasis, the objective of this study was to investigate the transcriptional effect of dithranol .... N.E. Fusenig, German Cancer Research Centre, Heidelberg, ... RT-PCR analysis of EGFR expression in HaCaT cells treated with ... reliability. ... relationship to cancer risk and therapy response.

  17. Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

    Science.gov (United States)

    Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

    2014-05-01

    Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

  18. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Hiroki [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Nakamura, Seikou [Department of Pharmacognosy, Kyoto Pharmaceutical University, Kyoto (Japan); Chisaki, Yugo [Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto (Japan); Takada, Tetsuya [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Toda, Yuki [Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Murata, Hiroaki [Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Department of Orthopedic Surgery, Matsushita Memorial Hospital, Osaka (Japan); Itoh, Kazuyuki [Department of Biology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka (Japan); Yano, Yoshitaka [Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto (Japan); Takata, Kazuyuki [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Ashihara, Eishi, E-mail: ash@mb.kyoto-phu.ac.jp [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan)

    2016-02-26

    Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.

  19. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

    International Nuclear Information System (INIS)

    Fukuda, Hiroki; Nakamura, Seikou; Chisaki, Yugo; Takada, Tetsuya; Toda, Yuki; Murata, Hiroaki; Itoh, Kazuyuki; Yano, Yoshitaka; Takata, Kazuyuki; Ashihara, Eishi

    2016-01-01

    Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.

  20. In situ breast cancer

    International Nuclear Information System (INIS)

    Pacheco, Luis

    2004-01-01

    In situ breast cancer, particularly the ductal type, is increasing in frequency in the developed countries as well as in Ecuador, most probably. These lesions carry a higher risk of developing a subsequent invasive cancer. Treatment has changed recently due to results of randomized studies, from classical mastectomy to conservative surgery associated to radiotherapy. The Van Nuys Prognostic Index is currently the most usual instrument to guide diagnosis and treatment. Tamoxifen seems to decrease significantly the risk of tumor recurrence after initial treatment. (The author)