Auraptene Induces Apoptosis via Myeloid Cell Leukemia 1-Mediated Activation of Caspases in PC3 and DU145 Prostate Cancer Cells.

PubMed

Lee, Jae Chul; Shin, Eun Ah; Kim, Bonglee; Kim, Bo-Im; Chitsazian-Yazdi, Mahsa; Iranshahi, Mehrdad; Kim, Sung-Hoon

2017-06-01

Although auraptene, a prenyloxy coumarin from Citrus species, was known to have anti-oxidant, anti-bacterial, antiinflammatory, and anti-tumor activities, the underlying anti-tumor mechanism of auraptene in prostate cancers is not fully understood to date. Thus, in the present study, we have investigated the anti-tumor mechanism of auraptene mainly in PC3 and DU145 prostate cancer cells, because auraptene suppressed the viability of androgen-independent PC3 and DU145 prostate cancer cells better than androgen-sensitive LNCaP cells. Also, auraptene notably increased sub-G1 cell population and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells as features of apoptosis in two prostate cancer cells compared with untreated control. Consistently, auraptene cleaved poly(ADP-ribose) polymerase, activated caspase-9 and caspase-3, suppressed the expression of anti-apoptotic proteins, including Bcl-2 and myeloid cell leukemia 1 (Mcl-1), and also activated pro-apoptotic protein Bax in both prostate cancer cells. However, Mcl-1 overexpression reversed the apoptotic effect of auraptene to increase sub-G1 population and induce caspase-9/3 in both prostate cancer cells. Taken together, the results support scientific evidences that auraptene induces apoptosis in PC3 and DU145 prostate cancer cells via Mcl-1-mediated activation of caspases as a potent chemopreventive agent for prostate cancer prevention and treatment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Global cancer research initiative

PubMed Central

Love, Richard R

2010-01-01

Cancer is an increasing problem for low- and middle-income countries undergoing an epidemiologic transition from dominantly acute communicable disease to more frequent chronic disease with increased public health successes in the former domain. Progress against cancer in high-income countries has been modest and has come at enormous expense. There are several well-conceived global policy and planning initiatives which, with adequate political will, can favorably impact the growing global cancer challenges. Most financial resources for cancer, however, are spent on diagnosis and management of patients with disease in circumstances where specific knowledge about effective approaches is significantly limited, and the majority of interventions, other than surgery, are not cost-effective in resource-limited countries by global standards. In summary, how to intervene effectively on a global scale for the majority of citizens who develop cancer is poorly defined. In contrast to technology-transfer approaches, markedly increased clinical research activities are more likely to benefit cancer sufferers. In these contexts, a global cancer research initiative is proposed, and mechanisms for realizing such an effort are suggested. PMID:21188101

Restauration fonctionnelle du rachis : effet du niveau initial de douleur sur les performances des sujets lombalgiques chroniques

PubMed Central

Caby, Isabelle; Olivier, N; Mendelek, F; Kheir, R Bou; Vanvelcenaher, J; Pelayo, P

2014-01-01

HISTORIQUE : La lombalgie chronique est une douleur lombaire persistante d’origine multifactorielle. Le niveau de douleur initial reste faiblement utilisé pour analyser et comparer les réponses des patients lombalgiques au programme de reconditionnement. OBJECTIFS : Apprécier et évaluer les réponses des sujets lombalgiques chroniques très douloureux à une prise en charge dynamique et intensive. MÉTHODOLOGIE : 144 sujets atteints de lombalgie chronique ont été inclus dans un programme de restauration fonctionnelle du rachis de 5 semaines. Les sujets ont été classés en deux groupes de niveau de douleur: un groupe atteint de douleur sévère (n = 28) et un groupe atteint de douleur légère à modérée (n = 106). L’ensemble des sujets ont bénéficié d’une prise en charge identique comprenant principalement de la kinésithérapie, de l’ergothérapie, du reconditionnement musculaire et cardio-vasculaire ainsi qu’un suivi psychologique. Les paramètres physiques (flexibilité, force musculaire) et psychologiques (qualité de vie) ont été mesurés avant (T0) et après le programme (T5sem). RÉSULTATS : L’ensemble des performances physiques et fonctionnelles des sujets très douloureux sont moins bonnes et le retentissement de la lombalgie sur la qualité de vie, pour ces mêmes sujets, est majoré à T0. Toutes les différences significatives constatées à T0 entre les deux groupes s’effacent à T5sem. CONCLUSIONS : Les sujets lombalgiques chroniques très douloureux répondent favorablement au programme dynamique et intensif. L’intensité douloureuse de la lombalgie n’aurait pas d’effet sur les réponses au programme. La restauration fonctionnelle du rachis apporterait aux sujets la possibilité de mieux gérer leur douleur quel que soit son niveau. PMID:25299476

Differential response of DU145 and PC3 prostate cancer cells to ionizing radiation: role of reactive oxygen species, GSH and Nrf2 in radiosensitivity.

PubMed

Jayakumar, Sundarraj; Kunwar, Amit; Sandur, Santosh K; Pandey, Badri N; Chaubey, Ramesh C

2014-01-01

Radioresistance is the major impediment in radiotherapy of many cancers including prostate cancer, necessitating the need to understand the factors contributing to radioresistance in tumor cells. In the present study, the role of cellular redox and redox sensitive transcription factor, Nrf2 in the radiosensitivity of prostate cancer cell lines PC3 and DU145, has been investigated. Differential radiosensitivity of PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. Their redox status was measured using DCFDA and DHR probes. Expression of Nrf2 and its dependent genes was measured by EMSA and real time PCR. Knockdown studies were done using shRNA transfection. PC3 and DU145 cells differed significantly in their radiosensitivity as observed by clonogenic survival, apoptosis and neutral comet assays. Both basal and inducible levels of ROS were higher in PC3 cells than that of DU145 cells. DU145 cells showed higher level of basal GSH content and GSH/GSSG ratio than that of PC3 cells. Further, significant increase in both basal and induced levels of Nrf2 and its dependent genes was observed in DU145 cells. Knock-down experiments and pharmacological intervention studies revealed the involvement of Nrf2 in differential radio-resistance of these cells. Cellular redox status and Nrf2 levels play a causal role in radio-resistance of prostate cancer cells. The pivotal role Nrf2 has been shown in the radioresistance of tumor cells and this study will further help in exploiting this factor in radiosensitization of other tumor cell types. © 2013.

Research Ethics Considerations Regarding the Cancer Moonshot Initiative.

PubMed

Hammer, Marilyn J

2016-07-01

If the Precision Medicine Initiative was the launching pad, the Cancer Moonshot Initiative is the liftoff. A billion-dollar mission to "eliminate cancer as we know it," the Cancer Moonshot Initiative underscores the Precision Medicine Initiative's near-term focus in oncology research and translation. Spearheaded by Vice President Biden, the goal is to condense a decade of research into actionable results within five years.

Epigenetic modulation of AR gene expression in prostate cancer DU145 cells with the combination of sodium butyrate and 5'-Aza-2'-deoxycytidine.

PubMed

Fialova, Barbora; Luzna, Petra; Gursky, Jan; Langova, Katerina; Kolar, Zdenek; Trtkova, Katerina Smesny

2016-10-01

The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. Castration-resistant prostate cancer (CRPC) is a consequence of androgen deprivation therapy. Unchecked CRPC followed by metastasis is lethal. Some CRPCs show decreased AR gene expression due to epigenetic mechanisms such as DNA methylation and histone deacetylation. The aim of this study was to epigenetically modulate the methylated state of the AR gene leading to targeted demethylation and AR gene expression in androgen-independent human prostate cancer DU145 cell line, representing the CRPC model with very low or undetectable AR levels. The cell treatment was based on single and combined applications of two epigenetic inhibitors, sodium butyrate (NaB) as histone deacetylases inhibitor and 5'-Aza-2'-deoxycytidine (Aza-dC) as DNA methyltransferases inhibitor. We found that the Aza-dC in combination with NaB may help reduce the toxicity of higher NaB concentrations in cancer cells. In normal RWPE-1 cells and even stronger in cancer DU145 cells, the combined treatment induced both AR gene expression on the mRNA level and increased histone H4 acetylation in AR gene promoter. Also activation and maintenance of G2/M cell cycle arrest and better survival in normal RWPE-1 cells compared to cancer DU145 cells were observed after the treatments. These results imply the selective toxicity effect of both inhibitors used and their potentially more effective combined use in the epigenetic therapy of prostate cancer patients.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer and other research.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

National Cancer Moonshot Initiative platform | Office of Cancer Genomics

Cancer.gov

As part of the Vice President’s National Cancer Moonshot Initiative, the National Cancer Institute has launched an online engagement platform to enable the research community and the public to submit cancer research ideas to a Blue Ribbon Panel of scientific experts. Any member of the public is encouraged to submit his or her ideas for reducing the incidence of cancer and developing better ways to prevent, treat, and cure all types of cancer. Research ideas may be submitted in the following areas:

Place du traitement chirurgical sous circulation extracorporelle à cœur battant dans les cancers du rein avec envahissement cave supra-diaphragmatique: à propos de sept cas

PubMed Central

Lahyani, Mounir; Karmouni, Tarik; Elkhader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Ibn Attya

2014-01-01

Ce travail vise à analyser les résultats de la néphrectomie avec thrombectomie atrio-cave sous circulation extracorporelle (CEC) chez sept patients ayant un cancer du rein avec envahissement cave supra-diaphragmatique et de discuter les indications opératoires. Sept patients, six hommes et une femme dont l’âge varie entre 46ans et 65ans, ont été opérés d'un cancer du rein avec extension atrio-cave. L’écho-doppler a toujours permis la mise en évidence de l'extension veineuse mais la limite supérieure du thrombus était formellement identifiée par l'examen tomodensitométrique quatre fois, et par la résonance magnétique nucléaire dans tous les cas. Tous les patients ont été opérés sous CEC à cœur battant en normothermie. Un seul décès postopératoire est survenu. La durée du séjour en réanimation a été de 4,5 jours. Cinq patients ont eu à distance une dissémination métastatique. Cinq malades ont eu une médiane de survie de 11,5 mois (de 7 à16). Un malade a subi une métastasectomie pulmonaire 6 mois après la néphrectomie. L'exérèse des thrombi atrio-caves a été facilitée par la CEC avec une mortalité et une morbidité postopératoires acceptables mais les résultats à distance ont été décevants. Cette intervention ne peut être proposée qu'aux patients n'ayant aucune extension locorégionale et générale décelable, ce qui souligne l'importance des examens morphologiques préopératoires. PMID:25995777

Community-campus partnership in action: lessons learned from the DuPage County Patient Navigation Collaborative.

PubMed

Samaras, Athena T; Murphy, Kara; Nonzee, Narissa J; Endress, Richard; Taylor, Shaneah; Hajjar, Nadia; Bularzik, Rosario; Frankovich, Carmi; Dong, XinQi; Simon, Melissa A

2014-01-01

Using community-based participatory research (CBPR), the DuPage County Patient Navigation Collaborative (DPNC) developed an academic campus-community research partnership aimed at increasing access to care for underserved breast and cervical cancer patients within DuPage County, a collar county of Chicago. Given rapidly shifting demographics, targeting CBPR initiatives among underserved suburban communities is essential. To discuss the facilitating factors and lessons learned in forging the DPNC. A patient navigation collaborative was formed to guide medically underserved women through diagnostic resolution and if necessary, treatment, after an abnormal breast or cervical cancer screening. Facilitating factors included (1) fostering and maintaining collaborations within a suburban context, (2) a systems-based participatory research approach, (3) a truly equitable community-academic partnership, (4) funding adaptability, (5) culturally relevant navigation, and (6) emphasis on co-learning and capacity building. By highlighting the strategies that contributed to DPNC success, we envision the DPNC to serve as a feasible model for future health interventions.

Cost trend analysis of initial cancer treatment in Taiwan.

PubMed

Li, Tsai-Yun; Hsieh, Jan-Sing; Lee, King-Teh; Hou, Ming-Feng; Wu, Chia-Ling; Kao, Hao-Yun; Shi, Hon-Yi

2014-01-01

Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment. The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI) system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05). Hospitalization costs comprised the largest portion of payments for all cancers. During 1996-2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05). In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share. In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit from these expensive treatments.

Mise à jour sur le nouveau vaccin 9-valent pour la prévention du virus du papillome humain

PubMed Central

Yang, David Yi; Bracken, Keyna

2016-01-01

Résumé Objectif Informer les médecins de famille quant à l’efficacité, à l’innocuité, aux effets sur la santé publique et à la rentabilité du vaccin 9-valent contre le virus du papillome humain (VPH). Qualité des données Des articles pertinents publiés dans PubMed jusqu’en mai 2015 ont été examinés et analysés. La plupart des données citées sont de niveau I (essais randomisés et contrôlés et méta-analyses) ou de niveau II (études transversales, cas-témoins et épidémiologiques). Des rapports et recommandations du gouvernement sont aussi cités en référence. Message principal Le vaccin 9-valent contre le VPH, qui offre une protection contre les types 6, 11, 16, 18, 31, 33, 45, 52 et 58 du VPH, est sûr et efficace et réduira encore plus l’incidence des infections à VPH, de même que les cas de cancer lié au VPH. Il peut également protéger indirectement les personnes non immunisées par l’entremise du phénomène d’immunité collective. Un programme d’immunisation efficace peut prévenir la plupart des cancers du col de l’utérus. Les analyses montrent que la rentabilité du vaccin 9-valent chez les femmes est comparable à celle du vaccin quadrivalent original contre le VPH (qui protège contre les types 6, 11, 16 et 18 du VPH) en usage à l’heure actuelle. Toutefois, il faut investiguer plus en profondeur l’utilité d’immuniser les garçons avec le vaccin 9-valent contre le VPH. Conclusion en plus d’être sûr, le vaccin 9-valent protège mieux contre le VPH que le vaccin quadrivalent. Une analyse coûtefficacité en favorise l’emploi, du moins chez les adolescentes. Ainsi, les médecins devraient recommander le vaccin 9-valent à leurs patients plutôt que le vaccin quadrivalent contre le VPH.

Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

NASA Technical Reports Server (NTRS)

Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

2000-01-01

We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

Rupture simultanée du ligament croisé antérieur et du ligament patellaire: à propos d'un cas

PubMed Central

Achkoun, Abdessalam; Houjairi, Khalid; Quahtan, Omar; Hassoun, Jalal; Arssi, Mohamed; Rahmi, Mohamed; Garch, Abdelhak

2016-01-01

La rupture simultanée du tendon rotulien et du ligament croisé antérieur est une lésion relativement rare. Son diagnostic peut facilement manquer lors de l'examen initial. Les options de traitement incluent la réparation immédiate du tendon rotulien avec soit la reconstruction simultanée ou différée de ligament croisé antérieur. Nous rapportons le cas d'une rupture combinée du tendon rotulien et du ligament croisé antérieur chez un jeune footballeur de 22 ans. Une approche de traitement en deux temps a été effectuée avec un excellent résultat fonctionnel. PMID:27366288

[Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate cancer cells by reducing TRAF4].

PubMed

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2018-01-01

Objective To observe the effect of microRNA-519d-3p (miR-519d-3p) on the proliferation of prostate cancer cells and explore the possible molecular mechanism. Methods The expression level of miR-519d-3p in PC-3, DU-145, 22RV1, PC-3M, LNCaP human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time quantitative PCR. miR-519d-3p mimics or negative control microRNAs (miR-NC) was transfected into the prostate cancer cells with the lowest level of miR-519d-3p expression. Transfection efficiency was examined. The effect of miR-519d-3p on the cell cycle of prostate cancer was detected by flow cytometry. MTT assay and plate clone formation assay were used to detect its effect on the proliferation of prostate cancer cells. Bioinformatics software was used to predict and dual luciferase reporter assay was used to validate the target gene of miR-519d-3p. Real-time quantitative PCR was used to detect the expression of miR-519d-3p target gene. Western blot analysis was used to detect the expression of target gene protein and downstream protein. Results The expression of miR-519d-3p in normal prostate epithelial cells was significantly higher than that in prostate cancer cells, and the lowest was found in DU-145 cells. After transfected with miR-519d-3p mimics, the expression level of miR-519d-3p in DU-145 cells increased significantly. Bioinformatics prediction and dual luciferase reporter gene confirmed that tumor necrosis factor receptor associated factor 4 (TRAF4) was the target gene of miR-519d-3p. Overexpression of miR-519d-3p significantly reduced the expression of TRAF4 gene and its downstream TGF-β signaling pathway proteins in the prostate cancer cells. Conclusion The expression of miR-519d-3p is down-regulated in prostate cancer cells. Overexpression of miR-519d-3p can inhibit the proliferation of prostate cancer cells. The possible mechanism is that miR-519d-3p inhibits the expression of TRAF4.

Etude descriptive et analytique du cancer de l’œsophage au Togo

PubMed Central

Oumboma, Bouglouga; Mawuli, Lawson-Ananissoh Laté; Aklesso, Bagny; Laconi, Kaaga; Datouda, Redah

2014-01-01

Introduction Décrire les aspects épidémiologiques, cliniques, endoscopiques et histologiques du cancer de l’œsophage (CO) au Togo. Méthodes Il s'agit d'une étude rétrospective descriptive et analytique menée sur 8 ans (Janvier 2005-Décembre 2012) dans le service d'hépato-gastroentérologie (HGE) du CHU Campus de Lomé. Etaient inclus les dossiers des patients hospitalisés pour CO confirmé histologiquement. Résultats Sur 8 ans, 24 patients remplissant nos critères d'inclusion ont été retenus soit 3cas de CO par an et 0,55% des hospitalisations. L’âge moyen des patients était de 57,08 ans (extrêmes: 32 et 82 ans). La dysphagie et l’épigastralgie étaient les motifs d'hospitalisation les plus rencontrés. L'alcool (n=15), le tabac (n=13) étaient les facteurs de risque les plus présents. A la fibroscopie, les lésions étaient ulcéro-bourgeonnantes et hémorragiques (n=12), ulcéro-bourgeonnantes (n=5); ces lésions siégeaient au niveau du 1/3 inférieur (n= 11), à l'union 1/3 supérieur 1/3moyen de l’œsophage (n= 13) et aucun au niveau du 1/3 supérieur. Seize lésions étaient des carcinomes épidermoïdes et 3 des adénocarcinomes. L’évolution dans le service a été fatale dans 2cas; 16 patients avaient été transférés en chirurgie pour des soins palliatifs et 5 patients (20,8%) étaient perdus de vue. Conclusion Le CO semble en augmentation au Togo. L'alcool et le tabac sont les facteurs de risque et le pronostic sévère dans notre série est lié au retard diagnostic. Son dépistage précoce passe par une consultation rapide devant toute dysphagie chez un sujet de 50 ans et plus. PMID:25883742

Evaluation of Trends in the Cost of Initial Cancer Treatment

PubMed Central

Yabroff, K. Robin; Meekins, Angela; Topor, Marie; Lamont, Elizabeth B.; Brown, Martin L.

2008-01-01

Background Despite reports of increases in the cost of cancer treatment, little is known about how costs of cancer treatment have changed over time and what services have contributed to the increases. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database for 306 709 persons aged 65 and older and diagnosed with breast, lung, colorectal, or prostate cancer between 1991 and 2002 to assess the number of patients assigned to initial cancer care, from 2 months before diagnosis to 12 months after diagnosis, and mean annual Medicare payments for this care according to cancer type and type of treatment. Mutually exclusive treatment categories were cancer-related surgery, chemotherapy, radiation therapy, and other hospitalizations during the period of initial cancer care. Linear regression models were used to assess temporal trends in the percentage of patients receiving treatment and costs for those treated. We extrapolated our results based on the SEER data to the US Medicare population to estimate national Medicare payments by cancer site and treatment category. All statistical tests were two-sided. Results For patients diagnosed in 2002, Medicare paid an average of $39 891 for initial care for each lung cancer patient, $41 134 for each colorectal cancer patient, and $20 964 for each breast cancer patient, corresponding to inflation-adjusted increases from 1991 of $7139, $5345, and $4189, respectively. During the same interval, the mean Medicare payment for initial care for prostate cancer declined by $196 to $18261 in 2002. Costs for any hospitalization accounted for the largest portion of payments for all cancers. Chemotherapy use increased markedly for all cancers between 1991 and 2002, as did radiation therapy use (except for colorectal cancers). Total 2002 Medicare payments for initial care for these four cancers exceeded $6.7 billion, with colorectal and lung cancers being the most costly overall

A role for SIRT1 in cell growth and chemoresistance in prostate cancer PC3 and DU145 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kojima, Keitaro; Department of Longevity and Aging Research, Gifu International Institute of Biotechnology, 1-1 Naka-fudogaoka, Kakamigahara, Gifu 504-0838; Ohhashi, Riyako

2008-08-29

SIRT1, which belongs to the family of type III histone deacetylase, is implicated in diverse cellular processes. We have determined the expression levels of SIRT1 in human prostate cancer cell lines and have examined the roles of SIRT1 in cell growth and chemoresistance. SIRT1 expression was markedly up-regulated in androgen-refractory PC3 and DU145 cells compared with androgen-sensitive LNCaP cells and its expression level was correlated with cell growth in PC3 cells. Treatment with a SIRT1 inhibitor, sirtinol, inhibited cell growth and increased sensitivity to camptothecin and cisplatin. Silencing of SIRT1 expression by siRNA also suppressed cell proliferation and reduced camptothecinmore » resistance in PC3 cells, mimicking the chemosensitizing effect caused by sirtinol. Also in DU145 cells, sirtinol treatment enhanced sensitivity to camptothecin and cisplatin. These results suggest that up-regulation of SIRT1 expression may play an important role in promoting cell growth and chemoresistance in androgen-refractory PC3 and DU145 cells.« less

Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.

PubMed

Taghiyev, Agshin F; Guseva, Natalya V; Sturm, Mary T; Rokhlin, Oskar W; Cohen, Michael B

2005-04-01

The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.

Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-1-0095 TITLE: Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...cells and in transformed ovarian cells affected by obesity that lead to ovarian cancer initiation and progression. 15. SUBJECT TERMS Obesity , Ovarian

Radionécrose cérébrale chez des patients irradiés pour cancers du nasopharynx: à propos de 3 cas

PubMed Central

El Mazghi, Abderrahman; Lalya, Issam; Loukili, Kaoutar; El Kacemi, Hanan; Kebdani, Taieb; Hassouni, Khalid

2014-01-01

La radionécrose cérébrale est une complication tardive, iatrogène, relativement rare de la radiothérapie qui survient après plus de six mois suivant le début du traitement. Elle pourrait s'expliquer par la conjonction de lésions vasculaires, gliales et d'ordre immunologiques. Elle peut mettre en jeu le pronostic fonctionnel et vital du malade. La prévention de cette affection redoutable est fondamentale vu l'absence de traitement potentiellement efficace. Nous rapportons 03 nouveaux cas, chez des patients traités par chimiothérapie d'induction puis radio- chimiothérapie concomitante pour des cancers localement avancés du nasopharynx. Le diagnostic a été orienté par l'IRM spectroscopique et l’évolution était favorable sous corticothérapie dans les 03 cas. PMID:25722784

Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression

DTIC Science & Technology

2016-05-01

AWARD NUMBER: W81XWH-15-1-0095 TITLE: Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...pathways in ovarian stem cells and in transformed ovarian cells affected by obesity that lead to ovarian cancer initiation and progression. 15. SUBJECT

GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiorentini, Chiara; Bodei, Serena; Bedussi, Francesca

2014-04-15

Non-metastatic glycoprotein melanoma protein B (GPNMB), also known as osteoactivin (OA) is expressed in a wide array of tumors and represents an emerging target for drug development. In this study, we investigated the role of GPNMB/OA in the progression of human metastatic DU145 and PC3 prostate cancer cells. GPNMB/OA contribution in PCa malignant phenotype has been analyzed by small interfering RNA-induced GPNMB/OA silencing. We found that following GPNMB/OA silencing the migration capability of both DU145 and PC3 cells, evaluated by using in vitro invasivity assay, as well as the metalloproteinases MMP-2 and MMP-9 activity were equally strongly inhibited. By contrastmore » knocking down GPNMB/OA weakly attenuated cell proliferation rate of DU145, an effect that paralleled with an increase number of apoptotic cells. However, PC3 cell growth seems to be not affected by GPNMB/OA. Together, these data reveal that GPNMB/OA acts as a critical molecular mediator promoting the acquisition of the more aggressive, pro-metastatic phenotype distinctive of human DU145 and PC3 cell lines. - Highlights: • GPNMB/OA expression correlates with DU145 and PC3 cells malignant phenotype. • GPNMB/OA silencing affects the migration capability of both DU145 and PC3 cells. • GPNMB/OA increases invasiveness by up-regulating MMPs activity. • GPNMB/OA promotes DU145 and PC3 cells progression into a more aggressive phenotype.« less

CRCHD Launches National Colorectal Cancer Outreach and Screening Initiative

Cancer.gov

The NCI CRCHD launches National Screen to Save Colorectal Cancer Outreach and Screening Initiative which aims to increase colorectal cancer screening rates among racially and ethnically diverse and rural communities.

LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

PubMed

Yue, Zhiying; Yuan, Zengjin; Zeng, Li; Wang, Ying; Lai, Li; Li, Jing; Sun, Peng; Xue, Xiwen; Qi, Junyi; Yang, Zhengfeng; Zheng, Yansen; Fang, Yuanzhang; Li, Dali; Siwko, Stefan; Li, Yi; Luo, Jian; Liu, Mingyao

2018-05-01

The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment.

PubMed

Willis, Rudolph E

2016-09-14

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

Les déterminants du statut “perdu de vue” chez les patients pris en charge pour cancer au Maroc: situation avant le Plan Cancer

PubMed Central

Najdi, Adil; Berraho, Mohamed; Bendahhou, Karima; Obtel, Majdouline; Zidouh, Ahmed; Errihani, Hassan; Nejjari, Chakib

2014-01-01

Introduction Le cancer au Maroc représente un problème majeur de santé publique, sa prise en charge doit être globale, active et complète pour tous les patients. L'objectif de ce travail était d'estimer la fréquence des perdus de vue « PDV » en oncologie au Maroc durant la première année de suivi et de déterminer les facteurs associés à ce problème. Méthodes Par une étude rétrospective portant sur 2854 dossiers de malades hospitalisés dans les trois principaux centres d'oncologie au Maroc depuis janvier 2003 jusqu’à juin 2007 et concernant les cinq principales localisations de cancer au Maroc, nous avons cherché la date des dernières nouvelles des patients ayant un recul de 18 mois minimum afin de déterminer le statut de ces malades après un an de suivi. Résultats La moyenne d’âge était de 52±14 ans, une proportion féminine de 63%, les sujets actifs constituaient 28%, les mariés 71%, les analphabètes 51%, 70% des patients habitaient en milieu urbain et seulement 11% des malades disposaient d'une couverture sociale. La localisation cancéreuse la plus fréquente était le poumon (23,8%) suivie du colon-rectum (23,5%) puis le col (21,9%), le sein (20,4%) et les lymphomes (10,4%). Le taux des «PDV» à un an de suivi était de 48%, ce statut était significativement lié au sexe, à l’âge, au NSE et au statut matrimonial. Sur le plan médical, le statut «PDV» était lié à la localisation du cancer, au stade de diagnostic et au type de traitement reçu. Conclusion Notre étude a mis en évidence la grande ampleur du problème des PDV en cancérologie au Maroc ainsi que ces déterminants. Ces résultats incitent tous les acteurs dans le domaine de la cancérologie à collaborer ensemble pour prendre les mesures qui s'imposent pour y pallier PMID:25400850

[Economic evaluation of the new national breast cancer screening programme in France: application to the Bouche-du-Rhone district].

PubMed

Giorgi, Roch; Reynaud, Julie; Wait, Suzanne; Seradour, Brigitte

2005-11-01

The purpose is to measure the costs of the new national breast cancer screening programme in France and to compare these with those of the previous programme in the Bouches-du-Rhône district. Direct screening costs and costs related to diagnosis and assessment were collected. Costs are presented by screening period, by organisms involved in the screening program and by corresponding phase within the screening process. The total cost of the screening program total cost has increased from 5587487 euros to 9345469 euros between the two campaigns. The main reasons are the investment costs in the new screening program, the increase in the target population and the increased fee for programs. This study presents a first estimate of the costs related to the new national breast cancer screening program. Results of this study may help to guide future decisions on the further development of breast cancer screening in France.

Cabozantinib for Initial Treatment of Kidney Cancer

Cancer.gov

FDA has approved cabozantinib (Cabometyx®) as an initial treatment for patients with advanced renal cell carcinoma. The approval adds another tyrosine kinase inhibitor to the available options for patients with advanced kidney cancer.

Participants, Physicians or Programmes: Participants' educational level and initiative in cancer screening.

PubMed

Willems, Barbara; Bracke, Piet

2018-04-01

This study is an in-depth examination of at whose initiative (participant, physician or screening programme) individuals participate in cervical, breast and colorectal cancer screening across the EU-28. Special attention is paid to (1) the association with educational attainment and (2) the country's cancer screening strategy (organised, pilot/regional or opportunistic) for each type of cancer screened. Data were obtained from Eurobarometer 66.2 'Health in the European Union' (2006). Final samples consisted of 10,186; 5443 and 9851 individuals for cervical, breast, and colorectal cancer, respectively. Multinomial logistic regressions were performed. Surprisingly, even in countries with organised screening programmes, participation in screenings for cervical, breast and colorectal cancer was most likely to be initiated by the general practitioner (GP) or the participant. In general, GPs were found to play a crucial role in making referrals to screenings, regardless of the country's screening strategy. The results also revealed differences between educational groups with regard to their incentive to participate in cervical and breast cancer screening and, to a lesser extent, in colorectal cancer screening. People with high education are more likely to participate in cancer screening at their own initiative, while people with less education are more likely to participate at the initiative of a physician or a screening programme. Albeit, the results varied according to type of cancer screening and national screening strategy. Copyright © 2018 Elsevier B.V. All rights reserved.

The Cancer Cell Map Initiative: Defining the Hallmark Networks of Cancer

PubMed Central

Krogan, Nevan J.; Lippman, Scott; Agard, David A.; Ashworth, Alan; Ideker, Trey

2017-01-01

Progress in DNA sequencing has revealed the startling complexity of cancer genomes, which typically carry thousands of somatic mutations. However, it remains unclear which are the key driver mutations or dependencies in a given cancer and how these influence pathogenesis and response to therapy. Although tumors of similar types and clinical outcomes can have patterns of mutations that are strikingly different, it is becoming apparent that these mutations recurrently hijack the same hallmark molecular pathways and networks. For this reason, it is likely that successful interpretation of cancer genomes will require comprehensive knowledge of the molecular networks under selective pressure in oncogenesis. Here we announce the creation of a new effort, called The Cancer Cell Map Initiative (CCMI), aimed at systematically detailing these complex interactions among cancer genes and how they differ between diseased and healthy states. We discuss recent progress that enables creation of these Cancer Cell Maps across a range of tumor types and how they can be used to target networks disrupted in individual patients, significantly accelerating the development of precision medicine. PMID:26000852

The cancer cell map initiative: defining the hallmark networks of cancer.

PubMed

Krogan, Nevan J; Lippman, Scott; Agard, David A; Ashworth, Alan; Ideker, Trey

2015-05-21

Progress in DNA sequencing has revealed the startling complexity of cancer genomes, which typically carry thousands of somatic mutations. However, it remains unclear which are the key driver mutations or dependencies in a given cancer and how these influence pathogenesis and response to therapy. Although tumors of similar types and clinical outcomes can have patterns of mutations that are strikingly different, it is becoming apparent that these mutations recurrently hijack the same hallmark molecular pathways and networks. For this reason, it is likely that successful interpretation of cancer genomes will require comprehensive knowledge of the molecular networks under selective pressure in oncogenesis. Here we announce the creation of a new effort, The Cancer Cell Map Initiative (CCMI), aimed at systematically detailing these complex interactions among cancer genes and how they differ between diseased and healthy states. We discuss recent progress that enables creation of these cancer cell maps across a range of tumor types and how they can be used to target networks disrupted in individual patients, significantly accelerating the development of precision medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

Cancer Services and Their Initiatives to Improve the Care of Indigenous Australians.

PubMed

Taylor, Emma V; Haigh, Margaret M; Shahid, Shaouli; Garvey, Gail; Cunningham, Joan; Thompson, Sandra C

2018-04-11

Indigenous Australians continue to experience significantly poorer outcomes from cancer than non-Indigenous Australians. Despite the importance of culturally appropriate cancer services in improving outcomes, there is a lack of awareness of current programs and initiatives that are aimed at meeting the needs of Indigenous patients. Telephone interviews were used to identify and describe the Indigenous-specific programs and initiatives that are implemented in a subset of the services that participated in a larger national online survey of cancer treatment services. Fourteen services located across Australia participated in the interviews. Participants identified a number of factors that were seen as critical to delivering culturally appropriate treatment and support, including having a trained workforce with effective cross-cultural communication skills, providing best practice care, and improving the knowledge, attitudes, and understanding of cancer by Indigenous people. However, over a third of participants were not sure how their service compared with others, indicating that they were not aware of how other services are doing in this field. There are currently many Indigenous-specific programs and initiatives that are aimed at providing culturally appropriate treatment and supporting Indigenous people affected by cancer across Australia. However, details of these initiatives are not widely known and barriers to information sharing exist. Further research in this area is needed to evaluate programs and initiatives and showcase the effective approaches to Indigenous cancer care.

Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

PubMed

Yanik, Elizabeth L; Napravnik, Sonia; Cole, Stephen R; Achenbach, Chad J; Gopal, Satish; Olshan, Andrew; Dittmer, Dirk P; Kitahata, Mari M; Mugavero, Michael J; Saag, Michael; Moore, Richard D; Mayer, Kenneth; Mathews, W Christopher; Hunt, Peter W; Rodriguez, Benigno; Eron, Joseph J

2013-09-01

Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

Rapport sur l'état du patrimoine astronomique dans les observatoires français de la fin du XIXè siècle

NASA Astrophysics Data System (ADS)

Damm, E.; Pécontal, E.

2012-12-01

Suite au colloque sur la sauvegarde du patrimoine astronomique organisé par le MAEE et la SAF, sous l'égide de l'UNESCO, qui a conduit à l'adoption de la Déclaration de Paris, les directeurs d'observatoires institutionnels qui étaient absents du colloque ont ressenti le besoin de discuter de ces conclusions prises en leur nom. L'initiative d'organiser une réunion des directeurs des Observatoires des Sciences de l'Univers (OSU) à ce sujet le 30 janvier 2012 a été prise par François Vernotte, directeur de l'Observatoire de Besançon. Le présent compte-rendu de visite résulte d'une initiative spontanée d'Emmanuel Pécontal, astronome responsable du Patrimoine à l'observatoire de Lyon, et d'Evelyne Damm, membre de la Commission Nationale de classement des Monuments Historiques (CNMH) et élue à la communauté d'agglomération des Portes de l'Essonne oû est sis l'observatoire de Camille Flammarion.

Reducing WBC background in cancer cell separation products by negative acoustic contrast particle immuno-acoustophoresis.

PubMed

Cushing, Kevin; Undvall, Eva; Ceder, Yvonne; Lilja, Hans; Laurell, Thomas

2018-02-13

Cancer cells display acoustic properties enabling acoustophoretic separation from white blood cells (WBCs) with 2-3 log suppression of the WBC background. However, a subset of WBCs has overlapping acoustic properties with cancer cells, which is why label-free acoustophoretic cancer cell isolation needs additional purification prior to analysis. This paper reports for the first time a proof of concept for continuous flow acoustophoretic negative selection of WBCs from cancer cells using negative acoustic contrast elastomeric particles (EPs) activated with CD45-antibodies that specifically bind to WBCs. The EP/WBC complexes align at the acoustic pressure anti-nodes along the channel walls while unbound cancer cells focus to the pressure node in the channel center, enabling continuous flow based depletion of WBC background in a cancer cell product. The method does not provide a single process solution for the CTC separation challenge, but provides an elegant part to a multi-step process by further reducing the WBC background in cancer cell separation products derived from an initial step of label-free acoustophoresis. We report the recorded performance of the negative selection immuno-acoustophoretic WBC depletion and cancer cell recovery. To eliminate the negative impact of the separation due to the known problems of aggregation of negative acoustic contrast particles along the sidewalls of the acoustophoresis channel and to enable continuous separation of EP/WBC complexes from cancer cells, a new acoustic actuation method has been implemented where the ultrasound frequency is scanned (1.991MHz ± 100 kHz, scan rate 200 kHz ms -1 ). Using this frequency scanning strategy EP/WBC complexes were acoustophoretically separated from mixtures of WBCs spiked with breast and prostate cancer cells (DU145 and MCF-7). An 86-fold (MCF-7) and 52-fold (DU145) reduction of WBCs in the cancer cell fractions were recorded with separation efficiencies of 98.6% (MCF-7) and 99

Approche de prise en charge du trouble du spectre de l’autisme

PubMed Central

Lee, Patrick F.; Thomas, Roger E.; Lee, Patricia A.

2015-01-01

Résumé Objectif Se pencher sur les critères diagnostiques du trouble du spectre de l’autisme (TSA) comme les définit le Manuel diagnostique et statistique des troubles mentaux, cinquième édition (DSM-V), et concevoir une approche de prise en charge du TSA à l’aide du cadre CanMEDS–Médecine familiale (CanMEDS-MF). Sources d’information Le DSM-V, publié par l’American Psychiatric Association en mai 2013, énonce de nouveaux critères diagnostiques du TSA. Le cadre CanMEDS-MF du Collège des médecins de famille du Canada fournit un plan d’orientation pour la prise en charge complexe du TSA. Nous avons utilisé des données recueillies par le Centers for Disease Control and Prevention afin de déterminer la prévalence du TSA, ainsi que la revue systématique et méta-analyse détaillée effectuée par le National Institute for Health and Care Excellence du R.-U. pour ses lignes directrices sur le TSA dans le but d’évaluer les données probantes issues de plus de 100 interventions. Message principal Selon les données du Centers for Disease Control and Prevention, la prévalence du TSA se chiffrait à 1 sur 88 en 2008 aux États-Unis. La classification du TSA dans la quatrième édition du DSM incluait l’autisme, le syndrome d’Asperger, le trouble envahissant du développement et le trouble désintégratif de l’enfance. La dernière révision du DSM-V réunit tous ces troubles sous la mention TSA, avec différents niveaux de sévérité. La prise en charge du TSA est complexe; elle exige les efforts d’une équipe multidisciplinaire ainsi que des soins continus. Les rôles CanMEDS-MF fournissent un cadre de prise en charge. Conclusion Les médecins de famille sont au cœur de l’équipe de soins multidisciplinaire pour le TSA, et le cadre CanMEDS-MF tient lieu de plan détaillé pour guider la prise en charge d’un enfant atteint de TSA et aider la famille de cet enfant.

Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: The Breast Cancer Quality of Care (BQUAL) Study.

PubMed

Greenlee, Heather; Neugut, Alfred I; Falci, Laura; Hillyer, Grace Clarke; Buono, Donna; Mandelblatt, Jeanne S; Roh, Janise M; Ergas, Isaac J; Kwan, Marilyn L; Lee, Marion; Tsai, Wei Yann; Shi, Zaixing; Lamerato, Lois; Kushi, Lawrence H; Hershman, Dawn L

2016-09-01

Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among

Properties, use and health effects of depleted uranium (DU): a general overview.

PubMed

Bleise, A; Danesi, P R; Burkart, W

2003-01-01

Depleted uranium (DU), a waste product of uranium enrichment, has several civilian and military applications. It was used as armor-piercing ammunition in international military conflicts and was claimed to contribute to health problems, known as the Gulf War Syndrome and recently as the Balkan Syndrome. This led to renewed efforts to assess the environmental consequences and the health impact of the use of DU. The radiological and chemical properties of DU can be compared to those of natural uranium, which is ubiquitously present in soil at a typical concentration of 3 mg/kg. Natural uranium has the same chemotoxicity, but its radiotoxicity is 60% higher. Due to the low specific radioactivity and the dominance of alpha-radiation no acute risk is attributed to external exposure to DU. The major risk is DU dust, generated when DU ammunition hits hard targets. Depending on aerosol speciation, inhalation may lead to a protracted exposure of the lung and other organs. After deposition on the ground, resuspension can take place if the DU containing particle size is sufficiently small. However, transfer to drinking water or locally produced food has little potential to lead to significant exposures to DU. Since poor solubility of uranium compounds and lack of information on speciation precludes the use of radioecological models for exposure assessment, biomonitoring has to be used for assessing exposed persons. Urine, feces, hair and nails record recent exposures to DU. With the exception of crews of military vehicles having been hit by DU penetrators, no body burdens above the range of values for natural uranium have been found. Therefore, observable health effects are not expected and residual cancer risk estimates have to be based on theoretical considerations. They appear to be very minor for all post-conflict situations, i.e. a fraction of those expected from natural radiation.

Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

PubMed

Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

2017-07-01

We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

North American cranberry (Vaccinium macrocarpon) stimulates apoptotic pathways in DU145 human prostate cancer cells in vitro.

PubMed

MacLean, Malcolm A; Scott, Bradley E; Deziel, Bob A; Nunnelley, Melissa C; Liberty, Anne M; Gottschall-Pass, Katherine T; Neto, Catherine C; Hurta, Robert A R

2011-01-01

Diets rich in fruits and vegetables have been shown to improve patient prognosis in a variety of cancers, a benefit partly derived from phytochemicals, many of which target cell death pathways in tumor cells. Cranberries (Vaccinium macrocarpon) are a phytochemical-rich fruit containing a variety of polyphenolic compounds. As flavonoids have been shown to induce apoptosis in human tumor cells, this study investigated the hypothesis that cranberry-mediated cytotoxicity in DU145 human prostate adenocarcinoma cells involves apoptosis. The results showed that induction of apoptosis in these cells occurred in response to treatment with whole cranberry extract and occurred through caspase-8 mediated cleavage of Bid protein to truncated Bid resulting in cytochrome-C release from the mitochondria. Subsequent activation of caspase-9 ultimately resulted in cell death as characterized by DNA fragmentation. Increased Par-4 protein expression was observed, and this is suggested to be at least partly responsible for caspase-8 activation. Proanthocyanidin-enriched and flavonol-enriched fractions of cranberry also increased caspase-8 and caspase-9 activity, suggesting that these compounds play a possible role in apoptosis induction. These findings indicate that cranberry phytochemicals can induce apoptosis in prostate cancer cells in vitro, and these findings further establish the potential value of cranberry phytochemicals as possible agents against prostate cancer.

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

PubMed

Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation | Office of Cancer Genomics

Cancer.gov

Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten.

Spatial Moran models, II: cancer initiation in spatially structured tissue

PubMed Central

Foo, J; Leder, K

2016-01-01

We study the accumulation and spread of advantageous mutations in a spatial stochastic model of cancer initiation on a lattice. The parameters of this general model can be tuned to study a variety of cancer types and genetic progression pathways. This investigation contributes to an understanding of how the selective advantage of cancer cells together with the rates of mutations driving cancer, impact the process and timing of carcinogenesis. These results can be used to give insights into tumor heterogeneity and the “cancer field effect,” the observation that a malignancy is often surrounded by cells that have undergone premalignant transformation. PMID:26126947

Radio-sensitizing Effects of Novel Histone De-Acetylase Inhibitors in Prostate Cancer

DTIC Science & Technology

2007-03-01

were investigated in PC-3, LN -3 and DU-145 cells. (S)-HDAC-42 and SAHA could sensitize PC-3 and DU-145 cells to radiation. Aim 2: Effects of VAD- 18 ...combined effects of HDAC inhibitors and ionizing radiation on prostate cancer cell lines (PC-3, LN -3, LnCAP, DU-145 and 22Rv1). Aim 2. To understand the...cancer cell lines. Aim 3. To determine the combined effects of HDAC inhibitors plus ionizing radiation on the regression of (i) prostate cancer xenografts

Alginate Nanoparticles Containing Curcumin and Resveratrol: Preparation, Characterization, and In Vitro Evaluation Against DU145 Prostate Cancer Cell Line.

PubMed

Saralkar, Pushkar; Dash, Alekha K

2017-10-01

Curcumin and resveratrol are naturally occurring polyphenolic compounds having anti-cancer potential. However, their poor aqueous solubility and bioavailability limit their clinical use. Entrapment of hydrophobic drugs into hydrophilic nanoparticles such as calcium alginate presents a means to deliver these drugs to their target site. Curcumin and resveratrol-loaded calcium alginate nanoparticles were prepared by emulsification and cross-linking process. The nanoparticles were characterized for particle size, zeta potential, moisture content, physical state of the drugs, physical stability, and entrapment efficiency. An UPLC method was developed and validated for the simultaneous analysis of curcumin and resveratrol. Alginate nanoformulation was tested for in vitro efficacy on DU145 prostate cancer cells. The particle size of the nanosuspension and freeze-dried nanoparticles was found to be 12.53 ± 1.06 and 60.23 ± 15 nm, respectively. Both DSC and powder XRD studies indicated that curcumin as well as resveratrol were present in a non-crystalline state, in the nanoparticles. The entrapment efficiency for curcumin and resveratrol was found to be 49.3 ± 4.3 and 70.99 ± 6.1%, respectively. Resveratrol showed a higher percentage of release than curcumin (87.6 ± 7.9 versus 16.3 ± 3.1%) in 24 h. Curcumin was found to be taken up by the cells from solution as well as the nanoparticles. Resveratrol had a poor cellular uptake. The drug-loaded nanoparticles exhibit cytotoxic effects on DU145 cells. At high concentration, drug solution exhibited greater toxicity than nanoparticles. The alginate nanoformulation was found to be safe for intravenous administration.

Stem cells in prostate cancer initiation and progression

PubMed Central

Lawson, Devon A.; Witte, Owen N.

2007-01-01

Peter Nowell and David Hungerford’s discovery of the Philadelphia chromosome facilitated many critical studies that have led to a paradigm shift in our understanding of cancer as a disease of stem cells. This Review focuses on the application of these concepts to investigation of the role of stem cells in prostate cancer initiation and progression. Major strides in the development of in vitro and in vivo assays have enabled identification and characterization of prostate stem cells as well as functional evaluation of the tumorigenic effects of prostate cancer–related genetic alterations. PMID:17671638

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

PubMed

Yueh, Alexander E; Payne, Susan N; Leystra, Alyssa A; Van De Hey, Dana R; Foley, Tyler M; Pasch, Cheri A; Clipson, Linda; Matkowskyj, Kristina A; Deming, Dustin A

2016-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling.

Etude de l'affaiblissement du comportement mecanique du pergelisol du au rechauffement climatique

NASA Astrophysics Data System (ADS)

Buteau, Sylvie

Le rechauffement climatique predit pour les prochaines decennies, aura des impacts majeurs sur le pergelisol qui sont tres peu documentes pour l'instant. La presente etude a pour but d'evaluer ces impacts sur les proprietes mecaniques du pergelisol et sa stabilite a long terme. Une nouvelle technique d'essai de penetration au cone a taux de deformation controle, a ete developpee pour caracteriser en place le pergelisol. Ces essais geotechniques et la mesure de differentes proprietes physiques ont ete effectues sur une butte de pergelisol au cours du printemps 2000. Le developpement et l'utilisation d'un modele geothermique 1D tenant compte de la thermodependance du comportement mecanique ont permis d'evaluer que les etendues de pergelisol chaud deviendraient instables a la suite d'un rechauffement de l'ordre de 5°C sur cent ans. En effet, la resistance mecanique du pergelisol diminuera alors rapidement jusqu'a 11,6 MPa, ce qui correspond a une perte relative de 98% de la resistance par rapport a un scenario sans rechauffement.

Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells

PubMed Central

Lee, Won Sup; Jung, Ji Hyun; Panchanathan, Radha; Yun, Jeong Won; Kim, Dong Hoon; Kim, Hye Jung; Kim, Gon Sup; Ryu, Chung Ho; Shin, Sung Chul; Hong, Soon Chan; Choi, Yung Hyun; Jung, Jin-Myung

2017-01-01

Background Bile acids have anti-cancer properties in a certain types of cancers. We determined anticancer activity and its underlying molecular mechanism of ursodeoxycholic acid (UDCA) in human DU145 prostate cancer cells. Methods Cell viability was measured with an MTT assay. UDCA-induced apoptosis was determined with flow cytometric analysis. The expression levels of apoptosis-related signaling proteins were examined with Western blotting. Results UDCA treatment significantly inhibited cell growth of DU145 in a dose-dependent manner. It induced cellular shrinkage and cytoplasmic blebs and accumulated the cells with sub-G1 DNA contents. Moreover, UDCA activated caspase 8, suggesting that UDCA-induced apoptosis is associated with extrinsic pathway. Consistent to this finding, UDCA increased the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, death receptor 4 (DR4) and death receptor 5 (DR5), and TRAIL augmented the UDCA-induced cell death in DU145 cells. In addition, UDCA also increased the expressions of Bax and cytochrome c and decreased the expression of Bcl-xL in DU145 cells. This finding suggests that UDCA-induced apoptosis may be involved in intrinsic pathway. Conclusions UDCA induces apoptosis via extrinsic pathway as well as intrinsic pathway in DU145 prostate cancer cells. UDCA may be a promising anti-cancer agent against prostate cancer. PMID:28382282

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish

PubMed Central

Kanada, Masamitsu; Zhang, Jinyan; Yan, Libo; Sakurai, Takashi

2014-01-01

The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies. PMID:25551022

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish.

PubMed

Kanada, Masamitsu; Zhang, Jinyan; Yan, Libo; Sakurai, Takashi; Terakawa, Susumu

2014-01-01

The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies.

Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

PubMed Central

Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

2012-01-01

Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

Daughter-Initiated Cancer Screening Appeals to Mothers.

PubMed

Mosavel, M; Genderson, M W

2016-12-01

Youth-initiated health interventions may provide a much needed avenue for intergenerational dissemination of health information among families who bear the greatest burden from unequal distribution of morbidity and mortality. The findings presented in this paper are from a pilot study of the feasibility and impact of female youth-initiated messages (mostly daughters) encouraging adult female relatives (mostly mothers) to obtain cancer screening within low-income African American families living in a Southern US state. Results are compared between an intervention and control group. Intervention group youth (n = 22) were exposed to a 60-min interactive workshop where they were assisted to prepare a factual and emotional appeal to their adult relative to obtain specific screening. The face-to-face workshops were guided by the Elaboration Likelihood Model (ELM) and the Theory of Planned Behavior (TPB). Control group girls (n = 18) were only provided with a pamphlet with information about cancer screening and specific steps about how to encourage their relative to obtain screening. Intervention youth (86 %) and adults (82 %) reported that the message was shared while 71 % in the control group reported sharing or receiving the message. Importantly, more women in the intervention group reported that they obtained a screen (e.g., mammogram, Pap smear) directly based on the youth's appeal. These findings can have major implications for youth-initiated health promotion efforts, especially among hard-to-reach populations.

Daughter-Initiated Cancer Screening Appeals to Mothers

PubMed Central

Mosavel, Maghboeba; Genderson, Maureen Wilson

2015-01-01

Youth-initiated health interventions may provide a much needed avenue for intergenerational dissemination of health information among families who bear the greatest burden from unequal distribution of morbidity and mortality. The findings presented in this paper are from a pilot study of the feasibility and impact of female youth-initiated messages (mostly daughters) encouraging adult female relatives (mostly mothers) to obtain cancer screening within low income African American families living in a Southern US state. Results are compared between an intervention and control group. Intervention group youth (n=22) were exposed to a 60-minute interactive workshop where they were assisted to prepare a factual and emotional appeal to their adult relative to obtain specific screening. The face-to-face workshops were guided by the Elaboration Likelihood Model (ELM) and the Theory of Planned Behavior (TPB). Control group girls (n=18) were only provided with a pamphlet with information about cancer screening and specific steps about how to encourage their relative to obtain screening. Intervention youth (86%) and adults (82%) reported that the message was shared while 71% in the control group reported sharing or receiving the message. Importantly, more women in the intervention group reported that they obtained a screen (e.g., mammogram, Pap smear) directly based on the youth's appeal. These findings can have major implications for youth-initiated health promotion efforts, especially among hard-to-reach populations. PMID:26590969

Comparing Web-Based Provider-Initiated and Patient-Initiated Survivorship Care Planning for Cancer Patients: A Randomized Controlled Trial

PubMed Central

Tolbert, Elliott; Hannum, Susan M; Radhakrishnan, Archana; Zorn, Kelsey; Blackford, Amanda; Greco, Stephen; Smith, Karen; Snyder, Claire F

2016-01-01

Background Survivorship care plans (SCPs) are intended to facilitate communication and coordination between patients, oncologists, and primary care providers. Most SCP initiatives have focused on oncology providers initiating the SCP process, but time and resource barriers have limited uptake. Objective This trial compares the feasibility and value of 2 Web-based SCP tools: provider-initiated versus patient-initiated. Methods This mixed-methods study recruited clinicians from 2 academically-affiliated community oncology practices. Eligible patients were treated by a participating oncologist, had nonmetastatic cancer, completed acute treatment ≤ 2 months before enrollment, and had no evidence of disease. Patients were randomized 1:1 to either provider-initiated or patient-initiated SCPs—both are Web-based tools. We conducted qualitative interviews with providers at baseline and follow-up and with patients 2 months after enrollment. In addition, patients were administered the Preparing for Life as a (New) Survivor (PLANS) and Cancer Survivors’ Unmet Needs (CaSUN) surveys at baseline and 2 months. Results A total of 40 providers were approached for the study, of whom 13 (33%) enrolled. Providers or clinic staff required researcher assistance to identify eligible patients; 41 patients were randomized, of whom 25 completed follow-up (61%; 13 provider-initiated, 12 patient-initiated). Of the 25, 11 (44%) had initiated the SCP; 5 (20%) provided the SCP to their primary care provider. On the Preparing for Life as a (New) Survivor and Cancer Survivors’ Unmet Needs, patients in both arms tended to report high knowledge and confidence and few unmet needs. In qualitative interviews, providers and patients discussed SCPs’ value. Conclusions Regardless of patient- versus provider-initiated templates and the Web-based design of these tools, barriers to survivorship care planning persist. Further efforts should emphasize workflow functions for identifying and completing

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K

PubMed Central

Yueh, Alexander E.; Payne, Susan N.; Leystra, Alyssa A.; Van De Hey, Dana R.; Foley, Tyler M.; Pasch, Cheri A.; Clipson, Linda; Matkowskyj, Kristina A.; Deming, Dustin A.

2016-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling. PMID:26863299

Spectral biopsy for skin cancer diagnosis: initial clinical results

NASA Astrophysics Data System (ADS)

Moy, Austin J.; Feng, Xu; Nguyen, Hieu T. M.; Zhang, Yao; Sebastian, Katherine R.; Reichenberg, Jason S.; Tunnell, James W.

2017-02-01

Skin cancer is the most common form of cancer in the United States and is a recognized public health issue. Diagnosis of skin cancer involves biopsy of the suspicious lesion followed by histopathology. Biopsies, which involve excision of the lesion, are invasive, at times unnecessary, and are costly procedures ( $2.8B/year in the US). An unmet critical need exists to develop a non-invasive and inexpensive screening method that can eliminate the need for unnecessary biopsies. To address this need, our group has reported on the continued development of a noninvasive method that utilizes multimodal spectroscopy towards the goal of a "spectral biopsy" of skin. Our approach combines Raman spectroscopy, fluorescence spectroscopy, and diffuse reflectance spectroscopy to collect comprehensive optical property information from suspicious skin lesions. We previously described an updated spectral biopsy system that allows acquisition of all three forms of spectroscopy through a single fiber optic probe and is composed of off-the-shelf OEM components that are smaller, cheaper, and enable a more clinic-friendly system. We present initial patient data acquired with the spectral biopsy system, the first from an extensive clinical study (n = 250) to characterize its performance in identifying skin cancers (basal cell carcinoma, squamous cell carcinoma, and melanoma). We also present our first attempts at analyzing this initial set of clinical data using statistical-based models, and with models currently being developed to extract biophysical information from the collected spectra, all towards the goal of noninvasive skin cancer diagnosis.

An integrated multidisciplinary model describing initiation of cancer and the Warburg hypothesis

PubMed Central

2013-01-01

Background In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells. We show that this may result in cancer via mitotic failure, recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer, to a biophysical defect that may contribute to cancer initiation. Model Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance, disrupted microtubule dynamics, and finally, genomic instability, from which cancers can arise. Specifically, we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer. Conclusions A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell. Contrary to current understanding, this effect may precipitate cancer development, rather than follow from it, providing new insights into carcinogenesis, cancer treatment, and prevention. PMID:23758735

Cirque du Monde as a health intervention

PubMed Central

Fournier, Cynthia; Drouin, Mélodie-Anne; Marcoux, Jérémie; Garel, Patricia; Bochud, Emmanuel; Théberge, Julie; Aubertin, Patrice; Favreau, Gil; Fleet, Richard

2014-01-01

Abstract Objective To present Cirque du Soleil’s social circus program, Cirque du Monde, to explore its potential as a primary health care tool for family physicians. Data sources A review of the literature in PubMed, the Cochrane Library, PsycINFO, LaPresse, Eureka, Google Scholar, and Érudit using the key words circus, social circus, Cirque du Monde, and Cirque du Soleil; a Montreal-based initiative, Espace Transition, modeled on Cirque du Monde; and personal communication with Cirque du Soleil’s Social Circus Training Advisor. Study selection The first 50 articles or websites identified for each key word in each of the databases were examined on the basis of their titles and abstracts in the case of articles, and on the basis of their titles and page content in the case of websites. Articles and websites that explored an aspect of social circuses or that described an intervention that involved circuses were then retained for analysis. Because all literature on social circuses was searched, no criterion for year of publication was used. Synthesis No articles on the social circus as a health intervention were found. One study on the use of the circus as an intervention in schools was identified. It demonstrated an increase in self-esteem in the children who took part. One study on the use of the circus in a First Nations community was found; it contained nonspecific, qualitative findings. The other articles identified were merely descriptions of social circuses. One website was identified on the use of the social circus to help youth who had been treated in a hospital setting for major psychiatric disorders to re-enter the community. The team in the pediatric psychiatry department at Centre Hospitalier Universitaire Sainte-Justine, the children’s hospital in Montreal, Que, was contacted; they were leading this project, called Espace Transition. The unpublished preliminary findings of its pilot project demonstrate substantial improvements in overall patient

[Initial clinical experience of proton therapy at Shizuoka Cancer Center].

PubMed

Murayama, Shigeyuki; Fuji, Hiroshi; Yamashita, Haruo; Futami, Yasuyuki; Numano, Masumi; Harada, Hideyuki; Kamata, Minoru; Nishimura, Tetsuo

2005-10-01

To present the initial experience and preliminary clinical results of patients treated mainly with proton irradiation at the newly developed proton therapy facility at Shizuoka Cancer Center. We reviewed 125 patients who underwent proton therapy between July 2003 and December 2004. Of these 125 patients, 11 had head and neck malignancies, 15 non-small cell lung cancers, 22 hepatocellular carcinomas, 62 prostate cancers, and 15 other malignant tumors. Most patients experienced Grade 0-1 acute morbidities (NCI-CTC) in skin or mucosa, while a temporary Grade 2-3 reaction was observed in a high dose area. Response rates were 73% for H & N malignancies, 100% for NSCLC, and 77% for HCC. PSA evaluation for patients with prostate cancer revealed a high rate of complete response. The efficacy and safety of proton therapy at Shizuoka Cancer Center was demonstrated for patients with early-stage cancer or locally advanced disease.

Cirque du Monde en tant qu’intervention en santé

PubMed Central

Fournier, Cynthia; Drouin, Mélodie-Anne; Marcoux, Jérémie; Garel, Patricia; Bochud, Emmanuel; Théberge, Julie; Aubertin, Patrice; Favreau, Gil; Fleet, Richard

2014-01-01

Résumé Objectif Présenter le programme Cirque du Monde du Cirque du Soleil et son potentiel en tant qu’intervention en soins de santé de première ligne pour les médecins de famille. Sources des données Une revue de la littérature menée dans les bases de données PubMed, Cochrane Library, PsycINFO, La Presse, Eureka, Google Scholar et Érudit à l’aide des mots-clés circus, social circus, Cirque du Monde et Cirque du Soleil. Une initiative à Montréal nommée Espace Transition qui s’inspire directement de Cirque du Monde. Communication personnelle avec le conseiller principal en formation en cirque social du Cirque du Soleil. Sélection d’études Les 50 premiers articles ou sites Internet répertoriés pour chaque mot-clé dans chacune des bases de données ciblées ont été révisés sur la base des titres et des résumés, s’il s’agissait d’un article, ou sur la base du titre et du contenu de la page, s’il s’agissait d’une page Internet. Ensuite, les articles et les sites Internet qui étudiaient un aspect du cirque social ou qui présentaient une intervention impliquant le cirque étaient retenus pour une révision. Aucune contrainte d’année de publication n’a été appliquée étant donné qu’on cherchait une littérature générale sur le cirque social. Synthèse Aucun article n’a été trouvé sur le cirque social en tant qu’intervention en santé. Nous avons trouvé une étude sur l’utilisation du cirque en tant qu’intervention en milieu scolaire. Cette étude a démontré une augmentation de l’estime personnelle des enfants grâce à l’intervention. Nous avons trouvé une étude sur l’utilisation du cirque en tant qu’intervention sur une réserve amérindienne. Cette étude présente des résultats qualitatifs non spécifiques au programme du cirque social. Les autres articles répertoriés n’étaient que des descriptions du cirque social. Un site web concernant l’utilisation du cirque social pour

Health initiatives for the prevention of skin cancer.

PubMed

Greinert, Rüdiger; Breitbart, Eckhard W; Mohr, Peter; Volkmer, Beate

2014-01-01

Skin cancer is the most frequent type of cancer in white population worldwide. However, because the most prominent risk factor-solar UV-radiation and/or artificial UV from sunbeds-is known, skin cancer is highly preventable be primary prevention. This prevention needs, that the public is informed by simple and balanced messages about the possible harms and benefits of UV-exposure and how a person should behave under certain conditions of UV-exposure. For this purpose information and recommendations for the public must be age- and target-group specific to cover all periods of life and to reach all sub-groups of a population, continuously. There is a need that political institutions together with Health Institutions and Societies (e.g., European Commission, WHO, EUROSKIN, ICNIRP, etc.), which are responsible for primary prevention of skin cancer, find a common language to inform the public, in order not to confuse it. This is especially important in connection with the ongoing Vitamin D debate, where possible positive effects of UV have to be balanced with the well known skin cancer risk of UV. A continuously ongoing evaluation of interventions and programs in primary prevention is a pre-requisite to assess the effectiveness of strategies. There is surely no "no message fits all" approach, but balanced information in health initiatives for prevention of skin cancer, which use evidence-base strategies, will further be needed in the future to reduce the incidence, morbidity and mortality skin cancer.

Pet Ownership and Cancer Risk in the Women's Health Initiative.

PubMed

Garcia, David O; Lander, Eric M; Wertheim, Betsy C; Manson, JoAnn E; Volpe, Stella L; Chlebowski, Rowan T; Stefanick, Marcia L; Lessin, Lawrence S; Kuller, Lewis H; Thomson, Cynthia A

2016-09-01

Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders. There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Pet ownership had no association with overall cancer incidence. This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311-6. ©2016 AACR. ©2016 American Association for Cancer Research.

The European initiative for quality management in lung cancer care.

PubMed

Blum, Torsten G; Rich, Anna; Baldwin, David; Beckett, Paul; De Ruysscher, Dirk; Faivre-Finn, Corinne; Gaga, Mina; Gamarra, Fernando; Grigoriu, Bogdan; Hansen, Niels C G; Hubbard, Richard; Huber, Rudolf Maria; Jakobsen, Erik; Jovanovic, Dragana; Konsoulova, Assia; Kollmeier, Jens; Massard, Gilbert; McPhelim, John; Meert, Anne-Pascale; Milroy, Robert; Paesmans, Marianne; Peake, Mick; Putora, Paul-Martin; Scherpereel, Arnaud; Schönfeld, Nicolas; Sitter, Helmut; Skaug, Knut; Spiro, Stephen; Strand, Trond-Eirik; Taright, Samya; Thomas, Michael; van Schil, Paul E; Vansteenkiste, Johan F; Wiewrodt, Rainer; Sculier, Jean-Paul

2014-05-01

Lung cancer is the commonest cause of cancer-related death worldwide and poses a significant respiratory disease burden. Little is known about the provision of lung cancer care across Europe. The overall aim of the Task Force was to investigate current practice in lung cancer care across Europe. The Task Force undertook four projects: 1) a narrative literature search on quality management of lung cancer; 2) a survey of national and local infrastructure for lung cancer care in Europe; 3) a benchmarking project on the quality of (inter)national lung cancer guidelines in Europe; and 4) a feasibility study of prospective data collection in a pan-European setting. There is little peer-reviewed literature on quality management in lung cancer care. The survey revealed important differences in the infrastructure of lung cancer care in Europe. The European guidelines that were assessed displayed wide variation in content and scope, as well as methodological quality but at the same time there was relevant duplication. The feasibility study demonstrated that it is, in principle, feasible to collect prospective demographic and clinical data on patients with lung cancer. Legal obligations vary among countries. The European Initiative for Quality Management in Lung Cancer Care has provided the first comprehensive snapshot of lung cancer care in Europe.

Glycolytic reprogramming through PCK2 regulates tumor initiation of prostate cancer cells

PubMed Central

Zhao, Jiangsha; Li, Jieran; Fan, Teresa W.M.; Hou, Steven X.

2017-01-01

Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates. PCK2 knockdown resulted in low TIC numbers, increased cytosolic acetyl-CoA and cellular protein acetylation. Our data suggest PCK2 promotes tumor initiation by lowering acetyl-CoA level through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate tumors. PMID:29137367

Cancer risk in HIV patients with incomplete viral suppression after initiation of antiretroviral therapy.

PubMed

Lee, Jennifer S; Cole, Stephen R; Achenbach, Chad J; Dittmer, Dirk P; Richardson, David B; Miller, William C; Mathews, Christopher; Althoff, Keri N; Moore, Richard D; Eron, Joseph J

2018-01-01

Cancer causes significant morbidity and mortality among HIV patients in the US due to extended life expectancy with access to effective antiretroviral therapy. Low, detectable HIV RNA has been studied as a risk factor for adverse health outcomes, but its clinical impact on cancer risk remains unclear. The objective of this study was to determine whether HIV RNA <1,000 copies/mL six months after starting therapy was associated with 10-year first cancer risk. We followed 7,515 HIV therapy initiators from a US-based multicenter clinical cohort from 1998 to 2014. We used nonparametric multiple imputation to account for viral loads that fell below assay detection limits, and categorized viral loads six months after therapy initiation into four groups: <20, 20-199, 200-999, and >999 copies/mL. We calculated estimates of the cumulative incidence of cancer diagnosis, accounting for death as a competing event. Inverse probability of exposure and censoring weights were used to control for confounding and differential loss to follow up, respectively. Crude 10-year first cancer risk in the study sample was 7.03% (95% CI: 6.08%, 7.98%), with the highest risk observed among patients with viral loads between 200 and 999 copies/mL six months after ART initiation (10.7%). After controlling for baseline confounders, 10-year first cancer risk was 6.90% (95% CI: 5.69%, 8.12%), and was similar across viral load categories. Overall risk of first cancer was not associated with incomplete viral suppression; however, cancer remains a significant threat to HIV patients after treatment initiation. As more HIV patients gain access to treatment in the current "treat all" era, occurrences of incomplete viral suppression will be observed more frequently in clinical practice, which supports continued study of the role of low-level HIV RNA on cancer development.

Annealing of (DU-10Mo)-Zr Co-Rolled Foils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pacheco, Robin Montoya; Alexander, David John; Mccabe, Rodney James

2017-01-20

Producing uranium-10wt% molybdenum (DU-10Mo) foils to clad with Al first requires initial bonding of the DU-10Mo foil to zirconium (Zr) by hot rolling, followed by cold rolling to final thickness. Rolling often produces wavy (DU-10Mo)-Zr foils that should be flattened before further processing, as any distortions could affect the final alignment and bonding of the Al cladding to the Zr co-rolled surface layer; this bonding is achieved by a hot isostatic pressing (HIP) process. Distortions in the (DU-10Mo)-Zr foil may cause the fuel foil to press against the Al cladding and thus create thinner or thicker areas in the Almore » cladding layer during the HIP cycle. Post machining is difficult and risky at this stage in the process since there is a chance of hitting the DU-10Mo. Therefore, it is very important to establish a process to flatten and remove any waviness. This study was conducted to determine if a simple annealing treatment could flatten wavy foils. Using the same starting material (i.e. DU-10Mo coupons of the same thickness), five different levels of hot rolling and cold rolling, combined with five different annealing treatments, were performed to determine the effect of these processing variables on flatness, bonding of layers, annealing response, microstructure, and hardness. The same final thickness was reached in all cases. Micrographs, textures, and hardness measurements were obtained for the various processing combinations. Based on these results, it was concluded that annealing at 650°C or higher is an effective treatment to appreciably reduce foil waviness.« less

Florida Initiative for Quality Cancer Care: improvements on colorectal cancer quality of care indicators during a 3-year interval.

PubMed

Siegel, Erin M; Jacobsen, Paul B; Lee, Ji-Hyun; Malafa, Mokenge; Fulp, William; Fletcher, Michelle; Smith, Jesusa Corazon R; Brown, Richard; Levine, Richard; Cartwright, Thomas; Abesada-Terk, Guillermo; Kim, George; Alemany, Carlos; Faig, Douglas; Sharp, Philip; Markham, Merry-Jennifer; Shibata, David

2014-01-01

The quality of cancer care has become a national priority; however, there are few ongoing efforts to assist medical oncology practices in identifying areas for improvement. The Florida Initiative for Quality Cancer Care is a consortium of 11 medical oncology practices that evaluates the quality of cancer care across Florida. Within this practice-based system of self-assessment, we determined adherence to colorectal cancer quality of care indicators (QCIs) in 2006, disseminated results to each practice and reassessed adherence in 2009. The current report focuses on evaluating the direction and magnitude of change in adherence to QCIs for colorectal cancer patients between the 2 assessments. Medical records were reviewed for all colorectal cancer patients seen by a medical oncologist in 2006 (n = 489) and 2009 (n = 511) at 10 participating practices. Thirty-five indicators were evaluated individually and changes in QCI adherence over time and by site were examined. Significant improvements were noted from 2006 to 2009, with large gains in surgical/pathological QCIs (eg, documenting rectal radial margin status, lymphovascular invasion, and the review of ≥ 12 lymph nodes) and medical oncology QCIs (documenting planned treatment regimen and providing recommended neoadjuvant regimens). Documentation of perineural invasion and radial margins significantly improved; however, adherence remained low (47% and 71%, respectively). There was significant variability in adherence for some QCIs across institutions at follow-up. The Florida Initiative for Quality Cancer Care practices conducted self-directed quality-improvement efforts during a 3-year interval and overall adherence to QCIs improved. However, adherence remained low for several indicators, suggesting that organized improvement efforts might be needed for QCIs that remained consistently low over time. Findings demonstrate how efforts such as the Florida Initiative for Quality Cancer Care are useful for evaluating and

Building an International Initiative to Infuse Novel Cancer Models into the Research Community | Office of Cancer Genomics

Cancer.gov

My name is Caitlyn Barrett and I am the Scientific Program Manager for the Human Cancer Model Initiative (HCMI) in the Office of Cancer Genomics (OCG). In my role within the HCMI, I am helping to establish communication pathways and build the foundation for collaboration that will enable the completion of the Initiative’s aim to develop as many as 1000 next-generation cancer models, established from patient tumors and accompanied by clinical and molecular data.

Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

PubMed

Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

2015-01-15

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.

Targeting the cancer initiating cell: the Achilles' heel of cancer.

PubMed

McCubrey, James A; Chappell, William H; Abrams, Stephen L; Franklin, Richard A; Long, Jacquelyn M; Sattler, Jennifer A; Kempf, C Ruth; Laidler, Piotr; Steelman, Linda S

2011-01-01

We have isolated cell with the cancer initiating cell (CIC) phenotype from PC3 cells. The PC3/(CIC) cells are more resistant than the PC3/(BC) cells to chemotherapeutic drugs such as docetaxel which is used to treat prostate cancer. Thus these prostate CICs could lay dormant and persist even after chemotherapeutic drug treatment. Then when the chemotherapeutic drug is removed, they could potentially repopulate the original tumor site or metastize to a distant site. However, the prostate CICs were not significantly more resistant to drugs which target EGFR, NF-κB, Smo and the natural product genistein. Interesting the prostate CICs could be rendered more sensitive to docetaxel by inclusion of suboptimal doses of genistein, cyclopamine, and EGFR inhibitors. In contrast, addition of suboptimal amounts of genistein, cyclopamine, or EGFR inhibitors did not increase the sensitivity of the PC/(BC) cells to docetaxel. Similar results were observed when combination experiments were performed with cyclopamine and suboptimal doses of either genistein or docetaxel. The BC cells are usually more rapidly proliferating than the CICs. Thus the CICs are not as sensitive to docetaxel which targets replication. In contrast, the CICs could be rendered sensitive to docetaxel or cyclopamine by co-treatment with certain other drugs, including the natural product genistein which is present in the human diet of many people, especially Asians. Genistein is by itself only weakly toxic to prostate and other cancer cells. That is probably one of the big reasons that it can be used as a dietary supplement for prostate and breast cancers. It is clear from our studies that low doses of genistein can increase the sensitivity of prostate CICs to drugs such as docetaxel and cyclopamine, two drugs either used or under consideration for prostate cancer therapy.

Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel

PubMed Central

Kharaziha, Pedram; Chioureas, Dimitris; Rutishauser, Dorothea; Baltatzis, George; Lennartsson, Lena; Fonseca, Pedro; Azimi, Alireza; Hultenby, Kjell; Zubarev, Roman; Ullén, Anders; Yachnin, Jeffrey; Nilsson, Sten; Panaretakis, Theocharis

2015-01-01

Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy. PMID:25844599

Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.

PubMed

Kharaziha, Pedram; Chioureas, Dimitris; Rutishauser, Dorothea; Baltatzis, George; Lennartsson, Lena; Fonseca, Pedro; Azimi, Alireza; Hultenby, Kjell; Zubarev, Roman; Ullén, Anders; Yachnin, Jeffrey; Nilsson, Sten; Panaretakis, Theocharis

2015-08-28

Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy.

Diagnostic et prise en charge du psoriasis

PubMed Central

Kim, Whan B.; Jerome, Dana; Yeung, Jensen

2017-01-01

Résumé Objectif Présenter aux cliniciens en soins primaires un aperçu pratique et à jour du diagnostic et de la prise en charge du psoriasis. Sources des données Une recension a été effectuée dans les bases de données de PubMed, MEDLINE, EMBASE et Cochrane pour trouver des méta-analyses, des études randomisées contrôlées, des revues systématiques et des études observationnelles pertinentes portant sur le diagnostic et la prise en charge du psoriasis. Message principal Le psoriasis est une maladie inflammatoire chronique et multisystémique qui affecte principalement la peau et les articulations. En plus des dimensions physiques de la maladie, le psoriasis a des répercussions émotionnelles et psychosociales considérables sur les patients, et nuit au fonctionnement social et aux relations interpersonnelles. En tant que maladie inflammatoire systémique, le psoriasis est associé à de multiples comorbidités, dont les maladies cardiovasculaires et les cancers. Le diagnostic est principalement d’ordre clinique et une biopsie de la peau est rarement nécessaire. Selon la sévérité de la maladie, un traitement approprié peut être amorcé. Pour les cas de légers à modérés, le traitement de première intention comporte des thérapies topiques, dont les corticostéroïdes, les analogues de la vitamine D3 et des produits combinés. Ces traitements topiques sont efficaces et peuvent être initiés et prescrits en toute sécurité par des médecins de soins primaires. Les patients dont les symptômes sont plus graves et réfractaires pourraient devoir être envoyés en consultation auprès d’un dermatologue pour une évaluation plus approfondie et une thérapie systémique. Conclusion De nombreux patients atteints de psoriasis consultent leur médecin de soins primaires pour une évaluation initiale et pour recevoir un traitement. La reconnaissance du psoriasis, de même que des comorbidités médicales et psychiatriques qui lui sont associ

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Results of initial low-dose computed tomographic screening for lung cancer.

PubMed

Church, Timothy R; Black, William C; Aberle, Denise R; Berg, Christine D; Clingan, Kathy L; Duan, Fenghai; Fagerstrom, Richard M; Gareen, Ilana F; Gierada, David S; Jones, Gordon C; Mahon, Irene; Marcus, Pamela M; Sicks, JoRean D; Jain, Amanda; Baum, Sarah

2013-05-23

Lung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer-screening programs. At 33 U.S. centers, from August 2002 through April 2004, we enrolled asymptomatic participants, 55 to 74 years of age, with a history of at least 30 pack-years of smoking. The participants were randomly assigned to undergo annual screening, with the use of either low-dose CT or chest radiography, for 3 years. Nodules or other suspicious findings were classified as positive results. This article reports findings from the initial screening examination. A total of 53,439 eligible participants were randomly assigned to a study group (26,715 to low-dose CT and 26,724 to chest radiography); 26,309 participants (98.5%) and 26,035 (97.4%), respectively, underwent screening. A total of 7191 participants (27.3%) in the low-dose CT group and 2387 (9.2%) in the radiography group had a positive screening result; in the respective groups, 6369 participants (90.4%) and 2176 (92.7%) had at least one follow-up diagnostic procedure, including imaging in 5717 (81.1%) and 2010 (85.6%) and surgery in 297 (4.2%) and 121 (5.2%). Lung cancer was diagnosed in 292 participants (1.1%) in the low-dose CT group versus 190 (0.7%) in the radiography group (stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112). Sensitivity and specificity were 93.8% and 73.4% for low-dose CT and 73.5% and 91.3% for chest radiography, respectively. The NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography, suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that

Use of appropriate initial treatment among adolescents and young adults with cancer.

PubMed

Potosky, Arnold L; Harlan, Linda C; Albritton, Karen; Cress, Rosemary D; Friedman, Debra L; Hamilton, Ann S; Kato, Ikuko; Keegan, Theresa H M; Keel, Gretchen; Schwartz, Stephen M; Seibel, Nita L; Shnorhavorian, Margarett; West, Michele M; Wu, Xiao-Cheng

2014-11-01

There has been little improvement in the survival of adolescent and young adult (AYA) cancer patients aged 15 to 39 years relative to other age groups, raising the question of whether such patients receive appropriate initial treatment. We examined receipt of initial cancer treatment for a population-based sample of 504 AYAs diagnosed in 2007-2008 with acute lymphoblastic leukemia (ALL), Hodgkin's or non-Hodgkin's lymphoma, germ cell cancer, or sarcoma. Registry data, patient surveys, and detailed medical record reviews were used to evaluate the association of patient demographic, socioeconomic, and health care setting characteristics with receipt of appropriate initial treatment, which was defined by clinical specialists in AYA oncology based on adult guidelines and published literature available before 2009 and analyzed with multivariable logistic regression. All statistical tests were two-sided. Approximately 75% of AYA cancer patients in our sample received appropriate treatment, 68% after excluding stage I male germ cell patients who all received appropriate treatment. After this exclusion, appropriate treatment ranged from 79% of sarcoma patients to 56% of ALL patients. Cancer type (P < .01) and clinical trial participation (P = .04) were statistically significantly associated with appropriate treatment in multivariable analyses. Patients enrolled in clinical trials were more likely to receive appropriate therapy relative to those not enrolled (78% vs 67%, adjusted odds ratio = 2.6, 95% confidence interval = 1.1 to 6.4). Except for those with early stage male germ cell tumors, approximately 30% (or 3 in 10) AYA cancer patients did not receive appropriate therapy. Further investigation is required to understand the reasons for this potential shortfall in care delivery. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

California Breast Cancer Prevention Initiatives: Setting a research agenda for prevention.

PubMed

Sutton, P; Kavanaugh-Lynch, M H E; Plumb, M; Yen, I H; Sarantis, H; Thomsen, C L; Campleman, S; Galpern, E; Dickenson, C; Woodruff, T J

2015-07-01

The environment is an underutilized pathway to breast cancer prevention. Current research approaches and funding streams related to breast cancer and the environment are unequal to the task at hand. We undertook the California Breast Cancer Prevention Initiatives, a four-year comprehensive effort to set a research agenda related to breast cancer, the environment, disparities and prevention. We identified 20 topics for Concept Proposals reflecting a life-course approach and the complex etiology of breast cancer; considering the environment as chemical, physical and socially constructed exposures that are experienced concurrently: at home, in the community and at work; and addressing how we should be modifying the world around us to promote a less carcinogenic environment. Redirecting breast cancer research toward prevention-oriented discovery could significantly reduce the incidence and associated disparities of the disease among future generations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Colorectal Cancer Initial Diagnosis: Screening Colonoscopy, Diagnostic Colonoscopy, or Emergent Surgery, and Tumor Stage and Size at Initial Presentation.

PubMed

Moreno, Courtney C; Mittal, Pardeep K; Sullivan, Patrick S; Rutherford, Robin; Staley, Charles A; Cardona, Kenneth; Hawk, Natalyn N; Dixon, W Thomas; Kitajima, Hiroumi D; Kang, Jian; Small, William C; Oshinski, John; Votaw, John R

2016-03-01

Rates of colorectal cancer screening are improving but remain suboptimal. Limited information is available regarding how patients are diagnosed with colorectal cancer (for example, asymptomatic screened patients or diagnostic workup because of the presence of symptoms). The purpose of this investigation was to determine how patients were diagnosed with colorectal cancer (screening colonoscopy, diagnostic colonoscopy, or emergent surgery) and tumor stage and size at diagnosis. Adults evaluated between 2011 and 2014 with a diagnosis of colorectal cancer were identified. Clinical notes, endoscopy reports, surgical reports, radiology reports, and pathology reports were reviewed. Sex, race, ethnicity, age at the time of initial diagnosis, method of diagnosis, presenting symptom(s), and primary tumor size and stage at diagnosis were recorded. Colorectal cancer screening history was also recorded. The study population was 54% male (265 of 492) with a mean age of 58.9 years (range, 25-93 years). Initial tissue diagnosis was established at the time of screening colonoscopy in 10.7%, diagnostic colonoscopy in 79.2%, and during emergent surgery in 7.1%. Cancers diagnosed at the time of screening colonoscopy were more likely to be stage 1 than cancers diagnosed at the time of diagnostic colonoscopy or emergent surgery (38.5%, 7.2%, and 0%, respectively). Median tumor size was 3.0 cm for the screening colonoscopy group, 4.6 cm for the diagnostic colonoscopy group, and 5.0 cm for the emergent surgery group. At least 31% of patients diagnosed at the time of screening colonoscopy, 19% of patients diagnosed at the time of diagnostic colonoscopy, and 26% of patients diagnosed at the time of emergent surgery had never undergone a screening colonoscopy. Nearly 90% of colorectal cancer patients were diagnosed after development of symptoms and had more advanced disease than asymptomatic screening patients. Colorectal cancer outcomes will be improved by improving rates of colorectal

DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines.

PubMed

Adjakly, Mawussi; Bosviel, Rémy; Rabiau, Nadège; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2011-12-01

DNA hypermethylation is an epigenetic mechanism which induces silencing of tumor-suppressor genes in prostate cancer. Many studies have reported that specific components of food plants like soy phytoestrogens may have protective effects against prostate carcinogenesis or progression. Genistein and daidzein, the major phytoestrogens, have been reported to have the ability to reverse DNA hypermethylation in cancer cell lines. The aim of this study was to investigate the potential demethylating effects of these two soy compounds on BRCA1, GSTP1, EPHB2 and BRCA2 promoter genes. Prostate cell lines DU-145 and PC-3 were treated with genistein 40 µM, daidzein 110 µM, budesonide (methylating agent) 2 µM and 5-azacytidine (demethylating agent) 2 µM. In these two human prostate cancer cell lines we performed methylation quantification by using Methyl Profiler DNA methylation analysis. This technique is based on a methylation-specific digestion followed by quantitative PCR. We analyzed the corresponding protein expression by western blotting. Soy phytoestrogens induced a demethylation of all promoter regions studied except for BRCA2, which is not methylated in control cell lines. An increase in their protein expression was also demonstrated by western blot analysis and corroborated the potential demethylating effect of soy phytoestrogens. This study showed that the soy phytoestrogens, genistein and daidzein, induce a decrease of methylation of BRCA1, GSTP1 and EPHB2 promoters. Therefore, soy phytoestrogens may have a protective effect on prostate cancer. However, more studies are needed in order to understand the mechanism by which genistein and daidzein have an inhibiting action on DNA methylation.

Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A

PubMed Central

Lotti, Fiorenza; Jarrar, Awad M.; Pai, Rish K.; Hitomi, Masahiro; Lathia, Justin; Mace, Adam; Gantt, Gerald A.; Sukhdeo, Kumar; DeVecchio, Jennifer; Vasanji, Amit; Leahy, Patrick; Hjelmeland, Anita B.

2013-01-01

Many solid cancers display cellular hierarchies with self-renewing, tumorigenic stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often exhibit relative resistance to conventional cancer therapies, they also receive critical maintenance cues from supportive stromal elements that also respond to cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs, we investigated cellular heterogeneity in human colorectal cancers. Colorectal CICs were resistant to conventional chemotherapy in cell-autonomous assays, but CIC chemoresistance was also increased by cancer-associated fibroblasts (CAFs). Comparative analysis of matched colorectal cancer specimens from patients before and after cytotoxic treatment revealed a significant increase in CAFs. Chemotherapy-treated human CAFs promoted CIC self-renewal and in vivo tumor growth associated with increased secretion of specific cytokines and chemokines, including interleukin-17A (IL-17A). Exogenous IL-17A increased CIC self-renewal and invasion, and targeting IL-17A signaling impaired CIC growth. Notably, IL-17A was overexpressed by colorectal CAFs in response to chemotherapy with expression validated directly in patient-derived specimens without culture. These data suggest that chemotherapy induces remodeling of the tumor microenvironment to support the tumor cellular hierarchy through secreted factors. Incorporating simultaneous disruption of CIC mechanisms and interplay with the tumor microenvironment could optimize therapeutic targeting of cancer. PMID:24323355

The du Bois sign.

PubMed

Voelpel, James H; Muehlberger, Thomas

2011-03-01

According to the current literature, the term "du Bois sign" characterizes the condition of a shortened fifth finger as a symptom of congenital syphilis, Down syndrome, dyscrania, and encephalic malformation. Modern medical dictionaries and text books attribute the eponym to the French gynecologist Paul Dubois (1795-1871). Yet, a literature analysis revealed incorrect references to the person and unclear definitions of the term. Our findings showed that the origin of the term is based on observations made by the Swiss dermatologist Charles du Bois (1874-1947) in connection with congenital syphilis. In addition, a further eponymical fifth finger sign is closely associated with the du Bois sign. In conclusion, the du Bois sign has only limited diagnostic value and is frequently occurring in the normal healthy population.

Pet Ownership and Cancer Risk in the Women’s Health Initiative

PubMed Central

Garcia, David O.; Lander, Eric M.; Wertheim, Betsy C.; Manson, JoAnn E.; Volpe, Stella L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Lessin, Lawrence S.; Kuller, Lewis H.; Thomson, Cynthia A.

2016-01-01

Background Pet ownership and cancer are both highly prevalent in the U.S. Evidence suggest associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. Methods A prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women’s Health Initiative (WHI) observational study and clinical trials. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between pet ownership and cancer, adjusted for potential confounders. Results There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Conclusion Pet ownership had no association with overall cancer incidence. Impact This is the first large epidemiological study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. PMID:27365150

Oleanolic acid induces p53-dependent apoptosis via the ERK/JNK/AKT pathway in cancer cell lines in prostatic cancer xenografts in mice.

PubMed

Kim, Gyeong-Ji; Jo, Hyeon-Ju; Lee, Kwon-Jai; Choi, Jeong Woo; An, Jeung Hee

2018-05-29

We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), U87 (human glioblastoma), normal murine liver cell (BNL CL.2) and human foreskin fibroblast cell lines (Hs 68). The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA did not exhibit toxicity in BNL CL. 2 and Hs 68 cell lines in our experiments. OA, at 100 µg/mL, increased the number of apoptotic cells to 27.0% in DU145, 27.0% in MCF-7, and 15.7% in U87, when compared to control cells. This enhanced apoptosis was due to increases in p53, cytochrome c, Bax, PARP-1 and caspase-3 expression in DU145, MCF-7 and U87 cell lines. OA-treated DU145 cells were arrested in G2 because of the activation of p-AKT, p-JNK, p21 and p27, and the decrease in p-ERK, cyclin B1 and CDK2 expression; OA-treated MCF-7 cells were arrested in G1 owing to the activation of p-JNK, p-ERK, p21, and p27, and the decrease in p-AKT, cyclin D1, CDK4, cyclin E, and CDK2; and OA-treated U87 cells also exhibited G1 phase arrest caused by the increase in p-ERK, p-JNK, p-AKT, p21, and p27, and the decrease in cyclin D1, CDK4, cyclin E and CDK2. Thus, OA arrested the cell cycle at different phases and induced apoptosis in cancer cells. These results suggested that OA possibly altered the expression of the cell cycle regulatory proteins differently in varying types of cancer.

Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative

PubMed Central

Thomson, Cynthia A.; McCullough, Marjorie L.; Wertheim, Betsy C.; Chlebowski, Rowan T.; Martinez, Maria Elena; Stefanick, Marcia L.; Rohan, Thomas E.; Manson, JoAnn E.; Tindle, Hilary A.; Ockene, Judith; Vitolins, Mara Z.; Wactawski-Wende, Jean; Sarto, Gloria E.; Lane, Dorothy S.; Neuhouser, Marian L.

2014-01-01

Healthy lifestyle behaviors are recommended to reduce cancer risk and overall mortality. Adherence to cancer-preventive health behaviors and subsequent cancer risk has not been evaluated in a diverse sample of postmenopausal women. We examined the association between the American Cancer Society (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines score and risk of incident cancer, cancer-specific mortality, and all-cause mortality in 65,838 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. ACS guidelines scores (0–8 points) were determined from a combined measure of diet, physical activity, body mass index (current and at age 18 years), and alcohol consumption. After a mean follow-up of 12.6 years, 8,632 incident cancers and 2,356 cancer deaths were identified. The highest ACS guidelines scores compared with the lowest were associated with a 17% lower risk of any cancer [HR, 0.83; 95% confidence interval (CI), 0.75–0.92], 22% lower risk of breast cancer (HR, 0.78; 95% CI, 0.67–0.92), 52% lower risk of colorectal cancer (HR, 0.48; 95% CI, 0.32–0.73), 27% lower risk of all-cause mortality, and 20% lower risk of cancer-specific mortality (HR, 0.80; 95% CI, 0.71–0.90). Associations with lower cancer incidence and mortality were generally strongest among Asian, black, and Hispanic women and weakest among non-Hispanic whites. Behaviors concordant with Nutrition and Physical Activity Cancer Prevention Guidelines were associated with lower risk of total, breast, and colorectal cancers and lower cancer-specific mortality in postmenopausal women. PMID:24403289

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasuda, Kazuyo; Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp; Kuroda, Takafumi

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver andmore » kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.« less

"Cirque du Freak."

ERIC Educational Resources Information Center

Rivett, Miriam

2002-01-01

Considers the marketing strategies that underpin the success of the "Cirque du Freak" series. Describes how "Cirque du Freak" is an account of events in the life of schoolboy Darren Shan. Notes that it is another reworking of the vampire narrative, a sub-genre of horror writing that has proved highly popular with both adult and…

Proteolysis-a characteristic of tumor-initiating cells in murine metastatic breast cancer

PubMed Central

Hillebrand, Larissa E.; Bengsch, Fee; Hochrein, Jochen; Hülsdünker, Jan; Bender, Julia; Follo, Marie; Busch, Hauke; Boerries, Melanie; Reinheckel, Thomas

2016-01-01

Tumor initiating cells (TICs) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potential, TICs are founder cells for metastasis formation and are involved in chemotherapy resistance. In this study we explored molecular pathways which enable this tumor initiating potential for a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45−, showed a high tumorigenicity compared to non-CD24+CD90+CD45− cancer cells in colony formation assays, as well as upon orthotopic transplantation into the mammary fat pad of mice. In addition, these orthotopically grown CD24+CD90+CD45− TICs metastasized to the lungs. The transcriptome of TICs freshly isolated from primary tumors by cell sorting was compared with that of sorted non-CD24+CD90+CD45− cancer cells by RNA-seq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in the TICs. Accordingly, TICs showed high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on colony morphology in 3D cell culture assays. We conclude that CD24+CD90+CD45− cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature which could very well represent a functional hallmark of metastatic TICs from mammary carcinomas. PMID:27542270

[Sport coaching for psychological and social recovery after hematological cancer: An innovative perspective].

PubMed

Calvin, Sarah; Blaise, Didier; Ben Soussan, Patrick; Cuvelier, Sarah; Cicut, Nicolas; Caymaris, Laurence; Arnault, Yolande; Onesta, Claude; Dantin, Pierre; Viens, Patrice

2017-10-01

This study is a first step towards the transfer of knowledge and practices between psychological support and performance in elite sport and a patient's "social recovery" in oncology. This proposal brings together people engaged in a variety of healthcare and relationship support roles, and aims to set up a support system beyond the hospital context. It questions the ability of elite sport management and its main actors, the "Great Coaches", to contribute to the support of patients in cancer remission through an onco-coaching approach. This innovative proposal is initiated by a life coaching pilot study designed for hematologic cancer patients in remission after a hematopoietic stem cell transplantation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Lung cancer pathogenesis associated with wood smoke exposure.

PubMed

Delgado, Javier; Martinez, Luis M; Sánchez, Therasa T; Ramirez, Alejandra; Iturria, Cecilia; González-Avila, Georgina

2005-07-01

Tobacco is considered the most important cause of lung cancer, but other factors could also be involved in its pathogenesis. The aim of the present work was to establish an association between wood smoke exposure and lung cancer pathogenesis, and to analyze the effects of wood smoke on p53 and murine double minute 2 (MDM2) protein expression. Blood samples were obtained from 62 lung cancer patients, 9 COPD patients, and 9 control subjects. Of the 62 lung cancer patients, 23 were tobacco smokers (lung cancer associated with tobacco [LCT] group), 24 were exposed to wood smoke (lung cancer associated with wood smoke [LCW] group), and 15 could not be included in these groups. Western blot assays were performed to identify the presence of p53, phospho-p53, and murine double minute 2 (MDM2) isoforms in plasma samples. Densitometric analysis was used to determine the intensity of p53, phospho-p53, and MDM2 bands. Approximately 38.7% of the lung cancer patients examined had an association with wood smoke exposure, most of them women living in rural areas. Adenocarcinoma was present in 46.7% of these patients. The p53 and phospho-p53 proteins were significantly increased in LCW samples (56,536.8 +/- 4,629 densitometry units [DU] and 58,244.8 +/- 7,492 DU, respectively [+/- SD]), in comparison with the other groups. The 57-kD MDM2 isoform plasma concentration was very high in LCW and LCT samples (75,696.4 +/- 11,979 DU and 78,551.7 +/- 11,548 DU, respectively). MDM2-p53 complexes were present in a high concentration in control and COPD subjects. This allows p53 degradation and explains the low concentrations of p53 found in these groups. MDM2-phospho-p53 complexes were observed in COPD but not in the other samples. This correlates with the low concentration of p53 observed in the COPD group (13,657 +/- 2,012 DU), and could explain the different clinic evolution of this smoker population in comparison with the LCT subjects. This study suggests that there is a possible

Trends in initial management of prostate cancer in New Hampshire.

PubMed

Ingimarsson, Johann P; Celaya, Maria O; Laviolette, Michael; Rees, Judy R; Hyams, Elias S

2015-06-01

Prostate cancer management strategies are evolving with increased understanding of the disease. Specifically, there is emerging evidence that "low-risk" cancer is best treated with observation, while localized "high-risk" cancer requires aggressive curative therapy. In this study, we evaluated trends in management of prostate cancer in New Hampshire to determine adherence to evidence-based practice. From the New Hampshire State Cancer Registry, cases of clinically localized prostate cancer diagnosed in 2004-2011 were identified and classified according to D'Amico criteria. Initial treatment modality was recorded as surgery, radiation therapy, expectant management, or hormone therapy. Temporal trends were assessed by Chi-square for trend. Of 6,203 clinically localized prostate cancers meeting inclusion criteria, 34, 30, and 28% were low-, intermediate-, and high-risk disease, respectively. For low-risk disease, use of expectant management (17-42%, p < 0.001) and surgery (29-39%, p < 0.001) increased, while use of radiation therapy decreased (49-19 %, p < 0.001). For intermediate-risk disease, use of surgery increased (24-50%, p < 0.001), while radiation decreased (58-34%, p < 0.001). Hormonal therapy alone was rarely used for low- and intermediate-risk disease. For high-risk patients, surgery increased (38-47%, p = 0.003) and radiation decreased (41-38%, p = 0.026), while hormonal therapy and expectant management remained stable. There are encouraging trends in the management of clinically localized prostate cancer in New Hampshire, including less aggressive treatment of low-risk cancer and increasing surgical treatment of high-risk disease.

Work situation and sickness absence in the initial period after breast cancer surgery.

PubMed

Petersson, Lena-Marie; Wennman-Larsen, Agneta; Nilsson, Marie; Olsson, Mariann; Alexanderson, Kristina

2011-02-01

Breast cancer is the most common cancer diagnosis in women, many of whom are of working age, and the five-year survival rate in Sweden is approaching 90%. Accordingly, aspects of working life and sickness absence are of increasing importance for breast cancer survivors and may have a long-term impact on health and quality of life of these women. The aim was to elucidate the work situation and sickness absence during the initial period after breast cancer surgery and to explore factors associated with sickness absence. This is a cross-sectional questionnaire study 4-6 weeks after breast cancer surgery of women aged 20-63 years, and living in Stockholm. A consecutive sample of 933 women were invited and 756 (81%) accepted to participate. Logistic regression analyses were computed to estimate crude and adjusted odds ratios for associations between sick leave and other variables. Most women (86%) were employed (including self-employed) at diagnosis, and 91% of those worked ≥75% of full-time. At time of survey, 56% were on sick leave, the majority for full-time. Low self-rated health, poorer health than before diagnosis, having a strenuous work posture, and younger age were associated with sick leave during the initial period after breast cancer surgery in both univariate and multivariate analyses. The results of this study is not fully consistent compared to previous studies in this field, often performed in later phases after breast cancer surgery or after other cancer diagnoses. Therefore our results indicate that knowledge is needed during all phases of the breast cancer trajectory to determine factors of importance regarding sick leave and their impact throughout the disease trajectory.

Prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang à Kisangani, République Démocratique du Congo

PubMed Central

Bassandja, Jacques Ossinga; Agasa, Salomon Batina; Likwela, Joris Losimba

2014-01-01

Introduction Le paludisme transfusionnel est une réalité en Afrique Sub-saharienne, en raison des transfusions sanguines répétées, peu ou non contrôlées et où les donneurs sont en majorité potentiellement porteurs d'hématozoaires. L'objectif de cette étude était de déterminer la prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang à Kisangani. Méthodes Une étude transversale a été menée au Centre Provincial de Transfusion Sanguine à Kisangani du 1er Décembre 2012 au 31 Mars 2013 et a concerné 480 donneurs bénévoles de sang. Résultats La prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang était de 28,3%. Plasmodium falciparum était l'espèce la plus répandue (96,3%). Près de la moitié des donneurs avait une parasitémie supérieure à 2000 parasites/µl. Les facteurs qui étaient significativement associés à la parasitémie étaient le jeune âge, le 1er don, et la non utilisation de la moustiquaire imprégnée d'insecticide à longue durée (MILD). Conclusion Les résultats de cette étude montrent que la prévalence du portage asymptomatique du plasmodium chez les donneurs bénévoles de sang était élevée, constituant ainsi un risque important de transmission du parasite aux receveurs souvent en mauvais état général. Cependant, l'utilisation de la MILD et la fidélisation des donneurs bénévoles semblent constituer des moyens utiles de réduction du risque de portage asymptomatique du Plasmodium. Une sensibilisation et éventuellement des distributions ciblées de MILD aux donneurs, en particuliers les plus jeunes, pourraient réduire considérablement le portage du Plasmodium parmi les donneurs de sang et ainsi réduire le risque de paludisme transfusionnel. PMID:25328616

Radiology as the Point of Cancer Patient and Care Team Engagement: Applying the 4R Model at a Patient's Breast Cancer Care Initiation.

PubMed

Weldon, Christine B; Friedewald, Sarah M; Kulkarni, Swati A; Simon, Melissa A; Carlos, Ruth C; Strauss, Jonathan B; Bunce, Mikele M; Small, Art; Trosman, Julia R

2016-12-01

Radiologists aspire to improve patient experience and engagement, as part of the Triple Aim of health reform. Patient engagement requires active partnerships among health providers and patients, and rigorous teamwork provides a mechanism for this. Patient and care team engagement are crucial at the time of cancer diagnosis and care initiation but are complicated by the necessity to orchestrate many interdependent consultations and care events in a short time. Radiology often serves as the patient entry point into the cancer care system, especially for breast cancer. It is uniquely positioned to play the value-adding role of facilitating patient and team engagement during cancer care initiation. The 4R approach (Right Information and Right Care to the Right Patient at the Right Time), previously proposed for optimizing teamwork and care delivery during cancer treatment, could be applied at the time of diagnosis. The 4R approach considers care for every patient with cancer as a project, using project management to plan and manage care interdependencies, assign clear responsibilities, and designate a quarterback function. The authors propose that radiology assume the quarterback function during breast cancer care initiation, developing the care initiation sequence, as a project care plan for newly diagnosed patients, and engaging patients and their care teams in timely, coordinated activities. After initial consultations and treatment plan development, the quarterback function is transitioned to surgery or medical oncology. This model provides radiologists with opportunities to offer value-added services and solidifies radiology's relevance in the evolving health care environment. To implement 4R at cancer care initiation, it will be necessary to change the radiology practice model to incorporate patient interaction and teamwork, develop 4R content and local adaption approaches, and enrich radiology training with relevant clinical knowledge, patient interaction

Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness.

PubMed

Jiang, Wei; Zheng, Yi; Huang, Zhongxian; Wang, Muwen; Zhang, Yinan; Wang, Zheng; Jin, Xunbo; Xia, Qinghua

2014-05-01

To investigate the influence of the histone deacetylase inhibitor valproic acid (VPA) on SMAD4 expression and invasive ability of prostate cancer cell lines. DU145 and PC3 cell lines were treated with 0, 2, and 5 mMol/l of VPA; invasion of DU145 and PC3 cells were then examined by transwell assay. Immunohistochemistry and Western blot were used to examine SMAD4 protein expression in DU145 and PC3 cells. Compared with controls, VPA significantly suppressed invasiveness in both PC3 and DU145 cells in a dose-dependent way (P < 0.05). VPA also inhibited AKT protein (which was regarded as an effective indicator here), and meanwhile, SMAD4 expression was down-regulated after VPA treatment in a dose-dependent manner in both DU145 (P < 0.05) and PC3 (P < 0.01) cells. Valproic acid could suppress invasiveness of prostate cancer cell lines PC3 and Du145, possibly through multiple pathways other than the SAMD4 pathway. This implies that VPA treatment combined with other SMAD4 enhancers could form a basis for a novel prostate cancer treatment.

Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

PubMed

Beebe-Dimmer, Jennifer L; Yee, Cecilia; Paskett, Electra; Schwartz, Ann G; Lane, Dorothy; Palmer, Nynikka R A; Bock, Cathryn H; Nassir, Rami; Simon, Michael S

2017-12-13

Evidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated. Analyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White). Of 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54). Our findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers.

Epidémiologie du cancer gastrique: expérience d'un centre hospitalier marocain

PubMed Central

Mellouki, Ihsane; laazar, Nawal; Benyachou, Bahija; Aqodad, Nouredine; Ibrahimi, Adil

2014-01-01

Le cancer de l'estomac est représenté essentiellement par Les adénocarcinomes gastriques, ces derniers demeurent l'une des dix premières causes mondiales de mortalité avec un pronostic qui est péjoratif. Son incidence reste variable à travers le monde, elle est caractérisée par une importante disparité géographique. Le but de notre travail est de décrire les caractéristiques épidémiologiques de l'adénocarcinome gastrique dans notre contexte à travers une étude rétrospective, observationnelle étalée sur une période de 10 ans (Janvier 2001- Janvier 2011), incluant tous les malades admis au service d'hépato-gastroentérologie du CHU Hassan II de Fès pour prise en charge d'un adénocarcinome gastrique. Durant cette période, 343 patients étaient admis pour prise en charge d'une tumeur gastrique, dont 170 patients avaient un adénocarcinome gastrique (49.5%). L’âge moyen de ces patients était de 58±13.4 ans [16 ans-0 ans]. Dans 43.7% des cas, les patients provenaient de la région de Fès, souvent du milieu rurale. On note une nette prédominance masculine, avec une différence significative entre les 2 sexes (p < ;0.05). Les patients âgés de moins de 60ans représentaient la tranche d’âge prédominante (63%) par rapports aux patients âgés de plus de 60ans (p = 0.02). 61% des patients consultaient dans un délai allant de 1 mois à 6 mois, 30.4% des patients étaient tabagiques, ce facteur avait une relation statistiquement significative avec l'adénocarcinome gastrique (p = 0.02). la non consommation de l'alcool est inversement liée et de façon significative à l'apparition de l'adénocarcinome gastrique (p = 0.03) dans notre contexte. L'infection par Hélicobacter pylori n’était mentionnée que chez peu de malades. Les formes métastatiques au moment du diagnostic dépassaient 50% avec un taux de décès au cours de l'hospitalisation de 2.6%. Sur le plan endoscopique, la localisation antropylorique, et la forme ulc

Tumor initiation in human malignant melanoma and potential cancer therapies.

PubMed

Ma, Jie; Frank, Markus H

2010-02-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.

Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies

PubMed Central

Ma, Jie; Frank, Markus H.

2010-01-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545

Bioenergetic and Antiapoptotic Properties of Mitochondria from Cultured Human Prostate Cancer Cell Lines PC-3, DU145 and LNCaP

PubMed Central

Panov, Alexander; Orynbayeva, Zulfiya

2013-01-01

The purpose of this work was to reveal the metabolic features of mitochondria that might be essential for inhibition of apoptotic potential in prostate cancer cells. We studied mitochondria isolated from normal prostate epithelial cells (PrEC), metastatic prostate cancer cell lines LNCaP, PC-3, DU145; and non-prostate cancer cells - human fibrosarcoma HT1080 cells; and normal human lymphoblastoid cells. PrEC cells contained 2 to 4 times less mitochondria per gram of cells than the three PC cell lines. Respiratory activities of PrEC cell mitochondria were 5-20-fold lower than PC mitochondria, depending on substrates and the metabolic state, due to lower content and lower activity of the respiratory enzyme complexes. Mitochondria from the three metastatic prostate cancer cell lines revealed several features that are distinctive only to these cells: low affinity of Complex I for NADH, 20-30 mV higher electrical membrane potential (ΔΨ). Unprotected with cyclosporine A (CsA) the PC-3 mitochondria required 4 times more Ca2+ to open the permeability transition pore (mPTP) when compared with the PrEC mitochondria, and they did not undergo swelling even in the presence of alamethicin, a large pore forming antibiotic. In the presence of CsA, the PC-3 mitochondria did not open spontaneously the mPTP. We conclude that the low apoptotic potential of the metastatic PC cells may arise from inhibition of the Ca2+-dependent permeability transition due to a very high ΔΨ and higher capacity to sequester Ca2+. We suggest that due to the high ΔΨ, mitochondrial metabolism of the metastatic prostate cancer cells is predominantly based on utilization of glutamate and glutamine, which may promote development of cachexia. PMID:23951286

Genome-wide DNA methylation modified by soy phytoestrogens: role for epigenetic therapeutics in prostate cancer?

PubMed

Karsli-Ceppioglu, Seher; Ngollo, Marjolaine; Adjakly, Mawussi; Dagdemir, Aslihan; Judes, Gaëlle; Lebert, André; Boiteux, Jean-Paul; Penault-LLorca, Frédérique; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2015-04-01

In prostate cancer, DNA methylation is significantly associated with tumor initiation, progression, and metastasis. Previous studies have suggested that soy phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for prostate cancer. The purpose of our study was to examine the modulation effects of phytoestrogens on a genome-wide scale in regards to DNA methylation in prostate cancer. Prostate cancer cell lines DU-145 and LNCaP were treated with 40 μM of genistein and 110 μM of daidzein. DNMT inhibitor 5-azacytidine (2 μM) and the methylating agent budesonide (2 μM) were used to compare their demethylation/methylation effects with phytoestrogens. The regulatory effects of phytoestrogens on DNA methylation were analyzed by using a methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by genistein and daidzein treatments in DU-145 and LNCaP prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by genistein treatment. Our results suggest that the modulation effects of phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of prostate cancer.

German "National Cancer Aid Monitoring" 2015-2019 - study protocol and initial results.

PubMed

Schneider, Sven; Görig, Tatiana; Schilling, Laura; Breitbart, Eckhard W; Greinert, Rüdiger; Diehl, Katharina

2017-09-01

The National Cancer Aid Monitoring of Tanning Bed Use (NCAM) project is a major German study that aims to observe the most significant risk factors for skin cancer: natural sunlight and artificial UV radiation. NCAM is a nationwide cross-sectional survey that will initially involve four rounds of data collection (so-called waves) between 2015 and 2018. Every year, a representative nationwide sample consisting of 3,000 individuals aged between 14 and 45 years will be surveyed. The cross-sectional survey will be complemented by a panel of n  =  450 current tanning bed users. The initial wave in 2015 shows an overall prevalence of tanning bed use of 29.5 %. Eleven percent of all participants had used a tanning bed within the past twelve months. Determinants of current tanning bed use included younger age, female gender, and full-time/part-time employment. The main motivations for tanning bed use reported were relaxation and increased attractiveness. NCAM is the first study worldwide to monitor skin cancer risk factors at one-year intervals using a large, nationally representative sample. Initial results indicate that, despite WHO warnings, millions of Germans use tanning beds, and that many of these users are adolescents despite legal restrictions aimed at preventing minors from using tanning beds. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Metformin suppresses cancer initiation and progression in genetic mouse models of pancreatic cancer.

PubMed

Chen, Ke; Qian, Weikun; Jiang, Zhengdong; Cheng, Liang; Li, Jie; Sun, Liankang; Zhou, Cancan; Gao, Luping; Lei, Meng; Yan, Bin; Cao, Junyu; Duan, Wanxing; Ma, Qingyong

2017-07-24

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide with an overall five-year survival rate less than 7%. Accumulating evidence has revealed the cancer preventive and therapeutic effects of metformin, one of the most widely prescribed medications for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully elucidated. Herein, we aimed to further study the preventive and therapeutic effects of metformin in genetically engineered mouse models of pancreatic cancer. LSL-Kras G12D/+ ; Pdx1-Cre (KC) mouse model was established to investigate the effect of metformin in pancreatic tumorigenesis suppression; LSL-Kras G12D/+ ; Trp53 fl/+ ; Pdx1-Cre (KPC) mouse model was used to evaluate the therapeutic efficiency of metformin in PDAC. Chronic pancreatitis was induced in KC mice by peritoneal injection of cerulein. Following metformin treatment, pancreatic acinar-to-ductal metaplasia (ADM) and mouse pancreatic intraepithelial neoplasia (mPanIN) were decreased in KC mice. Chronic pancreatitis induced a stroma-rich and duct-like structure and increased the formation of ADM and mPanIN lesions, in line with an increased cytokeratin 19 (CK19)-stained area. Metformin treatment diminished chronic pancreatitis-mediated ADM and mPanIN formation. In addition, it alleviated the percent area of Masson's trichrome staining, and decreased the number of Ki67-positive cells. In KPC mice, metformin inhibited tumor growth and the incidence of abdominal invasion. More importantly, it prolonged the overall survival. Metformin inhibited pancreatic cancer initiation, suppressed chronic pancreatitis-induced tumorigenesis, and showed promising therapeutic effect in PDAC.

How does initial treatment choice affect short-term and long-term costs for clinically localized prostate cancer?

PubMed

Snyder, Claire F; Frick, Kevin D; Blackford, Amanda L; Herbert, Robert J; Neville, Bridget A; Carducci, Michael A; Earle, Craig C

2010-12-01

Data regarding costs of prostate cancer treatment are scarce. This study investigates how initial treatment choice affects short-term and long-term costs. This retrospective, longitudinal cohort study followed prostate-cancer cases diagnosed in 2000 for 5 years using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Men age≥66 years, in Medicare fee for service, diagnosed with clinically localized prostate cancer in 2000 while residing in a SEER region, were matched to noncancer controls using age, sex, race, region, comorbidity, and survival. On the basis of treatment received during the first 9 months postdiagnosis, patients were assigned to watchful waiting, radiation, hormonal therapy, hormonal+radiation, and surgery (may have received other treatments). Incremental costs for prostate cancer were the difference in costs for prostate cancer cases versus matched controls. Costs were divided into initial treatment (months -1 to 12), long-term (each 12 months thereafter), and total (months -1 to 60). Sensitivity analyses excluded the last 12 months of life. A total of 13,769 prostate-cancer cases were matched to 13,769 noncancer controls. Watchful waiting had the lowest initial treatment ($4270) and 5-year total costs ($9130). Initial treatment costs were highest for hormonal+radiation ($17,474) and surgery ($15,197). At $26,896, 5-year total costs were highest for hormonal therapy only followed by hormonal+radiation ($25,097) and surgery ($19,214). After excluding the last 12 months of life, total costs were highest for hormonal+radiation ($23,488) and hormonal therapy ($23,199). Patterns of costs vary widely based on initial treatment. These data can inform patients and clinicians considering treatment options and policy makers interested in patterns of costs. Copyright © 2010 American Cancer Society.

PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy.

PubMed

Elshafei, Ahmed; Chevli, K Kent; Moussa, Ayman S; Kara, Onder; Chueh, Shih-Chieh; Walter, Peter; Hatem, Asmaa; Gao, Tianming; Jones, J Stephen; Duff, Michael

2015-12-01

To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS-PBx). Data were collected on 3,675 men with serum prostate specific antigen level (PSA) ≤ 20 ng/ml who underwent initial prostate biopsy with at least 10 cores sampling at time of the biopsy. Two logistic regression models were constructed to predict overall PCa and HGPCa incorporating age, race, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and digital rectal exam (DRE). One thousand six hundred twenty (44%) patients had biopsy confirmed PCa with 701 men (19.1%) showing HGPCa. Statistically significant predictors of overall PCa were age (P < 0.0001, OR. 1.51), PSA at diagnosis (P < 0.0001, OR.1.95), PCA3 (P < 0.0001, OR.3.06), TPV (P < 0.0001, OR.0.47), FH (P = 0.003, OR.1.32), and abnormal DRE (P = 0.001, OR. 1.32). While for HGPCa, predictors were age (P < 0.0001, OR.1.77), PSA (P < 0.0001, OR.2.73), PCA3 (P < 0.0001, OR.2.26), TPV (P < 0.0001, OR.0.4), and DRE (P < 0.0001, OR.1.53). Two nomograms were reconstructed for predicted overall PCa probability at time of initial biopsy with a concordance index of 0.742 (Fig. 1), and HGPCa with a concordance index of 0.768 (Fig. 2). Our internally validated initial biopsy PCA3 based nomogram is reconstructed based on a large dataset. The c-index indicates high predictive accuracy, especially for high grade PCa and improves the ability to predict biopsy outcomes. © 2015 Wiley Periodicals, Inc.

Initiators and promoters for the occurrence of screen-detected breast cancer and the progression to clinically-detected interval breast cancer.

PubMed

Yen, Amy Ming-Fang; Wu, Wendy Yi-Ying; Tabar, Laszlo; Duffy, Stephen W; Smith, Robert A; Chen, Hsiu-Hsi

2017-03-01

The risk factors responsible for breast cancer have been well documented, but the roles of risk factors as initiators, causing the occurrence of screen-detected breast cancer, or promoters, responsible for the progression of the screen-detected to the clinically-detected breast cancer, have been scarcely evaluated. We used data from women in a cohort in Kopparberg (Dalarna), Sweden between 1977 and 2010. Conventional risk factors, breast density, and tumor-specific biomarkers are superimposed to the temporal course of the natural history of the disease. The results show that older age at first full-term pregnancy, dense breast, and a family history of breast cancer increased the risk of entering the preclinical screen-detectable phase of breast cancer by 23%, 41%, and 89%, respectively. Overweight/obesity (body mass index ≥25 kg/m 2 ) was a significant initiator (adjusted relative risk [aRR] 1.15; 95% confidence interval [CI], 0.99-1.33), but was inversely associated with the role of promoter (aRR 0.65; 95% CI, 0.51-0.82). Dense breast (aRR 1.46; 95% CI, 1.12-1.91), triple-negative (aRR 2.07; 95% CI, 1.37-3.15), and Ki-67 positivity (aRR 1.66; 95% CI, 1.19-2.30) were statistically significant promoters. When the molecular biomarkers were considered collectively as one classification, the basal-like subtype was the most influential subtype on promoters (aRR 4.24; 95% CI, 2.56-7.02) compared with the Luminal A subtype. We ascertained state-dependent covariates of initiators and promoters to classify the risk of the two-step progression of breast cancer. The results of the current study are useful for individually-tailored screening and personalized clinical surveillance of patients with breast cancer that was detected at an early stage. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The EMT universe: space between cancer cell dissemination and metastasis initiation.

PubMed

Ombrato, Luigi; Malanchi, Ilaria

2014-01-01

Tumor metastasis, the cause of more than 90% of cancer cell mortality, is a multistep process by which tumor cells disseminate from their primary site via local invasion and intravasation into blood or lymphatic vessels and reach secondary distant sites, where they survive and reinitiate tumor growth. Activation of a developmental program called the epithelial-to-mesenchymal transition (EMT) has been shown to be a very efficient strategy adopted by epithelial cancer cells to promote local invasion and dissemination at distant organs. Remarkably, the activation of EMT programs in epithelial cells correlates with the appearance of stemness. This finding suggests that the EMT process also drives the initial cancer cell colonization at distant sites. However, recent studies support the concept that its reverse program, a mesenchymal-to-epithelial transition, is required for efficient metastatic colonization and that EMT is not necessarily associated with stemness. This review analyzes the conflicting experimental evidence linking epithelial plasticity to stemness in the light of an "EMT gradient model," according to which the outcome of EMT program activation in epithelial cells would be bimodal: coupled to stemness during initial activation, but when forced to reach an advanced mesenchymal status, it would become incompatible with stem cell abilities.

Male breast cancer is rare: an initial presentation may be as an abscess.

PubMed

Ventham, N T; Hussien, M I

2010-08-06

Breast cancer in men is rare. Breast cancer presenting initially as an abscess has been described only a handful of times in the literature. We present the first described case of invasive adenocarcinoma presenting as an abscess in a man. An 80-year-old diabetic man presented with symptoms typical of a breast abscess. The abscess failed to respond to percutaneous therapy and excision of breast abscess was performed. Histology revealed an invasive carcinoma. He went on to have a mastectomy. Histology should be obtained from breast abscesses not resolving within 2 months of initial percutaneous therapy. Histology could be obtained by ultrasound-guided fine-needle aspiration (FNA), core or vacuum assisted biopsy, or by formal incision and drainage.

Secreted factors from metastatic prostate cancer cells stimulate mesenchymal stem cell transition to a pro-tumourigenic 'activated' state that enhances prostate cancer cell migration.

PubMed

Ridge, Sarah M; Bhattacharyya, Dibyangana; Dervan, Eoin; Naicker, Serika D; Burke, Amy J; Murphy, J M; O'leary, Karen; Greene, John; Ryan, Aideen E; Sullivan, Francis J; Glynn, Sharon A

2018-05-15

Mesenchymal stem cells (MSCs) are a heterogeneous population of multipotent cells that are capable of differentiating into osteocytes, chondrocytes and adipocytes. Recently, MSCs have been found to home to the tumour site and engraft in the tumour stroma. However, it is not yet known whether they have a tumour promoting or suppressive function. We investigated the interaction between prostate cancer cell lines 22Rv1, DU145 and PC3, and bone marrow-derived MSCs. MSCs were 'educated' for extended periods in prostate cancer cell conditioned media and PC3-educated MSCs were found to be the most responsive with a secretory profile rich in pro-inflammatory cytokines. PC3-educated MSCs secreted increased osteopontin (OPN), interleukin-8 (IL-8) and fibroblast growth factor-2 (FGF-2) and decreased soluble fms-like tyrosine kinase-1 (sFlt-1) compared to untreated MSCs. PC3-educated MSCs showed a reduced migration and proliferation capacity that was dependent on exposure to PC3-conditioned medium. Vimentin and α-smooth muscle actin (αSMA) expression was decreased in PC3-educated MSCs compared to untreated MSCs. PC3 and DU145 education of healthy donor and prostate cancer patient-derived MSCs led to a reduced proportion of FAP+ αSMA+ cells contrary to characteristics commonly associated with cancer associated fibroblasts (CAFs). The migration of PC3 cells was increased toward both PC3-educated and DU145-educated MSCs compared to untreated MSCs, while DU145 migration was only enhanced toward patient-derived MSCs. In summary, MSCs developed an altered phenotype in response to prostate cancer conditioned medium which resulted in increased secretion of pro-inflammatory cytokines, modified functional activity and the chemoattraction of prostate cancer cells. © 2017 UICC.

Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy.

PubMed

Wang, Lei; Huang, Xing; Zheng, Xinmin; Wang, Xinghuan; Li, Shiwen; Zhang, Lin; Yang, Zhonghua; Xia, Zhiping

2013-01-01

The discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. As CSCs demonstrate resistance to chemoradiation therapy relative to other cancer cells, this allows the enrichment of CSC populations by killing apoptosis-susceptible cancer cells. In this study, three commonly used human prostate cancer (PCa) cell lines (DU145, PC-3 and LNCaP) were examined for their expression of the putative stem cell markers CD133 and CD44 via flow cytometric analysis. Under normal culture conditions, CD133(+)/CD44(+) cells were only present in the DU145 cell line, and comprised only a minor percentage (0.1% ± 0.01%) of the total population. However, the proportion of these CD133(+)/CD44(+) prostate CSCs could be increased in these cell lines via culture in serum-free medium (SFM), or through chemotherapy or radiotherapy. Indeed, after culture in SFM, the proportion of CD133(+)/CD44(+) cells in DU145 and PC-3 had increased to 10.3% and 3.0%, respectively. Moreover, the proportion had increased to 9.8% enriched by chemotherapy and 3.5% by radiotherapy in DU145. Colony-formation tests, cell invasion assays, and tumor xenografts in BALB/c nude mice were used to evaluate the stem cell properties of CD133(+)/CD44(+) PCa cells that were isolated via fluorescence-activated cell sorting (FACS). CD133(+)/CD44(+) cells had an enhanced colony-formation capability and invasive ability in vitro, and displayed greater tumorigenic properties in vivo. These results demonstrate the presence of CD133(+)/CD44(+) prostate CSCs in established PCa cell lines and that populations of these cells can be enriched by culture in SFM or chemoradiotherapy. Finding novel therapies to override chemoradiation resistance in the prostate CSCs is the key to improve long-term results in PCa management.

Command and Control (C2) Agility (Agilite du commandement et du controle (C2))

DTIC Science & Technology

2014-10-01

de la rigueur et de l’emploi des méthodes de mesure et d’amélioration de l’agilité du C2. Le spectre des missions... Control and Intelligence (C2I) Section DRDC Valcartier 2459 de la Bravoure Road Québec (Québec) G3J 1X5 CANADA Email: Micheline.Belanger@drdc...Agilité du commandement et du contrôle (C2) (STO-TR-SAS-085) Synthèse L’agilité est la capacité à effectuer avec succès, s’occuper de

Comparison of curative surgery and definitive chemoradiotherapy as initial treatment for patients with cervical esophageal cancer.

PubMed

Takebayashi, Katsushi; Tsubosa, Yasuhiro; Matsuda, Satoru; Kawamorita, Keisuke; Niihara, Masahiro; Tsushima, Takahiro; Yokota, Tomoya; Sato, Hiroshi; Onozawa, Yusuke; Ogawa, Hirofumi; Kamijo, Tomoyuki; Onitsuka, Tetsuro; Nakagawa, Masahiro; Yasui, Hirofumi

2017-02-01

Esophagectomy and definitive chemoradiotherapy are recognized standard initial treatment modalities for cervical esophageal cancer. The goal of this study was to compare the treatment outcomes of curative surgery with those of chemoradiotherapy in patients who had potentially resectable tumor and who were candidates for surgery. We evaluated the data from 49 consecutive patients who were diagnosed with potentially resectable cervical esophageal cancer and who were deemed candidates for surgery. Thirteen patients were included in the surgery group, and 36 patients were included in chemoradiotherapy group. Baseline characteristics were balanced between the two groups. In the chemoradiotherapy group, the complete response rate was 58.3%. There was no significant difference in 5-year overall survival when comparing the surgery group and the chemoradiotherapy group (surgery, 60.6%; chemoradiotherapy, 51.4%; P = 0.89). In the chemoradiotherapy group, of the 15 patients who failed to respond to initial treatment, 11 patients subsequently underwent salvage surgery. In conclusion, curative surgery and chemoradiotherapy as initial treatment for cervical esophageal cancer have comparable survival outcomes. Chemoradiotherapy should be selected as the initial larynx-preserving treatment for patients with cervical esophageal cancer although chemoradiotherapy non-responders require additional treatment, including salvage surgery. © 2016 International Society for Diseases of the Esophagus.

Chemical species of sulfur in prostate cancer cells studied by XANES spectroscopy

NASA Astrophysics Data System (ADS)

Czapla, Joanna; Kwiatek, Wojciech M.; Lekki, Janusz; Dulińska-Litewka, Joanna; Steininger, Ralph; Göttlicher, Jörg

2013-12-01

The role of sulfur in prostate cancer progression may be significant for understanding the process of carcinogenesis. This work, based on X-ray Absorption Near Edge Structure (XANES) spectroscopy, is focused on determination of sulfur chemical species occurring in prostate cancer cell lines. The experimental material consisted of four commercially available cell lines: three from metastasized prostate cancer (PC3, LNCaP, and DU145) and one, used as a control, from the non-tumourigenic peripheral zone of the prostate (PZ-HPV-7). The experiment was performed at the SUL-X beamline of the synchrotron radiation source ANKA, Karlsruhe (Germany). The K-edge XANES spectra of sulfur were analyzed by deconvolution in order to establish sulfur species that occur in prostate cancer cells and to find out whether there are any differences in their content between various cell lines. Experimental spectra were fitted in two ways: with two Gaussian peaks and one arctangent step function, and additionally by a Linear Combination Fit with spectra of reference compounds in order to obtain quantitative chemical information. All fitting procedures were performed with the Athena code (Ravel and Newville, 2005) and the results of deconvolution were used to determine the fraction of each sulfur form. The results of data analysis showed that cell lines from different metastasis had different ratio of reduced to oxidized sulfur species. The LCF analysis demonstrated that the highest content of GSH, one of the most important sulfur-bearing compounds in cells, was observed in DU145 cells. These findings may confirm the hypothesis of changes in redox balance in case of cancer initiation and progression.

YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression.

PubMed

He, C; Lv, X; Hua, G; Lele, S M; Remmenga, S; Dong, J; Davis, J S; Wang, C

2015-12-10

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces the expression of epidermal growth factor (EGF) receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, whereas knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF & NRGs/ERBBs/YAP/HBEGF & NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression.

YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression

PubMed Central

He, Chunbo; Lv, Xiangmin; Hua, Guohua; Lele, Subodh M; Remmenga, Steven; Dong, Jixin; Davis, John S; Wang, Cheng

2014-01-01

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces expression of EGF receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, while knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF&NRGs/ERBBs/YAP/HBEGF&NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression. PMID:25798835

Antioxidant effects of gamma-oryzanol on human prostate cancer cells.

PubMed

Klongpityapong, Papavadee; Supabphol, Roongtawan; Supabphol, Athikom

2013-01-01

To assess the antioxidant effects of gamma-oryzanol on human prostate cancer cells. Cytotoxic activity of gamma-oryzanol on human DU145 and PC3 prostate cancer cells was determined by proliferation assay using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reagent. mRNA levels of genes involved in the intracellular antioxidant system, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GSR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Cancer cell lysates were used to measure lipid peroxidation using thiobarbituric acid reactive substance (TBARS). Glutathione contents of the cell lysates were estimated by the reaction between sulfhydryl group of 5, 5'-dithio (bis) nitrobenzoic acid (DTNB) to produce a yellow- color of 5-thio-2-nitrobenzoic acid using colorimetric assay. Catalase activity was also analysed by examining peroxidative function. Protein concentration was estimated by Bradford's assay. All concentrations of gamma-oryzanol, 0.1-2.0mg/ml, significantly inhibited cell growth in a dose- and time-dependent fashion in both prostate cancer cell lines, DU145 and PC3. Gene expression of catalase in DU145 and PC3 exposed to gamma-orizanol at 0.5mg/ml for 14 days was down regulated, while mRNA of GPX was also down regulated in PC3. The MDA and glutathione levels including catalase activity in the cell lysates of DU145 and PC3 treated with gamma-oryzanol 0.1 and 0.5mg/ml were generally decreased. This study highlighted effects of gamma-oryzanol via the down-regulation of antioxidant genes, catalase and GPX, not cytotoxic roles. This might be interesting for adjuvant chemotherapy to make prostate cancer cells more sensitive to free radicals. It might be useful for the reduction of cytotoxic agents and cancer chemoprevention.

Cancer Patient and Survivor Research from the Cancer Information Service Research Consortium: A Preview of Three Large Randomized Trials and Initial Lessons Learned

PubMed Central

MARCUS, ALFRED C.; DIEFENBACH, MICHAEL A.; STANTON, ANNETTE L.; MILLER-HALEGOUA, SUZANNE N.; FLEISHER, LINDA; RAICH, PETER C.; MORRA, MARION E.; PEROCCHIA, ROSEMARIE SLEVIN; TRAN, ZUNG VU; BRIGHT, MARY ANNE

2014-01-01

Three large randomized trials are described from the Cancer Information Service Research Consortium (CISRC). Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 is also testing a telephone callback intervention delivered by a cancer information specialist. All participants receive standard print material specific to each project. Preliminary results from the two-month follow-up interviews are reported for the initial wave of enrolled participants, most of whom were recruited from the Cancer Information Service (1-800-4-CANCER) telephone information program (Project 1 = 208, Project 2 = 340, Project 3 = 792). Self-reported use of the multimedia program was 51%, 52% and 67% for Projects 1–3, respectively. Self-reported use of the print materials (read all, most or some) was 90%, 85% and 83% for Projects 1–3, respectively. The callback intervention was completed by 92% of Project 3 participants. Among those using the CISRC interventions, perceived utility and benefit was high, and more than 90% would recommend them to other cancer patients. Five initial lessons learned are presented that may help inform future cancer communications research. PMID:23448232

Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell.

PubMed

Lee, Song-Tay; Wu, Yi-Ling; Chien, Lan-Hsiang; Chen, Szu-Ting; Tzeng, Yu-Kai; Wu, Ting-Feng

2012-11-01

Prostate cancer has been known to be the second highest cause of death in cancer among men. Pomegranate is rich in polyphenols with the potent antioxidant activity and inhibits cell proliferation, invasion, and promotes apoptosis in various cancer cells. This study demonstrated that pomegranate fruit juice could effectively hinder the proliferation of human prostate cancer DU145 cell. The results of apoptotic analyses implicated that fruit juice might trigger the apoptosis in DU145 cells via death receptor signaling and mitochondrial damage pathway. In this study, we exploited 2DE-based proteomics to compare nine pairs of the proteome maps collected from untreated and treated DU145 cells to identify the differentially expressed proteins. Comparative proteomics indicated that 11 proteins were deregulated in affected DU145 cells with three upregulated and eight downregulated proteins. These dys-regulated proteins participated in cytoskeletal functions, antiapoptosis, proteasome activity, NF-κB signaling, cancer cell proliferation, invasion, and angiogenesis. Western immunoblotting were implemented to confirm the deregulated proteins and the downstream signaling proteins. The analytical results of this study help to provide insight into the molecular mechanism of inducing prostate cancer cell apoptosis by pomegranate fruit juice and to develop a novel mechanism-based chemopreventive strategy for prostate cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.

PubMed

Breugom, A J; Boelens, P G; van den Broek, C B M; Cervantes, A; Van Cutsem, E; Schmoll, H J; Valentini, V; van de Velde, C J H

2014-08-01

Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Analyse des facteurs histo-pronostiques du cancer du rectum non métastatique dans une série ouest Algérienne de 58 cas au CHU-Tlemcen

PubMed Central

Mesli, Smain Nabil; Regagba, Derbali; Tidjane, Anisse; Benkalfat, Mokhtar; Abi-Ayad, Chakib

2016-01-01

Introduction L'objectif de notre travail est d'analyser les facteurs histo-pronostiques des cancers du rectum non métastatique opérés au service de chirurgie «A» de Tlemcen à ouest Algérien durant une période de six ans. Méthodes Etude rétrospective de 58 patients qui avait un adénocarcinome rectal. Le critère de jugement était la survie. Les paramètres étudiés, le sexe, l’âge, stade tumoral, et les récidives tumorales. Résultats L’âge moyen était de 58 ans. Avec 52% d'hommes contre 48% femmes avec sex-ratio (1,08). Le siège tumoral était: moyen rectum avec 41,37%, 34,48% au bas rectum et dans 24,13% au haut rectum. La classification TNM avec 17,65% au stade I, 18,61% au stade II, 53, 44% au stade III et 7,84% au stade IV. La survie médiane globale était de 40 mois ±2,937 mois. La survie en fonction du stade tumoral, le stade III et IV avait un faible taux de survie (19%) a 3 ans contre le stade I, II avait un taux de survie de (75%) (P = 0,000) (IC 95%). Les patients avec récidives tumorales avaient un taux de survie faible à 3 ans par rapport à ceux n'ayant pas eu de récidive (30,85% Vs 64,30% P = 0,043). Conclusion Dans cette série, l’étude uni varié des différents facteurs pronostiques conditionnant la survie n'a permis de retenir que trois facteurs influençant la survie, à savoir la taille tumorale, le stade, et les récidives tumorales. En analyse multi variée en utilisant le modèle Cox un seul facteur été retenu la récidive tumorale. PMID:27583069

The characteristics of national health initiatives promoting earlier cancer diagnosis among adult populations: a systematic review protocol

PubMed Central

Calanzani, Natalia; Weller, David; Campbell, Christine

2017-01-01

Introduction The increasing burden of cancer morbidity and mortality has led to the development of national health initiatives to promote earlier cancer diagnosis and improve cancer survival. This protocol describes a systematic review aiming to identify the evidence about such initiatives among the adult population. We will describe their components, stakeholders and target populations, and summarise their outcomes. Methods and analysis We will search databases and websites for peer-reviewed publications and grey literature on national health initiatives in high-income countries as defined by the World Bank. Quantitative, qualitative and mixed-methods studies will be included and assessed for their methodological quality. Study selection, quality assessment and data extraction will be carried out independently by two reviewers. Narrative synthesis will be used to analyse the findings. Ethics and dissemination This systematic review analyses secondary data and ethical approval is not required. Review findings will be helpful to researchers, policy makers, governments and other key stakeholders developing similar initiatives and assessing cancer outcomes. The results will be submitted to a peer-reviewed journal in order to reach a diverse group of healthcare professionals, researchers and policy makers. This systematic review protocol is registered at PROSPERO (CRD42016047233). PMID:28698336

Identification and Targeting of Tyrosine Kinase Activity in Prostate Cancer Initiation, Progression, and Metastasis

DTIC Science & Technology

2012-10-01

accomplishments. Aim 1: Identify the specific tyrosine kinases activated during initiation and progression of genetically altered prostate cancer... Genetics Departmental Retreat (October 2011). (see appendices) • Presented research findings at the AACR Advances in Prostate Cancer Research Conference... genetic backgrounds. However, preliminary data suggests that phosphopeptides from metastatic tumors do indeed segregate from primary prostate tumors and

Cancer patient and survivor research from the cancer information service research consortium: a preview of three large randomized trials and initial lessons learned.

PubMed

Marcus, Alfred C; Diefenbach, Michael A; Stanton, Annette L; Miller, Suzanne M; Fleisher, Linda; Raich, Peter C; Morra, Marion E; Perocchia, Rosemarie Slevin; Tran, Zung Vu; Bright, Mary Anne

2013-01-01

The authors describe 3 large randomized trials from the Cancer Information Service Research Consortium. Three web-based multimedia programs are being tested to help newly diagnosed prostate (Project 1) and breast cancer patients (Project 2) make informed treatment decisions and breast cancer patients prepare for life after treatment (Project 3). Project 3 also tests a telephone callback intervention delivered by a cancer information specialist. All participants receive standard print material specific to each project. Preliminary results from the 2-month follow-up interviews are reported for the initial wave of enrolled participants, most of whom were recruited from the Cancer Information Service (1-800-4-CANCER) telephone information program (Project 1: n =208; Project 2: n =340; Project 3: n =792). Self-reported use of the multimedia program was 51%, 52%, and 67% for Projects 1, 2, and 3, respectively. Self-reported use of the print materials (read all, most, or some) was 90%, 85%, and 83% for Projects 1, 2, and 3, respectively. The callback intervention was completed by 92% of Project 3 participants. Among those using the Cancer Information Service Research Consortium interventions, perceived usefulness and benefit was high, and more than 90% reported that they would recommend them to other cancer patients. The authors present 5 initial lessons learned that may help inform future cancer communications research.

Male breast cancer is rare: an initial presentation may be as an abscess

PubMed Central

Ventham, N T; Hussien, M I

2010-01-01

Breast cancer in men is rare. Breast cancer presenting initially as an abscess has been described only a handful of times in the literature. We present the first described case of invasive adenocarcinoma presenting as an abscess in a man. An 80-year-old diabetic man presented with symptoms typical of a breast abscess. The abscess failed to respond to percutaneous therapy and excision of breast abscess was performed. Histology revealed an invasive carcinoma. He went on to have a mastectomy. Histology should be obtained from breast abscesses not resolving within 2 months of initial percutaneous therapy. Histology could be obtained by ultrasound-guided fine-needle aspiration (FNA), core or vacuum assisted biopsy, or by formal incision and drainage. PMID:22767683

Breast cancer screening initiation after turning 40 years of age within the PROSPR consortium.

PubMed

Beaber, Elisabeth F; Tosteson, Anna N A; Haas, Jennifer S; Onega, Tracy; Sprague, Brian L; Weaver, Donald L; McCarthy, Anne Marie; Doubeni, Chyke A; Quinn, Virginia P; Skinner, Celette Sugg; Zauber, Ann G; Barlow, William E

2016-11-01

Although United States clinical guidelines differ, the earliest recommended age for average risk breast cancer screening is 40 years. Little is known about factors influencing screening initiation. We conducted a cohort study within the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We identified 3413 women on their 40th birthday in primary care networks at Geisel School of Medicine at Dartmouth (DH) and Brigham and Women's Hospital (BWH) during 2011-2013 with no prior breast imaging or breast cancer. Cumulative incidence curves and Cox modeling were used to determine time from the 40th birthday to first breast cancer screening, cohort exit, or 42nd birthday. We calculated hazards ratios and 95 % confidence intervals from multivariable Cox proportional hazards models. Breast cancer screening cumulative incidence by the 42nd birthday was 62.9 % (BWH) and 39.8 % (DH). Factors associated with screening initiation were: a primary care visit within a year (HR 4.99, 95 % CI 4.23-5.89), an increasing number of primary care visits within a year (p for trend <0.0001), ZIP code of residence annual median household income ≤$52,000 (HR 0.79, 95 % CI 0.68-0.92), and health insurance type (Medicaid HR 0.72, 95 % CI 0.58-0.88; Medicare HR 0.55, 95 % CI 0.39-0.77; uninsured HR 0.37, 95 % CI 0.25-0.57). Breast cancer screening uptake after the 40th birthday varies by health system, primary care visits, median household income, and health insurance type, suggesting the need for further exploration. Future research should evaluate screening performance metrics after initiation and consider cumulative benefits and risks associated with breast cancer screening over time.

Élimination du bore du silicium par plasma inductif sous champ électrique

NASA Astrophysics Data System (ADS)

Combes, R.; Morvan, D.; Picard, G.; Amouroux, J.

1993-05-01

We analyzed purification mechanisms of silicon by inductive plasma with a fluoride slag. The aim is to study boron elimination from doped electronic grade silicon in function of the nature of the slag to obtain a photovoltaic grade silicon. The steady began with the calculation and the comparison of the stability diagram of boron compounds in presence of CaF2, BaF2 and MgF2. This study led us to conclude that BaF2 is the better slag for silicon purification. This has been confirmed by experience. In a second time, we made purifications under electric bias to enhance slag efficiency. We noticed that BaF2 is more sensitive to electric bias than other slags. Nous avons analysé le mécanisme de purification du silicium sous plasma inductif en présence d'un laitier fluoré. L'objectif principal est d'étudier l'élimination du bore du silicium électronique dopé en fonction de la nature du fluorure pour obtenir un silicium de qualité photovoltaïque. L'étude a commencé par l'établissement et la comparaison de diagrammes des composés du bore en présence de CaF2, de MgF2 et de BaF2. Nous avons déduit de cette première étude que BaF2 est le meilleur laitier pour la purification du silicium. Ceci a été corroboré par l'expérience. Nous avons ensuite opéré en présence d'un champ électrique dans le but d'améliorer encore l'efficacité des laitiers. Nous avons constaté que BaF2 est plus sensible au champ électrique que les deux autres laitiers utilisés.

TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome.

PubMed

Taghiyev, Agshin F; Guseva, Natalya V; Glover, Rebecca A; Rokhlin, Oskar W; Cohen, Michael B

2006-09-01

The histone deacetylase inhibitor Trichostatin A (TSA) has previously been found to induce caspase activity in the human prostate cancer cell lines DU145 and LNCaP. TSA treatment resulted in the release of cytochrome c and Smac/DIABLO from mitochondria in DU145, and activation of caspase-9 in both cell lines. We concluded that TSA mediated its effect via the mitochondrial pathway. The aim of the current study was to determine how TSA initiated the caspase cascade. The results revealed that caspase-2 plays an important role in TSA-induced apoptosis. Inhibition of caspase-2 by siRNA or expression of caspase-2dn substantially decreased caspase activity after TSA treatment in both cell lines, siRNA caspase-2 also inhibited TSA-induced cell death. Caspase-2 acts upstream of caspase-8 and -9 and mediates mitochondrial cytochrome c release. Coimmunoprecipitation experiments show that caspase-2 formed protein complexes with RADD/RAIDD and PIDD. Together, these data indicate that caspase-2 initiates caspase cascade after TSA treatment and involves the formation of the PIDDosome.

Vulnerabilities in Older Patients when Cancer Treatment is Initiated: Does a Cognitive Impairment Impact the Two-Year Survival?

PubMed Central

Borghgraef, Cindy; Etienne, Anne-Marie; Merckaert, Isabelle; Paesmans, Marianne; Reynaert, Christine; Roos, Myriam; Slachmuylder, Jean-Louis; Vandenbossche, Sandrine; Bron, Dominique; Razavi, Darius

2016-01-01

Introduction Dementia is a known predictor of shorter survival times in older cancer patients. However, no empirical evidence is available to determine how much a cognitive impairment shortens survival in older patients when cancer treatment is initiated. Purpose To longitudinally investigate how much a cognitive impairment detected at the initiation of cancer treatment influences survival of older patients during a two-year follow-up duration and to compare the predictive value of a cognitive impairment on patients survival with the predictive value of other vulnerabilities associated with older age. Methods Three hundred and fifty-seven consecutive patients (≥65 years old) admitted for breast, prostate, or colorectal cancer surgeries were prospectively recruited. A cognitive impairment was assessed with the Montreal Cognitive Assessment (MoCA<26). Socio-demographic, disease-related, and geriatric vulnerabilities were assessed using validated tools. Univariate and subsequent multivariate Cox proportional hazards models stratified for diagnosis (breast/prostate cancer versus colorectal cancer) and disease status (metastatic versus non-metastatic) were used. Results A cognitive impairment was detected in 46% (n = 163) of patients. Survival was significantly influenced by a cognitive impairment (HR = 6.13; 95% confidence interval [CI] = 2.07–18.09; p = 0.001), a loss in instrumental autonomy (IADL ≤7) (HR = 3.06; 95% CI = 1.31–7.11; p = 0.009) and fatigue (Mob-T<5) (HR = 5.98; 95% CI = 2.47–14.44; p <0.001). Conclusions During the two years following cancer treatment initiation, older patients with a cognitive impairment were up to six times more likely to die than patients without. Older patients should be screened for cognitive impairments at cancer treatment initiation to enable interventions to reduce morbidity and mortality. Further studies should address processes underlying the relationship between cognitive impairments and an increased risk of dying

Consequences experimentales des effets des fluctuations du vide sur la fluorescence parametrique et la generation du second harmonique en milieu confine

NASA Astrophysics Data System (ADS)

Robichaud, Luc

Les fluctuations du vide, qui consistent en l'apparition momentanee de particules, ce qui est permit par le principe d'incertitude de Heisenberg, joue un role primordial dans les processus photoniques, en particulier les processus non-lineaires. Par la manipulation de ces fluctuations du vide a l'aide de confinement optique, on retrouve deux phenomenes particuliers : l'intensification de la fluorescence parametrique (Walker, 2008) et l'inhibition de la generation du second harmonique (Collette, 2013). Dans ce travail, on presente les resultats dans le cas classique ; c'est-a-dire sans fluctuations du vide et confinement. Par la suite, on presente les effets des fluctuations du vide et du confinement, ce qui mene aux deux effets mentionnes. Dans le cas de la fluorescence parametrique, le bruit quantique sur le champ interne et externe est calcule, le role du desaccord de phase dans le modele est expose et une generalisation tridimensionnelle est etudiee afin de generaliser la conception du modele d'un cas unidimensionnel a un cas tridimensionnel planaire. Dans le cas de la generation du second harmonique, les difficultes d'un modele purement tridimensionnel sont exposees et ensuite le cas limite planaire est etudie.

Initial metformin or sulphonylurea exposure and cancer occurrence among patients with type 2 diabetes mellitus.

PubMed

Qiu, H; Rhoads, G G; Berlin, J A; Marcella, S W; Demissie, K

2013-04-01

This was a retrospective cohort study of type 2 diabetes patients, to evaluate the association between initial metformin or sulphonylurea treatment and cancer incidence. Patients identified in the UK Clinical Practice Research Datalink (CPRD), previously General Practice Research Database, during 1995-2008 who were initially stabilized on OHA monotherapy, including metformin, sulphonylurea, thiazolidinediones (TZDs) or meglitinides, were included in the cohort. New diagnoses of cancer, including malignant solid tumours and haematological malignancies, occurring during the follow-up were identified from the cohort. Age-standardized incidence rates were estimated and compared between metformin and sulphonylurea exposure groups. The age standardized incidences of cancer were 7.5 and 8.5 per 1000 person-years for the metformin and sulphonylurea exposure groups, respectively. After adjusting for potential confounders, the hazard ratios (HR) for malignant solid tumours and haematological malignancies were 1.06 (95% CI: 0.98, 1.15) and 0.98 (95% CI: 0.67, 1.43) for sulphonylurea group as compared to the metformin group, respectively. For individual cancers, the HRs were 1.17 (95% CI: 0.95, 1.44), 1.04 (95% CI: 0.83, 1.31) and 0.88 (95% CI: 0.71, 1.11) for colorectal cancer, breast cancer and prostate cancer, respectively. This study provides evidence that cancer incidence in the first few years after starting metformin or sulphonylurea therapy in type 2 diabetes patients is not much affected by choice of hypoglycaemic drug class. © 2012 Blackwell Publishing Ltd.

Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses.

PubMed

Kim, S B; Bozeman, R G; Kaisani, A; Kim, W; Zhang, L; Richardson, J A; Wright, W E; Shay, J W

2016-06-30

Proton radiotherapy is becoming more common as protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared with conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole-body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIRs), which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence-associated gene (P19Arf), are markedly increased. Following these changes, loss of Casein kinase Iα and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (CDDO-EA), reduces proton irradiation-associated SIR and tumorigenesis. Thus exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA.

The Project Data Sphere Initiative: Accelerating Cancer Research by Sharing Data

PubMed Central

Reeder-Hayes, Katherine E.; Corty, Robert W.; Basch, Ethan; Milowsky, Mathew I.; Dusetzina, Stacie B.; Bennett, Antonia V.; Wood, William A.

2015-01-01

Background. In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community. Potential Benefits and Risks of Data Sharing. For researchers, shared data have the potential to foster a more collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are

Study of NGEP expression in androgen sensitive prostate cancer cells: A potential target for immunotherapy

PubMed Central

Mohsenzadegan, Monireh; Tajik, Nader; Madjd, Zahra; Shekarabi, Mehdi; Farajollahi, Mohammad M

2015-01-01

Background: Prostate cancer is one of the leading causes of cancer deaths among men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed only in normal prostate and prostate cancer tissue. Because of its selective expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic target. To target the NGEP in prostate cancer, it is essential to investigate its expression in prostate cancer cells. Methods: In the present study, we investigated NGEP expression in LNCaP and DU145 cells by real time and RT-PCR, flow cytometric and immunocytochemical analyses. Results: Real time and RT-PCR analyses of NGEP expression showed that NGEP was expressed in the LNCaP cells but not in DU145 cells. The detection of NGEP protein by flow cytometric and immunocytochemistry analyses indicated that NGEP protein was weakly expressed only in LNCaP cell membrane. Conclusion: Our results demonstrate that LNCaP cell line is more suitable than DU145 for NGEP expression studies; however, its low-level expression is a limiting issue. NGEP expression may be increased by androgen supplementation of LNCaP cell culture medium. PMID:26000254

Clinical and Organizational Factors in the Initial Evaluation of Patients With Lung Cancer

PubMed Central

Jim Yeung, Sai-Ching; Tanoue, Lynn T.; Gould, Michael K.

2013-01-01

Background: This guideline is intended to provide an evidence-based approach to the initial evaluation of patients with known or suspected lung cancer. It also includes an assessment of the impact of timeliness of care and multidisciplinary teams on outcome. Methods: The applicable current medical literature was identified by a computerized search and evaluated using standardized methods. Recommendations were framed using the approach described by the Guidelines Oversight Committee of the American College of Chest Physicians. Data sources included MEDLINE and the Cochrane Database of Systematic Reviews. Results: Initial evaluation should include a thorough history and physical examination; CT imaging; pulmonary function tests; and hemoglobin, electrolyte, liver function, and calcium levels. Additional testing for distant metastases and paraneoplastic syndromes should be determined on the basis of these results. Paraneoplastic syndromes may have an adverse impact on cancer treatment, so they should be controlled rapidly with the goal of proceeding with definitive cancer treatment in a timely manner. Although the relationship between timeliness of care and survival is difficult to quantify, efforts to deliver timely care are reasonable and should be balanced with the need to attend to other dimensions of health-care quality (eg, safety, effectiveness, efficiency, equality, consistency with patient values and preferences). Quality care will require multiple disciplines. Although it is difficult to assess the impact, we suggest that a multidisciplinary team approach to care be used, particularly for patients requiring multimodality therapy. Conclusions: The initial evaluation of patients with lung cancer should include a thorough history and physical examination, pulmonary function tests, CT imaging, basic laboratory tests, and selective testing for distant metastases and paraneoplastic syndromes. PMID:23649435

Analysis of TP53 gene expression and p53 level of human hypopharyngeal FaDu (HTB-43) head and neck cancer cell line after microRNA-181a inhibition.

PubMed

Cheah, Y K; Cheng, R W; Yeap, S K; Khoo, C H; See, H S

2014-03-17

The identification of new biomarkers for early detection of highly recurrent head and neck cancer is urgently needed. MicroRNAs (miRNAs) are small and non-coding RNAs that regulate cancer-related gene expression, such as tumor protein 53 (TP53) gene expression. This study was carried out to analyze TP53 gene expression using real-time PCR and to determine changes in intracellular p53 level by flow cytometry after downregulation of miRNA-181a miRNA inhibitor in the FaDu cell line. TP53 gene expression showed a 3-fold increment and the p53 protein level was also increased in the miRNA-181a-treated cells. In conclusion, miRNA-181a binds to the TP53 gene and inhibits its expression, decreasing the synthesis of p53.

Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

PubMed Central

Buganim, Yosef; Solomon, Hilla; Goldfinger, Naomi; Hovland, Randi; Ke, Xi-Song; Oyan, Anne M.; Kalland, Karl-H.; Rotter, Varda; Domany, Eytan

2011-01-01

Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification. PMID:21297939

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

PubMed

Cressman, Sonya; Lam, Stephen; Tammemagi, Martin C; Evans, William K; Leighl, Natasha B; Regier, Dean A; Bolbocean, Corneliu; Shepherd, Frances A; Tsao, Ming-Sound; Manos, Daria; Liu, Geoffrey; Atkar-Khattra, Sukhinder; Cromwell, Ian; Johnston, Michael R; Mayo, John R; McWilliams, Annette; Couture, Christian; English, John C; Goffin, John; Hwang, David M; Puksa, Serge; Roberts, Heidi; Tremblay, Alain; MacEachern, Paul; Burrowes, Paul; Bhatia, Rick; Finley, Richard J; Goss, Glenwood D; Nicholas, Garth; Seely, Jean M; Sekhon, Harmanjatinder S; Yee, John; Amjadi, Kayvan; Cutz, Jean-Claude; Ionescu, Diana N; Yasufuku, Kazuhiro; Martel, Simon; Soghrati, Kamyar; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Peacock, Stuart J

2014-10-01

It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400-$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553-$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254-$52,200; p = 0.061). In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

Resource Utilization and Costs during the Initial Years of Lung Cancer Screening with Computed Tomography in Canada

PubMed Central

Lam, Stephen; Tammemagi, Martin C.; Evans, William K.; Leighl, Natasha B.; Regier, Dean A.; Bolbocean, Corneliu; Shepherd, Frances A.; Tsao, Ming-Sound; Manos, Daria; Liu, Geoffrey; Atkar-Khattra, Sukhinder; Cromwell, Ian; Johnston, Michael R.; Mayo, John R.; McWilliams, Annette; Couture, Christian; English, John C.; Goffin, John; Hwang, David M.; Puksa, Serge; Roberts, Heidi; Tremblay, Alain; MacEachern, Paul; Burrowes, Paul; Bhatia, Rick; Finley, Richard J.; Goss, Glenwood D.; Nicholas, Garth; Seely, Jean M.; Sekhon, Harmanjatinder S.; Yee, John; Amjadi, Kayvan; Cutz, Jean-Claude; Ionescu, Diana N.; Yasufuku, Kazuhiro; Martel, Simon; Soghrati, Kamyar; Sin, Don D.; Tan, Wan C.; Urbanski, Stefan; Xu, Zhaolin; Peacock, Stuart J.

2014-01-01

Background: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Methods: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer’s perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. Results: The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400–$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553–$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254–$52,200; p = 0.061). Conclusion: In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure. PMID:25105438

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer].

PubMed

Grünewaldt, A; Hügel, C; Hermann, E; Wagner, T O F

2017-02-01

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods  In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results  We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion  We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.

Benzoxazinoids from Scoparia dulcis (sweet broomweed) with antiproliferative activity against the DU-145 human prostate cancer cell line.

PubMed

Wu, Wan-Hsun; Chen, Tzu-Yu; Lu, Rui-Wen; Chen, Shui-Tein; Chang, Chia-Chuan

2012-11-01

Sweet broomweed (Scoparia dulcis) is an edible perennial medicinal herb widely distributed in tropical and subtropical regions of Asia, Africa, and the Americas. Four compounds, (2R)-7-methoxy-2H-1,4-benzoxazin-3(4H)-one 2-O-β-galactopyranoside [(2R)-HMBOA-2-O-Gal], 3,6-dimethoxy-benzoxazolin-2(3H)-one (3,6-M2BOA), 3-hydroxy-6-methoxy-2-benzoxazolinone (3-OH-MBOA), and scutellarein 7-O-β-glucuronamide, along with eight known compounds, including two 7-methoxy-1,4-benzoxazin-3(2H)-one 3-O-hexopyranosides [(2R)-HMBOA-2-O-Glc and (2R)-HDMBOA-2-O-Glc], 6-methoxy-benzoxazolin-2(3H)-one (MBOA), acteoside, sodium scutellarin, p-coumaric acid, and two monosaccharides (fructose and glucose), were isolated from the aqueous extract of S. dulcis. Antiproliferative activities of the six benzoxazinoid compounds against the DU-145 human prostate cancer cell line were assayed, and one of these displayed an IC₅₀ of 65.8 μg/mL. Copyright © 2012 Elsevier Ltd. All rights reserved.

Le role du phytoplancton de petite taille (<20 mum) dans les variations des proprietes optiques des eaux du Saint-Laurent

NASA Astrophysics Data System (ADS)

Mas, Sebastien

Les mesures satellitaires de couleur des oceans sont largement determinees par les proprietes optiques inherentes (IOPs) des eaux de surface. D'autre part, le phytoplancton de petite taille (<20 mum) est le plus souvent dominant dans les oceans, et peut donc etre une source importante de variation des IOPs dans les oceans. Dans ce contexte, le but principal de ce doctorat etait de definir l'impact du phytoplancton (<20 mum) sur les variations des proprietes optiques de l'Estuaire et du Golfe du Saint-Laurent (Canada). Afin d'atteindre cet objectif, il etait necessaire de determiner en milieu controle les facteurs de variabilite des proprietes optiques cellulaires et des IOPs du phytoplancton (<20 mum) des eaux du Saint-Laurent, et d'evaluer la contribution du phytoplancton (<20 mum) aux proprietes optiques totales des eaux du Saint-Laurent. Des experiences en laboratoire ont montre que les variations des proprietes optiques des cellules phytoplanctoniques soumises a un cycle jour-nuit, ainsi qu'a des changements concomitants d'intensite lumineuse, peuvent contribuer significativement a la variabilite des proprietes optiques observee en milieu naturel. D'autres experiences ont, quant a elles, mis en evidence que les variations des proprietes optiques des cellules phytoplanctoniques dues aux phases de croissance peuvent alterer les IOPs des oceans, particulierement pendant les periodes de floraison. De plus, la presence de bacteries et de particules detritiques peut egalement affecter la variabilite des IOPs totales, notamment la diffusion. Au printemps, dans l'Estuaire et le Golfe du Saint-Laurent, la contribution du phytoplancton <20 mum aux IOPs presentait des differences regionales evidentes pour les proprietes d'absorption et de diffusion. En plus de la variabilite spatiale, les proprietes optiques cellulaires presentaient des variations journalieres, et ce particulierement pour le picophytoplancton. Enfin, la plupart des differences observees dans les

Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression.

PubMed

Lee, Jong Hun; Khor, Tin Oo; Shu, Limin; Su, Zheng-Yuan; Fuentes, Francisco; Kong, Ah-Ng Tony

2013-02-01

Reactive metabolites from carcinogens and oxidative stress can drive genetic mutations, genomic instability, neoplastic transformation, and ultimately carcinogenesis. Numerous dietary phytochemicals in vegetables/fruits have been shown to possess cancer chemopreventive effects in both preclinical animal models and human epidemiological studies. These phytochemicals could prevent the initiation of carcinogenesis via either direct scavenging of reactive oxygen species/reactive nitrogen species (ROS/RNS) or, more importantly, the induction of cellular defense detoxifying/antioxidant enzymes. These defense enzymes mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against ROS/RNS and reactive metabolites of carcinogens. In addition, these compounds would kill initiated/transformed cancer cells in vitro and in in vivo xenografts via diverse anti-cancer mechanisms. These mechanisms include the activation of signaling kinases (e.g., JNK), caspases and the mitochondria damage/cytochrome c pathways. Phytochemicals may also have anti-cancer effects by inhibiting the IKK/NF-κB pathway, inhibiting STAT3, and causing cell cycle arrest. In addition, other mechanisms may include epigenetic alterations (e.g., inhibition of HDACs, miRNAs, and the modification of the CpG methylation of cancer-related genes). In this review, we will discuss: the current advances in the study of Nrf2 signaling; Nrf2-deficient tumor mouse models; the epigenetic control of Nrf2 in tumorigenesis and chemoprevention; Nrf2-mediated cancer chemoprevention by naturally occurring dietary phytochemicals; and the mutation or hyper-expression of the Nrf2-Keap1 signaling pathway in advanced tumor cells. The future development of dietary phytochemicals for chemoprevention must integrate in vitro signaling mechanisms, relevant biomarkers of human diseases, and combinations of different phytochemicals and/or non-toxic therapeutic drugs, including

Increasing time to treatment initiation for head and neck cancer: an analysis of the National Cancer Database.

PubMed

Murphy, Colin T; Galloway, Thomas J; Handorf, Elizabeth A; Wang, Lora; Mehra, Ranee; Flieder, Douglas B; Ridge, John A

2015-04-15

The objective of this study was to identify trends and predictors of the time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). The National Cancer Database (NCDB) was reviewed for the following head and neck cancer sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was defined as the number of days from diagnosis to the initiation of definitive treatment and was measured according to covariates. Significant differences in the median TTI across each covariate were measured using the Kruskal-Wallis test, and the Spearman test was used to measure trends within covariates. For multivariate analysis, a zero-inflated, negative, binomial regression model was used to estimate the expected TTI, which was expressed in the predicted number of days; and the Vuong test was used to identify the predictors of TTI. In total, 274,630 patients were included. Between 1998 and 2011, the median TTI for all patients was 26 days, and it increased from 19 days to 30 days (P < .0001). Treatment with chemoradiation (CRT) (P < .0001), treatment at academic facilities (P < .0001), and stage IV disease (P < .0001) were associated with increased TTI. TTI significantly increased for each disease stage (P < .0001), treatment modality (P < .0001), and facility type (P < .0001) over time. In addition, patients became more likely to transition care between facilities after diagnosis for treatment initiation (P < .0001) over time. On multivariate analysis, treatment at academic facilities (33 days), transitioning care (37 days), and receipt of CRT (39 days) predicted for a longer TTI. TTI is rising for patients with HNSCC. Those who have advanced-stage disease, receive treatment with CRT, are treated at academic facilities, and who have a transition in care realized the greatest increases in TTI. © 2014 American Cancer Society.

Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

PubMed Central

Gai, Wen-Tao; Yu, Da-Peng; Wang, Xin-Sheng; Wang, Pei-Tao

2016-01-01

Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. PMID:27698874

Patterns of initial management of node-negative breast cancer in two Canadian provinces

PubMed Central

Goel, V; Olivotto, I; Hislop, T G; Sawka, C; Coldman, A; Holowaty, E J

1997-01-01

OBJECTIVE: To describe the patterns of initial management of node-negative breast cancer in Ontario and British Columbia and to compare the characteristics of the patients and tumours and of the physicians and hospitals involved in management. DESIGN: Retrospective, population-based, cohort study. PARTICIPANTS: All 942 newly diagnosed cases of node-negative breast cancer in 1991 in British Columbia and a random sample of 938 newly diagnosed cases in Ontario in the same year. OUTCOME MEASURES: Number and proportion of patients with newly diagnosed node-negative breast cancer who received breast-conserving surgery (BCS) or mastectomy and who received radiation therapy after BCS. RESULTS: BCS was used in 413 cases (43.8%) in British Columbia and in 634 cases (67.6%) in Ontario (p < 0.001). After BCS, radiation therapy was received by 378 patients (91.5% of those who had undergone BCS) in British Columbia and 479 patients (75.6% of those who had undergone BCS) in Ontario (p < 0.001). In both provinces, lower patient age, smaller tumour size, a noncentral unifocal tumour, absence of extensive ductal carcinoma in situ and initial surgery by a surgeon with an academic affiliation were associated with greater use of BCS. Lower patient age and larger tumour size were associated with greater use of radiation therapy after BCS in both provinces. CONCLUSION: Patient, tumour and physician factors are associated with the choice of initial management of breast cancer in these two Canadian provinces. However, the differences in management between the two provinces are only partly explained by these factors. Other possible explanations, such as the presence of provincial guidelines, differences in the organization of the health care system or differences in patient preference, require further research. PMID:9006561

The project data sphere initiative: accelerating cancer research by sharing data.

PubMed

Green, Angela K; Reeder-Hayes, Katherine E; Corty, Robert W; Basch, Ethan; Milowsky, Mathew I; Dusetzina, Stacie B; Bennett, Antonia V; Wood, William A

2015-05-01

In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community. For researchers, shared data have the potential to foster a more collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are deidentified to maintain anonymity. To address industry

La reconstruction du sourcil par greffon composite du cuir chevelu: une astuce pour faciliter la technique

PubMed Central

El Omari, Mounia; El Mazouz, Samir; Gharib, Noureddine; EL Abbassi, Abdallah

2015-01-01

Les sourcils jouent un rôle important dans l’équilibre esthétique du visage. Leur reconstruction ou ophriopoïése, après séquelle de brûlure fait partie intégrante du programme de réhabilitation de la face brûlée. Plusieurs techniques ont été décrites. Nous insistons ici sur l'intérêt d'une technique simple, à la portée de tous les chirurgiens, et dont la méthode et les résultats peuvent être améliorés par un dessin bien planifié des zones donneuse et receveuse: la greffe composite prélevée au niveau du cuir chevelu dessinée à l'aide d'un calque du sourcil controlatéral. PMID:26401195

The Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study: Description and Baseline Characteristics of Participants.

PubMed

Paskett, Electra D; Caan, Bette J; Johnson, Lisa; Bernardo, Brittany M; Young, Gregory S; Pennell, Michael L; Ray, Roberta M; Kroenke, Candyce H; Porter, Peggy L; Anderson, Garnet L

2018-02-01

Background: The Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study offers an important opportunity to advance cancer research by extending the original WHI studies to examine survivorship in women diagnosed with cancer during their participation in WHI. Methods: The goals of LILAC are to (i) obtain cancer treatment information and long-term cancer outcomes for women diagnosed with one of eight selected cancers (breast, endometrial, ovarian, lung, and colorectal cancers, and melanoma, lymphoma, and leukemia); (ii) augment the existing WHI biorepository with fixed tumor tissue from the solid tumor sites for cancers diagnosed since 2002; and (iii) develop, refine, and validate methods to use administrative data to capture treatment and recurrence data. Methods for accomplishing these goals are described, as are results from the initial LILAC participant survey. Results: A total of 9,934 WHI participants living with cancer were eligible for LILAC participation, of which 78% ( N = 7,760) agreed to participate. Among the three most prevalent cancer types, 54% are breast cancer survivors, 11% are melanoma survivors, and 10% are survivors of colorectal cancer. Conclusions: In addition to describing this resource, we present pertinent lessons that may assist other investigators interested in embedding survivorship research into existing large epidemiologic cohorts. Impact: The LILAC resource offers a valuable opportunity for researchers to study cancer survivorship and issues pertinent to cancer survivors in future studies. Cancer Epidemiol Biomarkers Prev; 27(2); 125-37. ©2017 AACR . ©2017 American Association for Cancer Research.

Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

PubMed

Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

2016-09-01

Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared

Boric acid inhibits human prostate cancer cell proliferation.

PubMed

Barranco, Wade T; Eckhert, Curtis D

2004-12-08

The role of boron in biology includes coordinated regulation of gene expression in mixed bacterial populations and the growth and proliferation of higher plants and lower animals. Here we report that boric acid, the dominant form of boron in plasma, inhibits the proliferation of prostate cancer cell lines, DU-145 and LNCaP, in a dose-dependent manner. Non-tumorigenic prostate cell lines, PWR-1E and RWPE-1, and the cancer line PC-3 were also inhibited, but required concentrations higher than observed human blood levels. Studies using DU-145 cells showed that boric acid induced a cell death-independent proliferative inhibition, with little effect on cell cycle stage distribution and mitochondrial function.

Effets de l'humidite sur la propagation du delaminage dans un composite carbone/epoxy sollicite en mode mixte I/II

NASA Astrophysics Data System (ADS)

LeBlanc, Luc R.

Les materiaux composites sont de plus en plus utilises dans des domaines tels que l'aerospatiale, les voitures a hautes performances et les equipements sportifs, pour en nommer quelques-uns. Des etudes ont demontre qu'une exposition a l'humidite nuit a la resistance des composites en favorisant l'initiation et la propagation du delaminage. De ces etudes, tres peu traitent de l'effet de l'humidite sur l'initiation du delaminage en mode mixte I/II et aucune ne traite des effets de l'humidite sur le taux de propagation du delaminage en mode mixte I/II dans un composite. La premiere partie de cette these consiste a determiner les effets de l'humidite sur la propagation du delaminage lors d'une sollicitation en mode mixte I/II. Des eprouvettes d'un composite unidirectionnel de carbone/epoxy (G40-800/5276-1) ont ete immergees dans un bain d'eau distillee a 70°C jusqu'a leur saturation. Des essais experimentaux quasi-statiques avec des chargements d'une gamme de mixites des modes I/II (0%, 25%, 50%, 75% et 100%) ont ete executes pour determiner les effets de l'humidite sur la resistance au delaminage du composite. Des essais de fatigue ont ete realises, avec la meme gamme de mixite des modes I/II, pour determiner 1'effet de 1'humidite sur l'initiation et sur le taux de propagation du delaminage. Les resultats des essais en chargement quasi-statique ont demontre que l'humidite reduit la resistance au delaminage d'un composite carbone/epoxy pour toute la gamme des mixites des modes I/II, sauf pour le mode I ou la resistance au delaminage augmente apres une exposition a l'humidite. Pour les chargements en fatigue, l'humidite a pour effet d'accelerer l'initiation du delaminage et d'augmenter le taux de propagation pour toutes les mixites des modes I/II. Les donnees experimentales recueillies ont ete utilisees pour determiner lesquels des criteres de delaminage en statique et des modeles de taux de propagation du delaminage en fatigue en mode mixte I/II proposes dans la

Holoclone Forming Cells from Pancreatic Cancer Cells Enrich Tumor Initiating Cells and Represent a Novel Model for Study of Cancer Stem Cells

PubMed Central

Tan, Lei; Sui, Xin; Deng, Hongkui; Ding, Mingxiao

2011-01-01

Background Pancreatic cancer is one of the direct causes of cancer-related death. High level of chemoresistance is one of the major obstacles of clinical treatment. In recent years, cancer stem cells have been widely identified and indicated as the origin of chemoresistance in multi-types of solid tumors. Increasing evidences suggest that cancer stem cells reside in the cells capable of forming holoclones continuously. However, in pancreatic cancer, holoclone-forming cells have not been characterized yet. Therefore, the goal of our present study was to indentify the holoclone-forming pancreatic cancer stem cells and develop an in vitro continuous colony formation system, which will greatly facilitate the study of pancreatic cancer stem cells. Methodology/Principal Findings Pancreatic cancer cell line BxPC3 was submitted to monoclonal cultivation to generate colonies. Based on the morphologies, colonies were classified and analyzed for their capacities of secondary colony formation, long-term survival in vitro, tumor formation in vivo, and drug resistance. Flowcytometry and quantitative RT-PCR were performed to detect the expression level of cancer stem cells associated cell surface markers, regulatory genes and microRNAs in distinct types of colonies. Three types of colonies with distinct morphologies were identified and termed as holo-, mero-, and paraclones, in which only holoclones generated descendant colonies of all three types in further passages. Compared to mero- and paraclones, holoclones possessed higher capacities of long-term survival, tumor initiation, and chemoresistance. The preferential expression of cancer stem cells related marker (CXCR4), regulatory genes (BMI1, GLI1, and GLI2) and microRNAs (miR-214, miR-21, miR-221, miR-222 and miR-155) in holoclones were also highlighted. Conclusions/Significance Our results indicate that the pancreatic tumor-initiating cells with high level of chemoresistance were enriched in holoclones derived from BxPC3

Zoledronic acid overcomes chemoresistance by sensitizing cancer stem cells to apoptosis.

PubMed

Rouhrazi, H; Turgan, N; Oktem, G

2018-01-01

Unlike low tumorigenic bulk tumor cells (non-CSCs), cancer stem cells (CSCs) are a subset of tumor cells that can self-renew and differentiate into different cancer subtypes. CSCs are considered responsible for tumor recurrence, distant metastasis, angiogenesis, and drug or radiation resistance. CSCs also are resistant to apoptosis. Zoledronic acid (ZA) is a third generation bisphosphonate that reduces cell proliferation and exhibits anti-tumor effects by inducing cell death in some malignancies; however, the effects of ZA on CSCs are unclear. We investigated the anti-cancer effects of ZA on two epithelial cancer cell lines, prostate DU-145 and breast MCF7, focusing primarily on induction and activation of apoptosis. Cluster of differentiation (CD) 133 + /CD44 + prostate CSCs and CD 44 + /CD24 breast CSCs were isolated from the DU-145 human prostate cancer and MCF-7 human breast cancer cell lines, respectively, using FACSAria flow cytometry cell sorting. CSCs and non-CSCs were exposed to increasing concentrations of ZA for 24, 48 and 72 h to determine the IC 50 dose. Annexin-V assay for detecting cell death and cell cycle was performed using the Muse™ Cell Analyzer. Prostate CSCs and non-CSCs were assayed by quantitative reverse transcription PCR (qRT-PCR) array for detecting 84 key apoptosis related genes. Gene regulation at the protein level was investigated by immunofluorescence. ZA caused a dose- and time-dependent decrease in cell viability. Treatment with ZA resulted in a concomitant increase in apoptosis and cell cycle arrest at S-phase in CSCs. Significant over/under-expressions were detected in seven of the genes of ZA-treated DU-145 CSCs cells. Expressions of CASP9, CASP4, BAX and BAD genes increased, while the expressions of BIRC3, BIRC2 and BCL2 genes decreased. In the DU-145 non-CSCs, five genes exhibited changes in gene expression after ZA treatment, two exhibited increased expression (CASP7 and BAD) and three exhibited decreased expression (BIRC3

Évolution des conditions d’initiation du traitement antirétroviral des patients infectés par le VIH en Afrique de l’Ouest

PubMed Central

Bashi, J.; Balestre, E.; Messou, E.; Maiga, M.; Coffie, P.A.; Zannou, D.M.; Ba-Gomis, O.; Traore, H.A.; Eholie, S.; Minga, A.; Sow, P.S.; Bissagnene, E.; Dabis, F.; Ekouevi, D.K.

2013-01-01

Résumé Objectif Étudier entre 1996 et 2006, l’évolution des schémas thérapeutiques et du profil clinique et immunologique des patients infectés par le VIH au début du traitement antirétroviral (TARV) en Afrique de l’Ouest. Cadre et méthode Les données issues de 12 centres cliniques adultes (IeDEA West Africa réseau collaboratif de prise en charge de l’infection à VIH) de cinq pays (Bénin, Cote d’Ivoire, Sénégal, Gambie, Mali) ont été mises en commun et analysées. Les patients âgés de 16 ans et plus dont le sexe, la date de naissance et la date d’initiation du TARV étaient connus ont été inclus dans cette étude. Résultats Quatorze mille quatre-cent-quatre-vingt-seize patients avaient débuté un TARV entre 1996–2006 avec 55 % des patients l’ayant débuté entre 2005–2006. La proportion de femmes était de 46 % en 1996–2000 et de 63 % en 2005–2006. L’âge médian à la mise sous traitement était constant: 35 ans chez les femmes et 40 ans chez les hommes. La proportion de patients qui ont débuté le TARV avec un taux de CD4 inférieur à 200 cellules/µl était de 54 % en 1996–2000 et de 64 % en 2005–2006. Les combinaisons thérapeutiques les plus prescrites étaient: AZT/3TC (ou d4T/DDI)/IDV (27 %) en 1996–2000; d4T (ou AZT)/3TC/EFV (59 %) en 2003–2004; et d4T/3TC/NVP (49 %) en 2005–2006. Les traitements de première ligne recommandés par l’OMS étaient débutés dans 83 % de cas en 2005–2006. Conclusion De nouvelles approches pour débuter un TARV plus précocement doivent être développées pour améliorer la survie des patients sous TARV. PMID:20045273

Mortality due to respiratory cancers in the coke oven plants of the Lorraine coalmining industry (Houillères du Bassin de Lorraine).

PubMed Central

Bertrand, J P; Chau, N; Patris, A; Mur, J M; Pham, Q T; Moulin, J J; Morviller, P; Auburtin, G; Figueredo, A; Martin, J

1987-01-01

The main activity of the Houillères du Bassin de Lorraine (Lorraine Collieries), employing 23,000 operatives and executives, is coalmining. The coke production is carried out by two coke oven plants with a workforce of respectively 747 and 552 workers. The coal coking process entails the emission of noxious products such as polycyclic aromatic hydrocarbons (PAH) from the ovens. The influence of occupational exposure on mortality due to respiratory cancers, and particularly to lung and upper respiratory and alimentary tracts cancer, was investigated among a cohort of 534 male workers from the two coke oven plants who had retired from work between 1963 and 1982. The job history of each subject has been precisely reconstructed by indicating the duration of exposure on the ovens, close to the ovens, and in maintenance occupations. The cohort mortality has been analysed according to the method of indirect standardisation with reference to the French male population and by a case-control study concerning the consumption of tobacco per cohort. The mortality due to lung cancer is 2.51 times higher than expected. This excess of mortality differs, but not significantly, between the two coke oven plants (standardised mortality ratio equals 3.05 and 1.75 respectively). It is not significantly higher among subjects exposed for more than five years, directly exposed on the ovens or working near the ovens or at maintenance occupations on the ovens (SMR = 2.78), than among those exposed for less than five years (SMR = 2.35) or those not exposed at all. Even taking into account the excess of mortality due to lung cancers in the Moselle district (1.6 time that of France), the excess of lung cancers does not seem to be explained by the regional factor, or by tobacco and alcohol consumption. Although no significant relation was offered between lung cancer and the duration of exposure to PAH, even when taking smoking habits into account, the carcinogenic role of occupational nuisances

Genetically engineered oncolytic Newcastle disease virus mediates cytolysis of prostate cancer stem like cells.

PubMed

Raghunath, Shobana; Pudupakam, Raghavendra Sumanth; Allen, Adria; Biswas, Moanaro; Sriranganathan, Nammalwar

2017-10-20

Oncolytic virotherapy is a promising novel approach that overcomes the limitations posed by radiation and chemotherapy. In this study, the oncolytic efficacy of a recombinant Newcastle disease virus (rNDV) BC-KLQL-GFP, against prostate cancer stem-like/tumor initiating cells was evaluated. Xenograft derived prostaspheres (XPS) induced tumor more efficiently than monolayer cell derived prostaspheres (MCPS) in nude mice. Primary and secondary XPS show enhanced self-renewal and clonogenic potential compared to MCPS. XPS also expressed embryonic stem cell markers, such as Nanog, CD44 and Nestin. Further, prostate specific antigen (PSA) activated recombinant Newcastle Disease Virus (rNDV) was selectively cytotoxic to tumor derived DU145 prostaspheres. An effective concentration (EC 50 ) of 0.11-0.14 multiplicity of infection was sufficient to cause prostasphere cell death in serum free culture. DU145 tumor xenograft derived prostaspheres were used as tumor surrogates as they were enriched for a putative tumor initiating cell population. PSA activated rNDV was efficient in inducing cell death of cells and prostaspheres derived from primary xenografts ex-vivo, thus signifying a potential in vivo efficacy. The EC 50 (∼0.1 MOI) for cytolysis of tumor initiating cells was slightly higher than that was required for the parental cell line, but within the therapeutic margin for safety and efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

Carcinome à cellule vitreuse du col de l'utérus: à propos d'un cas et revue de littérature

PubMed Central

Hakimi, Ihssane; Zazi, Abdelghani; Chahdi, Hafsa; Guelzim, Khalid; Kouach, Jaouad; Babahabib, Myabdellah; Elhassani, Myehdi; Rahali, Driss Moussaoui; Dehayni, Mohammed

2015-01-01

Le carcinome à cellule vitreuse du col de l'utérus est un type de histologique rare de cancer du col de l'utérus qui survient à un âge plus jeune, et s'associe au risque élevé d’échec thérapeutique et le pronostic est plus mauvais en comparaison au type cellulaire squameux. La radiothérapie est associée au risque diminué de récidive. Le but de cette étude est de récapituler à travers d'une observation et une revue de littérature les données sur l'incidence, le comportement clinique et la survie globale de patients avec le carcinome à cellule vitreuse du col de l'utérus. PMID:26664556

Association between Sleep and Breast Cancer Incidence among Postmenopausal Women in the Women's Health Initiative

PubMed Central

Vogtmann, Emily; Levitan, Emily B.; Hale, Lauren; Shikany, James M.; Shah, Neomi A.; Endeshaw, Yohannes; Lewis, Cora E.; Manson, JoAnn E.; Chlebowski, Rowan T.

2013-01-01

Study Objectives: To determine whether the duration of sleep, sleep quality, insomnia, or sleep disturbance was associated with incident breast cancer in the Women's Health Initiative (WHI). Design: Prospective cohort study. Setting: Women enrolled in one of the Clinical Trial (CT) arms or the Observational Study (OS) from the WHI conducted in the United States. Participants: This study included 110,011 women age 50 to 79 years with no history of cancer. Measurements and Results: Typical sleep duration, sleep quality, and other self-reported sleep measures over the past 4 weeks were assessed during the screening visits for both the CT and OS participants. The presence of insomnia and level of sleep disturbance was calculated from an index of the WHI Insomnia Rating Scale. The outcome for this study was primary, invasive breast cancer. A total of 5,149 incident cases of breast cancer were identified in this study. No statistically significant associations were found between sleep duration, sleep quality, insomnia, or level of sleep disturbance with the risk of breast cancer after multivariable adjustment. A positive trend was observed for increasing sleeping duration with the risk of estrogen receptor positive breast cancer, but the association estimates for each sleep duration category were weak and nonsignificant. Conclusions: This study does not provide strong support for an association between self-reported sleep duration, sleep quality, insomnia, or sleep disturbance with the risk of breast cancer. Citation: Vogtmann E; Levitan EB; Hale L; Shikany JM; Shah NA; Endeshaw Y; Lewis CE; Manson JE; Chlebowski RT. Association between sleep and breast cancer incidence among postmenopausal women in the Women's Health Initiative. SLEEP 2013;36(10):1437-1444. PMID:24082303

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

PubMed Central

Guo, Lixia; Fan, Dominic; Zhang, Fahao; Price, Janet E.; Lee, Ju-Seog; Marchetti, Dario; Fidler, Isaiah J.; Langley, Robert R.

2011-01-01

An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic potential is highly desirable. Here, we demonstrate that plating GI-101A human breast cancer cells on hard (0.9%) agar selects for the subpopulation of metastasis-initiating cells. The agar-selected cells, designated GI-AGR, were homogeneous for CD44+ and CD133+ and five times more invasive than the parental GI-101A cells. Moreover, mice injected with GI-AGR cells had significantly more experimental brain metastases and shorter overall survival than did mice injected with GI-101A cells. Comparative gene expression analysis revealed that GI-AGR cells were markedly distinct from the parental cells but shared an overlapping pattern of gene expression with the GI-101A subline GI-BRN, which was generated by repeated in vivo recycling of GI-101A cells in an experimental brain metastasis model. Data mining on 216 genes shared between GI-AGR and GI-BRN breast cancer cells suggested that the molecular phenotype of these cells is consistent with that of cancer stem cells and the aggressive basal subtype of breast cancer. Collectively, these results demonstrate that analysis of cell growth in a hard agar assay is a powerful tool for selecting metastasis-initiating cells in a heterogeneous population of breast cancer cells, and that such selected cells have properties similar to those of tumor cells that are selected based on their potential to form metastases in mice. PMID:21514446

A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

PubMed

Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

1999-01-01

We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

Hypoexpression and epigenetic regulation of candidate tumor suppressor gene CADM-2 in human prostate cancer.

PubMed

Chang, Guimin; Xu, Shuping; Dhir, Rajiv; Chandran, Uma; O'Keefe, Denise S; Greenberg, Norman M; Gingrich, Jeffrey R

2010-11-15

Cell adhesion molecules (CADM) comprise a newly identified protein family whose functions include cell polarity maintenance and tumor suppression. CADM-1, CADM-3, and CADM-4 have been shown to act as tumor suppressor genes in multiple cancers including prostate cancer. However, CADM-2 expression has not been determined in prostate cancer. The CADM-2 gene was cloned and characterized and its expression in human prostatic cell lines and cancer specimens was analyzed by reverse transcription-PCR and an immunohistochemical tissue array, respectively. The effects of adenovirus-mediated CADM-2 expression on prostate cancer cells were also investigated. CADM-2 promoter methylation was evaluated by bisulfite sequencing and methylation-specific PCR. We report the initial characterization of CADM-2 isoforms: CADM-2a and CADM-2b, each with separate promoters, in human chromosome 3p12.1. Prostate cancer cell lines, LNCaP and DU145, expressed negligible CADM-2a relative to primary prostate tissue and cell lines, RWPE-1 and PPC-1, whereas expression of CADM-2b was maintained. Using immunohistochemistry, tissue array results from clinical specimens showed statistically significant decreased expression in prostate carcinoma compared with normal donor prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and normal tissue adjacent to tumor (P < 0.001). Adenovirus-mediated CADM-2a expression suppressed DU145 cell proliferation in vitro and colony formation in soft agar. The decrease in CADM-2a mRNA in cancer cell lines correlated with promoter region hypermethylation as determined by bisulfite sequencing and methylation-specific PCR. Accordingly, treatment of cells with the demethylating agent 5-aza-2'-deoxycytidine alone or in combination with the histone deacetylase inhibitor trichostatin A resulted in the reactivation of CADM-2a expression. CADM-2a protein expression is significantly reduced in prostate cancer. Its expression is regulated in part by

KML001 Induces Apoptosis and Autophagic Cell Death in Prostate Cancer Cells via Oxidative Stress Pathway

PubMed Central

You, Dalsan; Kim, Yunlim; Jang, Myoung Jin; Lee, Chunwoo; Jeong, In Gab; Cho, Yong Mee; Hwang, Jung Jin; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2015-01-01

We investigated the effects of KML001 (NaAsO2, sodium metaarsenite, Kominox), an orally bioavailable arsenic compound, on the growth and death of human prostate cancer cells and its mechanism of action. Growth inhibition was assessed by cytotoxicity assays in the presence or absence of inhibitor of apoptosis, inhibitor of autophagy or antioxidant N-Acetyl-L-cysteine to study mechanism of cell death induced by KML001 in PC3, DU145 and LNCaP prostate cancer cell lines. Electron microscopy, flow cytometry and Western blotting were used to study apoptotic and autophagic mechanisms. The DU145 xenograft model was used to determine the efficacy of KML001 in vivo. KML001 decreased the viability of cells and increased the percentage of annexin V-positive cells dose-dependently in prostate cancer cells, and LNCaP cells were more sensitive to KML001 than PC3 or DU145 cells. Electron microscopy revealed typical apoptotic characters and autophagic vacuoles in cells treated with KML001. Exposure to KML001 in prostate cancer cells induced apoptosis and autophagy in a time- and dose-dependent manner. KML001 induced dose-dependent accumulation of reactive oxygen species, and scavenging the reactive oxygen species with N-Acetyl-L-cysteine reduced LC3 and cleaved poly (ADP-ribose) polymerase. KML001 significantly inhibited tumor growth in the DU145 xenograft model. In addition, significant decrease of proliferation and significant increases of apoptosis and autophagy were observed in KML001-treated tumors than in vehicle-treated tumors. Exposure of human prostate cancer cells to KML001 induced both apoptosis and autophagic cell death via oxidative stress pathway. And KML001 had an antiproliferative effect on DU145 cells in xenograft mice. PMID:26352139

KML001 Induces Apoptosis and Autophagic Cell Death in Prostate Cancer Cells via Oxidative Stress Pathway.

PubMed

You, Dalsan; Kim, Yunlim; Jang, Myoung Jin; Lee, Chunwoo; Jeong, In Gab; Cho, Yong Mee; Hwang, Jung Jin; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2015-01-01

We investigated the effects of KML001 (NaAsO2, sodium metaarsenite, Kominox), an orally bioavailable arsenic compound, on the growth and death of human prostate cancer cells and its mechanism of action. Growth inhibition was assessed by cytotoxicity assays in the presence or absence of inhibitor of apoptosis, inhibitor of autophagy or antioxidant N-Acetyl-L-cysteine to study mechanism of cell death induced by KML001 in PC3, DU145 and LNCaP prostate cancer cell lines. Electron microscopy, flow cytometry and Western blotting were used to study apoptotic and autophagic mechanisms. The DU145 xenograft model was used to determine the efficacy of KML001 in vivo. KML001 decreased the viability of cells and increased the percentage of annexin V-positive cells dose-dependently in prostate cancer cells, and LNCaP cells were more sensitive to KML001 than PC3 or DU145 cells. Electron microscopy revealed typical apoptotic characters and autophagic vacuoles in cells treated with KML001. Exposure to KML001 in prostate cancer cells induced apoptosis and autophagy in a time- and dose-dependent manner. KML001 induced dose-dependent accumulation of reactive oxygen species, and scavenging the reactive oxygen species with N-Acetyl-L-cysteine reduced LC3 and cleaved poly (ADP-ribose) polymerase. KML001 significantly inhibited tumor growth in the DU145 xenograft model. In addition, significant decrease of proliferation and significant increases of apoptosis and autophagy were observed in KML001-treated tumors than in vehicle-treated tumors. Exposure of human prostate cancer cells to KML001 induced both apoptosis and autophagic cell death via oxidative stress pathway. And KML001 had an antiproliferative effect on DU145 cells in xenograft mice.

Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism.

PubMed

Bednar, Filip; Schofield, Heather K; Collins, Meredith A; Yan, Wei; Zhang, Yaqing; Shyam, Nikhil; Eberle, Jaime A; Almada, Luciana L; Olive, Kenneth P; Bardeesy, Nabeel; Fernandez-Zapico, Martin E; Nakada, Daisuke; Simeone, Diane M; Morrison, Sean J; Pasca di Magliano, Marina

2015-07-01

Epigenetic dysregulation is involved in the initiation and progression of many epithelial cancers. BMI1, a component of the polycomb protein family, plays a key role in these processes by controlling the histone ubiquitination and long-term repression of multiple genomic loci. BMI1 has previously been implicated in pancreatic homeostasis and the function of pancreatic cancer stem cells. However, no work has yet addressed its role in the early stages of pancreatic cancer development. Here, we show that BMI1 is required for the initiation of murine pancreatic neoplasia using a novel conditional knockout of Bmi1 in combination with a Kras(G12D)-driven pancreatic cancer mouse model. We also demonstrate that the requirement for Bmi1 in pancreatic carcinogenesis is independent of the Ink4a/Arf locus and at least partially mediated by dysregulation of reactive oxygen species. Our data provide new evidence of the importance of this epigenetic regulator in the genesis of pancreatic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

IDENTIFYING AND TARGETING TUMOR-INITIATING CELLS IN THE TREATMENT OF BREAST CANCER

PubMed Central

Wei, Wei; Lewis, Michael T.

2015-01-01

Breast cancer is the most common cancer in women (exclusive of skin cancer), and is the second leading cause of cancer-related deaths. Although conventional and targeted therapies have improved survival rates, there are still considerable challenges in treating breast cancer, including treatment resistance, disease recurrence, and metastasis. Treatment resistance can be either de novo - due to traits that tumor cells possess prior to treatment, or acquired, - due to traits that tumor cells gain in response to treatment. A recently proposed mechanism of de novo resistance invokes existence of a specialized subset of cancer cells defined as tumor-initiating cells (TICs), or cancer stem cells (CSC). TICs have the capacity to self-renew and regenerate new tumors that consist of all clonally-derived cell types present in the parental tumor. There are data to suggest that TICs are resistant to many conventional cancer therapies, and survive treatment in spite of dramatic shrinkage of the tumor. Residual TICs can then eventually regrow resulting in disease relapse. It is also hypothesized that TIC may be responsible for metastatic disease. If these hypotheses are correct, targeting TICs may be imperative to achieve cure. In this review, we discuss evidence for breast TICs and their apparent resistance to conventional chemotherapy and radiotherapy, as well as to various targeted therapies. We also address the potential impact of breast TIC plasticity and metastatic potential on therapeutic strategies. Finally, we describe several genes and signaling pathways that appear important for TIC function that may represent promising therapeutic targets. PMID:25876646

Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is necessary for prostate cancer metastasis via epithelial-mesenchymal transition.

PubMed

Luo, Weijia; Tan, Peng; Rodriguez, Melissa; He, Lian; Tan, Kunrong; Zeng, Li; Siwko, Stefan; Liu, Mingyao

2017-09-15

Prostate cancer is a highly penetrant disease among men in industrialized societies, but the factors regulating the transition from indolent to aggressive and metastatic cancer remain poorly understood. We found that men with prostate cancers expressing high levels of the G protein-coupled receptor LGR4 had a significantly shorter recurrence-free survival compared with patients with cancers having low LGR4 expression. LGR4 expression was elevated in human prostate cancer cell lines with metastatic potential. We therefore generated a novel transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model to investigate the role of Lgr4 in prostate cancer development and metastasis in vivo TRAMP Lgr4 -/- mice exhibited an initial delay in prostate intraepithelial neoplasia formation, but the frequency of tumor formation was equivalent between TRAMP and TRAMP Lgr4 -/- mice by 12 weeks. The loss of Lgr4 significantly improved TRAMP mouse survival and dramatically reduced the occurrence of lung metastases. LGR4 knockdown impaired the migration, invasion, and colony formation of DU145 cells and reversed epithelial-mesenchymal transition (EMT), as demonstrated by up-regulation of E-cadherin and decreased expression of the EMT transcription factors ZEB, Twist, and Snail. Overexpression of LGR4 in LNCaP cells had the opposite effects. Orthotopic injection of DU145 cells stably expressing shRNA targeting LGR4 resulted in decreased xenograft tumor size, reduced tumor EMT marker expression, and impaired metastasis, in accord with our findings in TRAMP Lgr4 -/- mice. In conclusion, we propose that Lgr4 is a key protein necessary for prostate cancer EMT and metastasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging.

PubMed

Caresia Aroztegui, Ana Paula; García Vicente, Ana María; Alvarez Ruiz, Soledad; Delgado Bolton, Roberto Carlos; Orcajo Rincon, Javier; Garcia Garzon, Jose Ramon; de Arcocha Torres, Maria; Garcia-Velloso, Maria Jose

2017-10-01

Current guidelines do not systematically recommend 18F-FDG PET/CT for breast cancer staging; and the recommendations and level of evidence supporting its use in different groups of patients vary among guidelines. This review summarizes the evidence about the role of 18F-FDG PET/CT in breast cancer staging and the therapeutic and prognostic impact accumulated in the last decade. Other related aspects, such as the association of metabolic information with biology and prognosis are considered and evidence-based recommendations for the use of 18F-FDG PET/CT in breast cancer staging are offered. We systematically searched MEDLINE for articles reporting studies with at least 30 patients related to clinical questions following the Problem/Population, Intervention, Comparison, and Outcome framework. We critically reviewed the selected articles and elaborated evidence tables structuring the summarized information into methodology, results, and limitations. The level of evidence and the grades of recommendation for the use of 18F-FDG PET/CT in different contexts are summarized. Level III evidence supports the use of 18F-FDG PET/CT for initial staging in patients with recently diagnosed breast cancer; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a weak recommendation in this population. In patients with locally advanced breast cancer, level II evidence supports the use of 18F-FDG PET/CT for initial staging; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a strong recommendation in this population. In patients with recently diagnosed breast cancer, the metabolic information from baseline 18F-FDG PET/CT is associated with tumor biology and has prognostic implications, supported by level II evidence. In conclusion, 18F-FDG PET/CT is not recommended for staging all patients with early breast cancer, although evidence of improved regional and systemic staging supports its use in locally advanced

Controlling female cancer in Argentina. Divergent initiatives and the road to fragmentation

PubMed Central

Eraso, Yolanda

2014-01-01

This article analyses the organisation of cancer control in Argentina, with a special focus on the initiatives, institutions, and models that targeted female or gynaecological cancers. It identifies and examines the main factors in the process of elaborating a national policy to control the disease drawing on a series of actors and instruments such as the state, medical professionals, institutions and services, and the use of technology (notably diagnostic tools) for the detection of the disease. It traces the developments in the organisation highlighting its transformations from a centralising to a decentralised model of service provision. Using the concept of «path-dependence» the article examines the continuities and changes observed in the organisation of female cancer critically signalling the particular time at which a path was taken where «fragmentation» became consolidated within the health system. It also argues that it was within the field of cancer diagnosis that Argentinian doctors first sought to create the foundational structures of cancer organisation. The article contends that the path-dependence analytical approach helps us acknowledge the importance of historical analysis in the identification of factors that led to the lack of service coordination, including the persistent strain between national/provincial states that hampered the development of comprehensive programmes, aspects that have continued to mark efforts in the elaboration of cancer policies to the present day. PMID:24944432

Controlling female cancer in Argentina. Divergent initiatives and the road to fragmentation.

PubMed

Eraso, Yolanda

2014-01-01

This article analyses the organisation of cancer control in Argentina, with a special focus on the initiatives, institutions, and models that targeted female or gynaecological cancers. It identifies and examines the main factors in the process of elaborating a national policy to control the disease drawing on a series of actors and instruments such as the state, medical professionals, institutions and services, and the use of technology (notably diagnostic tools) for the detection of the disease. It traces the developments in the organisation highlighting its transformations from a centralising to a decentralised model of service provision. Using the concept of "path-dependence" the article examines the continuities and changes observed in the organisation of female cancer critically signalling the particular time at which a path was taken where "fragmentation" became consolidated within the health system. It also argues that it was within the field of cancer diagnosis that Argentinian doctors first sought to create the foundational structures of cancer organisation. The article contends that the path-dependence analytical approach helps us acknowledge the importance of historical analysis in the identification of factors that led to the lack of service coordination, including the persistent strain between national/provincial states that hampered the development of comprehensive programmes, aspects that have continued to mark efforts in the elaboration of cancer policies to the present day.

76 FR 66932 - The National Cancer Institute (NCI) Announces the Initiation of a Public Private Industry...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-28

...The Alliance for Nanotechnology in Cancer of the National Cancer Institute (NCI) is initiating a public private industry partnership called TONIC (Translation Of Nanotechnology In Cancer) to promote translational research and development opportunities of nanotechnology-based cancer solutions. An immediate consequence of this effort will be the formation of a consortium involving government and pharmaceutical, and biotechnology companies. This consortium will evaluate promising nanotechnology platforms and facilitate their successful translation from academic research to clinical environment, resulting in safe, timely, effective and novel diagnosis and treatment options for cancer patients. The purpose of this notice is to inform the community about the Alliance for Nanotechnology in Cancer of NCI's intention to form the consortium and to invite eligible companies (as defined in last paragraph) to participate.

Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in the implementation of precision medicine.

PubMed

Tsimberidou, Apostolia-Maria

In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center. We demonstrated that in patients referred for Phase I clinical trials, the use of tumor molecular profiling and treatment with matched targeted therapy was associated with encouraging rates of response, progression-free survival and overall survival compared to non-matched therapy. We are currently conducting IMPACT2, a randomized study evaluating molecular profiling and targeted agents in patients with metastatic cancer. Optimization of innovative biomarker-driven clinical trials that include targeted therapy and/or immunotherapeutic approaches for carefully selected patients will accelerate the development of novel drugs and the implementation of precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer cells.

PubMed

Qu, Lijun; Li, Sumei; Zhuo, Yumin; Chen, Jianfan; Qin, Xiaoping; Guo, Guoqing

2017-12-01

Ganoderma lucidum , within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted from G. lucidum have revealed anticancer, antioxidant and liver protective effects. G. lucidum has been associated with prostate cancer cells. G. lucidum extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from G. lucidum (GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer.

PubMed

Graboyes, Evan M; Garrett-Mayer, Elizabeth; Ellis, Mark A; Sharma, Anand K; Wahlquist, Amy E; Lentsch, Eric J; Nussenbaum, Brian; Day, Terry A

2017-12-15

The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline-adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival. This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score-matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively). Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017;123:4841-50. © 2017 American Cancer Society. © 2017 American Cancer Society.

Ubiquitin ligase CHIP functions as an oncogene and activates the AKT signaling pathway in prostate cancer.

PubMed

Cheng, Li; Zang, Jin; Dai, Han-Jue; Li, Feng; Guo, Feng

2018-07-01

Carboxyl terminus of Hsc-70-interacting protein (CHIP) is an E3 ubiquitin ligase that induces the ubiquitination and degradation of numerous tumor-associated proteins and serves as a suppressor or promoter in tumor progression. To date, the molecular mechanism of CHIP in prostate cancer remains unknown. Therefore, the present study investigated the biological function of CHIP in prostate cancer cells and obtained evidence that CHIP expression is upregulated in prostate cancer tissues. The CHIP vector was introduced into DU145 cancer cells and the cell biological behaviour was examined through a series of experiments, including cell growth, cell apoptosis and migration and invasion assays. The results indicated that the overexpression of CHIP in DU145 prostatic cancer cells promoted cell proliferation through activation of the protein kinase B (AKT) signaling pathway, which subsequently increased cyclin D1 protein levels and decreased p21 and p27 protein levels. The overexpression of CHIP significantly increased the migration and invasion of the DU145 cells, which is possible due to activation of the AKT signaling pathway and upregulation of vimentin. The expression level of CHIP was observed to be increased in human prostate cancer tissues compared with the adjacent normal tissue. Furthermore, the CHIP expression level exhibited a positively association with the Gleason score of the patents. These findings indicate that CHIP functions as an oncogene in prostate cancer.

Information Framing Reduces Initial Negative Attitudes in Cancer Patients' Decisions About Hospice Care.

PubMed

Fridman, Ilona; Glare, Paul A; Stabler, Stacy M; Epstein, Andrew S; Wiesenthal, Alison; Leblanc, Thomas W; Higgins, E Tory

2018-06-01

Negative attitudes toward hospice care might prevent patients with cancer from discussing and choosing hospice as they approach end of life. When making a decision, people often naturally focus on either expected benefits or the avoidance of harm. Behavioral research has demonstrated that framing information in an incongruent manner with patients' underlying motivational focus reduces their negative attitudes toward a disliked option. Our study tests this communication technique with cancer patients, aiming to reduce negative attitudes toward a potentially beneficial but often-disliked option, that is, hospice care. Patients (n = 42) with active cancer of different types and/or stages completed a paper survey. Participants read a vignette about a patient with advanced cancer and a limited prognosis. In the vignette, the physician's advice to enroll in a hospice program was randomized, creating a congruent message or an incongruent message with patients' underlying motivational focus (e.g., a congruent message for someone most interested in benefits focuses on the benefits of hospice, whereas an incongruent message for this patient focuses on avoiding harm). Patients' attitudes toward hospice were measured before and after receiving the physician's advice. Regression analyses indicated that information framing significantly influenced patients with strong initial negative attitudes. Patients were more likely to reduce intensity of their initial negative attitude about hospice when receiving an incongruent message (b = -0.23; P < 0.01) than a congruent one (b = -0.13; P = 0.08). This finding suggests a new theory-driven approach to conversations with cancer patients who may harbor negative reactions toward hospice care. Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

PubMed

Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

2016-02-01

The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

PubMed

Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

2013-04-05

Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

[Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

PubMed

Lyu, J M; Xiong, H C; Wu, B; Zhou, X Q; Hu, J

2018-02-23

Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P <0.05). Conclusions: The second primary cancers of MPC cases initially diagnosed of digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

[Molecular biology of castration-resistant prostate cancer].

PubMed

Doucet, Ludovic; Terrisse, Safae; Gauthier, Hélène; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

2015-06-01

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

National Cancer Institute's Precision Medicine Initiatives for the new National Clinical Trials Network.

PubMed

Abrams, Jeffrey; Conley, Barbara; Mooney, Margaret; Zwiebel, James; Chen, Alice; Welch, John J; Takebe, Naoko; Malik, Shakun; McShane, Lisa; Korn, Edward; Williams, Mickey; Staudt, Louis; Doroshow, James

2014-01-01

The promise of precision medicine will only be fully realized if the research community can adapt its clinical trials methodology to study molecularly characterized tumors instead of the traditional histologic classification. Such trials will depend on adequate tissue collection, availability of quality controlled, high throughput molecular assays, and the ability to screen large numbers of tumors to find those with the desired molecular alterations. The National Cancer Institute's (NCI) new National Clinical Trials Network (NCTN) is well positioned to conduct such trials. The NCTN has the ability to seamlessly perform ethics review, register patients, manage data, and deliver investigational drugs across its many sites including both in cities and rural communities, academic centers, and private practices. The initial set of trials will focus on different questions: (1) Exceptional Responders Initiative-why do a minority of patients with solid tumors or lymphoma respond very well to some drugs even if the majority do not?; (2) NCI MATCH trial-can molecular markers predict response to targeted therapies in patients with advanced cancer resistant to standard treatment?; (3) ALCHEMIST trial-will targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors improve survival for adenocarcinoma of the lung in the adjuvant setting?; and (4) Lung Cancer Master Protocol trial for advanced squamous cell lung cancer-is there an advantage to developing drugs for small subsets of molecularly characterized tumors in a single, multiarm trial design? These studies will hopefully spawn a new era of treatment trials that will carefully select the tumors that may respond best to investigational therapy.

Research Programs & Initiatives

Cancer.gov

CGH develops international initiatives and collaborates with other NCI divisions, NCI-designated Cancer Centers, and other countries to support cancer control planning, encourage capacity building, and support cancer research and research networks.

Sortilin regulates progranulin action in castration-resistant prostate cancer cells.

PubMed

Tanimoto, Ryuta; Morcavallo, Alaide; Terracciano, Mario; Xu, Shi-Qiong; Stefanello, Manuela; Buraschi, Simone; Lu, Kuojung G; Bagley, Demetrius H; Gomella, Leonard G; Scotlandi, Katia; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2015-01-01

The growth factor progranulin is as an important regulator of transformation in several cellular systems. We have previously demonstrated that progranulin acts as an autocrine growth factor and stimulates motility, proliferation, and anchorage-independent growth of castration-resistant prostate cancer cells, supporting the hypothesis that progranulin may play a critical role in prostate cancer progression. However, the mechanisms regulating progranulin action in castration-resistant prostate cancer cells have not been characterized. Sortilin, a single-pass type I transmembrane protein of the vacuolar protein sorting 10 family, binds progranulin in neurons and negatively regulates progranulin signaling by mediating progranulin targeting for lysosomal degradation. However, whether sortilin is expressed in prostate cancer cells and plays any role in regulating progranulin action has not been established. Here, we show that sortilin is expressed at very low levels in castration-resistant PC3 and DU145 cells. Significantly, enhancing sortilin expression in PC3 and DU145 cells severely diminishes progranulin levels and inhibits motility, invasion, proliferation, and anchorage-independent growth. In addition, sortilin overexpression negatively modulates Akt (protein kinase B, PKB) stability. These results are recapitulated by depleting endogenous progranulin in PC3 and DU145 cells. On the contrary, targeting sortilin by short hairpin RNA approaches enhances progranulin levels and promotes motility, invasion, and anchorage-independent growth. We dissected the mechanisms of sortilin action and demonstrated that sortilin promotes progranulin endocytosis through a clathrin-dependent pathway, sorting into early endosomes and subsequent lysosomal degradation. Collectively, these results point out a critical role for sortilin in regulating progranulin action in castration-resistant prostate cancer cells, suggesting that sortilin loss may contribute to prostate cancer progression.

Sortilin Regulates Progranulin Action in Castration-Resistant Prostate Cancer Cells

PubMed Central

Tanimoto, Ryuta; Morcavallo, Alaide; Terracciano, Mario; Xu, Shi-Qiong; Stefanello, Manuela; Buraschi, Simone; Lu, Kuojung G.; Bagley, Demetrius H.; Gomella, Leonard G.; Scotlandi, Katia; Belfiore, Antonino; Iozzo, Renato V.

2015-01-01

The growth factor progranulin is as an important regulator of transformation in several cellular systems. We have previously demonstrated that progranulin acts as an autocrine growth factor and stimulates motility, proliferation, and anchorage-independent growth of castration-resistant prostate cancer cells, supporting the hypothesis that progranulin may play a critical role in prostate cancer progression. However, the mechanisms regulating progranulin action in castration-resistant prostate cancer cells have not been characterized. Sortilin, a single-pass type I transmembrane protein of the vacuolar protein sorting 10 family, binds progranulin in neurons and negatively regulates progranulin signaling by mediating progranulin targeting for lysosomal degradation. However, whether sortilin is expressed in prostate cancer cells and plays any role in regulating progranulin action has not been established. Here, we show that sortilin is expressed at very low levels in castration-resistant PC3 and DU145 cells. Significantly, enhancing sortilin expression in PC3 and DU145 cells severely diminishes progranulin levels and inhibits motility, invasion, proliferation, and anchorage-independent growth. In addition, sortilin overexpression negatively modulates Akt (protein kinase B, PKB) stability. These results are recapitulated by depleting endogenous progranulin in PC3 and DU145 cells. On the contrary, targeting sortilin by short hairpin RNA approaches enhances progranulin levels and promotes motility, invasion, and anchorage-independent growth. We dissected the mechanisms of sortilin action and demonstrated that sortilin promotes progranulin endocytosis through a clathrin-dependent pathway, sorting into early endosomes and subsequent lysosomal degradation. Collectively, these results point out a critical role for sortilin in regulating progranulin action in castration-resistant prostate cancer cells, suggesting that sortilin loss may contribute to prostate cancer progression

Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening.

PubMed

Christensen, Anne G; Ehmsen, Sidse; Terp, Mikkel G; Batra, Richa; Alcaraz, Nicolas; Baumbach, Jan; Noer, Julie B; Moreira, José; Leth-Larsen, Rikke; Larsen, Martin R; Ditzel, Henrik J

2017-08-01

A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics. Within these pairs, one, but not the other, resulted in tumors in immunodeficient NOD/Shi-scid/IL-2 Rγ null mice and efficiently formed mammospheres. Quantitative proteomics and phosphoproteomics were used to map signaling pathways associated with the tumor-initiating ability. Signaling associated with apoptosis was suppressed in tumor-initiating versus nontumorigenic counterparts with pro-apoptotic proteins, such as Bcl2-associated agonist of cell death (BAD), FAS-associated death domain protein (FADD), and myeloid differentiation primary response protein (MYD88), downregulated in tumor-initiating epithelial-like cells. Functional studies confirmed significantly lower apoptosis in tumor-initiating versus nontumorigenic cells. Moreover, central pathways, including β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signaling, exhibited increased activation in the tumor-initiating cells. To evaluate the CSC model as a tool for drug screening, we assessed the effect of separately blocking NF-κB and Wnt/β-catenin signaling and found markedly reduced mammosphere formation, particularly for tumor-initiating cells. Similar reduction was also observed using patient-derived primary cancer cells. Furthermore, blocking NF-κB signaling in mice transplanted with tumor-initiating cells significantly reduced tumor outgrowth. Our study demonstrates that suppressed apoptosis, activation

Séroprévalence et facteurs associés à l’acceptation du Conseil et Dépistage Volontaire du VIH chez l’enfant à Lubumbashi, République Démocratique du Congo

PubMed Central

Ngwej, Dieudonné Tshikwej; Mukuku, Olivier; Malonga, Françoise Kaj; Luboya, Oscar Numbi; Kakoma, Jean-Baptiste Sakatolo; Wembonyama, Stanis Okitotsho

2017-01-01

Résumé Introduction Malgré le dépistage du VIH proposé lors de la naissance ou au cours des consultations préscolaires, la proportion des enfants qui croissent ou décèdent sous statut sérologique au VIH inconnu est importante en République Démocratique du Congo (RDC). L’objectif de cette étude était de déterminer la séroprévalence au cours d’un dépistage volontaire et d’identifier les facteurs associés à l’acceptation du conseil et dépistage du VIH (CDV) en dehors de la maladie ou de toute exposition au VIH dans une population pédiatrique à Lubumbashi, RDC. Méthodes Il s’agissait d’une étude prospective transversale à visée analytique menée du 1er août 2006 au 31 septembre 2007. Elle avait été réalisée dans 4 centres communautaires de CDV répartis dans 4 zones de santé de la ville de Lubumbashi en RDC (Lubumbashi, Ruashi, Kampemba et de Kenya). L’étude avait consisté à faire le dépistage volontaire du VIH chez les enfants de moins de 15 ans. Les caractéristiques sociodémographiques et les paramètres relatifs au conseil et dépistage volontaire ont été étudiés. Les analyses statistiques descriptives usuelles et une régression logistique ont été réalisées. Résultats Sur 463 enfants dépistés du VIH, 41 (8,9%; IC 95%: 6,5%-11,9%) ont été testés positifs. L’acceptation du conseil et dépistage volontaire du VIH en dehors de la maladie ou de l’exposition au VIH était significativement plus élevée lorsque l’enfant était âgé de plus de 2 ans (Odds ratio ajusté (ORa) = 3,6 [IC 95%: 1,1-12,2]), lorsque le statut sérologique du VIH des parents était négatif ou inconnu (ORa = 27,4 [IC 95%: 9,4-80,0]), lorsque l’un ou l’autre ou les deux parents biologiques étaient en vie (ORa = 24,9 [IC 95%: 2,4-250,8]) et lorsque la connaissance du lieu de dépistage était fait par des moyens autres que le professionnel de santé (ORa = 2,9 [IC 95%: 1,0-7,9]). Conclusion Notre étude montre une forte

[The Relationship Between Coping Behaviors and Symptom Distress in Elderly Patients With Cancer Undergoing Initial Chemotherapy].

PubMed

Wu, Shih-Ping; Hsu, Ya-Chuan

2016-12-01

Elderly cancer patients undergoing initial chemotherapy often suffer discomfort from medication-related symptom distress. This discomfort may affect treatment responses and outcomes negatively. This correlational, cross-sectional design study used a purposive sample of 100 patients who were both over 60 years of age and currently undergoing initial chemotherapy. The participants completed a structured questionnaire that was administered at a medical center in southern Taiwan. The questionnaire included a demographics datasheet, Coping Behavior Scale, and Symptom Distress Scale. Data was analyzed using descriptive statistics, Pearson's correlations, Mann-Whitney U, and Kruskal Wallis tests, which were run on SPSS 19.0 software. This correlational, cross-sectional design study used a purposive sample of 100 patients who were both over 60 years of age and currently undergoing initial chemotherapy. The participants completed a structured questionnaire that was administered at a medical center in southern Taiwan. The questionnaire included a demographics datasheet, Coping Behavior Scale, and Symptom Distress Scale. Data was analyzed using descriptive statistics, Pearson's correlations, Mann-Whitney U, and Kruskal Wallis tests, which were run on SPSS 19.0 software. Three-quarters (78%) of participants reported that they suffered from more than four distress symptoms. The top distress symptoms in terms of severity included: fatigue, poor appetite, insomnia, dry mouth, and altered bowel habits. The top distress symptoms in terms of frequency included: fatigue, dry mouth, poor appetite, insomnia, and altered bowel habits. "Problem-focused" coping was the most frequent type of coping behavior (mean = 3.19, SD = 0.24) that was used by participants. Furthermore, more frequent use of "emotions-focused" coping behaviors was associated with a greater risk of experiencing serious distress symptoms (r =.44, p < .001). Number of chronic diseases, cancer stage, and type of cancer

Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer A Cost-Effectiveness Analysis

PubMed Central

Hayes, Julia H.; Ollendorf, Daniel A.; Pearson, Steven D.; Barry, Michael J.; Kantoff, Philip W.; Lee, Pablo A.; McMahon, Pamela M.

2015-01-01

Background Observation is underused among men with localized, low-risk prostate cancer. Objective To assess the costs and benefits of observation versus initial treatment. Design Decision analysis simulating treatment or observation. Data Sources Medicare schedules, published literature. Target Population Men ages 65 and 75 years with newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 μg/L, stage ≤T2a, Gleason score ≤3+3). Time Horizon Lifetime. Perspective Societal. Intervention Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). Outcome Measures Quality-adjusted life expectancy, costs. Results of Base-Case Analysis Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15 374 ($24 520 vs. $39 894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11 746 ($18 302 vs. $30 048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. Results of Sensitivity Analysis Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. Limitation Results depend on outcomes reported in the published literature, which is limited. Conclusion Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. Primary

Clinical initiatives linking Japanese and Swedish healthcare resources on cancer studies utilizing Biobank Repositories.

PubMed

Nishimura, Toshihide; Kawamura, Takeshi; Sugihara, Yutaka; Bando, Yasuhiko; Sakamoto, Shigeru; Nomura, Masaharu; Ikeda, Norihiko; Ohira, Tatsuo; Fujimoto, Junichiro; Tojo, Hiromasa; Hamakubo, Takao; Kodama, Tatsuhiko; Andersson, Roland; Fehniger, Thomas E; Kato, Harubumi; Marko-Varga, György

2014-12-01

The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. An establishment of protein targets characteristic of LCNEC is quite helpful for decision of optimal therapeutic strategy by diagnosing individual patients. Proteoform annotation and clinical biobanking is part of the HUPO initiative (http://www.hupo.org) within chromosome 10 and chromosome 19 consortia.

DuCLOX-2/5 Inhibition Attenuates Inflammatory Response and Induces Mitochondrial Apoptosis for Mammary Gland Chemoprevention

PubMed Central

Gautam, Swetlana; Rawat, Atul K.; Sammi, Shreesh R.; Roy, Subhadeep; Singh, Manjari; Devi, Uma; Yadav, Rajnish K.; Singh, Lakhveer; Rawat, Jitendra K.; Ansari, Mohd N.; Saeedan, Abdulaziz S.; Kumar, Dinesh; Pandey, Rakesh; Kaithwas, Gaurav

2018-01-01

The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments. PMID:29681851

Weight Fluctuation and Cancer Risk in Postmenopausal Women: The Women's Health Initiative.

PubMed

Welti, Laura M; Beavers, Daniel P; Caan, Bette J; Sangi-Haghpeykar, Haleh; Vitolins, Mara Z; Beavers, Kristen M

2017-05-01

Background: Weight cycling, defined by an intentional weight loss and subsequent regain, commonly occurs in overweight and obese women and is associated with some negative health outcomes. We examined the role of various weight-change patterns during early to mid-adulthood and associated risk of highly prevalent, obesity-related cancers (breast, endometrial, and colorectal) in postmenopausal women. Methods: A total of 80,943 postmenopausal women (age, 63.4 ± 7.4 years) in the Women's Health Initiative Observational Study were categorized by self-reported weight change (weight stable; weight gain; lost weight; weight cycled [1-3, 4-6, 7-10, >10 times]) during early to mid-adulthood (18-50 years). Three site-specific associations were investigated using Cox proportional hazard models [age, race/ethnicity, income, education, smoking, alcohol, physical activity, hormone therapy, diet, and body mass index (BMI)]. Results: A total of 7,464 (breast = 5,564; endometrial = 788; and colorectal = 1,290) incident cancer cases were identified between September 1994 and August 2014. Compared with weight stability, weight gain was significantly associated with risk of breast cancer [hazard ratio (HR), 1.11; 1.03-1.20] after adjustment for BMI. Similarly, weight cycling was significantly associated with risk of endometrial cancer (HR = 1.23; 1.01-1.49). Weight cycling "4 to 6 times" was most consistently associated with cancer risk, showing a 38% increased risk for endometrial cancer [95% confidence interval (CI), 1.08-1.76] compared with weight stable women. Conclusions: Weight gain and weight cycling were positively associated with risk of breast and endometrial cancer, respectively. Impact: These data suggest weight cycling and weight gain increase risk of prevalent cancers in postmenopausal women. Adopting ideal body-weight maintenance practices before and after weight loss should be encouraged to reduce risk of incident breast and endometrial cancers. Cancer Epidemiol

L'Aventure du LHC

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2010-06-11

Cette présentation s’adressera principalement aux personnes qui ont construit le LHC. La construction du LHC fut longue et difficile. De nombreux problèmes sont apparus en cours de route. Tous ont été résolus grâce au dévouement et à l’engagement du personnel et des collaborateurs. Je reviendrai sur les coups durs et les réussites qui ont marqués ces 15 dernières années et je vous montrerai combien cette machine, le fruit de vos efforts, est extraordinaire.

Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.

PubMed

Cohn, Joshua A; Vekhter, Benjamin; Lyttle, Christopher; Steinberg, Gary D; Large, Michael C

2014-02-15

Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria. This study sought to determine the difference in timing from presentation with hematuria to diagnosis of bladder cancer in women versus men. This is a retrospective population-based study examining the timing from presentation with hematuria to diagnosis of bladder cancer, based on data from the MarketScan databases, which include enrollees of more than 100 health insurance plans of approximately 40 large US employers from 2004 through 2010. All study patients presented with hematuria and were subsequently diagnosed with bladder cancer. The primary outcome measure was number of days between initial presentation with hematuria and diagnosis of bladder cancer by sex. A total of 5416 men and 2233 women met inclusion criteria. Mean days from initial hematuria claim to bladder cancer claim was significantly longer in women (85.4 versus 73.6 days, P < .001), and the proportion of women with >6 month delay in bladder cancer diagnosis was significantly higher (17.3% versus 14.1%, P < .001). Women were more likely to be diagnosed with urinary tract infection (odds ratio = 2.32, 95% confidence interval = 2.07-2.59) and less likely to undergo abdominal or pelvic imaging (odds ratio = 0.80, 95% confidence interval = 0.71-0.89). Both men and women experience significant delays between presentation with hematuria and diagnosis of bladder cancer, with longer delays for women. This may be partly responsible for the sex-based discrepancy in outcomes associated with bladder cancer. © 2013 American Cancer Society.

Intervention of Prostate Cancer by a Flavonoid Antioxidant Silymarin

DTIC Science & Technology

1999-10-01

receptor and cytoplasmic levels. Treatment of LNCaP and DU145 human prostate carcinoma cells with silibinin (the pure form of silymarin) resulted in... silibinin does not result in the inhibition of intrinsic tyrosine kinase activity of erbB 1 in both LNCaP and DU 145 cells. The observed inhibitory...suggest that more detailed mechanistic and tumor studies are needed to assess both preventive and interventive effects of silymarin (or silibinin ) against human rostate cancer.

Non-destructive analysis of DU content in the NIF hohlraums

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gharibyan, Narek; Moody, Ken J.; Shaughnessy, Dawn A.

2015-12-16

The advantage of using depleted uranium (DU) hohlraums in high-yield deuterium-tritium (DT) shots at the National Ignition Facility (NIF) is addressed by Döppner, et al., in great detail [1]. This DU based hohlraum incorporates a thin layer of DU, ~7 μm thick, on the inner surface along with a thin layer of a gold coating, ~0.7 μm thick, while the outer layer is ~22 μm thick gold. A thickness measurement of the DU layer can be performed using an optical microscope where the total DU weight can be computed provided a uniform DU layer. However, the uniformity of the thicknessmore » is not constant throughout the hohlraum since CAD drawing calculations of the DU weight do not agree with the computed values from optical measurements [2]. Therefore, a non-destructive method for quantifying the DU content in hohlraums has been established by utilizing gamma-ray spectroscopy. The details of this method, along with results from several hohlraums, are presented in this report.« less

Targeting the Neural Microenvironment in Prostate Cancer

DTIC Science & Technology

2015-10-01

nerve-prostate cancer cell interactions. Subtask 1: Sub-aim 2.1. DRG PNI studies with DU145 prostate cancer cells (months 4-15) We have received...Subtask 2: Sub-aim 2.2. DRG PNI studies with other prostate cancer cell lines (months 12- 36) This will be carried beginning in Year 2 Subtask 3: Sub...targets of these pathways such as p70S6 kinase. We are well positioned to proceed with DRG and in vivo mouse studies as well as immunohistochemistry

Targeting the Neural Microenvironment in Prostate Cancer

DTIC Science & Technology

2015-10-01

nerve-prostate cancer cell interactions. Subtask 1: Sub-aim 2.1. DRG PNI studies with DU145 prostate cancer cells (months 4-15) We have received...Subtask 2: Sub-aim 2.2. DRG PNI studies with other prostate cancer cell lines (months 12- 36) This will be carried beginning in Year 2 Subtask 3: Sub...potentiated by GFRA1. These studies suggest that GFRA1 may be partially limiting in our system . Moving forward we will need explore whether GFRA1

Jarid2 is essential for the maintenance of tumor initiating cells in bladder cancer.

PubMed

Zhu, Xin-Xing; Yan, Ya-Wei; Ai, Chun-Zhi; Jiang, Shan; Xu, Shan-Shan; Niu, Min; Wang, Xiang-Zhen; Zhong, Gen-Shen; Lu, Xi-Feng; Xue, Yu; Tian, Shaoqi; Li, Guangyao; Tang, Shaojun; Jiang, Yi-Zhou

2017-04-11

Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance. The goal of our study was to examine whether Jarid2 plays a role in the regulation of TICs in bladder cancer. We found that knockdown of Jarid2 was able to inhibit the invasive ability and sphere-forming capacity in bladder cancer cells. Moreover, knockdown of Jarid2 reduced the proportion of TICs and impaired the tumorigenicity of bladder cancer TICs in vivo. Conversely, ectopic overexpression of Jarid2 promoted the invasive ability and sphere-forming capacity in bladder cancer cells. Mechanistically, reduced Jarid2 expression led to the upregulation of p16 and H3K27me3 level at p16 promoter region. Collectively, we provided evidence that Jarid2 via modulation of p16 is a putative novel therapeutic target for treating malignant bladder cancer.

Portage vaginal du streptocoque du groupe B chez la femme enceinte au niveau de la région de Marrakech

PubMed Central

Bassir, Ahlam; Dhibou, Hanane; Farah, Majdi; Mohamed, Lharmis; Amal, Addebous; Nabila, Souraa; Abderahim, Aboulfalah; Asmouki, Hamid; Soummani, Abderraouf

2016-01-01

Introduction Le streptocoque du groupe B est le principal agent impliqué dans les infections materno-fœtales, les septicémies et les méningites du nouveau-né à terme. L'objectif est de déterminer le taux de portage maternel du streptocoque du groupe B (SGB) à terme. Méthodes Un prélèvement vaginal a été réalisé de manière prospective chez 275 parturientes lors de l'entrée en salle d'accouchement sur une période de 06 mois. Résultats Le taux de portage était de 20,2%. Le portage était variable en fonction de l’âge gestationnel, il constitue 57.5% entre 37 et 38 semaines d'aménorrhée. Aucun des facteurs de risque n'a était statistiquement prédictif du portage maternel du SGB. Conclusion Le dépistage doit être réalisé à partir de 37 semaines d'aménorrhée, et comme le portage est intermittent, un prélèvement négatif ne garantirait pas que le portage soit négatif à l'accouchement. PMID:27222693

Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells.

PubMed

Jose, Caroline; Hebert-Chatelain, Etienne; Dias Amoedo, Nivea; Roche, Emmanuel; Obre, Emilie; Lacombe, Didier; Rezvani, Hamid Reza; Pourquier, Philippe; Nouette-Gaulain, Karine; Rossignol, Rodrigue

2018-05-31

Anti-cancer effects of local anesthetics have been reported but the mode of action remains elusive. Here, we examined the bioenergetic and REDOX impact of levobupivacaine on human prostate cancer cells (DU145) and corresponding non-cancer primary human prostate cells (BHP). Levobupivacaine induced a combined inhibition of glycolysis and oxidative phosphorylation in cancer cells, resulting in a reduced cellular ATP production and consecutive bioenergetic crisis, along with reactive oxygen species generation. The dose-dependent inhibition of respiratory chain complex I activity by levobupivacaine explained the alteration of mitochondrial energy fluxes. Furthermore, the potency of levobupivacaine varied with glucose and oxygen availability as well as the cellular energy demand, in accordance with a bioenergetic anti-cancer mechanism. The levobupivacaine-induced bioenergetic crisis triggered cytostasis in prostate cancer cells as evidenced by a S-phase cell cycle arrest, without apoptosis induction. In DU145 cells, levobupivacaine also triggered the induction of autophagy and blockade of this process potentialized the anti-cancer effect of the local anesthetic. Therefore, our findings provide a better characterization of the REDOX mechanisms underpinning the anti-effect of levobupivacaine against human prostate cancer cells. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

DTIC Science & Technology

2012-03-01

After 1 week of tumor inoculation, vehicle (10% ethanol, 90% corn oil ), 10 mg/kg body weight (BW) of daidzein, or combined soy isoflavones 10 mg/kg BW...Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression. PRINCIPAL INVESTIGATOR: Columba de la Parra Simental CONTRACTING...00935 Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression Columba de la Parra Simental

Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology).

PubMed

Woodward, Wendy Ann; Bristow, Robert Glen

2009-04-01

Mounting evidence suggests that parallels between normal stem cell biology and cancer biology may provide new targets for cancer therapy. Prospective identification and isolation of cancer-initiating cells from solid tumors has promoted the descriptive and functional identification of these cells allowing for characterization of their response to contemporary cancer therapies, including chemotherapy and radiation. In clinical radiation therapy, the failure to clinically eradicate all tumor cells (eg, a lack of response, partial response, or nonpermanent complete response by imaging) is considered a treatment failure. As such, biologists have explored the characteristics of the small population of clonogenic cancer cells that can survive and are capable of repopulating the tumor after subcurative therapy. Herein, we discuss the convergence of these clonogenic studies with contemporary radiosensitivity studies that use cell surface markers to identify cancer-initiating cells. Implications for and uncertainties regarding incorporation of these concepts into the practice of modern radiation oncology are discussed.

Dietary Cadmium Exposure and Risk of Breast, Endometrial, and Ovarian Cancer in the Women’s Health Initiative

PubMed Central

Quraishi, Sabah M.; Shafer, Martin M.; Passarelli, Michael N.; Freney, Emily P.; Chlebowski, Rowan T.; Luo, Juhua; Meliker, Jaymie R.; Mu, Lina; Neuhouser, Marian L.; Newcomb, Polly A.

2014-01-01

Background: In vitro and animal data suggest that cadmium, a heavy metal that contaminates some foods and tobacco plants, is an estrogenic endocrine disruptor. Elevated estrogen exposure is associated with breast, endometrial, and ovarian cancer risk. Objectives: We examined the association between dietary cadmium intake and risk of these cancers in the large, well-characterized Women’s Health Initiative (WHI). Methods: A total of 155,069 postmenopausal women, 50–79 years of age, who were enrolled in the WHI clinical trials or observational study, participated in this study. We estimated dietary cadmium consumption by combining baseline food frequency questionnaire responses with U.S. Food and Drug Administration data on food cadmium content. Participants reported incident invasive breast, endometrial, or ovarian cancer, and WHI centrally adjudicated all cases through August 2009. We applied Cox regression to estimate adjusted hazard ratios (HRs) and 95% CIs for each cancer, comparing quintiles of energy-adjusted dietary cadmium intake. Results: Over an average of 10.5 years, 6,658 invasive breast cancers, 1,198 endometrial cancers, and 735 ovarian cancers were reported. We observed no statistically significant associations between dietary cadmium and risk of any of these cancers after adjustment for potential confounders including total dietary energy intake. Results did not differ in any subgroup of women examined. Conclusions: We found little evidence that dietary cadmium is a risk factor for breast, endometrial, or ovarian cancers in postmenopausal women. Misclassification in dietary cadmium assessment may have attenuated observed associations. Citation: Adams SV, Quraishi SM, Shafer MM, Passarelli MN, Freney EP, Chlebowski RT, Luo J, Meliker JR, Mu L, Neuhouser ML, Newcomb PA. 2014. Dietary cadmium exposure and risk of breast, endometrial, and ovarian cancer in the Women’s Health Initiative. Environ Health Perspect 122:594–600; http://dx.doi.org/10

CD133+ tumor initiating cells in a syngenic murine model of pancreatic cancer respond to Minnelide.

PubMed

Banerjee, Sulagna; Nomura, Alice; Sangwan, Veena; Chugh, Rohit; Dudeja, Vikas; Vickers, Selwyn M; Saluja, Ashok

2014-05-01

Pancreatic adenocarcinoma is the fourth leading cause for cancer-related mortality with a survival rate of less than 5%. Late diagnosis and lack of effective chemotherapeutic regimen contribute to these grim survival statistics. Relapse of any tumor is largely attributed to the presence of tumor-initiating cells (TIC) or cancer stem cells (CSC). These cells are considered as hurdles to cancer therapy as no known chemotherapeutic compound is reported to target them. Thus, there is an urgent need to develop a TIC-targeted therapy for pancreatic cancer. We isolated CD133(+) cells from a spontaneous pancreatic ductal adenocarcinoma mouse model and studied both surface expression, molecular markers of pancreatic TICs. We also studied tumor initiation properties by implanting low numbers of CD133(+) cells in immune competent mice. Effect of Minnelide, a drug currently under phase I clinical trial, was studied on the tumors derived from the CD133(+) cells. Our study showed for the first time that CD133(+) population demonstrated all the molecular markers for pancreatic TIC. These cells initiated tumors in immunocompetent mouse models and showed increased expression of prosurvival and proinvasive proteins compared to the CD133(-) non-TIC population. Our study further showed that Minnelide was very efficient in downregulating both CD133(-) and CD133(+) population in the tumors, resulting in a 60% decrease in tumor volume compared with the untreated ones. As Minnelide is currently under phase I clinical trial, its evaluation in reducing tumor burden by decreasing TIC as well as non-TIC population suggests its potential as an effective therapy. ©2014 AACR.

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women's health initiative

PubMed Central

McGinn, A. P.; Budrys, N.; Chlebowski, R.; Ho, G. Y.; Johnson, K. C.; Lane, D. S.; Li, W.; Neuhouser, M. L.; Saquib, J.; Shikany, J. M.; Song, Y.; Thomson, C.

2014-01-01

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50–79 at enrollment in the women's health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60–0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation. PMID:24104882

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women's health initiative.

PubMed

Wassertheil-Smoller, S; McGinn, A P; Budrys, N; Chlebowski, R; Ho, G Y; Johnson, K C; Lane, D S; Li, W; Neuhouser, M L; Saquib, J; Shikany, J M; Song, Y; Thomson, C

2013-10-01

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50-79 at enrollment in the women's health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60-0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation.

MLN8054, A Small Molecule Inhibitor of Aurora Kinase A, Sensitizes Androgen-Resistant Prostate Cancer to Radiation;Aurora kinase A; MLN8054; Prostate cancer; Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moretti, Luigi; Department of Radiation Oncology, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels; Niermann, Kenneth

2011-07-15

Purpose: To determine whether MLN8054, an Aurora kinase A (Aurora-A) inhibitor causes radiosensitization in androgen-insensitive prostate cancer cells in vitro and in vivo. Methods and Materials: In vitro studies consisted of culturing PC3 and DU145 prostate cancer cells and then immunoblotting Aurora A and phospho-Aurora A after radiation and/or nocodazole with MLN8054. Phases of the cell cycle were measured with flow cytometry. PC3 and DU145 cell lines were measured for survival after treatment with MLN8054 and radiation. Immunofluorescence measured {gamma}-H2AX in the PC3 and DU145 cells after treatment. In vivo studies looked at growth delay of PC3 tumor cells inmore » athymic nude mice. PC3 cells grew for 6 to 8 days in mice treated with radiation, MLN8054, or combined for 7 more days. Tumors were resected and fixed on paraffin and stained for von Willebrand factor, Ki67, and caspase-3. Results: In vitro inhibition of Aurora-A by MLN8054 sensitized prostate cancer cells, as determined by dose enhancement ratios in clonogenic assays. These effects were associated with sustained DNA double-strand breaks, as evidenced by increased immunofluorescence for {gamma}-H2AX and significant G2/M accumulation and polyploidy. In vivo, the addition of MLN8054 (30 mg/kg/day) to radiation in mouse prostate cancer xenografts (PC3 cells) significantly increased tumor growth delay and apoptosis (caspase-3 staining), with reduction in cell proliferation (Ki67 staining) and vascular density (von Willebrand factor staining). Conclusion: MLN8054, a novel small molecule Aurora-A inhibitor showed radiation sensitization in androgen-insensitive prostate cancer in vitro and in vivo. This warrants the clinical development of MLN8054 with radiation for prostate cancer patients.« less

Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

PubMed Central

Kwon, Mi Jeong; Shin, Young Kee

2013-01-01

Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

CRISPR/Cas9-mediated gene knockout of NANOG and NANOGP8 decreases the malignant potential of prostate cancer cells.

PubMed

Kawamura, Norihiko; Nimura, Keisuke; Nagano, Hiromichi; Yamaguchi, Sohei; Nonomura, Norio; Kaneda, Yasufumi

2015-09-08

NANOG expression in prostate cancer is highly correlated with cancer stem cell characteristics and resistance to androgen deprivation. However, it is not clear whether NANOG or its pseudogenes contribute to the malignant potential of cancer. We established NANOG- and NANOGP8-knockout DU145 prostate cancer cell lines using the CRISPR/Cas9 system. Knockouts of NANOG and NANOGP8 significantly attenuated malignant potential, including sphere formation, anchorage-independent growth, migration capability, and drug resistance, compared to parental DU145 cells. NANOG and NANOGP8 knockout did not inhibit in vitro cell proliferation, but in vivo tumorigenic potential decreased significantly. These phenotypes were recovered in NANOG- and NANOGP8-rescued cell lines. These results indicate that NANOG and NANOGP8 proteins are expressed in prostate cancer cell lines, and NANOG and NANOGP8 equally contribute to the high malignant potential of prostate cancer.

Partial purification and characterization of bacteriocin produced by Enterococcus faecalis DU10 and its probiotic attributes.

PubMed

Perumal, Venkatesh; Repally, Ayyanna; Dasari, Ankaiah; Venkatesan, Arul

2016-10-02

A novel bacteriocin produced by avian duck isolated lactic acid bacterium Enterococcus faecalis DU10 was isolated. This bacteriocin showed a broad spectrum of antibacterial activity against important food-borne pathogens and was purified by size exclusion chromatography followed by reverse-phase high-performance liquid chromatography in a C-18 column. Tricine-SDS PAGE revealed the presence of a band with an estimated molecular mass of 6.3 kDa. The zymogram clearly linked the antimicrobial activity with this band. This result was further confirmed by mass-assisted laser desorption ionization time-of-flight mass spectrometry, since a sharp peak corresponding to 6.313 kDa was detected and the functional groups were revealed by Fourier transform infrared spectroscopy. Bacteriocin DU10 activity was found sensitive to proteinase-K and pepsin and partially affected by trypsin and α-chymotrypsin. The activity of bacteriocin DU10 was partially resistant to heat treatments ranging from 30 to 90°C for 30 min. It also withstood a treatment at 121°C for 10 min. Cytotoxicity of bacteriocin DU10 by methyl-thiazolyl-diphenyl-tetrazolium bromide assay showed that the viability of HT-29 and HeLa cells decreased 60 ± 0.7% and 43 ± 4.8%, respectively, in the presence of 3,200 AU/mL of bacteriocin. The strain withstood 0.3% w/v of bile oxgall and pH 2 affected the bacterial growth between 2 and 4 hr of incubation. Adhesion properties examined with HT-29 cell line showed 69.85% initial population of strain E. faecalis DU10, which was found to be strongly adhered to this cell line. These results conclude bacteriocin DU10 may be used as a potential biopreservative and E. faecalis DU10 may be used as a potential probiont to control Salmonella infections.

Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines.

PubMed

Nagakawa, O; Murakami, K; Yamaura, T; Fujiuchi, Y; Murata, J; Fuse, H; Saiki, I

2000-07-31

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates proMMP-2 and expressed on the cell surface in many invasive cancer cells. We investigated the expression of MT1-MMP in prostate cancer cell lines. MT1-MMP protein and mRNA were expressed in PC-3, DU-145 and TSU-pr1 cells (androgen-independent prostate cancer cell lines), but in LNCaP cells (androgen-dependent prostate cancer cell line). MT1-MMP protein was negative and mRNA was low to detect by RT-PCR. Cell lysate of PC-3 cleaved proMMP-2 to the active form. In addition, both hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) increased Matrigel invasion and induced the expression of MT1-MMP protein in DU-145 prostate cancer cells. These results suggest that MT1-MMP is indeed the tumor-specific activator of proMMP-2 in androgen-independent prostate cancer cells and plays an important role in the invasive properties of prostate cancer cells.

Implementation and assessment of a fast-track programme to improve communication between primary and specialized care in patients with suspected cancer: how to shorten time between initial symptoms of cancer, diagnosis and initiation of treatment.

PubMed

Martínez, M T; González, I; Tarazona, N; Roselló, S; Saiz, R; Sanmartín, A; Martínez-Agulló, Á; Caballero, A; Mas, P; Franco, J; Martínez-Jabaloyas, J; García-Callejo, J; Martín, V; Navarro, J; Teruel, A; Lluch, A; Chirivella, I

2015-02-01

This study aims to asses a cancer fast-track programme (CFP) to shorten the time since a patient with suspicion of cancer is referred by the primary care (PC) physician to the specialized medical team. Guidelines for main suspected tumours were designed to help PC physicians to detect and rapidly refer cases to the CFP oncology coordinator, who sent them to the appropriate department to accelerate diagnosis, staging and therapy. All patients analysed in this report were referred from June 2009 to July 2012. A total of 897 suspected cancer cases were submitted and finally 705 were studied. In 205 (29 %) a cancer diagnosis was confirmed within 23 days (median). Therapy was initiated within 46 days after referral (median). Early diagnoses with a potential curative approach were made in 166 (82 %). This CFP decreased the waiting time for cancer diagnosis, by improving communication between PC physician and specialized care teams. Most patients included in this program could get therapy with curative intent.

Cirque du Monde as a health intervention: perceptions of medical students and social circus experts.

PubMed

Fournier, Cynthia; Drouin, Mélodie-Anne; Marcoux, Jérémie; Garel, Patricia; Bochud, Emmanuel; Théberge, Julie; Aubertin, Patrice; Favreau, Gil; Fleet, Richard

2014-11-01

To present Cirque du Soleil's social circus program, Cirque du Monde, to explore its potential as a primary health care tool for family physicians. A review of the literature in PubMed, the Cochrane Library, PsycINFO, LaPresse, Eureka, Google Scholar, and Érudit using the key words circus, social circus, Cirque du Monde, and Cirque du Soleil; a Montreal-based initiative, Espace Transition, modeled on Cirque du Monde; and personal communication with Cirque du Soleil's Social Circus Training Advisor. The first 50 articles or websites identified for each key word in each of the databases were examined on the basis of their titles and abstracts in the case of articles, and on the basis of their titles and page content in the case of websites. Articles and websites that explored an aspect of social circuses or that described an intervention that involved circuses were then retained for analysis. Because all literature on social circuses was searched, no criterion for year of publication was used. No articles on the social circus as a health intervention were found. One study on the use of the circus as an intervention in schools was identified. It demonstrated an increase in self-esteem in the children who took part. One study on the use of the circus in a First Nations community was found; it contained nonspecific, qualitative findings. The other articles identified were merely descriptions of social circuses. One website was identified on the use of the social circus to help youth who had been treated in a hospital setting for major psychiatric disorders to re-enter the community. The team in the pediatric psychiatry department at Centre Hospitalier Universitaire Sainte-Justine, the children's hospital in Montreal, Que, was contacted; they were leading this project, called Espace Transition. The unpublished preliminary findings of its pilot project demonstrate substantial improvements in overall patient functioning. According to Cirque du Soleil, there are several

The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer.

PubMed

Tirino, Virginia; Camerlingo, Rosa; Franco, Renato; Malanga, Donatella; La Rocca, Antonello; Viglietto, Giuseppe; Rocco, Gaetano; Pirozzi, Giuseppe

2009-09-01

Emerging evidence suggests that specific sub-populations of cancer cells with stem cell characteristics within the bulk of tumours are implicated in the pathogenesis of heterogeneous malignant tumours. The cells that drive tumour growth have been denoted cancer-initiating cells or cancer stem cells (hereafter CSCs). CSCs have been isolated initially from leukaemias and subsequently from several solid tumours including brain, breast, prostate, colon and lung cancer. This study aimed at isolating and characterising the population of tumour-initiating cells in non-small-cell lung cancer (NSCLC). Specimens of NSCLC obtained from 89 patients undergoing tumour resection at the Cancer National Institute of Naples were analysed. Three methods to isolate the tumour-initiating cells were used: (1) flow cytometry analysis for identification of positive cells for surface markers such as CD24, CD29, CD31, CD34, CD44, CD133 and CD326; (2) Hoechst 33342 dye exclusion test for the identification of a side-population characteristic for the presence of stem cells; (3) non-adherent culture condition able to form spheres with stem cell-like characteristics. Definition of the tumourigenic potential of the cells through soft agar assay and injection into NOD/SCID mice were used to functionally define (in vitro and in vivo) putative CSCs isolated from NSCLC samples. Upon flow cytometry analysis of NSCLC samples, CD133-positive cells were found in 72% of 89 fresh specimens analysed and, on average, represented 6% of the total cells. Moreover, the number of CD133-positive cells increased markedly when the cells, isolated from NSCLC specimens, were grown as spheres in non-adherent culture conditions. Cells from NSCLC, grown as spheres, when assayed in soft agar, give rise to a 3.8-fold larger number of colonies in culture and are more tumourigenic in non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice compared with the corresponding adherent cells. We have isolated and

Enhanced Peptide Radiotherapy of Prostate Cancer Using Targeted Adenoviral Vectors

DTIC Science & Technology

2004-06-01

regard to binding of 64Cu - octreotide. In vitro experiments were performed with DU-145 and PC-3 human prostate cancer cells. Expression levels of SSTR2...were determined using a 64Cu -octreotide saturation binding assay on cell membrane preparations. In vivo experiments were conducted in scid mice bearing...subcutaneous DU-l45 or PC-3 cells. AdSSTR2 was injected intratumorally followed 48 h later by an i.v. injection of 64Cu -octreotide. The mice were

Blockade of Fas Signaling in Breast Cancer Cells Suppresses Tumor Growth and Metastasis via Disruption of Fas Signaling-initiated Cancer-related Inflammation*

PubMed Central

Liu, Qiuyan; Tan, Qinchun; Zheng, Yuanyuan; Chen, Kun; Qian, Cheng; Li, Nan; Wang, Qingqing; Cao, Xuetao

2014-01-01

Mechanisms for cancer-related inflammation remain to be fully elucidated. Non-apoptotic functions of Fas signaling have been proposed to play an important role in promoting tumor progression. It has yet to be determined if targeting Fas signaling can control tumor progression through suppression of cancer-related inflammation. In the current study we found that breast cancer cells with constitutive Fas expression were resistant to apoptosis induction by agonistic anti-Fas antibody (Jo2) ligation or Fas ligand cross-linking. Higher expression of Fas in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. To determine whether blockade of Fas signaling in breast cancer could suppress tumor progression, we prepared an orthotopic xenograft mouse model with mammary cancer cells 4T1 and found that blockade of Fas signaling in 4T1 cancer cells markedly reduced tumor growth, inhibited tumor metastasis in vivo, and prolonged survival of tumor-bearing mice. Mechanistically, blockade of Fas signaling in cancer cells significantly decreased systemic or local recruitment of myeloid derived suppressor cells (MDSCs) in vivo. Furthermore, blockade of Fas signaling markedly reduced IL-6, prostaglandin E2 production from breast cancer cells by impairing p-p38, and activity of the NFκB pathway. In addition, administration of a COX-2 inhibitor and anti-IL-6 antibody significantly reduced MDSC accumulation in vivo. Therefore, blockade of Fas signaling can suppress breast cancer progression by inhibiting proinflammatory cytokine production and MDSC accumulation, indicating that Fas signaling-initiated cancer-related inflammation in breast cancer cells may be a potential target for treatment of breast cancer. PMID:24627480

Prostate cancer stem-like cells proliferate slowly and resist etoposide-induced cytotoxicity via enhancing DNA damage response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Judy; Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada L8N 4A6; The Hamilton Centre for Kidney Research

Despite the development of chemoresistance as a major concern in prostate cancer therapy, the underlying mechanisms remain elusive. In this report, we demonstrate that DU145-derived prostate cancer stem cells (PCSCs) progress slowly with more cells accumulating in the G1 phase in comparison to DU145 non-PCSCs. Consistent with the important role of the AKT pathway in promoting G1 progression, DU145 PCSCs were less sensitive to growth factor-induced activation of AKT in comparison to non-PCSCs. In response to etoposide (one of the most commonly used chemotherapeutic drugs), DU145 PCSCs survived significantly better than non-PCSCs. In addition to etoposide, PCSCs demonstrated increased resistancemore » to docetaxel, a taxane drug that is commonly used to treat castration-resistant prostate cancer. Etoposide produced elevated levels of γH2AX and triggered a robust G2/M arrest along with a coordinated reduction of the G1 population in PCSCs compared to non-PCSCs, suggesting that elevated γH2AX plays a role in the resistance of PCSCs to etoposide-induced cytotoxicity. We have generated xenograft tumors from DU145 PCSCs and non-PCSCs. Consistent with the knowledge that PCSCs produce xenograft tumors with more advanced features, we were able to demonstrate that PCSC-derived xenograft tumors displayed higher levels of γH2AX and p-CHK1 compared to non-PCSC-produced xenograft tumors. Collectively, our research suggests that the elevation of DNA damage response contributes to PCSC-associated resistance to genotoxic reagents. - Highlights: • Increased survival in DU145 PCSCs following etoposide-induced cytotoxicity. • PCSCs exhibit increased sensitivity to etoposide-induced DDR. • Resistance to cytotoxicity may be due to slower proliferation in PCSCs. • Reduced kinetics to growth factor induced activation of AKT in PCSCs.« less

Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative

PubMed Central

Adams, Scott V.; Shafer, Martin M.; Bonner, Matthew R.; LaCroix, Andrea Z.; Manson, JoAnn E.; Meliker, Jaymie R.; Neuhouser, Marian L.; Newcomb, Polly A.

2016-01-01

Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993–2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)2) less than 25. Results were consistent in both estrogen receptor–positive and estrogen receptor–negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer. PMID:27037269

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

PubMed Central

Reiter, Russel J.; Rosales-Corral, Sergio A.; Tan, Dun-Xian; Acuna-Castroviejo, Dario; Qin, Lilan; Yang, Shun-Fa; Xu, Kexin

2017-01-01

There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level

Effects of tumour necrosis factor α upon the metabolism of the endocannabinoid anandamide in prostate cancer cells.

PubMed

Karlsson, Jessica; Gouveia-Figueira, Sandra; Alhouayek, Mireille; Fowler, Christopher J

2017-01-01

Tumour necrosis factor α (TNFα) is involved in the pathogenesis of prostate cancer, a disease where disturbances in the endocannabinoid system are seen. In the present study we have investigated whether treatment of DU145 human prostate cancer cells affects anandamide (AEA) catabolic pathways. Additionally, we have investigated whether cyclooxygenase-2 (COX-2) can regulate the uptake of AEA into cells. Levels of AEA synthetic and catabolic enzymes were determined by qPCR. AEA uptake and hydrolysis in DU145 and RAW264.7 macrophage cells were assayed using AEA labeled in the arachidonic and ethanolamine portions of the molecule, respectively. Levels of AEA, related N-acylethanolamines (NAEs), prostaglandins (PG) and PG-ethanolamines (PG-EA) in DU145 cells and medium were quantitated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. TNFα treatment of DU145 cells increased mRNA levels of PTSG2 (gene of COX-2) and decreased the mRNA of the AEA synthetic enzyme N-acyl-phosphatidylethanolamine selective phospholipase D. mRNA levels of the AEA hydrolytic enzymes fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase were not changed. AEA uptake in both DU145 and RAW264.7 cells was inhibited by FAAH inhibition, but not by COX-2 inhibition, even in RAW264.7 cells where the expression of this enzyme had greatly been induced by lipopolysaccharide + interferon γ treatment. AEA and related NAEs were detected in DU145 cells, but PGs and PGE2-EA were only detected when the cells had been preincubated with 100 nM AEA. The data demonstrate that in DU145 cells, TNFα treatment changes the relative expression of the enzymes involved in the hydrolytic and oxygenation catabolic pathways for AEA. In RAW264.7 cells, COX-2, in contrast to FAAH, does not regulate the cellular accumulation of AEA. Further studies are necessary to determine the extent to which inflammatory mediators are involved in the abnormal

African American women's experiences with the initial discovery, diagnosis, and treatment of breast cancer.

PubMed

Lackey, N R; Gates, M F; Brown, G

2001-04-01

To describe the experiences of African American women living with breast cancer following the primary diagnosis and while undergoing initial treatment. Phenomenologic. 13 African American women (ages 30-66) purposefully selected from two oncology clinics in the mid-South. Phenomenologic interviews (transcribed verbatim) and field notes were analyzed using Colaizzi's method of phenomenologic description and analysis. Experience Trajectory, Femininity, and Spirituality were the three major themes. The Experience Trajectory subthemes were finding the lump, getting the diagnosis, undergoing surgery and adjuvant treatment. The Femininity subthemes were loss of all or part of the breast, loss of hair, and sexual attractiveness to a man. Spirituality was reflected as a reliance on God. Telling the story of their experience trajectory during their breast cancer experience is valuable in assessing African American women's feelings, emotions, and fears of body changes that occur during surgery and treatment. Their spirituality helps them through this experience. Research involving both African American women and their partners would provide greater insight into specific relationship patterns and communication related to sexuality during this experience. Nurses need to listen to the stories of African American women about the initial experience of discovery, diagnosis, and treatment of breast cancer so they can be more informed advocates for these women. African American women need more information from healthcare providers regarding the whole experience trajectory.

Ethyl acetate fraction from methanol extraction of Vitis thunbergii var. taiwaniana induced G0 /G1 phase arrest via inhibition of cyclins D and E and induction of apoptosis through caspase-dependent and -independent pathways in human prostate carcinoma DU145 cells.

PubMed

Lin, Chia-Hsin; Chan, Hsiao-Sung; Tsay, Hsin-Sheng; Funayama, Shinji; Kuo, Chao-Lin; Chung, Jing-Gung

2018-01-01

Vitis thunbergii var. taiwaniana (VTT) is a wild grape native to Taiwan, belonging to the Vitaceae family and Vitis genus, and widely used as folk herbal medicine. It is traditionally used for the treatment of diarrhea, hypertension, neuroprotection, jaundice, and arthritis. We used the wild-collected VTT and sterilized them to establish the plant tissue culture, and then took the leaves for DNA sequencing to determine its original base. We use methanol to extract VTT in four different solvents: 1-butanol, n-hexane, ethyl acetate, and water. These four preliminary extracts were used to treat human prostate cancer DU145 cells in vitro. We use the flow cytometry to check the cell survival situation. Finally, we found the ethyl acetate layer roughing product (referred VTEA) in human prostate cancer apoptotic effects of cell line DU-145. In the present studies, we use the crude extract of VTT to examine whether or not it can induce apoptosis of DU145 cells in vitro. Viability assays for extracts of VTT treatment showed that it had dose-dependent effect on human prostate cancer DU145 cells. We also found that the extract of VTT induces time-dependent mitochondrial and intrinsic-dependent apoptosis pathways. The in vitro cytotoxic effects were investigated by cell cycle analysis and the determination of apoptotic DNA fragmentation in DU145 cells. The cell cycle analysis showed that extracts of VTT induced a significant increase in the number of cells in G 0 /G 1 phase. The extract of VTT induced chromatin changes and apoptosis of DU145 cells also were confirmed by DAPI and PI staining that were measured by fluorescence microscopy and flow cytometry, respectively. Finally, the expression of relevant proteins was analyzed by Western blot analysis. These results promoted us to further evaluate apoptosis associated proteins and elucidate the possible signal pathway in DU-145 cells after treated with the extract of VTT. © 2017 Wiley Periodicals, Inc.

L'Aventure du LHC

ScienceCinema

None

2018-05-16

Cette présentation s’adressera principalement aux personnes qui ont construit le LHC. La construction du LHC fut longue et difficile. De nombreux problèmes sont apparus en cours de route. Tous ont été résolus grâce au dévouement et à l’engagement du personnel et des collaborateurs. Je reviendrai sur les coups durs et les réussites qui ont marqués ces 15 dernières années et je vous montrerai combien cette machine, le fruit de vos efforts, est extraordinaire.

Cytotoxic effects of treosulfan on prostate cancer cell lines.

PubMed

Feyerabend, Susan; Feil, Gerhard; Krug, Jutta; Kassen, Annette; Stenzl, Arnulf

2007-01-01

Despite various therapeutical options in metastatic prostate cancer, the lack of a curative approach motivates further investigations. Treosulfan is an alkylating agent that has proven its indication in the treatment of e.g. ovarian carcinoma. This study focused on the objective of evaluating the effect of in vitro intoxication of human prostate carcinoma cell lines with treosulfan. Human prostate cancer cell lines LNCaP, DU145 and PC3 were treated with treosulfan concentrations from 0.5-500 microM for up to six days. Analysis of cell viability was performed using colorimetric WST-1 assay. Control data were obtained from identical cell lines cultivated without treosulfan. Incubation with treosulfan inhibited cell viability and led to cell death in all cell lines in a dose- and time-dependent manner. After one day, viability of LNCaP, DU145 and PC3 cells was constantly reduced with a dose rate of at least 10 microM (p < 0.001), 10 microM (p < 0.0001) and 100 microM (p < 0.0001) treosulfan, respectively. Minimum dose rates leading to death of nearly all LNCaP, DU145 and PC3 cells were 250 microM, 100 microM and 200 microM treosulfan, respectively. The results demonstrate a sensitivity of prostate carcinoma cells to the cytotoxic activity of treosulfan. Therefore, treosulfan might be a promising compound for novel treatment protocols for prostate cancer.

External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy.

PubMed

Greene, Daniel J; Elshafei, Ahmed; Nyame, Yaw A; Kara, Onder; Malkoc, Ercan; Gao, Tianming; Jones, J Stephen

2016-08-01

The aim of this study was to externally validate a previously developed PCA3-based nomogram for the prediction of prostate cancer (PCa) and high-grade (intermediate and/or high-grade) prostate cancer (HGPCa) at the time of initial prostate biopsy. A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P < 0.001). Despite the differences in PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dedicated Caravan Sites for French Gens du Voyage

PubMed Central

2017-01-01

Abstract In France, gens du voyage (“people who travel” or “travellers”) is a term used by the government to categorize various itinerant populations, the majority of which are diverse Romani groups. People categorized as gens du voyage are legally required to reside in particular locations called “dedicated caravan sites.” Parliamentary debates about these dedicated caravan sites have clarified that one of the objectives of such sites is to help fulfill the gens du voyage’s right to health. However, there is a significant gap between the officially stated goals of such sites and the reality of life within them. This paper draws on research finding that the conditions in most dedicated caravan sites do not conform with the rights of gens du voyage to acceptable sanitary conditions and other underlying determinants of health. PMID:29302165

[What specific socialisation, social, educational and professional for teenagers and young adults with cancer?

PubMed

Roesler, Caroline; Pautre, Isabelle; Thirry, Dominique; Flores, Soccoro; Chabbert, Catherine; Savre, Nikita; Pibarot, Michèle; Seveau, Marie-Aude; Dugas, Karyn; Rollin, Zoé; Dumont, Sarah; Gaspar, Nathalie

2016-12-01

Socialisation, education, first jobs and autonomy are key steps to teenagers and young adults (TYA) integration into the society. The occurrence of a cancer in this population increases the difficulties. Although, suffering of cancer do affect TYA life journey at social, scholar and professional levels, from diagnosis to the after-cancer live and sometime forever, few studies exist in France. A national study on TYA with cancer (TYAC) social, scholar and professional pathways is on-going (ESPOIR-AJA). A national survey of the existing TYAC insertion support in 2013 by the "Insertion group" of groupe onco-hématologie adolescents et jeunes adultes (GO-AJA) revealed structured and ancient support at scholar level based on national governmental or associative structures, but insufficient and non-specific scholar help in secondary school and professional help. Specific initiatives have emerged since 2012 with the "Plan cancer 2". All these helps remain unequal across the country. A referential on TYAC social, scholar and professional insertion has been prepared by GO-AJA in collaboration with the association francophone des soins oncologiques de support (AFSOS). The impact of the action 9 of the nation "plan cancer 3" is awaited. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

How doctors communicate the initial diagnosis of cancer matters: cancer disclosure and its relationship with Patients' hope and trust.

PubMed

Cao, Weidan; Qi, Xiaona; Yao, Ting; Han, Xuanye; Feng, Xujing

2017-05-01

The study is to examine the relationships between perceived initial cancer disclosure communication with doctors, levels of hope, and levels of trust in doctors among cancer patients in China. A total number of 192 cancer inpatients in a cancer hospital in China were surveyed. Perceived disclosure strategies, levels of hope, levels of trust in their doctors, as well as the demographic information were obtained from the participants. In addition to age, patients who had higher levels of perceived emotional support from doctors, or higher levels of perceived personalized disclosure from doctors, or higher levels of perceived discussion of multiple treatment plans with doctors were more likely to have higher levels of trust in doctors. In addition to perceived health status, perceived emotional support from doctors significantly predicted participants' levels of hope. That is, patients who had higher higher levels of perceived doctors' emotional support were more likely to have higher levels of hope. Key disclosure person was a marginally significant variable, that is, patients who were mainly disclosed by family members might have higher levels of hope compared with patients who were mainly disclosed by doctors. When communicating with a cancer patient, doctors might not ignore the importance of emotional support during cancer diagnosis communication. Doctors might want to involve family and collaborate with family to find out ways of personalized disclosure. During the communication process, doctors could provide their patients with multiple treatment options and discuss the benefits and side effects of each treatment. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Molecular Validation of PACE4 as a Target in Prostate Cancer12

PubMed Central

D'Anjou, François; Routhier, Sophie; Perreault, Jean-Pierre; Latil, Alain; Bonnel, David; Fournier, Isabelle; Salzet, Michel; Day, Robert

2011-01-01

Prostate cancer remains the single most prevalent cancer in men. Standard therapies are still limited and include androgen ablation that initially causes tumor regression. However, tumor cells eventually relapse and develop into a hormone-refractory prostate cancer. One of the current challenges in this disease is to define new therapeutic targets, which have been virtually unchanged in the past 30 years. Recent studies have suggested that the family of enzymes known as the proprotein convertases (PCs) is involved in various types of cancers and their progression. The present study examined PC expression in prostate cancer and validates one PC, namely PACE4, as a target. The evidence includes the observed high expression of PACE4 in all different clinical stages of human prostate tumor tissues. Gene silencing studies targeting PACE4 in the DU145 prostate cancer cell line produced cells (cell line 4-2) with slower proliferation rates, reduced clonogenic activity, and inability to grow as xenografts in nude mice. Gene expression and proteomic profiling of the 4-2 cell line reveals an increased expression of known cancer-related genes (e.g., GJA1, CD44, IGFBP6) that are downregulated in prostate cancer. Similarly, cancer genes whose expression is decreased in the 4-2 cell line were upregulated in prostate cancer (e.g., MUC1, IL6). The direct role of PACE4 in prostate cancer is most likely through the upregulated processing of growth factors or through the aberrant processing of growth factors leading to sustained cancer progression, suggesting that PACE4 holds a central role in prostate cancer. PMID:21633671

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

PubMed Central

Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

2008-01-01

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic

Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.

PubMed

Wubetu, Gizachew Yismaw; Utsunomiya, Tohru; Ishikawa, Daichi; Ikemoto, Tetsuya; Yamada, Shinichiro; Morine, Yuji; Iwahashi, Shuichi; Saito, Yu; Arakawa, Yusuke; Imura, Satoru; Arimochi, Hideki; Shimada, Mitsuo

2014-09-01

Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Polymorphisme de l'apolipoprotéine E dans la population du nord du Maroc: fréquence et influence sur les paramètres lipidiques

PubMed Central

Benyahya, Fatiha; Barakat, Amina; Ghailani, Naima; Bennani, Mohcine

2013-01-01

Introduction L'objectif de ce travail est de déterminer les fréquences alléliques et génotypiques des sites polymorphes situés dans le gène de l'apolipoprotéine E (apo E) ainsi que leur impact sur les paramètres cliniques et lipidiques dans un échantillon de la population du nord du Maroc cliniquement diagnostiqué ADH. Méthodes Le génotype de l'apo E a été analysé par séquençage direct chez 46 patients cliniquement diagnostiqués ADH selon les critères standards. Résultats Les fréquences des allèles epsilon 3, epsilon 2 et epsilon 4 ont été respectivement 78.3%, 2.2% et 19.6%. La fréquence de l'allèle epsilon 4 est très élevée chez la population du nord du Maroc en comparaison avec les populations des autres régions marocaines. Elle est similaire à celle rapportée dans les pays de l'Europe du nord. Les taux du cholestérol total, du cholestérol LDL ainsi que la présence des xanthomes et les maladies cardiovasculaires ne différent pas entre les génotypes de l'apoE. En revanche, les résultats ont montré une influence de l'allèle epsilon4 sur le taux des triglycérides chez les sujets obèses. Conclusion Le génotype de l'apoE ne peut expliquer le phénotype clinique et biochimique présenté par des patients du Nord du Maroc cliniquement diagnostiqués ADH. PMID:24396563

Étude des déterminants individuels de l’adoption du dossier de santé électronique du Québec

PubMed Central

Mezni, H; M-P, Gagnon; Duplantie, J

2016-01-01

Résumé Objectif Selon des études précédentes, les dossiers de santé électroniques peuvent améliorer l’efficacité, la sécurité et la qualité de la prise en charge médicale. Cependant, les prestataires de soins restent réticents quant à son utilisation, ce qui limite son impact sur le système de santé. La présente étude avait pour objectif d’évaluer les perceptions des médecins face au dossier de santé du Québec. Méthodes À partir d’une revue de la littérature sur les facteurs influençant l’adoption des nouvelles technologies de l’information et des communications (NTIC) en général et de la cybersanté en particulier, nous avons élaboré un questionnaire semi-structuré. Au total, 12 médecins utilisateurs potentiels du dossier de santé du Québec (DSQ) ont complété et retourné le questionnaire. Par la suite, nous avons opéré une analyse thématique de contenu, suivie par une théorisation des concepts obtenus. Résultats L’intention d’adopter le DSQ est influencée positivement par l’utilité perçue, la facilité d’utilisation perçue, la démonstrabilité des résultats, la compatibilité du système avec la pratique et l’autoefficacité informatique perçue par les médecins. Inversement, la résistance au changement influence négativement l’adoption du DSQ par les médecins. Conclusion L’identification des déterminants de l’adoption du dossier de santé du Québec est cruciale pour les responsables du secteur de la santé au Québec. Il sera ainsi possible de saisir les attentes des utilisateurs potentiels et d’ajuster les stratégies d’implantation en vue de favoriser une meilleure intégration de cette technologie dans les pratiques médicales. PMID:27867453

Differential role of PTEN in transforming growth factor β (TGF-β) effects on proliferation and migration in prostate cancer cells.

PubMed

Kimbrough-Allah, Mawiyah N; Millena, Ana C; Khan, Shafiq A

2018-04-01

Transforming growth factor-β (TGF-β) acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-β effects on proliferation and migration in prostate cancer cells. Expression of PTEN mRNA and proteins were determined using RT-PCR and Western blotting in RWPE1 and DU145 cells. We also studied the role of PTEN in TGF-β effects on cell proliferation and migration in DU145 cells after transient silencing of endogenous PTEN. Conversely, we determined the role of PTEN in cell proliferation and migration after over-expression of PTEN in PC3 cells which lack endogenous PTEN. TGF-β1 and TGF-β3 had no effect on PTEN mRNA levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells indicating that PTEN may mediate TGF-β effects on cell proliferation. Knockdown of PTEN in DU145 cells resulted in significant increase in cell proliferation which was not affected by TGF-β isoforms. PTEN overexpression in PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced cell migration in DU145 cells, whereas PTEN overexpression reduced migration in PC3 cells and reduced phosphorylation of AKT in response to TGF-β. We conclude that PTEN plays a role in inhibitory effects of TGF-β on cell proliferation whereas its absence may enhance TGF-β effects on activation of PI3-kinase pathway and cell migration. © 2018 Wiley Periodicals, Inc.

Induction of the p75NTR by Aryl Propionic Acids in Prostate Cancer Cells

DTIC Science & Technology

2008-12-01

and ketoprofen among others. Long term ibuprofen use is associated with a decreased risk of prostate cancer (9-10). Treatment with the enantiomer R...different metastatic hormone-refractory prostate cancer cell lines, PC-3 and DU-145. Of those tested, the enantiomer R-flurbiprofen and ibuprofen were...class of NSAIDs. Treatment of T24 bladder cancer cells and HCT-116 colon cancer cells with ibuprofen or the enantiomer R- flurbiprofen, which lacks COX

Induction of the p75NTR by Aryl Propionic Acids in Prostate Cancer Cells

DTIC Science & Technology

2007-12-01

among others. Long term ibuprofen use is associated with a decreased risk of prostate cancer (9-10). Treatment with the enantiomer R-flurbiprofen...cancer cell lines, PC-3 and DU-145. Of those tested, the enantiomer R-flurbiprofen and ibuprofen were the most effective. These drugs were also...Treatment of T24 bladder cancer cells and HCT-116 colon cancer cells with ibuprofen or the enantiomer R-flurbiprofen, which lacks COX inhibitory

Le kyste hydatique du cordon spermatique: une localisation exceptionnelle

PubMed Central

Hamdane, Mohamed Moncef; Bougrine, Fethi; Msakni, Issam; Dhaoui-Ghozzi, Amen; Bouziani, Ammar

2011-01-01

L’ hydatidose est une anthropo-zoonose due au développement chez l'homme de la forme larvaire du taenia Echinococcus granulosis. La plupart des kystes hydatiques se localisent dans le foie et les poumons. Le kyste hydatique du cordon spermatique est extrêmement rare avec seulement 4 cas rapportés dans la littérature. Les auteurs rapportent dans cet article un nouveau cas d'hydatidose du cordon spermatique. Il s'agissait d'un homme de 40 ans qui consultait pour des douleurs scrotales évoluant depuis huit mois. L'examen clinique a mis en évidence une tuméfaction mobile, inguino-scrotale, droite. L’échographie testiculaire a objectivé une hernie inguinale droite associée à deux kystes épididymaires bilatéraux. Le patient a été opéré pour cure de son hernie avec découverte en per-opératoire d'un kyste du cordon spermatique qui a été réséqué. L'examen anatomopathologique a conclu à une hydatidose du cordon spermatique. PMID:22384304

Social relationships, inflammation markers, and breast cancer incidence in the Women's Health Initiative.

PubMed

Busch, Evan L; Whitsel, Eric A; Kroenke, Candyce H; Yang, Yang C

2018-06-01

Previous research has reported associations between social relationships and carcinogenesis. Inflammation is a potential mediator of these associations. To clarify these links for one tumor site, we examined associations between social relationships, circulating inflammation markers, and breast cancer incidence. Among 132,262 participants from the prospective Women's Health Initiative, we used linear and logistic regression to evaluate associations between social relationship characteristics (social support, social strain, social network size) and inflammation markers of C-reactive protein (CRP) and white blood cell count (WBC). Cox regression was used to evaluate associations between inflammation markers and breast cancer incidence, as well as associations between social relationship characteristics and breast cancer incidence with and without adjustment for inflammation markers. Larger social networks were associated with lower continuous CRP (beta = -0.22, 95% CI -0.36, -0.08) and WBC (beta = -0.23, 95% CI -0.31, -0.16). Greater social strain was associated with higher continuous CRP (beta = 0.24, 95% CI 0.14, 0.33) and WBC (beta = 0.09, 95% CI 0.04, 0.14). When WBC was dichotomized at 10,000 cells/uL, high WBC was associated with greater hazards of in situ breast cancer (HR = 1.65, 95% CI 1.17, 2.33) but not invasive breast cancer. Social relationship characteristics were not associated with incidence of invasive or in situ breast cancer. Larger social networks were associated with lower inflammation and greater social strain was associated with higher inflammation. Higher inflammation might be associated with development of in situ breast cancer, but this appeared to be due to factors other than social relationships. Copyright © 2018 Elsevier Ltd. All rights reserved.

Co-targeting androgen receptor and DNA for imaging and molecular radiotherapy of prostate cancer: in vitro studies.

PubMed

Han, Guang; Kortylewicz, Zbigniew P; Enke, Thomas; Baranowska-Kortylewicz, Janina

2014-12-01

The androgen receptor (AR) axis, the key growth and survival pathway in prostate cancer, remains a prime target for drug development. 5-Radioiodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridin-5'-yl phosphate (RISAD-P) is the AR-seeking reagent developed for noninvasive assessment of AR and proliferative status, and for molecular radiotherapy of prostate cancer with Auger electron-emitting radionuclides. RISAD-P radiolabeled with 123I, 124I, and 125I were synthesized using a common stannylated precursor. The cellular uptake, subcellular distribution, and radiotoxicity of 123I-, 124I-, and (125) IRISAD-P were measured in LNCaP, DU145, and PC-3 cell lines expressing various levels of AR. The uptake of RISAD-P by prostate cancer cells is proportional to AR levels and independent of the radionuclide. The intracellular accumulation of radioactivity is directly proportional to the extracellular concentration of RISAD-P and the duration of exposure. Initially, RISAD-P is trapped in the cytoplasm. Within 24 hr, radioactivity is associated exclusively with DNA. The RISAD-P radiotoxicity is determined by the radionuclide; however, the cellular responses are directly proportional to the AR expression levels. LNCaP cells expressing high levels of AR are killed at the rate of up to 60% per day after a brief 1 hr RISAD-P treatment. For the first time, the AR expression in PC-3 and DU 145 cells, generally reported as AR-negative, was quantitated by the ultra sensitive RISAD-P-based method. RISAD-P is a theranostic drug, which targets AR. Its subcellular metabolite participates in DNA synthesis. RISAD-P is a promising candidate for imaging of the AR expression and tumor proliferation as well as molecular radiotherapy of prostate cancer. © 2014 Wiley Periodicals, Inc.

Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es

2015-07-15

Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT inductionmore » (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in

Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

2008-05-15

Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygenmore » species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.« less

Weight Fluctuation and Cancer Risk in Post-Menopausal Women: The Women’s Health Initiative

PubMed Central

Welti, Laura M.; Beavers, Daniel P.; Caan, Bette J.; Sangi-Haghpeykar, Haleh; Vitolins, Mara Z.; Beavers, Kristen M.

2017-01-01

Background Weight cycling, defined by an intentional weight loss and subsequent regain, commonly occurs in overweight and obese women and is associated with some negative health outcomes. We examined the role of various weight-change patterns during early to mid- adulthood and associated risk of highly prevalent, obesity-related cancers (breast, endometrial, colorectal) in postmenopausal women. Methods 80,943 postmenopausal women (age: 63.4±7.4 years) in the Women’s Health Initiative Observational Study were categorized by self-reported weight change (weight stable; weight gain; lost weight; weight cycled [1–3, 4–6, 7–10, >10 times]) during early to mid- adulthood (18–50 years). Three site-specific associations were investigated using Cox proportional hazard models (age, race/ethnicity, income, education, smoking, alcohol, physical activity, hormone therapy, diet, BMI). Results 7,464 (breast=5,564; endometrial=788; colorectal=1,290) incident cancer cases were identified between September 1994 and August 2014. Compared with weight stability, weight gain was significantly associated with risk of breast cancer (HR=1.11, 1.03–1.20) after adjustment for BMI. Similarly, weight cycling was significantly associated with risk of endometrial cancer (HR=1.23, 1.01–1.49). Weight cycling “4–6 times” was most consistently associated with cancer risk, showing a 38% increased risk for endometrial cancer (95% CI: 1.08–1.76) compared to weight stable women. Conclusions Weight gain and weight cycling were positively associated with risk of breast and endometrial cancer, respectively. Impact These data suggest weight cycling and weight gain increase risk of prevalent cancers in postmenopausal women. Adopting ideal body weight maintenance practices before and after weight loss should be encouraged to reduce risk of incident breast and endometrial cancers. PMID:28069684

Plasminogen activator inhibitor-1 as regulator of tumor-initiating cell properties in head and neck cancers.

PubMed

Lee, Yueh-Chun; Yu, Cheng-Chia; Lan, Chih; Lee, Che-Hsin; Lee, Hsueh-Te; Kuo, Yu-Liang; Wang, Po-Hui; Chang, Wen-Wei

2016-04-01

The existence of tumor-initiating cells (TICs) has been described in head and neck cancers. Plasminogen activator inhibitor-1 (PAI-1) has been demonstrated to act as a prognostic factor in head and neck cancers. Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, and PAI-1-specific siRNA were used to examine the role of PAI-1 in the self-renewal property of head and neck cancer-TICs by tumorsphere formation. Western blot, real-time polymerase chain reaction, and luciferase-based reporter assay were used to study the effect of PAI-039 in the sex-determining region Y-box 2 (Sox2) expression. PAI-039 suppressed the self-renewal capability of head and neck cancer-TICs derived from head and neck cancer cell lines through the inhibition of Sox2 expression. PAI-039 decreased the activity of the core promoter and the enhancer of the Sox2 gene in head and neck cancer-TICs. Knockdown of PAI-1 expression also inhibited self-renewal and radioresistance properties of head and neck cancer-TICs. The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and neck cancer-TICs within head and neck cancer cell lines through the downregulation of Sox2. © 2015 Wiley Periodicals, Inc. Head Neck 38: E895-E904, 2016. © 2015 Wiley Periodicals, Inc.

Acceptabilité du test VIH proposé aux nourrissons dans les services pédiatriques, en Côte d'Ivoire, Significations pour la couverture du diagnostic pédiatrique

PubMed Central

Oga, Maxime; Brou, Hermann; Dago-Akribi, Hortense; Coffie, Patrick; Amani-Bossé, Clarisse; Ékouévi, Didier; Yapo, Vincent; Menan, Hervé; Ndondoki, Camille; Timité-Konan, M.; Leroy, Valériane

2014-01-01

Résumé Problème: Le dépistage VIH chez les enfants a rarement été au centre des préoccupations des chercheurs. Quand le dépistage pédiatrique a retenu l'attention, cela a été pour éclairer seulement sur les performances diagnostiques en ignorant même que le test pédiatrique comme bien d'autres peut s'accepter ou se refuser. Cet article met au cœur de son analyse les raisons qui peuvent expliquer qu'on accepte ou qu'on refuse de faire dépister son enfant. Objectif: Etudier chez les parents, les mères, les facteurs explicatifs de l'acceptabilité du test VIH des nourrissons de moins de six mois. Méthodes: Entretien semi-directif à passages répétés avec les parents de nourrissons de moins de six mois dans les formations sanitaires pour la pesée/vaccination et les consultations pédiatriques avec proposition systématique d'un test VIH pour leur nourrisson. Résultats: Nous retenons que la réalisation effective du test pédiatrique du VIH chez le nourrisson repose sur trois éléments. Primo, le personnel de santé par son discours (qui dénote de ses connaissances et perceptions même sur l'infection) orienté vers les mères influence leur acceptation ou non du test. Secundo, la mère qui par ses connaissances et perceptions même sur le VIH, dont le statut particulier, l'impression de bien-être chez elle et son enfant influence toute réalisation du test pédiatrique VIH. Tertio, l'environnement conjugal de la mère, particulièrement caractérisé par les rapports au sein du couple, sur la facilité de parler du test VIH et sa réalisation chez les deux parents ou chez la mère seulement sont autant de facteurs qui influencent la réalisation effective du dépistage du VIH chez l'enfant. Le principe préventif du VIH, et le désir de faire tester l'enfant ne suffisent pas à eux seuls pour aboutir à sa réalisation effective, selon certaines mères confrontées au refus du conjoint. A l'opposé, les autres mères refusant la r

[It is time to take cancer prevention seriously].

PubMed

Hill, Catherine

2015-06-01

Preventing cancer by reducing exposure to carcinogens is the only way to reduce the frequency of cancers in the population. We discuss the current situation of cancer prevention in France in the order of importance as measured by the risk, demonstrating the recent reversal of the national anti-tobacco policy, the large benefit that could be expected from a reduction in alcohol consumption, the low coverage of the population for papillomavirus and hepatitis B virus vaccinations. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

Phthalate induced toxicity in prostate cancer cell lines and effects of alpha lipoic acid.

PubMed

Kismali, G; Yurdakok-Dikmen, B; Kuzukiran, O; Arslan, P; Filazi, A

2017-01-01

The effects of dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate were investigated on human prostate cancer cell lines DU145 and PC3 in vitro. Standards of dimethyl phthalate, diethyl phthalate, di-isobutyl phthalate, dibutyl phthalate, benzyl butyl phthalate, and di-ethyl hexyl phthalate were used. Alpha lipoic acid was used as antioxidant compound. DU145 and PC3 human prostate carcinoma cells were used. MTT assay were used for cytotoxicity assay. A low dose proliferative effect of phthalates in vitro was observed. With the hypothesis of the inhibition of aerobic glycolysis activity in cancer treatment, α-lipoic acid was applied to cells; where as a contrary to previous studies, no change in the cell proliferation was observed. In combination with ALA, at IC50 and lower doses, an increase of the cytotoxic effect was found for DIBP, DBP and BBP; while for DMP, DEP and DEHP, a decrease was observed for DU145 cells. In PC3 cells, a decrease was observed for DMP, DEP and DBPs; while no significant difference were observed for DEHP, DIBP and BBP. The present study demonstrates preliminary information regarding the low dose proliferative effects of phthalates in prostate cancer in vitro (Tab. 2, Fig. 2, Ref. 65).

Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells.

PubMed

Eckman, Allison M; Tsakalozou, Eleftheria; Kang, Nayon Y; Ponta, Andrei; Bae, Younsoo

2012-07-01

To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG-p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na-micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively.

PMCA2 silencing potentiates MDA-MB-231 breast cancer cell death initiated with the Bcl-2 inhibitor ABT-263.

PubMed

Curry, Merril; Roberts-Thomson, Sarah J; Monteith, Gregory R

2016-09-30

PMCA2 overexpression in some breast cancers suggests that this calcium pump isoform may play a role in breast pathophysiology. To investigate PMCA2 as a potential drug target for breast cancer therapy, we assessed the functional consequence of PMCA2 silencing on cell death pathways and calcium signals in the basal-like MDA-MB-231 breast cancer cell line. Silencing PMCA2 expression alone has no effect on MDA-MB-231 cell viability, however, PMCA2 silencing promotes calcium-induced cell death initiated with the calcium ionophore ionomycin. Assessment of cytoplasmic calcium responses generated with various agents including ionomycin demonstrates that in MDA-MB-231 cells, PMCA2 does not play a major role in shaping global calcium signals. We also examined the ability of PMCA2 silencing to modulate caspase-dependent cell death triggered by a Bcl-2 inhibitor that is in clinical development for the treatment of various cancers, ABT-263 (Navitoclax). Despite the lack of effect on global calcium responses, PMCA2 silencing augmented Bcl-2 inhibitor (ABT-263)-mediated MDA-MB-231 breast cancer cell death. These studies provide evidence that PMCA2 inhibitors could sensitize PMCA2-positive breast cancers to cell death initiators that work through mechanisms involving the Bcl-2 survival pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

γ-Oryzanol reduces caveolin-1 and PCGEM1 expression, markers of aggressiveness in prostate cancer cell lines.

PubMed

Hirsch, Gabriela E; Parisi, Mariana M; Martins, Leo A M; Andrade, Claudia M B; Barbé-Tuana, Florencia M; Guma, Fátima T C R

2015-06-01

Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. γ-oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that γ-oryzanol may affect prostate cancer cells through the down regulation of the antioxidant genes and that phytosterols have anti-proliferative and apoptotic effects. There are evidences showing that some of the components of γ-oryzanol can modulate genes involved in the development and progression of prostate cancer, as caveolin-1 (Cav-1) and prostate specific androgen-regulated gene (PCGEM1). To determine the effects of γ-oryzanol on prostate cancer cell survival we evaluated the cell viability and biomass by MTT and sulforhodamine B assays, respectively. Cell death, cell cycle and pERK1/2 activity were assessed by flow cytometry. The changes in gene expression involved in the survival and progression of prostate cancer cav-1 and PCGEM1 genes were evaluated by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) and cav-1 protein by immunofluorescence followed by confocal microscopy analysis. We found that γ-oryzanol decreases cell viability and culture biomass by apoptosis and/or necrosis death in androgen unresponsive (PC3 and DU145) and responsive (LNCaP) cell lines, and signals through pERK1/2 in LNCaP and DU145 cells. γ-oryzanol also appears to block cell cycle progression at the G2/M in PC3 and LNCaP cells and at G0/G1 in DU145 cells. These effects were accompanied by a down regulation in the expression of the cav-1 in both androgen unresponsive cell lines and PCGEM1 gene in DU145 and LNCaP cells. In summary, we used biochemical and genetics approaches to demonstrate that γ-oryzanol show a promising adjuvant role in the treatment of prostate cancer. © 2015 Wiley Periodicals, Inc.

Seventh Joint Meeting of K-J-CaP and CaPSURE: extending the global initiative to improve prostate cancer management

PubMed Central

Akaza, Hideyuki; Kim, Choung Soo; Carroll, Peter; Choi, In Young; Chung, Byung Ha; Cooperberg, Matthew R.; Hirao, Yoshihiko; Hinotsu, Shiro; Horie, Shigeo; Lee, Ji Youl; Namiki, Mikio; Ng, Chi-Fai; Onozawa, Mizuki; Ozono, Seiichiro; Ueno, Satoru; Umbas, Rainy; Ye, Dingwei; Zhu, Gang

2014-01-01

This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea–Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year’s meeting was hosted for the first time in Korea which has recently established its own national database–K-CaP–to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable ‘template’ for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving

Seventh Joint Meeting of K-J-CaP and CaPSURE: extending the global initiative to improve prostate cancer management.

PubMed

Akaza, Hideyuki; Kim, Choung Soo; Carroll, Peter; Choi, In Young; Chung, Byung Ha; Cooperberg, Matthew R; Hirao, Yoshihiko; Hinotsu, Shiro; Horie, Shigeo; Lee, Ji Youl; Namiki, Mikio; Ng, Chi-Fai; Onozawa, Mizuki; Ozono, Seiichiro; Ueno, Satoru; Umbas, Rainy; Ye, Dingwei; Zhu, Gang

2014-01-01

This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea-Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year's meeting was hosted for the first time in Korea which has recently established its own national database-K-CaP-to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable 'template' for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving the

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

PubMed Central

Xie, Min; Vesuna, Farhad; Tantravedi, Saritha; Bol, Guus M.; Heerma van Voss, Marise R.; Nugent, Katriana; Malek, Reem; Gabrielson, Kathleen; van Diest, Paul J.; Tran, Phuoc T.; Raman, Venu

2017-01-01

Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. RK-33 treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) decreased proliferation and induced a G1 phase cell-cycle arrest. Conversely, the low DDX3–expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a radiosensitizer. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer. PMID:27634756

ICI 182,780-regulated gene expression in DU145 prostate cancer cells is mediated by estrogen receptor-beta/NFkappaB crosstalk.

PubMed

Leung, Yuet-Kin; Gao, Ying; Lau, Kin-Mang; Zhang, Xiang; Ho, Shuk-Mei

2006-04-01

Estrogen receptor (ER)-beta is the predominant ER subtype in prostate cancer (PCa). We previously demonstrated that ICI 182,780 (ICI), but not estrogens, exerted dose-dependent growth inhibition on DU145 PCa cells by an ER-beta-mediated pathway. Transcriptional profiling detected a greater than three-fold upregulation of seven genes after a 12-hour exposure to 1 microM ICI. Semiquantitative reverse transcriptase polymerase chain reaction confirmed the upregulation of four genes by ICI: interleukin-12alpha chain, interleukin-8, embryonic growth/differentiation factor, and RYK tyrosine kinase. Treatment with an ER-beta antisense oligonucleotide reduced cellular ER-beta mRNA and induced loss of expression of these genes. Sequence analysis revealed the presence of consensus NFkappaB sites, but not estrogen-responsive elements, in promoters of all four genes. Reporter assay and chromatin immunoprecipitation experiments demonstrated that ICI-induced gene expression could be mediated by crosstalk between ER-beta and the NFkappaB signaling pathway, denoting a novel mechanism of ER-beta-mediated ICI action. Therefore, combined therapies targeting ER-beta and NFkappaB signaling may be synergistic as treatment for PCa.

Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells

PubMed Central

Zhang, Yifei; Huang, Yixian; Zhang, Peng; Gao, Xiang; Gibbs, Robert B; Li, Song

2012-01-01

Background: The sigma-2 receptor is an attractive target for tumor imaging and targeted therapy because it is overexpressed in multiple types of solid tumors, including prostate cancer, breast cancer, and lung cancer. SV119 is a synthetic small molecule that binds to sigma-2 receptors with high affinity and specificity. This study investigates the utility of SV119 in mediating the selective targeting of liposomal vectors in various types of cancer cells. Methods: SV119 was covalently linked with polyethylene glycol-dioleyl amido aspartic acid conjugate (PEG-DOA) to generate a novel functional lipid, SV119-PEG-DOA. This lipid was utilized for the preparation of targeted liposomes to enhance their uptake by cancer cells. Liposomes with various SV119 densities (0, 1, 3, and 5 mole%) were prepared and their cellular uptake was investigated in several tumor cell lines. In addition, doxorubicin (DOX) was loaded into the targeted and unmodified liposomes, and the cytotoxic effect on the DU-145 cells was evaluated by MTT assay. Results: Liposomes with or without SV119-PEG-DOA both have a mean diameter of approximately 90 nm and a neutral charge. The incorporation of SV119-PEG-DOA significantly increased the cellular uptake of liposomes by the DU-145, PC-3, A549, 201T, and MCF-7 tumor cells, which was shown by fluorescence microscopy and the quantitative measurement of fluorescence intensity. In contrast, the incorporation of SV119 did not increase the uptake of liposomes by the normal BEAS-2B cells. In a time course study, the uptake of SV119 liposomes by DU-145 cells was also significantly higher at each time point compared to the unmodified liposomes. Furthermore, the DOX-loaded SV119 liposomes showed significantly higher cytotoxicity to DU-145 cells compared to the DOX-loaded unmodified liposomes. Conclusion: SV119 liposomes were developed for targeted drug delivery to cancer cells. The targeting efficiency and specificity of SV119 liposomes to cancer cells was

Brain stem hypoplasia associated with Cri-du-Chat syndrome.

PubMed

Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

2013-01-01

Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

Tobacco Use Initiation | Cancer Trends Progress Report

Cancer.gov

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Information non précise sur la taille du pénis en République Démocratique du Congo: à propos de 21 sources

PubMed Central

Mulenga, Philippe Cilundika; Kazadi, Alex Bukasa

2016-01-01

Introduction La taille du pénis constitue une préoccupation de beaucoup des gens actuellement et certains ne sont pas satisfaits de la dimension de leur pénis comme le montre l’étude de Tiggemann en 2008. Il existe relativement peu d'études sur le pénis en érection. Cela peut refléter les tabous culturels des chercheurs ou des médecins en interaction avec les hommes qui sont dans un état d’excitation sexuelle. Toutes fois, il est important pour les personnes qui annoncent des détails sur la taille du pénis d’annoncer d’abord les repères de la mesure du pénis puis ensuite donner les chiffres que proposent les chercheurs. Méthodes Notre enquête de type descriptif transversale s’est effectuée dans les deux grandes villes de la République Démocratique du Congo à savoir la ville de Kinshasa et la ville de Lubumbashi, pendant une période de deux ans soit de Mai 2014 à Mai 2016. Au total, 21 sources d’information ont constitué notre échantillon dont 8 à Kinshasa et 13 à Lubumbashi et nous avons trouvé cela suffisant car les sujets à caractère sexuel sont souvent rares chez nous. Les paramètres étudiés étaient: la nature de la source, la précision de la technique de la mesure, la présence de référence bibliographique, la longueur annoncée du pénis. Résultats La majorité des sources d’information sont faites des émissions de radio et de télévision (23,8%), ceci pourra s’expliquer par le fait que dans notre milieu il y a de plus en plus des chaines de radio et télévision et surtout dans les grandes villes. Concernant la précision de la technique de la mesure du pénis lors du partage du message sur la taille du pénis, l’étude nous montre que la majorité des sources d’information ne signale pas cela lorsqu’elles annoncent la taille du pénis au public soit 85,7%. Plusieurs sources ne déclarent pas les références bibliographiques (57,1%). Lorsqu’on regarde même les chiffres de la taille du p

TGF-Beta Induction of PMEPA1: Role in Bone Metastasis Due to Prostate Cancer

DTIC Science & Technology

2009-01-01

expresses renilla luciferase, in PC-3 (prostate cancer cells), and HepG2 ( hepatocarcinoma ) and A459 (lung cancer cells) known for their sensitivity to...bound PMEPA1 in prostate, breast, lung cancer cells and hepatocarcinoma cells. Prostate (PC-3, DU-145), breast (MDA-MB-231) and lung (A549) cancer...cells and hepatocarcinoma cells (HepG2) were grown until reaching cell layer reached near confluency. Cells were serum-starved for 4 hours and further

Small molecules, big players: the National Cancer Institute's Initiative for Chemical Genetics.

PubMed

Tolliday, Nicola; Clemons, Paul A; Ferraiolo, Paul; Koehler, Angela N; Lewis, Timothy A; Li, Xiaohua; Schreiber, Stuart L; Gerhard, Daniela S; Eliasof, Scott

2006-09-15

In 2002, the National Cancer Institute created the Initiative for Chemical Genetics (ICG), to enable public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. The ICG is a public-access research facility consisting of a tightly integrated team of synthetic and analytical chemists, assay developers, high-throughput screening and automation engineers, computational scientists, and software developers. The ICG seeks to facilitate the cross-fertilization of synthetic chemistry and cancer biology by creating a research environment in which new scientific collaborations are possible. To date, the ICG has interacted with 76 biology laboratories from 39 institutions and more than a dozen organic synthetic chemistry laboratories around the country and in Canada. All chemistry and screening data are deposited into the ChemBank web site (http://chembank.broad.harvard.edu/) and are available to the entire research community within a year of generation. ChemBank is both a data repository and a data analysis environment, facilitating the exploration of chemical and biological information across many different assays and small molecules. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings.

Cholestéatome du méat acoustique externe

PubMed Central

Azeddine, Lachkar; Aabach, Ahmed; Chouai, Mohamed; Elayoubi, Fahd; Ghailan, Mohamed Rachid

2016-01-01

Le cholestéatome du méat acoustique externe se définit comme une accumulation de kératine en regard d’une érosion osseuse de nature ostéitique. C’est une entité otologique rare ou peut diagnostiquée. Le but de notre travail est d’illustrer sur la base d’un cas un cholestéatome du méat acoustique externe. Il s’agit d’un patient âgé de 65 ans diabétique et hypertendu sous traitement, présentant depuis 3 mois une otalgie droite intense, insomniante, avec hypoacousie, otorrhée purulente minime et paralysie faciale droite grade V. Le diagnostic évoqué était dans un premier temps celui d’otite externe maligne. Il a été mis sous traitement antibiotique sans amélioration. L’examen otologique a trouvé une lésion ulcéro-bourgeonnante de la paroi postérieure du méat acoustique externe droit, une biopsie systématique de la lésion a été pratiquée et a conclu à un cholestéatome. Le patient a bénéficié d’une tympanoplastie en technique ouverte. Le cholestéatome du méat acoustique externe est rare, la symptomatologie clinique n’est pas spécifique, le scanner des rocher est d’un grand apport pour le diagnostic positif montrant un cratère osseux du méat acoustique externe. Le traitement dépend de l’extension des lésions allant des simples soins locaux à une tympanoplastie en technique ouverte. Le cholestéatome du méat acoustique externe peut revêtir plusieurs aspects, et prêter confusion avec d’autres pathologies du méat acoustique externe. PMID:28154624

Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis.

PubMed

De Lena, M; Barletta, A; Marzullo, F; Rabinovich, M; Leone, B; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriguez, R; Schittulli, F; Paradisco, A

1996-01-01

The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis. Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

PubMed

Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study.

PubMed

Bae, Sajin; Ulrich, Cornelia M; Neuhouser, Marian L; Malysheva, Olga; Bailey, Lynn B; Xiao, Liren; Brown, Elissa C; Cushing-Haugen, Kara L; Zheng, Yingye; Cheng, Ting-Yuan David; Miller, Joshua W; Green, Ralph; Lane, Dorothy S; Beresford, Shirley A A; Caudill, Marie A

2014-12-15

Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer. Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine, and trimethylamine N-oxide (TMAO)] and colorectal cancer risk among postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. We selected 835 matched case-control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). Colorectal cancer was assessed by self-report and confirmed by medical records over the mean of 5.2 years of follow-up. Baseline plasma choline metabolites were measured by LC/MS-MS. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% confidence interval, CI)(highest vs. lowest quartile) = 2.44 (0.93-6.40); P trend = 0.08], whereas plasma betaine was inversely associated with colorectal cancer overall [0.68 (0.47-0.99); P trend = 0.01] and with local/regional tumors [0.64 (0.42-0.99); P trend = 0.009]. Notably, the plasma betaine:choline ratio was inversely associated with colorectal cancer overall [0.56 (0.39-0.82); P trend = 0.004] as well as with proximal [0.66 (0.41-1.06); P trend = 0.049], rectal [0.27 (0.10-0.78); P trend = 0.02], and local/regional [0.50 (0.33-0.76); P trend = 0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25-9.16); P trend = 0.02] and with overall colorectal cancer risk among women with lower (vs. higher) plasma vitamin B12 levels (P interaction = 0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of colorectal cancer. The positive association between plasma TMAO and

Identification d'une loi thermo-élasto-viscoplastique en vue de la modélisation du laminage à chaud du cuivre

NASA Astrophysics Data System (ADS)

Moureaux, P.; Moto Mpong, S.; Remy, M.; Bouffioux, C.; Lecomte-Beckers, J.; Habraken, A. M.

2002-12-01

la mise au point d'un modèle de simulation de la dernière passe du laminage à chaud du cuivre ne présente à priori pas de problème du point de vue numérique pour un code d'éléments finis non linéaire. La collecte d'informations précises tant sur le procédé industriel que sur le comportement du matériau est par contre une opération non triviale. Cet article présente les diverses méthodes expérimentales mises en œuvre pour caractériser le matériau : essais de compression à chaud, mesures d'analyse thermique différentielle, essais de dilatométrie et de diffusivité. Les méthodes permettant d'identifier les paramètres de la loi élasto-visco-plastique de type Norton-Hoff à partir des essais sont présentées et une analyse bibliographique investigue le problème de la détermination du module de Young à haute température. Tant les hypothèses supplémentaires relatives au procédé et nécessaires au modèle que les résultats finaux sont résumés.

First breast cancer mammography screening program in Mexico: initial results 2005-2006.

PubMed

Rodríguez-Cuevas, Sergio; Guisa-Hohenstein, Fernando; Labastida-Almendaro, Sonia

2009-01-01

Breast cancer is the most frequent malignant neoplasia worldwide. In emergent countries as Mexico, an increase has been shown in frequency and mortality, unfortunately, most cases in advanced loco-regional stages developed in young women. The success of breast screening in mortality reduction has been observed since 1995 in Western Europe and the United States, where as many as 40% mortality reduction has been achieved. Most countries guidelines recommends an annual or biannual mammography for all women >40 years of age. In 2005, FUCAM, a nonlucrative civil foundation in Mexico join with Mexico City government, initiated the first voluntary mammography screening program for women >40 years of age residing in Mexico City's Federal District. Mammographies were carried out with analogical mammographs in specially designed mobile units and were performed in the area of women's domiciles. This report includes data from the first 96,828 mammographies performed between March 2005 and December 2006. There were 1% of mammographies in Breast Imaging Reporting and Data System 0, 4, or 5 and 208 out of 949 women with abnormal mammographies (27.7%) had breast cancer, a rate of 2.1 per thousand, most of them in situ or stage I (29.4%) or stage II (42.2%) nevertheless 21% of those women with abnormal mammography did not present for further clinical and radiologic evaluation despite being personally notified at their home addresses. The breast cancer rate of Mexican women submitted to screening mammography is lower than in European or North American women. Family history of breast cancer, nulliparity, absence of breast feeding, and increasing age are factors that increase the risk of breast cancer. Most cancers were diagnosed in women's age below 60 years (68.5%) with a mean age of 53.55 corroborating previous data published. It is mandatory to sensitize and educate our population with regard to accepting to visit the Specialized Breast Centers.

Cellular glutathione level does not predict ovarian cancer cells' resistance after initial or repeated exposure to cisplatin.

PubMed

Nikounezhad, Nastaran; Nakhjavani, Maryam; Shirazi, Farshad H

2017-05-01

Cisplatin resistance development is a major obstacle in ovarian cancer treatment. One of the most important mechanisms underlying cisplatin resistance is drug detoxification by glutathione. In the present study, the importance of initial or repeated exposure to cisplatin in glutathione dependent resistance was investigated. To this purpose, some cisplatin sensitive and resistant variants of human ovarian cancer cell lines providing an appropriate range of cisplatin sensitivity were selected. Clonogenic survival assay was performed to evaluate cisplatin resistance and intracellular contents of reduced (GSH) and oxidized (GSSG) glutathione were analyzed using an HPLC method. Our results indicated that the intracellular GSH and GSSG concentrations were nearly equal in A2780 and A2780CP cells, while the A2780CP cells showed 14 times more resistance than the A2780 cells after initial exposure to cisplatin. A2780-R1 and A2780-R3 cells which have been repeatedly exposed to cisplatin also showed no significant difference in glutathione content, even though A2780-R3 was about two times more resistant than A2780-R1. Moreover, intracellular GSH/GSSG ratio decreased in the resistant cells, reflecting a shift towards a more oxidizing intracellular environment indicative of oxidative stress. As a conclusion, it seems that although the intracellular glutathione concentration increases after repeated exposure to cisplatin, there is no clear correlation between the intracellular GSH content in ovarian cancer cells and their resistance to cisplatin neither after initial nor after repeated exposure to this drug.

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non-Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center.

PubMed

Dinglin, Xiao-Xiao; Ma, Shu-Xiang; Wang, Fang; Li, De-Lan; Liang, Jian-Zhong; Chen, Xin-Ru; Liu, Qing; Zeng, Yin-Duo; Chen, Li-Kun

2017-05-01

The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non-small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs. Copyright © 2017 Elsevier Inc. All rights

Conjugated Equine Estrogens and Breast Cancer Risk in the Women’s Health Initiative Clinical Trial and Observational Study

PubMed Central

Prentice, Ross L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Manson, JoAnn E.; Langer, Robert D.; Pettinger, Mary; Hendrix, Susan L.; Hubbell, F. Allan; Kooperberg, Charles; Kuller, Lewis H.; Lane, Dorothy S.; McTiernan, Anne; O’Sullivan, Mary Jo; Rossouw, Jacques E.; Anderson, Garnet L.

2009-01-01

The Women’s Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogenalone preparations. In 1993–2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women’s Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index. PMID:18448442

The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography.

PubMed

Beinat, Corinne; Haywood, Tom; Chen, Yun-Sheng; Patel, Chirag B; Alam, Israt S; Murty, Surya; Gambhir, Sanjiv Sam

2018-05-07

There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [ 18 F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer. The cellular uptake of [ 18 F]DASA-23 was evaluated in a panel of prostate cancer cell lines and compared to that of [ 18 F]FDG. The specificity of [ 18 F]DASA-23 to measure PKM2 levels in cell culture was additionally confirmed through the use of PKM2-specific siRNA. PET imaging studies were then completed utilizing subcutaneous prostate cancer xenografts using either PC3 or DU145 cells in mice. [ 18 F]DASA-23 uptake values over 60-min incubation period in PC3, LnCAP, and DU145 respectively were 23.4 ± 4.5, 18.0 ± 2.1, and 53.1 ± 4.6 % tracer/mg protein. Transient reduction in PKM2 protein expression with siRNA resulted in a 50.1 % reduction in radiotracer uptake in DU145 cells. Small animal PET imaging revealed 0.86 ± 0.13 and 1.6 ± 0.2 % ID/g at 30 min post injection of radioactivity in DU145 and PC3 subcutaneous tumor bearing mice respectively. Herein, we evaluated a F-18-labeled PKM2-specific radiotracer, [ 18 F]DASA-23, for the molecular imaging of prostate cancer with PET. [ 18 F]DASA-23 revealed rapid and extensive uptake levels in cellular uptake studies of prostate cancer cells; however, there was only modest tumor uptake when evaluated in mouse subcutaneous tumor models.

Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: a possible radioimmunotherapy to prostate carcinoma.

PubMed

Wang, Hsin-Yi; Lin, Wan-Yu; Chen, Mei-Chih; Lin, Teh; Chao, Chih-Hao; Hsu, Fu-Ning; Lin, Eugene; Huang, Chih-Yang; Luo, Tsai-Yueh; Lin, Ho

2013-05-01

Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our previous results have indicated the relevance of Her2 in the transition of the androgen requirement in prostate cancer cells. In this study, the effects of radioimmunotherapy against Her2 in prostate cancer were investigated. DU145, an androgen receptor-negative prostate cancer cell line, was used in vitro and in vivo to evaluate the effects of Herceptin labeled with a beta emitter, Rhenium-188 (Re-188). Its effects on cell growth, extent of apoptosis, the bio-distribution of Re-188 labeled Herceptin (Re-H), and protein levels were determined. Treatments with Re-188 and Re-H reduced the proliferation of DU145 cells in dose- and time-dependent manners compared to the Herceptin-treated group. Growth inhibition and apoptosis were induced after Re-H treatment; growth inhibition was more distinct in cells with high Her2/p-Her2 levels. Our in vivo xenograft studies revealed that Re-H treatment significantly retarded tumor growth and altered the levels of apoptosis-related proteins. The bio-distribution of Re-H in mice demonstrated a tissue-specific pattern. Importantly, the levels of p35 protein, which is related to cancer cell survival and invasion, dramatically decreased after Re-H treatment. Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer.

Trends in use and cost of initial cancer treatment in Ontario: a population-based descriptive study.

PubMed

de Oliveira, Claire; Bremner, Karen E; Pataky, Reka; Gunraj, Nadia; Haq, Mahbubul; Chan, Kelvin; Cheung, Winson Y; Hoch, Jeffrey S; Peacock, Stuart; Krahn, Murray D

2013-10-01

Cancer incidence and treatment-related costs are rising in Canada. We estimated health care use and costs in the first year after diagnosis for patients with 7 common types of cancer in Ontario to examine temporal trends in patterns of care and costs. We selected patients aged 19-44 years who had received a diagnosis of melanoma, breast cancer (female only), testicular cancer or thyroid cancer, in addition to patients aged 45 years and older who had received a diagnosis of breast (female only), prostate, lung or colorectal cancer, between 1997 and 2007. Patients were identified from the Ontario Cancer Registry. Using linked administrative databases, we determined use and costs of chemotherapy, radiotherapy, cancer-related surgery, other admissions to hospital and home care. We adjusted all costs to 2009 Canadian dollars. We identified 20 821 patients aged 19-44 years and 178 797 patients aged 45 years and older. The greatest increases in costs during the study period were for melanoma, breast cancer, colorectal cancer, lung cancer and prostate cancer (p < 0.05). For prostate and lung cancers, mean costs increased 50% (from $11 490 and $22 037 to $15 170 and $34 473, respectively). Mean costs doubled for breast (from $15 460 and $12 909 to $35 977 and $29 362 for younger and older patients, respectively) and colorectal cancers (from $24 769 to $43 964), and nearly tripled for melanoma (from $3581 to $8934). Costs related to hospital admissions accounted for the largest portion of total costs. The use of chemotherapy, radiotherapy and home care generally increased for all cancers. The significant increase in mean costs of initial cancer treatment among the patients included in this study was primarily due to more patients receiving adjuvant therapy and home care, and to the increasing expenditures for these services and cancer-related surgeries. Understanding trends in health care use and costs can help policy-makers to take the necessary measures to achieve a more

The Combined Association of Modifiable Risk Factors with Breast Cancer Risk in the Women's Health Initiative.

PubMed

Arthur, Rhonda; Wassertheil-Smoller, Sylvia; Manson, JoAnn E; Luo, Juhua; Snetselaar, Linda; Hastert, Theresa; Caan, Bette; Qi, Lihong; Rohan, Thomas

2018-06-01

Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of selected modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with risk of invasive breast cancer in the Women's Health Initiative (WHI). This study comprised 131,833 postmenopausal women, of whom 8,168 had breast cancer, who were enrolled in the WHI Observational Study or the WHI clinical trials. Cox proportional hazards regression was used to estimate the HRs and 95% confidence intervals (CI) for the association of the score with the risk of developing breast cancer overall and according to specific breast cancer clinicopathologic characteristics. There was a 4% reduction in the risk of breast cancer per unit increase in the HLI score. Compared with those with an HLI score in the lowest quintile level, those in the highest quintile level had 30%, 37%, and 30% lower risk for overall, ER + /PR + , and HER2 + breast cancer, respectively (HR = 0.70; 95% CI, 0.64-0.76; 0.63, 0.57-0.69; and 0.70; 0.55-0.90, respectively). We also observed inverse associations between the score and risk of breast cancer irrespective of nodal status, tumor grade, and stage of the disease. Most individual lifestyle factors were independently associated with the risk of breast cancer. Our findings support the view that promoting healthy lifestyle practices may be beneficial with respect to lowering risk of breast cancer among postmenopausal women. Cancer Prev Res; 11(6); 317-26. ©2018 AACR See related editorial by Friedenreich and McTiernan, p. 313 . ©2018 American Association for Cancer Research.

Green tea extract (epigallocatechin-3-gallate) reduces efficacy of radiotherapy on prostate cancer cells.

PubMed

Thomas, Francis; Holly, Jeff M P; Persad, Rajendra; Bahl, Amit; Perks, Claire M

2011-08-01

To assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. Prostate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potential was assessed using Western immunoblotting for manganese superoxide dismutase and copper zinc superoxide dismutase enzymes. Radiotherapy was delivered using a linear accelerator. Cell cycle analysis was performed using flow cytometry. Radiotherapy at 3.5 Gy induced a 5.9-fold increase in apoptosis of DU145 cells. Subapoptotic doses of EGCG (1.5-7.5 μM) significantly reduced ionizing radiation-induced apoptosis (P < .001), with the inhibitory effect of EGCG on ionizing radiation being most effective when added 30 minutes before radiotherapy (P < .001). In addition, when radiotherapy and EGCG were used together, an approximate 1.5-fold increase in manganese superoxide dismutase levels was seen compared with the control and a 2-fold increase compared with radiotherapy alone. Radiotherapy is effective in inducing apoptosis in DU145 cells, but its effect was significantly reduced in the presence of EGCG, and this was associated with an increase in the induction of manganese superoxide dismutase. Copyright © 2011 Elsevier Inc. All rights reserved.

Changing organizational culture: using the CEO cancer gold standard policy initiatives to promote health and wellness at a school of public health.

PubMed

Towne, Samuel D; Anderson, Kelsey E; Smith, Matthew Lee; Dahlke, Deborah Vollmer; Kellstedt, Debra; Purcell, Ninfa Pena; Ory, Marcia G

2015-09-03

Worksite wellness initiatives for health promotion and health education have demonstrated effectiveness in improving employee health and wellness. We examined the effects of a multifaceted health promotion campaign on organizational capacity to meet requirements to become CEO Cancer Gold Standard Accredited. We conducted an online survey to assess perceived organizational values and support for the five CEO Cancer Gold Standard Pillars for cancer prevention: tobacco cessation; physical activity; nutrition; cancer screening and early detection; and accessing information on cancer clinical trials. Baseline and follow-up surveys were sent 6-months apart to faculty, staff, and students at a school of public health to test the impact of a multifaceted health promotion campaign on perceived organizational change. Descriptive analyses were used to characterize percent improvement. Multivariate logistic regression analyses were used to control for participants' university status. The current organizational culture highly supported tobacco cessation at both time points. Significant improvements (p < .05) from baseline to follow-up were observed for questions measuring organizational values for 'prevention, screening, and early detection of cancer' and 'accessing cancer treatment and clinical trials'. Health promotion and education efforts using multiple approaches were effective to improve perceived organizational values and support for cancer prevention and early detection, and increase access to information about cancer clinical trials. Future studies are needed to examine broader impacts of implementing worksite health promotion initiatives.

Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells

PubMed Central

Liu, Chen-Chi; Lin, Shih-Pei; Hsu, Han-Shui; Yang, Shung-Haur; Lin, Chiu-Hua; Yang, Muh-Hwa; Hung, Mien-Chie; Hung, Shih-Chieh

2016-01-01

Targeting tumour-initiating cells (TICs) would lead to new therapies to cure cancer. We previously demonstrated that TICs have the capacity to survive under suspension conditions, while other cells undergo anoikis. Here we show that TICs exhibit increased phosphorylation levels of S727STAT3 because of PP2A inactivation. Collagen 17 gene expression is upregulated in a STAT3-dependent manner, which also stabilizes laminin 5 and engages cells to form hemidesmosome-like junctions in response. Blocking the PP2A-S727STAT3-collagen 17 pathway inhibits the suspension survival of TICs and their ability to form tumours in mice, while activation of the same pathway increases the suspension survival and tumour-initiation capacities of bulk cancer cells. The S727STAT3 phosphorylation levels correlate with collagen 17 expression in colon tumour samples, and correlate inversely with survival. Finally, this signalling axis enhances the ability of TIC to form tumours in mouse models of malignant lung cancer pleural effusion and spontaneous colon cancer metastasis. PMID:27306323

Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells.

PubMed

Liu, Chen-Chi; Lin, Shih-Pei; Hsu, Han-Shui; Yang, Shung-Haur; Lin, Chiu-Hua; Yang, Muh-Hwa; Hung, Mien-Chie; Hung, Shih-Chieh

2016-06-16

Targeting tumour-initiating cells (TICs) would lead to new therapies to cure cancer. We previously demonstrated that TICs have the capacity to survive under suspension conditions, while other cells undergo anoikis. Here we show that TICs exhibit increased phosphorylation levels of S727STAT3 because of PP2A inactivation. Collagen 17 gene expression is upregulated in a STAT3-dependent manner, which also stabilizes laminin 5 and engages cells to form hemidesmosome-like junctions in response. Blocking the PP2A-S727STAT3-collagen 17 pathway inhibits the suspension survival of TICs and their ability to form tumours in mice, while activation of the same pathway increases the suspension survival and tumour-initiation capacities of bulk cancer cells. The S727STAT3 phosphorylation levels correlate with collagen 17 expression in colon tumour samples, and correlate inversely with survival. Finally, this signalling axis enhances the ability of TIC to form tumours in mouse models of malignant lung cancer pleural effusion and spontaneous colon cancer metastasis.

Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

PubMed

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

ERBB2 Increases Metastatic Potentials Specifically in Androgen-Insensitive Prostate Cancer Cells

PubMed Central

Tome-Garcia, Jessica; Li, Dan; Ghazaryan, Seda; Shu, Limin; Wu, Lizhao

2014-01-01

Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145), it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP). In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines. PMID:24937171

Circulating estrogens and postmenopausal ovarian cancer risk in the Women’s Health Initiative Observational Study

PubMed Central

Trabert, Britton; Brinton, Louise A.; Anderson, Garnet L.; Pfeiffer, Ruth M.; Falk, Roni T.; Strickler, Howard D.; Sliesoraitis, Sarunas; Kuller, Lewis H.; Gass, Margery L.; Fuhrman, Barbara J.; Xu, Xia; Wentzensen, Nicolas

2016-01-01

Background Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women’s Health Initiative (WHI) Observational Study (OS). Methods We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via LC-MS/MS. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/non-serous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results Overall we observed modest ovarian cancer risk associations among women with higher levels of estrone [Odds Ratio (95% Confidence Interval) quintile (Q)5 vs. Q1: 1.54 (0.82–2.90), p-trend=0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06–3.88), p-trend=0.02; 1.86 (0.98–3.56), p-trend=0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone (2.65 (1.09–6.45), p-trend=0.01, p-heterogeneity=0.04), unconjugated estradiol (2.72 (1.04–7.14), p-trend=0.03, p-heterogeneity=0.02) and many of the 2-, 4-, and 16-pathway metabolites were positively associated with non-serous tumors. Conclusions Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with non-serous ovarian cancers. Impact These findings further support the heterogeneous etiology of ovarian cancer. PMID:26908437

Cancer initiation and progression: an unsimplifiable complexity

PubMed Central

Grizzi, Fabio; Di Ieva, Antonio; Russo, Carlo; Frezza, Eldo E; Cobos, Everardo; Muzzio, Pier Carlo; Chiriva-Internati, Maurizio

2006-01-01

Background Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. Conclusion There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours. PMID:17044918

ICI 182,780-Regulated Gene Expression in DU145 Prostate Cancer Cells Is Mediated by Estrogen Receptor-β/NFκB Crosstalk1

PubMed Central

Leung, Yuet-Kin; Gao, Ying; Lau, Kin-Mang; Zhang, Xiang; Ho, Shuk-Mei

2006-01-01

Abstract Estrogen receptor (ER)-β is the predominant ER subtype in prostate cancer (PCa). We previously demonstrated that ICI 182,780 (ICI), but not estrogens, exerted dose-dependent growth inhibition on DU145 PCa cells by an ER-β-mediated pathway. Transcriptional profiling detected a greater than three-fold upregulation of seven genes after a 12-hour exposure to 1 µM ICI. Semi-quantitative reverse transcriptase polymerase chain reaction confirmed the upregulation of four genes by ICI: interleukin-12α chain, interleukin-8, embryonic growth/differentiation factor, and RYK tyrosine kinase. Treatment with an ER-β antisense oligonucleotide reduced cellular ER-β mRNA and induced loss of expression of these genes. Sequence analysis revealed the presence of consensus NFκB sites, but not estrogen-responsive elements, in promoters of all four genes. Reporter assay and chromatin immunoprecipitation experiments demonstrated that ICI-induced gene expression could be mediated by crosstalk between ER-α and the NFκB signaling pathway, denoting a novel mechanism of ER-β-mediated ICI action. Therefore, combined therapies targeting ER-β and NFκB signaling may be synergistic as treatment for PCa. PMID:16756716

Le traumatisme du colon: l'expérience du CHU Hassan II de Fès

PubMed Central

Benjelloun, El Bachir; Hafid, Hasnai; Karim, Ibnmajdoub; Ousadden, Abdelmalek; Mazaz, Khalid; Taleb, Kahlid Ait

2012-01-01

Introduction Les traumatismes du colon sont associés à un risque majeur de complications septiques et de mortalité. Le but de notre étude est d’évaluer les circonstances, la prise en charge, le suivi et les facteurs pronostic de morbidité postopératoire des malades victimes d'un traumatisme colique. Méthodes Il s'agit d'une étude rétrospective sur une série de 49 patients opérés pour des plaies coliques aux services de chirurgie viscérale du CHU HASSAN II de Fès sur une période de 8 ans de juillet 2003 à juillet 2011. Résultats L’âge moyen de nos patients était de 25ans (16-70) avec une nette prédominance masculine (93.8%). Les plaies coliques secondaires à un traumatisme par arme blanche représentent 85% des cas (42 patients), suivi par les plaies iatrogènes au cours d'une coloscopie chez 6 patients (13%), puis les contusions abdominales chez 1 patient (2%). Les parties du cadre colique les plus touchées étaient le colon transverse chez 19 patients (38%) et le colon descendant chez 12 patients (24, 5%). Le colon sigmoïde était le segment le plus touché au cours d'une coloscopie4/6. Quarante-deux patients (85%) ont eu une suture primaire des plaies coliques, six patients (13%) une diversion fécale et un patient (2%) une résection-anastomose. Deux patients (4%) sont décédés suite à un choc septique. La morbidité globale était de 38,7% dominé essentiellement par l'infection de la paroi chez 14 patients et une péritonite post opératoire chez 3 patients. L'analyse univarié a montré une différence significatif en terme d'infection de la paroi entre le groupe colostomie versus suture simple (50% vs 20,9% p<0,05). L'atteinte du colon gauche et la réalisation d'une colostomie sont associés à un risque plus élevés de complications postopératoires. Conclusion La suture primaire peut être effectuée avec un faible taux de complications postopératoire chez la majorité des patients suite à un traumatisme du colon. PMID

Lay Patient Navigators' Perspectives of Barriers, Facilitators and Training Needs in Initiating Advance Care Planning Conversations With Older Patients With Cancer.

PubMed

Niranjan, Soumya J; Huang, Chao-Hui S; Dionne-Odom, J Nicholas; Halilova, Karina I; Pisu, Maria; Drentea, Patricia; Kvale, Elizabeth A; Bevis, Kerri S; Butler, Thomas W; Partridge, Edward E; Rocque, Gabrielle B

2018-04-01

Respecting Choices is an evidence-based model of facilitating advance care planning (ACP) conversations between health-care professionals and patients. However, the effectiveness of whether lay patient navigators can successfully initiate Respecting Choices ACP conversations is unknown. As part of a large demonstration project (Patient Care Connect [PCC]), a cohort of lay patient navigators underwent Respecting Choices training and were tasked to initiate ACP conversations with Medicare beneficiaries diagnosed with cancer. This article explores PCC lay navigators' perceived barriers and facilitators in initiating Respecting Choices ACP conversations with older patients with cancer in order to inform implementation enhancements to lay navigator-facilitated ACP. Twenty-six lay navigators from 11 PCC cancer centers in 4 states (Alabama, George, Tennessee, and Florida) completed in-depth, one-on-one semistructured interviews between June 2015 and August 2015. Data were analyzed using a thematic analysis approach. This evaluation identifies 3 levels-patient, lay navigator, and organizational factors in addition to training needs that influence ACP implementation. Key facilitators included physician buy-in, patient readiness, and navigators' prior experience with end-of-life decision-making. Lay navigators' perceived challenges to initiating ACP conversations included timing of the conversation and social and personal taboos about discussing dying. Our results suggest that further training and health system support are needed for lay navigators playing a vital role in improving the implementation of ACP among older patients with cancer. The lived expertise of lay navigators along with flexible longitudinal relationships with patients and caregivers may uniquely position this workforce to promote ACP.

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

PubMed

Goetz, Matthew P; Toi, Masakazu; Campone, Mario; Sohn, Joohyuk; Paluch-Shimon, Shani; Huober, Jens; Park, In Hae; Trédan, Olivier; Chen, Shin-Cheh; Manso, Luis; Freedman, Orit C; Garnica Jaliffe, Georgina; Forrester, Tammy; Frenzel, Martin; Barriga, Susana; Smith, Ian C; Bourayou, Nawel; Di Leo, Angelo

2017-11-10

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

[Hormonotherapy for breast cancer prevention: What about women with genetic predisposition to breast cancer?].

PubMed

Sénéchal, Claire; Reyal, Fabien; Callet, Nasrine; This, Pascale; Noguès, Catherine; Stoppa-Lyonnet, Dominique; Fourme, Emmanuelle

2016-03-01

In France, women carrying BRCA1/2 mutation, at an identified high risk of breast cancer are recommended to undergo breast MRI screening. That screening does not however prevent the risk of developing a breast cancer. The only alternative to breast cancer screening available in France is surgical prevention by prophylactic mastectomy. An interesting option for women who wish to reduce their breast cancer risk, but are unready for prophylactic mastectomy is a preventive hormonal treatment by aromatase inhibitors, or selective estrogens receptor modulators (SERMs). Reliable clinical trials show the efficiency of tamoxifen, raloxifen, exemestane, and anastrozole especially, in reducing breast cancer incidence by 33%, 34%, 65% and 53% respectively. This article tries to sum up the main published trials of breast cancer prevention with hormonal treatment, and presents the latest American and English clinical guidelines concerning hormonal prevention for women at high risk of breast cancer, and starts thinking about the possibilities of hormonoprevention, especially among women carrying a BRCA1/2 mutation in France. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection.

PubMed

Hwang, Jae Jin; Lee, Dong Ho; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

2015-04-28

To evaluate the incidence and clinical characteristics of gastric cancer (GC) in peptic ulcer patients with Helicobacter pylori (H. pylori) infection. Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed. Those with previous gastric ulcer (GU) and H. pylori infection were assigned to the HpGU-GC group (n = 86) and those with previous duodenal ulcer (DU) disease and H. pylori infection were assigned to the HpDU-GC group (n = 35). The incidence rates of GC in the HpGU-GC and HpDU-GC groups were analyzed. Data on demographics (age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia (IM)], outcome of eradication therapy for H. pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed. Univariate and multivariate analyses were performed to identify factors influencing GC development. The relative risk of GC was evaluated using a Cox proportional hazards model. The incidence rates of GC were 3.60% (86/2387) in the HpGU-GC group and 1.66% (35/2098) in the HpDU-GC group. The annual incidence was 0.41% in the HpGU-GC group and 0.11% in the HpDU-GC group. The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the HpGU-GC group than in the HpDU-GC group (86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P < 0.05). In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H. pylori infection were significantly associated with the development of GC (P < 0.05). There was no significant difference in the prognosis of GC patients between the HpGU-GC and HpDU-GC groups (P = 0.347). The relative risk of GC development in the HpGU-GC group compared to that of the HpDU-GC group, after correction for age and gender, was 1.71 (95%CI

Evaluating a bilingual patient navigation program for uninsured women with abnormal screening tests for breast and cervical cancer: implications for future navigator research.

PubMed

Simon, Melissa A; Tom, Laura S; Nonzee, Narissa J; Murphy, Kara R; Endress, Richard; Dong, XinQi; Feinglass, Joe

2015-05-01

The DuPage Patient Navigation Collaborative evaluated the Patient Navigation Research Program (PNRP) model for uninsured women receiving free breast or cervical cancer screening through the Illinois Breast and Cervical Cancer Program in DuPage County, Illinois. We used medical records review and patient surveys of 477 women to compare median follow-up times with external Illinois Breast and Cervical Cancer Program and Chicago PNRP benchmarks of performance. We examined the extent to which we mitigated community-defined timeliness risk factors for delayed follow-up, with a focus on Spanish-speaking participants. Median follow-up time (29.0 days for breast and 56.5 days for cervical screening abnormalities) compared favorably to external benchmarks. Spanish-speaking patients had lower health literacy, lower patient activation, and more health care system distrust than did English-speaking patients, but despite the prevalence of timeliness risk factors, we observed no differences in likelihood of delayed (> 60 days) follow-up by language. Our successful replication and scaling of the PNRP navigation model to DuPage County illustrates a promising approach for future navigator research.

Lapatinib-resistant cancer cells possessing epithelial cancer stem cell properties develop sensitivity during sphere formation by activation of the ErbB/AKT/cyclin D2 pathway.

PubMed

Ohnishi, Yuichi; Yasui, Hiroki; Kakudo, Kenji; Nozaki, Masami

2016-11-01

Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR)/ErbB2, has antiproliferative effects and is used to treat patients with ErbB2-positive metastatic breast cancer. In the present study, we examined the effects of lapatinib on growth of oral and prostate cancer cells. Oral squamous cell carcinoma (OSCC) cell lines HSC3, HSC4 and Ca9-22 were sensitive to the antiproliferative effects of lapatinib in anchorage-dependent culture, but the OSCC cell lines KB and SAS and the prostate cancer cell line DU145 were resistant to lapatinib. Phosphorylation levels of EGFR in all cell lines decreased during lapatinib treatment in anchorage‑dependent culture. Furthermore, the phosphorylation levels of ErbB2, ErbB3 and Akt and the protein levels of cyclin D1 were decreased by lapatinib treatment of HSC3, HSC4 and Ca9-22 cells. ErbB3 was not expressed and cyclin D1 protein levels were not altered by lapatinib treatment in KB, DU145 and SAS cells. The phosphorylation of ErbB2 and AKT was not affected by lapatinib in SAS cells and was not detected in KB and DU145 cells. Lapatinib-resistant cell lines exhibited sphere-forming ability, and SAS cells developed sensitivity to lapatinib during sphere formation. The phosphorylation levels of ErbB2 and AKT and protein levels of cyclin D2 increased during sphere formation of SAS cells and decreased with lapatinib treatment. In addition, sphere formation of SAS cells was inhibited by the AKT inhibitor MK2206. AKT phosphorylation and cyclin D2 levels in SAS spheres were decreased by MK2206 treatment. SAS cells expressed E-cadherin, but not vimentin and KB cells expressed vimentin, but not E-cadherin. DU145 cells expressed vimentin and E-cadherin. These results suggested that phosphorylation of EGFR and ErbB2 by cell detachment from the substratum induces the AKT pathway/cyclin D2-dependent sphere growth in SAS epithelial cancer stem-like cells, thereby rendering SAS spheres sensitive to lapatinib treatment.

[Cancer prevention in France: Implication of health professionals].

PubMed

Lasserre, Andrea; Gaillot, Julie; Deutsch, Antoine; Chauvet, Claire; Bessette, Dominique; Ancellin, Raphaëlle

2017-03-01

Almost 40% of cancers are attributable to preventable cancer risk factors related to behavior. Health professionals must take into account the respective weight of the different causes of cancer to enforce effective cancer prevention. Their involvement is needed on several levels. In primary prevention, not only for vaccinations, detection and support the withdrawal of addiction, but also by a greater consideration in their patients of all cancer risk behavioral factors. This involvement is essential in the care and monitoring of patients with cancer. Thus, enhancing patient compliance with cancer prevention tips (stopping smoking, reducing alcohol consumption, practice physical activity, physical inactivity reduction, reduction of overweight, adopting a diversified and balanced diet) appears as a new challenge of personalized care in oncology that not only aims to reduce the incidence of cancer but also to reduce the risks of morbidity and long-term mortality. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Initial Results of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome.

PubMed

Howarth, Dt R; Lum, Sharon S; Esquivel, Pamela; Garberoglio, Carlos A; Senthil, Maheswari; Solomon, Naveenraj L

2015-10-01

Multigene panel testing for hereditary cancer risk has recently become commercially available; however, the impact of its use on patient care is undefined. We sought to evaluate results from implementation of panel testing in a multidisciplinary cancer center. We performed a retrospective review of consecutive patients undergoing genetic testing after initiating use of multigene panel testing at Loma Linda University Medical Center. From February 13 to August 25, 2014, 92 patients were referred for genetic testing based on National Comprehensive Cancer Network guidelines. Testing was completed in 90 patients. Overall, nine (10%) pathogenic mutations were identified: five BRCA1/2, and four in non-BRCA loci. Single-site testing identified one BRCA1 and one BRCA2 mutation. The remaining mutations were identified by use of panel testing for hereditary breast and ovarian cancer. There were 40 variants of uncertain significance identified in 34 patients. The use of panel testing more than doubled the identification rate of clinically significant pathogenic mutations that would have been missed with BRCA testing alone. The large number of variants of uncertain significance identified will require long-term follow-up for potential reclassification. Multigene panel testing provides additional information that may improve patient outcomes.

Body Mass Index and Waist Circumference in Relation to Lung Cancer Risk in the Women's Health Initiative

PubMed Central

Kim, Mimi; Hunt, Julie R.; Chlebowski, Rowan T.; Rohan, Thomas E.

2008-01-01

Investigators in several epidemiologic studies have observed an inverse association between body mass index (BMI) and lung cancer risk, while others have not. The authors used data from the Women's Health Initiative to study the association of anthropometric factors with lung cancer risk. Over 8 years of follow-up (1998–2006), 1,365 incident lung cancer cases were ascertained among 161,809 women. Cox proportional hazards models were used to estimate hazard ratios adjusted for covariates. Baseline BMI was inversely associated with lung cancer in current smokers (highest quintile vs. lowest: hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.42, 0.92). When BMI and waist circumference were mutually adjusted, BMI was inversely associated with lung cancer risk in both current smokers and former smokers (HR = 0.40 (95% CI: 0.22, 0.72) and HR = 0.61 (95% CI: 0.40, 0.94), respectively), and waist circumference was positively associated with risk (HR = 1.56 (95% CI: 0.91, 2.69) and HR = 1.50 (95% CI: 0.98, 2.31), respectively). In never smokers, height showed a borderline positive association with lung cancer. These findings suggest that in smokers, BMI is inversely associated with lung cancer risk and that waist circumference is positively associated with risk. PMID:18483121

Initial perceptions of palliative care: An exploratory qualitative study of patients with advanced cancer and their family caregivers.

PubMed

Collins, Anna; McLachlan, Sue-Anne; Philip, Jennifer

2017-10-01

Despite evidence for early integration of palliative care for people with advanced cancer and their families, patterns of late engagement continue. Prior research has focused on health professionals' attitudes to palliative care with few studies exploring the views of patients and their carers. To explore initial perceptions of palliative care when this is first raised with patients with advanced cancer and their families in Australian settings. Cross-sectional, prospective, exploratory qualitative design, involving narrative-style interviews and underpinned by an interpretative phenomenological framework. Purposively sampled, English-speaking, adult patients with advanced cancer ( n = 30) and their nominated family caregivers ( n = 25) recruited from cancer services at a tertiary metropolitan hospital in Melbourne, Victoria, Australia. Three major themes evolved which represent the common initial perceptions of palliative care held by patients with advanced cancer and their carers when this concept is first raised: (1) diminished care, (2) diminished possibility and (3) diminished choice. Palliative care was negatively associated with a system of diminished care which is seen as a 'lesser' treatment alternative, diminished possibilities for hope and achievement of ambitions previously centred upon cure and diminished choices for the circumstances of one's care given all other options have expired. While there is an increasing move towards early integration of palliative care, this study suggests that patient and caregiver understandings have not equally progressed. A targeted public health campaign is warranted to disentangle understandings of palliative care as the 'institutional death' and to reframe community rhetoric surrounding palliative care from that of disempowered dying to messages of choice, accomplishment and possibility.

Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

NASA Astrophysics Data System (ADS)

Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

2017-08-01

This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

Knowledge, attitude, and experience of cervical cancer and screening among Sub-saharan African female students in a UK University.

PubMed

Ogbonna, Faith Sopuruchukwu

2017-01-01

Cervical cancer is one of the major diseases that affect women of child bearing age. Its main cause is the human papilloma virus; although, other associated factors have been evidenced to increase its risk. Pap-smear screening and vaccination which has been shown to be successful in reducing the incidence and prevalence of the disease in developed countries, has been neglected in developing countries due to lack of knowledge, misconceptions, and cultural beliefs. A cross-sectional study involving only female Sub-Saharan Africa (SSA) students in a UK university setting. One hundred and eighty-six (42%) African female students were recruited from the 442 SSA students attending one of the major Universities in the UK. Seventy-one (38.2%) of the students were aware of cervical screening, but only 20 (10.8%) reported having knowledge of cervical cancer. A small percentage of about 26.9% (50 Students) were already part of this screening program; although, 81 (43.5%) showed willingness to participate in future screening programs. More so, it was evident that student's perception was dependent on their experience of the disease (P = 000) just as their participation in screening program was dependent on their awareness level (P ≤ 0.01). Female African students from the SSA region have poor knowledge of the disease which influenced their attitude toward screening. More needs to be carried out to increase awareness and uptake of screening within the school environment as university setting provides a viable platform to promote healthy behavior. Résumé Contexte: Le cancer du col de l'utérus est l'une des principales maladies qui touchent les femmes en âge de procréer. Sa principale cause est le virus du papillome humain; Bien que, d'autres facteurs associés ont été mis en évidence pour augmenter son risque. Le dépistage du Pap et la vaccination, qui s'est avéré efficace pour réduire l'incidence et la prévalence de la maladie dans les pays développés, a �

Piwil2 is reactivated by HPV oncoproteins and initiates cell reprogramming via epigenetic regulation during cervical cancer tumorigenesis.

PubMed

Feng, Dingqing; Yan, Keqin; Zhou, Ying; Liang, Haiyan; Liang, Jing; Zhao, Weidong; Dong, Zhongjun; Ling, Bin

2016-10-04

The human papillomavirus (HPV) oncoproteins E6 and E7 are risk factors that are primarily responsible for the initiation and progression of cervical cancer, and they play a key role in immortalization and transformation by reprogramming differentiating host epithelial cells. It is unclear how cervical epithelial cells transform into tumor-initiating cells (TICs). Here, we observed that the germ stem cell protein Piwil2 is expressed in pre-cancerous and malignant lesions of the cervix and cervical cancer cell lines with the exception of the non-HPV-infected C33a cell line. Knockdown of Piwil2 by shRNA led to a marked reduction in proliferation and colony formation, in vivo tumorigenicity, chemo-resistance, and the proportion of cancer stem-like cells. In contrast, Piwil2 overexpression induced malignant transformation of HaCaT cells and the acquisition of tumor-initiating capabilities. Gene-set enrichment analysis revealed embryonic stem cell (ESC) identity, malignant biological behavior, and specifically, activation targets of the cell reprogramming factors c-Myc, Klf4, Nanog, Oct4, and Sox2 in Piwil2-overexpressing HaCaT cells. We further confirmed that E6 and E7 reactivated Piwil2 and that E6 and E7 overexpression resulted in a similar gene-set enrichment pattern as Piwil2 overexpression in HaCaT cells. Moreover, Piwil2 overexpression or E6 and E7 activation induced H3K9 acetylation but reduced H3K9 trimethylation, which contributed to the epigenetic reprogramming and ESC signature maintenance, as predicted previously. Our study demonstrates that Piwil2, reactivated by the HPV oncoproteins E6 and E7, plays an essential role in the transformation of cervical epithelial cells to TICs via epigenetics-based cell reprogramming.

[Detection and evaluation of malnutrition in oncology: What tools, what type of cancer and for what purposes?].

PubMed

Khan, Sylvie; Alibay, Taher Arif; Merad, Mansouria; DiPalma, Mario; Raynard, Bruno; Antoun, Sami

2016-09-01

Malnutrition is frequently observed in oncology. The consequences on patient survival, chemotherapy toxicities and quality of life need to be identified and treated appropriately. A set of tools are available that enable clinicians to diagnose and detect malnutrition. Each tool must consider three items: the patient's current nutritional status, reduced food intake and the characteristics of the underlying disease. The parameters and thresholds used to detect malnutrition differ according to the objective pursued. It can be economic, increasing the reimbursement of hospital stays, it can help define prognostic risk groups or its purpose can be to initiate nutritional treatment. Recent data support the assessment of parameters such as inflammatory markers, decreased muscle mass (i.e. sarcopenia) whose diagnosis is associated with a worse outcome and the quantification of food intake with simplified methods. The benefit for the patient of detecting malnutrition will be the initiation of a nutritional treatment when its efficacy has been demonstrated. A case in point is the nutritional support provided to malnourished patients before surgery with benefits in terms of mortality and morbidity and in certain head and neck cancer situations where nutritional support is systematically implemented. It is probably relevant to detect and initiate treatment early in order to promote muscle anabolism. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Salen-Mn compounds induces cell apoptosis in human prostate cancer cells through promoting AMPK activity and cell autophagy

PubMed Central

Tang, Xiaoshuang; Jia, Jing; Li, Feng; Liu, Wei; Yang, Chao; Jin, Bin; Shi, Qi; Wang, Xinyang; He, Dalin; Guo, Peng

2017-01-01

Currently only docetaxel has been approved to be used in the chemotherapy of prostate cancer and new drugs are urgent need. Salen-Mn is a novel type of synthetic reagent bionic and exerts remarkable anticancer activities. However, the effect of Salen-Mn on human prostate cancer has not been elucidated yet. In this study, we found that treatment of PC-3 and DU145 human prostate cancer cells with Salen-Mn inhibited cell growth in dose and time dependent manner. Moreover, Salen-Mn induced cell apoptosis, and increased the expression of apoptotic proteins, such as cleaved caspase-3, cleaved PARP, and Bax, in PC-3 and DU145 prostate cancer cells. Furthermore, we found that Salen-Mn induced expression of LC3-I/II, which is protein marker of cell autophagy, in both dose and time dependent manners; in addition, Salen-Mn increased the phosphorylation of AMPK, suggesting that Salen-Mn increase cell autophagy through activating AMPK pathway. On the other hand, when PC-3 and DU145 cells were treated with Salen-Mn and 3-MA, an inhibitor of cell autophagy, the inhibitory effect of Salen-Mn on cell growth and the induction of apoptotic proteins were decreased. In addition, we found that Salen-Mn inhibited the growth of PC-3 cell xenografts in nude mice. In summary, our results indicate that Salen-Mn suppresses cell growth through inducing AMPK activity and autophagic cell death related cell apoptosis in prostate cancer cells and suggest that Salen-Mn and its derivatives could be new options for the chemical therapeutics in the treatment of prostate cancer. PMID:29156794

An alternative for cost-effective remediation of depleted uranium (DU) at certain environmental restoration sites.

PubMed

Miller, M; Galloway, B; VanDerpoel, G; Johnson, E; Copland, J; Salazar, M

2000-02-01

Numerous sites in the United States and around the world are contaminated with depleted uranium (DU) in various forms. A prevalent form is fragmented DU originating from various scientific tests involving high explosives and DU during weapon development programs, at firing practice ranges, or war theaters where DU was used in armor-piercing projectiles. The contamination at these sites is typically very heterogeneous, with discreet, visually identifiable DU fragments mixed with native soil. That is, the bulk-averaged DU activity is quite low, while specific DU fragments, which are distinct from the soil matrix, have much higher specific activity. DU is best known as a dark, black metal that is nearly twice as dense as lead, but DU in the environment readily weathers (oxidizes) to a distinctive bright yellow color that is readily visible. While the specific activity (amount of radioactivity per mass of soil) of DU is relatively low and presents only a minor radiological hazard, the fact that it is radioactive and visually identifiable makes it desirable to remove the DU "contamination" from the environment. The typical approach to conducting this DU remediation is to use radiation detection instruments to identify the contaminant and separate it from the adjacent soil, packaging it for disposal as radioactive waste. This process can be performed manually or by specialized, automated equipment. Alternatively, in certain situations a more cost-effective approach might be simple mechanical or gravimetric separation of the DU fragments from the host soil matrix. At SNL/NM, both the automated and simple mechanical approaches have recently been employed. This paper discusses the pros/cons of the two approaches.

[The construction of cancer as an object of scientific study and sanitary problem in Argentina: discourses, experimental practices and institutional initiatives, 1903-1922].

PubMed

Buschini, José D

2014-01-01

This article analyzes the construction of cancer as a sanitary problem and an object of scientific inquiry in Argentina in the first two decades of the twentieth century. It considers the acquisition and circulation of foreign knowledge on the subject, the context in which the first experimental developments arose, the institutional initiatives promoted by the medical profession and the way in which state authorities and civil society were enlisted to further these initiatives. There is a detailed examination of the process of creating the Instituto de Medicina Experimental, a center wholly devoted to the study and treatment of cancer, which was inaugurated in 1922, symbolically ending the first phase of constructing cancer as a problem in the country.

W.E.B. DuBois and the Concepts of Race and Class.

ERIC Educational Resources Information Center

Green, Dan S.; Smith, Earl

1983-01-01

Summarizes and analyzes W.E.B. DuBois's publications on race and class, particularly as he observed the relationships between White and Black Americans from about 1890 to the 1960s. Contends that DuBois's work has been seriously underrated and cites William J. Wilson's work as corroborating and extending DuBois's theories. (CJM)

Non-steroidal Anti-inflammatory Drugs and Cancer Risk in Women: Results from the Women’s Health Initiative

PubMed Central

Brasky, Theodore M.; Liu, Jingmin; White, Emily; Peters, Ulrike; Potter, John D.; Walter, Roland B.; Baik, Christina S.; Lane, Dorothy S.; Manson, JoAnn E.; Vitolins, Mara Z.; Allison, Matthew A.; Tang, Jean Y.; Wactawski-Wende, Jean

2017-01-01

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risks of cancers at several sites in some studies; however, we recently reported no association between their use and total cancer risk in women in a prospective study. Here we examine the association between NSAIDs and total and site-specific cancer incidence in the large, prospective Women’s Health Initiative (WHI). 129,013 women were recruited to participate in the WHI at 40 US clinical centers from 1993 to 1998 and followed prospectively. After 9.7 years of follow-up, 12,998 incident, first primary, invasive cancers were diagnosed. NSAID use was systematically collected at study visits. We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs use and total and site-specific cancer risk. Relative to non-use, consistent use (i.e., use at baseline and year 3 of follow-up) of any NSAID was not associated with total cancer risk (HR 1.00, 95% CI: 0.94–1.06). Results for individual NSAIDs were similar to the aggregate measure. In site-specific analyses, NSAIDs were associated with reduced risks of colorectal cancer, ovarian cancer, and melanoma. Our study confirms a chemopreventive benefit for colorectal cancer in women and gives preliminary evidence for a reduction of the risk of some rarer cancers. NSAIDs’ benefit on cancer risk was limited to specific sites and not evident when total cancer risk was examined. This information may be of importance when NSAIDs are considered as chemopreventive agents. PMID:24599876

Sustainable growth, the DuPont way.

PubMed

Holliday, C

2001-09-01

Like many manufacturers, DuPont traditionally has grown by making more and more "stuff." And its business growth has been proportional to the amount of raw materials and energy used--as well as the resulting waste and emissions from operations. Over the years, though, DuPont became aware that cheap supplies of nonrenewable resources wouldn't be endlessly available and that the earth's ecosystems couldn't indefinitely absorb the waste and emissions of production and consumption. Chad Holliday, chairman and CEO of DuPont, believes strongly in the challenge of sustainable growth and makes the business case for it: By using creativity and scientific knowledge effectively, he says, companies can provide strong returns for shareholders and grow their businesses--while also meeting the human needs of societies around the world and reducing the environmental footprint of their operations and products. In fact, a focus on sustainability can help identify new products, markets, partnerships, and intellectual property and lead to substantial business growth. Holliday describes how DuPont developed a three-pronged strategy to translate the concept of sustainability into nuts-and-bolts business practices. Focusing on integrated science, knowledge intensity, and productivity improvement, the strategy was accompanied by a new way to measure progress quantitatively. Sustainable growth should be viewed not as a program for stepped-up environmental performance but as a comprehensive way of doing business, one that delivers tremendous economic value and opens up new opportunities. Ultimately, companies will find that they can generate substantial business value through sustainability while both enhancing the quality of life around the world and protecting the environment.

A TRACER 3D Co-Culture tumour model for head and neck cancer.

PubMed

Young, Miki; Rodenhizer, Darren; Dean, Teresa; D'Arcangelo, Elisa; Xu, Bin; Ailles, Laurie; McGuigan, Alison P

2018-05-01

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment and have been shown to play an important role in the progression of cancer. To probe these tumour-stroma interactions, we incorporated CAFs derived from head and neck cancer patients and squamous carcinoma cells of the hypopharynx (FaDu) into the Tissue Roll for the Analysis of Cellular Environment and Response (TRACER) platform to establish a co-culture platform that simulates the CAF-tumour microenvironmental interactions in head and neck tumours. TRACER culture involves infiltrating cells into a thin fibrous scaffold and then rolling the resulting biocomposite around a mandrel to generate a 3D and layered structure. Patterning the fibrous scaffold biocomposite during fabrication enables control over the specific location of different cell populations in the rolled configuration. Here, we optimized the seeding densities and configurations of the CAF and FaDu cell tissue sections to enable a robust 3D co-culture system under normoxic conditions. Co-culture of CAFs with FaDu cells produced negligible effects on radiation resistance, but did produce increases in proliferation rate and invasive cell migration at 24 and 48 h of culture. Our study provides the basis for use of our in vitro co-culture TRACER model to investigate the tumour-stroma interactions, and to bridge the translational gap between preclinical and clinical studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

The HSP90 inhibitor 17-PAG effectively inhibits the proliferation and migration of androgen-independent prostate cancer cells

PubMed Central

Peng, Ruixian; Li, Zhenyu; Lin, Zhiyuan; Wang, Yang; Wang, Wei; Hu, Bo; Wang, Xilong; Zhang, Jun; Wang, Yangyun; Zhou, Renyuan; Lu, Chunhua; Shen, Yuemao; Wang, Jifeng; Shi, Guowei

2015-01-01

Castration-resistant prostate cancer (CRPC) ultimately occurs after a period of treatment with androgen deprivation therapy. Furthermore, CRPC patients can only derive limited survival benefits from traditional cytotoxic drugs. HSP90, which is a molecular chaperone, plays a vital role in client protein processing and maintaining the function of cells. HSP90 is usually overexpressed in prostate cancer tissues, which makes it a potential target for managing prostate cancer. Geldanamycin (GA), which was recognized as the first natural HSP90 inhibitor, has demonstrated potent anti-tumor efficacy in large-scale pre-clinical studies, but its application in the clinic is not permitted due to its liver toxicity and unstable physical properties. In this study, we report a new GA derivative, 17-PAG (17-(propynylamino)-17-demethoxygeldanamycin), which demonstrates highly effective anti-tumor activity against androgen-independent prostate cancer cells. Treating cells with 17-PAG dose-dependently suppressed proliferation, reduced colony formation and induced apoptosis of DU-145/C4-2B cells. Moreover, 17-PAG suppressed the migration and invasion of DU-145/C4-2B cells by regulating epithelial mesenchymal transition (EMT). 17-PAG also downregulated the HSP90 client proteins, including Her2, EGFR, C-Raf, AKT, p-AKT, and CDK4. Animal assays confirmed that 17-PAG shows strong anti-tumor effects with no obvious organ toxicity in DU-145 cell xenografted nude mice. These results provide us with a potential target for treating androgen-independent prostate cancer in a safe and effective manner. PMID:26693070

Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

PubMed Central

Virant-Klun, Irma; Stimpfel, Martin

2016-01-01

Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

Using Collaborative Simulation Modeling to Develop a Web-Based Tool to Support Policy-Level Decision Making About Breast Cancer Screening Initiation Age

PubMed Central

Burnside, Elizabeth S.; Lee, Sandra J.; Bennette, Carrie; Near, Aimee M.; Alagoz, Oguzhan; Huang, Hui; van den Broek, Jeroen J.; Kim, Joo Yeon; Ergun, Mehmet A.; van Ravesteyn, Nicolien T.; Stout, Natasha K.; de Koning, Harry J.; Mandelblatt, Jeanne S.

2017-01-01

Background There are no publicly available tools designed specifically to assist policy makers to make informed decisions about the optimal ages of breast cancer screening initiation for different populations of US women. Objective To use three established simulation models to develop a web-based tool called Mammo OUTPuT. Methods The simulation models use the 1970 US birth cohort and common parameters for incidence, digital screening performance, and treatment effects. Outcomes include breast cancers diagnosed, breast cancer deaths averted, breast cancer mortality reduction, false-positive mammograms, benign biopsies, and overdiagnosis. The Mammo OUTPuT tool displays these outcomes for combinations of age at screening initiation (every year from 40 to 49), annual versus biennial interval, lifetime versus 10-year horizon, and breast density, compared to waiting to start biennial screening at age 50 and continuing to 74. The tool was piloted by decision makers (n = 16) who completed surveys. Results The tool demonstrates that benefits in the 40s increase linearly with earlier initiation age, without a specific threshold age. Likewise, the harms of screening increase monotonically with earlier ages of initiation in the 40s. The tool also shows users how the balance of benefits and harms varies with breast density. Surveys revealed that 100% of users (16/16) liked the appearance of the site; 94% (15/16) found the tool helpful; and 94% (15/16) would recommend the tool to a colleague. Conclusions This tool synthesizes a representative subset of the most current CISNET (Cancer Intervention and Surveillance Modeling Network) simulation model outcomes to provide policy makers with quantitative data on the benefits and harms of screening women in the 40s. Ultimate decisions will depend on program goals, the population served, and informed judgments about the weight of benefits and harms. PMID:29376135

In vivo anti-cancer activity of Korean Angelica gigas and its major pyranocoumarin decursin.

PubMed

Lee, Hyo Jeong; Lee, Hyo Jung; Lee, Eun Ok; Lee, Jae Ho; Lee, Kuen Sung; Kim, Kwan Hyun; Kim, Sung-Hoon; Lü, Junxuan

2009-01-01

We have reported that a 10-herbal traditional formula containing Korean Angelica gigas Nakai (AGN) exerts potent anti-cancer efficacy and identified decursin and decursinol angelate (DA) from AGN as novel anti-androgens. Here, we determined whether AGN would exert in vivo anti-cancer activity and whether decursin or DA could account for its efficacy. The AGN ethanol extract was tested against the growth of mouse Lewis lung cancer (LLC) allograft in syngenic mice or human PC-3 and DU145 prostate cancer xenograft in immunodeficient mice. The pharmacokinetics of decursin and DA were determined. The AGN extract significantly inhibited LLC allograft growth (30 mg/kg) and PC-3 and DU145 xenograft growth (100 mg/kg) without affecting the body weight of the host mice. Biomarker analyses revealed decreased cell proliferation (Ki67, PCNA), decreased angiogenesis (VEGF, microvessel density) and increased apoptosis (TUNEL, cPARP) in treated tumors. Decursin and DA injected intraperitoneally were rapidly hydrolyzed to decursinol. Decursinol and decursin at 50 mg/kg inhibited LLC allograft growth to the same extent, comparable to 30 mg AGN/kg. Therefore the AGN extract possessed significant in vivo anti-cancer activity, but decursin and DA only contributed moderately to that activity, most likely through decursinol.

Tectonic-1 contributes to the growth and migration of prostate cancer cells in vitro

PubMed Central

WANG, ZHIJUN; GAO, YI; LIU, YUSHAN; CHEN, JIE; WANG, JUNKAI; GAN, SISHUN; XU, DANFENG; CUI, XINGANG

2015-01-01

Tectonic-1 (TCTN1) is an upstream gene involved in embryonic development. The aim of the present study was to investigate the effect of the TCTN1 gene on the viability and migration of prostate cancer cells. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of TCTN1 in PC-3 and DU145 prostate cancer cells. Cell viability and proliferation were measured using MTT and colony formation assays, and the distribution of cells in phases of the cell cycle was determined using flow cytometry. Cell migration was detected using a Transwell assay. The results demonstrated that TCTN1 was widely expressed in several human prostate cancer cell lines. Knockdown of the TCTN1 gene by RNA interference markedly suppressed cell viability and colony formation in the PC-3 and DU145 cell lines. Cell cycle progression was also arrested by TCTN1 silencing. In addition, knockdown of the TCTN1 gene led to the inhibition of cell migration in the two cell lines. These findings confirmed the direct association between the TCTN1 gene and prostate cancer growth in vitro. With further understanding and clinical investigation, this indicates the potential for future development of a novel marker for early detection and gene therapy for prostate cancer. PMID:26310786

Lambeaux autofermants pour le traitement des brulures electriques du scalp par haut voltage

PubMed Central

Hafidi, J.; El Mazouz, S.; El Mejatti, H.; Fejjal, N.; Gharib, N.E.; Abbassi, A.; Belmahi, A.M.

2011-01-01

Summary Les brûlures électriques par haut voltage sont responsables de gros dégâts tissulaires en immédiat et dans les jours suivant l’accident du fait de la chaleur importante dégagée par effet joule et de la thrombose microvasculaire évolutive. Les pertes de substances du scalp secondaires à ces brûlures nécessitent une couverture par lambeaux vu la destruction du périoste et du calvarium en regard. De juin 1997 à juin 2008, 15 patients ont été traités pour des pertes de substance du scalp secondaires à des brûlures électriques par haut voltage de diamètre allant de 8 à 11 cm et siégeant dans la région tonsurale. Ces patients ont été opérés dans la première semaine suivant l’accident. Les pertes de substance du scalp de taille moyenne secondaires à ces brûlures peuvent être couvertes per primam de façon fiable par des lambeaux locaux axialisés et multiples. Nous relatons l’expérience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc, dans la gestion et la prise en charge de ces brûlures. PMID:22262963

Bladder cancer discussed on the internet: a systematic analysis of gender differences of initial posters on an online discussion board.

PubMed

Lippka, Yannick; Patschan, Oliver; Todenhöfer, Tilmann; Schwentner, Christian; Gutzeit, Andreas; Merseburger, Axel S; Horstmann, Marcus

2013-01-01

To evaluate gender differences of initial posters in threads dealing with bladder cancer on an online discussion board. 529 threads opened between 09/2005 and 03/2012 were screened on the largest German speaking bladder cancer online discussion board. 366 threads fulfilled the requirements for this study. Gender, age, number, status of concern and oncological situation of initiating posters as well as their motives and language style were analyzed following a standardized protocol. Threads were initiated in 45% (164/366) by men and in 55% (202/366) by women. Mean age of male initiating posters was 50 years and of female posters 44 years (p < 0.001). Of males 80% (132/164) were concerned patients and 20% (32/164) relatives or friends. Of females they were 39% (78/202) and 61% (124/202), respectively (p < 0.001). In general motives for initial posting were focused on medical information and did not differ between both genders. 81% of the posters asked for medical information or therapeutic recommendations regarding diagnosis, treatment and prognosis. However, women significantly more often expressed their wish for emotional support (p = 0.034) and in tendency wanted to share their experiences with others (p = 0.057). Language analysis revealed that women significantly more often used a tentative language style than men (p = 0.003). Even though women are less often affected by bladder cancer, they are more active -especially for their concerned family members - on the evaluated discussion board than men. Whereas both genders equally often ask for medical information, women more often want to share their experiences and look for emotional support.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro.

PubMed

Palethorpe, Helen M; Leach, Damien A; Need, Eleanor F; Drew, Paul A; Smith, Eric

2018-04-10

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo , providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro

PubMed Central

Palethorpe, Helen M.; Leach, Damien A.; Need, Eleanor F.; Drew, Paul A.; Smith, Eric

2018-01-01

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo, providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome. PMID:29721186

Small RNAs Targeting Transcription Start Site Induce Heparanase Silencing through Interference with Transcription Initiation in Human Cancer Cells

PubMed Central

Pu, Jiarui; Mei, Hong; Zhao, Jun; Huang, Kai; Zeng, Fuqing; Tong, Qiangsong

2012-01-01

Heparanase (HPA), an endo-h-D-glucuronidase that cleaves the heparan sulfate chain of heparan sulfate proteoglycans, is overexpressed in majority of human cancers. Recent evidence suggests that small interfering RNA (siRNA) induces transcriptional gene silencing (TGS) in human cells. In this study, transfection of siRNA against −9/+10 bp (siH3), but not −174/−155 bp (siH1) or −134/−115 bp (siH2) region relative to transcription start site (TSS) locating at 101 bp upstream of the translation start site, resulted in TGS of heparanase in human prostate cancer, bladder cancer, and gastric cancer cells in a sequence-specific manner. Methylation-specific PCR and bisulfite sequencing revealed no DNA methylation of CpG islands within heparanase promoter in siH3-transfected cells. The TGS of heparanase did not involve changes of epigenetic markers histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 27 trimethylation (H3K27me3) or active chromatin marker acetylated histone H3 (AcH3). The regulation of alternative splicing was not involved in siH3-mediated TGS. Instead, siH3 interfered with transcription initiation via decreasing the binding of both RNA polymerase II and transcription factor II B (TFIIB), but not the binding of transcription factors Sp1 or early growth response 1, on the heparanase promoter. Moreover, Argonaute 1 and Argonaute 2 facilitated the decreased binding of RNA polymerase II and TFIIB on heparanase promoter, and were necessary in siH3-induced TGS of heparanase. Stable transfection of the short hairpin RNA construct targeting heparanase TSS (−9/+10 bp) into cancer cells, resulted in decreased proliferation, invasion, metastasis and angiogenesis of cancer cells in vitro and in athymic mice models. These results suggest that small RNAs targeting TSS can induce TGS of heparanase via interference with transcription initiation, and significantly suppress the tumor growth, invasion, metastasis and angiogenesis of cancer cells. PMID

Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound.

PubMed

Weitz, Andrew C; Lee, Nan Sook; Yoon, Chi Woo; Bonyad, Adrineh; Goo, Kyo Suk; Kim, Seaok; Moon, Sunho; Jung, Hayong; Zhou, Qifa; Chow, Robert H; Shung, K Kirk

2017-01-01

Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145) and bladder (T24/83) cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84). In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making.

Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound

PubMed Central

Weitz, Andrew C.; Lee, Nan Sook; Yoon, Chi Woo; Bonyad, Adrineh; Goo, Kyo Suk; Kim, Seaok; Moon, Sunho; Jung, Hayong; Zhou, Qifa; Chow, Robert H.; Shung, K. Kirk

2017-01-01

Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145) and bladder (T24/83) cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84). In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making. PMID:28824873

Proprietes ionochromes et photochromes de derives du polythiophene

NASA Astrophysics Data System (ADS)

Levesque, Isabelle

La synthese et la caracterisation de derives regioreguliers du polythiophene ont ete effectuees en solution et sur des films minces. La spectroscopie UV-visible de ces derives a permis de constater qu'ils peuvent posseder des proprietes chromiques particulieres selon le stimulus auquel ils sont soumis. Par exemple, une augmentation de la temperature permet en effet aux polymeres de passer d'une couleur violette a jaune, et ce, a l'etat solide aussi bien qu'en solution. Ces proprietes chromiques semblent regies par une transition conformationnelle (plane a non-plane) de la chaine principale. Ce travail avait pour but de mieux comprendre l'influence de l'organisation des chaines laterales sur les transitions chromiques. Deux derives synthetises possedant des chaines laterales sensibles aux cations alcalins se sont averes etre ionochromes en plus d'etre thermochromes. Il s'agit d'un polymere comportant des chaines laterales de type oligo(oxyethylene) et d'un autre comportant un groupement ether couronne specifique aux ions lithium. Les effets chromiques observes sont expliques par des interactions non-covalentes des cations avec les atomes d'oxygene des chaines laterales dans le cas du premier polymere, et par l'insertion de l'ion Li + dans la cavite de l'ether couronne dans le cas du second polymere. Ces interactions semblent provoquer une diminution de l'organisation induisant ainsi une torsion de la chaine principale. Les deux polymeres semblent specifiques a certains cations et pourraient donc servir comme detecteurs optiques. La specificite aux ions Li+ du second polymere pourrait aussi permettre la conduction ionique, en plus de la conductivite electronique caracteristique des polythiophenes, ce qui pourrait s'averer utile dans le cas de batteries legeres entierement faites de polymeres et de sels de lithium. D'autres derives comportant des chaines laterales de type azobenzene se sont averes etre photochromes en plus d'etre thermochromes. Le groupement lateral a

Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

Cancer.gov

DESCRIPTION (provided by applicant): Cancer stem cells (CSC) are now recognized as the main cause for initiation, promotion and progression of most of the cancers, including colorectal cancer (CRC). Despite this fact, efficacy of chemopreventive agents towards CSC generation leading to cancer initiation and tumorigenesis has not yet been well- defined. |

Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

PubMed Central

Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-01-01

Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative.

PubMed

Bogaerts, Jan; Sydes, Matthew R; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J; Law, Kate; Trimble, Ted; Seymour, Matthew

2015-02-01

The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

DU Processing Efficiency and Reclamation: Plasma Arc Melting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imhoff, Seth D.; Aikin, Jr., Robert M.; Swenson, Hunter

The work described here corresponds to one piece of a larger effort to increase material usage efficiency during DU processing operations. In order to achieve this goal, multiple technologies and approaches are being tested. These technologies occupy a spectrum of technology readiness levels (TRLs). Plasma arc melting (PAM) is one of the technologies being investigated. PAM utilizes a high temperature plasma to melt materials. Depending on process conditions, there are potential opportunities for recycling and material reclamation. When last routinely operational, the LANL research PAM showed extremely promising results for recycling and reclamation of DU and DU alloys. The currentmore » TRL is lower due to machine idleness for nearly two decades, which has proved difficult to restart. This report describes the existing results, promising techniques, and the process of bringing this technology back to readiness at LANL.« less

Initial results of the oesophageal and gastric cancer registry from the Comunidad Valenciana.

PubMed

Escrig, Javier; Mingol, Fernando; Martí, Roberto; Puche, José; Trullenque, Ramón; Barreras, José Antonio; Asencio, Francisco; Aguiló, Javier; Navarro, José Manuel; Alberich, Carmen; Salas, Dolores; Lacueva, Francisco Javier

2017-10-01

To evaluate the initial results of the oesophagogastric cancer registry developed for the Sociedad Valenciana de Cirugía and the Health Department of the Comunidad Valenciana (Spain). Fourteen of the 24 public hospitals belonging to the Comunidad Valenciana participated. All patients with diagnosis of oesophageal or gastric carcinomas operated from January 2013 to December 2014 were evaluated. Demographic, clinical and pathological data were analysed. Four hundred and thirty-four patients (120 oesophageal carcinomas and 314 gastric carcinomas) were included. Only two hospitals operated more than 10 patients with oesophageal cancer per year. Transthoracic oesophaguectomy was the most frequent approach (84.2%) in tumours localized within the oesophagus. A total gastrectomy was performed in 50.9% patients with gastroesophageal junction (GOJ) carcinomas. Postoperative 30-day and 90-day mortality were 8% and 11.6% in oesophageal carcinoma and 5.9 and 8.6% in gastric carcinoma. Before surgery, middle oesophagus carcinomas were treated mostly (76,5%) with chemoradiotherapy. On the contrary, lower oesophagus and GOJ carcinomas were treated preferably with chemotherapy alone (45.5 and 53.4%). Any neoadjuvant treatment was administered to 73.6% of gastric cancer patients. Half patients with oesophageal carcinoma or gastric carcinoma received no adjuvant treatment. This registry revealed that half patients with oesophageal cancer were operated in hospitals with less than 10 cases per year at the Comunidad Valenciana. Also, it detected capacity improvement for some clinical outcomes of oesophageal and gastric carcinomas. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Identification of CD166 as a Surface Marker for Enriching Prostate Stem/Progenitor and Cancer Initiating Cells

PubMed Central

Wang, Shunyou; Tran, Linh M.; Goldstein, Andrew S.; Lawson, Devon; Chen, Donghui; Li, Yunfeng; Guo, Changyong; Zhang, Baohui; Fazli, Ladan; Gleave, Martin; Witte, Owen N.; Garraway, Isla P.; Wu, Hong

2012-01-01

New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin-;Sca1+;CD49fhi (LSChi), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSChi subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSChi and Pten null LSChi. Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics. PMID:22880034

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

PubMed

Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+- liver cells deficient for p53 and Rb.

PubMed

Matondo, Ramadhan B; Toussaint, Mathilda Jm; Govaert, Klaas M; van Vuuren, Luciel D; Nantasanti, Sathidpak; Nijkamp, Maarten W; Pandit, Shusil K; Tooten, Peter Cj; Koster, Mirjam H; Holleman, Kaylee; Schot, Arend; Gu, Guoqiang; Spee, Bart; Roskams, Tania; Rinkes, Inne Borel; Schotanus, Baukje; Kranenburg, Onno; de Bruin, Alain

2016-08-23

The long term prognosis of liver cancer patients remains unsatisfactory because of cancer recurrence after surgical interventions, particularly in patients with viral infections. Since hepatitis B and C viral proteins lead to inactivation of the tumor suppressors p53 and Retinoblastoma (Rb), we hypothesize that surgery in the context of p53/Rb inactivation initiate de novo tumorigenesis.We, therefore, generated transgenic mice with hepatocyte and cholangiocyte/liver progenitor cell (LPC)-specific deletion of p53 and Rb, by interbreeding conditional p53/Rb knockout mice with either Albumin-cre or Cytokeratin-19-cre transgenic mice.We show that liver cancer develops at the necrotic injury site after surgical resection or radiofrequency ablation in p53/Rb deficient livers. Cancer initiation occurs as a result of specific migration, expansion and transformation of cytokeratin-19+-liver (CK-19+) cells. At the injury site migrating CK-19+ cells formed small bile ducts and adjacent cells strongly expressed the transforming growth factor β (TGFβ). Isolated cytokeratin-19+ cells deficient for p53/Rb were resistant against hypoxia and TGFβ-mediated growth inhibition. CK-19+ specific deletion of p53/Rb verified that carcinomas at the injury site originates from cholangiocytes or liver progenitor cells.These findings suggest that human liver patients with hepatitis B and C viral infection or with mutations for p53 and Rb are at high risk to develop tumors at the surgical intervention site.

Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+- liver cells deficient for p53 and Rb

PubMed Central

Govaert, Klaas M; van Vuuren, Luciel D; Nantasanti, Sathidpak; Nijkamp, Maarten W; Pandit, Shusil K; Tooten, Peter CJ; Koster, Mirjam H; Holleman, Kaylee; Schot, Arend; Gu, Guoqiang; Spee, Bart; Roskams, Tania; Rinkes, Inne Borel; Schotanus, Baukje; Kranenburg, Onno; de Bruin, Alain

2016-01-01

The long term prognosis of liver cancer patients remains unsatisfactory because of cancer recurrence after surgical interventions, particularly in patients with viral infections. Since hepatitis B and C viral proteins lead to inactivation of the tumor suppressors p53 and Retinoblastoma (Rb), we hypothesize that surgery in the context of p53/Rb inactivation initiate de novo tumorigenesis. We, therefore, generated transgenic mice with hepatocyte and cholangiocyte/liver progenitor cell (LPC)-specific deletion of p53 and Rb, by interbreeding conditional p53/Rb knockout mice with either Albumin-cre or Cytokeratin-19-cre transgenic mice. We show that liver cancer develops at the necrotic injury site after surgical resection or radiofrequency ablation in p53/Rb deficient livers. Cancer initiation occurs as a result of specific migration, expansion and transformation of cytokeratin-19+-liver (CK-19+) cells. At the injury site migrating CK-19+ cells formed small bile ducts and adjacent cells strongly expressed the transforming growth factor β (TGFβ). Isolated cytokeratin-19+ cells deficient for p53/Rb were resistant against hypoxia and TGFβ-mediated growth inhibition. CK-19+ specific deletion of p53/Rb verified that carcinomas at the injury site originates from cholangiocytes or liver progenitor cells. These findings suggest that human liver patients with hepatitis B and C viral infection or with mutations for p53 and Rb are at high risk to develop tumors at the surgical intervention site. PMID:27323406

Immunotherapy and patients treated for cancer with microsatellite instability.

PubMed

Colle, Raphaël; Cohen, Romain; Cochereau, Delphine; Duval, Alex; Lascols, Olivier; Lopez-Trabada, Daniel; Afchain, Pauline; Trouilloud, Isabelle; Parc, Yann; Lefevre, Jérémie H; Fléjou, Jean-François; Svrcek, Magali; André, Thierry

2017-01-01

Microsatellite instability (MSI) is a tumor phenotype linked to somatic or germline (Lynch syndrome) inactivating alterations of DNA mismatch repair genes. A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer. MSI tumors are characterized by dense immune infiltration and high load of tumor neo-antigens. Growing evidence is accumulating on the efficacy of immune checkpoint inhibition for patients treated for MSI solid tumors. We present a comprehensive overview of MSI phenotype, its biological landscape and current diagnostic methods. Then we focus on MSI as a predictive biomarker of response to immune checkpoint inhibition in the context of colorectal cancer and non-colorectal tumors. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Detection of skeletal muscle metastases on initial staging of lung cancer: a retrospective case series.

PubMed

Bocchino, Marialuisa; Valente, Tullio; Somma, Francesco; de Rosa, Ilaria; Bifulco, Marco; Rea, Gaetano

2014-03-01

Estimation of skeletal muscle metastases (SMMs) at the time of diagnosis and/or initial staging of lung cancer. Retrospective evaluation of clinical charts and imaging data suggestive of SMMs of patients with histology-proved lung cancer over a 5-year period. SMMs were identified in 46 out of 1,754 patients. Single and multiple (62.9% of cases) SMMs were detected by total body multi-detector computed tomography (MDCT). They were associated with poorly differentiated (43%) and advanced adenocarcinomas (52%) without clinically relevant symptoms and/or signs. Psoas and buttock muscles were most frequently involved (33.3%). MDCT findings consisted of well-defined homogeneously hyperdense oval masses (31%), lesions with ring-like enhancement and central hypoattenuation (68%), or large abscess-like necrotic lesions (24%). Sonography revealed well-defined hypoechoic masses (41.6%), ill-defined hypoechoic lesions (33.3%), or anechoic areas with a necrotic centre (25%). Positron emission tomography revealed that all SMMs were metabolically active. SMMs are uncommon but not negligible in lung cancer, with an estimated prevalence of 2.62% in our series. Although histology remains the recommended method, use of high-performance imaging techniques and increased clinical suspicion may improve their early detection. Efforts addressing their effect on the natural history of lung cancer are needed.

Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

PubMed Central

Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

2013-01-01

Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

Curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.

PubMed

Liu, Jianbo; Li, Min; Wang, Yuewei; Luo, Jianchao

2017-08-01

Curcumin has been reported as a radiosensitizer in prostate cancer. But the underlying mechanism is not well understood. In this study, we firstly assessed how curcumin affects the expression of miR-143/miR-145 cluster. Then, we investigated whether miR-143 is involved in regulation of radiosensitivity and its association with autophagy in prostate cancer cells. Our data showed that PC3, DU145 and LNCaP cells treated with curcumin had significantly restored miR-143 and miR-145 expression. Curcumin showed similar effect as 5-AZA-dC on reducing methylation of CpG dinucleotides in miR-143 promoter. In addition, curcumin treatment reduced the expression of DNMT1 and DNMT3B, which contribute to promoter hypermethylation of the miR-143/miR-145 cluster. Therefore, we infer that curcumin can restore miR-143 and miR-145 expression via hypomethylation. MiR-143 overexpression and curcumin pretreatment enhanced radiation induced cancer cell growth inhibition and apoptosis. MiR-143 and curcumin remarkably reduced radiation-induced autophagy in PC3 and DU145 cells. MiR-143 overexpression alone also reduced the basal level of autophagy in DU145 cells. Mechanistically, miR-143 can suppress autophagy in prostate cancer cells at least via downregulating ATG2B. Based on these findings, we infer that curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.

[Homeopathy in cancer patients: What does the "best" evidence tell us?

PubMed

de Nonneville, Alexandre; Gonçalves, Anthony

2018-04-01

Homeopathic medicines are used by many patients with cancer, usually alongside conventional treatment. A recent report by the European Academies' Science Advisory Council concluded that "that there are no robust and reproducible evidence that homeopathy is effective". This literature review aims to make the analysis of published controlled randomized trials involving homeopathic treatment in the field of oncology. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

In Vivo Imaging of Branched Chain Amino Acid Metabolism in Prostate Cancer

DTIC Science & Technology

2013-08-01

model more closely mimicking human metabolism by assessing four prostate cancer cell lines: PC-3, DU-145, LNCaP and LAPC-4. The PC-3 cells had...Although the xenograph BCAT activity was 2.5 fold higher than cells alone (approaching human levels), the tumors grew very poorly (volumes ≤ 0.2 cc...assessment of prostate cancer (see Appendix 1: Revised Statement of Work). Specifically, as part of these cell - culture and xenograph experiments we

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women’s Health Initiative Randomized Trial

PubMed Central

Anderson, G. L.; Sarto, G. E.; Haque, R.; Runowicz, C. D.; Aragaki, A. K.; Thomson, C. A.; Howard, B. V.; Wactawski-Wende, J.; Chen, C.; Rohan, T. E.; Simon, M. S.; Reed, S. D.; Manson, J. E.

2016-01-01

Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women’s Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results: After 5.6 years’ median intervention and 13 years’ median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. PMID:26668177

Les inconvénients de perdre du poids

PubMed Central

Bosomworth, N. John

2012-01-01

Résumé Objectif Explorer les raisons pour lesquelles la perte de poids à long terme échoue la plupart du temps et évaluer les conséquences de diverses trajectoires pondérales, y compris la stabilité, la perte et le gain. Source des données Les études qui évaluent les paramètres pondéraux dans la population sont en majorité observationnelles. Des données probantes de niveau I ont été publiées pour évaluer l’influence des interventions relatives au poids sur la mortalité et la qualité de vie. Message principal Seulement un petit pourcentage des personnes qui désirent perdre du poids réussissent à le faire de manière durable. La mortalité est la plus faible chez les personnes se situant dans la catégorie de poids élevé-normal et surpoids. La trajectoire pondérale la plus sécuritaire est la stabilité du poids avec une optimisation de la condition physique et métabolique. Il est démontré que la mortalité est plus faible chez les personnes ayant des comorbidités reliées à l’obésité si elles perdent du poids. Il est aussi établi que la qualité de vie sur le plan de la santé est meilleure chez les personnes obèses qui perdent du poids. Par contre, la perte de poids chez une personne obèse autrement en santé est associée à une mortalité accrue. Conclusion La perte de poids est recommandable seulement chez les personnes qui ont des comorbidités reliées à l’obésité. Les personnes obèses en santé qui veulent perdre du poids devraient être informées qu’il peut y avoir des risques à le faire. Une stratégie qui se traduit par un indice de masse corporelle stable avec une condition physique et métabolique optimisée, peu importe le poids, est l’option d’intervention la plus sécuritaire en ce qui concerne le poids.

American Cancer Society lung cancer screening guidelines.

PubMed

Wender, Richard; Fontham, Elizabeth T H; Barrera, Ermilo; Colditz, Graham A; Church, Timothy R; Ettinger, David S; Etzioni, Ruth; Flowers, Christopher R; Gazelle, G Scott; Kelsey, Douglas K; LaMonte, Samuel J; Michaelson, James S; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Sullivan, Daniel C; Travis, William; Walter, Louise; Wolf, Andrew M D; Brawley, Otis W; Smith, Robert A

2013-01-01

Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. Copyright © 2013 American Cancer Society, Inc.

Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort.

PubMed

Nwizu, Ngozi N; Marshall, James R; Moysich, Kirsten; Genco, Robert J; Hovey, Kathleen M; Mai, Xiaodan; LaMonte, Michael J; Freudenheim, Jo L; Wactawski-Wende, Jean

2017-08-01

Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women's Health Initiative Observational Study. Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. All analyses were conducted two-sided. Results: During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95% CI, 1.08-1.20); findings were similar in analyses limited to 34,097 never-smokers (HR, 1.12; 95% CI, 1.04-1.22). Associations were observed for breast (HR, 1.13; 95% CI, 1.03-1.23), lung (HR, 1.31; 95% CI, 1.14-1.51), esophagus (HR, 3.28; 95% CI, 1.64-6.53), gallbladder (HR, 1.73; 95% CI, 1.01-2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02-1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94-2.67). Conclusions: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255-65. ©2017 AACR . ©2017 American Association for Cancer

Dépistage précoce des retards du développement moteur

PubMed Central

Harris, Susan R.

2016-01-01

Résumé Objectif Décrire le test HINT (Harris Infant Neuromotor Test), un test d’évaluation du développement neuromoteur chez les nourrissons publié en 2010, qui s’appuie sur les normes canadiennes et peut être utilisé pour dépister les retards du développement moteur durant la première année de la vie. Qualité des données D’abondantes recherches ont été publiées sur la fiabilité intra-évaluateur, inter-évaluateur et test-retest ainsi que sur la validité convergente, prédictive, du contenu et des groupes connus du test HINT, de même que sur la sensibilité, la spécificité et les valeurs prédictives négatives et positives des inquiétudes des parents, telles qu’évaluées par le test HINT. La plupart des données probantes sont de niveau II. Message principal Il est important de diagnostiquer les retards du développement moteur durant la première année de vie, car ils sont souvent le signe de retards du développement généralisés ou de déficiences précises, telles que la paralysie cérébrale. Les inquiétudes des parents quant au développement moteur de leur enfant sont une valeur prédictive robuste de diagnostics subséquents de retard du développement moteur. Conclusion Seul le dépistage précoce des retards du développement moteur, initialement par l’entremise d’outils de dépistage comme le test HINT, permet de recommander le patient à une intervention précoce qui profiterait tant à l’enfant qu’à sa famille. PMID:27521405

Cancer métaplasique du sein: à propos d'un cas

PubMed Central

Babahabib, Moulay Abdellah; Chennana, Adil; Hachi, Aymen; Kouach, Jaoud; Moussaoui, Driss; Dhayni, Mohammed

2014-01-01

Les carcinomes métaplasiques du sein sont des tumeurs rares. Ils constituent un groupe hétérogène de tumeurs définis selon l'organisation mondiale de la santé comme étant un carcinome canalaire infiltrant mais comportant des zones de remaniements métaplasiques (de type épidermoïde, à cellules fusiformes, chondroïde et osseux ou mixte), qui varient de quelques foyers microscopiques à un remplacement glandulaire complet. Les aspects cliniques et radiologiques ne sont pas spécifiques. Le traitement associe la chirurgie, la radiothérapie et la chimiothérapie. L'hormonothérapie n'a pas de place. Le pronostic est sombre. L'histopathologie combinée à l'immunohistochimie permet de poser un diagnostic sure. Etant donné que la prise en charge thérapeutique est limitée, une nouvelle approche moléculaire pourrait modifier cette contribution faible et mal cernée des traitements systémiques classiques. Les patientes atteintes de carcinome métaplasique mammaire pourraient bénéficier de traitements ciblés, ce qui reste à confirmer par des essais cliniques. PMID:25870723

Long Island Breast Cancer Study Project (Past Initiative)

Cancer.gov

The Long Island Breast Cancer Study Project is a multistudy effort to investigate whether environmental factors are responsible for breast cancer in Suffolk and Nassau counties, NY, as well as in Schoharie County, NY, and Tolland County, CT.

Evaluating a Bilingual Patient Navigation Program for Uninsured Women With Abnormal Screening Tests for Breast and Cervical Cancer: Implications for Future Navigator Research

PubMed Central

Tom, Laura S.; Nonzee, Narissa J.; Murphy, Kara R.; Endress, Richard; Dong, XinQi; Feinglass, Joe

2015-01-01

Objectives. The DuPage Patient Navigation Collaborative evaluated the Patient Navigation Research Program (PNRP) model for uninsured women receiving free breast or cervical cancer screening through the Illinois Breast and Cervical Cancer Program in DuPage County, Illinois. Methods. We used medical records review and patient surveys of 477 women to compare median follow-up times with external Illinois Breast and Cervical Cancer Program and Chicago PNRP benchmarks of performance. We examined the extent to which we mitigated community-defined timeliness risk factors for delayed follow-up, with a focus on Spanish-speaking participants. Results. Median follow-up time (29.0 days for breast and 56.5 days for cervical screening abnormalities) compared favorably to external benchmarks. Spanish-speaking patients had lower health literacy, lower patient activation, and more health care system distrust than did English-speaking patients, but despite the prevalence of timeliness risk factors, we observed no differences in likelihood of delayed (> 60 days) follow-up by language. Conclusions. Our successful replication and scaling of the PNRP navigation model to DuPage County illustrates a promising approach for future navigator research. PMID:25713942

Hazardous Waste Cleanup: DuPont Imaging Department in Parlin, New Jersey

EPA Pesticide Factsheets

DuPont has owned and operated a chemical manufacturing plant on Cheesequake Road in Parlin, New Jersey, since 1904. DuPont manufactured a variety of products at the plant including, photographic films, automotive paints, pigments, adhesives, thinners,

Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells.

PubMed

Cheng, Wan-Li; Huang, Chien-Yu; Tai, Cheng-Jeng; Chang, Yu-Jia; Hung, Chin-Sheng

2018-02-01

Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Maspin can enhance the sensitivity of HRPC cells to curcumin treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women’s Health Initiative Randomized Clinical Trial

PubMed Central

Ritenbaugh, Cheryl; Stanford, Janet L.; Wu, LieLing; Shikany, James M.; Schoen, Robert E.; Stefanick, Marcia L.; Taylor, Vicky; Garland, Cedric; Frank, Gail; Lane, Dorothy; Mason, Ellen; McNeeley, S. Gene; Ascensao, Joao; Chlebowski, Rowan T.

2010-01-01

Background In separate Women’s Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine survival of women following colorectal cancer diagnosis in the latter trial. Participants and Methods 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/day) or matching placebo. Colorectal cancer incidence was a component of the study’s monitoring global index but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined but information on their use was collected. Results After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group (hazard ratio [HR] 1.12, 95% Confidence Interval [CI] 0.77–1.63). Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34 % compared to 30 % in the placebo group (HR 1.34, 95% CI 0.58–3.19). Conclusions In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis. PMID:18829444

American Cancer Society Lung Cancer Screening Guidelines

PubMed Central

Wender, Richard; Fontham, Elizabeth T. H.; Barrera, Ermilo; Colditz, Graham A.; Church, Timothy R.; Ettinger, David S.; Etzioni, Ruth; Flowers, Christopher R.; Gazelle, G. Scott; Kelsey, Douglas K.; LaMonte, Samuel J.; Michaelson, James S.; Oeffinger, Kevin C.; Shih, Ya-Chen Tina; Sullivan, Daniel C.; Travis, William; Walter, Louise; Wolf, Andrew M. D.; Brawley, Otis W.; Smith, Robert A.

2013-01-01

Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. PMID:23315954

[Aspirin and colorectal cancer].

PubMed

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.

Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells.

PubMed

Price, R S; Cavazos, D A; De Angel, R E; Hursting, S D; deGraffenried, L A

2012-06-01

Obesity is associated with larger tumors, shorter time to PSA failure, and higher Gleason scores. However, the mechanism(s) by which obesity promotes aggressive prostate cancer remains unknown. We hypothesize that circulating factors related to obesity promote prostate cancer progression by modulating components of the metastatic cascade. Male C57BL/6 mice (6 weeks) were fed an ad libitum diet-induced obesity (60% fat) or control diet (10% fat) for 12 weeks. Serum was collected, metabolic and inflammatory proteins were measured by an antibody array. Sera were used to measure, in vitro, characteristics of a metastatic phenotype. Comparable to obese men, obese sera contained higher levels or leptin, vascular endothelial growth factor, PAI-1, interleukin-6 (IL-6) and lower levels of testosterone. In prostate cells, serum was used to assess: proliferation, invasion, migration, epithelial-mesenchymal-transition (EMT) and matrix metalloproteinase (MMP) activity. LNCaP and PacMetUT1 cells exposed to obese sera increased proliferation, whereas PrEC and DU145 were unaffected. LNCaP, PacMetUT1 and DU145 cancer cells exposed to obese sera resulted in increased invasion, migration and MMP-9 activity. Prostate cancer cells exposed to obese sera showed increased vimentin, dispersion of e-cadherin and β-catenin from the plasma membrane. We report, prostate cancer cells exposed to sera from obese mice increases proliferation, invasion, migration, MMP activity and induces changes in proteins critical for EMT.

Cancer Systems Biology Consortium | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer.

MYC activation is a hallmark of cancer initiation and maintenance.

PubMed

Gabay, Meital; Li, Yulin; Felsher, Dean W

2014-06-02

The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth.

PubMed

Fort, Rafael Sebastián; Mathó, Cecilia; Geraldo, Murilo Vieira; Ottati, María Carolina; Yamashita, Alex Shimura; Saito, Kelly Cristina; Leite, Katia Ramos Moreira; Méndez, Manuel; Maedo, Noemí; Méndez, Laura; Garat, Beatriz; Kimura, Edna Teruko; Sotelo-Silveira, José Roberto; Duhagon, María Ana

2018-02-02

Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer. Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort. Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD. Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in

Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size.

PubMed

Fallenberg, E M; Dromain, C; Diekmann, F; Engelken, F; Krohn, M; Singh, J M; Ingold-Heppner, B; Winzer, K J; Bick, U; Renz, D M

2014-01-01

To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography (CESM) is slowly being introduced into clinical practice. • Access to breast MRI is limited by availability and lack of reimbursement. • Initial results show a better sensitivity of CESM and MRI than conventional mammography. • CESM showed a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography offers promise, seemingly providing information comparable to MRI.

Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer

PubMed Central

Chuang, Hui-Yu; Jiang, Jeng-Kae; Yang, Muh-Hwa; Wang, Hsei-Wei; Li, Ming-Chun; Tsai, Chan-Yen; Jhang, Yau-Yun; Huang, Jason C.

2017-01-01

Metastasis accounts for the high mortality rate associated with colorectal cancer (CRC), but metastasis regulators are not fully understood. To identify a novel gene involved in tumor metastasis, we used oligonucleotide microarrays, transcriptome distance analyses, and machine learning algorithms to determine links between primary and metastatic colorectal cancers. Aminopeptidase A (APA; also known as ENPEP) was selected as our focus because its relationship with colorectal cancer requires clarification. Higher APA mRNA levels were observed in patients in advanced stages of cancer, suggesting a correlation between ENPEP and degree of malignancy. Our data also indicate that APA overexpression in CRC cells induced cell migration, invasion, anchorage-independent capability, and mesenchyme-like characteristics (e.g., EMT markers). We also observed TWIST induction in APA-overexpressing SW480 cells and TWIST down-regulation in HT29 cells knocked down with APA. Both APA silencing and impaired APA activity were found to reduce migratory capacity, cancer anchorage, stemness properties, and drug resistance in vitro and in vivo. We therefore suggest that APA enzymatic activity affects tumor initiation and cancer malignancy in a TWIST-dependent manner. Results from RT-qPCR and the immunohistochemical staining of specimens taken from CRC patients indicate a significant correlation between APA and TWIST. According to data from SurvExpress analyses of TWIST1 and APA mRNA expression profiles, high APA and TWIST expression are positively correlated with poor CRC prognosis. APA may act as a prognostic factor and/or therapeutic target for CRC metastasis and recurrence. PMID:28177885

RAS Initiative - Events

Cancer.gov

The NCI RAS Initiative has organized multiple events with outside experts to discuss how the latest scientific and technological breakthroughs can be applied to discover vulnerabilities in RAS-driven cancers.

Hazardous Waste Cleanup: E.I. DuPont de Nemours & Company in Pompton Lakes, New Jersey

EPA Pesticide Factsheets

E.I. DuPont De Nemours & Company is located at 2000 Cannonball Road, Pompton Lakes, New Jersey. The DuPont Pompton Lakes Works site (DuPont) occupies approximately 570 acres of land in Pompton Lakes and Wanaque.

Combination of Anti-IGF-1R Antibody A12 and Ionizing Radiation in Upper Respiratory Tract Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riesterer, Oliver; Yang Qiuan; Raju, Uma

2011-03-15

Purpose: The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers. Methods and Materials: Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25-2 mg x 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis,more » necrosis, and vascular endothelial growth factor expression at Days 1 and 6 after start of treatment. Results: A12 enhanced the radiosensitivity of HN5 and FaDu head-and-neck carcinomas in vitro (p < 0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner, with enhancement factors ranging from 1.2 to 1.8 (p < 0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (p < 0.05) and vascular endothelial growth factor expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted until 6 days from the start of treatment and in increased necrosis at Day 1 (p < 0.01, respectively). Combined treatment with A12 and radiation resulted in additive or subadditive growth delay in H460 or A549 xenografts, respectively. Conclusions: The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aerodigestive tract cancers.« less

Patient Navigators: Agents of Creating Community-Nested Patient-Centered Medical Homes for Cancer Care

PubMed Central

Simon, Melissa A.; Samaras, Athena T.; Nonzee, Narissa J.; Hajjar, Nadia; Frankovich, Carmi; Bularzik, Charito; Murphy, Kara; Endress, Richard; Tom, Laura S.; Dong, XinQi

2016-01-01

Patient navigation is an internationally utilized, culturally grounded, and multifaceted strategy to optimize patients’ interface with the health-care team and system. The DuPage County Patient Navigation Collaborative (DPNC) is a campus–community partnership designed to improve access to care among uninsured breast and cervical cancer patients in DuPage County, IL. Importantly, the DPNC connects community-based social service delivery with the patient-centered medical home to achieve a community-nested patient-centered medical home model for cancer care. While the patient navigator experience has been qualitatively documented, the literature pertaining to patient navigation has largely focused on efficacy outcomes and program cost effectiveness. Here, we uniquely highlight stories of women enrolled in the DPNC, told from the perspective of patient navigators, to shed light on the myriad barriers that DPNC patients faced and document the strategies DPNC patient navigators implemented. PMID:27594792

DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells.

PubMed

Fukuhara, Shinichiro; Chang, Inik; Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

2014-11-30

Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis.

DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells

PubMed Central

Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K.; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

2014-01-01

Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis. PMID:25526032

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

PubMed

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.

The Significance of Ras Activity in Pancreatic Cancer Initiation

PubMed Central

Logsdon, Craig D.; Lu, Weiqin

2016-01-01

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

The Significance of Ras Activity in Pancreatic Cancer Initiation.

PubMed

Logsdon, Craig D; Lu, Weiqin

2016-01-01

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Ras(mt). Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Ras(mt) is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Ras(mt) activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Ras(mt). Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Ras(mt) activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease.

Localisation inhabituelle de la tuberculose: ostéoarthrite tuberculose du pouce

PubMed Central

Mortaji, Aziz; Koulali, Khalid; Galuia, Farid

2014-01-01

L'ostéoarthrite tuberculose est rare au niveau des doigts. Nous rapportons une observation d'atteinte du pouce chez un patient de 55 ans. Il avait présenté une tuméfaction douloureuse du pouce droit suite à un traumatisme du pouce. L’étude bactériologique et une biopsie avaient permis de confirmer le diagnostic. Un traitement antibacillaire de 12 mois avait donné des résultats satisfaisants. Les particularités de la prise en charge sont discutées par rapport aux données de la littérature. PMID:25932075

The RAS Initiative

Cancer.gov

NCI established the RAS Initiative to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers.

[Clues to differentiate pregnancy-associated breast cancer from those diagnosed in postpartum period: A monocentric experience of pregnancy-associated cancer network (CALG)].

PubMed

Boudy, Anne-Sophie; Naoura, Iptissem; Zilberman, Sonia; Gligorov, Joseph; Chabbert-Buffet, Nathalie; Ballester, Marcos; Selleret, Lise; Darai, Emile

2017-06-01

To compare epidemiological, histological, therapeutic characteristics and prognosis of patients with breast cancer diagnosed during pregnancy with those diagnosed in postpartum period at a national expert center, « Cancer Associé à La Grossesse » network. Retrospective study of 108 patients with a pregnancy-associated breast cancer (PABC) between 2002 and 2016 comparing 51 patients with PABC during pregnancy and 57 patients with PABC of postpartum. Median gestational age at diagnosis was 16 weeks of gestation (WG). Median size (P=0.92), initial axillary pathology (P=0.29), histological type (P=0.33) and hormone receptor positive (P=0.93), were similar between groups. PABC during pregnancy overexpressed less frequently HER2 (12 % vs 36 %, P=0.003) and were less proliferant (Ki67≥15 %; 64 % vs 75 %, P=0.018) with less radical surgery (45 % vs 70 %, P=0.008). Sentinel lymph node biopsy was performed in 8 patients during pregnancy. Less patients of PABC during pregnancy received trastuzumab 12 % vs 37 %, P=0.003. Median delivery term was 37 WG. Median follow-up 3.2 vs 5.6 years (P=0.002) and recurrence rate for PABC during pregnancy and of postpartum were 3.2 vs 5.6 years (P=0.002) and 12 % vs 32 % (P=0.01), respectively. Our results emphasize histological, surgical and adjuvant treatment differences imposing differentiating PABC during pregnancy from those diagnosed in the postpartum period. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Etude thermo-hydraulique de l'ecoulement du moderateur dans le reacteur CANDU-6