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Sample records for initial du cancer

  1. Métastases gastro-intestinales du cancer du sein: à propos de 2 cas

    PubMed Central

    Loubna, Mezouar; Mohamed, El Hfid; Tijani, El Harroudi; Fouzia, Ghadouani; Hanane, Haj Kacem; Zouhour, Bourhaleb; Asmae, Ouabdelmoumen

    2013-01-01

    Le cancer du sein est le cancer le plus fréquent chez la femme, notamment au Maroc, avec un taux de mortalité élevé. Les métastases gastro-intestinales d'un carcinome canalaire du sein sont rares. Leur diagnostic est difficile du fait de la nature non spécifique des symptômes. Nous rapportons deux observations originales de métastases gastroduodénales d'un cancer canalaire infiltrant du sein. Les métastases gastro-intestinales du cancer du sein sont très rares; la présence de symptômes gastro-intestinaux chez une malade ayant un antécédent de cancer du sein doit faire suspecter une atteinte métastatique gastro-intestinale. PMID:24198876

  2. Suivi après le traitement du cancer du sein

    PubMed Central

    Sisler, Jeffrey; Chaput, Geneviève; Sussman, Jonathan; Ozokwelu, Emmanuel

    2016-01-01

    Résumé Objectif Offrir aux médecins de famille un résumé des recommandations fondées sur les données probantes pour guider les soins aux survivantes traitées pour le cancer du sein. Qualité des données Une recherche documentaire a été effectuée dans MEDLINE entre 2000 et 2016 à l’aide des mots-clés anglais suivants : breast cancer, survivorship, follow-up care, aftercare, guidelines et survivorship care plans, en se concentrant sur la revue des lignes directrices publiées récemment par les organismes nationaux de cancérologie. Les données étaient de niveaux I à III. Message principal Les soins aux survivantes comportent 4 facettes : surveillance et dépistage, prise en charge des effets à long terme, promotion de la santé et coordination des soins. La surveillance des récidives ne se traduit que par une mammographie annuelle, et le dépistage d’autres cancers doit suivre les lignes directrices basées sur la population. La prise en charge des effets à long terme du cancer et de son traitement aborde des problèmes courants tels la douleur, la fatigue, le lymphœdème, la détresse et les effets indésirables des médicaments, de même que les préoccupations à long terme comme la santé du cœur et des os. La promotion de la santé met en relief les bienfaits de l’activité chez les survivantes du cancer, avec l’accent mis sur l’activité physique. Les soins aux survivantes sont de meilleure qualité lorsque divers services et professionnels de la santé participent aux soins, et le médecin de famille joue un rôle important dans la coordination des soins. Conclusion Les médecins de famille sont de plus en plus souvent les principaux fournisseurs de soins de suivi après le traitement du cancer du sein. Le cancer du sein doit être considéré comme une affection médicale chronique, même chez les femmes en rémission, et les patientes profitent de la même approche que celle utilisée pour les autres affections chroniques en

  3. DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention.

    PubMed

    Gautam, Swetlana; Roy, Subhadeep; Ansari, Mohd Nazam; Saeedan, Abdulaziz S; Saraf, Shubhini A; Kaithwas, Gaurav

    2017-03-01

    Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.

  4. Oncoplastie avec conservation mammaire dans le traitement du cancer du sein: à propos de 16 cas

    PubMed Central

    Bouzoubaa, Wail; Laadioui, Meryam; Jayi, Sofia; Alaoui, Fatime Zahra Fdili; Bouguern, Hakima; Chaara, Hikmat; Melhouf, Moulay Abdelilah

    2015-01-01

    Le cancer du sein est actuellement le cancer le plus fréquent chez la femme, et pose un véritable problème diagnostique et thérapeutique. Le dépistage des lésions à un stade de plus en plus précoce, a permis une extension des indications du traitement conservateur radiochirurgical, qui était initialement limitées aux tumeurs de moins de 3 cm, unifocales, non inflammatoires. Par ailleurs, l'utilisation de traitements préopératoires permet d’étendre les indications du traitement conservateur à des tumeurs plus volumineuses. Parallèlement à cette extension des indications de conservation mammaire, on a observé le développement de nouvelles approches thérapeutiques notamment la chirurgie oncoplastique, technique du ganglion sentinelle et chirurgie stéréotaxique, dont les résultats initiaux sont très encouragent. A travers cette étude réalisée dans le service de gynécologie et obstétrique II du CHU HASSAN II de FES au MAROC, après l'analyse rétrospective de 16 patientes traitées par traitement conservateur et oncoplastie, nous avons voulus montrer notre aptitude a réalisé ses techniques chirurgicales et a bien prendre en charge ces patientes, mais aussi évaluer ces techniques en termes de résultat carcinologique et de résultat esthétique, aussi en terme de survie globale, survie sans métastase et en termes de récidive locale entre les plasties mammaires et les traitements usuels: mastectomie et traitement conservateur classique. PMID:26430477

  5. Classification moléculaire du cancer du sein au Maroc

    PubMed Central

    Fouad, Abbass; Yousra, Akasbi; Kaoutar, Znati; Omar, El Mesbahi; Afaf, Amarti; Sanae, Bennis

    2012-01-01

    Introduction La classification moléculaire des cancers du sein basée sur l'expression génique puis sur le profil protéique a permis de distinguer cinq groupes moléculaires: luminal A, luminal B, Her2/neu, basal-like et non-classées. L'objectif de cette étude réalisée au CHU Hassan II de Fès est de classer 335 cancers du sein infiltrant en groupes moléculaires, puis de les corréler avec les caractéristiques clinicopathologiques. Méthodes Etude rétrospective étalée sur 45 mois, comportant 335 patientes colligées au CHU pour le diagnostic et le suivi. Les tumeurs sont analysées histologiquement et classées après une étude immunohistochimique en groupes: luminal A, luminal B, Her2+, basal-like et non-classées. Résultats 54.3% des tumeurs sont du groupe luminal A, 16% luminal B, 11.3% Her2+, 11.3% basal-like et 7% non-classées. Le groupe luminal A renferme le plus faible taux de grade III, d'emboles vasculaires ainsi que de métastases; alors que le groupe des non-classées et basal-like représentent un taux élevé de grade III, une faible proportion d'emboles vasculaires et d'envahissement ganglionnaire. Ces facteurs sont significativement élevés dans les groupes luminal B et Her2+ avec un taux de survie globale de 78% et 76% respectivement. Dans le groupe luminal A, la survie globale des patientes est élevée (87%) alors qu'elle n'est que de 49% dans le groupe des triples négatifs (basal-like et non-classés). Conclusion Le groupe luminal B est différent du luminal A et il est de pronostic péjoratif vis à vis du groupe Her2+. Les caractéristiques clinicopathologiques concordent avec le profil moléculaire donc devraient être pris en considération comme facteurs pronostiques. PMID:23396646

  6. Le cancer en Mauritanie : résultats sur 10 ans du registre hospitalier de Nouakchott

    PubMed Central

    Baba, Nacer Dine Ould Mohamed; Sauvaget, Catherine

    2013-01-01

    Le fardeau du cancer reste mal connu en Mauritanie. Il n'est basé que sur des extrapolations de l'incidence des cancers des pays avoisinants. Les données du registre de l'hôpital national permettent de décrire les cas avec un diagnostic histologique. Tous les cas de cancers enregistrés par le service d'anatomo-pathologie de l'hôpital national de Nouakchott de 2000 à 2009 ont été analysés. En 10 ans, 3305 prélèvements histologiques ont été analysés (hommes:42%, femmes:58%). Chez l'homme, le cancer le plus fréquemment analysé était le cancer de la peau (218 cas au total, 189 cas en excluant mélanome), suivi de la prostate (203), des cancers digestifs (179, colorectal et ‘sophage), et des lymphomes (151). Chez la femme, un quart des biopsies était des cancers du sein (485), suivi du col utérin (344), de la sphère gynécologique (218, ovaire et corps utérin), et de la peau (114). Les cancers du foie, du poumon ou de la vessie étaient peu fréquents. Ces résultats ne reflètent pas l'incidence ni l'actuel fardeau du cancer en Mauritanie puisque de nombreux patients diagnostiqués avec un cancer ne reçoivent pas d'examen anatomopathologique. Si, comme dans les pays avoisinants du Maroc et du Mali, les cancers du col et du sein sont les pathologies les plus fréquentes chez la femme, la distribution des cancers chez l'homme dans ce registre hospitalier diffère des résultats des registres de population du Maroc et du Mali où les cancers du poumon, du foie, de la prostate et de la vessie dominent. PMID:23785554

  7. Prise en charge du cancer du col utérin durant la grossesse: à propos de 05 cas

    PubMed Central

    El Mazghi, Abderrahman; Bouhafa, Touria; Loukili, Kaoutar; El Kacemi, Hanan; Lalya, Issam; Hassouni, Khalid

    2014-01-01

    L'association d'un cancer du col utérin avec une grossesse est une éventualité rare. Son incidence est assez mal évaluée, elle se situe selon les études entre 1 et 2/10 000. Lorsque la découverte en est faite, il faut conjuguer deux impératifs parfois totalement divergents: le traitement de la mère et la prise en charge du foetus. Cette association pose schématiquement quatre grands problèmes, qui sont: Celui du diagnostic, qui est loin d’être évident, compte tenu des remaniements cervicaux observés en début de gestation, le pronostic de l'affection, la date du traitement chirurgical et du délai entre le diagnostic et la prise en charge thérapeutique, enfin et de manière plus accessoire, le devenir de la grossesse et le mode d'accouchement. Nous rapportons une série de 5 cas de cancer du col utérin découverts au cours de la grossesse colligés dans notre service entre 2010 et 2013. La prise en charge thérapeutique est identique à celle des patientes en dehors de la grossesse même si quelques adaptations sont nécessaires du fait de l’état gravide, le pronostic du cancer ne semble pas être modifié par la grossesse. PMID:25852788

  8. Cancer du sein bilatéral synchrone: expériences du centre Mohammed VI pour le traitement des cancers CHU Ibn Rochd Casablanca

    PubMed Central

    Khalil, Ahmadaye Ibrahim; Bendahhou, Karima; Mestaghanmi, Houriya; Saile, Rachid; Benider, Abdellatif

    2016-01-01

    Les cancers du sein bilatéraux synchrones (CSBS) sont des maladies qui se caractérisent par une importante hétérogénéité clinique et morphologique avec une fréquence entre 1,5 et 3,2%. Les femmes traitées pour un cancer du sein unilatéral sont à haut risque de développer un cancer au niveau controlatéral. Le dépistage et les progrès de l’imagerie mammaire ont permis une augmentation de découverte des CSBS. L’objectif de notre travail est d’étudier les caractéristiques épidémiologiques, cliniques, histologiques, et thérapeutiques du cancer du sein bilatéral. Il s’agit d’une étude transversale étalée sur deux années des patientes prise en charge au centre Mohammed VI pour le traitement des cancers. L’analyse statistique des résultats a été réalisée par le logiciel R. 31 patientes ont présenté un CSBS, représentant 2,4% des cas du cancer du sein dans notre Centre. L’âge moyen était 47,8 ± 8,4 ans, 22,6% utilisaient des contraceptifs oraux. Une histoire familiale de cancer du sein était observée dans 22,6% des cas. Le type histologique le plus fréquent était le carcinome canalaire infiltrant (58,1%), Le grade SBR II et III étaient fréquents (38,7%). Les récepteurs hormonaux entaient positifs, aux progestérones (38,7%) et aux œstrogènes (41,9%). Le récepteur HER2 était surexprimé dans 20,0% des cas. 29,0% des cas ont bénéficié d’une hormonothérapie et 3,2% de thérapies ciblées. Notre étude a montré que le cancer du sein bilatéral représente une proportion faible, mais avec certaines particularités cliniques, différant du cancer du sein unilatéral. PMID:28292084

  9. Cancer du sein historique à propos d'un cas!!! Comment réagir

    PubMed Central

    Laghzaoui, Omar

    2016-01-01

    Le cancer du sein localement avancé est une entité qui se fait rare dans les pays développés alors qu'on continue de recevoir des patientes à un stade avancé dans les pays africains. Nous proposant le cas d'une patiente intellectuelle prise en charge à l'hôpital militaire, Meknès, Maroc; qui a décelé la présence d'un nodule du sein droit par l'autopalpation mais elle n'a consulté le médecin que six mois après, dans un état historique de cancer du sein localement avancé. Le but de notre publication est donc de soulever les anomalies contemporaines aboutissant au retard diagnostic du cancer du sein et de proposer des solutions pour mieux sensibiliser la population. PMID:27642397

  10. 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

  11. Facteurs liés au diagnostic tardif du cancer du sein: expérience du CHU Mohammed VI Marrakech

    PubMed Central

    Aloulou, Sofia; El Mahfoudi, Amal; El Omrani, Abdelhamid; Khouchani, Mouna

    2015-01-01

    Le cancer du sein est le premier cancer féminin en termes d'incidence et de mortalité. Au Maroc, il vient au premier rang des cancers de la femme avant celui du col utérin Il constitue un problème de santé publique. Son pronostic est étroitement lié au stade auquel le diagnostic est posé. Il s'agit d'une pathologie dont les moyens diagnostiques sont de nos jours développés, allant de la détection précoce à la mise en évidence de lésions infra-cliniques, ce qui a nettement amélioré le pronostic dans les pays développés. Ce travail que nous présentons a pour objectif d'identifier dans notre pratique quotidienne, les facteurs qui amènent les patientes à consulter à des stades tardifs. Une étude rétrospective a été menée de janvier 2012 à janvier 2013 portant sur 130 patientes porteuses d'un cancer du sein au sein du service d'onco-radiotherapie CHU Mohammed VI Marrakech. Un questionnaire a été élaboré et dument renseigné en ayant recours aux dossiers des malades. Ainsi 63,07% des patientes consultaient au-delà de six mois avec un délai moyen de consultation de 8,47 mois avec comme motif de consultation des lésions classées T4 dans 27,69%, et des tumeurs d'emblée métastatiques dans 13,84%. Les facteurs retrouvés à l'interrogatoire étaient le manque de moyens financiers 40%, l’éloignement des structures sanitaires dans 23%, les habitudes socioculturelles avec les traitements traditionnels en première intention 20%, et l'insuffisance de prise en charge thérapeutique 7%. Cependant, pris individuellement, aucune concordance significative n’était retrouvée entre ces facteurs et le long délai diagnostique. Dans notre pratique, c'est la conjonction de la triade ignorance, indigence et habitudes socioculturelles qui constituent le facteur essentiel du diagnostic tardif des cancers du sein. PMID:26327999

  12. Le traitement conservateur du cancer du sein: expérience d'une équipe tunisienne

    PubMed Central

    Dimassi, Kaouther; Gharsa, Anissa; Chanoufi, Mohammed Badis; Sfar, Ezzeddine; Chelli, Dalenda

    2014-01-01

    En Tunisie, le cancer du sein touche des femmes jeunes avec une taille moyenne au moment du diagnostic à 5 cm. Ces particularités font que la chirurgie radicale reste prédominante. Nous présentons dans ce travail l'expérience de notre équipe en matière de chirurgie conservatrice du cancer du sein. Le but de ce travail est d’évaluer les résultats de ce traitement. Etude rétrospective longitudinale, sur une période de 75 mois. Nous avons inclus toutes les patientes ayant bénéficié d'un traitement conservateur pour une tumeur maligne du sein. Ont été analysés: les caractéristiques épidémiologiques, les aspects radiologiques et histologiques. Le suivi des malades s'est basé sur la détection des récidives. Nous avons évalué le résultat esthétique à la fin de la radiothérapie. Le traitement conservateur a été réalisé dans 23.8% des cas. Le taux de récidives locales était de 6.8% avec une corrélation significative pour une taille tumorale > 30 mm (p= 0.009), l'association d'une composante intracanalaire (p= 0.035), le statut triple négatif (p= 0.003) et des marges d'exérèse < 5mm sans recoupes per-opératoires (p = 0.045). Les facteurs suivants étaient significativement liés au risque de survenue de métastases à distance: le statut triple négatif (p= 0.003), taille tumorale > 30mm (p = 0.006) et l'atteinte ganglionnaire (p = 0.001). Le résultat esthétique était satisfaisant dans 90% des cas. L'augmentation du nombre de patientes pouvant bénéficier d'une chirurgie conservatrice, doit passer impérativement par le développement et la promotion du diagnostic précoce et du dépistage par la mammographie. PMID:25810795

  13. Participation des médecins généralistes de la province de Benimellal (Maroc) dans le dépistage du cancer du col

    PubMed Central

    Nani, Samira; Benallal, Mohamed; Hassoune, Samira; Kissi, Dounia; Maaroufi, Abderrahmane

    2013-01-01

    Introduction Au Maroc, chaque année il y aurait environ 2000 nouveaux cas de cancer du col et les 2/3 des cas sont pris en charge à un stade très avancé. Nous avons mené une étude transversale, exhaustive incluant les 71 médecins généralistes exerçant dans les établissements de soins de santé de base du secteur public et privé de la province de Benimellal. Le but était d’évaluer leurs connaissances et leur participation au dépistage du cancer du col. Méthodes Nous avons mené une étude transversale, exhaustive incluant les 71 médecins généralistes exerçant dans les établissements de soins de santé de base du secteur public et privé de la province de Benimellal. Le but était d’évaluer leurs connaissances et leur participation au dépistage du cancer du col. Résultats Le niveau de connaissance était relativement modeste, 22 médecins généraliste avaient répondu à la question sur l'incidence du cancer du col au Maroc, Parmi eux (81,8%) avaient donné une réponse incorrecte. L'Herpes Papilloma virus comme facteur de risque du cancer du col a été identifié par seulement 21% des médecins généralistes. La participation au dépistage était également défaillante, 92,8% n'avaient jamais pratiqué le FCV chez leurs patientes à cause principalement du manque de formation (95,5%). Conclusion Les résultats montrent la nécessité d'améliorer les connaissances théoriques et pratique des médecins généralistes concernant le dépistage du cancer du col. PMID:23785557

  14. [Cancer initiating cell theory: popularity and controversies].

    PubMed

    Chen, Hua; Huang, Qiang; Dong, Jun; Lan, Qing

    2006-06-01

    The cancer stem cell model proposes that most tumors are derived from a single cell that is transformed into a cancer-initiating cell (cancer stem cell). Cancer stem cells have the capacity to proliferate, differentiate, and form tumors in vivo. However, the origin of cancer stem cells remains controversial. Normal stem cells are regarded as an ideal candidate for the origin of cancer stem cells when take similar characters and signaling pathways between them into consideration. In addition,cell fusion is an important physiologic process during development and tissue repair,and is closely related to several fundamental features of tumors,and thus could be involved in the development of cancer stem cells.

  15. Connaissances des médecins généralistes de Mohammedia (Maroc) concernant le dépistage du cancer du sein

    PubMed Central

    Zine, Karima; Nani, Samira; Lahmadi, Imad Ait; Maaroufi, Abderrahmane

    2016-01-01

    Introduction Le cancer du sein représente un problème de santé publique majeur au Maroc. C'est le premier cancer chez la femme. L'objectif de ce travail était d'évaluer les connaissances des médecins généralistes (MG) en matière de dépistage du cancer du sein dans la préfecture de Mohammedia Maroc. Méthodes Nous avons mené une étude transversale, descriptive, exhaustive incluant les 97 MG exerçant dans les établissements de soins de santé de base du secteur public et privé de la province de Mohammedia. Résultats Le taux de participation était de 87%. L'âge moyen des MG était de 49,6 ± 8,1. Quatre-vingt pour cent (n=55) des MG ont donné une incidence incorrecte, 77,6% (n=85) ont reconnu l'existence d'un plan national de prévention et de contrôle du cancer (PNPCC) au Maroc, et 67,1 des MG ont rapporté l'existence d'un registre du cancer au Maroc. Le secteur d'activité était associé significativement avec les connaissances des MG sur le PNPCC et sur l'existence d'un guide de détection précoce du cancer du sein avec respectivement (p=0,003 et p=0,001). Une association significative entre l'ancienneté et l'existence d'un guide de détection précoce du cancer du sein et d'un registre du cancer du sein a été retrouvée avec (respectivement p=0,005 et p=0.002). Conclusion À la lumière de ces résultats il faudra renforcer les connaissances et les pratiques des MG par la promotion de la formation initiale et continue sur le dépistage. PMID:27800098

  16. Cancer du sein au Maroc: profil phénotypique des tumeurs

    PubMed Central

    Khalil, Ahmadaye Ibrahim; Bendahhou, Karima; Mestaghanmi, Houriya; Saile, Rachid; Benider, Abdellatif

    2016-01-01

    Le cancer du sein est le plus fréquent chez la femme et figure parmi les principales causes de mortalité liées au cancer. La curabilité de ce type tumoral est en augmentation, grâce aux programmes de dépistage et aux progrès thérapeutiques, qui ont certes augmenté la survie des patients. Mais des défis restent à relever en rapport avec l’instabilité phénotypique des cellules cancéreuses. L’objectif de ce travail est d’étudier le profil phénotypique du cancer du sein chez les patients pris en charge au Centre Mohammed VI pour le traitement des Cancers, durant les années 2013-2014. Il s’agit d’une étude transversale sur deux années, incluant les cas du cancer du sein pris en charge au Centre. Le recueil des données était fait à partir des dossiers des patients et analysés par le logiciel Epi Info. 1277 patients ont été pris en charge au sein de notre centre. 99,5% des cas de sexe féminin, l’âge moyen était 50,20 ± 11,34 ans. Le type histologique le plus fréquent était le carcinome canalaire infiltrant (80,7% des cas). Le stade diagnostic était précoce (56,9%). Le phénotype moléculaire le plus fréquent était le luminal A (41,4% des cas). Le luminal B, le HER2 et les triples négatifs étaient dans respectivement 10,4%, 6,3%, 11,2% des cas. L’étude du phénotype tumoral des patients atteints du cancer du sein permet l’orientation du clinicien dans le choix du traitement, et des décideurs dans la planification de programmes de lutte contre cette pathologie. PMID:28292037

  17. 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:

  18. 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.

  19. Survie au cancer du sein à Rabat (Maroc) 2005-2008

    PubMed Central

    Mechita, Nada Bennani; Tazi, Mohammed Adnane; Er-Raki, Abdelouahed; Mrabet, Mustapha; Saadi, Asma; Benjaafar, Noureddine; Razine, Rachid

    2016-01-01

    Introduction Le cancer du sein représente un problème de santé publique au Maroc. L’objectif de ce travail était d’estimer le taux de survie au cancer du sein chez les patientes habitant la ville de Rabat. Méthodes Etude pronostique réalisée chez les patientes diagnostiquées pour cancer du sein de 2005 à 2008, habitant la ville de Rabat et enregistrées au registre des cancers de Rabat. La date d’inclusion dans l’étude correspondait à la date de confirmation histologique du cancer. L’estimation de la survie a été réalisée par la méthode de Kaplan Meier, et la comparaison entre les différentes classes d’une variable a été réalisée par le test de log rank. L’étude des facteurs associés à la survie a été effectuée par le modèle de Cox. Résultats Durant la période d’étude 628 cas de cancer du sein ont été collectés. Le pourcentage de décès était de 19,9%. La survie globale à un an était de 97,1%, elle était de 89,2% à 3 ans et de 80,6 % à 5 ans. En analyse multivariée la survie au cancer du sein était statistiquement moins bonne chez les patientes âgées de plus de 70 ans (p<0,001), ayantune grande taille de tumeur (p<0,001), un stade avancé d’adénopathies (p=0,007), présentant des métastases (p<0,001) et non traitées par hormonothérapie (p=0,002). Conclusion Une grande taille de la tumeur et la présence de métastases sont des facteurs de mauvais pronostic du cancer du sein d’où la nécessité de renforcer les programmes de dépistage. PMID:28292106

  20. Cancer du sein de l'homme: à propos de 6 cas

    PubMed Central

    Laabadi, Kamilia; Jayi, Sofia; Alaoui, Fatimazohra Fdili; Bouguern, Hakima; Chaara, Hikmat; Melhouf, My Abdelilah; Hassani, Karim Ibn Majdoub; Laalim, Said Ait; Anoun, Hicham; Toughrai, Imane; Mazaz, Khalid

    2013-01-01

    Le but de ce travail était d'analyser les caractéristiques cliniques, histologiques, thérapeutiques et pronostiques du cancer du sein chez l'homme. Il s'agissait d'une étude rétrospective portant sur six patients colligés au service de gynécologie obstétrique II, CHU Hassan II durant la période 2009-2012. L’âge moyen de nos patients est de 65.3 ans. Il s'agit dans 83.3% des cas, d'une tumeur rétroaréolaire dont la taille moyenne est de 44.16 mm. Nous avons retrouvé 4 (66.7%) T4, 1 (16.7%) T3 et dans un cas, une tumeur inclassable. Le type histologique le plus représenté est le carcinome canalaire infiltrant (66.7%). Le taux d'envahissement ganglionnaire axillaire est de 66.7%. L'hormonodépendance de ces tumeurs est prouvée dans 100% des cas. La survie à cinq ans est en cours d’évaluation. L'envahissement ganglionnaire, l'invasion du derme, le stade clinique TNM sont des facteurs qui influencent significativement la survenue de métastases. Aucun de ces facteurs de risque n'est apparu significatif en termes de survie globale. Le cancer du sein chez l'homme est une maladie rare (environ 1% des cancers du sein) au pronostic sombre. Le diagnostic est le plus souvent tardif et les lésions sont traitées à des stades avancés. PMID:24711870

  1. Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells.

    PubMed

    Jeon, Yoon Jung; Jung, Seung-Nam; Chang, Hyeyoun; Yun, Jieun; Lee, Chang Woo; Lee, Joonku; Choi, Sangho; Nash, Oyekanmi; Han, Dong Cho; Kwon, Byoung-Mog

    2015-05-01

    Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose-dependent manner. To identify the active components, a bioassay-guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down-regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase-3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3-related diseases, including cancer and inflammation.

  2. 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.

  3. Aspects cliniques des cancers bronchopulmonaires primitifs au service d'oncologie du CHUA-HUJRA Antananarivo

    PubMed Central

    Refeno, Valéry; Hasiniatsy, Nomeharisoa Rodrigue Emile; Andrianandrasana, Ny Ony Tiana Florence; Ramahandrisoa, Andriatsihoarana Voahary Nasandratriniavo; Rakotonarivo, Jean Marc; Maevazaka, Joée Larissa; Rakotovao, Hanitrala Jean Louis; Rafaramino, Florine

    2015-01-01

    Le retard de diagnostic des cancers broncho-pulmonaires est l'une des sources du retard de leur prise en charge dans les pays en développement. A notre connaissance, l'aspect clinique des cancers broncho-pulmonaires au Centre Hospitalier Universitaire d'Antananarivo-Hôpital Universitaire Joseph Ravoahangy Andrianavalona (CHUA-HUJRA) n'a jamais été étudié. L'objectif était de décrire les aspects cliniques des cancers broncho-pulmonaires primitifs dans le plus grand centre de cancérologie de Madagascar. C'est une étude rétrospective et descriptive des patients atteints de cancers broncho-pulmonaires primitifs vus au service d'oncologie du CHUA-HUJRA du 1er janvier 2008 au 31 décembre 2013. Nous avons recensé 101 patients (80 hommes et 21 femmes). Les circonstances de découverte sont principalement la toux chronique (n = 29), la dyspnée (n = 16) et l'association d'une hémoptysie à la toux chronique (n = 12). Soixante et onze patients avaient un index de performans status ≥ à 2 au moment du diagnostic. On a retrouvé des bacilles de Koch actives dans le crachat de deux patients. Le délai moyen entre l'apparition des premiers signes et la première consultation était de 11 mois. Le délai moyen entre la première consultation et le diagnostic anatomopathologique était de 3 mois. Le cancer broncho-pulmonaire peut avoir des manifestations cliniques non spécifiques parfois trompeuses qui peuvent retarder leur prise en charge. De ce fait, il doit être recherché devant tout signe respiratoire persistant. Par ailleurs, le délai de prise en charge pré-hospitalière et hospitalière de ces cancers doit être amélioré. PMID:26958134

  4. Imagerie par modulation acoustique de conductivite electrique destinee au diagnostic du cancer du sein

    NASA Astrophysics Data System (ADS)

    Gendron, Mathieu

    used to reconstruct the electrical conductivity distribution. The second model presented in the thesis uses a unipolar acoustic wave to generate AECM signals of relatively large amplitude. There are two aspects related to this type of wave. The first aspect is that the acoustic modulation is unidirectional if the applied pressure is unidirectional. As a result, a positive pressure only produces an increase in electrical conductivity and this will result in a large AECM signal even when the thickness of the object is large. The second aspect concerns the shape of the acoustic field. Since the unipolar acoustic wave is not focused, it modulates the conductivity over a large area, and thus the associated AECM signals needs to be processed through a reconstruction algorithm so as to recover local conductivity. In this model, the data required for image reconstruction are acquired by rotating the transducer around the target object. An experimental setup has been developed during our project to get values of certain parameter that are required to define the numerical models. The setup comprises a large tank which is filled with water and in which are immersed the ultrasound transducer, a hydrophone and a measurement cell. The acousto-electric interaction takes place within this cell. A computer controlled positioning system allows precise displacements of the transducer relative to the hydrophone and the measurement cell. This cell comprises a cavity in which the object to be analyzed is placed and that is then filled with an electrolytic solution. The cavity is closed on two sides by an acoustic window to allow propagation of the ultrasound wave and on another side by six Ag/AgCl electrodes that are used to apply current and to measure the resulting electrical potential. Mammography is presently the most widely used medical imaging procedure for breast cancer screening. The average sensitivity of this technique is 80 % but it is less for younger women. According to recent

  5. 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.

  6. Curiethérapie dans le traitement palliatif du cancer de l’œsophage

    PubMed Central

    Toulba, Ahmedou; Bakkali, Hanae; Boutayeb, Salwa; Kebdani, Tayeb; Ahid, Samir; Benjaafar, Noureddine

    2015-01-01

    Les patients atteints du cancer de l’œsophage ont souvent une maladie localement avancée, la dysphagie est le symptôme majeur chez la plupart de ces patients, plusieurs modalités thérapeutiques ont été utilisées pour améliorer cette dysphagie. Le but de ce travail est d’étudier l'efficacité et la tolérance de la curiethérapie haut débit de dose (HDR) endo-luminale dans le traitement palliatif des cancers de l’œsophage inopérable. Sur une période de 15 ans, l’étude a inclus les patients atteints de cancer de l’œsophage inopérable et/ou métastatique avec une dysphagie, sans extension à l'hypopharynx ou a la trachée et qui ont bénéficié d'une curiethérapie HDR avec ou sans radiothérapie externe à visée palliative. Au total 46 patients ont été inclus dans l’étude, 58,7% étaient des hommes, 42,2% avaient une dysphagie grade 2 et 37,8% étaient aphagiques, 78,6% des patients étaient performance satus PS 2, l'amaigrissement à été trouvé chez 81,4%, la localisation de la tumeur était surtout au niveau du tiers moyen et inférieur dans 97,8%, la hauteur médiane de la tumeur était de 7 cm (5,5-9), le carcinome épidermoïde était le type histologique le plus fréquent chez 31 patients (70,5%). Après un médiane de suivi de 5 mois, l'amélioration de la dysphagie a été retrouvée chez 76% des malades (p1]. L′incidence la plus élevée est observée dans certains pays notamment en Asie et en Afrique, et l′incidence dans les pays développés occidentaux est en augmentation [2]. Selon le registre du cancer de Rabat 2006-2008, le cancer de l’œsophage est rare et constitue 1,5% de tous les cancers chez l'homme [3]. Le taux de survie globale à 5 ans est de 8%, avec 80% des décès liés à l’évolution locale de la maladie [4]. Pour la minorité des patients avec une maladie localisée, le traitement par radiochimiothérapie concomitante avec ou sans chirurgie permet une amélioration de la survie [5]. Plus de 50

  7. Immunological Targeting of Tumor Initiating Prostate Cancer Cells

    DTIC Science & Technology

    2014-10-01

    AD Award Number: W81XWH-13-1-0369 TITLE: Immunological Targeting of Tumor Initiating Prostate Cancer Cells PRINCIPAL...5a. CONTRACT NUMBER Immunological Targeting of Tumor Initiating Prostate Cancer Cells 5b. GRANT NUMBER W81XWH13-1-0369 5c... prostate cancer . In two specific aims, we proposed to first identify novel antigenic targets on these castrate resistant luminal epithelial cells (CRLEC

  8. Initial surgical management of thyroid cancer.

    PubMed

    Witt, Robert L

    2008-01-01

    The rapid increase in the rate of papillary thyroid cancer is likely caused by improved surveillance. A significant trend toward total thyroidectomy for low-risk differentiated thyroid cancer is present in the United States after a paradigm shift from treatment of macroscopic disease to the treatment of macroscopic and microscopic disease by increasingly sensitive tests. Compelling arguments for thyroid lobectomy and total thyroidectomy for low-risk thyroid cancer remain. The relatively small number of deaths from thyroid cancer, the small number of clinical thyroid cancers, and the huge number of incidental thyroid cancers are indicative of how little we understand the biology of this disease. Clinical medicine awaits biologic markers to refine treatment recommendations.

  9. Targeted Radiation Therapy for Cancer Initiative

    DTIC Science & Technology

    2013-09-01

    5 equally-spaced axial CT slices we calculated necessary PTV margins for each fraction. We then auto -fused each CBCT scan with the treatment...and veterans, such as breast cancer and metastatic cancer. The Calypso® 4D Localization System is a FDA Class II device, utilized to track both...treating left-sided breast cancer, which allows sparing of the heart. We have thus far treated 23 patients using these approved external beacons. The

  10. Up-regulating of RASD1 and apoptosis of DU-145 human prostate cancer cells induced by formononetin in vitro.

    PubMed

    Liu, Xiao-Jia; Li, Yun-Qian; Chen, Qiu-Yue; Xiao, Sheng-Jun; Zeng, Si-En

    2014-01-01

    Prostate cancer is one of the most prevalent malignant cancers in men. The isoflavone formononetin is a main active component of red clover plants. In the present study, we assessed the effect of formononetin on human prostate cancer DU-145 cells in vitro, and elucidated possible mechanisms. DU-145 cells were treated with different concentrations of formononetin and cell proliferation was assessed by MTT assay, cell apoptosis by Hoechst 33258 and flow cytometry, and protein levels of RASD1, Bcl-2 and Bax by Western blotting. The results showed that formononetin inhibited the proliferation of DU-145 cells in a dose-dependent manner. DU-145 cells treated with different concentrations of formononetin displayed obvious morphological changes of apoptosis under fluorescence microscopy. In addition, formononetin increased the proportion of early apoptotic DU-145 cells, down-regulated the protein levels of Bcl-2 and up-regulated those of RASD1 and Bax. The level of RASD1 reached its maximum at 48 h post-treatment, and rapidly decreased thereafter. Together, we present evidence that formononetin triggered cell apoptosis through the mitochondrial apoptotic pathway by up-regulating RASD1.

  11. Case-control study of cancer among Du Pont employees with potential for exposure to dimethylformamide

    SciTech Connect

    Walrath, J.; Fayerweather, W.E.; Gilby, P.G.; Pell, S.

    1989-05-01

    This case-control study was undertaken to determine whether the risk of developing cancers of the buccal cavity and pharynx (N = 39), liver (N = 6), prostate (N = 43), testis (N = 11), or malignant melanoma of the skin (N = 39) is related to exposure to dimethylformamide (DMF). Case and control subjects were obtained from four Du Pont plants. DMF is produced at one plant and used at the other three. Cancer cases identified from the company Cancer Registry comprise those reported among active male employees at the study plants during 1956 to 1985. For each case, two control subjects were selected, matched on sex, payroll class (wage or salary), birth year, and plant. To determine whether an employee could have been exposed to DMF during his career at the plant, all jobs with potential for exposure to DMF were identified. Each job was assigned an exposure ranking based on DMF industrial hygiene air monitoring, DMF metabolite (measured as N-methylformamide in urine) monitoring, and knowledge of the evolution of manufacturing processes and workplace exposure controls. Each employee's DMF exposure pattern was then characterized as (a) ever v never having been exposed to DMF and (b) highest DMF exposure experienced. Summary analyses for all plants combined showed no statistically significant association between ever having been exposed to DMF and subsequent development of cancers of the buccal cavity and pharynx, liver, malignant melanoma, prostate, and testis. Examined by plant site, prostate cancer at one plant was significantly elevated, based on three case subjects exposed out of four.

  12. Id4 Promotes Senescence and Sensitivity to Doxorubicin-induced Apoptosis in DU145 Prostate Cancer Cells

    PubMed Central

    Carey, Jason P.; Knowell, Ashley Evans; Chinaranagari, Swathi; Chaudhary, Jaideep

    2014-01-01

    Inhibitor of differentiation proteins (Id1, 2, 3 and 4) are dominant negative regulators of basic helix loop helix transcription factors and play dominant roles in cancer cells, spanning several molecular pathways including senescence, invasion, metastasis, proliferation and apoptosis. In contrast to high Id1, Id2 and Id3 expression, the expression of Id4 is epigenetically silenced in prostate cancer. In the present study we demonstrated a novel role of Id4, that of promotion of cellular senescence in prostate cancer cells. Materials and Methods: Id4 was ectopically expressed in DU145 cells (DU145+Id4). The cells treated with Doxorubicin (0–500 nm) or vehicle control were analyzed for apoptosis, senescence (SA-beta Galactosidase), and expression of CDKN1A (p21), CDKN1B(p27), CDKN2A (p16), E2F1, vimentin and E-cadherin by immuno-histochemistry and/or Western blot. Results: In the present study we demonstrated that Id4 promotes cellular senescence in prostate cancer cell line DU145. Ectopic overexpression of Id4 in androgen receptor-negative DU145 prostate cancer cells resulted in increased expression of p16, p21, p27, E-cadherin and vimentin but down-regulated E2F1 expression. Id4 also potentiated the effect of doxorubicin induced senescence and apoptosis. Conclusion: The absence of functional p16, pRB and p53 in DU145 suggests that Id4 could alter additional molecular pathways such as those involving E2F1 to promote senescence and increased sensitivity to doxorubicin-induced apoptosis. The results of the present study support the role of Id4 as a tumor suppressor in prostate cancer. PMID:24122992

  13. The AURORA initiative for metastatic breast cancer.

    PubMed

    Zardavas, D; Maetens, M; Irrthum, A; Goulioti, T; Engelen, K; Fumagalli, D; Salgado, R; Aftimos, P; Saini, K S; Sotiriou, C; Campbell, P; Dinh, P; von Minckwitz, G; Gelber, R D; Dowsett, M; Di Leo, A; Cameron, D; Baselga, J; Gnant, M; Goldhirsch, A; Norton, L; Piccart, M

    2014-11-11

    Metastatic breast cancer is one of the leading causes of cancer-related mortality among women in the Western world. To date most research efforts have focused on the molecular analysis of the primary tumour to dissect the genotypes of the disease. However, accumulating evidence supports a molecular evolution of breast cancer during its life cycle, with metastatic lesions acquiring new molecular aberrations. Recognising this critical gap of knowledge, the Breast International Group is launching AURORA, a large, multinational, collaborative metastatic breast cancer molecular screening programme. Approximately 1300 patients with metastatic breast cancer who have received no more than one line of systemic treatment for advanced disease will, after giving informed consent, donate archived primary tumour tissue, as well as will donate tissue collected prospectively from the biopsy of metastatic lesions and blood. Both tumour tissue types, together with a blood sample, will then be subjected to next generation sequencing for a panel of cancer-related genes. The patients will be treated at the discretion of their treating physicians per standard local practice, and they will be followed for clinical outcome for 10 years. Alternatively, depending on the molecular profiles found, patients will be directed to innovative clinical trials assessing molecularly targeted agents. Samples of outlier patients considered as 'exceptional responders' or as 'rapid progressors' based on the clinical follow-up will be subjected to deeper molecular characterisation in order to identify new prognostic and predictive biomarkers. AURORA, through its innovative design, will shed light onto some of the unknown areas of metastatic breast cancer, helping to improve the clinical outcome of breast cancer patients.

  14. Targeted Radiation Therapy for Cancer Initiative

    DTIC Science & Technology

    2012-09-01

    technique for treating left-sided breast cancer, which allows sparing of the heart. The Calypso system provides a previously unavailable level of...from both centers. Task 6. Post-prostatectomy Daily Target Guided Radiotherapy Using Real-Time, State-of-the-Art Motion Tracking with the Calypso...the skin surface to track breathing motion during a breath-hold technique for left-sided breast cancer treatment. Analysis would reveal the

  15. L’effet du yoga chez les patients atteints de cancer

    PubMed Central

    Côté, Andréanne; Daneault, Serge

    2012-01-01

    Résumé Objectif Déterminer si le yoga thérapeutique améliore la qualité de vie de patients atteints de cancer. Sources des données Recherche effectuée avec la base de données MEDLINE (1950–2010) en utilisant les mots-clés yoga, cancer et quality of life. Sélection des études Priorité accordée aux études cliniques randomisées contrôlées évaluant l’effet du yoga sur différents symptômes susceptibles de se présenter chez des patients atteints de cancer en Amérique du Nord. Synthèse Quatre études cliniques randomisées contrôlées ont d’abord été analysées, puis 2 études sans groupe-contrôle. Trois études réalisées en Inde et au Proche-Orient ont également apporté des éléments intéressants au plan méthodologique. Les interventions proposées comprenaient des séances de yoga d’une durée et d’une fréquence variables. Les paramètres mesurés variaient également d’une étude à l’autre. Plusieurs symptômes ont connu des améliorations significatives avec le yoga (meilleure qualité du sommeil, diminution des symptômes anxieux ou dépressifs, amélioration du bien-être spirituel, etc.). Il a aussi semblé que la qualité de vie, dans sa globalité ou dans certaines de ses composantes spécifiques, s’améliorait. Conclusion La variété des effets bénéfiques produits, l’absence d’effet secondaire et le rapport coût-bénéfice avantageux du yoga thérapeutique en fait une intervention intéressante à suggérer par les médecins de famille aux patients atteints de cancer. Certaines lacunes méthodologiques ont pu diminuer la puissance statistique des études présentées, à commencer par la taille restreinte des échantillons et par l’assiduité variable des patients soumis à l’intervention. Il est également possible que les échelles de mesure utilisées ne convenaient pas à ce type de situation et de clientèle pour qu’en soit dégagé un effet significatif. Toutefois, les commentaires

  16. 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

  17. Drug-tolerant cancer cells show reduced tumor-initiating capacity: depletion of CD44 cells and evidence for epigenetic mechanisms.

    PubMed

    Yan, Hong; Chen, Xin; Zhang, Qiuping; Qin, Jichao; Li, Hangwen; Liu, Can; Calhoun-Davis, Tammy; Coletta, Luis Della; Klostergaard, Jim; Fokt, Izabela; Skora, Stanislaw; Priebe, Waldemar; Bi, Yongyi; Tang, Dean G

    2011-01-01

    Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44(+) cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration, whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many "stemness" genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44(+) tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms.

  18. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  19. Identification et prise en charge des femmes ayant des antécédents familiaux de cancer du sein

    PubMed Central

    Heisey, Ruth; Carroll, June C.

    2016-01-01

    Résumé Objectif Résumer les meilleures données portant sur les stratégies d’identification et de prise en charge des femmes qui présentent des antécédents familiaux de cancer du sein. Sources d’information Une recherche a été effectuée sur PubMed à l’aide des mots-clés anglais suivants : breast cancer, guidelines, risk, family history, management et magnetic resonance imaging screening, entre 2000 et 2016. La plupart des données sont de niveau II. Message principal Une bonne anamnèse familiale est essentielle lors de l’évaluation du risque de cancer du sein afin d’identifier les femmes qui sont candidates à une recommandation en counseling génétique pour un éventuel test génétique. On peut sauver des vies en offrant aux femmes porteuses d’une mutation au gène BRCA des interventions chirurgicales de réduction des risques (mastectomie bilatérale prophylactique, salpingo-ovariectomie bilatérale). Il faut encourager toutes les femmes qui présentent des antécédents familiaux de cancer du sein à demeurer actives et à limiter leur consommation d’alcool à moins de 1 verre par jour; certaines femmes sont admissibles à la chimioprévention. Il faut offrir aux femmes dont le risque à vie de cancer du sein est de 20 à 25 % ou plus un dépistage poussé par imagerie par résonance magnétique en plus d’une mammographie. Conclusion Une vie saine et la chimioprévention (chez les candidates) pourraient réduire l’incidence du cancer du sein; le dépistage poussé pourrait entraîner une détection plus précoce. Le fait d’aiguiller des femmes porteuses d’une mutation au BRCA vers la chirurgie de réduction des risques sauve des vies. PMID:27737991

  20. 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

  1. c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation

    SciTech Connect

    Yu, Hongliang; Li, Xiaoying; Sun, Shaoqian; Gao, Xianshu; Zhou, Demin

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer c-Met inhibition could significantly enhance the radiosensitivity of DU145 cells. Black-Right-Pointing-Pointer The mechanisms of the radiosensitization effect of c-Met inhibition on DU145 cells were also presented in this paper. Black-Right-Pointing-Pointer This is the first study demonstrating the effectiveness of c-Met inhibition on treating HRPC cells with radiotherapy. -- Abstract: Hormone-refractory prostate cancer shows substantial resistance to most conventional therapies including radiotherapy, constitutes a key impediment to curing patients with the disease. c-Met overexpression plays a key role in prostate cancer tumorigenesis and disease progression. Here, we demonstrate that c-Met inhibition by SU11274 could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. The underlying mechanisms of the effects of SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death. Our study is the first to show the effectiveness of combining c-Met inhibition with ionizing radiation to cure hormone-refractory prostate cancer.

  2. Targeted Radiation Therapy for Cancer Initiative

    DTIC Science & Technology

    2015-09-01

    and whether this difference changed the outcome for palliative patients, 6) use of the Calypso system, and other advanced radiation therapy equipment...use of advanced technology radiation therapy techniques, such as IMRT and VMAT, in treating palliative patients. The main obstacle to overcome in...treating low-to-intermediate risk prostate cancer with intensity modulated radiation therapy (IMRT) using an electromagnetic localization system. IMRT

  3. Targeted Radiation Therapy for Cancer Initiative

    DTIC Science & Technology

    2014-09-01

    routine clinical use, 2) whether the use of Vac-Lok® immobilization devices are necessary when patients are treated using the Calypso system, 3...using breath-hold technique for left-sided breast cancer patients treated with adjuvant radiation therapy, with the benefit of confirmatory tracking...required for each patient thereby reducing the cost of care and increasing treatment capacity within the military delivery system; enabling research to

  4. Sodium orthovanadate affects growth of some human epithelial cancer cells (A549, HTB44, DU145).

    PubMed

    Klein, Andrzej; Holko, Przemyslaw; Ligeza, Janusz; Kordowiak, Anna M

    2008-01-01

    Within the concentration range of 1-20 microM, orthovanadate (Na3VO4) demonstrated a time and dose-dependent inhibition of autocrine growth of the human carcinoma cell lines A549 (lung), HTB44 (kidney) and DU145 (prostate), as compared to appropriate controls (without Na3VO4). The investigation was conducted by two methods: staining with N-hexa-methylpararosaniline (crystal violet=CV) or bromide3-(4,5-dimethyltio-azo-2)-2,5-diphenyl-tetrazole (MTT). In 5, 10 and 20 microM of Na3VO4 in serum-free medium, the mean values of these two tests for A549 were approximately 40%, 45% or 65% as compared to the appropriate controls. HTB44 had the greatest opportunity (statistically insignificant) at lower vanadium concentrations (up to 10 microM), whereas at 20 microM growth inhibition of these cells was approximately 50% of the controls. DU145 showed approximately 33%, 65% and 98% growth inhibition for 5, 10 and 20 microM of Na3VO4, respectively Additionally, hypothetical curves obtained by a MANOVA test based on the CV results after 72 h incubation with Na3VO4 in serum-free medium, and an example of a time-dependent effect of Na3VO4 on A549 cells, were also presented. Sodium orthovanadate was also examined for its cytotoxic capabilities, especially its ability to induce tumor cell apoptosis; the results were compared with the effect of paclitaxel. The target cells were dyed by differential staining (HOECHST33258 and propidium iodide) after 3 h and 24 h (DU145) or 3 h and 72 h (A549) of incubation with the vanadium compound. Contrary to the two cancer cell lines (viable, apoptotic or necrotic in experimental conditions), the renal HTB44 cells were insensitive up to 15 microM Na3VO4 concentrations. After 3 h incubation with Na3VO4, both lung (A549) and prostate (DU145) cancer cells showed a slight but significant reduction in the percentage of viable cells, and an increased amount of apoptotic cells. In contrast to the lung cells, DU145 prostate cells after 24 h were more

  5. Incidence of brain metastasis at initial presentation of lung cancer

    PubMed Central

    Villano, J. Lee; Durbin, Eric B.; Normandeau, Chris; Thakkar, Jigisha P.; Moirangthem, Valentina; Davis, Faith G.

    2015-01-01

    Background No reliable estimates are available on the incidence of brain metastasis (BM) in cancer patients. This information is valuable for planning patient care and developing measures that may prevent or decrease the likelihood of metastatic brain disease. Methods We report the first population-based analysis on BM incidence at cancer diagnosis using the Kentucky Cancer Registry (KCR) and Alberta Cancer Registry (ACR). All cancer cases with BM were identified from KCR and ACR, with subsequent focus on metastases from lung primaries; the annual number of BMs at initial presentation was derived. Comparisons were made between Kentucky and Alberta for the stage and site of organ involvement of lung cancer. Results Low incidence of BM was observed in the United States until mandatory reporting began in 2010. Both the KCR and ACR recorded the highest incidence of BM from lung cancer, with total BM cases at initial presentation occurring at 88% and 77%, respectively. For lung cancer, stage IV was the most common stage at presentation for both registries and ranged from 45.9% to 57.2%. When BM from lung was identified, the most common synchronous organ site of metastasis was osseous, occurring at 28.4%. Conclusion Our analysis from the Kentucky and Alberta cancer registries similarly demonstrated the aggressive nature of lung cancer and its propensity for BM at initial presentation. Besides widespread organ involvement, no synchronous organ site predicted BM in lung cancer. BM is a common and important clinical outcome, and use of registry data is becoming more available. PMID:24891450

  6. Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells.

    PubMed

    Lewinska, Anna; Jarosz, Paulina; Czech, Joanna; Rzeszutek, Iwona; Bielak-Zmijewska, Anna; Grabowska, Wioleta; Wnuk, Maciej

    2015-02-01

    Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥ 100 μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250 μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer.

  7. Cancer du sein au Cameroun, profil histo-épidémiologique: à propos de 3044 cas

    PubMed Central

    Engbang, Jean Paul Ndamba; Essome, Henri; Koh, Valère Mve; Simo, Godefroy; Essam, Jean Daniel Sime; Mouelle, Albert Sone; Essame, Jean Louis Oyono

    2015-01-01

    Décrire les caractéristiques épidémiologiques et histo-pathologiques des tumeurs malignes du sein au Cameroun. Il s'agissait d'une étude rétrospective descriptive portant sur les tumeurs malignes du sein, colligées, dans les registres des différents laboratoires d'Anatomie Pathologique publiques et privés repartis dans cinq régions (centre, littoral, Ouest, Nord-ouest, Sud-ouest), pendant une période de 10 ans (2004-2013). Les paramètres étudiés étaient la fréquence, l’âge, le sexe, la localisation, le type et le grade histologique, et les récepteurs hormonaux. Un total de 3044 cas de cancers du sein a été recensé, soit une fréquence annuelle de 304,4 cas en moyenne. Le sexe féminin était le plus représenté avec 2971 cas (97,60%) et les hommes avec 73 cas (2,40%), soit un sexe ratio (H/F) de 0,02. L’âge moyen des patients était de 46±15,87 ans, avec des extrêmes de 13 et 95 ans. Selon la localisation, le sein gauche était atteint dans 1244 cas (52%) et le sein droit dans 1115 cas (47%). Au plan histologique, on retrouvait essentiellement des carcinomes avec 96,50% des cas, des sarcomes 1,39%, des lymphomes 1,07% et la maladie de Paget du mamelon, 1,03%. Les tumeurs épithéliales étaient infiltrantes dans 2049 cas (84,46%), avec une prédominance du carcinome canalaire infiltrant (1870 cas) et non infiltrantes dans 377 cas (15,54%). Le grade histo-pronostic de SBR avait révélé une prédominance du grade II dans 66% des cas. Les cancers du sein restent une pathologie fréquente au Cameroun et atteignent principalement la population féminine en âge de procréer. Ils sont caractérisés par la prédominance du carcinome canalaire infiltrant. PMID:26523182

  8. Rectal prolapse as initial clinical manifestation of colon cancer.

    PubMed

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  9. Reprogramming bladder cancer cells for studying cancer initiation and progression.

    PubMed

    Iskender, Banu; Izgi, Kenan; Canatan, Halit

    2016-10-01

    The induced pluripotent stem cell (iPSC) technology is the forced expression of specific transcription factors in somatic cells resulting in transformation into self-renewing, pluripotent cells which possess the ability to differentiate into any type of cells in the human body. While malignant cells could also be reprogrammed into iPSC-like cells with lower efficiency due to the genetic and epigenetic barriers in cancer cells, only a limited number of cancer cell types could be successfully reprogrammed until today. In the present study, we aimed at reprogramming two bladder cancer cell lines HTB-9 and T24 using a non-integrating Sendai virus (SeV) system. We have generated six sub-clones using distinct combinations of four factors-OCT4, SOX2, KLF4 and c-MYC-in two bladder cancer cell lines. Only a single sub-clone, T24 transduced with 4Fs, gave rise to iPSC-like cells. Bladder cancer cell-derived T24 4F cells represent unique features of pluripotent cells such as epithelial-like morphology, colony-forming ability, expression of pluripotency-associated markers and bearing the ability to differentiate in vitro. This is the first study focusing on the reprogramming susceptibility of two different bladder cancer cell lines to nuclear reprogramming. Further molecular characterisation of T24 4F cells could provide a better insight for biomarker research in bladder carcinogenesis and could offer a valuable tool for the development of novel therapeutic approaches in bladder carcinoma.

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

    PubMed

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

    2013-03-01

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

  11. Brain derived metastatic prostate cancer DU-145 cells are effectively inhibited in vitro by guava (Psidium gujava L.) leaf extracts.

    PubMed

    Chen, Kuan-Chou; Hsieh, Chiu-Lan; Peng, Chiung-Chi; Hsieh-Li, Hsiu-Mei; Chiang, Han-Sun; Huang, Kuan-Dar; Peng, Robert Y

    2007-01-01

    The aqueous extract of Psidium guajava L. (PE) inhibited the cancer cell DU-145 in a dose- and time-dependent manner. At 1.0 mg/mL, PE reduced the viability of PCa DU-145 (the androgen independent PCa cells) to 36.1 and 3.59%, respectively after 48 h and 72 h of incubations. The absolute cell viability suppressing capability (VSC)(AC) could reach 262.5 cells-mL-h/mg on exposure to PE for 72 h, corresponding to the safe ranges, i.e. the percent viability suppressing rates (PVSR) of 2.72 and 2.41 folds for DU-145 comparing to PZ-HPV-7 cells when treated with PE at 0.5 and 1.0 mg/mL respectively for 72 h. In addition, the colony forming capability of DU-145 cells was apparently lowered. The suppressing rates of which reached 8.09 and 5.96 colony/mg/day for D-145 and PZ-HPV-7 cells, respectively within the concentration range of PE at 0.1 asymptotically equal to 0.25 mg/mL. Cell cycle arrests at G0/G1 phase in both cells were observed by TUNEL assay and flow cytometric analysis, yet more prominently evident in DU-145. In addition, suppression of the matrix metalloproteinases MMP-2 and MMP-9, and the upregulation of active caspase-3 at 0.10 to 1.0 mg/mL in DU-145 were also effected in a dose-dependent manner by PE at 0.25 to 1.0 mg/mL, implicating a potent anti-metastasis power of PE. Conclusively, we ascribe the anticancer activity of PE to its extraordinarily high polyphenolic (165.61 +/- 10.39 mg/g) and flavonoid (82.85 +/- 0.22 mg/g) contents. Furthermore, PE might be useful for treatment of brain derived metastatic cancers such as DU-145, acting simultaneously as both a chemopreventive and a chemotherapeutic.

  12. 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

    ... Initiation of a Public Private Industry Partnership on Translation of Nanotechnology in Cancer (TONIC) To Promote Translational Research and Development Opportunities of Nanotechnology-Based Cancer Solutions AGENCY: National Cancer Institute (NCI), Office of Cancer Nanotechnology Research (OCNR),...

  13. Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells.

    PubMed

    Chang, Hyun-Kyung; Shin, Mal-Soon; Yang, Hye-Young; Lee, Jin-Woo; Kim, Young-Sick; Lee, Myoung-Hwa; Kim, Jullia; Kim, Khae-Hawn; Kim, Chang-Ju

    2006-08-01

    Prostate cancer is one of the most common non-skin cancers in men. Amygdalin is one of the nitrilosides, natural cyanide-containing substances abundant in the seeds of plants of the prunasin family that have been used to treat cancers and relieve pain. In particular, D-amygdalin (D-mandelonitrile-beta-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. Apoptosis, programmed cell death, is an important mechanism in cancer treatment. In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells. In the present results, DU145 and LNCaP cells treated with amygdalin exhibited several morphological characteristics of apoptosis. Treatment with amygdalin increased expression of Bax, a pro-apoptotic protein, decreased expression of Bcl-2, an anti-apoptotic protein, and increased caspase-3 enzyme activity in DU145 and LNCaP prostate cancer cells. Here, we have shown that amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. The present study reveals that amygdalin may offer a valuable option for the treatment of prostate cancers.

  14. Cancers du sein bilatéraux synchrones et grossesse a l'institut Joliot Curie de Dakar (Sénégal)

    PubMed Central

    Zongo, Nayi; Sawadogo, Yobi Alexis; Some, Some Ollo Roland; Bagre, Sidpawalmdé Carine; Ka, Sidy; Diouf, Doudou; Dieng, Mamadou Moustapha; Gaye, Papa Macoumba; Dem, Ahmadou

    2016-01-01

    Décrire notre stratégie diagnostique et thérapeutique dans les cancers du sein bilatéraux synchrones pendant la grossesse. L’âge gestationnel au moment du diagnostic du cancer était respectivement de 7; 21 et 25 semaines. Il s'agissait de stade IV et IIIA respectivement dans deux et un cas. Elles ont toutes bénéficié d'une chimiothérapie dans deux cas pendant la grossesse (6TEC et 3AC) et dans un cas après l'accouchement. Une mastectomie bilatérale a été réalisée dans un cas. Une patiente est décédée. Les autres étaient vivantes mais toutes métastatiques. Une hypotrophie fœtale a été notée dans un cas. Le diagnostic du cancer est tardif dans cette association. La chirurgie est faisable et le type de chirurgie serait seulement fonction du stade du cancer. La chimiothérapie est possible avec moins de complications fœtales aux deux derniers trimestres. PMID:27279967

  15. 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.

  16. Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells.

    PubMed

    Barranco, Wade T; Kim, Danny H; Stella, Salvatore L; Eckhert, Curtis D

    2009-08-01

    Boron (B) is a developmental and reproductive toxin. It is also essential for some organisms. Plants use uptake and efflux transport proteins to maintain homeostasis, and in humans, boron has been reported to reduce prostate cancer. Ca2+ signaling is one of the primary mechanisms used by cells to respond to their environment. In this paper, we report that boric acid (BA) inhibits NAD+ and NADP+ as well as mechanically induced release of stored Ca2+ in growing DU-145 prostate cancer cells. Cell proliferation was inhibited by 30% at 100 microM, 60% at 250 microM, and 97% at 1,000 microM BA. NAD+-induced Ca2+ transients were partly inhibited at 250 microM BA and completely at 1,000 microM BA, whereas both NADP+ and mechanically induced transients were inhibited by 1,000 microM BA. Expression of CD38 protein increased in proportion to BA exposure (0-1,000 microM). In vitro mass spectrometry analysis showed that BA formed adducts with the CD38 products and Ca2+ channel agonists cyclic adenosine diphosphate ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). Vesicles positive for the Ca2+ fluorophore fluo-3 acetoxymethyl ester accumulated in cells exposed to 250 and 1,000 microM BA. The BA analog, methylboronic acid (MBA; 250 and 1,000 microM), did not inhibit cell proliferation or NAD+, NADP+, or mechanically stimulated Ca2+ store release. Nor did MBA increase CD38 expression or cause the formation of intracellular vesicles. Thus, mammalian cells can distinguish between BA and its synthetic analog MBA and exhibit graded concentration-dependent responses. Based on these observations, we hypothesize that toxicity of BA stems from the ability of high concentrations to impair Ca2+ signaling.

  17. Métastase osseuse isolée du radius métachrone d’un cancer rectal

    PubMed Central

    Eddekkaoui, Houda; Chekrine, Tarik; Sahraoui, Souha; Marouane, Sofia; Alj, Amina; Zamiati, Soumaya; Nechad, Mohamed; Benider, Abdellatif

    2013-01-01

    Les métastases osseuses isolées des cancers colorectaux sont très rares. Le squelette axial est habituellement le plus atteint. La localisation au niveau du radius est exceptionnelle. Nous rapportons l'observation d'une femme âgée de 60 ans avec une métastase du radius distal isolée métachrone d'un cancer du haut rectum opéré un an auparavant. La métastase a été découverte sur les examens d'imagerie et confirmée par biopsie. Une amputation a été réalisée suite à une progression de la maladie après une radiothérapie palliative. L'évolution était marquée par l'apparition de métastases pulmonaires et le décès est survenu dans un tableau de défaillance respiratoire. PMID:23819003

  18. Pratiques médicales de dépistage du cancer du sein chez les femmes de 35 à 49 ans et 70 ans et plus

    PubMed Central

    Kadaoui, Nabila; Guay, Maryse; Baron, Geneviève; St-Cerny, José; Lemaire, Jacques

    2012-01-01

    Résumé Objectif Décrire les pratiques des médecins concernant le dépistage opportuniste du cancer du sein chez les femmes de 35 à 49 ans et de 70 ans et plus et identifier les déterminants associés à la pratique de prescription de la mammographie de dépistage. Type d’étude Enquête postale. Contexte Le Québec. Participants Échantillon aléatoire simple de 1400 médecins omnipraticiens en exercice au Québec en 2009. Principaux paramètres à l’étude 5 pratiques de dépistage du cancer chez 4 types de clientèle de femmes et les facteurs qui influencent les médecins dans leur pratique de prescription de la mammographie de dépistage. Résultats Le taux de réponse était de 36 %. Pour les femmes de 35 à 49 ans, plus de 80 % des médecins rapportaient faire la pratique jugée adéquate sauf pour l’enseignement de l’auto-examen des seins et la référence en consultation génétique (60 % et 54 % respectivement). Pour les femmes de 70 ans et plus avec une bonne espérance de vie, seulement 50 % des omnipraticiens prescrivaient la mammographie de dépistage. Toutefois, pour les 70 ans et plus sans bonne espérance de vie où le dépistage n’est pas indiqué, près de la moitié des médecins continuaient à faire l’examen clinique des seins et plus du tiers à réviser les antécédents familiaux. Les déterminants de la pratique de prescription de la mammographie sont surtout: l’attitude favorable au dépistage, les habiletés de dépistage, le support des pairs, la croyance en l’efficacité de la mammographie ainsi que les connaissances adéquates de la problématique et des recommandations. Conclusion Il y a lieu d’améliorer les pratiques de l’enseignement de l’auto-examen des seins aux femmes de 35 à 49 ans et leur référence en consultation génétique ainsi que la prescription de la mammographie chez les femmes de 70 ans et plus en bonne santé. Les actions de santé publique pour améliorer ces pratiques devraient miser

  19. Vertebral Metastasis as the Initial Manifestation of Colon Cancer

    PubMed Central

    Jain, Tushina; Williams, Renee; Liechty, Benjamin

    2016-01-01

    Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis. PMID:27807574

  20. Vertebral Metastasis as the Initial Manifestation of Colon Cancer.

    PubMed

    Jain, Tushina; Williams, Renee; Liechty, Benjamin; Ann Chen, Lea

    2016-08-01

    Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis.

  1. Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles’ heel?

    PubMed Central

    Sabharwal, Simran S.; Schumacker, Paul T.

    2015-01-01

    Mitochondria cooperate with their host cells by contributing to bioenergetics, metabolism, biosynthesis, and cell death or survival functions. Reactive oxygen species (ROS) generated by mitochondria participate in stress signalling in normal cells but also contribute to the initiation of nuclear or mitochondrial DNA mutations that promote neoplastic transformation. In cancer cells, mitochondrial ROS amplify the tumorigenic phenotype and accelerate the accumulation of additional mutations that lead to metastatic behaviour. As mitochondria carry out important functions in normal cells, disabling their function is not a feasible therapy for cancer. However, ROS signalling contributes to proliferation and survival in many cancers, so the targeted disruption of mitochondria-to-cell redox communication represents a promising avenue for future therapy. PMID:25342630

  2. A novel synthetic protoapigenone analogue, WYC02-9, induces DNA damage and apoptosis in DU145 prostate cancer cells through generation of reactive oxygen species.

    PubMed

    Chen, Huei-Mei; Chang, Fang-Rong; Hsieh, Ya-Ching; Cheng, Yu-Jen; Hsieh, Kun-Chou; Tsai, Lih-Min; Lin, An-Shen; Wu, Yang-Chang; Yuan, Shyng-Shiou

    2011-05-01

    The protoapigenone analogue WYC02-9, a novel synthetic flavonoid, has been shown to act against a variety of experimental tumors. However, its effects on prostate cancer and its mechanism of action are unknown. Thus, WYC02-9 was investigated for its cytotoxicity against DU145 prostate cancer cells, as was the underlying mechanisms by which WYC02-9 might induce DNA damage and apoptotic cell death through reactive oxygen species (ROS). WYC02-9 inhibited the cell growth of three prostate cancer cell lines, especially DU145 cells. In DU145 cells, WYC02-9 increased the generation of intracellular ROS, followed by induction of DNA damage and activation of the ATM-p53-H2A.X pathway and checkpoint-related signals Chk1/Chk2, which led to increased numbers of cells in the S and G2/M phases of the cell cycle. Furthermore, WYC02-9 induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9, caspase-3, and PARP. The above effects were all prevented by the ROS scavenger N-acetylcysteine. Administration of WYC02-9 in a nude mouse DU145 xenograft model further identified the anti-cancer activity of WYC02-9. These findings therefore suggest that WYC02-9-induced DNA damage and mitochondria-dependent cell apoptosis in DU145 cells are mediated via ROS generation.

  3. Apoptosis of DU145 human prostate cancer cells induced by dehydrocostus lactone isolated from the root of Saussurea lappa.

    PubMed

    Kim, Eun Ji; Lim, Soon Sung; Park, So Young; Shin, Hyun-Kyung; Kim, Jong-Sang; Park, Jung Han Yoon

    2008-12-01

    Saussurea lappa (SL) is a plant regularly utilized in traditional herbal medicine, and in vitro cell culture studies have demonstrated that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. In order to explore the possibility that SL exerts chemopreventive effects in androgen-independent prostate cancer, we attempted to determine whether the hexane extract of SL (HESL) induces apoptosis of DU145 cells, as well as the mechanisms underlying this effect. HESL substantially reduced the number of viable cells and induced apoptosis in DU145 cells in a dose-dependent manner. HESL-induced the cleavage of poly (ADP-ribose) polymerase (PARP) and caspases 8, 9, 7, and 3. HESL increased the protein levels of Bax, Bak, Bok, Bik, truncated Bid (t-Bid), and Bmf with a concomitant increase in the permeability of the mitochondrial membrane and in the release of cytochrome c from the mitochondria. The active fraction of HESL was isolated by column chromatography and the structure of the active compound dehydrocostus lactone (DHCL) was identified via (1)H NMR and (13)C NMR. DHCL promoted apoptosis with increased activation of caspases 8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid. We have demonstrated that HESL and its active principle, DHCL, inhibit cell growth and induce apoptosis in DU145 cells.

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

    SciTech Connect

    Kojima, Keitaro; Ohhashi, Riyako; Fujita, Yasunori; Hamada, Nanako; Akao, Yukihiro; Nozawa, Yoshinori; Deguchi, Takashi; Ito, Masafumi

    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 camptothecin 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.

  5. Effects of miR-200c on the migration and invasion abilities of human prostate cancer Du145 cells and the corresponding mechanism.

    PubMed

    Shi, Runlin; Xiao, Haibing; Yang, Tao; Chang, Lei; Tian, Yuanfeng; Wu, Bolin; Xu, Hua

    2014-12-01

    microRNAs (miRNAs) have played a key role in human tumorigenesis, tumor progression, and metastasis. On the one hand, miRNAs are aberrantly expressed in many types of human cancer; on the other hand, miRNAs can function as tumor suppressors or oncogenes that target many cancer-related genes. This study aimed to investigate the effects of miRNA-200c (miR-200c) on the biological behavior and mechanism of proliferation, migration, and invasion in the prostate cancer cell line Du145. In this study, Du145 cells were transfected with miR-200c mimics or negative control miR-NC by using an X-tremeGENE siRNA transfection reagent. The relative expression of miR-200c was measured by RT-PCR. The proliferation, migration, and invasion abilities of Du145 cells were detected by CCK8 assays, migration assays and invasion assays, respectively. The expressions of ZEB1, E-cadherin, and vimentin were observed by western blot. Results showed that DU145 cells exhibited a high expression of miR-200c compared with immortalized normal prostate epithelial cell RWPE-1. Du145 cells were then transfected with miR-200c mimics and displayed lower abilities of proliferation, migration, and invasion than those transfected with the negative control. The protein levels of ZEB1 and vimentin were expressed at a low extent in Du145 cells, which were transfected with miR-200c mimics; by contrast, E-cadherin was highly expressed. Hence, miR-200c could significantly inhibit the proliferation of the prostate cancer cell line Du145; likewise, miR-200c could inhibit migration and invasion by epithelial-mesenchymal transition.

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

    SciTech Connect

    Fiorentini, Chiara; Bodei, Serena; Bedussi, Francesca; Fragni, Martina; Bonini, Sara Anna; Simeone, Claudio; Zani, Danilo; Berruti, Alfredo; Missale, Cristina; Memo, Maurizio; Spano, PierFranco; Sigala, Sandra

    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 contrast 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.

  7. Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy

    PubMed Central

    Poillet-Perez, Laura; Despouy, Gilles; Delage-Mourroux, Régis; Boyer-Guittaut, Michaël

    2014-01-01

    Cancer formation is a complex and highly regulated multi-step process which is highly dependent of its environment, from the tissue to the patient. This complexity implies the development of specific treatments adapted to each type of tumor. The initial step of cancer formation requires the transformation of a healthy cell to a cancer cell, a process regulated by multiple intracellular and extracellular stimuli. The further steps, from the anarchic proliferation of cancer cells to form a primary tumor to the migration of cancer cells to distant organs to form metastasis, are also highly dependent of the tumor environment but of intracellular molecules and pathways as well. In this review, we will focus on the regulatory role of reactive oxygen species (ROS) and autophagy levels during the course of cancer development, from cellular transformation to the formation of metastasis. These data will allow us to discuss the potential of this molecule or pathway as putative future therapeutic targets. PMID:25590798

  8. Timing of multikinase inhibitor initiation in differentiated thyroid cancer.

    PubMed

    Brose, Marcia S; Smit, Jan Wa; Lin, Chia-Chi; Pitoia, Fabian; Fellous, Marc; DeSanctis, Yoriko; Schlumberger, Martin; Tori, Masayuki; Sugitani, Iwao

    2017-03-07

    There are limited treatment options for patients with radioactive iodine-refractory, progressive differentiated thyroid cancer. Although there is consensus that multikinase inhibitor therapy should be considered in patients with progressive disease with considerable tumor load or symptomatic disease, uncertainty exists on the optimal timing to treat with a multikinase inhibitor, especially for asymptomatic patients. RIFTOS MKI is an international, prospective, open-label, multicenter, noninterventional study with the primary objective to compare the time to symptomatic progression from study entry in asymptomatic patients with radioactive iodine -refractory, progressive differentiated thyroid cancer for whom there is a decision to initiate multikinase inhibitors at study entry (cohort 1) with those for whom there is a decision to not initiate multikinase inhibitors at study entry (cohort 2). Secondary endpoints are overall survival and progression-free survival, which will be compared between cohorts 1 and 2. Additional secondary endpoints are postprogression survival from time of symptomatic progression, duration of and response to each systemic treatment regimen, and dosing of sorafenib throughout the treatment period. Asymptomatic, multikinase inhibitor-naive patients aged ≥18 years with histologically/cytologically documented differentiated thyroid cancer that is radioactive iodine-refractory are eligible. Patients may receive any therapy for differentiated thyroid cancer, including sorafenib or other multikinase inhibitors if indicated and decided on by the treating physician. In total, 700 patients are estimated to be enrolled from >20 countries. Final analysis will be performed once the last enrolled patient has been followed up with for 24 months. (ClinicalTrials.gov identifier: NCT02303444).

  9. [Autophagy contributes to the initiation of pancreatic cancer].

    PubMed

    Iovanna, Juan L

    2017-03-01

    The pancreatic adenocarcinoma initiation results from the interaction of genetic events combined with multiple other factors. Among the genetic alterations that contribute to the pathogenesis of this disease, the mutation of the KRAS oncogene is required but not sufficient to trigger this cancer. Pancreatitis, an inflammatory disease, facilitates and accelerates the transformation of pancreatic cells when the KRAS oncogene is mutated. Of note, the repertoire of molecular mediators of pancreatitis which are responsible of the promotion of KRAS-mediated transformation is not completely defined. Importantly, autophagy has been proposed as one of the cellular mechanisms contributing to pancreatic carcinogenesis, especially in the initial phases, in which the oncogene KRAS appears to play its leading role. In addition, autophagy is strongly induced during pancreatitis. Although some aspects of autophagy in pancreatic cancer development are not completely established, we can affirm that overexpression of VMP1, an inducer of autophagy which is specifically activated in pancreas during pancreatitis, improves the development of pancreatic precancerous lesions PanINs when the oncogene KRAS is mutated. In addition, inhibition of the autophagic flux with chloroquine inhibits the KRAS pro-tumor effect in the pancreas. In conclusion, activation of expression of VMP1 improves the pro-tumor role of KRAS in pancreas.

  10. 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.

  11. Sister Mary Joseph's nodule as initial pancreatic cancer manifestation.

    PubMed

    Vallejo Bernad, Cristina; Casamayor Franco, María Carmen; Hakim Alonso, Sofía

    2017-02-01

    We report the case of an 85-year-old female patient who presented with umbilical pain associated with an indurated growth, the whole being apparently consistent with incarcerated umbilical hernia, which prompted an urgent surgical procedure for its removal. The pathology study revealed dermal infiltration by a malignancy. Gland tumor cells expressed an immunohistochemical profile initially consistent with a pancreatic origin. In view of these findings a CT scan was performed, which revealed a pancreatic tail tumor as well as multiple hepatic metastasis. Skin metastasis is a rare sign usually reflecting a carcinoma of unknown origin. Umbilical skin metastasis, called Sister Mary Joseph´s nodule, reflect an intra-abdominal tumor, being pancreatic cancer strange.

  12. 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.

  13. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    PubMed

    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

    2012-04-01

    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.

  14. 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

  15. 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

  16. Plumbagin elicits differential proteomic responses mainly involving cell cycle, apoptosis, autophagy, and epithelial-to-mesenchymal transition pathways in human prostate cancer PC-3 and DU145 cells.

    PubMed

    Qiu, Jia-Xuan; Zhou, Zhi-Wei; He, Zhi-Xu; Zhao, Ruan Jin; Zhang, Xueji; Yang, Lun; Zhou, Shu-Feng; Mao, Zong-Fu

    2015-01-01

    Plumbagin (PLB) has exhibited a potent anticancer effect in preclinical studies, but the molecular interactome remains elusive. This study aimed to compare the quantitative proteomic responses to PLB treatment in human prostate cancer PC-3 and DU145 cells using the approach of stable-isotope labeling by amino acids in cell culture (SILAC). The data were finally validated using Western blot assay. First, the bioinformatic analysis predicted that PLB could interact with 78 proteins that were involved in cell proliferation and apoptosis, immunity, and signal transduction. Our quantitative proteomic study using SILAC revealed that there were at least 1,225 and 267 proteins interacting with PLB and there were 341 and 107 signaling pathways and cellular functions potentially regulated by PLB in PC-3 and DU145 cells, respectively. These proteins and pathways played a critical role in the regulation of cell cycle, apoptosis, autophagy, epithelial to mesenchymal transition (EMT), and reactive oxygen species generation. The proteomic study showed substantial differences in response to PLB treatment between PC-3 and DU145 cells. PLB treatment significantly modulated the expression of critical proteins that regulate cell cycle, apoptosis, and EMT signaling pathways in PC-3 cells but not in DU145 cells. Consistently, our Western blotting analysis validated the bioinformatic and proteomic data and confirmed the modulating effects of PLB on important proteins that regulated cell cycle, apoptosis, autophagy, and EMT in PC-3 and DU145 cells. The data from the Western blot assay could not display significant differences between PC-3 and DU145 cells. These findings indicate that PLB elicits different proteomic responses in PC-3 and DU145 cells involving proteins and pathways that regulate cell cycle, apoptosis, autophagy, reactive oxygen species production, and antioxidation/oxidation homeostasis. This is the first systematic study with integrated computational, proteomic, and

  17. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

    SciTech Connect

    Gough, Mallory Blanthorn-Hazell, Sophee Delury, Craig Parkin, Edward

    2014-10-31

    Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  18. 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

  19. 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

  20. 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.

  1. Aspects histo-épidémiologiques des cancers génitaux de la femme dans la région du Littoral, Cameroun

    PubMed Central

    Engbang, Jean Paul Ndamba; Koh, Valère Mve; Tchente, Charlotte Nguefack; Fewou, Amadou

    2015-01-01

    Décrire les caractéristiques épidémiologiques et histopathologiques des tumeurs malignes génitales de la femme dans la région du littoral du Cameroun. Il s'agissait d'une étude rétrospective descriptive et analytique portant sur les cancers des organes génitaux de la femme, histologiquement prouvés pendant une période de 10 ans (2004-2013), répertoriés dans les registres des trois laboratoires d'anatomopathologie de la région (Hôpital Laquintinie de Douala, Hôpital Général de Douala, laboratoire Anapathos) et des services d'oncologie de ces hôpitaux. Les variables étudiées étaient: la fréquence, l’âge, le sexe, la localisation de la tumeur et le type histopathologique. Au total, 802 cas de cancers génitaux de la femme ont été recensés, soit une fréquence annuelle de 80,2 cas en moyenne. Le col utérin avec 580 cas (72,32%) a été la localisation la plus fréquente; suivi de l'endomètre (corps utérin) avec 93 cas (11,60%), puis des ovaires 91 cas (11,35%). L’âge moyen des patientes était de 50, 30±12,67 ans, avec les extrêmes allant de 14 à 85 ans. Selon le type histologique, les tumeurs épithéliales ont été les plus fréquemment rencontrées, soit 758 patientes (94,51%), les lymphomes venaient en seconde position avec 29 cas (3, 62%), les autres variétés histologiques (sarcomes, tumeurs germinales, tumeurs du mésenchyme et du cordon) représentant moins chacune de 1%. Les tumeurs malignes des organes génitaux féminins sont fréquentes dans la région du littoral du Cameroun, elles sont dominées essentiellement par le cancer du col utérin. Les tumeurs épithéliales sont le type histologique le plus fréquent. PMID:26327953

  2. 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.

  3. Résultat de la radio chimiothérapie concomitante du cancer du col utérin au service oncologie-radiothérapie à l'hôpital universitaire Joseph Ravoahangy Andrianavalona de 2007 à 2009

    PubMed Central

    Randriamanovontsoa, Ezra Niaina; Ratsimandresy, Dera Andraina; Rakotonarivo, Jean Marc; Rakototiana, Auberlin Felantsoa; Rantomalala, Harinirina Yoël Honora; Rafaramino, Florine

    2014-01-01

    La radiochimiothérapie devient un standard pour le traitement du cancer du col utérin à partir de IB de mauvais pronostic. L'objectif de ce travail est de rapporter les résultats de cette modalité thérapeutique. Il s'agissait d'une étude rétrospective descriptive des dossiers des patientes atteintes d'un cancer du col utérin du Janvier 2007 au Décembre 2009 traitées par une radiochimiothérapie concomitante. Les patientes ayant reçu une dose inférieure à 45Gy étaient éliminées dans cette étude. Les critères de l'OMS ont été utilisés pour évaluer la réponse tumorale. Au total 46patientes étaient retenues avec un âge moyen de 47ans. Le carcinome épidermoide représentait 89,13%, diagnostiqués au stade localement avancé dans 82,60%. Seulement 26,08% de nos patients ont bénéficié d'une tomodensitométrie abdominale et pelvienne. La dose reçue variait de 45 à 75 Gy. Les résultats thérapeutiques à un mois de la fin du traitement montraient: 45,63% de rémission complète et 30,42% de rémission partielle supérieure à 50%. La toxicité précoce était dominée par la neutropénie chiffrée à 30,55%. A travers de cette étude, la radiochimiothérapie concomitante a amélioré les résultats thérapeutiques à court terme. PMID:25883726

  4. Lignes directrices sur l’aiguillage des cas soupçonnés de cancer du poumon par un médecin de famille ou autre professionnel des soins primaires

    PubMed Central

    Del Giudice, M. Elisabeth; Young, Sheila-Mae; Vella, Emily T.; Ash, Marla; Bansal, Praveen; Robinson, Andrew; Skrastins, Roland; Ung, Yee; Zeldin, Robert; Levitt, Cheryl

    2014-01-01

    Résumé Objectif Les présentes lignes directrices visent à aider les médecins de famille et autres généralistes à reconnaître les manifestations cliniques devant éveiller les soupçons quant à la présence d’un cancer du poumon chez les patients. Composition du comité Les membres du comité ont été choisis parmi les leaders régionaux en soins primaires du Réseau provincial des soins primaires et de la lutte contre le cancer d’Action Cancer Ontario et parmi les membres du Groupe sur le siège de la maladie, Cancer du poumon d’Action Cancer Ontario. Méthodes Les présentes lignes directrices sont le fruit d’une revue systématique des données probantes, d’une synthèse des données et d’un examen externe formel effectué par des intervenants canadiens qui ont validé la pertinence des recommandations. Rapport Ces lignes directrices fondées sur des données probantes ont été formulées pour améliorer la prise en charge en contexte canadien des patients qui présentent des manifestations cliniques du cancer du poumon. Conclusion Le dépistage et l’aiguillage précoces des patients atteints de cancer du poumon pourraient en fin de compte aider à réduire les morbidités et mortalités liées au cancer. Ces lignes directrices pourraient aussi s’avérer utiles dans la mise sur pied de programmes de diagnostic du cancer du poumon et pour aider les décideurs à veiller à ce que les ressources appropriées soient en place.

  5. [Which recent results in Oncology and Hematology will have an impact on our practices? The point of vue of Bulletin du Cancer editorial board].

    PubMed

    Vignot, Stéphane; André, Thierry; Gonçalves, Anthony; Guièze, Romain; Magné, Nicolas; Orbach, Daniel; Penel, Nicolas; Thariat, Juliette; Wislez, Marie; Bay, Jacques-Olivier

    2017-01-01

    Among the results presented at international congresses or published in scientific journals, which are those that have a real impact on daily practice? Every year, the editorial board of the Bulletin du Cancer proposes a selection of key data in oncology and hematology. The objective is to discuss results that change or reinforce the strategies in 2016 but also identify key information for our reflections in 2017.

  6. Detection of a Pancreatic Cancer-Associated Antigen (DU-PAN-2 Antigen) in Serum and Ascites of Patients with Adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Metzgar, Richard S.; Rodriguez, Ned; Finn, Olivera J.; Lan, Michael S.; Daasch, Vicki N.; Fernsten, Philip D.; Meyers, William C.; Sindelar, William F.; Sandler, Robert S.; Seigler, H. F.

    1984-08-01

    A competition radioimmunoassay was developed, utilizing a murine monoclonal antibody to human pancreatic adenocarcinoma cells. Immunoblotting of a standard antigen preparation from either serum or ascites fluid after electrophoresis in 1% agarose showed that the specific DUPAN-2 activity resided in two major high molecular weight bands. DU-PAN-2 antigen levels were expressed as arbitrary units based on a standard partially purified antigen preparation. The inhibition curve with standard antigen was reproducible (SD < 10%) and essentially linear from 25 to 200 units/ml. The mean DU-PAN-2 antigen concentration for the sera from 126 normal individuals was 81 units/ml. Sera from pediatric patients with malignancy had a mean of 127 units/ml, while nasopharyngeal, stage III melanoma, and ovarian carcinoma patients had means of 89, 92, and 119 units/ml, respectively. All values in normal subjects as well as the melanoma, nasopharyngeal, ovarian, and pediatric cancer patients were less than 400 units/ml. Intermediate antigen levels were detected in patients with alimentary tract malignancies. Eight of 20 gastric cancer and 8 of 76 colorectal carcinoma patients and 3 patients with benign or nonmalig nant gastrointestinal tract disease had DU-PAN-2 values exceeding 400 units/ml. Ascites fluids from 6/6 and pancreatic juice from 2/2 pancreatic cancer patients had values greater than 750 units/ml. Serum from 68% of the 89 pancreatic cancer patients tested had DU-PAN-2 antigen levels greater than 400 units/ml. The mean serum value in this patient population was 4888 units/ml.

  7. Problématique de la prise en charge des cancers du sein au Sénégal: une approche transversale

    PubMed Central

    Gueye, Serigne Modou Kane; Gueye, Mamour; Coulbary, Sophie Aminata; Diouf, Alassane; Moreau, Jean Charles

    2016-01-01

    L’heure où les thérapeutiques innovantes se multiplient dans le cancer du sein, des pays moins nantis comme le Sénégal accusent encore un retard considérable dans la prise en charge globale de ce type de cancer. Au Sénégal, même si la prise en charge des cancers du sein avancés est actuellement bien codifiée, les résultats en terme de survie et de morbidités sont encore médiocres vu les retards diagnostiques et les traitements mutilants, parfois onéreux et mal tolérés, devenus nécessaires. Pour ces cancers avancés, les défis qui restent à relever résident dans l’érection de centres de soins palliatifs et le développement de la pluridisciplinarité pour améliorer la qualité de vie et l’accompagnement des malades. En revanche, pour les cancers infracliniques ou potentiellement guérissables, les défis restent immenses car il s’agira de les dépister, de bien les localiser et les diagnostiquer aussitôt (biopsie écho guidée ou stéréotaxique) mais également de les opérer de façon précise et entière (repérage – exérèse in sano et radiographie de pièce opératoire) tout en limitant les complications comme celles du curage classique (biopsie du ganglion sentinelle). Il s’agit là autant d’objectifs auxquels nos structures de santé ne sont pas toujours préparées. Cette mise au point est une analyse situationnelle sur les écueils contextuels qui grèvent encore la prise en charge globale des cancers du sein au Sénégal. PMID:28154696

  8. Targeting breast cancer-initiating/stem cells with melanoma differentiation-associated gene-7/interleukin-24

    PubMed Central

    Bhutia, Sujit K.; Das, Swadesh K.; Azab, Belal; Menezes, Mitchell E.; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

    2015-01-01

    Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) displays a broad range of antitumor properties including cancer-specific induction of apoptosis, inhibition of tumor angiogenesis and modulation of antitumor immune responses. In our study, we elucidated the role of MDA-7/IL-24 in inhibiting growth of breast cancer-initiating/stem cells. Ad.mda-7 infection decreased proliferation of breast cancer-initiating/stem cells without affecting normal breast stem cells. Ad.mda-7 induced apoptosis and endoplasmic reticulum stress in breast cancer-initiating/stem cells similar to unsorted breast cancer cells and inhibited the self-renewal property of breast cancer-initiating/stem cells by suppressing Wnt/β-catenin signaling. Prevention of inhibition of Wnt signaling by LiCl increased cell survival upon Ad.mda-7 treatment, suggesting that Wnt signaling inhibition might play a key role in MDA-7/IL-24-mediated death of breast cancer-initiating/stem cells. In a nude mouse subcutaneous xenograft model, Ad.mda-7 injection profoundly inhibited growth of tumors generated from breast cancer-initiating/stem cells and also exerted a potent “bystander” activity inhibiting growth of distant uninjected tumors. Further studies revealed that tumor growth inhibition by Ad.mda-7 was associated with a decrease in proliferation and angiogenesis, two intrinsic features of MDA-7/IL-24, and a reduction in vivo in the percentage of breast cancer-initiating/stem cells. Our findings demonstrate that MDA-7/IL-24 is not only nontoxic to normal cells and normal stem cells but also can kill both unsorted cancer cells and enriched populations of cancer-initiating/stem cells, providing further documentation that MDA-7/IL-24 might be a safe and effective way to eradicate cancers and also potentially establish disease-free survival. PMID:23720015

  9. Do subtle breast cancers attract visual attention during initial impression?

    NASA Astrophysics Data System (ADS)

    Nodine, Calvin F.; Mello-Thoms, Claudia; Weinstein, Susan P.; Kundel, Harold L.; Toto, Lawrence C.

    2000-04-01

    Women who undergo regular mammographic screening afford mammographers a unique opportunity to compare current mammograms with prior exams. This comparison greatly assists mammographers in detecting early breast cancer. A question that commonly arises when a cancer is detected under regular periodic screening conditions is whether the caner is new, or was it missed on the prior exam? This is a difficult question to answer by retrospective analysis, because knowledge of the status of the current exam biases the interpretation of the prior exam. To eliminate this bias and provide some degree of objectivity in studying this question, we looked at whether experienced mammographers who had no prior knowledge of a set of test cases fixated on potential cancer-containing regions on mammograms from cases penultimate to cancer detection. The results show that experienced mammographers cannot recognize most malignant cancers selected by retrospective analysis.

  10. Infection par le VIH chez les patientes atteintes de cancer du sein en Guinée (Afrique de l'Ouest)

    PubMed Central

    Traore, Bangaly; Diane, Solomana; Sow, Mamadou Saliou; Keita, Mamady; Conde, Mamoudou; Traore, Fodé Amara; Kourouma, Tidiane

    2015-01-01

    L'objectif était de déterminer la prévalence de l'infection à VIH chez les patientes atteintes de cancer du sein et de comparer les caractéristiques anatomocliques et thérapeutiques de ces cancers du sein par rapports aux patientes non infectées par le VIH. Il s'agissait d'une étude rétrospective et analytique comparant les dossiers de patientes atteintes de cancers du sein histologiquement confirmés, infectées ou non par le VIH à l'unité de chirurgie oncologique de Donka, CHU de Conakry, de 2007 à 2012. Nous avons colligé 278 patientes présentant un cancer du sein dont 14 (5,0%) infectées par le VIH et 264 (95,0%) non infectées par le VIH. Les différences observées entre ces deux groupes de patientes étaient respectivement: âge médian (36,8 vs 49,0 ans), la ménopause (21,4% vs 53,4%), le nombre des patientes traitées (50,0% contre 77,1%) et la survenue de décès (78,6% vs 50,8%). Aucune différence n'a été notée dans la présentation clinique, histologique et le retard de consultation. Dans notre étude, la prévalence de l'infection à VIH chez les patients atteints de cancer du sein est élevée. L’âge jeune des patients, la faible accessibilité au traitement et la mortalité élevée doivent être confirmés par une étude sur un échantillon plus large. PMID:26523196

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

    PubMed Central

    Willis, Rudolph E.

    2016-01-01

    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. PMID:27649156

  12. L'intérêt de la sélection du faisceau (12)C par rapport au (13)C pour la radiothérapie du cancer

    NASA Astrophysics Data System (ADS)

    Farés, G.; Hachem, A.; Bimbot, R.; Roussel-Chomaz, P.; Anne, R.; Mirea, M.; Belahbib, S.; Benfoughal, T.; Cabot, C.; Clapier, F.; Freeman, R.; Lewitowicz, M.; Saint-Laurent, M. G.; Sauvestre, J. E.; Sida, J. L.

    1998-04-01

    Heavy ions having interesting properties as Bragg's peak require an important energy in order to attain a deep tumor. At intermediate and relativist energies, fragmentation reactions occur throughout their path and produce fragments lighter than the projectile. Consequently, the product fragments give a residual dose beyond the Bragg peak. For these reasons, the interesting ions in radiotherapy of cancer converge toward heavy light ions (C - Ne). Moreover, for a better treatment safety, it is envisaged also to use β(+) transmitting radioactive ion beams. This allows to provide the picture of the really irradiated volume by using a positon camera. In this context, our works essentially is concentrated on production rates and cross sections calculations for nucleus products in the fragmentation of (12)C at 95 MeV/u and (13)C at 75 MeV/u. Les ions lourds possédant des propriétés balistiques importantes tel que le pic de Bragg nécessitent une énergie importante pour atteindre une tumeur profonde. Aux énergies intermédiaires et relativistes, des réactions de fragmentation se produisent tout au long de leur trajet et donnent naissance à des fragments plus légers que le projectile. Ces derniers entraînent une dose résiduelle au-delà du pic de Bragg. Pour cette raison, les ions les plus intéressants en radiothérapie convergent vers les ions lourds - légers (C à Ne). Par ailleurs, pour une sécurité accrue du traitement, on envisage d'utiliser aussi des faisceaux d'ions radioactifs émetteurs β(+). Ceci permet de fournir l'image du volume réellement irradié en utilisant une caméra à positon. Dans ce contexte, nos travaux ont porté essentiellement sur le calcul de taux de production et de la section efficace des noyaux issus de la fragmentation du (12)C à 95 MeV/u et du (13)C à 75 MeV/u.

  13. 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.

  14. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

    PubMed

    Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

    2016-01-19

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

  15. Targeting cancer-initiating cell drug-resistance: a roadmap to a new-generation of cancer therapies?

    PubMed

    Alama, Angela; Orengo, Anna Maria; Ferrini, Silvano; Gangemi, Rosaria

    2012-05-01

    The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating cells display a range of self-defense systems that include almost all mechanisms of drug-resistance. Different molecular pathways and markers, identified in this malignant sub-population, are becoming targets for novel compounds and for monoclonal antibodies, which may be combined with conventional drugs. These interventions might eliminate drug-resistant cancer-initiating cells and lead to remission or cure of cancer patients.

  16. Complications de l’hormonothérapie anti-androgénique du cancer de la prostate

    PubMed Central

    Ziouziou, Imad; Karmouni, Tariq; Khader, Khalid El; Koutani, Abdellatif; Andaloussi, Ahmed Iben Attya

    2014-01-01

    Résumé Les effets indésirables de l’hormonothérapie anti-androgénique (HAA) dans le traitement du cancer de la prostate sont attribuables à la carence d’androgènes. L’HAA entraîne le syndrome de castration, qui se caractérise par une diminution de la libido, la dysfonction érectile, l’asthénie, des bouffées de chaleur, la diminution des capacités intellectuelles et la dépression. Il en résulte également une augmentation de la graisse abdominale, ce qui favorise l’insulinorésistance et le diabète. La perte de la densité minérale osseuse secondaire à l’HAA entraîne un risque fracturaire accru. Il existe de plus un risque cardiovasculaire important dû aux facteurs métaboliques. L’effet thérapeutique de l’HAA doit donc être soupesé en regard de la toxicité liée à l’hypogonadisme. PMID:24678355

  17. Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells

    PubMed Central

    Morrison, Brian J.

    2012-01-01

    Cancer initiating cells (CICs) represent a unique cell population essential for the maintenance and growth of tumors. Most in vivo studies of CICs utilize human tumor xenografts in immunodeficient mice. These models provide limited information on the interaction of CICs with the host immune system and are of limited value in assessing therapies targeting CICs, especially immune-based therapies. To assess this, a syngeneic cancer model is needed. We examined the sphere-forming capacity of thirteen murine lung cancer cell lines and identified TC-1 and a metastatic subclone of Lewis lung carcinoma (HM-LLC) as cell lines that readily formed and maintained spheres over multiple passages. TC-1 tumorspheres were not enriched for expression of CD133 or CD44, putative CIC markers, nor did they demonstrate Hoechst 33342 side population staining or Aldefluor activity compared to adherent TC-1 cells. However, in tumorsphere culture, these cells exhibited self-renewal and long-term symmetric division capacity and expressed more Oct-4 compared to adherent cells. HM-LLC sphere-derived cells exhibited increased Oct-4, CD133, and CD44 expression, demonstrated a Hoechst 33342 side population and Aldefluor activity compared to adherent cells or a low metastatic subclone of LLC (LM-LLC). In syngeneic mice, HM-LLC sphere-derived cells required fewer cells to initiate tumorigenesis compared to adherent or LM-LLC cells. Similarly TC-1 sphere-derived cells were more tumorigenic than adherent cells in syngeneic mice. In contrast, in immunocompromised mice, less than 500 sphere or adherent TC-1 cells and less than 1,000 sphere or adherent LLC cells were required to initiate a tumor. We suggest that no single phenotypic marker can identify CICs in murine lung cancer cell lines. Tumorsphere culture may provide an alternative approach to identify and enrich for murine lung CICs. Furthermore, we propose that assessing tumorigenicity of murine lung CICs in syngeneic mice better models the

  18. 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

  19. 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

  20. Therapeutic Targeting of Alternative Translation Initiation in Breast Cancer

    DTIC Science & Technology

    2009-04-01

    investigation within the next 6 months. Cell type specific cancer cell killing of the prototype oncolytic poliovirus , PVS-RIPO, depends on selective...demanded by FDA. 15. SUBJECT TERMS Translation, eIF4E, eIF4G, IRES, Cancer, Poliovirus 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...genetically recombinant poliovirus . Moreover, my work has laid the groundwork for correlative testing and efficacy studies of a vast array of protein kinase

  1. HIV Testing in Patients With Cancer at the Initiation of Therapy at a Large US Comprehensive Cancer Center

    PubMed Central

    Hwang, Jessica P.; Granwehr, Bruno P.; Torres, Harrys A.; Suarez-Almazor, Maria E.; Giordano, Thomas P.; Barbo, Andrea G.; Lin, Heather Y.; Fisch, Michael J.; Chiao, Elizabeth Y.

    2015-01-01

    Purpose: To determine the rates of HIV testing and infection among patients with cancer at initiation of systemic cancer therapy. Methods: We conducted a retrospective cohort study of adults with cancer who registered at a comprehensive cancer center from January 2004 through April 2011 and received systemic cancer therapy. We determined rates of HIV-1/2 and/or Western blot testing and HIV positivity at initiation of systemic cancer therapy. Multivariable logistic regression was used to determine predictors of HIV testing. Results: Of 18,874 patients with cancer who received systemic cancer therapy during the study period, 3,514 (18.6%) were tested for HIV at initiation of cancer therapy. The prevalence of positive HIV test results was 1.2% (41 of 3,514), and the prevalence of newly diagnosed HIV was 0.3% (12 of 3,514). The HIV testing rate was lower in black than in white patients (13.7% v 19.2%), but the prevalence of positive test results was higher in black patients (4.5%) than in any other racial/ethnic group. Among patients with AIDS-defining cancers (eg, non-Hodgkin lymphoma and cervical cancer), predictors of HIV testing were history of non-Hodgkin lymphoma, younger age, and registration after 2006. Among patients with non–AIDS-defining cancers, predictors of HIV testing were younger age, registration after 2006, male sex, history of illicit drug use or sexually transmitted disease, having a hematologic malignancy, and black race. Conclusion: The prevalence of HIV infection among patients with cancer was 1.2%, higher than the 0.1% prevalence threshold above which national guidelines recommend routine opt-out testing; however, the overall HIV testing rate was low. PMID:26243649

  2. 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

  3. Necrosis in DU145 prostate cancer spheroids induces COX-2/mPGES-1-derived PGE2 to promote tumor growth and to inhibit T cell activation.

    PubMed

    Sha, Weixiao; Olesch, Catherine; Hanaka, Hiromi; Rådmark, Olof; Weigert, Andreas; Brüne, Bernhard

    2013-10-01

    Cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2 ) supports the growth of a spectrum of cancers. The potential benefit of COX-2-inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) for cancer treatment is however limited by their well-known cardiovascular side-effects. Therefore, targeting microsomal PGE synthase 1 (mPGES-1), the downstream enzyme in the COX-2-dependent pathway of PGE2 production might be attractive, although conflicting data regarding a potential tumor-supporting function of mPGES-1 were reported. We determined the impact of mPGES-1 in human DU145 prostate cancer cell growth. Surprisingly, knockdown of mPGES-1 did not alter growth of DU145 monolayer cells, but efficiently inhibited the growth of DU145 multicellular tumor spheroids (MCTS). Opposed to MCTS, monolayer cells did not secrete PGE2 due to a lack of COX-2 expression, which was induced during spheroid formation. Pharmacological inhibition of COX-2 and mPGES-1 supported the crucial role of PGE2 for growth of MCTS. The functionality of spheroid-derived PGE2 was demonstrated by its ability to inhibit cytotoxic T cell activation. When investigating mechanisms of spheroid-induced COX-2 induction, we observed that among microenvironmental factors neither glucose deprivation, hypoxia nor tumor cell apoptosis enhanced COX-2 expression. Interestingly, interfering with apoptosis in spheroids triggered a shift towards necrosis, thus augmenting COX-2 expression. We went on to demonstrate that necrotic cells induced COX-2 mRNA expression and PGE2 secretion from live tumor cells. In conclusion, necrosis-dependent COX-2 upregulation in MCTS promoted PGE2 -dependent tumor growth and inhibited activated cytotoxic T cells. Hence, blocking mPGES-1 as a therapeutic option may be considered for COX-2/mPGES-1-positive solid cancers.

  4. VEGF-mediated angiogenesis links EMT-induced cancer stemness to tumor initiation.

    PubMed

    Fantozzi, Anna; Gruber, Dorothea C; Pisarsky, Laura; Heck, Chantal; Kunita, Akiko; Yilmaz, Mahmut; Meyer-Schaller, Nathalie; Cornille, Karen; Hopfer, Ulrike; Bentires-Alj, Mohamed; Christofori, Gerhard

    2014-03-01

    An epithelial-mesenchymal transition (EMT) underlies malignant tumor progression and metastatic spread by enabling cancer cells to depart from the primary tumor, invade surrounding tissue, and disseminate to distant organs. EMT also enriches for cancer stem cells (CSC) and increases the capacity of cancer cells to initiate and propagate tumors upon transplantation into immune-deficient mice, a major hallmark of CSCs. However, the molecular mechanisms promoting the tumorigenicity of cancer cells undergoing an EMT and of CSCs have remained widely elusive. We here report that EMT confers efficient tumorigenicity to murine breast cancer cells by the upregulated expression of the proangiogenic factor VEGF-A and by increased tumor angiogenesis. On the basis of these data, we propose a novel interpretation of the features of CSCs with EMT-induced, VEGF-A-mediated angiogenesis as the connecting mechanism between cancer cell stemness and tumor initiation.

  5. Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene

    DTIC Science & Technology

    2006-09-01

    AD_________________ Award Number: W81XWH-05-1-0502 TITLE: Mouse Model of Human Breast Cancer ...TYPE Final 3. DATES COVERED (From - To) 15 AUG 2005 - 14 AUG 2006 4. TITLE AND SUBTITLE Mouse Model of Human Breast Cancer Initiated by a Fusion...SUPPLEMENTARY NOTES 14. ABSTRACT: In this study, we generated a novel mouse model of human breast cancer based on a recurrent chromosomal

  6. Experiencing Health Advocacy During Cervical Cancer Awareness Week: A National Initiative for Obstetrics and Gynaecology Residents.

    PubMed

    Posner, Glenn; Finlayson, Sarah; Luna, Vilma; Miller, Dianne; Fung-Kee-Fung, Michael

    2015-07-01

    Objectif : Le Collège royal des médecins et chirurgiens du Canada exige que les résidents fassent preuve de compétence dans le rôle de promoteur de la santé (PS ou promotion de la santé). Nous avons cherché à élaborer et à mettre en œuvre, à l’intention des résidents en obstétrique-gynécologie, un module pédagogique national traitant de ce rôle de PS. Ce programme pilote était centré sur la prévention du cancer du col utérin, soit un sujet se prêtant bien à l’application des principes de la promotion de la santé. Méthodes : Un module pédagogique a été élaboré et transmis à tous les programmes de résidence en obstétrique-gynécologie au Canada. Ce module décrit les options de PS mettant en jeu le dépistage de la dysplasie cervicale (telles qu’une clinique visant l’élargissement de la population desservie ou un forum d’éducation visant le public / la population étudiante) qui devaient être mises en œuvre au cours de la Semaine de sensibilisation au cancer du col de l’utérus. La réussite a été mesurée en fonction du nombre de programmes mettant en œuvre le curriculum, du nombre de résidents y ayant participé, de la diversité des projets mis en œuvre, de la nature des personnes (patientes ou apprenants) atteintes par le programme et de l’expérience globale des stagiaires. Résultats : Trois programmes ont mis en œuvre le curriculum en 2011, un programme l’a fait en 2012 et sept l’ont fait en 2013. Après trois ans, le module s’est attiré la participation directe ou indirecte de sept des 16 facultés de médecine, de plus de 100 résidents et de milliers de femmes. De plus, les attributs de la PS vécus par les résidents ont été identifiés : travail d’équipe, leadership, connaissances accrues au sujet des systèmes, capital social accru au sein de la communauté, créativité, innovation et adaptabilité. Conclusion : Nous avons démontré qu’un module pédagogique, visant

  7. Differential roles of STAT3 in the initiation and growth of lung cancer.

    PubMed

    Zhou, J; Qu, Z; Yan, S; Sun, F; Whitsett, J A; Shapiro, S D; Xiao, G

    2015-07-01

    Signal transducer and activator of transcription 3 (STAT3) is linked to multiple cancers, including pulmonary adenocarcinoma. However, the role of STAT3 in lung cancer pathogenesis has not been determined. Using lung epithelial-specific inducible knockout strategies, we demonstrate that STAT3 has contrasting roles in the initiation and growth of both chemically and genetically induced lung cancers. Selective deletion of lung epithelial STAT3 in mice before cancer induction by the smoke carcinogen, urethane, resulted in increased lung tissue damage and inflammation, K-Ras oncogenic mutations and tumorigenesis. Deletion of lung epithelial STAT3 after establishment of lung cancer inhibited cancer cell proliferation. Simultaneous deletion of STAT3 and expression of oncogenic K-Ras in mouse lung elevated pulmonary injury, inflammation and tumorigenesis, but reduced tumor growth. These studies indicate that STAT3 prevents lung cancer initiation by maintaining pulmonary homeostasis under oncogenic stress, whereas it facilitates lung cancer progression by promoting cancer cell growth. These studies also provide a mechanistic basis for targeting STAT3 to lung cancer therapy.

  8. Interleukin-6 Prevents the Initiation but Enhances the Progression of Lung Cancer.

    PubMed

    Qu, Zhaoxia; Sun, Fan; Zhou, Jingjiao; Li, Liwen; Shapiro, Steven D; Xiao, Gutian

    2015-08-15

    Recent studies suggest that high expression of the proinflammatory cytokine IL6 is associated with poor survival of lung cancer patients. Accordingly, IL6 has been a target of great interest for lung cancer therapy. However, the role of IL6 in lung cancer has not been determined yet. Here, we demonstrate that IL6 plays opposite roles in the initiation and growth of lung cancer in a mouse model of lung cancer induced by the K-Ras oncogene. We find that compared with wild-type mice, IL6-deficient mice developed much more lung tumors after an activating mutant of K-Ras was induced in the lungs. However, lung tumors developed in IL6-deficient mice were significantly smaller. Notably, both the lung tumor-suppressing and -promoting functions of IL6 involve its ability in activating the transcription factor STAT3. IL6/STAT3 signaling suppressed lung cancer initiation through maintaining lung homeostasis, regulating lung macrophages, and activating cytotoxic CD8 T cells under K-Ras oncogenic stress, whereas it promoted lung cancer cell growth through inducing the cell proliferation regulator cyclin D1. These studies reveal a previously unexplored role of IL6/STAT3 signaling in maintaining lung homeostasis and suppressing lung cancer induction. These studies also significantly improve our understanding of lung cancer and provide a molecular basis for designing IL6/STAT3-targeted therapies for this deadliest human cancer.

  9. 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.

  10. Human chorionic gonadotropin β induces migration and invasion via activating ERK1/2 and MMP-2 in human prostate cancer DU145 cells.

    PubMed

    Li, Zongwen; Li, Chunliu; Du, Lianlian; Zhou, Yan; Wu, Wei

    2013-01-01

    We previously demonstrated that human chorionic gonadotropin β (hCGβ) induced migration and invasion in human prostate cancer cells. However, the involved molecular mechanisms are unclear. Here, we established a stable prostate cancer cell line overexpressing hCGβ and tested hCGβ-triggered signaling pathways causing cell migration and invasion. ELISA showed that the hCGβ amount secreted into medium increased with culture time after the hCGβ-transfected cells were incubated for 3, 6, 9, 12 and 24 h. More, hCGβ standards promoted MAPK (ERK1/2) phosphorylation and increased MMP-2 expression and activity in both dose- and time-dependent manners in hCGβ non-transfected cells. In addition, hCGβ promoted ERK1/2 phosphorylation and increased MMP-2 expression and activity significantly in hCGβ transfected DU145 cells. Whereas ERK1/2 blocker PD98059 (25 µM) significantly downregulated phosphorylated ERK1/2 and MMP-2. Particularly, hCGβ promoted cell migration and invasion, yet the PD98059 diminished the hCGβ-induced cell motility under those conditions. These results indicated that hCGβ induced cell motility via promoting ERK1/2 phosphorylation and MMP-2 upregulation in human prostate cancer DU145 cells.

  11. 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

  12. Place de la chirurgie dans la prise en charge des cancers du sein chez la femme au Centre Hospitalier Universitaire Yalgado Ouedraogo: à propos de 81 cas

    PubMed Central

    Zongo, Nayi; Millogo-Traore, Timonga Françoise Danielle; Bagre, Sidpawalmdé Carine; Bagué, Abdoul-Halim; Ouangre, Edgar; Zida, Maurice; Bambara, Aboubacar; Bambara, Tozoula Augustin; Traoré, Si Simon

    2015-01-01

    Etudier la place de la chirurgie dans la prise en charge des cancers du sein au centre hospitalier universitaire Yalgado Ouédraogo. Nous avons réalisé une étude prospective et descriptive sur dix (10) mois portant sur la place de la chirurgie dans le cancer du sein. Elle a eu pour cadre les services de gynécologie-obstétrique et de chirurgie viscérale et digestive du centre hospitalier universitaire Yalgado Ouédraogo. Ont été pris en compte les indications, les gestes et les résultats de la chirurgie. Nous avons colligé 81 cancers mammaires. Le délai moyen de consultation a été de 14,26 mois. Les tumeurs T3 à T4 représentaient 82,71% des cas. Trente-huit patientes (46,91%) ont été opérées. La chimiothérapie néo adjuvante a été réalisée dans 29,63% des cas. Trente-quatre patientes (41,97%) étaient opérables d'emblée. Il s'agissait de mastectomie selon Madden dans 94,74% des cas et de chirurgie de propreté dans 2 cas (5,26% des cas). Une chimiothérapie adjuvante a été réalisée chez 52,63% des patientes opérées. Des complications à type de lymphocèle ont été notées dans 23,68% des cas. Leur traitement a consisté en des ponctions évacuatrices. Les indications de la chirurgie sont limitées par le retard diagnostique corollaire de stades avancés des cancers du sein. L'absence de la radiothérapie rend délicate la pratique de la chirurgie conservatrice et la mastectomie occupe toujours une place importante. Un diagnostic précoce permettrait d'augmenter les indications chirurgicales. PMID:26848364

  13. Pharmacoproteomic study of the natural product Ebenfuran III in DU-145 prostate cancer cells: the quantitative and temporal interrogation of chemically induced cell death at the protein level.

    PubMed

    Roumeliotis, Theodoros I; Halabalaki, Maria; Alexi, Xanthippi; Ankrett, Dyan; Giannopoulou, Eugenia G; Skaltsounis, Alexios-Leandros; Sayan, Berna S; Alexis, Michael N; Townsend, Paul A; Garbis, Spiros D

    2013-04-05

    A naturally occurring benzofuran derivative, Ebenfuran III (Eb III), was investigated for its antiproliferative effects using the DU-145 prostate cell line. Eb III was isolated from Onobrychis ebenoides of the Leguminosae family, a plant endemic in Central and Southern Greece. We have previously reported that Eb III exerts significant cytotoxic effects on certain cancer cell lines. This effect is thought to occur via the isoprenyl moiety at the C-5 position of the molecule. The study aim was to gain a deeper understanding of the pharmacological effect of Eb III on DU-145 cell death at the translational level using a relative quantitative and temporal proteomics approach. Proteins extracted from the cell pellets were subjected to solution phase trypsin proteolysis followed by iTRAQ-labeling. The labeled tryptic peptide extracts were then fractionated using strong cation exchange chromatography and the fractions were analyzed by nanoflow reverse phase ultraperformance liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry analysis using a hybrid QqTOF platform. Using this approach, we compared the expression levels of 1360 proteins analyzed at ≤ 1% global protein false discovery rate (FDR), commonly present in untreated (control, vehicle only) and Eb III-treated cells at the different exposure time points. Through the iterative use of Ingenuity Pathway Analysis with hierarchical clustering of protein expression patterns, followed by bibliographic research, the temporal regulation of the Calpain-1, ERK2, PAR-4, RAB-7, and Bap31 proteins were identified as potential nodes of multipathway convergence to Eb III induced DU-145 cell death. These proteins were further verified with Western blot analysis. This gel-free, quantitative 2DLC-MS/MS proteomics method effectively captured novel modulated proteins in the DU-145 cell line as a response to Eb III treatment. This approach also provided greater insight to the multifocal and combinatorial signaling

  14. Cancer initiating-cells are enriched in the CA9 positive fraction of primary cervix cancer xenografts

    PubMed Central

    Marie-Egyptienne, Delphine Tamara; Chaudary, Naz; Kalliomäki, Tuula; Hedley, David William; Hill, Richard Peter

    2017-01-01

    Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied. Analyses of the expression of the stem cell markers Oct4, Notch1, Sca-1 & Bmi1 showed a trend toward an increase in the CA9+ populations, albeit not significant. We present evidence that enhanced autophagy does not play a role in the enhanced growth of the CA9+ cells. Our study suggests a direct in vivo functional link between hypoxic cells and CICs in primary cervix cancer xenografts. PMID:27901496

  15. 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.

  16. Yin and Yang of Heparanase in Breast Cancer Initiation

    DTIC Science & Technology

    2012-04-01

    less effective in stimulating breast tumor initiation and progression. Experimental procedures and results Sulodexide treatment accelerates PyMT...mediated tumorigenesis. Sulodexide is a mixture of dermatan sulfate (20%) and low-molecular-weight heparin (80%) (Keryx Biopharmaceuticals, Inc...New York). We examined the ability of sulodexide to inhibit HPR1 activity by using a novel ELISA method developed in my laboratory (3-7). As shown

  17. The Haiti Breast Cancer Initiative: Initial Findings and Analysis of Barriers-to-Care Delaying Patient Presentation

    PubMed Central

    Sharma, Ketan; Costas, Ainhoa; Damuse, Ruth; Hamiltong-Pierre, Jean; Pyda, Jordan; Ong, Cecilia T.; Shulman, Lawrence N.; Meara, John G.

    2013-01-01

    Background. In Haiti, breast cancer patients present at such advanced stages that even modern therapies offer modest survival benefit. Identifying the personal, sociocultural, and economic barriers-to-care delaying patient presentation is crucial to controlling disease. Methods. Patients presenting to the Hôpital Bon Sauveur in Cange were prospectively accrued. Delay was defined as 12 weeks or longer from initial sign/symptom discovery to presentation, as durations greater than this cutoff correlate with reduced survival. A matched case-control analysis with multivariate logistic regression was used to identify factors predicting delay. Results. Of N = 123 patients accrued, 90 (73%) reported symptom-presentation duration and formed the basis of this study: 52 patients presented within 12 weeks of symptoms, while 38 patients waited longer than 12 weeks. On logistic regression, lower education status (OR = 5.6, P = 0.03), failure to initially recognize mass as important (OR = 13.0, P < 0.01), and fear of treatment cost (OR = 8.3, P = 0.03) were shown to independently predict delayed patient presentation. Conclusion. To reduce stage at presentation, future interventions must educate patients on the recognition of initial breast cancer signs and symptoms and address cost concerns by providing care free of charge and/or advertising that existing care is already free. PMID:23840209

  18. 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

  19. Molecular genetics of bladder cancer: Emerging mechanisms of tumor initiation and progression.

    PubMed

    McConkey, David J; Lee, Sangkyou; Choi, Woonyoung; Tran, Mai; Majewski, Tadeusz; Lee, Sooyong; Siefker-Radtke, Arlene; Dinney, Colin; Czerniak, Bogdan

    2010-01-01

    Urothelial cancer has served as one of the most important sources of information about the mutational events that underlie the development of human solid malignancies. Although "field effects" that affect the entire bladder mucosa appear to initiate disease, tumors develop along 2 distinct biological "tracks" that present vastly different challenges for clinical management. Recent whole genome methodologies have facilitated even more rapid progress in the identification of the molecular mechanisms involved in bladder cancer initiation and progression. Specifically, whole organ mapping combined with high resolution, high throughput SNP analyses have identified a novel class of candidate tumor suppressors ("forerunner genes") that localize near more familiar tumor suppressors but are disrupted at an earlier stage of cancer development. Furthermore, whole genome comparative genomic hybridization (CGH) and mRNA expression profiling have demonstrated that the 2 major subtypes of urothelial cancer (papillary/superficial and non-papillary/muscle-invasive) are truly distinct molecular entities, and in recent work our group has discovered that muscle-invasive tumors express molecular markers characteristic of a developmental process known as "epithelial-to-mesenchymal transition" (EMT). Emerging evidence indicates that urothelial cancers contain subpopulations of tumor-initiating cells ("cancer stem cells") but the phenotypes of these cells in different tumors are heterogeneous, raising questions about whether or not the 2 major subtypes of cancer share a common precursor. This review will provide an overview of these new insights and discuss priorities for future investigation.

  20. Putative cancer-initiating stem cells in cell culture models for molecular subtypes of clinical breast cancer

    PubMed Central

    TELANG, NITIN

    2015-01-01

    Cancer-initiating stem cells (CISC) represent a minor subpopulation of heterogeneous breast cancer. CISC are responsible for the acquired resistance to conventional chemoendocrine therapy and eventual relapse observed in patients with breast cancer. Certain molecular subtypes of clinical breast cancer that exhibit differential expression of genes coding for hormone and growth factor receptors differ in their response to conventional chemoendocrine therapy and targeted therapeutic inhibitors. Thus, the development of reliable cell culture models for CISC may provide a valuable experimental approach for the study of stem cell-targeted therapy for the treatment of breast cancer. The present study utilized optimized cell culture systems as experimental models for different molecular subtypes of clinical breast cancer, including luminal A, human epidermal growth factor receptor (HER)-2-enriched and triple negative breast cancer. Biomarker end points, including control of homeostatic growth, cancer risk and drug resistance, were quantitatively analyzed in the selected models. The results of the analyses indicated that, compared with the non-tumorigenic controls, the cell models representing the aforementioned molecular subtypes of clinical breast cancer exhibited aberrant cell cycle progression, downregulated cellular apoptosis and loss of control of homeostatic growth, as evidenced by hyperproliferation. Additionally, these models displayed persistent cancer risk, as indicated by their high incidence and frequency of anchorage-independent (AI) colony formation in vitro and their tumor development capacity in vivo. Furthermore, in the presence of maximum cytostatic drug concentrations, the drug-resistant phenotypes isolated from the parental drug-sensitive cell lines representing luminal A, HER-2-enriched and triple negative breast cancer exhibited an 11.5, 5.0 and 6.2 fold increase in cell growth, and a 5.6, 5.4 and 4.4 fold increase in the number of AI colonies

  1. Deciphering the Translational Determinants of Prostate Cancer Initiation and Progression

    DTIC Science & Technology

    2012-07-01

    cellular invasion ( P -value 0.009), cell proliferation ( P -value 0.04), metabolism ( P -value 0.0002), and regulators of protein modification ( P -value 0.01...ribosomal proteins, 6 elongation factors, and 4 translation initiation factors ( P -value 7.5e-82)(Fig. 2a). Therefore, this class of mTOR responsive mRNAs...pre-treatment with 1µg/ml doxycycline followed by transfection of respective 5’UTR constructs (mean + SEM, n = 9, * P ɘ.0001, t-test)(Right panel

  2. Early versus delayed initiation of adjuvant treatment for pancreatic cancer

    PubMed Central

    Kim, Hyoung Woo; Lee, Jong-Chan; Lee, Jongchan; Kim, Jin Won; Kim, Jaihwan; Hwang, Jin-Hyeok

    2017-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC. Methods We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20–83 days]). Results Patient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334–6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081–3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160–3.862) were significantly associated with shorter OS. Conclusions Adjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications. PMID:28301556

  3. [Mechanisms of plant polyphenols anti-cancer effects. I. Blockade of carcinogenesis initiation].

    PubMed

    Zinov'eva, V N; Spasov, A A

    2012-01-01

    Mechanisms of anti-cancer effects of polyphenols, found in fruits, vegetables, spices and representing parts of daily nutrition, have been considered. These compounds may be the basis for development of cancer preventive preparations. They can block carcinogenesis initiation by inactivation of exogenous or endogenous genotoxic molecules including reactive oxygen species. Another mechanism consists in inhibition of activity and synthesis of carcinogen-metabolizing enzymes. Plant polyphenols also induce expression of antioxidant and detoxification enzymes genes.

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

    DTIC Science & Technology

    2012-10-01

    Tyrosine Kinase Activity in Prostate Cancer Initiation, Progression, and Metastasis PRINCIPAL INVESTIGATOR: Justin Drake CONTRACTING...PROJECT NUMBER Justin Drake and Owen Witte 5e. TASK NUMBER Email: jdrake@mednet.ucla.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S...of tyrosine kinase networks during prostate cancer progression Justin M. Drakea, Nicholas A. Grahamb,c, Tanya Stoyanovaa, Amir Sedghia, Andrew S

  5. Tubal ligation and risk of endometrial cancer: Findings from the Women’s Health Initiative

    PubMed Central

    Winer, Ira; Lehman, Amy; Wactawski-Wende, Jean; Robinson, Randall; Simon, Michael; Cote, Michele

    2015-01-01

    Objective Bilateral tubal ligation (BTL) is a common form of birth control in the United States. There is limited, contradictory data examining BTL and the risk of endometrial cancer and none examining type I and type II cancers separately. We investigated the association between BTL and endometrial cancer risk utilizing the Women’s Health Initiative (WHI) Observational (OS) and Dietary Modification (DM) Studies. Methods Demographic information and history of BTL were obtained from the baseline questionnaires from 76,483 WHI participants in the OS and DM. Univariable and multivariable models were used to examine the association of BTL with type I and type II endometrial cancers. Results 1,137 women were diagnosed with incident endometrial cancer (972 type I and 128 type II) over a mean follow-up of 11.3 years. Overall, 14,499 women (19%) had undergone BTL. There were no statistically significant associations noted between BTL or age at BTL for type I or type II cancers. Conclusion We examined the largest patient cohort to date in an effort to determine the impact of BTL on endometrial cancer risk. In the WHI trial we observed no overall effect of BTL on the risk of type I or type II endometrial cancer, suggesting that patients undergoing this popular birth-control method likely do not have an associated change in their baseline risk for endometrial cancer. PMID:26825831

  6. Physician-Initiated Stop-Smoking Program for Patients Receiving Treatment for Early-Stage Cancer

    ClinicalTrials.gov

    2015-10-06

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Head and Neck Cancer; Lung Cancer; Lymphoma; Prostate Cancer; Testicular Germ Cell Tumor; Tobacco Use Disorder; Unspecified Adult Solid Tumor, Protocol Specific

  7. 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

  8. Assessment of duration until initial treatment and its determining factors among newly diagnosed oral cancer patients

    PubMed Central

    Chiou, Shang-Jyh; Lin, Wender; Hsieh, Chi-Jeng

    2016-01-01

    Abstract Few studies have focused on the early treatment stages of cancer, and the impact of treatment delay on oncologic outcomes is poorly defined. We used oral cancer as an example to investigate the distribution of durations until initial treatment. This study was conducted using the National Health Insurance Research Database, which is linked to Taiwan's Cancer Registry and Death Registry databases. We defined “cutoff points for first-time treatment” according to a weekly schedule and sorted the patients into 2 groups based on whether their duration until initial treatment was longer or shorter than each cutoff. We then calculated the Kaplan–Meier estimator to determine the difference in survival rates between the 2 groups and performed logistic regression to identify determining factors. The average time between diagnosis and initial treatment was approximately 22.45 days. The average survival duration was 1363 days (standard deviation: 473.06 days). Oral cancer patients had no statistically significant differences in survival until a cutoff point of 3 weeks was used (with survival duration 71 days longer if initial treatment was received within 3 weeks). Patients with higher incomes or higher Charlson comorbidity index scores and patients treated at a hospital in a region with medium urbanization had lower likelihoods of treatment delay, whereas older patients were at higher risk of treatment delay. The attitudes, beliefs, and social contexts of oral cancer patients influence the treatment-seeking behaviors of these patients. Therefore, the government should advocate the merits of the referral system for cancer treatment or improve quality assurance for cancer diagnoses across different types of hospitals. Health authorities should also educate patients or use a case manager to encourage prompt treatment within 3 weeks and should provide screening and prevention services, particularly for high-risk groups, to reduce mortality risk. PMID:27977607

  9. Anticancer Effect of Fucoidan on DU-145 Prostate Cancer Cells through Inhibition of PI3K/Akt and MAPK Pathway Expression

    PubMed Central

    Choo, Gang-Sik; Lee, Hae-Nim; Shin, Seong-Ah; Kim, Hyeong-Jin; Jung, Ji-Youn

    2016-01-01

    In this study, we showed that PI3K/Akt signaling mediates fucoidan’s anticancer effects on prostate cancer cells, including suppression of proliferation. Fucoidan significantly decreased viability of DU-145 cancer cells in a concentration-dependent manner as shown by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The drug also significantly increased chromatin condensation, which indicates apoptosis, in a concentration-dependent manner as shown by DAPI (4′,6-diamidino-2-phenylindole) staining. Fucoidan increased expression of Bax, cleaved poly-ADP ribose polymerase and cleaved caspase-9, and decreased of the Bcl-2, p-Akt, p-PI3K, p-P38, and p-ERK in a concentration-dependent manner. In vivo, fucoidan (at 5 and 10 mg/kg) significantly decreased tumor volume, and increased apoptosis as assessed by the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, confirming the tumor inhibitory effect. The drug also increased expression of p-Akt and p-ERK as shown by immunohistochemistry staining. Therefore, fucoidan may be a promising cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human prostate cancer cells. PMID:27399727

  10. Solitary Fibrous Tumor of the Prostate Which Was Initially Misdiagnosed as Prostate Cancer

    PubMed Central

    Osamu, Soma; Murasawa, Hiromi; Yoneyama, Takahiro; Koie, Takuya; Ohyama, Chikara

    2017-01-01

    Solitary fibrous tumor (SFT) of the prostate is a very rare tumor. We report a case of 65-year-old man with SFT of the prostate which was initially misdiagnosed as prostate cancer. Finally, we performed total prostatectomy and the tumor was histologically diagnosed as SFT of the prostate. The patient's clinical course has progressed favorably with no obvious recurrence 18 months postoperatively.

  11. Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis.

    PubMed

    Colombo, Michela; Mirandola, Leonardo; Reidy, Adair; Suvorava, Natallia; Konala, Venu; Chiaramonte, Raffaella; Grizzi, Fabio; Rahman, Rakhshanda Layeequr; Jenkins, Marjorie R; Nugyen, Diane D; Dalhbeck, Scott; Cobos, Everardo; Figueroa, Jose A; Chiriva-Internati, Maurizio

    2015-03-01

    Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer.

  12. Advancing Transdisciplinary Research: The Transdisciplinary Research on Energetics and Cancer Initiative.

    PubMed

    Gehlert, Sarah; Hall, Kara; Vogel, Amanda; Hohl, Sarah; Hartman, Sheri; Nebeling, Linda; Redline, Susan; Schmitz, Kathryn; Thornquist, Mark; Patterson, Ruth; Thompson, Beti

    2014-09-01

    Strategies for constructing and maintaining cross-disciplinary teams are in their infancy. We outline strategies to support one form, transdisciplinary research, in a major initiative of the National Cancer Institute, the Transdisciplinary Research in Energetics and Cancer 2 (TREC2) initiative. Discussion of the TREC2 sites' experiences with transdisciplinarity is structured around a conceptual model that identifies four iterative phases of transdisciplinary research. An active coordination center, regular face-to-face meetings, and input from external advisors were instrumental in moving TREC2 to the translation phase. The possibilities for advancements in the science of energetics and cancer increased as investigator ties became denser. TREC2 can be seen as a flagship effort in transdisciplinary science that provides lessons on moving ideas from development to translation.

  13. Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21.

    PubMed

    Zhou, Benhong; Wang, Jing; Zheng, Guohua; Qiu, Zhenpeng

    2016-11-01

    Urolithins are bioactive ellagic acid-derived metabolites produced by human colonic microflora. Although previous studies have demonstrated the cytotoxicity of urolithins, the effect of urolithins on miRNAs is still unclear. In this study, the suppressing effects of methylated urolithin A (mUA) on cell viability in human prostate cancer DU145 cells was investigated. mUA induced caspase-dependent cell apoptosis, mitochondrial depolarization and down-regulation of Bcl-2/Bax ratio. The results showed that upon exposure to mUA, miR-21 expression was decreased and the expression of PTEN and Pdcd4 protein was elevated. mUA could further suppress Akt phosphorylation and increase protein expression of FOXO3a, and the effects of mUA on Akt phosphorylation and protein expression of FOXO3a were blocked by PTEN silence. Moreover, mUA suppressed the Wnt/β-catenin-mediated transcriptional activation of MMP-7 and c-Myc, and this function of mUA on MMP-7 and c-Myc was attenuated by over-expression of miR-21. In conclusion, our data suggest that mUA can suppress cell viability in DU145 cells through modulating miR-21 and its downstream series-wound targets, including PTEN, Akt and Wnt/β-catenin signaling.

  14. Nuclear-Shell Biopolymers Initiated by Telomere Elongation for Individual Cancer Cell Imaging and Drug Delivery.

    PubMed

    Zhang, Zhen; Jiao, Yuting; Zhu, Mengting; Zhang, Shusheng

    2017-04-04

    Here, we propose a strategy for unique nuclear-shell biopolymers initiated by telomere elongation for telomerase activity detection and precise drug delivery to individual cancer cells. Telomerase-triggered DNA rolling-circle amplification (RCA) is used to assemble nuclear-shell biopolymers with signal molecules for selective cancer cell recognition and efficient drug delivery to targeted individual cells. This strategy not only should allow the creation of clustered 5-carboxyfluorescein (FAM)-fluorescence spots in response to human-telomerase activity in individual cancer cells but also could efficiently deliver drugs to reduce the undesired death of healthy cells. These findings offer new opportunities to improve the efficacy of cancer cell imaging and therapy.

  15. Impact of hyperhomocysteinemia on breast cancer initiation and progression: epigenetic perspective.

    PubMed

    Naushad, Shaik Mohammad; Reddy, Cheruku Apoorva; Kumaraswami, Konda; Divyya, Shree; Kotamraju, Srigiridhar; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadha Rao; Kutala, Vijay Kumar

    2014-03-01

    Our recent study showing association of hyperhomocysteinemia and hypomethioninemia in breast cancer and other studies indicating association of hyperhomocysteinemia with metastasis and development of drug resistance in breast cancer cells treated with homocysteine lead us to hypothesize that homocysteine might modulate the expression of certain tumor suppressors, i.e., RASSF1, RARβ1, CNND1, BRCA1, and p21, and might influence prognostic markers such as BNIP3 by inducing epigenetic alteration. To demonstrate this hypothesis, we have treated MCF-7 and MDA-MB-231 cells with different doses of homocysteine and observed dose-dependent inhibition of BRCA1 and RASSF1, respectively. In breast cancer tissues, we observed the following expression pattern: BNIP3 > BRCA1 > RARβ1 > CCND1 > p21 > RASSF1. Hyperhomocysteinemia was positively associated with BRAC1 hypermethylation both in breast cancer tissue and corresponding peripheral blood. Peripheral blood CpG island methylation of BRCA1 in all types of breast cancer and methylation of RASSF1 in ER/PR-negative breast cancers showed positive correlation with total plasma homocysteine. The methylation of RASSF1 and BRCA1 was associated with breast cancer initiation as well as progression, while BRCA1 methylation was associated with DNA damage. Vitamin B12 showed inverse association with the methylation at both the loci. RFC1 G80A and cSHMT C1420T variants showed positive association with methylation at both the loci. Genetic variants influencing remethylation step were associated positively with BRCA1 methylation and inversely with RASSF1 methylation. GCPII C1561T variant showed inverse association with BRCA1 methylation. We found good correlation of BRAC1 (r = 0.90) and RASSF1 (0.92) methylation pattern between the breast cancer tissue and the corresponding peripheral blood. To conclude, elevated homocysteine influences methionine dependency phenotype of breast cancer cells and is associated with breast cancer progression by

  16. Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

    PubMed Central

    Noto, A; Raffa, S; De Vitis, C; Roscilli, G; Malpicci, D; Coluccia, P; Di Napoli, A; Ricci, A; Giovagnoli, M R; Aurisicchio, L; Torrisi, M R; Ciliberto, G; Mancini, R

    2013-01-01

    In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These

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

    SciTech Connect

    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 oxygen 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.

  18. Short-form Ron is a novel determinant of ovarian cancer initiation and progression

    PubMed Central

    Moxley, Katherine M.; Wang, Luyao; Welm, Alana L.; Bieniasz, Magdalena

    2016-01-01

    Short-form Ron (sfRon) is an understudied, alternative isoform of the full-length Ron receptor tyrosine kinase. In contrast to Ron, which has been shown to be an important player in many cancers, little is known about the role of sfRon in cancer pathogenesis. Here we report the striking discovery that sfRon expression is required for development of carcinogen-induced malignant ovarian tumors in mice. We also show that sfRon is expressed in several subtypes of human ovarian cancer including high-grade serous carcinomas, which is in contrast to no detectable expression in healthy ovaries. In addition, we report that introduction of sfRon into OVCAR3 cells resulted in epithelial-to-mesenchymal transition, activation of the PI3K and PDK1 pathway, and inhibition of the MAPK pathway. We demonstrated that sfRon confers an aggressive cancer phenotype in vitro characterized by increased proliferation and migration, and decreased adhesion of ovarian cancer cells. Moreover, the in vivo studies show that OVCAR3 tumors expressing sfRon exhibit significantly more robust growth and spreading to the abdominal cavity when compared with the parental sfRon negative OVCAR3 cells. These data suggest that sfRon plays a significant role in ovarian cancer initiation and progression, and may represent a promising therapeutic target for ovarian cancer treatment. PMID:27551332

  19. Tight Junctions: A Barrier to the Initiation and Progression of Breast Cancer?

    PubMed Central

    Brennan, Kieran; Offiah, Gozie; McSherry, Elaine A.; Hopkins, Ann M.

    2010-01-01

    Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression. PMID:19920867

  20. Electric Blanket Use and Risk of Thyroid Cancer in the Women's Health Initiative Observational Cohort.

    PubMed

    Kato, Ikuko; Young, Alicia; Liu, Jingmin; Abrams, Judith; Bock, Cathryn; Simon, Michael

    2015-01-01

    Thyroid cancer disproportionally affects more women than men. The aim of this study was to assess whether exposure to extremely low frequency electric magnetic fields from electric blankets (EBs) was associated with the development of thyroid cancer. Data were analyzed from 89,527 women who participated in the Women's Health Initiative Observational Study and who responded to questions concerning prior use of EBs. During a mean follow-up of 12.2 years, 190 incident cases of thyroid cancer were identified. We estimated the hazard ratio (HR) and 95 percent confidence interval (CI) of incident thyroid cancer associated with EB use by Cox's proportional hazard model, adjusted for selected covariates. A majority, 57 percent, of the women in the cohort reported the use of EBs while sleeping and/or for warming the bed before sleep. No association was found between use of EBs and subsequent risk of thyroid cancer (HR = 0.98, 95 percent CI 0.72-1.32). Duration of EB use measured in years, months, or hours had no effect on risk. These results did not change when the cases were limited to papillary thyroid cancer, the most frequently occurring histologic type. The results of this study do not support possible health hazards of EBs in regards to thyroid cancer risk.

  1. 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

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

    PubMed Central

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

    2013-01-01

    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

  3. Selection of brain metastasis-initiating breast cancer cells determined by growth on hard agar.

    PubMed

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

    2011-05-01

    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.

  4. The Asian-American and Pacific Islander population and the American Cancer Society initiative.

    PubMed

    Vance, Ralph

    2005-12-15

    The American Cancer Society (ACS) Nationwide Asian-American/Pacific Islander (AAPI) Initiative is a continuing collaboration between the ACS and other organizations and community groups. With a view to incorporating access to quality treatment as an over-arching principal, the objectives of the AAPI Initiative are to provide strategic oversight to the ACS for outreach to AAPI populations and to develop a nationwide plan for the purpose of making ACS programs and services available to these populations. After a series of meetings in 2002, including a joint meeting between the Asian American Network for Cancer Awareness, Research, and Training (AANCART) and the ACS, the first ACS Nationwide AAPI Council meeting was held in early 2003. The goals and objectives of this initiative are 1) to develop a plan for delivery of ACS programs and services to the AAPI population, 2) to develop a program for collaboration with organizations that can help the ACS reach its objectives, 3) to develop an advocacy program that enables the ACS to reach its objectives, and 4) to develop an income-development program to both reach and maintain these objectives. The ACS-AANCART collaboration is a great example of the type of collaboration that will make not only the ACS but also the cancer community as a whole successful in eradicating cancer as a major public health problem.

  5. The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression

    PubMed Central

    Sansone, Luigi; Limana, Federica; Arcangeli, Tania; De Santis, Elena; Polese, Milena; Fini, Massimo; Russo, Matteo A.

    2016-01-01

    The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from the initiation to the malignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a “physiological” response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progression. PMID:26798421

  6. In utero-initiated cancer: the role of reactive oxygen species.

    PubMed

    Wan, Joanne; Winn, Louise M

    2006-12-01

    It is becoming more evident that not only can drugs and environmental chemicals interfere with normal fetal development by causing structural malformations, such as limb defects, but that xenobiotic exposure during development can also cause biochemical and functional abnormalities that may ultimately lead to cancer later on in life. Fetal toxicity may be partly mediated by the embryonic bioactivation of xenobiotics to free radical intermediates that can lead to oxidative stress and potentially lead, in some cases, to carcinogenesis. Using a number of examples, this review will focus on the role of reactive oxygen species (ROS) in the mechanisms pertaining to in utero initiated cancers.

  7. Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression

    PubMed Central

    Sharma, Divya Khandige; Bressler, Kamiko; Patel, Harshil; Balasingam, Nirujah

    2016-01-01

    Protein synthesis can be segmented into distinct phases comprising mRNA translation initiation, elongation, and termination. Translation initiation is a highly regulated and rate-limiting step of protein synthesis that requires more than 12 eukaryotic initiation factors (eIFs). Extensive evidence shows that the transcriptome and corresponding proteome do not invariably correlate with each other in a variety of contexts. In particular, translation of mRNAs specific to angiogenesis, tumor development, and apoptosis is altered during physiological and pathophysiological stress conditions. In cancer cells, the expression and functions of eIFs are hampered, resulting in the inhibition of global translation and enhancement of translation of subsets of mRNAs by alternative mechanisms. A precise understanding of mechanisms involving eukaryotic initiation factors leading to differential protein expression can help us to design better strategies to diagnose and treat cancer. The high spatial and temporal resolution of translation control can have an immediate effect on the microenvironment of the cell in comparison with changes in transcription. The dysregulation of mRNA translation mechanisms is increasingly being exploited as a target to treat cancer. In this review, we will focus on this context by describing both canonical and noncanonical roles of eIFs, which alter mRNA translation. PMID:28083147

  8. 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

  9. Surveillance After Initial Treatment for Breast Cancer: A Population-Based Study of Variation In and Outcomes of Care

    DTIC Science & Technology

    1996-10-01

    Ft Detrick, MD. THIS PAGE IS UNCLASSIFIED AAD GRANT NUMBER DAMDI7-94-J-4043 TITLE: Surveillance After Initial Treatment for Breast Cancer: A...NUMBERS Surveillance After Initial Treatment for Breast Cancer: DAMDI7-94-J-4043 A Population-Based Study of Variation In and Outcomes of Care 6. AUTHOR(S...ABSTRACT (Maximum 200 We have utilized SEER and Medicare data bases to study patterns of care related to the treatment of local/regional breast cancer. In

  10. Effects of Androgen and Estrogen Receptor Signaling Pathways on Bladder Cancer Initiation and Progression

    PubMed Central

    Godoy, Guilherme; Gakis, Georgios; Smith, Carolyn L.; Fahmy, Omar

    2016-01-01

    Epidemiologic studies have long demonstrated clear differences in incidence and progression of bladder cancer between genders suggesting that the mechanisms of development and progression in these tumors have a strong association with steroid hormonal pathways. Such observations led to preclinical studies investigating the role of androgen and estrogen receptors, as well as their cognate hormones in bladder cancer initiation and progression. Using various in vitro cell line assays and in vivo mouse models, studies have elucidated different mechanisms and signaling pathways through which these steroid receptors may participate in this disease. More recently, RNA expression data from multiple studies revealed a luminal subtype of bladder cancer that exhibited an estrogen receptor signaling pathway, making it a strong candidate for further consideration of targeted therapies in the future. Despite the promising preclinical data demonstrating potential roles for both antiandrogen and antiestrogen strategies targeting these pathways in different stages of bladder cancer, only two clinical trials are currently active and accruing patients for such clinical studies. Targeted therapies in bladder cancer are a large unmet need and have the potential to change treatment paradigms and improve oncological outcomes of patients with bladder cancer. PMID:27376135

  11. 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

  12. 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

  13. Cardiovascular Health and Incident Cardiovascular Disease and Cancer: The Women's Health Initiative

    PubMed Central

    Foraker, Randi E.; Abdel-Rasoul, Mahmoud; Kuller, Lewis H.; Jackson, Rebecca D.; Van Horn, Linda; Seguin, Rebecca A.; Safford, Monika M.; Wallace, Robert B.; Kucharska-Newton, Anna M.; Robinson, Jennifer G.; Martin, Lisa W.; Agha, Golareh; Hou, Lifang; Allen, Norrina B.; Tindle, Hilary A.

    2015-01-01

    Introduction The American Heart Association's “Simple 7” offers a practical public health conceptualization of cardiovascular health (CVH). CVH predicts incident cardiovascular disease (CVD) in younger populations, but has not been studied in a large, diverse population of aging postmenopausal women. The extent to which CVH predicts cancer in postmenopausal women is unknown. Methods Multivariable Cox regression estimated hazard ratios and 95% CIs for the association between CVH and incident CVD, any cancer, and cancer subtypes (lung, colorectal, and breast) among 161,809 Women's Health Initiative observational study and clinical trial participants followed from 1993 through 2010. Data were analyzed in 2013. CVH score was characterized as the number (0 [worst] to 7 [best]) of the American Heart Association's ideal CVH behaviors and factors at baseline: smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting glucose. Results Median follow-up was approximately 13 years. Fewer minorities and less educated women achieved ideal CVH, a common benchmark. In adjusted models, compared with women with the highest (best) CVH scores, those with the lowest (worst) CVH scores had nearly seven times the hazard of incident CVD (6.83, 95% CI=5.83, 8.00), and 52% greater risk of incident cancer (1.52, 95% CI=1.35, 1.72). Ideal CVH was most strongly inversely associated with lung cancer, then colorectal cancer, and then breast cancer. Conclusions Lower ideal CVH is more common among minority and less educated postmenopausal women, and predicts increased risk of CVD and cancer in this population, emphasizing the importance of prevention efforts among vulnerable older adults. PMID:26456876

  14. Statins and breast cancer stage and mortality in the Women’s Health Initiative

    PubMed Central

    Desai, Pinkal; Lehman, Amy; Chlebowski, Rowan T.; Kwan, Marilyn L.; Arun, Monica; Manson, JoAnn E.; Lavasani, Sayeh; Wasswertheil-Smoller, Sylvia; Sarto, Gloria E.; LeBoff, Meryl; Cauley, Jane; Cote, Michele; Beebe-Dimmer, Jennifer; Jay, Allison

    2016-01-01

    Purpose To evaluate the association between statins and breast cancer stage and mortality in the Women’s Health Initiative. Methods The study population included 128,675 post-menopausal women aged 50–79 years, out of which there were 7,883 newly diagnosed cases of in situ (19 %), local (61 %)-, regional (19 %)- and distant (1 %)-stage breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD = 3.7) years of follow-up. Stage was coded using SEER criteria and was stratified into early (in situ and local)- versus late (regional and distant)-stage disease. Information on statins and other risk factors were collected by self- and interviewer-administered questionnaires. Cause of death was based on medical record review. Multivariable-adjusted hazards ratios (HR) and 95 % confidence intervals (CIs) evaluating the relationship between statin use (at baseline only and in a time-dependent manner) and diagnosis of late-stage breast cancer and breast cancer-specific mortality were computed from Cox proportional hazards analyses after adjusting for appropriate confounders. Results Statins were used by 10,474 women (8 %) at baseline. In the multivariable-adjusted time-dependent model, use of lipophilic statins was associated with a reduction in diagnosis of late-stage breast cancer (HR 0.80, 95 % CI 0.64–0.98, p = 0.035) which was also significant among women with estrogen receptor-positive disease (HR 0.72, 95 % CI 0.56–0.93, p = 0.012). Breast cancer mortality was marginally lower in statin users compared with nonusers (HR 0.59, 95 % CI 0.32–1.06, p = 0.075). Conclusions Prior statin use is associated with lower breast cancer stage at diagnosis. PMID:25736184

  15. Exercise in Regulation of Inflammation-Immune Axis Function in Cancer Initiation and Progression

    PubMed Central

    Koelwyn, Graeme J.; Wennerberg, Erik; Demaria, Sandra; Jones, Lee W.

    2016-01-01

    Pharmacologic manipulation of the immune system is emerging as a viable and robust treatment for some cancer patients. Exercise-induced modulation of the immune system may be another adjunctive strategy for inhibiting tumor initiation and progression. In healthy individuals, exercise has been shown to modulate a number of cell subsets involved in innate and adaptive immunity. Here, we provide an overview of the current state of knowledge pertaining to exercise modulation of the inflammation-immune axis in cancer. The current evidence suggests that exercise may be a promising adjunctive strategy that can favorably alter numerous components of the immune system, which, in turn, may modulate tumorigenesis. However, many important knowledge gaps are evident. To this end, we propose a framework to guide future research efforts investigating the immune effects of exercise in cancer. PMID:26676894

  16. A Mathematical-Biological Joint Effort to Investigate the Tumor-Initiating Ability of Cancer Stem Cells

    PubMed Central

    Fornari, Chiara; Beccuti, Marco; Lanzardo, Stefania; Conti, Laura; Balbo, Gianfranco; Cavallo, Federica; Calogero, Raffaele A.; Cordero, Francesca

    2014-01-01

    The involvement of Cancer Stem Cells (CSCs) in tumor progression and tumor recurrence is one of the most studied subjects in current cancer research. The CSC hypothesis states that cancer cell populations are characterized by a hierarchical structure that affects cancer progression. Due to the complex dynamics involving CSCs and the other cancer cell subpopulations, a robust theory explaining their action has not been established yet. Some indications can be obtained by combining mathematical modeling and experimental data to understand tumor dynamics and to generate new experimental hypotheses. Here, we present a model describing the initial phase of ErbB2+ mammary cancer progression, which arises from a joint effort combing mathematical modeling and cancer biology. The proposed model represents a new approach to investigate the CSC-driven tumorigenesis and to analyze the relations among crucial events involving cancer cell subpopulations. Using in vivo and in vitro data we tuned the model to reproduce the initial dynamics of cancer growth, and we used its solution to characterize observed cancer progression with respect to mutual CSC and progenitor cell variation. The model was also used to investigate which association occurs among cell phenotypes when specific cell markers are considered. Finally, we found various correlations among model parameters which cannot be directly inferred from the available biological data and these dependencies were used to characterize the dynamics of cancer subpopulations during the initial phase of ErbB2+ mammary cancer progression. PMID:25184361

  17. 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

  18. 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.

  19. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression

    PubMed Central

    Madka, Venkateshwar; Brewer, Misty; Ritchie, Rebekah L.; Lightfoot, Stan; Kumar, Gaurav; Sadeghi, Michael; Patlolla, Jagan Mohan R.; Yamada, Hiroshi Y.; Cruz-Monserrate, Zobeida; May, Randal; Houchen, Courtney W.; Steele, Vernon E.; Rao, Chinthalapally V.

    2015-01-01

    Recent development of genetically engineered mouse models (GEMs) for pancreatic cancer (PC) that recapitulates human disease progression has helped to identify new strategies to delay/inhibit PC development. We first found that expression of the pancreatic tumor-initiating/cancer stem cells (CSC) marker DclK1 occurs in early stage PC and in both early and late pancreatic intraepithelial neoplasia (PanIN) and that it increases as disease progresses in GEM and also in human PC. Genome-wide next generation sequencing of pancreatic ductal adenocarcinoma (PDAC) from GEM mice revealed significantly increased DclK1 along with inflammatory genes. Genetic ablation of cyclo-oxygenase-2 (COX-2) decreased DclK1 in GEM. Induction of inflammation/pancreatitis with cerulein in GEM mice increased DclK1, and the novel dual COX/5-lipoxygenase (5-LOX) inhibitor licofelone reduced it. Dietary licofelone significantly inhibited the incidence of PDAC and carcinoma in situ with significant inhibition of pancreatic CSCs. Licofelone suppressed pancreatic tumor COX-2 and 5-LOX activities and modulated miRNAs characteristic of CSC and inflammation in correlation with PDAC inhibition. These results offer a preclinical proof of concept to target the inflammation initiation to inhibit cancer stem cells early for improving the treatment of pancreatic cancers, with immediate clinical implications for repositioning dual COX/5-LOX inhibitors in human trials for high risk patients. PMID:25906749

  20. Radiation Promotes Colorectal Cancer Initiation and Progression by Inducing Senescence-Associated Inflammatory Responses

    PubMed Central

    Kim, Sang Bum; Bozeman, Ronald; Kaisani, Aadil; Kim, Wanil; Zhang, Lu; Richardson, James A.; Wright, Woodring E.; Shay, Jerry W.

    2015-01-01

    Proton radiotherapy is becoming more common since 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 to 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 (SIR) 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 (CKIα) and induction of chronic DNA damage and TP53 mutations are increased compared to x-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 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. PMID:26477319

  1. Serotonin transporter antagonists target tumor-initiating cells in a transgenic mouse model of breast cancer

    PubMed Central

    Hallett, Robin M.; Girgis-Gabardo, Adele; Gwynne, William D.; Giacomelli, Andrew O.; Bisson, Jennifer N.P.; Jensen, Jeremy E.; Dvorkin-Gheva, Anna; Hassell, John A.

    2016-01-01

    Accumulating data suggests that the initiation and progression of human breast tumors is fueled by a rare subpopulation of tumor cells, termed breast tumor-initiating cells (BTIC), which resist radiotherapy and chemotherapy. Consequently, therapies that abrogate BTIC activity are needed to achieve durable cures for breast cancer patients. To identify such therapies we used a sensitive assay to complete a high-throughput screen of small molecules, including approved drugs, with BTIC-rich mouse mammary tumor cell populations. We found that inhibitors of the serotonin reuptake transporter (SERT) and serotonin receptors, which include approved drugs used to treat mood disorders, were potent inhibitors of mouse BTIC activity as determined by functional sphere-forming assays and the initiation of tumor formation by transplant of drug-exposed tumor cells into syngeneic mice. Moreover, sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), synergized with docetaxel (Taxotere) to shrink mouse breast tumors in vivo. Hence drugs targeting the serotonergic system might be repurposed to treat breast cancer patients to afford more durable breast cancer remissions. PMID:27447971

  2. Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy.

    PubMed

    Ahuja, Shradha; Makkar, Priyanka; Gupta, Sorab; Vigoda, Ivette

    2016-05-01

    Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer.

  3. Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells.

    PubMed

    Peng, Xiaohui; Zhou, Yan; Tian, Hua; Yang, Gaoxiang; Li, Chunliu; Geng, Yang; Wu, Sai; Wu, Wei

    2015-09-01

    Advanced prostate cancer has highly invasive potential, which may lead to metastasis associated with poor prognosis. Sulforaphane (SFN), abundant in cruciferous vegetables, exhibited effective resistance to carcinogenesis in a variety of tumors. The aim of the present study was to investigate whether SFN inhibited invasion in human prostate cancer cells via sustained activation of ERK1/2 and downstream signaling by an invasion assay, gelatin zymography and western blot analysis. The results showed that SFN inhibited invasion and we characterized the underlying mechanisms in human DU145 prostate cancer cells. SFN (15 µM) changed cell morphology leading to short‑cell pseudopodia which may suppress tumor migration and invasion. The Transwell assay showed that SFN phosphorylated ERK1/2 in a dose- and time-dependent manner and significantly inhibited cell invasion, while the effect was reduced by the ERK1/2 blocker PD98059 (25 µM). Furthermore, these effects contributed to the upregulation of E-cadherin and the downregulation of CD44v6 and were eradicated by PD98059. Western blot analysis and gelatin zymography showed that SFN decreased the expression and activity of MMP-2. Thus, SFN inhibited invasion by activating ERK1/2 to upregulate E-cadherin and downregulate CD44v6, thereby reducing MMP-2 expression and activity. E-cadherin is an invasion inhibitor, while CD44v6 and MMP-2 are invasion promoters. Therefore, SFN is a prospective therapeutic agent that may be used to prevent invasion in prostate cancer.

  4. Initial Experience of Head and Neck Cancer Patients Treated in an Oncologist Led Palliative Cancer Care Clinic at a Tertiary Cancer Care Center in Uttar Pradesh: Is the Initiative of a Full-fledged Palliative Care for Cancer Patients Justified

    PubMed Central

    Lal, Punita; Verma, Mranalini; Kumar, Gaurav; Shrivastava, Resham; Kumar, Shaleen

    2016-01-01

    Introduction: Poor socioeconomic status and illiteracy attribute to the advanced presentation of head and neck cancer (HNC) patients in India and are candidates for palliation in our setup. We set up a palliative cancer care clinic (PCCC), and an audit of initial 153 HNC patients is presented. Aims and Objectives: To assess the impact of palliative cancer care services. Methodology: Data of advanced HNC patients suited for palliation were collected to document demography, symptomatology, cancer treatment, and supportive care. Results: One hundred and fifty-three patients were seen during January 2013 to March 2015 in the PCCC. Seventy-two (47%) referral cases were due to disease progression and 81 (53%) due to de novo advanced cases. Median follow-up for this group was 5.3 months. Ninety (59%) cases needed some degree of assistance for their normal activities. Sixty-seven (44%) patients belonged to poor socioeconomic status and 65 (43%) were educated up to equivalent of high school. One hundred and thirty-five (88%) patients had an adequate family support. Pain was the most common presenting symptom in 134 (87%) cases with adequate relief in 112 (84%) patients with another 13 (09%) could not be assessed. Overall median duration of symptoms was 6 months. Cancer-directed therapy was used in 143 (93%) patients. Near the end of life in 47 (73%) out of 63 documented cases, caregivers were psychologically prepared for the inevitable. Conclusion: The role of palliative care team in alleviating physical, psychosocial, and emotional issues of patient and family members was significant. PCCC seems to be a feasible working model in our setup. PMID:27803571

  5. Neutrophils support lung colonization of metastasis-initiating breast cancer cells.

    PubMed

    Wculek, Stefanie K; Malanchi, Ilaria

    2015-12-17

    Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.

  6. 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

  7. Treating persistent distress and anxiety in parents of children with cancer: an initial feasibility trial.

    PubMed

    Warner, Carrie Masia; Ludwig, Kristy; Sweeney, Corinne; Spillane, Clare; Hogan, Laura; Ryan, Julie; Carroll, William

    2011-01-01

    Persistent anxiety is common among parents of children with cancer and may affect the family's well-being and adjustment. The goals of this pilot study are to determine the feasibility and potential efficacy of a brief cognitive-behavioral parent intervention aimed at reducing parental distress and anxiety related to their child's cancer diagnosis. Parents of children with cancer, at least 1 month postdiagnosis, were screened at an outpatient oncology clinic, and those reporting elevated levels of distress were offered a 4-session cognitive-behavioral intervention based on a modified version of the Surviving Cancer Competently Intervention Program-Newly Diagnosed. Five parents reporting persistent distress received the intervention. Results revealed decreases in parents' distress, state anxiety, and depressive symptoms, as well as in parents' feelings of burden associated with their children's cancer. This initial study suggests that identification of parents with prolonged heightened psychological distress is feasible and acceptable and that offering them a brief intervention within a pediatric oncology setting may be beneficial.

  8. Neutrophils support lung colonization of metastasis-initiating breast cancer cells

    PubMed Central

    Wculek, Stefanie K.; Malanchi, Ilaria

    2015-01-01

    Despite progress in the development of drugs efficiently targeting cancer cells, treatments of metastatic tumours are often ineffective. The now well established dependency of cancer cells on their microenvironment1 suggests that targeting the non-cancer cell component of the tumour might form the basis for the development of novel therapeutic approaches. However, the as yet poorly characterised contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumourigenesis is still controversial2-4. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissue by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacologic inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression. PMID:26649828

  9. 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

  10. HORMONE USE, REPRODUCTIVE HISTORY AND RISK OF LUNG CANCER: THE WOMEN'S HEALTH INITIATIVE STUDIES

    PubMed Central

    Schwartz, Ann G.; Ray, Roberta M.; Cote, Michele L.; Abrams, Judith; Sokol, Robert J.; Hendrix, Susan L.; Chen, Chu; Chlebowski, Rowan T.; Hubbell, F. Allan; Kooperberg, Charles; Manson, JoAnn E.; Jo O'Sullivan, Mary; Rohan, Thomas; Stefanick, Marcia L.; Wactawski-Wende, Jean; Wakelee, Heather; Simon, Michael S.

    2015-01-01

    Introduction Results from the Women's Health Initiative (WHI) clinical trials (CT) demonstrated no increase in the risk of lung cancer in postmenopausal women treated with hormone therapy. We conducted a joint analysis of the WHI observational study data and CT data to further explore the association between estrogen and estrogen-related reproductive factors and lung cancer risk. Methods Reproductive history, oral contraceptive (OC) use, and postmenopausal hormone therapy (HT) was evaluated in 160,855 women with known HT exposures. Follow-up for lung cancer was through September 17, 2012; 2,467 incident lung cancer cases were ascertained, with median follow-up of 14 years. Results For all lung cancers, women with previous use of estrogen plus progestin of < 5 years (HR=0.84; 95% CI 0.71-0.99) were at reduced risk. A limited number of reproductive factors demonstrated associations with risk. There was a trend towards decreased risk with increasing age at menopause (ptrend=0.04) and a trend towards increased risk with increasing number of live births (ptrend=0.03). Reduced risk of non-small cell lung cancer was associated with age 20-29 at first live birth. Risk estimates varied with smoking history, years of HT use and previous bilateral oophorectomy. Conclusions Indirect measures of estrogen exposure to lung tissue, as used in this study, provide only weak evidence for an association between reproductive history or HT use and risk of lung cancer. More detailed mechanistic studies and evaluation of risk factors in conjunction with ER expression in the lung should continue as a role for estrogen can't be ruled out and may hold potential for prevention and treatment strategies. PMID:25852020

  11. Prevalence and Correlates of Postdiagnosis Initiation of Complementary and Alternative Medicine Among Patients at a Comprehensive Cancer Center

    PubMed Central

    Perlman, Adam; Lontok, Oliver; Huhmann, Maureen; Parrott, J. Scott; Simmons, Leigh Ann; Patrick-Miller, Linda

    2013-01-01

    Purpose: Patients with cancer increasingly use complementary and alternative medicine (CAM) in conjunction with conventional oncology treatments. Previous studies have not investigated postdiagnosis initiation of CAM therapies or independent correlates of use of individual CAM modalities. The purpose of this study was to determine the prevalence and correlates of individual CAM modalities initiated after cancer diagnosis. Methods: A cross-sectional survey was conducted of a random sample of adults with a cancer diagnosis (N = 1,228) seeking care at a National Cancer Institute–designated comprehensive cancer center within a 12-month period. Results: The majority of patients were female (64.7%), white (86.9%), and married (72.8%).Three-quarters (75.2%) used at least one CAM modality, and 57.6% of those using CAM initiated use after cancer diagnosis. For all CAM therapies combined, women were 1.7 times more likely than men to initiate any CAM therapy after cancer diagnosis. However, when CAM modalities were differentiated by type, men and women were equally likely to initiate all therapies except for psychotherapy and mind-body approaches. Postdiagnosis initiation of every CAM modality, except mind-body therapies, differed by cancer type. Conclusion: A significant proportion of patients initiated CAM use after diagnosis. However, specific type of CAM initiated varied by demographics and cancer type, suggesting there is not a “typology” of CAM user. Optimal comprehensive cancer treatment, palliation, and survivorship care will require patient and provider education regarding CAM use by modality type; improved provider-patient communication regarding potential benefits, limitations, and risks; and institutional policies to support integrated conventional and CAM treatment. PMID:23633969

  12. [A Case of Double Cancer of Initially Unresectable Sigmoid Colon Cancer and Advanced Gastric Cancer Treated with Curative Resection after mFOLFOX6 Therapy].

    PubMed

    Yoshikawa, Toru; Aoki, Kazunori; Mitsuhashi, Yuto; Tomiura, Satoko; Suto, Akiko; Miura, Takuya; Ikenaga, Shojirokazunori; Shibasaki, Itaru; Endo, Masaaki

    2016-03-01

    A 61-year-old man was admitted to our hospital because of a complaint of blood in stool. He was diagnosed with advanced colon and gastric cancers. Computed tomography (CT) revealed a sigmoid tumor with invasion to the bladder, a metastatic tumor in the lateral segmental branch of the left hepatic lobe, and ascites. He was diagnosed with initially unresectable double cancer. Ileostomy was performed immediately, and he was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). After 6 courses of the mFOLFOX6 regimen, CT revealed that the primary lesion of the sigmoid colon and liver metastasis had reduced in size, and the ascites had disappeared. Gastroscopy revealed that the gastric cancer had disappeared. Biopsy results were negative. Accordingly, his gastric cancer was diagnosed as treatment effect Grade 3. After 8 courses of mFOLFOX6 therapy, sigmoidectomy, partial resection of the bladder, and partial resection of the liver were performed. Gastric cancer was not resected in accordance with his will. Although 40 months has passed after the radical resection, neither the sigmoid colon cancer nor the gastric cancer recurred.

  13. CD44 and EpCAM: cancer-initiating cell markers.

    PubMed

    Marhaba, Rachid; Klingbeil, Pamela; Nuebel, Tobias; Nazarenko, Irina; Buechler, Markus W; Zoeller, Margot

    2008-12-01

    Embryonic stem cells are immortal, can self renew, and differentiate into all cells of the body. The adult organism maintains adult stem cells in regenerative organs that can differentiate into all cells of the respective organ. Virchow's hypothesis that cancer may arise from embryonic-like cells has received strong support, as it was demonstrated that tumors contain few cells, known as cancer stem or cancer-initiating cells (CIC), that account for primary and metastatic tumor growth. CIC are mostly defined by expression of CIC-markers that are associated and correlated with the potential of CIC to grow in xenogeneic mice. CIC marker profiles have been elaborated for many tumors, with several markers as CD24, CD44, CD133, CD166, EpCAM, and some integrins, being expressed by tumors of different histological type. Their function in promoting CIC maintenance and activity is largely unknown. The fate of stem cells, determined by their position, is minutely regulated by few adjacent cells creating a niche. CIC also require a niche, mostly for settlement and growth in distant organs. This so called pre-metastatic niche is initiated by the primary tumor before metastasizing cell arrival. How do CIC prepare the pre-metastatic niche? Cancer cells secrete a matrix that serves a cross-talk with surrounding tissues. Additionally, cancer cells can abundantly deliver exosomes, which function as long-distance intercellular communicators. Studies on a rat pancreatic adenocarcinoma support our hypothesis that tumor-derived matrix and exosomes are the main actors in forming the pre-metastatic niche with CIC markers being engaged in matrix preparation and/or exosome delivery.

  14. 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

  15. Quality evaluation of investigator-initiated trials using post-approval cancer drugs in Japan.

    PubMed

    Kondo, Shunsuke; Hosoi, Hiroko; Hashimoto, Jun

    2017-03-07

    Investigator-initiated trials (IITs) are important aspects of medical research and have contributed substantially to modern oncology. IITs using post-approval drugs have been conducted by domestic institutions in Japan. Data from this study were obtained by all IITs registered clinical trials for five cancers (lung, colorectal cancer, gastric cancer, liver cancer, and breast cancer) using drugs approved from 1999 to 2009 in Japan. The Kaplan-Meier method, analysis of variance (ANOVA), and Kruskal-Wallis test were used to estimate time to enrolment completion (TTEC) and time to enrolment per patient (TTEP). Of 1,222 trials eligible for analysis, 465 trials (38%) completed enrolment to the studies, and 203 trials (17%) published results. In the distribution according to trial phase, 98 (8%) were phase I, 1,058 (87%) were phase I/II + II, and 66 (5%) were phase II/III + III. The accrual achievement and publication rates were higher in late-phase than in early-phase trials. The median TTEC was 1,387 days (95% confidence interval [CI], 1,302 to 1,472). The median TTEP was 38.5 days (95% CI, 34.5 to 42.5). The median TTEC and TTEP were significantly different in each trial phase (P < 0.01), funding source (P < 0.01), and publication status (median TTEC published trials vs. unpublished trial; 720 days vs. 1,672 days, median TTEP; 16 days vs. 55.8 days; P < 0.001). Many IITs using approved cancer drugs have been conducted; however, the quality of the clinical trials was low in terms of accrual achievement, publication rate, and time to publication of trial results. This article is protected by copyright. All rights reserved.

  16. 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.

  17. Oral and gastrointestinal symptomatic metastases as initial presentation of lung cancer.

    PubMed

    Jeba, Jenifer; Backianathan, Selvamani; Ishitha, Gunadala; Singh, Ashish

    2016-11-18

    Metastasis to the tongue, duodenum or pancreas from primary lung cancer is uncommon. Primary lung cancer presenting with symptoms related to metastases at these sites, at initial presentation is extremely rare. We report a 45-year-old man with disseminated lung malignancy who presented with dyspepsia, melena, symptoms due to anaemia and swelling in the tongue. Oral examination revealed a hard submucosal anterior tongue lesion. Biopsies from the tongue lesion and the duodenal ulcer seen on upper gastrointestinal endoscopy were suggestive of metastasis from lung primary. CT revealed lung primary with disseminated metastasis to lung, liver, adrenals, kidneys, head and body of pancreas, duodenum and intra-abdominal lymph nodes. The patient was treated with palliative chemotherapy. The unusual presentation and diagnostic details are discussed.

  18. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    SciTech Connect

    Neuzil, Jiri; E-mail: j.neuzil@griffith.edu.au; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

    2007-04-20

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133{sup +} cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well.

  19. Ovarian hormones through Wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions

    PubMed Central

    Nagendra, Prathima B.; Goad, Jyoti; Nielsen, Sarah; Rassam, Loui; Lombard, Janine M.; Nahar, Pravin; Tanwar, Pradeep S.

    2016-01-01

    Ovarian cancer (OC) is the most deadly gynaecological disease largely because the majority of patients are asymptomatic and diagnosed at later stages when cancer has spread to other vital organs. Therefore, the initial stages of this disease are poorly characterised. Women with BRCA1/2 mutations have a genetic predisposition for developing OC, but not all of these women develop the disease. Epidemiological findings show that lifestyle factors such as contraceptive use and pregnancy, a progesterone dominant state, decrease the risk of getting OC. How ovarian hormones modify the risk of OC is currently unclear. Our study identifies activated Wnt signalling to be a marker for precursor lesions of OC and successfully develops a mouse model that mimics the earliest events in pathogenesis of OC by constitutively activating βcatenin. Using this model and human OC cells, we show that oestrogen promotes and progesterone suppresses the growth of OC cells. PMID:27588493

  20. 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.

  1. Participation du patient Marocain atteint du cancer au choix thérapeutique: résultat d'une enquête réalisée auprès de 272 patient

    PubMed Central

    Boukir, Anwar; Azghari, Ilham; El Kabous, Mustapha; Jouid, Khalid; Boutayeb, Saber; El Ghissassi, Ibrahim; Mrabti, Hind; Errrihani, Hassan

    2015-01-01

    Introduction La décision médicale partagée ‘Shared decision making’ est un concept qui se développe depuis les années 1990. Il donne aux patients le soutien nécessaire pour exprimer leurs préférences et partager la décision médicale. Cette étude cherche à estimer le degré de participation du patient Marocain atteint de cancer au choix thérapeutique. Méthodes Cette enquête a été réalisée auprès de 272 malades sous chimiothérapie pour une pathologie cancéreuse sous forme d'un entretien verbal basé sur un questionnaire. Les patients ont été sélectionnés selon un mode d’échantillonnage aléatoire, le nombre de patients a été choisi pour une marge d'erreur de 5% et un seuil de probabilité qui approxime les 90%. Résultats Seulement 5.5% des patients dans l'enquête ont participé activement dans le choix thérapeutique. Pour 94% des patients de l’échantillon la stratégie thérapeutique adoptée par le médecin est la bonne et représente l'option optimale. Les principales causes retrouvées qui expliquent la non participation à la décision thérapeutique sont le bas niveau d'instruction, la non réceptivité à l'information ainsi que des défauts majeures dans la transmission et la perception de l'information. Conclusion Ces résultats prouvent que la relation médecin malade dans notre contexte baigne toujours dans le modèle paternaliste. La responsabilité de la décision thérapeutique est le plus souvent laissée au médecin. Il est nécessaire d'informer et d'impliquer le patient de façon active dans le choix thérapeutique afin de mieux sauvegarder la relation médecin-malade qui doit être fondée sur la confiance ainsi que sur une approche participative. PMID:26918070

  2. Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells.

    PubMed

    Abrams, Rachel P; Carroll, William L; Woerpel, K A

    2016-05-20

    A 1,2-dioxolane (FINO2) was identified as a lead compound from a screen of organic peroxides. FINO2 does not induce apoptosis, but instead initiates ferroptosis, an iron-dependent, oxidative cell death pathway. Few compounds are known to induce primarily ferroptosis. In contrast to the perceived instability of peroxides, FINO2 was found to be thermally stable to at least 150 °C. FINO2 was more potent in cancer cells than nonmalignant cells of the same type. One of the enantiomers was found to be more responsible for the observed activity.

  3. Investigating the association of lactation history and postmenopausal breast cancer risk in the Women's Health Initiative.

    PubMed

    Stendell-Hollis, Nicole R; Thompson, Patricia A; Thomson, Cynthia A; O'Sullivan, Mary J; Ray, Roberta M; Chlebowski, Rowan T

    2013-01-01

    Prolonged lactation (≥24 mo) has been associated with reduced breast cancer risk. This research examined this association in postmenopausal women in the Women's Health Initiative (WHI) Hormone Trial (HT) and Observational Study (OS). This retrospective cohort analysis included 69,358 predominantly overweight (65.4%), white (83.2%) postmenopausal women without breast cancer. Women in the HT were randomized to 0.625 mg conjugated equine estrogen (CEE), 0.625 CEE + 2.5 mg medroxyprogesterone acetate (CEE/MPA), or placebo. OS participants had no restrictions on hormone use. Lactation history was assessed via WHI Reproductive History Questionnaire. Most women breastfed at least 1 mo (58.0%); 35.4% breastfed 1-2 children; and 6.5% stated having breastfed ≥24mo. Women in the HT-CEE who breastfed their first child between 20-24 yr of age demonstrated a nonsignificant decreased risk of breast cancer (HR: 0.62; 95% CI: 0.38, 1.01). OS participants who reported CEE/MPA hormone use and age of first breastfeeding ≥30 yr showed a significant increased risk of breast cancer (HR: 1.66; 95% CI: 1.14, 2.41). Risk was increased if age of last breastfeeding was ≥35yr (HR: 1.50; 95% CI: 1.05, 2.14). This research did not demonstrate a significantly decreased risk of postmenopausal breast cancer in women who breastfed for ≥24 mo during their lifetime.

  4. Familial Clustering of Breast and Prostate Cancer and Risk of Postmenopausal Breast Cancer in the Women’s Health Initiative Study

    PubMed Central

    Beebe-Dimmer, Jennifer L.; Yee, Cecilia; Cote, Michele L.; Petrucelli, Nancie; Palmer, Nynikka; Bock, Cathryn; Lane, Dorothy; Agalliu, Ilir; Stefanick, Marcia L.; Simon, Michael S.

    2015-01-01

    BACKGROUND Evidence suggests that the risk of breast and prostate cancer is increased among those with a family history of the same disease and particularly among first-degree relatives. However, less is known about the relationship between breast and prostate cancer within families and particularly among minority populations. METHODS Analyses of participants in the Women’s Health Initiative observational cohort who were free of breast cancer at the time of their baseline examination were conducted. Subjects were followed for breast cancer through August 31, 2009. A Cox proportional hazards regression modeling approach was used to estimate the risk of breast cancer associated with a family history of prostate cancer, breast cancer, and both among first-degree relatives. RESULTS There were 78,171 eligible participants, and 3506 breast cancer cases were diagnosed during the study period. A family history of prostate cancer was associated with a modest increase in breast cancer risk after adjustments for confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.02-1.26). In a separate analysis examining the joint impact of both cancers, a family history of both breast and prostate cancer was associated with a 78% increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates associated with a family history of both breast and prostate cancer were higher among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women (aHR, 1.66; 95% CI, 1.33-2.08). CONCLUSIONS These findings suggest that prostate cancer diagnosed among first-degree family members increases a woman’s risk of developing breast cancer. Future studies are needed to determine the relative contributions of genes and a shared environment to the risk for both cancers. PMID:25754547

  5. Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy.

    PubMed

    Maccalli, Cristina; Parmiani, Giorgio; Ferrone, Soldano

    2017-04-01

    Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy.

  6. VEGFA activates an epigenetic pathway upregulating ovarian cancer-initiating cells.

    PubMed

    Jang, Kibeom; Kim, Minsoon; Gilbert, Candace A; Simpkins, Fiona; Ince, Tan A; Slingerland, Joyce M

    2017-03-01

    The angiogenic factor, VEGFA, is a therapeutic target in ovarian cancer (OVCA). VEGFA can also stimulate stem-like cells in certain cancers, but mechanisms thereof are poorly understood. Here, we show that VEGFA mediates stem cell actions in primary human OVCA culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. The VEGFA-mediated increase in spheres was abrogated by Src inhibition or SRC knockdown. VEGFA stimulated sphere formation only in the ALDH1(+) subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1. In contrast to its action in hemopoietic malignancies, DNA methyl transferase 3A (DNMT3A) appears to play a pro-oncogenic role in ovarian cancer. VEGFA-driven Src increased DNMT3A leading to miR-128-2 methylation and upregulation of Bmi1 to increase stem-like cells. SRC knockdown was rescued by antagomir to miR-128. DNMT3A knockdown prevented VEGFA-driven miR-128-2 loss, and the increase in Bmi1 and tumor spheres. Analysis of over 1,300 primary human OVCAs revealed an aggressive subset in which high VEGFA is associated with miR-128-2 loss. Thus, VEGFA stimulates OVCA stem-like cells through Src-DNMT3A-driven miR-128-2 methylation and Bmi1 upregulation.

  7. Oncolytic herpes simplex virus kills stem-like tumor-initiating colon cancer cells

    PubMed Central

    Warner, Susanne G; Haddad, Dana; Au, Joyce; Carson, Joshua S; O’Leary, Michael P; Lewis, Christina; Monette, Sebastien; Fong, Yuman

    2016-01-01

    Stem-like tumor-initiating cells (TICs) are implicated in cancer progression and recurrence, and can be identified by sphere-formation and tumorigenicity assays. Oncolytic viruses infect, replicate in, and kill a variety of cancer cells. In this study, we seek proof of principle that TICs are susceptible to viral infection. HCT8 human colon cancer cells were subjected to serum-free culture to generate TIC tumorspheres. Parent cells and TICs were infected with HSV-1 subtype NV1066. Cytotoxicity, viral replication, and Akt1 expression were assessed. TIC tumorigenicity was confirmed and NV1066 efficacy was assessed in vivo. NV1066 infection was highly cytotoxic to both parent HCT8 cells and TICs. In both populations, cell-kill of >80% was achieved within 3 days of infection at a multiplicity of infection (MOI) of 1.0. However, the parent cells required 2-log greater viral replication to achieve the same cytotoxicity. TICs overexpressed Akt1 in vitro and formed flank tumors from as little as 100 cells, growing earlier, faster, larger, and with greater histologic atypia than tumors from parent cells. Treatment of TIC-induced tumors with NV1066 yielded tumor regression and slowed tumor growth. We conclude that colon TICs are selected for by serum-free culture, overexpress Akt1, and are susceptible to oncolytic viral infection. PMID:27347556

  8. Clinical investigation into the initial diagnosis and treatment of 539 patients with stage IV lung cancer

    PubMed Central

    Shao, Qian; Liu, Shanshan; Wang, Wei; Zhang, Yingjie; Li, Fengxiang; Li, Jianbin

    2017-01-01

    Objective The aim of the study was to analyze clinical data, including the types of pathologic classification, metastatic organs, treatment strategy, and prognosis of patients with stage IV lung cancer. Methods A retrospective analysis of the clinical features of 539 patients with stage IV lung cancer who were initially diagnosed and treated in 2009 was conducted. There were 146 cases of single organ metastases and 393 cases of multiple organ metastases. The Kaplan-Meier method and multivariate Cox regression analysis were performed to analyze the influence of age, pathological classification, metastatic organs, and treatment strategy on overall survival. Results The 1-, 2-, and 3-year survival rates were 64.2% (n=346), 19.7% (n=106), and 1.5% (n=8), respectively. Metastases to the liver and pleura predicted poor prognosis, although bone metastases predicted relatively good prognosis. The prognosis of single brain metastasis was relatively better than that of multiple brain metastases. Multi-factor analysis showed that the patient’s age, different metastatic organs, the numbers of metastatic organs, and different treatment were independent risk factors for survival. Conclusion The prognosis for patients with stage IV lung cancer is poor. Patient’s age, the type and number of metastatic organs, and method of treatment are the main factors affecting survival. PMID:28203086

  9. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer

    PubMed Central

    Pasparakis, Manolis

    2015-01-01

    The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine. PMID:26621453

  10. Heterogeneity of tumor cells in terms of cancer-initiating cells

    PubMed Central

    Morii, Eiichi

    2016-01-01

    Tumors derive from a single cell clone but consist of heterogeneous cell subpopulations with diverse features and functions. A limited number of subclones with a selective advantage can initiate tumors when inoculated into immunocompromised mice, and are called cancer-initiating cells (CICs). CICs can be isolated from the bulk of tumors on the basis of their characteristics, such as high reagent efflux, degradation of reactive oxygen species, and aldehyde dehydrogenase (ALDH) activity. Under normal conditions, new CICs are produced by existing CICs rather than non-CICs. However, under stress conditions, non-CICs can occasionally produce CICs, a phenomenon known as plasticity. The dynamic exchange between CICs and non-CICs may enable tumors to survive under unfavorable conditions. CICs are located in a small portion of tumors. This suggests that microenvironmental factors induce or inhibit the CIC phenotype, which might be regulated by intercellular signaling between tumor cells. This review describes isolation of CICs from tumor cell populations and the microenvironmental factors that regulate CIC phenotypes in uterine cancer and lymphoma. PMID:28190919

  11. 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

  12. 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

  13. Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.

    PubMed

    Zimmerer, Rüdiger M; Matthiesen, Peter; Kreher, Fritjof; Kampmann, Andreas; Spalthoff, Simon; Jehn, Philipp; Bittermann, Gido; Gellrich, Nils-Claudius; Tavassol, Frank

    2016-03-01

    Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors.

  14. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.

    PubMed

    Sødring, Marianne; Gunnes, Gjermund; Paulsen, Jan Erik

    2016-04-15

    The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.

  15. Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

    PubMed

    Gong, Zhihong; Aragaki, Aaron K; Chlebowski, Rowan T; Manson, JoAnn E; Rohan, Thomas E; Chen, Chu; Vitolins, Mara Z; Tinker, Lesley F; LeBlanc, Erin S; Kuller, Lewis H; Hou, Lifang; LaMonte, Michael J; Luo, Juhua; Wactawski-Wende, Jean

    2016-04-15

    Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer.

  16. 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

  17. 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.

  18. 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

  19. Blockade of Fas signaling in breast cancer cells suppresses tumor growth and metastasis via disruption of Fas signaling-initiated cancer-related inflammation.

    PubMed

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

    2014-04-18

    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.

  20. Pten Inactivation Accelerates Oncogenic K-ras-Initiated Tumorigenesis in a Mouse Model of Lung Cancer

    PubMed Central

    Iwanaga, Kentaro; Yang, Yanan; Raso, Maria Gabriela; Ma, Lijiang; Hanna, Amy E.; Thilaganathan, Nishan; Moghaddam, Seyed; Evans, Christopher M.; Li, Huaiguang; Cai, Wei-Wen; Sato, Mitsuo; Minna, John D.; Wu, Hong; Creighton, Chad J.; Demayo, Francesco J.; Wistuba, Ignacio I.; Kurie, Jonathan M.

    2009-01-01

    Phosphatase and tensin homologue deleted from chromosome 10 (Pten) is expressed aberrantly in non-small cell lung cancer cells, but the role of Pten in lung neoplasia has not been fully elucidated. In this study, we used a genetic approach to inactivate Pten in the bronchial epithelium of mice. Although, by itself, Pten inactivation had no discernible effect on bronchial epithelial histology, it accelerated lung tumorigenesis initiated by oncogenic K-ras, causing more rapid lethality than that induced by oncogenic K-ras alone (8 weeks versus 24 weeks of median duration of survival, respectively). Lung tumors arose in K-ras mutant, Pten-deficient mice that rapidly obstructed bronchial lumina and replaced alveolar spaces. Relative to K-ras mutant tumors, the K-ras mutant, Pten-deficient tumors exhibited more advanced histologic severity and more prominent inflammation and vascularity. Thus, Pten inactivation cooperated with oncogenic K-ras in promoting lung tumorigenesis. PMID:18281487

  1. Understanding Regional Variation in Medicare Expenditures for Initial Episodes of Prostate Cancer Care

    PubMed Central

    Wang, Shi-Yi; Wang, Rong; Yu, James B.; Ma, Xiaomei; Xu, Xiao; Kim, Simon P.; Soulos, Pamela R.; Saraf, Avantika; Gross, Cary P.

    2014-01-01

    Objectives To evaluate the contributions of patient and treatment factors to overall expenditures and regional variation for initial treatment of localized prostate cancer (CaP) in the Medicare program. Research Design Using the Surveillance, Epidemiology, and End Results–Medicare database, we identified 47,517 beneficiaries with localized CaP during 2005–2009 and matched non-cancer controls. We employed hierarchical generalized linear models to estimate risk-standardized cancer-related expenditures for each hospital referral region. To identify key contributors to the variation, we sequentially added patient characteristics, treatment intensity (the percentage of patients receiving curative treatments), ancillary procedures (biopsy, hormone therapy, and imaging), and specific treatment modalities into the model. We categorized the expenditures according to the type of services to identify their relative impact on the expenditure variations. Results The mean expenditure on CaP-related care per CaP beneficiary was $15,900, including $1,800 on surgery, $11,200 on radiotherapy, and $1,900 on ancillary procedures. The expenditure difference between quintiles 5 and 1 was $6,200. Patient characteristics explained 8.4% of this difference. Treatment intensity and treatment modalities accounted for an additional 21.2% and 31.2% of the variation, respectively. Between the highest and lowest expenditure quintiles, the difference in radiotherapy expenditure was $5,000, whereas that in surgery or ancillary procedures was less than $200. Conclusions There is substantial geographic variation in CaP expenditures, and the specific modality of radiotherapy is the most important contributor to this variation. Efforts to address the CaP care costs, such as bundled payment development, require targeting both treatment intensity and use of costly modalities. PMID:25023913

  2. Laser immunotherapy: initial results from a human breast cancer pilot trial

    NASA Astrophysics Data System (ADS)

    Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Lunn, John A.; Adelsteinsson, Orn; Nordquist, Robert E.; Chen, Wei R.

    2010-02-01

    Laser Immunotherapy is an experimental treatment modality for late-stage, metastatic tumors, which targets solid primary and/or secondary tumors and utilizes an autologous vaccine-like approach to stimulate immune responses. Specifically, laser immunotherapy combines laser-induced in situ tumor devitalization with an immunoadjuvant for local immunostimulation. Here we report the initial results from a human breast cancer pilot trial with laser immunotherapy. Six stage III and IV cancer patients were treated, all of which were considered to be out of all other options, and preliminary data at the three-month examination are presented. The immediate goal of the trial was to determine the patient tolerance and the toxicity of the therapy, the optimal dose for the alteration of the course of the disease, and the reduction of the tumor burden. Each patient was individually evaluated for toxicity tolerance through physical exams and by appropriate supplemental and routine laboratory tests. Observable tumors in patients were followed with physical examination and radiological evaluations. Treatment efficacy was judged by the size and number of local and distant metastases before and after treatment.

  3. Combined laparoscopic and transanal total mesorectal excision for rectal cancer: Initial experience and early results

    PubMed Central

    Thomsen, Morten Holt; Ovesen, Henrik; Eriksen, Jens Ravn

    2017-01-01

    INTRODUCTION: Incomplete specimens resulting in residual mesorectum in the patient and an increased risk of local recurrence remains a problem. We have introduced transanal-total mesorectal excision (Ta-TME) in our department to potentially overcome this problem due to more direct access to the lower pelvis in patients undergoing TME for rectal cancer and this article presents our initial experience with the new procedure. MATERIALS AND METHODS: Patients with a T1-T3 mid or low rectal cancer eligible for TME or intersphincteric abdominoperineal excision were selected for a combined transanal and transabdominal laparoscopic resection. The primary aim of the study was to evaluate the feasibility and efficacy of the method with a special focus on the quality of the specimen. RESULTS: During a 9-month period, 11 patients were operated with this technique. All procedures resulted in complete or nearly complete specimen. We did, however, find the procedure technically demanding and experienced several complications with three anastomotic leaks (all with preserved intestinal continuity) and a urethral lesion. CONCLUSION: Ta-TME is feasible and might be the answer to obtaining good quality specimens and overcome some of the technical difficulties that can be encountered in the obese narrow male pelvis. The procedure however is technically demanding. PMID:28281474

  4. Implementation of Timeline Reforms Speeds Initiation of National Cancer Institute–Sponsored Trials

    PubMed Central

    2013-01-01

    Background The National Cancer Institute (NCI) organized the Operational Efficiency Working Group in 2008 to develop recommendations for improving the speed with which NCI-sponsored clinical trials move from the idea stage to a protocol open to patient enrollment. Methods Given the many stakeholders involved, the Operational Efficiency Working Group advised a multifaceted approach to mobilize the entire research community to improve their business processes. New staff positions to monitor progress, protocol-tracking Web sites, and strategically planned conference calls were implemented. NCI staff and clinical teams at Cooperative Groups and Cancer Centers strived to achieve new target timelines but, most important, agreed to abide by absolute deadlines. For phase I–II studies and phase III studies, the target timelines are 7 months and 10 months, whereas the absolute deadlines were set at 18 and 24 months, respectively. Trials not activated by the absolute deadline are automatically disapproved. Results The initial experience is encouraging and indicates a reduction in development times for phase I–II studies from the historical median of 541 days to a median of 442 days, an 18.3% decrease. The experience with phase III studies to date, although more limited (n = 25), demonstrates a 45.7% decrease in median days. Conclusions Based upon this progress, the NCI and the investigator community have agreed to reduce the absolute deadlines to 15 and 18 months for phase I–II and III trials, respectively. Emphasis on initiating trials rapidly is likely to help reduce the time it takes for clinical trial results to reach patients in need of new treatments. PMID:23776198

  5. Lessons Learned from the Initial 100 Patient Experience with Sentinel Lymph Node Mapping in the Evaluation of Breast Cancer

    PubMed Central

    Fuhrman, George M.; Burch, Ernest G.; Farr, Gist H.; King, Tari A.; Farkas, Emily; Bolton, John S.

    2000-01-01

    The initial reports of sentinel lymph node mapping for breast cancer currently appearing in the surgical literature are demonstrating the practicality and accuracy of the technique to evaluate patients for axillary nodal disease. We reviewed our initial 100 patient experience with sentinel node mapping to evaluate our ability to employ this technique in breast cancer patients. We combined a peritumoral injection of a radioactive substance and blue dye. Each sentinel node was evaluated with frozen section analysis, hematoxylin and eosin staining, and, if still negative, five re-cuts were taken from deeper levels of the node and evaluated for immunohistochemical evidence of cytokeratin staining. Sentinel node(s) were identified in all but two patients with 51% demonstrating metastasis. We have demonstrated the ability to accurately perform sentinel node mapping in the evaluation of our breast cancer patients. This exciting advance should become a standard part of breast cancer surgery. PMID:21765657

  6. Non-initiation of adjuvant hormonal therapy in women with hormone receptor-positive breast cancer: The Breast Cancer Quality of Care Study (BQUAL).

    PubMed

    Neugut, Alfred I; Hillyer, Grace Clarke; Kushi, Lawrence H; Lamerato, Lois; Leoce, Nicole; Nathanson, S David; Ambrosone, Christine B; Bovbjerg, Dana H; Mandelblatt, Jeanne S; Magai, Carol; Tsai, Wei-Yann; Jacobson, Judith S; Hershman, Dawn L

    2012-07-01

    Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation of hormonal therapy among women with newly diagnosed, non-metastatic HR-positive breast cancer recruited from three U.S. sites. Serial interviews were conducted at baseline and during treatment to examine sociodemographic factors, tumor characteristics, and treatment decision-making factors. Multivariate modeling assessed associations between variables of interest and hormonal therapy initiation. Of 1,050 breast cancer patients recruited, 725 (69%) had HR-positive breast cancer, of whom 87 (12.0%) based on self-report and 122 (16.8%) based on medical record/pharmacy fill rates did not initiate hormonal therapy. In a multivariable analysis, non-initiation of hormonal therapy, defined by medical record/pharmacy, was associated with having greater negative beliefs about efficacy of treatment (OR 1.42, 95% CI 1.18-1.70). Non-initiation was less likely in those who found the quality of patient/physician communication to be higher (OR 0.96, 95% CI 0.93-0.99), the hormonal therapy treatment decision an easy one to make (OR 0.45, 95% CI 0.23-0.90) or neither easy nor difficult (OR 0.34, 95% CI 0.20-0.58); and had more positive beliefs about hormonal therapy efficacy (OR 0.40, 95% CI 0.34-0.62). Factors influencing non-initiation of adjuvant hormonal therapy are complex and influenced by patient beliefs regarding treatment efficacy and side effects. Educational interventions to women about the benefits of hormonal therapy may decrease negative beliefs and increase hormone therapy initiation.

  7. Transition from colitis to cancer: high Wnt activity sustains the tumor-initiating potential of colon cancer stem cell precursors.

    PubMed

    Shenoy, Anitha K; Fisher, Robert C; Butterworth, Elizabeth A; Pi, Liya; Chang, Lung-Ji; Appelman, Henry D; Chang, Myron; Scott, Edward W; Huang, Emina H

    2012-10-01

    Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC), but the mechanisms involved in colitis-to-cancer transition (CCT) are not well understood. CCT may involve a inflammation-dysplasia-carcinoma progression sequence compared with the better characterized adenoma-carcinoma progression sequence associated with sporadic CRC. One common thread may be activating mutations in components of the Wnt/β-catenin signaling pathway, which occur commonly as early events in sporadic CRC. To examine this hypothesis, we evaluated possible associations between Wnt/β-catenin signaling and CCT based on the cancer stem cell (CSC) model. Wnt/β-catenin immunostaining indicated that UC patients have a level of Wnt-pathway-active cells that is intermediate between normal colon and CRC. These UC cells exhibiting activation of the Wnt pathway constituted a major subpopulation (52% + 7.21) of the colonic epithelial cells positive for aldehyde dehydrogenase (ALDH), a putative marker of precursor colon CSC (pCCSC). We further fractionated this subpopulation of pCCSC using a Wnt pathway reporter assay. Over successive passages, pCCSCs with the highest Wnt activity exhibited higher clonogenic and tumorigenic potential than pCCSCs with the lowest Wnt activity, thereby establishing the key role of Wnt activity in driving CSC-like properties in these cells. Notably, 5/20 single cell injections of high-Wnt pCCSC resulted in tumor formation, suggesting a correlation with CCT. Attenuation of Wnt/β-catenin in high-Wnt pCCSC by shRNA-mediated downregulation or pharmacological inhibition significantly reduced tumor growth rates. Overall, the results of our study indicates (i) that early activation of Wnt/β-catenin signaling is critical for CCT and (ii) that high levels of Wnt/β-catenin signaling can further demarcate high-ALDH tumor-initiating cells in the nondysplastic epithelium of UC patients. As such, our findings offer plausible diagnostic markers and therapeutic target in the

  8. Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145

    PubMed Central

    Kucukzeybek, Yuksel; Gul, Mustafa K; Cengiz, Ercument; Erten, Cigdem; Karaca, Burcak; Gorumlu, Gurbuz; Atmaca, Harika; Uzunoglu, Selim; Karabulut, Bulent; Sanli, Ulus A; Uslu, Ruchan

    2008-01-01

    Background The management of hormone-refractory prostate cancer (HRPC) still remains as an important challenge of daily oncology practice. Docetaxel has proved to be a first line treatment choice. All-trans retinoic acid (ATRA) could potently inhibit the growth of prostate cancer cells in vitro and its combination with various anticancer agents results in increased cytotoxicity. Based on these data, our aim was to examine the synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and ATRA, in hormone- and drug refractory human DU-145 prostate cancer cells. Furthermore, we have searched for the underlying mechanisms of apoptosis by demonstrating apoptosis-related genes. Methods XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. For detecting the mechanism of apoptosis induced by docetaxel-ATRA combination, OligoGeArray® which consists of 112 apoptosis related genes was used. Results Our results revealed that docetaxel and ATRA were synergistically cytotoxic and apoptotic in DU-145 cells, in a dose- and time dependent manner. It was also shown by our studies that apoptosis was induced in DU-145 prostate carcinoma cells with significant cytotoxicity, no matter which agent applied first. We have found out that docetaxel-ATRA combination significantly downregulates survivin (BIRC5), myeloid cell leukemia-1 (MCL-1) and lymphotoxin β-receptor (LTβR) genes, which all three have pivotal roles in regulation of apoptosis and cell cycle progression. Conclusion In conclusion, we strongly suggest that docetaxel and ATRA combination is a good candidate for this challenging era of daily oncologic practice. Also, the combination of docetaxel and ATRA might allow a reduction in docetaxel doses and by this way may diminish docetaxel adverse effects while maintaining the therapeutic effect in patients with HRPC. PMID:18789152

  9. La radiothérapie du cancer de l'endomètre: expérience de l'institut national d'oncologie à propos de 52 cas

    PubMed Central

    Mezouri, Imane; Berhili, Soufiane; Mouhajir, Nawal; Bellefqih, Sara; Elkacemi, Hanan; Kebdani, Tayeb; Benjaafar, Noureddine

    2016-01-01

    Le cancer de l'endomètre est le cancer gynécologique le plus fréquent en occident. Il concerne principalement les femmes ménopausées. L'objectif de notre travail est de rapporter l'expérience du service de radiothérapie à l'Institut National d'Oncologie (INO) dans la prise en charge du cancer de l'endomètre. Nous avons analysé rétrospectivement 52 cas de cancer de l'endomètre traités dans le service de radiothérapie de l'INO entre 2007 à 2009. Les données collectées à partir des dossiers médicaux de nos patientes concernaient les aspects épidémiologiques, cliniques, thérapeutiques et évolutifs de ce cancer. La médiane d’âge des patientes était de 57 ans, 87% étaient ménopausées. Le délai moyen de consultation était de six mois. Le maitre symptôme était des métrorragies chez 51 patientes. Le diagnostic histologique a été porté sur un curetage biopsique de l'endomètre dans 51% des cas. L'examen anatomopathologique a montré un adénocarcinome endométrioïde dans 92% des cas. Après le bilan, 27% des patientes étaient stade I, 30% stade II, 20% stade III et 1% stade IVA selon la classification de la Fédération Internationale de Gynécologie Obstétrique (FIGO). Après la chirurgie, 51% des patientes ont reçu une radiothérapie externe. La dose délivrée était de 46 Gray (Gy). Une curiethérapie du fond vaginal a été délivrée chez toutes les patientes. Sur le plan évolutif, 83% des patientes étaient toujours suivies en situation de bon contrôle de leur maladie, 8% ont eu une récidive locorégionale et 4% avaient des métastases à distance. Ainsi, le cancer de l'endomètre est un cancer dont le traitement repose sur la chirurgie. La radiothérapie est le traitement adjuvant principal. PMID:27279969

  10. RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells.

    PubMed

    Yang, Y; Xu, H; Shen, J; Yang, Y; Wu, S; Xiao, J; Xu, Y; Liu, X-Y; Chu, L

    2015-05-14

    Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carrying EGFP or TNF-related apoptosis-inducing ligand (TRAIL) gene (Onco(Ad).RGD-hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and cancer-initiating T24 sphere cells. Onco(Ad).RGD-hTERT-EGFP had enhanced infection ability and cytotoxic effect on T24 cells and T24 sphere cells, but little cytoxicity on normal urothelial SV-HUC-1 cells compared with the unmodified virus Onco(Ad).hTERT-EGFP. Notably, Onco(Ad).RGD-hTERT-TRAIL induced apoptosis in T24 cells and T24 sphere cells. Furthermore, it completely inhibited xenograft initiation established by the oncolytic adenovirus-pretreated T24 sphere cells, and significantly suppressed tumor growth by intratumoral injection. These results provided a promising therapeutic strategy for CAR-negative bladder cancer through targeting CICs.

  11. 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

  12. Genome-wide Association Studies from the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative | Office of Cancer Genomics

    Cancer.gov

    CGEMS identifies common inherited genetic variations associated with a number of cancers, including breast and prostate. Data from these genome-wide association studies (GWAS) are available through the Division of Cancer Epidemiology & Genetics website.

  13. Proteomic analysis of cancer stem cells in human prostate cancer cells

    SciTech Connect

    Lee, Eun-Kyung; Cho, Hyungdon; Kim, Chan-Wha

    2011-08-26

    Highlights: {yields} DU145 prostate cancer cell line was isolated into CD44+ or CD44- cells. {yields} We confirmed CD44+ DU145 cells are more proliferative and tumorigenic than CD44- DU145 cells. {yields} We analyzed and identified proteins that were differentially expressed between CD44+ and CD44- DU145 cells. {yields} Cofilin and Annexin A5 associated with cancer were found to be positively correlated with CD44 expression. -- Abstract: Results from recent studies support the hypothesis that cancer stem cells (CSCs) are responsible for tumor initiation and formation. Here, we applied a proteome profiling approach to investigate the mechanisms of CSCs and to identify potential biomarkers in the prostate cancer cell line DU145. Using MACS, the DU145 prostate cancer cell line was isolated into CD44+ or CD44- cells. In sphere culture, CD44+ cells possessed stem cell characteristics and highly expressed genes known to be important in stem cell maintenance. In addition, they showed strong tumorigenic potential in the clonogenic assay and soft agar colony formation assay. We then analyzed and identified proteins that were differentially expressed between CD44+ and CD44- using two-dimensional gel electrophoresis and LC-MS/MS. Cofilin and Annexin A5, which are associated with proliferation or metastasis in cancer, were found to be positively correlated with CD44 expression. These results provide information that will be important to the development of new cancer diagnostic tools and understanding the mechanisms of CSCs although a more detailed study is necessary to investigate the roles of Cofilin and Annexin A5 in CSCs.

  14. Biokinetics and dosimetry of depleted uranium (DU) in rats implanted with DU fragments.

    SciTech Connect

    Guilmette, Ray A.; Hahn, Fletcher F.; Durbin, P. W.

    2004-01-01

    A number of U. S. veterans of the Persian Gulf War were wounded with depleted uranium (DU) metal fragments as a result of 'friendly fire' incidents, in which Abrams tanks and Bradley fighting vehicles were struck by DU anti-armor munitions. Some of the crew members who survived were left with multiple small fragments of DU in their muscles and soft tissues. The number, size and location of the fragments made them inoperable in general, and therefore subject to long-term retention. Because there was inadequate data to predict the potential carcinogenicity of DU fragments in soft tissues, Hahn et al. (2003) conducted a lifespan cancer study in rats. As part of that study, a number of rats were maintained to study the biokinetics and dosimetry of DU implanted intramuscularly in male Wistar rats. Typically, four metal fragments, either as cylindrical pellets or square wafers were implanted into the biceps femoris muscles of the rats. Urine samples were collected periodically during their lifespans, and DU was analyzed in kidneys and eviscerated carcass (minus the implant sites) at death. The daily DU urinary excretion rate increased steeply during the first 30 d after implantation peaking at about 90 d at 3-10 x 10{sup -3}%/d. During the first 150 d, the average excretion rate was 2.4 x 10{sup -3}%/d, decreasing thereafter to about 1 x 10{sup -3}%/d. Serial radiographs were made of the wound sites to monitor gross morphologic changes in the DU implant and the surrounding tissue. As early as 1 w after implantation, radiographs showed the presence of surface corrosion and small, dense bodies near the original implant, presumably DU. This corrosion from the surface of the implant continued with time, but did not result in an increasing amount of DU reaching the blood and urine after the first 3 mo. During this 3-mo period, connective tissue capsules formed around the implants, and are hypothesized to have reduced the access of DU to tissue fluids by limiting the diffusion

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

    PubMed Central

    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.

    2014-01-01

    Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer (CRC). Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine and trimethylamine N-oxide (TMAO)] and CRC 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). CRC was assessed by self-report and confirmed by medical records over the mean 5.2y of follow-up. Baseline plasma choline metabolites were measured by liquid chromatography-tandem mass spectrometry. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% CI)highest vs. lowest quartile=2.44 (0.93–6.40);P-trend=0.08], while plasma betaine was inversely associated with CRC 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 CRC 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 CRC 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 CRC. The positive association between plasma TMAO and CRC risk is consistent with an involvement of the gut microbiome in CRC pathogenesis

  16. A new diagnostic for cancer dynamics: status and initial tests of the NANIVID

    NASA Astrophysics Data System (ADS)

    Raja, Waseem K.; Gligorijevic, Bojana; Condeelis, John S.; Castracane, James

    2009-02-01

    The Tumor MicroEnvironment for Metastasis (TMEM) is a critical determinant which will presage the evolution of primary tumors and the resulting metastatic dynamics. Primary tumor cells up and down regulate certain genes which increase motility and cause a disregard for positional information. We report on the development of a new tool for the documentation of cancer cell migration (initial targets: the rat mammary adenocarcinoma cell lines MTLn3 with an over expression of Mena+++). This tool, the NANo IntraVital Device (NANIVID), is a multi-functional nanosystem composed of a chemoattractant source (hydrogel-EGF), capsule (cell trap), counter (transparent, interdigitated electrode arrays for sensing cell arrival), and remote reporter (readout electronics). The device will be retrieved from the tumor site and the cells will be expelled for subsequent assay. The NANIVID will be used in conjunction with the current catheter-based approach in which a needle is loaded with a chemoattractant source and injected into the tumor. A major drawback in the catheter approach is the short cell collection time and lack of real time registering and reporting of cell arrival. This paper will present the current status of the NANIVID prototypes developed in which a transparent implantable device is loaded with chemoattractant source and placed near candidate mammary gland tumors in an established rat model for multiple days or weeks. This series of experiments will allow the comparison of methods and to benchmark the NANIVID for use in research. Initial results of these experiments and NANIVID design modifications will be presented.

  17. Constitutive expression and activation of stress response genes in cancer stem-like cells/tumour initiating cells: potent targets for cancer stem cell therapy.

    PubMed

    Torigoe, Toshihiko; Hirohashi, Yoshihiko; Yasuda, Kazuyo; Sato, Noriyuki

    2013-08-01

    Cancer stem-like cells (CSCs)/tumour-initiating cells (TICs) are defined as the small population of cancer cells that have stem cell-like phenotypes and high capacity for tumour initiation. These cells may have a huge impact in the field of cancer therapy since they are extremely resistant to standard chemoradiotherapy and thus are likely to be responsible for disease recurrence after therapy. Therefore, extensive efforts are being made to elucidate the pathological and molecular properties of CSCs/TICs and, with this information, to establish efficient anti-CSC/TIC targeting therapies. This review considers recent findings on stress response genes that are preferentially expressed in CSCs/TICs and their roles in tumour-promoting properties. Implications for a novel therapeutic strategy targeting CSCs/TICs are also discussed.

  18. Overview of the 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.

  19. [Conversion Surgery for Initially Unresectable Locally Advanced Pancreatic Cancer Following Gemcitabine plus Nab-Paclitaxel - A Case Report].

    PubMed

    Nakamoto, Shuji; Nishiyama, Ryo; Kaneda, Takayoshi; Yokota, Mitsuo; Kawamata, Hiroshi; Tajima, Hiroshi; Kaizu, Takashi; Kumamoto, Yusuke; Yamauchi, Hiroshi; Okuwaki, Kosuke; Iwai, Tomohisa; Imaizumi, Hiroshi; Suzuki, Erina; Hara, Atsuko; Ichinoe, Masaaki; Kida, Mitsuhiro; Watanabe, Masahiko

    2017-02-01

    We report a case of unresectable locally advanced pancreatic cancer successfully resected after gemcitabine(GEM)plus nab-paclitaxel(PTX)treatment. A 68-year-old man was referred to our institution with jaundice. We diagnosed pancreatic head cancer using computed tomography(CT)and endoscopic retrograde cholangiopancreatography. We initially diagnosed it as locally advanced unresectable pancreatic cancer because of extensive invasion to the portal vein. GEM plus nab- PTX was administered to the patient as systemic chemotherapy. After 9 courses of chemotherapy, a CT scan revealed that the tumor had significantly reduced in size and range of portal vein invasion. Therefore, we performed pancreaticoduodenectomy with resection of the portal vein and achieved R0 resection. Currently, the patient is alive without recurrence. Therefore, conversion surgery after treatment with GEM plus nab-PTX chemotherapy for unresectable pancreatic cancer should be considered.

  20. 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

  1. Optimal Cutoffs of Obesity Measures in Relation to Cancer Risk in Postmenopausal Women in the Women's Health Initiative Study

    PubMed Central

    Kabat, Geoffrey C.; Strickler, Howard D.; Lin, Juan; Hou, Lifang; Stefanick, Marcia L.; Anderson, Garnet L.; Rohan, Thomas E.

    2015-01-01

    Abstract Background: Obesity is a risk factor for several cancers in postmenopausal women. We attempted to determine cutoffs of adiposity measures in relation to risk of obesity-related cancers among postmenopausal women and to examine the effects of hormone therapy (HT) use on the cutoffs, neither of which has been broadly studied. Methods: We used data from the Women's Health Initiative cohort (n=144,701) and applied Cox-proportional hazards regressions to each combination of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI], weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist to height ratio). Interactions between the anthropometric measures and HT use were also examined. Cutoffs were determined by applying a grid search followed by a two-fold cross validation method. Survival ROC analysis of 5- and 10-year incidence followed. Results: Breast, colorectal, colon, endometrium, kidney, and all cancers combined were significantly positively associated with all six anthropometric measures, whereas lung cancer among ever smokers was significantly inversely associated with all measures except WHR. The derived cutoffs of each obesity measure varied across cancers (e.g., BMI cutoffs for breast and endometrium cancers were 30 kg/m2 and 34 kg/m2, respectively), and also depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10-year cancer incidence were higher among HT never users. Conclusion: Using a panel of different anthropometric measures, we derived optimal cut-offs categorizing populations into high- and low-risk groups, which differed by cancer type and HT use. Although the discrimination abilities of these risk categories were generally poor, the results of this study could serve as a starting point from which to determine adiposity cutoffs for inclusion in risk prediction models for specific cancer types. PMID:25587642

  2. Is there any association between imidapril hydrochloride stability profile under dry air conditions and cancer initiation?

    PubMed

    Regulska, Katarzyna; Murias, Marek; Stanisz, Beata; Regulski, Miłosz

    2013-11-18

    Stability study for imidapril hydrochloride (IMD) was performed under stress conditions of increased temperature (T=373 K) and decreased relative air humidity (RH=0%) in order to obtain and identify its degradation product. The degradation sample stored for 15 days under the above environmental conditions was analyzed by LC-MS technique and it was found that the only degradation impurity formed in the course of the investigated drug degradation was IMD diketopiperazine derivative (DKP) which was produced by dehydration and intramolecular cyclization. The kinetics of its formation was analyzed by a revalidated RP-HPLC method and the kinetic model of this reaction was established. It was concluded that the DKP formation follows Prout-Tompkins kinetics with the rate constant k±Δk=2.034±0.157×10(-6) [s(-1)]. The obtained degradation impurity was further assessed with respect to its mutagenic potential using commercial Ames MPF 98/100 microplate format mutagenicity assay kit equipped with Salmonella typhimurium strains TA 98 and TA 100. Both strains were exposed to six concentrations (in a range of 0.16-5.0mg/mL) of DKP in the presence and absence of metabolic activation system. No mutagenic effect was observed confirming that the presence of DKP in IMD final dosage form has no impact on cancer initiation.

  3. Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells.

    PubMed

    Dubash, Taronish D; Hoffmann, Christopher M; Oppel, Felix; Giessler, Klara M; Weber, Sarah; Dieter, Sebastian M; Hüllein, Jennifer; Zenz, Thorsten; Herbst, Friederike; Scholl, Claudia; Weichert, Wilko; Werft, Wiebke; Benner, Axel; Schmidt, Manfred; Schneider, Martin; Glimm, Hanno; Ball, Claudia R

    2016-02-28

    Within primary colorectal cancer (CRC) a subfraction of all tumor-initiating cells (TIC) drives long-term progression in serial xenotransplantation. It has been postulated that efficient maintenance of TIC activity in vitro requires serum-free spheroid culture conditions that support a stem-like state of CRC cells. To address whether tumorigenicity is indeed tightly linked to such a stem-like state in spheroids, we transferred TIC-enriched spheroid cultures to serum-containing adherent conditions that should favor their differentiation. Under these conditions, primary CRC cells did no longer grow as spheroids but formed an adherent cell layer, up-regulated colon epithelial differentiation markers, and down-regulated TIC-associated markers. Strikingly, upon xenotransplantation cells cultured under either condition equally efficient formed serially transplantable tumors. Clonal analyses of individual lentivirally marked TIC clones cultured under either culture condition revealed no systematic differences in contributing clone numbers, indicating that phenotypic differentiation does not select for few individual clones adapted to unfavorable culture conditions. Our results reveal that CRC TIC can be propagated under conditions previously thought to induce their elimination. This phenotypic plasticity allows addressing primary human CRC TIC properties in experimental settings based on adherent cell growth.

  4. Cancer-Associated Fibroblasts and Their Putative Role in Potentiating the Initiation and Development of Epithelial Ovarian Cancer1

    PubMed Central

    Schauer, Isaiah G; Sood, Anil K; Mok, Samuel; Liu, Jinsong

    2011-01-01

    The progression of ovarian cancer, from cell transformation through invasion of normal tissue, relies on communication between tumor cells and their adjacent stromal microenvironment. Through a natural selection process, an autocrine-paracrine communication loop establishes reciprocal reinforcement of growth and migration signals. Thus, the cancer-activated stromal response is similar to an off-switch-defective form of the normal, universal response needed to survive insult or injury. It is becoming clearer within the cancer literature base that tumor stroma plays a bimodal role in cancer development: it impedes neoplastic growth in normal tissue while encouraging migration and tumor growth in a co-opted desmoplastic response during tumor progression. In this review, we discuss this reciprocal influence that ovarian cancer epithelial cells may have on ovarian stromal cell-reactive phenotype, stromal cell behavior, disrupted signaling networks, and tumor suppressor status in the stroma, within the context of cancer fibroblast studies from alternate cancer tissue settings. We focus on the exchange of secreted factors, in particular interleukin 1β and SDF-1α, between activated fibroblasts and cancer cells as a key area for future investigation and therapeutic development. A better understanding of the bidirectional reliance of early epithelial cancer cells on activated stromal cells could lead to the identification of novel diagnostic stromal markers and targets for therapy. PMID:21532880

  5. Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer.

    PubMed

    Livaudais, Jennifer C; Hershman, Dawn L; Habel, Laurel; Kushi, Lawrence; Gomez, Scarlett Lin; Li, Christopher I; Neugut, Alfred I; Fehrenbacher, Louis; Thompson, Beti; Coronado, Gloria D

    2012-01-01

    Mortality after breast cancer diagnosis is known to vary by race/ethnicity even after adjustment for differences in tumor characteristics. As adjuvant hormonal therapy decreases risk of recurrence and increases overall survival among women with hormone receptor-positive tumors, treatment disparities may play a role. We explored racial/ethnic differences in initiation of adjuvant hormonal therapy, defined as two or more prescriptions for tamoxifen or aromatase inhibitor filled within the first year after diagnosis of hormone receptor-positive localized or regional-stage breast cancer. The sample included women diagnosed with breast cancer enrolled in Kaiser Permanente Northern California (KPNC). Odds ratios [OR] and 95% confidence intervals [CI] compared initiation by race/ethnicity (Hispanic, African American, Chinese, Japanese, Filipino, and South Asian vs. non-Hispanic White [NHW]) using logistic regression. Covariates included age and year of diagnosis, area-level socioeconomic status, co-morbidities, tumor stage, histology, grade, breast cancer surgery, radiation and chemotherapy use. Our sample included 13,753 women aged 20-79 years, diagnosed between 1996 and 2007, and 70% initiated adjuvant hormonal therapy. In multivariable analysis, Hispanic and Chinese women were less likely than NHW women to initiate adjuvant hormonal therapy ([OR] = 0.82; [CI] 0.71-0.96 and [OR] = 0.78; [CI] 0.63-0.98, respectively). Within an equal access, insured population, lower levels of initiation of adjuvant hormonal therapy were found for Hispanic and Chinese women. Findings need to be confirmed in other insured populations and the reasons for under-initiation among these groups need to be explored.

  6. Assessment of microsatellite instability status for the prediction of metachronous recurrence after initial endoscopic submucosal dissection for early gastric cancer

    PubMed Central

    Hasuo, T; Semba, S; Li, D; Omori, Y; Shirasaka, D; Aoyama, N; Yokozaki, H

    2006-01-01

    The technique of endoscopic submucosal dissection (ESD) has been developed for en bloc resection of early gastric cancer (EGC); however, little is known about the risk of metachronous cancer in the remnant stomach after initial ESD. In this study, we investigated the correlation between microsatellite instability (MSI) status and the incidence of metachronous recurrence of gastric cancer. According to the genetic/molecular background determined with MSI status and expression levels of hMLH1 and p53 tumour suppressor, 110 EGCs removed with ESD were subclassified into three groups: the mutator/MSI-type (8%), suppressor/p53-type (45%) and unclassified type (47%). Interestingly, patients with the mutator/MSI-type tumour had a high incidence (67%) of metachronous recurrence of gastric cancer within a 3-year observation after initial ESD, which was significantly higher than those with the suppressor/p53-type and unclassified type tumours (P<0.01). Although we investigated mucin phenotypes, there was no correlation between mucin phenotype and the recurrence of EGC. These findings suggest that subclassification of molecular pathological pathways in EGCs is required for the assessment of patients with a high risk of recurrent gastric cancer. The information delivered from our investigation is expected to be of value for decisions about therapy and surveillance after ESD. PMID:17179982

  7. Race/Ethnicity and the Receipt of Watchful Waiting for the Initial Management of Prostate Cancer

    PubMed Central

    Shavers, Vickie L; Brown, Martin L; Potosky, Arnold L; Klabunde, Carrie N; Davis, WW; Moul, Judd W; Fahey, Angela

    2004-01-01

    INTRODUCTION Several recent studies have noted that African Americans disproportionately receive “watchful waiting” for the initial management of their prostate cancer. To determine whether racial/ethnic differences in the receipt of watchful waiting are explained by differences in clinical presentation and life expectancy at the time of diagnosis, we examined Surveillance, Epidemiology, and End Results (SEER)-Medicare data for men diagnosed with prostate cancer in 1994 to 1996. METHODS Race/ethnicity, comorbidity, stage, grade, age, and expected lifespan and their association with the receipt of watchful waiting were examined in multivariate logistic regression analyses. Race-stratified logistic regression analyses were also used to examine racial/ethnic variation in the association of clinical and demographic factors with the receipt of watchful waiting among African-American, Hispanic, and non-Hispanic white men. RESULTS African-American (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.3 to 1.6) and Hispanic men (OR, 1.3; 95% CI, 1.1 to 1.5) were significantly more likely than non-Hispanic white men to receive watchful waiting in a multivariate model adjusted for age, comorbidity, stage, grade, and life expectancy. Advanced stage and grade, lower life expectancy, older age, and high comorbidity indices were also significantly associated with an increase in the odds of receipt of watchful waiting in multivariate analyses. In general, the association between the receipt of watchful waiting and the clinical characteristics (i.e., stage, grade, and age) were similar for the three racial/ethnic groups. In race-stratified logistic regression analyses, life expectancy was associated with an increase in the odds of receiving watchful waiting but results were statistically significant for whites only. There was also a statistically significant increase in the odds of receiving watchful waiting for African-American and white men with high comorbidity indices but

  8. miR-15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer.

    PubMed

    Wang, Xijun; Guo, Hongmei; Yao, Banjamin; Helms, Julia

    2017-03-27

    Oral tongue squamous cell carcinoma (TSCC) is one of the most lethal cancers within the oral cavity and its prognosis remains dismal due to the paucity of effective therapeutic targets. The formation of cancer-initiating cells (CICs) and epithelial-mesenchymal transition (EMT) are pivotal events involved in the dismal prognosis. They have been shown to be related to the resistance to cisplatin treatment. In the present study, we showed that TRIM14 induced formation of cancer-initiating cells and EMT in TSCC SCC25 cells. Its overexpression promoted cisplatin resistance in the SCC25 cells. We found that overexpression of miR-15b suppressed TRIM14 and inhibited CIC phenotypes in the SCC25 cells. Moreover, overexpression of miR-15b promoted mesenchymal-epithelial transition (MET) in the SCC25 cells and sensitized cisplatin-resistant SCC25 (SCC25-res) cells to cisplatin. Thus, we conclude that miR-15b inhibited cancer stem cell phenotypes and its restoration reversed the chemoresistance of cisplatin by targeting TRIM14 in TSCC. Elucidating the molecular mechanism of EMT and cancer stem cells in TSCC may further aid in the understanding of the pathogenesis and progression of the disease, and offer novel targets for the discovery of new drugs.

  9. Call for a Computer-Aided Cancer Detection and Classification Research Initiative in Oman.

    PubMed

    Mirzal, Andri; Chaudhry, Shafique Ahmad

    2016-01-01

    Cancer is a major health problem in Oman. It is reported that cancer incidence in Oman is the second highest after Saudi Arabia among Gulf Cooperation Council countries. Based on GLOBOCAN estimates, Oman is predicted to face an almost two-fold increase in cancer incidence in the period 2008-2020. However, cancer research in Oman is still in its infancy. This is due to the fact that medical institutions and infrastructure that play central roles in data collection and analysis are relatively new developments in Oman. We believe the country requires an organized plan and efforts to promote local cancer research. In this paper, we discuss current research progress in cancer diagnosis using machine learning techniques to optimize computer aided cancer detection and classification (CAD). We specifically discuss CAD using two major medical data, i.e., medical imaging and microarray gene expression profiling, because medical imaging like mammography, MRI, and PET have been widely used in Oman for assisting radiologists in early cancer diagnosis and microarray data have been proven to be a reliable source for differential diagnosis. We also discuss future cancer research directions and benefits to Oman economy for entering the cancer research and treatment business as it is a multi-billion dollar industry worldwide.

  10. CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer

    PubMed Central

    Li, Chong; Liu, Shengwu; Yan, Ruping; Han, Ning; Wong, Kwok-Kin; Li, Lei

    2017-01-01

    Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. Additional in vitro and in vivo assays showed that CD54 played a critical role in the self-renewal and tumorigenesis of prostate CSCs. Moreover, silencing CD54 greatly reduced the tumorigenesis of prostate cancers both in vitro and in vivo and significantly extended the survival time of tumor-bearing mice in a prostate cancer xenograft model. Dissection of the molecular mechanism revealed that the p38-Notch1 axis was the main downstream signaling pathway in CD54-mediated regulation of CSCs in prostate cancers. Together, these results established that CD54 could be a novel reliable prostate CSC marker and provided a new potential therapeutic target in prostate cancer via CD54-Notch1 signaling. PMID:28042317

  11. Role of Lysophospholipids in the Initiation, Progression and Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    autotaxin levels areincreased approximately 28 fold in breast cancer cells isolated directly from patients.This should result in increased LPA and S1P ...apoptosis in breast cancer cells.We have utilized a novel Si1P antibody to neutralize S1P in vitro and are currentlytreating mice with breast cancer...epithelium. We have obtained a LPP transgenic mouse to determine theeffects of degradation of LPA and S1P on breast function and tumorigenesis by

  12. 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

  13. Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women's Health Initiative.

    PubMed

    Kaklamani, Virginia G; Hoffmann, Thomas J; Thornton, Timothy A; Hayes, Geoffrey; Chlebowski, Rowan; Van Horn, Linda; Mantzoros, Christos

    2013-06-01

    Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women's Health Initiative SNP Health Association Resource cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1, and ADIPOR2. The genome-wide human SNP array 6.0 (909,622 SNPs) ( www.affymetrix.com ) was used. We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95 % CI 1.059-1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment.

  14. "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…

  15. Patient-Centered Cancer Care Programs in Italy: Benchmarking Global Patient Education Initiatives.

    PubMed

    Truccolo, Ivana; Cipolat Mis, Chiara; Cervo, Silvia; Dal Maso, Luigino; Bongiovanni, Marilena; Bearz, Alessandra; Sartor, Ivana; Baldo, Paolo; Ferrarin, Emanuela; Fratino, Lucia; Mascarin, Maurizio; Roncadin, Mario; Annunziata, Maria Antonietta; Muzzatti, Barbara; De Paoli, Paolo

    2016-06-01

    In Italy, educational programs for cancer patients are currently provided by the national government, scientific societies, and patient advocate organizations. Several gaps limit their effectiveness, including the lack of coordinated efforts, poor involvement of patient feedback in the planning of programs, as well as a lack of resources on innovative cancer-related topics. This process is parallel to a strong shift in the attitude of patients towards health in general and taking charge of their own health conditions in particular. The National Cancer Institute in the USA and the Organization of European Cancer Institutes encourage comprehensive cancer centers in providing educational programs conceived to overcome these gaps. The goal of this paper is to identify and describe the key elements necessary to develop a global patient education program and provide recommendations for strategies with practical examples for implementation in the daily activities of cancer institutes. A multidisciplinary committee was established for patient education, including patient representatives as equal partners, to define, implement, verify, and evaluate the fundamental steps for establishing a comprehensive education program. Six essential topics were identified for the program: appropriate communication of cancer epidemiology, clinical trial information, new therapeutic technologies, support in the use of medicines, psycho-oncological interventions, age-personalized approaches, and training programs for healthcare providers. Integration of these topics along with patient feedback is the key to a successful model for educational programs. An integrated educational program can transform a comprehensive cancer center to an institution that provides research and care for and with patients.

  16. Cancer Education Program Evaluation: A Responsive Approach to Planning an Evaluation and Initial Results.

    ERIC Educational Resources Information Center

    Pearsol, James A.

    This paper describes evaluation planning for the Cancer Education Program (CEP) at Ohio State University (OSU). The three-year OSU CEP project was designed as a multidisciplinary cancer education program. A responsive method, which trades off some measurement precision in order to increase the usefulness of the findings, was employed in the…

  17. Circles of care: development and initial evaluation of a peer support model for African Americans with advanced cancer.

    PubMed

    Hanson, Laura C; Armstrong, Tonya D; Green, Melissa A; Hayes, Michelle; Peacock, Stacie; Elliot-Bynum, Sharon; Goldmon, Moses V; Corbie-Smith, Giselle; Earp, Jo Anne

    2013-10-01

    Peer support interventions extend care and health information to underserved populations yet rarely address serious illness. Investigators from a well-defined academic-community partnership developed and evaluated a peer support intervention for African Americans facing advanced cancer. Evaluation methods used the Reach, Efficacy, Adoption, Implementation, Maintenance (RE-AIM) framework. Investigators initially recruited and trained 24 lay health advisors who shared information or support with 210 individuals. However, lay advisors reported barriers of medical privacy and lack of confidence working alone with people with cancer. Training was modified to match the support team model for peer support; training reached 193 volunteers, 104 of whom formed support teams for 47 persons with serious illness. Support teams were adopted by 23 community organizations, including 11 African American churches. Volunteers in teams felt prepared to implement many aspects of supportive care such as practical support (32%) or help with cancer or palliative care resources (43%). People with serious illness requested help with practical, emotional, spiritual, and quality of life needs; however, they rarely wanted advocacy (3%) or cancer or palliative care resources (5%) from support teams. Volunteers had difficulty limiting outreach to people with advanced cancer due to medical privacy concerns and awareness that others could benefit. Support teams are a promising model of peer support for African Americans facing advanced cancer and serious illness, with reach, adoption, and implementation superior to the lay advisor model. This formative initial evaluation provides evidence for feasibility and acceptance. Further research should examine the efficacy and potential for maintenance of this intervention.

  18. 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.

  19. Raising the Awareness of Undergraduate Nurses to the Psychosocial Impact of Living with Cancer: A Consumer Engagement in Teaching Initiative

    PubMed Central

    Zannettino, Lana; Thompson, Jan; Marker, Julie; Agius, Stephanie

    2016-01-01

    This article reflects on the development and implementation of a consumer engagement in teaching initiative by the authors. The authors highlight the challenges of engaging undergraduate nursing students on the psychosocial aspects of living with cancer and other chronic illnesses when students have very limited personal and professional experiences to draw on. The authors discuss how they have responded to these challenges by integrating the voices of consumers into their classrooms. Speakers from consumer advocacy organization, Cancer Voices SA, participated in a series of tutorials in a 1st year topic in the Undergraduate Nursing Program at the School of Nursing and Midwifery, Flinders University. Student feedback from the implementation of the initiative indicated that students found consumers’ stories and experiences of living with cancer, “moving and powerful” and that they encouraged students to question their assumptions about the psychosocial impacts of cancer on individuals and families. The importance of good communication in reducing patient distress was identified by students as an important element of consumers’ experiences of the health care system as was the need for transparency and information sharing between health care providers across the health care system. For many students, consumers’ stories and experiences had reinforced students’ commitment to studying nursing and pursuing a career in nursing. The article concludes that involving consumers in the education of health care professionals encourages a much deeper understanding of and empathy for how patients experience disease, which is integral to the provision of patient-centered and holistic care. PMID:27981150

  20. 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

  1. Complex role for the immune system in initiation and progression of pancreatic cancer.

    PubMed

    Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

    2014-08-28

    The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

  2. Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber).

    PubMed

    Delaney, M A; Ward, J M; Walsh, T F; Chinnadurai, S K; Kerns, K; Kinsel, M J; Treuting, P M

    2016-05-01

    Naked mole-rats (NMRs;Heterocephalus glaber) are highly adapted, eusocial rodents renowned for their extreme longevity and resistance to cancer. Because cancer has not been formally described in this species, NMRs have been increasingly utilized as an animal model in aging and cancer research. We previously reported the occurrence of several age-related diseases, including putative pre-neoplastic lesions, in zoo-housed NMR colonies. Here, we report for the first time 2 cases of cancer in zoo-housed NMRs. In Case No. 1, we observed a subcutaneous mass in the axillary region of a 22-year-old male NMR, with histologic, immunohistochemical (pancytokeratin positive, rare p63 immunolabeling, and smooth muscle actin negative), and ultrastructural characteristics of an adenocarcinoma possibly of mammary or salivary origin. In Case No. 2, we observed a densely cellular, poorly demarcated gastric mass of polygonal cells arranged in nests with positive immunolabeling for synaptophysin and chromogranin indicative of a neuroendocrine carcinoma in an approximately 20-year-old male NMR. We also include a brief discussion of other proliferative growths and pre-cancerous lesions diagnosed in 1 zoo colony. Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model. These reports also highlight the benefit of long-term disease investigations in zoo-housed populations to better understand naturally occurring disease processes in species used as models in biomedical research.

  3. Complex role for the immune system in initiation and progression of pancreatic cancer

    PubMed Central

    Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

    2014-01-01

    The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed. PMID:25170202

  4. A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239

    PubMed Central

    Wright, Frances C; Law, Calvin HL; Last, Linda D; Klar, Neil; Ryan, David P; Smith, Andrew J

    2006-01-01

    Background A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. Methods/Design Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. Discussion We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings. PMID:16412251

  5. Association synchrone d'un cancer du sein bilatéral et d'une tumeur stromale gastro-intestinale: à propos d'un rare cas

    PubMed Central

    Afif, Mohammed; Ouziane, Imane; Kouhen, Fadila; Khalil, Jihane; Elomrani, Fedwa; Elkacemi, Hanan; Kebdani, Tayeb; Errihani, Hassan; Benjaafar, Noureddine

    2015-01-01

    Les tumeurs stromales gastro-intestinales sont les tumeurs mésenchymateuses les plus fréquentes, pourtant, leur association avec les tumeurs du sein sont rares, seulement quelques cas cliniques sont rapportés dans la littérature. Nous rapportons l'observation d'une jeune femme de 41 ans, suivie à l'institut national d'oncologie de Rabat, pour un carcinome canalaire du sein, bilatéral, chez qui le bilan d'extension a objectivé une tumeur stromale de type gastro-intestinale aux dépens de l'estomac. Nous décrivons à travers cette observation les aspects épidémiologiques, cliniques, et les particularités de la prise en charge de cette association rare. PMID:26090003

  6. Regional Variation in Breast Cancer Rates in the United States (Past Initiative)

    Cancer.gov

    Five institutions are being funded to conduct research using epidemiologic and statistical methods for determining whether various factors may account for the geographic differences in breast cancer rates in the United States.

  7. Triathlon training for women breast cancer survivors: feasibility and initial efficacy.

    PubMed

    Ng, Alexander V; Cybulski, Alyson N; Engel, Ashley A; Papanek, Paula E; Sheffer, Megan A; Waltke, Leslie J; Tjoe, Judy A

    2016-12-24

    ᅟ: Exercise can improve quality of life (QOL) in breast cancer survivors. In contrast to many group or home-based exercise programs, little is known about the effectiveness of goal-oriented recreational activities.

  8. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2008-02-01

    either omega (n)-3 or n-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress human 15...effects of excessive n-6 LA diet consumption in the progression of PCa. 15. SUBJECT TERMS Linoleic acid ; LO or LOX, lipoxygenase; PUFA , Polyunsaturated... fatty acid ; PCa, Prostate Cancer, MMHCC, Mouse Models of Human Cancer Consortium; IHC, immunohistochemistry; H & E, Hematoxylin and Eosin; FLiMP

  9. Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway.

    PubMed

    Yang, Jingzhe; Wang, Chengli; Zhang, Zhijie; Chen, Xiaojun; Jia, Yusen; Wang, Bin; Kong, Tao

    2017-02-01

    Prostate cancer is one of the most common malignancies in men, and it urgently demands precise interventions that target the signaling pathways implicated in its initiation, progression, and metastasis. The Notch-1 signaling pathway is closely associated with the pathophysiology of prostate cancer. This study investigated the antitumor effects and mechanisms of curcumin, which is a well-known natural compound from curcuminoids, in prostate cancer cells. Viability, proliferation, and migration were analyzed in two prostate cancer cell lines, DU145 and PC3, after curcumin treatment. Whether the Notch-1 signaling pathway is involved in the antitumor effects of curcumin was examined. Curcumin inhibited the survival and proliferation of PC3 and DU145 cells in a dose- and time-dependent manner and inhibited DU145 migration. Curcumin did not affect the expression of Notch-1 or its active product NICD, but it did inhibit the expression of MT1-MMP and MMP2 proteins in DU145 cells. We found that curcumin inhibited the DNA-binding ability of NICD in DU145 cells. In conclusion, curcumin inhibited the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway.

  10. ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex

    PubMed Central

    Li, Zhe; Tognon, Cristina E.; Godinho, Frank J.; Yasaitis, Laura; Hock, Hanno; Herschkowitz, Jason I.; Lannon, Chris L.; Cho, Eunah; Kim, Seong-Jin; Bronson, Roderick T.; Perou, Charles M.; Sorensen, Poul H.; Orkin, Stuart H.

    2007-01-01

    SUMMARY To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61+ luminal progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models. SIGNIFICANCE For the largest class of human tumors, those of epithelial origin, little is known about their initiating genetic hits or cells of origin. Whether tissue stem cells or more committed progenitors are targets for transformation is uncertain. We developed a system in which epithelial tumorigenesis can be assessed from the initial event to frank malignancy. In this breast cancer model based on chromosomal translocation, we show through genetic marking that committed mammary progenitors, rather than mammary stem cells, are direct targets of transformation. We show that activation of the AP1 complex represents a critical downstream event of the ETV6-NTRK3 translocation. Further focus on this transcriptional complex as a target in human breast cancer is warranted. PMID:18068631

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

    PubMed Central

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

    2016-01-01

    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. PMID:27602489

  12. Role of autonomous androgen receptor signaling in prostate cancer initiation is dichotomous and depends on the oncogenic signal.

    PubMed

    Memarzadeh, Sanaz; Cai, Houjian; Janzen, Deanna M; Xin, Li; Lukacs, Rita; Riedinger, Mireille; Zong, Yang; DeGendt, Karel; Verhoeven, Guido; Huang, Jiaoti; Witte, Owen N

    2011-05-10

    The steroid hormone signaling axis is thought to play a central role in initiation and progression of many hormonally regulated epithelial tumors. It is unclear whether all cancer-initiating signals depend on an intact hormone receptor signaling machinery. To ascertain whether cell autonomous androgen receptor (AR) is essential for initiation of prostate intraepithelial neoplasia (PIN), the response of AR-null prostate epithelia to paracrine and cell autonomous oncogenic signals was assessed in vivo by using the prostate regeneration model system. Epithelial-specific loss of AR blocked paracrine FGF10-induced PIN, whereas the add back of exogenous AR restored this response. In contrast, PIN initiated by cell-autonomous, chronic-activated AKT developed independent of epithelial AR signaling. Our findings demonstrate a selective role for AR in the initiation of PIN, dependent on the signaling pathways driving tumor formation. Insights into the role of hormone receptor signaling in the initiation of epithelial tumors may help define this axis as a target for chemoprevention of carcinomas.

  13. Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative.

    PubMed

    Wang, Ange; Qin, FeiFei; Hedlin, Haley; Desai, Manisha; Chlebowski, Rowan; Gomez, Scarlett; Eaton, Charles B; Johnson, Karen C; Qi, Lihong; Wactawski-Wende, Jean; Womack, Catherine; Wakelee, Heather A; Stefanick, Marcia L

    2016-11-15

    Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50-79 years between 1993 and 1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)-min/week: none <100 (reference), low 100 to <500, medium 500 to <1,200, high 1,200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow-up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared with no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p = 0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76-0.96); medium, HR: 0.82 (0.73-0.93); and high, HR: 0.90 (0.79-1.03)], and mortality [p < 0.0001; low, HR: 0.80 (0.69-0.92); medium, HR: 0.68 (0.59-0.80); and high, HR: 0.78 (0.66-0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p = 0.01), with a stronger association in women with BMI < 30 kg/m(2) . Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non-obese women.

  14. Vascular-targeted photodynamic of prostate cancer phase with Tookad for recurrent prostate cancer following radiation therapy: initial clinical studies

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; Wilson, Brian C.; Bogaards, Arjen; Gertner, Mark R.; Davidson, Sean R. H.; Haider, Masoom A.; Elhilali, Mostafa; Trachtenberg, John

    2007-02-01

    We report on the first clinical application of vascular-targeted photodynamic therapy using a bacteriopheophorbide derivative, Tookad, in patients with localized prostate cancer following external beam radiation therapy. Patients received either escalating intravenous drug doses at a fixed light dose or escalated light doses at the highest photosensitizer dose. Two cylindrically diffusing fibers were placed transperineally in the prostate, along with light monitoring fibers in the prostate, urethra and rectum. Treatment response was assessed with 7-day gadolinium-enhanced T1-weighted MRI and 6-month biopsy. Lesion formation was strongly drug and light dose-dependent, with an apparent threshold response. Early biochemical and MRI responses support the clinical potential of TOOKAD-PDT to treat locally-recurrent prostate cancer.

  15. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets.

    PubMed

    Pode-Shakked, Naomi; Shukrun, Rachel; Mark-Danieli, Michal; Tsvetkov, Peter; Bahar, Sarit; Pri-Chen, Sara; Goldstein, Ronald S; Rom-Gross, Eithan; Mor, Yoram; Fridman, Edward; Meir, Karen; Simon, Amos; Magister, Marcus; Kaminski, Naftali; Goldmacher, Victor S; Harari-Steinberg, Orit; Dekel, Benjamin

    2013-01-01

    There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated-NCAM1 expressing-"blastema" phenotype, including a capacity to expand and differentiate into the mature renal-like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR-200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets.

  16. Fertility considerations, counseling, and semen cryopreservation for males prior to the initiation of cancer therapy.

    PubMed

    Leonard, Marcia; Hammelef, Karen; Smith, Gary D

    2004-04-01

    An innovative program jointly sponsored by members of the departments of obstetrics and urology and the Comprehensive Cancer Center at the University of Michigan began in 2002. The Fertility Counseling and Gamete Cryopreservation Program (FCGCP) was created to provide counseling and education about therapy-induced infertility to newly diagnosed patients with cancer as well as facilitating the semen cryopreservation process. Unlike most sperm banking facilities in this country, this program is coordinated by an oncology nurse practitioner whose understanding of cancer and cancer treatments provides patients and staff with a unique perspective. Oncology staff misconceptions about sperm banking were addressed through intensive staff education programs. Patient education materials covering all aspects of infertility and sperm banking were developed and made available in patient care areas and on the Internet. Material aimed at young adolescents and their parents is prominent. Developmentally appropriate discussions are held with adolescent patients and their parents, both individually and together. Communication among patients and their families, the oncology team, and the sperm bank is maintained, permitting efficient and timely service. FCGCP provides an important service by affording all males with cancer the potential to father a child in the future.

  17. The National Cancer Institute’s Community Networks Program Initiative to Reduce Cancer Health Disparities: Outcomes and Lessons Learned

    PubMed Central

    Braun, Kathryn L.; Stewart, Susan; Baquet, Claudia; Berry-Bobovski, Lisa; Blumenthal, Daniel; Brandt, Heather M.; Buchwald, Dedra S.; Campbell, Janis E.; Coe, Kathryn; Cooper, Leslie C.; Espinoza, Paula; Henry-Tillman, Ronda; Hargreaves, Margaret; James, Aimee; Kaur, Judith Salmon; Viswanath, K.; Ma, Grace X.; Mandelblatt, Jeanne; Meade, Cathy; Ramirez, Amelie; Scarinci, Isabel; Tanjasiri, Sora Park; Thompson, Beti; Vines, Anissa I.; Dignan, Mark

    2015-01-01

    Background We describe reach, partnerships, products, benefits, and lessons learned of the 25 Community Network Programs (CNPs) that applied community-based participatory research (CBPR) to reduce cancer health disparities. Methods Quantitative and qualitative data were abstracted from CNP final reports. Qualitative data were grouped by theme. Results Together, the 25 CNPs worked with more than 2,000 academic, clinical, community, government, faith-based, and other partners. They completed 211 needs assessments, leveraged funds for 328 research and service projects, trained 719 new investigators, educated almost 55,000 community members, and published 991 articles. Qualitative data illustrated how use of CBPR improved research methods and participation; improved knowledge, interventions, and outcomes; and built community capacity. Lessons learned related to the need for time to nurture partnerships and the need to attend to community demand for sustained improvements in cancer services. Implications Findings demonstrate the value of government-supported, community–academic, CBPR partnerships in cancer prevention and control research. PMID:26213401

  18. ERN1 and ALPK1 inhibit differentiation of bi-potential tumor-initiating cells in human breast cancer

    PubMed Central

    Strietz, Juliane; Stepputtis, Stella S.; Vannier, Corinne; Kim, Mihee M.; Castro, David J.; Au, Qingyan; Boerries, Melanie; Busch, Hauke; Aza-Blanc, Pedro; Heynen-Genel, Susanne; Bronsert, Peter; Kuster, Bernhard; Stickeler, Elmar; Brabletz, Thomas; Oshima, Robert G.; Maurer, Jochen

    2016-01-01

    Cancers are heterogeneous by nature. While traditional oncology screens commonly use a single endpoint of cell viability, altering the phenotype of tumor-initiating cells may reveal alternative targets that regulate cellular growth by processes other than apoptosis or cell division. We evaluated the impact of knocking down expression of 420 kinases in bi-lineage triple-negative breast cancer (TNBC) cells that express characteristics of both myoepithelial and luminal cells. Knockdown of ERN1 or ALPK1 induces bi-lineage MDA-MB-468 cells to lose the myoepithelial marker keratin 5 but not the luminal markers keratin 8 and GATA3. In addition, these cells exhibit increased β-casein production. These changes are associated with decreased proliferation and clonogenicity in spheroid cultures and anchorage-independent growth assays. Confirmation of these assays was completed in vivo, where ERN1- or ALPK1-deficient TNBC cells are less tumorigenic. Finally, treatment with K252a, a kinase inhibitor active on ERN1, similarly impairs anchorage-independent growth of multiple breast cancer cell lines. This study supports the strategy to identify new molecular targets for types of cancer driven by cells that retain some capacity for normal differentiation to a non-tumorigenic phenotype. ERN1 and ALPK1 are potential targets for therapeutic development. PMID:27829216

  19. Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.

    PubMed

    Morita, Rena; Nishizawa, Satoshi; Torigoe, Toshihiko; Takahashi, Akari; Tamura, Yasuaki; Tsukahara, Tomohide; Kanaseki, Takayuki; Sokolovskaya, Alice; Kochin, Vitaly; Kondo, Toru; Hashino, Satoshi; Asaka, Masahiro; Hara, Isao; Hirohashi, Yoshihiko; Sato, Noriyuki

    2014-04-01

    The aim of the present study was to establish cancer stem-like cell/cancer-initiating cell (CSC/CIC)-targeting immunotherapy. The CSC/CIC are thought to be essential for tumor maintenance, recurrence and distant metastasis. Therefore they are reasonable targets for cancer therapy. In the present study, we found that a heat shock protein (HSP) 40 family member, DnaJ (Hsp40) homolog, subfamily B, member 8 (DNAJB8), is preferentially expressed in CSC/CIC derived from colorectal cancer (CRC) cells rather than in non-CSC/CIC. Overexpression of DNAJB8 enhanced the expression of stem cell markers and tumorigenicity, indicating that DNAJB8 has a role in CRC CSC/CIC. A DNAJB8-specific cytotoxic T lymphocyte (CTL) response could be induced by a DNAJB8-derived antigenic peptide. A CTL clone specific for DNAJB8 peptide showed higher killing activity to CRC CSC/CIC compared with non-CSC/CIC, and CTL adoptive transfer into CRC CSC/CIC showed an antitumor effect in vivo. Taken together, the results indicate that DNAJB8 is expressed and has role in CRC CSC/CIC and that DNAJB8 is a novel target of CRC CSC/CIC-targeting immunotherapy.

  20. Changes in Initial Treatment for Prostate Cancer Among Medicare Beneficiaries, 1999-2007

    SciTech Connect

    Dinan, Michaela A.; Robinson, Timothy J.; Zagar, Timothy M.; Scales, Charles D.; Curtis, Lesley H.; Reed, Shelby D.; Lee, W. Robert; Schulman, Kevin A.

    2012-04-01

    Purpose: In the absence of evidence from large clinical trials, optimal therapy for localized prostate cancer remains unclear; however, treatment patterns continue to change. We examined changes in the management of patients with prostate cancer in the Medicare population. Methods and Materials: We conducted a retrospective claims-based analysis of the use of radiation therapy, surgery, and androgen deprivation therapy in the 12 months after diagnosis of prostate cancer in a nationally representative 5% sample of Medicare claims. Patients were Medicare beneficiaries 67 years or older with incident prostate cancer diagnosed between 1999 and 2007. Results: There were 20,918 incident cases of prostate cancer between 1999 and 2007. The proportion of patients receiving androgen deprivation therapy decreased from 55% to 36%, and the proportion of patients receiving no active therapy increased from 16% to 23%. Intensity-modulated radiation therapy replaced three-dimensional conformal radiation therapy as the most common method of radiation therapy, accounting for 77% of external beam radiotherapy by 2007. Minimally invasive radical prostatectomy began to replace open surgical approaches, being used in 49% of radical prostatectomies by 2007. Conclusions: Between 2002 and 2007, the use of androgen deprivation therapy decreased, open surgical approaches were largely replaced by minimally invasive radical prostatectomy, and intensity-modulated radiation therapy replaced three-dimensional conformal radiation therapy as the predominant method of radiation therapy in the Medicare population. The aging of the population and the increasing use of newer, higher-cost technologies in the treatment of patients with prostate cancer may have important implications for nationwide health care costs.

  1. La naissance du parsec

    NASA Astrophysics Data System (ADS)

    Arenou, F.

    2010-01-01

    Les définitions du parsec et de la magnitude absolue sont le fruit de compromis pour régler trois problèmes entremêlés au début du XXème siècle: quelle unité de distance stellaire adopter? Quel nom lui donner? Comment comparer les luminosités intrinsèques des différentes étoiles?

  2. Integration of Nuclear- and Extranuclear-Initiated Estrogen Receptor Signaling in Breast Cancer Cells

    ERIC Educational Resources Information Center

    Madak Erdogan, Zeynep

    2009-01-01

    Estrogenic hormones exert their effects through binding to Estrogen Receptors (ERs), which work in concert with coregulators and extranuclear signaling pathways to control gene expression in normal as well as cancerous states, including breast tumors. In this thesis, we have used multiple genome-wide analysis tools to elucidate various ways that…

  3. Working Alliance and Vocational Outcomes for Cancer Survivors: An Initial Analysis

    ERIC Educational Resources Information Center

    Strauser, David R.

    2010-01-01

    This study examines the sex differences in the perception of working alliance and the perceptions of optimism regarding future employment and job satisfaction with adult cancer survivors receiving vocational rehabilitation services. No significant differences were found between males and females in terms of the three components of the working…

  4. Initiating Events in Prostate Cancer: The Role of Somatic Activation of Beta-Catening

    DTIC Science & Technology

    2005-04-01

    B.Sc. 1978 Medical Biochemistry National Institute for Medical Research, London, U.K. PhD 1982 Genetics/Aging Rene Descartes University. Paris FR D.Sc...Rend Descartes , Paris, France. 1989-1998 Research Group Leader, Division of Tumor Immunology, German Cancer Research Center, Heidelberg, Germany

  5. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2012-12-01

    omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa...development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16...competing with ω-6 fatty acids for 15-LO-1, and COX-2 activities. REPORTABLE OUTCOMES: None. CONCLUSION: Omega (ω)-3 fatty acids can

  6. Use of Bone Scan During Initial Prostate Cancer Workup, Downstream Procedures, and Associated Medicare Costs

    SciTech Connect

    Falchook, Aaron D.; Salloum, Ramzi G.; Hendrix, Laura H.; Chen, Ronald C.

    2014-06-01

    Purpose: For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Methods and Materials: Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. Results: In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were found to have metastatic disease. The annual estimated Medicare cost for bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. Conclusions: There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely.

  7. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice

    PubMed Central

    Collins, Meredith A.; Bednar, Filip; Zhang, Yaqing; Brisset, Jean-Christophe; Galbán, Stefanie; Galbán, Craig J.; Rakshit, Sabita; Flannagan, Karen S.; Adsay, N. Volkan; Pasca di Magliano, Marina

    2012-01-01

    Pancreatic cancer is almost invariably associated with mutations in the KRAS gene, most commonly KRASG12D, that result in a dominant-active form of the KRAS GTPase. However, how KRAS mutations promote pancreatic carcinogenesis is not fully understood, and whether oncogenic KRAS is required for the maintenance of pancreatic cancer has not been established. To address these questions, we generated two mouse models of pancreatic tumorigenesis: mice transgenic for inducible KrasG12D, which allows for inducible, pancreas-specific, and reversible expression of the oncogenic KrasG12D, with or without inactivation of one allele of the tumor suppressor gene p53. Here, we report that, early in tumorigenesis, induction of oncogenic KrasG12D reversibly altered normal epithelial differentiation following tissue damage, leading to precancerous lesions. Inactivation of KrasG12D in established precursor lesions and during progression to cancer led to regression of the lesions, indicating that KrasG12D was required for tumor cell survival. Strikingly, during all stages of carcinogenesis, KrasG12D upregulated Hedgehog signaling, inflammatory pathways, and several pathways known to mediate paracrine interactions between epithelial cells and their surrounding microenvironment, thus promoting formation and maintenance of the fibroinflammatory stroma that plays a pivotal role in pancreatic cancer. Our data establish that epithelial KrasG12D influences multiple cell types to drive pancreatic tumorigenesis and is essential for tumor maintenance. They also strongly support the notion that inhibiting KrasG12D, or its downstream effectors, could provide a new approach for the treatment of pancreatic cancer. PMID:22232209

  8. Differential Requirement for Src-family Tyrosine Kinases in the Initiation, Progression and Metastasis of Prostate Cancer

    PubMed Central

    Gelman, Irwin H.; Peresie, Jennifer; Eng, Kevin H.; Foster, Barbara A.

    2014-01-01

    Prostate cancer (CaP) recurrence after androgen ablation therapy (ADT) remains a significant cause of mortality in aging men. Malignant progression and metastasis are typically driven by genetic and epigenetic changes controlled by the androgen receptor (AR). However, evidence suggests that activated non-receptor tyrosine kinases, including those of the Src family (SFK), directly phosphorylate AR, thereby activating its transcriptional activity in the absence of serum androgen levels. To ascertain whether CaP progression and metastasis require SFK members an autochthonous transgenic adenocarcinoma (AD) of the mouse prostate (TRAMP) model was crossed into Src-, Lyn- or Fyn-null backgrounds. Primary-site CaP formation was dependent on Src, to a lesser extent, Lyn, but not Fyn. Only Src−/−;TRAMP prostate tumors were marked by reactive stroma. SFK deficiency did not affect progression to neuroendocrine (NE) disease, although there were fewer new cancer cases initiating after 34 weeks in the SFK−/−;TRAMP mice compared to TRAMP controls. Fifteen to 21% of older (>33 weeks) Lyn- or Fyn-null TRAMP mice lacking primary-site tumors suffered from aggressive metastatic AD growths, compared with 3% of TRAMP mice. Taken with the data that TRAMP mice lacking Src or Lyn exhibited fewer macroscopic metastases compared to Fyn−/−;TRAMP and TRAMP controls, this suggests that SFK can either promote or suppress specific parameters of metastatic growth, possibly depending on cross-talk with primary tumors. These data identify critical, yet potentially opposing roles played by various SFKs in the initiation and metastatic potential of CaP using the TRAMP model. Implications: Genetically defined mouse models indicate a critical role for Src tyrosine kinase in prostate cancer initiation and metastatic progression. PMID:25053806

  9. La recherche de la surexpression de la protéine et l'amplification du gène HER2 dans le cancer de l'estomac par immunohistochimie et Hybridation in Situ: expérience du CHU HASSAN II de Fès

    PubMed Central

    El Fatemi, Hinde; Hammas, Nawal; Idrissi, Karima; Mellas, Nawfel; Bennani, Amal; Amarti, Afaf; Cayre, Anne; Penault-llorca, Frederique; Mesbahi, Omar

    2012-01-01

    La surexpression de l'Her2 a été détectée dans plusieurs cancers et a été particulièrement étudiée dans le cancer du sein. Elle est décrite dans 10 à 30% des adénocarcinomes gastriques. Un statut HER2 positif est un facteur de mauvais pronostic et un facteur prédictif de la réponse à l'herceptine (trastuzumab). Cet article présente les résultats d'une étude préliminaire portant sur 31 cas de tumeurs gastriques, et dont le but est d’évaluer la surexpression de l’ HER2 dans les adénocarcinomes gastriques avancés tout en comparant nos résultats avec ceux de la littérature. Le taux des cas surexprimant l'Her2 dans notre étude (35.5%) est proche de celui noté par Aoyaji et al (34%), mais il est supérieur à celui noté dans la plupart des séries de la littérature notamment une vaste étude baptisée TOGA. La poursuite de cette étude par un échantillon plus large est nécessaire afin de mieux comprendre les particularités de ce cancer dans notre contexte. PMID:23397021

  10. Improving Care for Children With Cancer in Low- and Middle-Income Countries--a SIOP PODC Initiative.

    PubMed

    Arora, Ramandeep Singh; Challinor, Julia M; Howard, Scott C; Israels, Trijn

    2016-03-01

    The Paediatric Oncology in Developing Countries (PODC) committee of International Society of Paediatric Oncology (SIOP) has 10 working groups that provide a forum for individuals to engage, network, and implement improvements in the care of children with cancer in low- and middle-income countries. The development of adapted guidelines (medulloblastoma, retinoblastoma, Wilms tumor, neuroblastoma, retinoblastoma, Burkitt lymphoma, supportive care), advocacy and awareness (on hospital detention and essential drugs), education and training, and global mapping (nutritional practice, abandonment rates, and twinning collaborations) have been the initial areas of focus, and the impact of some of these activities is evident, for example, in the SIOP Africa PODC Collaborative Wilms tumor project.

  11. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    PubMed

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-10-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  12. 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

  13. Importance of dietary fat during initiation versus promotion in rat mammary cancer

    SciTech Connect

    Hasler, C.M.; Bennink, M.R.

    1986-03-05

    This study was designed to determine if the fat content of the diet would alter 7,12-dimethylbenzanthracene (DMBA) initiation of mammary carcinogenesis. Female Sprague-Dawley rats were fed the AIN-76 (high carbohydrate, HC) diet or a modified AIN-76 diet (high fat (37/sup 5/), HF) prior to initiation. The HF diet had the same energy to nutrient ratio as the HC diet. Two groups were fed either the HC or the HF diet during the initiation and promotion phase (HC-HC and HF-HF groups). A third group was fed the HF diet 20 days before and 12 days after initiation and then were fed the HC diet during the promotion phase (HF-HC group). Weight gain during promotion was similar for the HC-HC and HF-HC groups, but the HF-HF group gained 41% more weight. The HC-HC group had significantly fewer tumors than the HF-HF or HF-HC groups (HC-HC = 1.45 tumors/rat; HF-HF = 2.75 and HF-HC = 3.63). Surprisingly, feeding the HC diet during promotion did not cause a decrease in tumorigenesis (there was actually a non-significant increase). This work demonstrates that the fat (energy) content of the diet during DMBA initiation is critical. Furthermore, the fat (energy) content of the diet during initiation was more critical than during promotion.

  14. LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells

    PubMed Central

    Zhu, Pingping; Wang, Yanying; Wu, Jiayi; Huang, Guanling; Liu, Benyu; Ye, Buqing; Du, Ying; Gao, Guangxia; Tian, Yong; He, Lei; Fan, Zusen

    2016-01-01

    Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRM associates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling. Moreover, expression levels of lncBRM together with YAP1 signalling targets are positively correlated with tumour severity of HCC patients. Therefore, lncBRM and YAP1 signalling may serve as biomarkers for diagnosis and potential drug targets for HCC. PMID:27905400

  15. [Fluorodeoxyglucose and bronchopulmonary cancer. Initial French results with positron emission tomography].

    PubMed

    Vaylet, F; Foehrenbach, H; De Dreuille, O; Maszelin, P; Merlet, P; Bendriem, B; L'Her, P; Syrota, A; Gaillard, J F

    1998-09-01

    Despite recent advances, the contribution of medical imaging techniques is limited, particularly in terms of tissue characterization, in the diagnosis of pulmonary nodules and search for extension of bronchogenic cancer. The metabolic properties of the glucose analog deoxyglucose labeled with 18F1 would allow metabolic imaging. Positron emission tomography (PET) provides clinicians with quality images with an interesting sensitivity. We report the results of a feasibility study conducted in our first 17 patients. We observed 14 true positives, 1 true negative and 1 false positive and 1 false negative in patients with a malignant primary lesion. We analyzed the causes of error. Ten disseminated localizations were identified. Possible developments in terms of therapeutic strategy are discussed. The agreement between our findings and data reported in the literature prompted us to develop a study protocol using 18-fluorodeoxyglucose PET in patients with bronchogenic cancer.

  16. The Role of the Membrane-Initiated Heat Shock Response in Cancer

    PubMed Central

    Bromberg, Zohar; Weiss, Yoram

    2016-01-01

    The heat shock response (HSR) is a cellular response to diverse environmental and physiological stressors resulting in the induction of genes encoding molecular chaperones, proteases, and other proteins that are essential for protection and recovery from cellular damage. Since different perturbations cause accumulation of misfolded proteins, cells frequently encounter fluctuations in the environment which alter proteostasis. Since tumor cells use their natural adaptive mechanism of coping with stress and misfolded proteins, in recent years, the proteostasis network became a promising target for anti-tumor therapy. The membrane is the first to be affected by heat shock and therefore may be the first one to sense heat shock. The membrane also connects between the extracellular and the intracellular signals. Hence, there is a “cross talk” between the HSR and the membranes since heat shock can induce changes in the fluidity of membranes, leading to membrane lipid remodeling that occurs in several diseases such as cancer. During the last decade, a new possible therapy has emerged in which an external molecule is used that could induce membrane lipid re-organization. Since at the moment there are very few substances that regulate the HSR effectively, an alternative way has been searched to modulate chaperone activities through the plasma membrane. Recently, we suggested that the use of the membrane Transient Receptor Potential Vanilloid-1 (TRPV1) modulators regulated the HSR in cancer cells. However, the primary targets of the signal transduction pathway are yet un-known. This review provides an overview of the current literature regarding the role of HSR in membrane remodeling in cancer since a deep understanding of the membrane biology in cancer and the membrane heat sensing pathway is essential to design novel efficient therapies. PMID:27200359

  17. Estrogen potentiates reactive oxygen species (ROS) tolerance to initiate carcinogenesis and promote cancer malignant transformation.

    PubMed

    Tian, Hui; Gao, Zhen; Wang, Gang; Li, Huizhong; Zheng, JunNian

    2016-01-01

    Estrogen-mediated high reactive oxygen species (ROS) tolerance plays an important role in driving carcinogenesis. ROS overproduction acts as the significant effector to increase genomic instability and transduce redox-related signal pathway. Especially, estrogen-mediated mitochondrial ROS promote the mutations in mitochondrial DNA (mtDNA) and the damage to mitochondrial proteins. Moreover, estrogen-mediated ROS contribute to the alteration of energy metabolism and modulate several redox-sensitive proteins responsible for cell proliferation and anti-apoptosis. On the other hand, estrogen simultaneously performs the antioxidative beneficial functions, which protects cancer cells from the potential cytotoxic effects of estrogen-mediated ROS through activation of nuclear factor-erythroid-2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) antioxidant response. Consequently, estrogen potentiates the high ROS tolerance through increase of ROS production as well as acceleration of ROS elimination, which ultimately results in estrogen-mediated carcinogenesis and malignant transformation. However, this overdependence on antioxidant response system to resist ROS-mediated cytotoxicity also represents the "Achilles' Heel" of estrogen-mediated cancer cells. In other words, the destruction of the high ROS tolerance using antioxidant inhibitors may provide a novel and efficacious measure to selectively eliminate these cancer cells without harming normal cells. Of course, it will be necessary to define the exact situation of ROS homeostasis in the different cellular microenvironment and further decipher the mechanisms of redox regulation, which is consequently used as a new avenue to optimize the clinical therapy for estrogen-mediated cancer.

  18. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2009-02-01

    in either omega (ω)-3 or ω-6 polyunsaturated fatty acids (PUFAs) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress ...monounsaturated fatty acid pathway enzyme, Δ-9-desaturase which is a member in the fatty acid synthase (FASN) pathway, increased in tumors from SDA... Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis. Carcinogenesis, 22, 1765-73. 6. Ziboh A and VangK

  19. MicroRNA biomarkers predicting risk, initiation and progression of colorectal cancer

    PubMed Central

    Lee, Kyungjin; Ferguson, Lynnette R

    2016-01-01

    Colorectal cancer is a major global cause of morbidity and mortality. Current strategies employed to increase detection of early, curable stages of this disease are contributing to a reduction of the negative health impact from it. While there is a genetic component to the risk of disease, diet and environment are known to have major effects on the risk of an individual for developing the disease. However, there is the potential to reduce the impact of this disease further by preventing disease development. Biomarkers which can either predict the risk for or early stages of colorectal cancer could allow intervention at a time when prospects could be modified by environmental factors, including lifestyle and diet choices. Thus, such biomarkers could be used to identify high risk individuals who would benefit from lifestyle and dietary interventions to prevent this disease. This review will give an overview on one type of biomarker in the form of microRNAs, which have the potential to predict an individual’s risk for colorectal cancer, as well as providing a highly sensitive and non-invasive warning of disease presence and/or progression. MicroRNA biomarkers which have been studied and whose levels look promising for this purpose include MiR-18a, MiR-21, MiR-92a, MiR-135b, MiR-760, MiR-601. Not only have several individual microRNAs appeared promising as biomarkers, but panels of these may be even more useful. Furthermore, understanding dietary sources and ways of dietary modulation of these microRNAs might be fruitful in reducing the incidence and slowing the progression of colorectal cancer. PMID:27672263

  20. Initial Evaluation of an Electronic Symptom Diary for Adolescents with Cancer

    PubMed Central

    Gibson, Faith; Coll, Beatriz; Kletter, Richard; Zeltzer, Paul; Miaskowski, Christine

    2012-01-01

    Background The delivery of optimal care depends on accurate communication between patients and clinicians regarding untoward symptoms. Documentation of patients’ symptoms necessitates reliance on memory, which is often imprecise. We developed an electronic diary (eDiary) for adolescents and young adults (AYAs) with cancer to record symptoms. Objective The purpose of this paper is to describe the utility of an eDiary designed for AYAs with cancer, including dependability of the mobile application, the reasons for any missing recorded data, patients’ adherence rates to daily symptom queries, and patients’ perceptions of the usefulness and acceptability of symptom data collection via mobile phones. Methods Our team developed an electronic symptom diary based on interviews conducted with AYAs with cancer and their clinicians. This diary included daily severity ratings of pain, nausea, vomiting, fatigue, and sleep. The occurrence of other selected physical sequelae was assessed daily. Additionally, patients selected descriptors of their mood. A 3-week trial of the eDiary was conducted with 10 AYA cancer patients. Mobile phones with service plans were loaned to patients who were instructed to report their symptoms daily. Patients completed a brief questionnaire and were interviewed to elicit their perceptions of the eDiary and any technical difficulties encountered. Results Overall adherence to daily symptom reports exceeded 90%. Young people experienced few technical difficulties and reported benefit from daily symptom reports. Symptom occurrence rates were high and considerable inter- and intra-patient variability was noted in symptom and mood reports. Conclusions We demonstrated the utility of an eDiary that may contribute insight into patients’ symptom patterns to promote effective symptom management. PMID:23612521

  1. A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation.

    PubMed

    Ho, Victor W; Leung, Kelvin; Hsu, Anderson; Luk, Beryl; Lai, June; Shen, Sung Yuan; Minchinton, Andrew I; Waterhouse, Dawn; Bally, Marcel B; Lin, Wendy; Nelson, Brad H; Sly, Laura M; Krystal, Gerald

    2011-07-01

    Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate (CHO) diets to a Western diet on the growth rate of tumors in mice. To avoid caloric restriction-induced effects, we designed the low CHO diets isocaloric with the Western diet by increasing protein rather than fat levels because of the reported tumor-promoting effects of high fat and the immune-stimulating effects of high protein. We found that both murine and human carcinomas grew slower in mice on diets containing low amylose CHO and high protein compared with a Western diet characterized by relatively high CHO and low protein. There was no weight difference between the tumor-bearing mice on the low CHO or Western diets. Additionally, the low CHO-fed mice exhibited lower blood glucose, insulin, and lactate levels. Additive antitumor effects with the low CHO diets were observed with the mTOR inhibitor CCI-779 and especially with the COX-2 inhibitor Celebrex, a potent anti-inflammatory drug. Strikingly, in a genetically engineered mouse model of HER-2/neu-induced mammary cancer, tumor penetrance in mice on a Western diet was nearly 50% by the age of 1 year whereas no tumors were detected in mice on the low CHO diet. This difference was associated with weight gains in mice on the Western diet not observed in mice on the low CHO diet. Moreover, whereas only 1 mouse on the Western diet achieved a normal life span, due to cancer-associated deaths, more than 50% of the mice on the low CHO diet reached or exceeded the normal life span. Taken together, our findings offer a compelling preclinical illustration of the ability of a low CHO diet in not only restricting weight gain but also cancer development and progression.

  2. Dietary Regulation of PTEN Signaling and Mammary Tumor Initiating Cells: Implications for Breast Cancer Prevention

    DTIC Science & Technology

    2012-01-01

    Institutional Animal Care and Use Committee. Time-mated Sprague Dawley rats ( Charles River Laboratories, Wilmington, MA) were individually housed in...collected at PND21 and PND50 were measured using a rat APN ELISA kit (Linco Research, St. Charles , MO). The assay sensi- tivity was 0.15 ng/ml, and intra...Stampfer MJ, Hunter DJ, Manson JE, Hennekens CH, Rosner B, Speizer FE, Willett WC 1997 Dual effects of weight and weight gain on breast cancer risk

  3. [The management by the processes in a cancer center, an utopian initiative?].

    PubMed

    Verger, David; Mihura, Jeanne; Sallé, Françoise; Sarini, Jérôme; Colin, Valérie

    2008-01-01

    The process approach is a mode of quality improvement. It leans on the cartography's establishment, allows to redefine organization around patients trajectory, the measure of defects and their correction. The process pilot is a new actor in the management of the establishment. It is developed since 3 years in the Institute Claudius Regaud, regional cancer center treatment of Midi-Pyrénées.

  4. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model By Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2011-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore, the FLiMP...polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing PCa growth by altering ω-6/ ω-3 ratios via diet

  5. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2010-02-01

    provide a valuable pre-clinical model for chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly...polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16. SECURITY CLASSIFICATION OF: 17...FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing PCa growth

  6. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2012-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore... acids effects on PIN development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer...compared to FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing

  7. Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer

    PubMed Central

    2016-01-01

    Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma. PMID:27550487

  8. Surgery-induced wound response promotes stem-like and tumor-initiating features of breast cancer cells, via STAT3 signaling

    PubMed Central

    Segatto, Ilenia; Berton, Stefania; Sonego, Maura; Massarut, Samuele; Perin, Tiziana; Piccoli, Erica; Colombatti, Alfonso; Vecchione, Andrea; Baldassarre, Gustavo; Belletti, Barbara

    2014-01-01

    Inflammation is clinically linked to cancer but the mechanisms are not fully understood. Surgery itself elicits a range of inflammatory responses, suggesting that it could represent a perturbing factor in the process of local recurrence and/or metastasis formation. Post-surgery wound fluids (WF), drained from breast cancer patients, are rich in cytokines and growth factors, stimulate the in vitro growth of breast cancer cells and are potent activators of the STAT transcription factors. We wondered whether STAT signaling was functionally involved in the response of breast cancer cells to post-surgical inflammation. We discovered that WF induced the enrichment of breast cancer cells with stem-like phenotypes, via activation of STAT3. In vitro, WF highly stimulated mammosphere formation and self-renewal of breast cancer cells. In vivo, STAT3 signaling was critical for breast cancer cell tumorigenicity and for the formation of local relapse after surgery. Overall, we demonstrate here that surgery-induced inflammation promotes stem-like phenotypes and tumor-initiating abilities of breast cancer cells. Interfering with STAT3 signaling with a peri-surgical treatment is sufficient to strongly suppress this process. The understanding of the crosstalk between breast tumor-initiating cells and their microenvironment may open the way to successful targeting of these cells in their initial stages of growth and be eventually curative. PMID:25026286

  9. Surgery-induced wound response promotes stem-like and tumor-initiating features of breast cancer cells, via STAT3 signaling.

    PubMed

    Segatto, Ilenia; Berton, Stefania; Sonego, Maura; Massarut, Samuele; Perin, Tiziana; Piccoli, Erica; Colombatti, Alfonso; Vecchione, Andrea; Baldassarre, Gustavo; Belletti, Barbara

    2014-08-15

    Inflammation is clinically linked to cancer but the mechanisms are not fully understood. Surgery itself elicits a range of inflammatory responses, suggesting that it could represent a perturbing factor in the process of local recurrence and/or metastasis. Post-surgery wound fluids (WF), drained from breast cancer patients, are rich in cytokines and growth factors, stimulate the in vitro growth of breast cancer cells and are potent activators of the STAT transcription factors. We wondered whether STAT signaling was functionally involved in the response of breast cancer cells to post-surgical inflammation. We discovered that WF induced the enrichment of breast cancer cells with stem-like phenotypes, via activation of STAT3. In vitro, WF highly stimulated mammosphere formation and self-renewal of breast cancer cells. In vivo, STAT3 signaling was critical for breast cancer cell tumorigenicity and for the formation of local relapse after surgery. Overall, we demonstrate here that surgery-induced inflammation promotes stem-like phenotypes and tumor-initiating abilities of breast cancer cells. Interfering with STAT3 signaling with a peri-surgical treatment was sufficient to strongly suppress this process. The understanding of the crosstalk between breast tumor-initiating cells and their microenvironment may open the way to successful targeting of these cells in their initial stages of growth and be eventually curative.

  10. Mutagens in human breast lipid and milk: the search for environmental agents that initiate breast cancer.

    PubMed

    Phillips, David H; Martin, Francis L; Williams, J Andrew; Wheat, Luise M C; Nolan, Lisa; Cole, Kathleen J; Grover, Philip L

    2002-01-01

    Epidemiological studies indicate the involvement of environmental factors in the etiology of breast cancer, but have not provided clear indications of the nature of the agents responsible. Several environmental carcinogens are known to induce mammary tumors in rodents, and the abundance of adipose tissue in the human breast suggests that the epithelial cells, from which breast tumors commonly arise, could be exposed to lipid-soluble carcinogens sequestered by the adipose tissue. In this report we review our studies in which we have examined human mammary lipid, obtained from elective reduction mammoplasties from healthy donors, and human milk from healthy mothers, for the presence of components with genotoxic activity in several in vitro assays. A significant proportion of lipid extracts induced mutations in bacteria and micronuclei in mammalian cells. They also caused DNA damage, detected as single-strand breaks in the alkaline single-cell gel electrophoresis (comet) assay, in both the MCL-5 cell line and in primary cultures of human mammary epithelial cells. Genotoxic activity was also found in a significant proportion of extracts of human breast milk. Viable cells recovered from milk samples showed evidence of DNA damage and were susceptible to comet formation by genotoxic agents in vitro. Genotoxic activity was found to be less prevalent in milk samples from countries of lower breast cancer incidence (the Far East) compared with that in samples from the UK. The agents responsible for the activity in milk appear to be moderately polar lipophilic compounds and of low molecular weight. Identification of these agents and their sources may hold clues to the origins of breast cancer.

  11. Initial results of the National Colorectal Cancer Screening Program in Lithuania.

    PubMed

    Poskus, Tomas; Strupas, Kestutis; Mikalauskas, Saulius; Bitinaitė, Dominyka; Kavaliauskas, Augustas; Samalavicius, Narimantas E; Saladzinskas, Zilvinas

    2015-03-01

    The aim of the present study was to review the National Colorectal Cancer Screening Program (the Program) in Lithuania according to the criteria set by the European Union. In Lithuania, screening services are provided free of charge to the population. The National Health Insurance Fund (NHIF) reimburses the institutions for performing each service; each procedure within the Program has its own administrative code. All the information about the performance of the Program is collected in one institution - the NHIF. The results of the Program were retrieved from the database of NHIF from the start of the Program from 1 July 2009 to 1 July 2012. Descriptive analysis of epidemiological indicators was carried out. Results were compared with the references in the guidelines of the European Union for quality assurance in colorectal cancer (CRC) screening and diagnosis. Information service [which involves fecal immunochemical test (FIT)] was provided to 271,396 of 890,309 50-74-year-old residents. The screening uptake was 46.0% over 3 years. During this period, 19,455 (7.2%) FITs were positive and 251,941 (92.8%) FITs were negative. Referral for colonoscopy was performed in 10,190 (52.4%) patients. Colonoscopy was performed in 12,864 (66.1%) patients. Colonoscopy did not indicate any pathological findings in 8613 (67.0%) patients. Biopsies were performed in 4251 (33.0%) patients. The rate of high-grade neoplasia reported by pathologists was 3.9%; the rate of cancer was 3.1% of all colonoscopies. The rate of CRC detected by the Program was 0.2%. The CRC screening program in Lithuania meets most of the requirements for standardized CRC screening programs. The invitation coverage and rate of referral for colonoscopy after positive FIT should be improved.

  12. BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions.

    PubMed

    Sinha, Abhilasha; Paul, Bibbin T; Sullivan, Lisa M; Sims, Hillary; El Bastawisy, Ahmed; Yousef, Hend F; Zekri, Abdel-Rahman N; Bahnassy, Abeer A; ElShamy, Wael M

    2017-02-07

    Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients.

  13. Preliminary results on the role of PET/CT in initial staging, restaging, and management of lung cancer

    NASA Astrophysics Data System (ADS)

    Malamitsi, J.; Valotassiou, B.; Iliadis, K.; Kosmidis, P.; Laspas, F.; Vasilaki, M.; Pipini, E.; Petounis, A.; Gogou, L.; Pagou, M.; Dalianis, K.; Efthimiadou, R.; Andreou, J.

    2006-12-01

    AimTo determine true-positive and true-negative rates of PET/CT studies in the staging of lung cancer as compared with conventional imaging (CT and bone scan and occasionally MRI) and the impact of PET/CT on the treatment strategy in patients with lung cancer. Materials and methodTwenty patients (21 studies) with known or suspected lung cancer (14 patients with non-small-cell lung cancer (NSCLC), three patients with small-cell lung cancer (SCLC), three patients with solitary pulmonary nodule underwent initial staging (seven studies) or restaging (14 studies) with combined FDG PET and CT scans on a PET/CT tomograph. PET/CT images were evaluated separately by two nuclear medicine physicians and two radiologists specialized on PET, CT, and MRI. Histology results and a more than 6 months follow-up served as the reference standards. ResultsAccurate diagnosis was achieved on 16 studies. Site-by-site analysis gave the following results: 16 true-positive sites (seven on histology, nine on >6 months follow-up), six true-negative sites (two on histology, four on >6 months follow-up). On PET/CT, six patients were correctly down-staged, three patients were correctly upstaged and seven patients were diagnosed correctly as being on the same stage (2/7 with increase of extent of disease, 5/7 with the same extent of disease). One patient was falsely upstaged and three patients were falsely down-staged. On the basis of PET/CT results, change of management was induced in six patients, while in 14 patients there was no change induced. In five cases PET/CT was partially accurate: on site-by-site analysis, four sites proved true positive (on histology), one site false positive (on histology), and four sites false negative (one on histology, three on >6 months follow-up). ConclusionIn our early experience, PET/CT contributed significantly to correct staging and management of patients with lung cancer.

  14. Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women’s health initiative

    PubMed Central

    Gong, Zhihong; Aragaki, Aaron K.; Chlebowski, Rowan T.; Manson, JoAnn E.; Rohan, Thomas E.; Chen, Chu; Vitolins, Mara Z.; Tinker, Lesley F.; LeBlanc, Erin S.; Kuller, Lewis H.; Hou, Lifang; LaMonte, Michael J.; Luo, Juhua; Wactawski-Wende, Jean

    2016-01-01

    Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women’s Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2–1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. PMID:26616262

  15. Roles of N‐Myc and STAT interactor in cancer: From initiation to dissemination

    PubMed Central

    Pruitt, Hawley C.; Devine, Daniel J.

    2016-01-01

    N‐myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. NMI is an inducible protein, thus its intracellular levels and location can vary dramatically, influencing a diverse array of cellular functions in a context‐dependent manner. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial‐to‐mesenchymal transition and stemness. Thus, discovering more details about the function(s) of NMI could reveal key insights into how transcription factors like c‐Myc, STATs and BRCA1 are contextually regulated. Although a normal, physiological function of NMI has not yet been discovered, it has potential roles in pathologies ranging from viral infection to cancer. This review provides a timely perspective of the unfolding roles of NMI with specific focus on cancer progression and metastasis. PMID:26874464

  16. Initial Characterization of Integrase-Defective Lentiviral Vectors for Pancreatic Cancer Gene Therapy.

    PubMed

    Hanoun, Naima; Gayral, Marion; Pointreau, Adeline; Buscail, Louis; Cordelier, Pierre

    2016-02-01

    The vast majority (85%) of pancreatic ductal adenocarcinomas (PDACs) are discovered at too of a late stage to allow curative surgery. In addition, PDAC is highly resistant to conventional methods of chemotherapy and radiotherapy, which only offer a marginal clinical benefit. Consequently, the prognosis of this cancer is devastating, with a 5-year survival rate of less than 5%. In this dismal context, we recently demonstrated that PDAC gene therapy using nonviral vectors is safe and feasible, with early signs of efficacy in selected patients. Our next step is to transfer to the clinic HIV-1-based lentiviral vectors (LVs) that outshine other therapeutic vectors to treat experimental models of PDAC. However, a primary safety issue presented by LVs that may delay their use in patients is the risk of oncogenesis after vector integration in the host's cell DNA. Thus, we developed a novel anticancerous approach based on integrase-defective lentiviral vectors (IDLVs) and demonstrated that IDLVs can be successfully engineered to transiently deliver therapeutic genes to inhibit pancreatic cancer cells proliferation. This work stems for the use of therapeutic IDLVs for the management of PDAC, in forthcoming early phase gene therapy clinical trial for this disease with no cure.

  17. CD133/Src Axis Mediates Tumor Initiating Property and Epithelial-Mesenchymal Transition of Head and Neck Cancer

    PubMed Central

    Chen, Yu-Syuan; Wu, Meng-Ju; Huang, Chih-Yang; Lin, Shu-Chun; Chuang, Tsung-Hsien; Yu, Cheng-Chia; Lo, Jeng-Fan

    2011-01-01

    Background Head and Neck squamous cell carcinoma (HNSCC) is a human lethal cancer with clinical, pathological, phenotypical and biological heterogeneity. Caner initiating cells (CICs), which are responsible for tumor growth and coupled with gain of epithelial-mesenchymal transition (EMT), have been identified. Previously, we enriched a subpopulation of head and neck cancer initiating cells (HN-CICs) with up-regulation of CD133 and enhancement of EMT. Others demonstrate that Src kinase interacts with and phosphorylates the cytoplasmic domain of CD133. However, the physiological function of CD133/Src signaling in HNSCCs has not been uncovered. Methodology/Principal Finding Herein, we determined the critical role of CD133/Src axis modulating stemness, EMT and tumorigenicity of HNSCC and HN-CICs. Initially, down-regulation of CD133 significantly reduced the self-renewal ability and expression of stemness genes, and promoted the differentiation and apoptotic capability of HN-CICs. Additionally, knockdown of CD133 in HN-CICs also lessened both in vitro malignant properties including cell migration/cell invasiveness/anchorage independent growth, and in vivo tumor growth by nude mice xenotransplantation assay. In opposite, overexpression of CD133 enhanced the stemness properties and tumorigenic ability of HNSCCs. Lastly, up-regulation of CD133 increased phosphorylation of Src coupled with EMT transformation in HNSCCs, on the contrary, silence of CD133 or treatment of Src inhibitor inversely abrogated above phenotypic effects, which were induced by CD133 up-regulation in HNSCCs or HN-CICs. Conclusion/Significance Our results suggested that CD133/Src signaling is a regulatory switch to gain of EMT and of stemness properties in HNSCC. Finally, CD133/Src axis might be a potential therapeutic target for HNSCC by eliminating HN-CICs. PMID:22140506

  18. Cancer Statistics

    MedlinePlus

    ... and the Precision Medicine Initiative® Cancer Moonshot℠ Progress Annual Report to the Nation Cancer Snapshots Milestones in Cancer ... Find research about a specific cancer type Progress Annual Report to the Nation Cancer Portfolio Snapshots Milestones in ...

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

    DTIC Science & Technology

    2013-12-01

    18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a . REPORT U b . ABSTRACT U c. THIS PAGE U UU 86 19b. TELEPHONE NUMBER...man. Parts a and b are completed. We have initiated Part c and currently developing a library of tyrosine kinases for functional validation. a . We...from primary prostate or metastatic tissue. ( B ) Further evaluation of a separate run of 10 metastatic CRPC lesions reveals patient-specific and

  20. Magnetic resonance imaging-guided brachytherapy for cervical cancer: initiating a program

    PubMed Central

    Prisciandaro, Joann I.; Soliman, Abraam; Ravi, Ananth; Song, William Y.

    2015-01-01

    Over the past decade, the application of magnetic resonance imaging (MRI) has increased, and there is growing evidence to suggest that improvements in accuracy of target delineation in MRI-guided brachytherapy may improve clinical outcomes in cervical cancer. To implement a high quality image guided brachytherapy program, a multidisciplinary team is required with appropriate expertise as well as an adequate patient load to ensure a sustainable program. It is imperative to know that the most important source of uncertainty in the treatment process is related to target delineation and therefore, the necessity of training and expertise as well as quality assurance should be emphasized. A short review of concepts and techniques that have been developed for implementation and/or improvement of workflow of a MRI-guided brachytherapy program are provided in this document, so that institutions can use and optimize some of them based on their resources to minimize their procedure times. PMID:26622249

  1. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

    PubMed

    Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

    2016-04-11

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention.

  2. Prospective Evaluation of Dual-Energy Imaging in Patients Undergoing Image Guided Radiation Therapy for Lung Cancer: Initial Clinical Results

    SciTech Connect

    Sherertz, Tracy; Hoggarth, Mark; Luce, Jason; Block, Alec M.; Nagda, Suneel; Harkenrider, Matthew M.; Emami, Bahman; Roeske, John C.

    2014-07-01

    Purpose: A prospective feasibility study was conducted to investigate the utility of dual-energy (DE) imaging compared to conventional x-ray imaging for patients undergoing kV-based image guided radiation therapy (IGRT) for lung cancer. Methods and Materials: An institutional review board-approved feasibility study enrolled patients with lung cancer undergoing IGRT and was initiated in September 2011. During daily setup, 2 sequential respiration-gated x-ray images were obtained using an on-board imager. Imaging was composed of 1 standard x-ray image at 120 kVp (1 mAs) and a second image obtained at 60 kVp (4 mAs). Weighted logarithmic subtraction of the 2 images was performed offline to create a soft tissue-selective DE image. Conventional and DE images were evaluated by measuring relative contrast and contrast-to-noise ratios (CNR) and also by comparing spatial localization, using both approaches. Imaging dose was assessed using a calibrated ion chamber. Results: To date, 10 patients with stage IA to IIIA lung cancer were enrolled and 57 DE images were analyzed. DE subtraction resulted in complete suppression of overlying bone in all 57 DE images, with an average improvement in relative contrast of 4.7 ± 3.3 over that of 120 kVp x-ray images (P<.0002). The improvement in relative contrast with DE imaging was seen for both smaller (gross tumor volume [GTV] ≤5 cc) and larger tumors (GTV >5 cc), with average relative contrast improvement ratios of 3.4 ± 4.1 and 5.4 ± 3.6, respectively. Moreover, the GTV was reliably localized in 95% of the DE images versus 74% of the single energy (SE images, (P=.004). Mean skin dose per DE image set was 0.44 ± 0.03 mGy versus 0.43 ± 0.03 mGy, using conventional kV imaging parameters. Conclusions: Initial results of this feasibility study suggest that DE thoracic imaging may enhance tumor localization in lung cancer patients receiving kV-based IGRT without increasing imaging dose.

  3. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer

    PubMed Central

    2012-01-01

    Introduction Overexpression of the oxygen-responsive transcription factor hypoxia-inducible factor 1α (HIF-1α) correlates with poor prognosis in breast cancer patients. The mouse mammary tumor virus polyoma virus middle T (MMTV-PyMT) mouse is a widely utilized preclinical mouse model that resembles human luminal breast cancer and is highly metastatic. Prior studies in which the PyMT model was used demonstrated that HIF-1α is essential to promoting carcinoma onset and lung metastasis, although no differences in primary tumor end point size were observed. Using a refined model system, we investigated whether HIF-1α is directly implicated in the regulation of tumor-initiating cells (TICs) in breast cancer. Methods Mammary tumor epithelial cells were created from MMTV-PyMT mice harboring conditional alleles of Hif1a, followed by transduction ex vivo with either adenovirus β-galactosidase or adenovirus Cre to generate wild-type (WT) and HIF-1α-null (KO) cells, respectively. The impact of HIF-1α deletion on tumor-initiating potential was investigated using tumorsphere assays, limiting dilution transplantation and gene expression analysis. Results Efficient deletion of HIF-1α reduced primary tumor growth and suppressed lung metastases, prolonging survival. Loss of HIF-1α led to reduced expression of markers of the basal lineage (K5/K14) in cells and tumors and of multiple genes involved in the epithelial-to-mesenchymal transition. HIF-1α also enhanced tumorsphere formation at normoxia and hypoxia. Decreased expression of several genes in the Notch pathway as well as Vegf and Prominin-1 (CD133)was observed in response to Hif1a deletion. Immunohistochemistry confirmed that CD133 expression was reduced in KO cells and in tumorspheres. Tumorsphere formation was enhanced in CD133hi versus CD133neg cells sorted from PyMT tumors. Limiting dilution transplantation of WT and KO tumor cells into immunocompetent recipients revealed > 30-fold enrichment of TICs in WT cells

  4. The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study.

    PubMed

    Huang, Jian; Zhang, Di; Xie, Fuqiang; Lin, Degui

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.

  5. African American Race is an Independent Risk Factor in Survival from Initially Diagnosed Localized Breast Cancer

    PubMed Central

    Wieder, Robert; Shafiq, Basit; Adam, Nabil

    2016-01-01

    BACKGROUND: African American race negatively impacts survival from localized breast cancer but co-variable factors confound the impact. METHODS: Data sets were analyzed from the Surveillance, Epidemiology and End Results (SEER) directories from 1973 to 2011 consisting of patients with designated diagnosis of breast adenocarcinoma, race as White or Caucasian, Black or African American, Asian, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, age, stage I, II or III, grade 1, 2 or 3, estrogen receptor or progesterone receptor positive or negative, marital status as single, married, separated, divorced or widowed and laterality as right or left. The Cox Proportional Hazards Regression model was used to determine hazard ratios for survival. Chi square test was applied to determine the interdependence of variables found significant in the multivariable Cox Proportional Hazards Regression analysis. Cells with stratified data of patients with identical characteristics except African American or Caucasian race were compared. RESULTS: Age, stage, grade, ER and PR status and marital status significantly co-varied with race and with each other. Stratifications by single co-variables demonstrated worse hazard ratios for survival for African Americans. Stratification by three and four co-variables demonstrated worse hazard ratios for survival for African Americans in most subgroupings with sufficient numbers of values. Differences in some subgroupings containing poor prognostic co-variables did not reach significance, suggesting that race effects may be partly overcome by additional poor prognostic indicators. CONCLUSIONS: African American race is a poor prognostic indicator for survival from breast cancer independent of 6 associated co-variables with prognostic significance. PMID:27698895

  6. Adaptive Radiotherapy for Head-and-Neck Cancer: Initial Clinical Outcomes From a Prospective Trial

    SciTech Connect

    Schwartz, David L.; Garden, Adam S.; Thomas, Jimmy; Chen Yipei; Zhang Yongbin; Lewin, Jan; Chambers, Mark S.; Dong, Lei

    2012-07-01

    Purpose: To present pilot toxicity and survival outcomes for a prospective trial investigating adaptive radiotherapy (ART) for oropharyngeal squamous cell carcinoma. Methods and Materials: A total of 24 patients were enrolled in an institutional review board-approved clinical trial; data for 22 of these patients were analyzed. Daily CT-guided setup and deformable image registration permitted serial mapping of clinical target volumes and avoidance structures for ART planning. Primary site was base of tongue in 15 patients, tonsil in 6 patient, and glossopharyngeal sulcus in 1 patient. Twenty patients (91%) had American Joint Committee on Cancer (AJCC) Stage IV disease. T stage distribution was 2 T1, 12 T2, 3 T3, 5 T4. N stage distribution was 1 N0, 2 N1, 5 N2a, 12 N2b, and 2 N2c. Of the patients, 21 (95%) received systemic therapy. Results: With a 31-month median follow-up (range, 13-45 months), there has been no primary site failure and 1 nodal relapse, yielding 100% local and 95% regional disease control at 2 years. Baseline tumor size correlated with absolute volumetric treatment response (p = 0.018). Parotid volumetric change correlated with duration of feeding tube placement (p = 0.025). Acute toxicity was comparable to that observed with conventional intensity-modulated radiotherapy (IMRT). Chronic toxicity and functional outcomes beyond 1 year were tabulated. Conclusion: This is the first prospective evaluation of morbidity and survival outcomes in patients with locally advanced head-and-neck cancer treated with automated adaptive replanning. ART can provide dosimetric benefit with only one or two mid-treatment replanning events. Our preliminary clinical outcomes document functional recovery and preservation of disease control at 1-year follow-up and beyond.

  7. Sinodielide A exerts thermosensitizing effects and induces apoptosis and G2/M cell cycle arrest in DU145 human prostate cancer cells via the Ras/Raf/MAPK and PI3K/Akt signaling pathways.

    PubMed

    Hatashita, Masanori; Taniguchi, Masahiko; Baba, Kimiye; Koshiba, Ken; Sato, Takefumi; Jujo, Yutaka; Suzuki, Ryuta; Hayashi, Sachiko

    2014-02-01

    Sinodielide A (SA) is a naturally occurring guaianolide, which is isolated from the root of Sinodielsia yunnanensis. This root, commonly found in Yunnan province, is used in traditional Chinese medicine as an antipyretic, analgesic and diaphoretic agent. A number of studies have reported that agents isolated from a species of Umbelliferae (Apiaceae) have antitumor activities. We previously reported, using combined treatments with this medicinal herb and hyperthermia at various temperatures, an enhanced cytotoxicity in the human prostate cancer androgen‑independent cell lines, PC3 and DU145, and analyzed the related mechanisms. In the present study, we investigated the effects of treatment with SA prior to hyperthermia on the thermosensitivity of DU145 cells, and the mechanisms related to the induction of apoptosis and G(2)/M cell cycle arrest via the activation of extracellular-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathways, as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. Cells were exposed to hyperthermia alone (40-44˚C) or hyperthermia in combination with SA. Lethal damage to cells treated with mild hyperthermia (40 or 42˚C) for up to 6 h was slight; however, hyperthermia in combination with SA synergistically enhanced thermosensivity. Lethal damage to cells treated with acute hyperthermia (43 or 44˚C) was more severe, but these effects were also enhanced and were more significant by the combined treatment with SA. The kinetics of apoptosis induction and cell cycle distribution were analyzed by flow cytometry. In addition, the levels of ERK1/2, JNK and Akt were determined by western blot analysis. The incidence of apoptotic cells after treatment with SA (20.0 µM) at 37˚C for 4 h, hyperthermia (44˚C) alone for 30 min, and the combination in sequence were examined. The sub-G1 division (%) in the diagram obtained by flow cytometry was applied to that assay. The

  8. Relationship of social support and social burden to repeated breast cancer screening in the women's health initiative.

    PubMed

    Messina, Catherine R; Lane, Dorothy S; Glanz, Karen; West, Delia Smith; Taylor, Vicky; Frishman, William; Powell, Lynda

    2004-11-01

    Direct and interactive effects of social support, social burden (caregiving, negative life events, and social strain), education, and income on repeated use of breast cancer screening among a large (N=55,278), national sample of postmenopausal women participating in the Women's Health Initiative observational study were examined. Repeated screening decreased as emotional/informational support and positive social interactions decreased (ps<.01). Repeated mammography decreased with frequent caregiving (p<.01). Less social strain reduced the frequency of repeated breast self-examinations (BSEs; ps<.01), but frequent caregiving and more negative life events increased repeated use of BSE (ps<.01). Interactive effects suggested that emotional/informational but not tangible support is associated with repeated mammography and clinical breast examinations (ps<.01) and may be particularly important among low-income older women, especially those burdened by caregiving.

  9. Initial Experience with Magnetic Resonance-Guided Vacuum-Assisted Biopsy in Korean Women with Breast Cancer

    PubMed Central

    Jung, Hye Na; Ko, Eun Young; Shin, Jung Hee

    2014-01-01

    Purpose The aim of this study is to describe our initial experience with magnetic resonance (MR)-guided biopsy and to determine the malignancy rate of additional lesions identified by MR only in Korean women with breast cancer. Methods A retrospective review identified 22 consecutive patients with breast cancer who had undergone MR-guided vacuum-assisted biopsies (VAB) of MR-only identified lesions from May 2009 to October 2011.We evaluated the rate of compliance, the technical success for MR-guided VAB and the MR imaging findings of the target lesions. VAB histology was compared with surgical histology and follow-up imaging findings. Results The biopsy recommendations for MR-only identified lesions were accepted in 46.8% (22/47) of patients. One of 22 procedures failed due to the target's posterior location. Among 21 MR-guided VAB procedures, the target lesions were considered as a mass in 12 cases and a nonmass enhancement in nine cases. VAB histology revealed malignancies in 14% (3/21) of cases, high-risk lesions in 24% (5/21) and benign lesions in 62% (13/21). Eleven cases (52%, 11/21) had a positive surgical correlation, and one of them was upgraded from atypical ductal hyperplasia to invasive ductal carcinoma. In the remaining 10 lesions, follow-up breast ultrasound and mammography were available (range, 15-44 months; mean, 32.1 months) and did not show suspicious lesions. The final malignancy rate was 19% (4/21). Conclusion MR-guided VAB for MR-only identified lesions yielded a 19% malignancy rate in Korean women with breast cancer. MR-guided VAB helps surgeons avoid an unnecessary wide excision or additional excisional biopsy. PMID:25320626

  10. Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative

    PubMed Central

    Wang, Ange; Stefanick, Marcia L; Kapphahn, Kristopher; Hedlin, Haley; Desai, Manisha; Manson, Jo Ann E; Strickler, Howard; Martin, Lisa; Wactawski-Wende, Jean; Simon, Michael; Tang, Jean Y

    2016-01-01

    Background: The relationship between statin use and non-melanoma skin cancer (NMSC) is unclear with conflicting findings in literature. Data from the Women's Health Initiative (WHI) Observational Study and WHI Clinical Trial were used to investigate the prospective relationship between statin use and NMSC in non-Hispanic white (NHW) postmenopausal women. Methods: The WHI study enrolled women aged 50–79 years at 40 US centres. Among 133 541 NHW participants, 118 357 with no cancer history at baseline and complete medication/covariate data comprised the analytic cohort. The association of statin use (baseline, overall as a time-varying variable, duration, type, potency, lipophilicity) and NMSC incidence was determined using random-effects logistic regression models. Results: Over a mean of 10.5 years of follow-up, we identified 11 555 NMSC cases. Compared with participants with no statin use, use of any statin at baseline was associated with significantly increased NMSC incidence (adjusted odds ratio (ORadj) 1.21; 95% confidence interval (CI): 1.07–1.35)). In particular, lovastatin (OR 1.52; 95% CI: 1.08–2.16), simvastatin (OR 1.38; 95% CI: 1.12–1.69), and lipophilic statins (OR 1.39; 95% CI: 1.18–1.64) were associated with higher NMSC risk. Low and high, but not medium, potency statins were associated with higher NMSC risk. No significant effect modification of the statin–NMSC relationship was found for age, BMI, smoking, solar irradiation, vitamin D use, and skin cancer history. Conclusions: Use of statins, particularly lipophilic statins, was associated with increased NMSC risk in postmenopausal white women in the WHI cohort. The lack of duration–effect relationship points to possible residual confounding. Additional prospective research should further investigate this relationship. PMID:26742009

  11. Protein Mis-Termination Initiates Genetic Diseases, Cancers, and Restricts Bacterial Genome Expansion.

    PubMed

    Wong, Tit-Yee; Schwartzbach, Steve D

    2015-01-01

    Protein termination is an important cellular process. Protein termination relies on the stop-codons in the mRNA interacting properly with the releasing factors on the ribosome. One third of inherited diseases, including cancers, are associated with the mutation of the stop-codons. Many pathogens and viruses are able to manipulate their stop-codons to express their virulence. The influence of stop-codons is not limited to the primary reading frame of the genes. Stop-codons in the second and third reading frames are referred as premature stop signals (PSC). Stop-codons and PSCs together are collectively referred as stop-signals. The ratios of the stop-signals (referred as translation stop-signals ratio or TSSR) of genetically related bacteria, despite their great differences in gene contents, are much alike. This nearly identical Genomic-TSSR value of genetically related bacteria may suggest that bacterial genome expansion is limited by their unique stop-signals bias. We review the protein termination process and the different types of stop-codon mutation in plants, animals, microbes, and viruses, with special emphasis on the role of PSCs in directing bacterial evolution in their natural environments. Knowing the limit of genomic boundary could facilitate the formulation of new strategies in controlling the spread of diseases and combat antibiotic-resistant bacteria.

  12. Cri du chat syndrome

    MedlinePlus

    ... the infant's cry, which is high-pitched and sounds like a cat. Causes Cri du chat syndrome is rare. It is caused by a missing piece of chromosome 5. Most cases are believed to occur during the development of ... Cry that is high-pitched and may sound like a cat Downward slant to the eyes ...

  13. The Interaction between Dietary Fiber and Fat and Risk of Colorectal Cancer in the Women’s Health Initiative

    PubMed Central

    Navarro, Sandi L.; Neuhouser, Marian L.; Cheng, Ting-Yuan David; Tinker, Lesley F.; Shikany, James M.; Snetselaar, Linda; Martinez, Jessica A.; Kato, Ikuko; Beresford, Shirley A. A.; Chapkin, Robert S.; Lampe, Johanna W.

    2016-01-01

    Combined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically) and fat (omega-6, omega-3, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), specifically) and colorectal cancer (CRC) risk in the Women’s Health Initiative prospective cohort (n = 134,017). During a mean 11.7 years (1993–2010), 1952 incident CRC cases were identified. Cox regression models computed multivariate adjusted hazard ratios to estimate the association between dietary factors and CRC risk. Assessing fiber and fat individually, there was a modest trend for lower CRC risk with increasing intakes of total and insoluble fiber (p-trend 0.09 and 0.08). An interaction (p = 0.01) was observed between soluble fiber and DHA + EPA, with protective effects of DHA + EPA with lower intakes of soluble fiber and an attenuation at higher intakes, however this association was no longer significant after correction for multiple testing. These results suggest a modest protective effect of higher fiber intake on CRC risk, but not in combination with dietary fat subtypes. Given the robust results in preclinical models and mixed results in observational studies, controlled dietary interventions with standardized intakes are needed to better understand the interaction of specific fat and fiber subtypes on colon biology and ultimately CRC susceptibility in humans. PMID:27916893

  14. CXCL12/CXCR4 Blockade by Oncolytic Virotherapy Inhibits Ovarian Cancer Growth by Decreasing Immunosuppression and Targeting Cancer Initiating Cells1

    PubMed Central

    Gil, Margaret; Komorowski, Marcin P.; Seshadri, Mukund; Rokita, Hanna; McGray, A. J Robert; Opyrchal, Mateusz; Odunsi, Kunle O.; Kozbor, Danuta

    2014-01-01

    Signals mediated by the chemokine CXCL12 and its receptor CXCR4 are involved in progression of ovarian cancer by enhancing tumor angiogenesis and immunosuppressive networks that regulate dissemination of peritoneal metastasis and development of cancer initiating cells (CICs). Here, we investigated the antitumor efficacy of a CXCR4 antagonist expressed by oncolytic vaccinia virus (OVV) against an invasive variant of the murine epithelial ovarian cancer cell line ID8-T. This variant harbors a high frequency of CICs that form multilayered spheroid cells and express the hyaluronan receptor CD44 as well as stem cell factor receptor CD117 (c-kit). Using an orthotopic ID8-T tumor model, we observed that intraperitoneal delivery of a CXCR4 antagonist-expressing OVV led to reduced metastatic spread of tumors and improved overall survival over that mediated by oncolysis alone. Inhibition of tumor growth with the armed virus was associated with efficient killing of CICs, reductions in expression of ascitic CXCL12 and VEGF, and decreases in intraperitoneal numbers of endothelial and myeloid cells as well as plasmacytoid dendritic cells (pDCs). These changes, together with reduced recruitment of T regulatory cells, were associated with higher ratios of IFN-γ+/IL-10+ tumor-infiltrating T lymphocytes as well as induction of spontaneous humoral and cellular antitumor responses. Similarly, the CXCR4 antagonist released from virally-infected human CAOV2 ovarian carcinoma cells inhibited peritoneal dissemination of tumors in SCID mice leading to improved tumor-free survival in a xenograft model. Our findings demonstrate that OVV armed with a CXCR4 antagonist represents a potent therapy for ovarian CICs with a broad antitumor repertoire. PMID:25320277

  15. CXCL12/CXCR4 blockade by oncolytic virotherapy inhibits ovarian cancer growth by decreasing immunosuppression and targeting cancer-initiating cells.

    PubMed

    Gil, Margaret; Komorowski, Marcin P; Seshadri, Mukund; Rokita, Hanna; McGray, A J Robert; Opyrchal, Mateusz; Odunsi, Kunle O; Kozbor, Danuta

    2014-11-15

    Signals mediated by the chemokine CXCL12 and its receptor CXCR4 are involved in the progression of ovarian cancer through enhancement of tumor angiogenesis and immunosuppressive networks that regulate dissemination of peritoneal metastasis and development of cancer-initiating cells (CICs). In this study, we investigated the antitumor efficacy of a CXCR4 antagonist expressed by oncolytic vaccinia virus (OVV) against an invasive variant of the murine epithelial ovarian cancer cell line ID8-T. This variant harbors a high frequency of CICs that form multilayered spheroid cells and express the hyaluronan receptor CD44, as well as stem cell factor receptor CD117 (c-kit). Using an orthotopic ID8-T tumor model, we observed that i.p. delivery of a CXCR4 antagonist-expressing OVV led to reduced metastatic spread of tumors and improved overall survival compared with oncolysis alone. Inhibition of tumor growth with the armed virus was associated with efficient killing of CICs, reduced expression of ascitic CXCL12 and vascular endothelial growth factor, and decreases in i.p. numbers of endothelial and myeloid cells, as well as plasmacytoid dendritic cells. These changes, together with reduced recruitment of T regulatory cells, were associated with higher ratios of IFN-γ(+)/IL-10(+) tumor-infiltrating T lymphocytes, as well as induction of spontaneous humoral and cellular antitumor responses. Similarly, the CXCR4 antagonist released from virally infected human CAOV2 ovarian carcinoma cells inhibited peritoneal dissemination of tumors in SCID mice, leading to improved tumor-free survival in a xenograft model. Our findings demonstrate that OVV armed with a CXCR4 antagonist represents a potent therapy for ovarian CICs with a broad antitumor repertoire.

  16. Recruiting and Surveying Catholic Parishes for Cancer Control Initiatives: Lessons Learned From the CRUZA Implementation Study

    PubMed Central

    Tom, Laura S.; Leyva, Bryan; Rustan, Sarah; Ospino, Hosffman; Negron, Rosalyn; Torres, Maria Idalí; Galeas, Ana V.

    2017-01-01

    Background We describe activities undertaken to conduct organizational surveys among faith-based organizations (FBOs) in Massachusetts (MA) as part of a larger study designed to promote parish-based cancer control programs for Latinos. Methods Catholic parishes located in MA that provided Spanish-language mass were eligible for study participation. Parishes were identified through diocesan records and online directories. Prior to parish recruitment, we implemented a variety of activities to gain support from Catholic leaders at the Diocesan level. We then recruited individual parishes to complete a four-part organizational survey, which assessed: (A) parish leadership; (B) financial resources; (C) involvement in Hispanic ministry; and (D) health and social service offerings. Our goal was to administer each survey component to a parish representatives who could best provide an organizational perspective on the content of each component (e.g., A=pastors; B= Business Managers; C=Hispanic Ministry Leaders; and D= Parish Nurse or Health Ministry leader. Here, we present descriptive statistics on recruitment and survey administration processes. Results Seventy-five percent of eligible parishes responded to the survey and of these, 92% completed all four components. Completed four-part surveys required an average of 16.6 contact attempts. There were an average of 2.1 respondents per site. Pastoral staff were the most frequent respondents (79%), but also required the most contact attempts (M = 9.3, range = 1 to 27). While most interviews were completed by phone (71%), one-quarter were completed during in-person site visits. Conclusions We achieved a high survey completion rate among organizational representatives. Our lessons learned may inform efforts to engage and survey FBOs for public health efforts. PMID:25878192

  17. Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

    SciTech Connect

    Zampino, Maria Giulia Magni, Elena; Leonardi, Maria Cristina; Petazzi, Elena; Santoro, Luigi; Luca, Fabrizio; Chiappa, Antonio; Petralia, Giuseppe; Trovato, Cristina; Fazio, Nicola; Orecchia, Roberto; Nole, Franco; Braud, Filippo de

    2009-10-01

    Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeks before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.

  18. Experiences of patients requiring strong opioid drugs for chronic non-cancer pain: a patient-initiated study

    PubMed Central

    Blake, Sue; Ruel, Brian; Seamark, Clare; Seamark, David

    2007-01-01

    Background Chronic non-cancer pain is an increasing problem in health care. This study was initiated by a patient wanting to discover more about the experiences of other patients requiring strong opioid analgesia for such pain. Aim To determine the attitudes and experiences of patients receiving long-term strong opioid medication for chronic non-cancer pain in primary care. Design of study Qualitative study using interpretative phenomenological analysis. Setting A semi-rural general practice in southwest England. Method The study data came from a focus group and 10 individual patient interviews. A patient researcher was involved in the design, conduct, and analysis of the project. Results The impact of pain affected participants in every aspect of their daily lives. Attitudes to strong opioid medication were both positive and negative. Concerns about starting medication usually centred on fears of addiction, being seen as an addict, or that the patients may have a more serious condition than they had previously thought. However, these fears were tempered by an appreciation of the benefits that strong opioids brought in terms of pain relief and consequent gains in a nearer-to-normal existence. The data did not produce any evidence of addictive behaviour or of tolerance despite these initial fears. Patients adopted a trade off approach, balancing pain relief with medication side effects, accepting more pain for a reduction in sedation and nausea. All patients described coping strategies they developed themselves and learned from outside influences, such as pain clinic courses and support from the GP. There was realism that total pain relief was not possible, but that a balance could be struck. Conclusion Chronic non-cancer pain is associated with high levels of distress and psychosocial impairment. Patients in this study appreciated the benefits of strong opioid medication, having come to terms with fears of addiction and learned coping strategies. These findings

  19. Optimization of the tissue source, malignancy, and initial substrate of tumor cell-derived matrices to increase cancer cell chemoresistance against 5-fluorouracil.

    PubMed

    Hoshiba, Takashi; Tanaka, Masaru

    2015-02-13

    The low chemoresistance of in vitro cancer cells inhibits the development of new anti-cancer drugs. Thus, development of a new in vitro culture system is required to increase the chemoresistance of in vitro cancer cells. Tumor cell-derived matrices have been reported to increase the chemoresistance of in vitro cancer cells. However, it remains unclear how tissue sources and the malignancy of cells used for the preparation of matrices affect the chemoresistance of tumor cell-derived matrices. Moreover, it remains unclear how the initial substrates used for the preparation of matrices affect the chemoresistance. In this study, we compared the effects of tissue sources and the malignancy of tumor cells, as well as the effect of the initial substrates on chemoresistance against 5-fluorouracil (5-FU). The chemoresistance of breast and colon cancer cells against 5-FU increased on matrices prepared with cells derived from the corresponding original tissues with higher malignancy. Moreover, the chemoresistance against 5-FU was altered on matrices prepared using different initial substrates that exhibited different characteristics of protein adsorption. Taken together, these results indicated that the appropriate selection of tissue sources, malignancy of tumor cells, and initial substrates used for matrix preparation is important for the preparation of tumor cell-derived matrices for chemoresistance assays.

  20. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    PubMed Central

    2012-01-01

    Background Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions We characterized a self-renewing subpopulation of CICs found among four well known human

  1. Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

    SciTech Connect

    Burri, Ryan J.; Stone, Nelson N.; Unger, Pam; Stock, Richard G.

    2010-08-01

    Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with {sup 103}Pd or {sup 125}I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade {>=}2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

  2. A convenient and effective strategy for the enrichment of tumor-initiating cell properties in prostate cancer cells.

    PubMed

    Zhang, Yiming; Huang, Yiqiang; Jin, Zhong; Li, Xiezhao; Li, Bingkun; Xu, Peng; Huang, Peng; Liu, Chunxiao

    2016-09-01

    Stem-like prostate cancer (PrCa) cells, also called PrCa stem cells (PrCSCs) or PrCa tumor-initiating cells (PrTICs), are considered to be involved in the mediation of tumor metastasis and may be responsible for the poor prognosis of PrCa patients. Currently, the methods for PrTIC sorting are mainly based on cell surface marker or side population (SP). However, the rarity of these sorted cells limits the investigation of the molecular mechanisms and therapeutic strategies targeting PrTICs. For PrTIC enrichment, we induced cancer stem cell (CSC) properties in PrCa cells by transducing three defined factors (OCT3/4, SOX2, and KLF4), followed by culture with conventional serum-containing medium. The CSC properties in the transduced cells were evaluated by proliferation, cell cycle, SP assay, drug sensitivity technology, in vivo tumorigenicity, and molecular marker analysis of PrCSCs compared with parental cells and spheroids. After culture with serum-containing medium for 8 days, the PrCa cells transduced with the three factors showed significantly enhanced CSC properties in terms of marker gene expression, sphere formation, chemoresistance to docetaxel, and tumorigenicity. The percentage of CD133(+)/CD44(+) cells was ninefold higher in the transduced cell population than in the adherent PC3 cell population (2.25 ± 0.62 vs. 0.25 ± 0.12 %, respectively), and the SP increased to 1.22 ± 0.18 % in the transduced cell population, but was undetectable in the adherent population. This method can be used to obtain abundant PrTIC material and enables a complete understanding of PrTIC biology and development of novel therapeutic agents targeting PrTICs.

  3. CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells

    PubMed Central

    Wang, Zhe; von Au, Anja; Schnölzer, Martina; Hackert, Thilo; Zöller, Margot

    2016-01-01

    Cancer-initiating cells (CIC) account for metastatic spread, which may rely mostly on CIC exosomes (TEX) that affect host cells and can transfer CIC features into Non-CIC. The CIC marker CD44 variant isoform v6 (CD44v6) being known for metastasis-promotion, we elaborated in cells its contribution to migration and invasion and in TEX the tranfer of migratory and invasive capacity to Non-CIC, using a CD44v6 knockdown (CD44v6kd) as Non-CIC model. A CD44v6kd in human pancreatic and colorectal cancer (PaCa, CoCa) lines led to loss of CIC characteristics including downregulation of additional CIC markers, particularly Tspan8. This aggravated the loss of CD44v6-promoted motility and invasion. Loss of motility relies on the distorted cooperation of CD44v6 and Tspan8 with associated integrins and loss of invasiveness on reduced protease expression. These deficits, transferred into TEX, severely altered the CD44v6kd-TEX composition. As a consequence, unlike the CIC-TEX, CD44v6kd TEX were not taken up by CD44v6kd cells and CIC. The uptake of CIC-TEX was accompanied by partial correction of CIC marker and protease expression in CD44v6kd cells, which regained migratory, invasive and metastatic competence. CIC-TEX also fostered angiogenesis and expansion of myeloid cells, likely due to a direct impact of CIC-TEX on the host, which could be supported by reprogrammed CD44v6kd cells. Taken together, the striking loss of tumor progression by a CD44v6kd relies on the capacity of CD44v6 to cooperate with associating integrins and proteases and its promotion of additional CIC marker expression. The defects by a CD44v6kd are efficiently corrected upon CIC-TEX uptake. PMID:27419629

  4. CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells.

    PubMed

    Wang, Zhe; von Au, Anja; Schnölzer, Martina; Hackert, Thilo; Zöller, Margot

    2016-08-23

    Cancer-initiating cells (CIC) account for metastatic spread, which may rely mostly on CIC exosomes (TEX) that affect host cells and can transfer CIC features into Non-CIC. The CIC marker CD44 variant isoform v6 (CD44v6) being known for metastasis-promotion, we elaborated in cells its contribution to migration and invasion and in TEX the tranfer of migratory and invasive capacity to Non-CIC, using a CD44v6 knockdown (CD44v6kd) as Non-CIC model.A CD44v6kd in human pancreatic and colorectal cancer (PaCa, CoCa) lines led to loss of CIC characteristics including downregulation of additional CIC markers, particularly Tspan8. This aggravated the loss of CD44v6-promoted motility and invasion. Loss of motility relies on the distorted cooperation of CD44v6 and Tspan8 with associated integrins and loss of invasiveness on reduced protease expression. These deficits, transferred into TEX, severely altered the CD44v6kd-TEX composition. As a consequence, unlike the CIC-TEX, CD44v6kd TEX were not taken up by CD44v6kd cells and CIC. The uptake of CIC-TEX was accompanied by partial correction of CIC marker and protease expression in CD44v6kd cells, which regained migratory, invasive and metastatic competence. CIC-TEX also fostered angiogenesis and expansion of myeloid cells, likely due to a direct impact of CIC-TEX on the host, which could be supported by reprogrammed CD44v6kd cells.Taken together, the striking loss of tumor progression by a CD44v6kd relies on the capacity of CD44v6 to cooperate with associating integrins and proteases and its promotion of additional CIC marker expression. The defects by a CD44v6kd are efficiently corrected upon CIC-TEX uptake.

  5. 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.

  6. Influence of a National Cancer Institute transdisciplinary research and training initiative on trainees' transdisciplinary research competencies and scholarly productivity.

    PubMed

    Vogel, Amanda L; Feng, Annie; Oh, April; Hall, Kara L; Stipelman, Brooke A; Stokols, Daniel; Okamoto, Janet; Perna, Frank M; Moser, Richard; Nebeling, Linda

    2012-12-01

    Over the past several decades, there has been burgeoning interest and investment in large transdisciplinary (TD) team science initiatives that aim to address complex societal problems. Despite this trend, TD training opportunities in the health sciences remain limited, and evaluations of these opportunities are even more uncommon due to funding constraints. We had the unique opportunity to conduct an exploratory study to examine the potential outcomes and impacts of TD training in a National Cancer Institute-supported initiative for TD research and training-the Transdisciplinary Research on Energetics and Cancer I (TREC I) initiative. This study used a retrospective mixed-methods approach leveraging secondary analysis of existing data sources to learn about TREC trainees' experiences with TREC training, TD research competencies, changes in scholarly productivity, and the associations among these domains. Results indicated that, on average, TREC trainees were satisfied with their TREC mentoring experiences and believed that TREC training processes were effective, in general. Participation in TREC training was associated with TD research competencies, including TD research orientation, positive general attitude toward TD training, development of scientific skills for TD research, and intrapersonal/interpersonal competencies for collaboration. There was also a significant increase in trainees' scholarly productivity from before to after starting in TREC training, as indicated by average annual number of publications and presentations and average number of coauthors per publication. Perceived effectiveness of TREC training was positively correlated with change in average annual number of research presentations from before to after starting in TREC training (r = 0.65, p < 0.05, N = 12), as well as TD research orientation (r = 0.36, p < 0.05), general attitude toward TD training (0.39, p < 0.05), scientific skills for TD research (r = 0

  7. Equol, an Isoflavone Metabolite, Regulates Cancer Cell Viability and Protein Synthesis Initiation via c-Myc and eIF4G*

    PubMed Central

    de la Parra, Columba; Borrero-Garcia, Luis D.; Cruz-Collazo, Ailed; Schneider, Robert J.; Dharmawardhane, Suranganie

    2015-01-01

    Epidemiological studies implicate dietary soy isoflavones as breast cancer preventives, especially due to their anti-estrogenic properties. However, soy isoflavones may also have a role in promoting breast cancer, which has yet to be clarified. We previously reported that equol, a metabolite of the soy isoflavone daidzein, may advance breast cancer potential via up-regulation of the eukaryotic initiation factor 4GI (eIF4GI). In estrogen receptor negative (ER−) metastatic breast cancer cells, equol induced elevated levels of eIF4G, which were associated with increased cell viability and the selective translation of mRNAs that use non-canonical means of initiation, including internal ribosome entry site (IRES), ribosome shunting, and eIF4G enhancers. These mRNAs typically code for oncogenic, survival, and cell stress molecules. Among those mRNAs translationally increased by equol was the oncogene and eIF4G enhancer, c-Myc. Here we report that siRNA-mediated knockdown of c-Myc abrogates the increase in cancer cell viability and mammosphere formation by equol, and results in a significant down-regulation of eIF4GI (the major eIF4G isoform), as well as reduces levels of some, but not all, proteins encoded by mRNAs that are translationally stimulated by equol treatment. Knockdown of eIF4GI also markedly reduces an equol-mediated increase in IRES-dependent mRNA translation and the expression of specific oncogenic proteins. However, eIF4GI knockdown did not reciprocally affect c-Myc levels or cell viability. This study therefore implicates c-Myc as a potential regulator of the cancer-promoting effects of equol via up-regulation of eIF4GI and selective initiation of translation on mRNAs that utilize non-canonical initiation, including certain oncogenes. PMID:25593313

  8. miR-21 Might be Involved in Breast Cancer Promotion and Invasion Rather than in Initial Events of Breast Cancer Development.

    PubMed

    Petrović, Nina

    2016-04-01

    Breast cancer (BC) is a heterogeneous disease that develops into a large number of varied phenotypes. One of the features used in its classification and therapy selection is invasiveness. MicroRNA-21 (miR-21) is considered to be an important element of BC invasiveness, and miR-21 levels are frequently increased in different tumor types compared with normal tissue, including the breast. Experimental and literature research has highlighted that miR-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. The main goal of this research was to specify the predominant role of miR-21 in the different phases of BC pathogenesis, i.e. whether it was involved in the early (initiation), later (promotion), or late (propagation, progression) phases. Our second goal was to explain the roles of miR-21 targets in BC by an in silico approach and literature review, and to associate the importance of miR-21 with particular phases of BC pathogenesis through the action of its target genes. Analysis has shown that changes in miR-21 levels might be important for the later and/or late phases of breast cancerogenesis rather than for the initial early phases. Targets of miR-21 (TIMP3, PDCD4, PTEN, TPM1 and RECK) are also primarily involved in BC promotion and progression, especially invasion, angiogenesis and metastasis. miR-21 expression levels could perhaps be used in conjunction with the standard diagnostic parameters as an indicator of BC presence, and to indicate a phenotype likely to show early invasion/metastasis detection and poor prognosis.

  9. Evaluation of Prostate Cancer with 11C- and 18F-Choline PET/CT: Diagnosis and Initial Staging.

    PubMed

    Nitsch, Sascha; Hakenberg, Oliver W; Heuschkel, Martin; Dräger, Desiree; Hildebrandt, Guido; Krause, Bernd J; Schwarzenböck, Sarah M

    2016-10-01

    Early diagnosis and adequate staging are crucial for the choice of adequate treatment in prostate cancer (PC). Morphologic and functional imaging modalities, such as CT and MRI, have had limited accuracy in the diagnosis and nodal staging of PC. Molecular PET/CT imaging with (11)C- or (18)F-choline-labeled derivatives is increasingly being used, but its role in the diagnosis and initial staging of PC is controversial because of limitations in sensitivity and specificity for the detection of primary PC. For T staging, functional MRI is superior to (11)C- or (18)F-choline PET/CT. For N staging, (11)C- or (18)F-choline PET/CT can provide potentially useful information that may influence treatment planning. For the detection of bone metastases, (11)C- or (18)F-choline PET/CT has had promising results; however, in terms of cost-effectiveness, the routine use of (11)C- or (18)F-choline PET/CT is still debatable. (11)C- or (18)F-choline PET/CT might be used in high-risk PC before radiation treatment planning, potentially affecting this planning (e.g., regarding dose escalation). This review provides an overview of the diagnostic accuracy and limitations of (11)C- or (18)F-choline PET/CT in the diagnosis and staging of PC.

  10. The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation.

    PubMed

    Coradini, Danila; Oriana, Saro

    2014-02-01

    During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.

  11. Tumor-derived mesenchymal stem cells and orthotopic site increase the tumor initiation potential of putative mouse mammary cancer stem cells derived from MMTV-PyMT mice.

    PubMed

    Lanza, Denise Grant; Ma, Jun; Guest, Ian; Uk-Lim, Chang; Glinskii, Anna; Glinsky, Gennadi; Sell, Stewart

    2012-12-01

    The ability to transplant mammary cancer stem cells, identified by the phenotype CD24(+)CD29(+)CD49f(+)Sca-1(low), is dependent on the microenvironment in which the cells are placed. Using the MMTV-PyMT mouse model of mammary cancer, we now report two methods of tumor growth enhancement: contributions of tumor stroma in the form of tumor-derived mesenchymal stem cells and orthotopic vs. heterotopic transplantation sites. To support evidence of stem cell function, tumor-derived mesenchymal stem cells differentiated into adipocyte- and osteocyte-like cells after culture in specific medium. Co-injection of tumor-initiating cells with tumor-derived mesenchymal stem cells significantly increased tumor initiation compared to subcutaneous injection of TICs alone; co-injection also allowed tumor initiation with a single TIC. Interestingly, we observed the formation of sarcomas after co-injections of tumor-derived mesenchymal stem cells or mouse embryonic fibroblasts with TICs; sarcomas are not observed in spontaneous MMTV-PyMT tumors and rarely observed in injections of TICs alone. Tumor initiation was also significantly increased in the orthotopic injection site compared to heterotopic injections. We conclude that tumor stroma and orthotopic sites both enhance tumor initiation by mammary cancer stem cells.

  12. Deletion at chromosome arms 6q16-22 and 10q22.3-23.1 associated with initiation of prostate cancer.

    PubMed

    Lu, T; Hano, H

    2008-01-01

    Loss of heterozygosity (LOH) at 6q16-22 and 10q22.3-23.1 is common chromosomal alteration in advanced prostate cancer and suggests that one or more tumor suppressor genes may lie within these chromosome arms. However, the genetic changes in early stage prostate cancer and premalignant lesions remain to be investigated. We used 11 informative microsatellite markers at 6q16-22 and 10q22.3-23.1 in Japanese patients to compare the frequency of LOH in 53 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC) and 107 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 6q16-22 with at least one marker was 38 and 49% in IPC and CPC cases, respectively. Similarly, allelic loss at 10q22.3-23.1 was present in 35 and 39% of IPC and CPC, respectively. High-frequency LOH was detected in both the clinically insignificant and significant prostate cancers at 6q16-22 and 10q22.3-23.1 (P>0.05). However, no allelic loss was detected in any markers at the same regions in HGPIN (0%), which is usually considered a premalignant lesion to prostate cancer. Deletions of both the chromosome regions, 6q16-22 and 10q22.3-23.1, are more likely important events in the initiation and/or promotion of prostate cancer.

  13. An integrated genomic approach identifies that the PI3K/AKT/FOXO pathway is involved in breast cancer tumor initiation.

    PubMed

    Smit, Linda; Berns, Katrien; Spence, Katherine; Ryder, W David; Zeps, Nik; Madiredjo, Mandy; Beijersbergen, Roderick; Bernards, René; Clarke, Robert B

    2016-01-19

    Therapy resistance is one of the major impediments to successful cancer treatment. In breast cancer, a small subpopulation of cells with stem cell features, named breast cancer stem cells (BCSC), is responsible for metastasis and recurrence of the tumor. BCSC have the unique ability to grow under non-adherent conditions in "mammospheres". To prevent breast cancer recurrence and metastasis it will be crucial to eradicate BCSC.We used shRNA genetic screening to identify genes that upon knockdown enhance mammosphere formation in breast cancer cells. By integration of these results with gene expression profiles of mammospheres and NOTCH-activated cells, we identified FOXO3A. Modulation of FOXO3A activity results in a change in mammosphere formation, expression of mammary stem cell markers and breast cancer initiating potential. Importantly, lack of FOXO3A expression in breast cancer patients is associated with increased recurrence rate. Our findings provide evidence for a role for FOXO3A downstream of NOTCH and AKT that may have implications for therapies targeting BCSCs.

  14. An integrated genomic approach identifies that the PI3K/AKT/FOXO pathway is involved in breast cancer tumor initiation

    PubMed Central

    Smit, Linda; Berns, Katrien; Spence, Katherine; Ryder, W. David; Zeps, Nik; Madiredjo, Mandy; Beijersbergen, Roderick; Bernards, René; Clarke, Robert B.

    2016-01-01

    Therapy resistance is one of the major impediments to successful cancer treatment. In breast cancer, a small subpopulation of cells with stem cell features, named breast cancer stem cells (BCSC), is responsible for metastasis and recurrence of the tumor. BCSC have the unique ability to grow under non-adherent conditions in “mammospheres”. To prevent breast cancer recurrence and metastasis it will be crucial to eradicate BCSC. We used shRNA genetic screening to identify genes that upon knockdown enhance mammosphere formation in breast cancer cells. By integration of these results with gene expression profiles of mammospheres and NOTCH-activated cells, we identified FOXO3A. Modulation of FOXO3A activity results in a change in mammosphere formation, expression of mammary stem cell markers and breast cancer initiating potential. Importantly, lack of FOXO3A expression in breast cancer patients is associated with increased recurrence rate. Our findings provide evidence for a role for FOXO3A downstream of NOTCH and AKT that may have implications for therapies targeting BCSCs. PMID:26595803

  15. Supportive care during treatment for breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement.

    PubMed

    Cardoso, Fatima; Bese, Nuran; Distelhorst, Sandra R; Bevilacqua, Jose Luiz B; Ginsburg, Ophira; Grunberg, Steven M; Gralla, Richard J; Steyn, Ann; Pagani, Olivia; Partridge, Ann H; Knaul, Felicia Marie; Aapro, Matti S; Andersen, Barbara L; Thompson, Beti; Gralow, Julie R; Anderson, Benjamin O

    2013-10-01

    Breast cancer patients may have unmet supportive care needs during treatment, including symptom management of treatment-related toxicities, and educational, psychosocial, and spiritual needs. Delivery of supportive care is often a low priority in low- and middle-income settings, and is also dependent on resources available. This consensus statement describes twelve key recommendations for supportive care during treatment in low- and middle-income countries, identified by an expert international panel as part of the 5th Breast Health Global Initiative (BHGI) Global Summit for Supportive Care, which was held in October 2012, in Vienna, Austria. Panel recommendations are presented in a 4-tier resource-stratified table to illustrate how health systems can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation and incrementally adding program resources as they become available. These recommendations include: health professional and patient and family education; management of treatment related toxicities, management of treatment-related symptoms of fatigue, insomnia and non-specific pain, and management of psychosocial and spiritual issues related to breast cancer treatment. Establishing supportive care during breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adherence to treatment recommendations, 2) manage treatment-related toxicities and other treatment related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and breast cancer treatments.

  16. GLI1 regulates a novel neuropilin-2/α6β1 integrin based autocrine pathway that contributes to breast cancer initiation.

    PubMed

    Goel, Hira Lal; Pursell, Bryan; Chang, Cheng; Shaw, Leslie M; Mao, Junhao; Simin, Karl; Kumar, Prashant; Vander Kooi, Craig W; Shultz, Leonard D; Greiner, Dale L; Norum, Jens Henrik; Toftgard, Rune; Kuperwasser, Charlotte; Mercurio, Arthur M

    2013-04-01

    The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin-2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the α6β1 integrin, focal adhesion kinase-mediated activation of Ras/MEK signalling and consequent expression of the Hedgehog effector GLI1. GLI1 also induces BMI-1, a key stem cell factor, and it enhances NRP2 expression and the function of α6β1, establishing an autocrine loop. NRP2 can be targeted in vivo to retard tumour initiation. These findings reveal a novel autocrine pathway involving VEGF/NRP2, α6β1 and GLI1 that contributes to the initiation of TNBC. They also support the feasibility of NRP2-based therapy for the treatment of TNBC that targets and impedes the function of TICs.

  17. Metastasis Initiating Cells in Primary Prostate Cancer Tissues From Transurethral Resection of the Prostate (TURP) Predicts Castration-Resistant Progression and Survival of Prostate Cancer Patients

    PubMed Central

    Li, Qinlong; Li, Quanlin; Nuccio, Jill; Liu, Chunyan; Duan, Peng; Wang, Ruoxiang; Jones, Lawrence W.; Chung, Leland W. K.; Zhau, Haiyen E.

    2016-01-01

    BACKGROUND We previouslyreported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. This study addresses whether a population of metastasis-initiating cells (MICs) known to express a stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected in PC tissues from patients subjected to transurethral resection of the prostate (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior hormonal manipulation, and whether the relative abundance of MICs over BDCs could predict castration-resistant progression and PC patient survival. METHODS We employed a multiplexed quantum-dot labeling (mQDL) protocol to detect and quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44 PC patients with documented overall survival and castration resistance status. RESULTS PC tissues with a higher number of MICs and an activated RANK signaling network, including increased expression of RANKL, p-c-Met, and NRP1 compared to BDCs, were found to correlate with the development of castration resistance and overall survival. CONCLUSIONS The assessment of PC cells with MIC and BDC phenotypes in primary PC tissues from hormone-naïve patients can predict the progression to castration resistance and the overall survival of PC patients. PMID:25990623

  18. 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

  19. Breast cancer screening in an era of personalized regimens: a conceptual model and National Cancer Institute initiative for risk-based and preference-based approaches at a population level.

    PubMed

    Onega, Tracy; Beaber, Elisabeth F; Sprague, Brian L; Barlow, William E; Haas, Jennifer S; Tosteson, Anna N A; D Schnall, Mitchell; Armstrong, Katrina; Schapira, Marilyn M; Geller, Berta; Weaver, Donald L; Conant, Emily F

    2014-10-01

    Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women's health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for "overdiagnosis," and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a "1-size-fits-all" guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women's risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform.

  20. ON NONLINEAR EQUATIONS OF THE FORM F(x,\\, u,\\, Du,\\, \\Delta u) = 0

    NASA Astrophysics Data System (ADS)

    Soltanov, K. N.

    1995-02-01

    The Dirichlet problem for equations of the form F(x,\\, u,\\, Du,\\, \\Delta u) = 0 and also the initial boundary value problem for a parabolic equation with a nonlinearity are studied.Bibliography: 11 titles.

  1. Initial Validation and Clinical Experience with 3D Optical-Surface-Guided Whole Breast Irradiation of Breast Cancer

    PubMed Central

    Li, S.; DeWeese, T.; Movsas, B.; Frassica, Deborah; Liu, Dezhi; Kim, Jinkoo; Chen, Qing; Walker, Eleanor

    2015-01-01

    We had introduced 3D optical surface-guided radiotherapy (SGRT) of the breast cancer (BC). We then initiated the feasibility, accuracy, and precision studies of stereovision in detection of any breast displacement through the course of treatment for total thirty breasts undertaken whole breast irradiation (WBI). In the SGRT, CT-based plan data were parsed into an in-house computer program through which the reference surfaces were generated in 3D video format. When patients were positioned on treatment Tables, real-time stereovisions were rapidly acquired while the live surface tracking shown steady thorax motion. The real-time surface images were automatically aligned with the reference surface and detected shape and location changes of the breast were online corrected through the Table and beam adjustments. Accumulated dose to each patient was computed according to the frequency distribution of the measured breast locations during beam on time. Application of SGRT had diminished large skin-marking errors of >5-mm and daily breast-setup errors of >10-mm that occurred on half of cases. Accuracy (mean) and precision (two standard deviations) of the breast displacements across the tangential field edges in the (U, V) directions were improved from (−0.5 ± 8.8, 2.2 ± 10.8) mm in conventional setup to (0.4 ± 4.6, 0.7 ± 4.4) mm in the final position while intra-fractional motion contributed only (0.1 ± 2.8, 0.0 ± 2.2) mm in free breathing. Dose uniformity and coverage to targets had both been increased by up to 10% and the lung or heart intersections have been decreased by half of those volumes if they were irradiated at the initial positions. SGRT of BC appears to be feasible regardless of skin tones, as fast as a snapshot for 3D imaging, and very accurate and precise for daily setup of flexible breast targets. Importantly, the technique allows us to verify the breast shape and position during beam-on time. PMID:22181332

  2. Comparison of Subjective and Objective Hot Flash Measures Over Time Among Breast Cancer Survivors Initiating Aromatase Inhibitor Therapy

    PubMed Central

    Otte, Julie L.; Flockhart, David; Storniolo, Anna Maria; Schneider, Bryan; Azzouz, Faouzi; Lemler, Suzanne; Jeter, Stacie; Carpenter, Janet S.; Hayes, Daniel; Stearns, Vered; Henry, N. Lynn; Nguyen, Anne; Hayden, Jill; Wright, Laurie

    2009-01-01

    Objective Hot flashes are valuable indicators of physiologic condition and drug effect; however, subjective and objective measures do not always agree. No study has examined both subjective and objective hot flashes in women prescribed aromatase inhibitors. The study (1) compared subjective and objective hot flash measures, (2) examined changes in subjective and objective hot flashes over time, and (3) evaluated predictors of change in hot flashes in aromatase inhibitor-treated women. Design Subjects (n=135) were enrolled in a randomized clinical trial comparing exemestane and letrozole for the treatment of breast cancer. Hot flashes were assessed prior to starting drug and 1, 3, and 6 months later. Subjects wore a sternal skin conductance monitor for ≥ 24 hours at each time point. With each perceived hot flash, women pressed an event button and rated intensity and bother in a paper diary. Results Subjects were a mean age of 60 years and mainly Caucasian (92%). Across time points, monitor hot flashes were (1) significantly more frequent than diary and/or event button flashes (p<.05) and (2) moderately correlated with subjective measures (.35< r <.56). Monitor hot flashes did not significantly change over time with aromatase inhibitor therapy, whereas both diary and event button frequency significantly varied but in dissimilar patterns (51% non-linear). No consistent predictors of hot flashes across measures or time points were identified. Conclusions Findings indicated dissimilarities between subjective and objective measures of hot flashes. Despite statistical significance, there was little clinically meaningful change in hot flashes after initiating aromatase inhibitor therapy. PMID:19455068

  3. Efficacy of Intra-Arterial Infusion Chemotherapy for Head and Neck Cancers Using Coaxial Catheter Technique: Initial Experience

    SciTech Connect

    Tsurumaru, Daisuke Kuroiwa, Toshiro; Yabuuchi, Hidetake; Hirata, Hideki; Higaki, Yuichiro; Tomita, Kichinobu

    2007-04-15

    The aim of this study was to evaluate the efficacy of intra-arterial infusion chemotherapy for head and neck cancers using a coaxial catheter technique: the superficial temporal artery (STA)-coaxial catheter method. Thirty-one patients (21 males and 10 females; 37-83 years of age) with squamous cell carcinoma of the head and neck (maxilla, 2; epipharynx, 4; mesopharynx, 8; oral floor, 4; tongue, 10; lower gingiva, 1; buccal mucosa, 2) were treated by intra-arterial infusion chemotherapy. Four patients were excluded from the tumor-response evaluation because of a previous operation or impossibility of treatment due to catheter trouble. Forty-eight sessions of catheterization were performed. A guiding catheter was inserted into the STA and a microcatheter was advanced into the tumor-feeding artery via the guiding catheter under angiographic guidance. When the location of the tumor or its feeding artery was uncertain on angiography, computed tomographic angiography was performed. The anticancer agent carboplatin (CBDCA) was continuously injected for 24 h through the microcatheter from a portable infusion pump attached to the patient's waist. The total administration dose was 300-1300 mg per body. External radiotherapy was administered during intra-arterial chemotherapy at a total dose of 21-70.5 Gy.The initial response was complete response in 15 patients, partial response in 7 patients, and no change in 5 patients; the overall response rate was 81.5% (22/27). Complication-related catheter maintenance was observed in 15 of 48 sessions of catheterization. Injury and dislocation of the microcatheter occurred 10 times in 7 patients. Catheter infection was observed three times in each of two patients, and catheter occlusion and vasculitis occurred in two patients. Intra-arterial infusion chemotherapy via the STA-coaxial catheter method could have potential as a favorable treatment for head and neck tumors.

  4. CD24 Is Not Required for Tumor Initiation and Growth in Murine Breast and Prostate Cancer Models.

    PubMed

    Cremers, Natascha; Neeb, Antje; Uhle, Tanja; Dimmler, Arno; Rothley, Melanie; Allgayer, Heike; Fodde, Riccardo; Sleeman, Jonathan Paul; Thiele, Wilko

    2016-01-01

    CD24 is a small, heavily glycosylated, GPI-linked membrane protein, whose expression has been associated with the tumorigenesis and progression of several types of cancer. Here, we studied the expression of CD24 in tumors of MMTV-PyMT, Apc1572/T+ and TRAMP genetic mouse models that spontaneously develop mammary or prostate carcinoma, respectively. We found that CD24 is expressed during tumor development in all three models. In MMTV-PyMT and Apc1572T/+ breast tumors, CD24 was strongly but heterogeneously expressed during early tumorigenesis, but decreased in more advanced stages, and accordingly was increased in poorly differentiated lesions compared with well differentiated lesions. In prostate tumors developing in TRAMP mice, CD24 expression was strong within hyperplastic lesions in comparison with non-hyperplastic regions, and heterogeneous CD24 expression was maintained in advanced prostate carcinomas. To investigate whether CD24 plays a functional role in tumorigenesis in these models, we crossed CD24 deficient mice with MMTV-PyMT, Apc1572T/+ and TRAMP mice, and assessed the influence of CD24 deficiency on tumor onset and tumor burden. We found that mice negative or positive for CD24 did not significantly differ in terms of tumor initiation and burden in the genetic tumor models tested, with the exception of Apc1572T/+ mice, in which lack of CD24 reduced the mammary tumor burden slightly but significantly. Together, our data suggest that while CD24 is distinctively expressed during the early development of murine mammary and prostate tumors, it is not essential for the formation of tumors developing in MMTV-PyMT, Apc1572T/+ and TRAMP mice.

  5. Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer.

    PubMed

    Ray, Saurabh; Dacosta-Byfield, Stacey; Ganguli, Arijit; Bonthapally, Vijayveer; Teitelbaum, April

    2013-08-01

    Brain metastases are a frequent complication of many systemic cancers and portend a poor prognosis. This retrospective analysis of health claims data compared survival, treatment and health care utilization and costs in patients with brain metastasis by primary tumor site. Adult commercial and Medicare Advantage enrollees newly diagnosed with brain metastasis in 01 Jan 2004 through 30 Apr 2010 were identified. Inclusion required at least 2 claims that identified the same primary cancer site prior to diagnosis of brain metastasis and no evidence of primary brain tumors. Health care utilization rates and costs were calculated at the patient level for each month of follow-up. Differences among primary cancer site cohorts were assessed by ANOVA (continuous variables), Chi square test (proportions) and the Poisson distribution (utilization rates). The primary cancer cohorts comprised 1,031 lung cancer, 93 melanoma and 395 female breast cancer patients. During the 6 months prior to brain metastasis diagnosis, 59 % of lung cancer patients had no evidence of lymph node involvement or other metastatic disease compared to 55 and 42 % of melanoma and breast cancer patients (P < 0.001). Survival after brain metastasis diagnosis was less than 3 months for 52, 43 and 39 % for lung cancer, breast cancer and melanoma, respectively (P < 0.001). Melanoma patients had the highest rate of inpatient stays and outpatient visits (P ≤ 0.003). Total monthly all-cause costs were: melanoma, $23,426; breast cancer $19,708; lung cancer, $17,007 (P = 0.003). Health care utilization and costs after brain metastasis diagnosis were substantial and differed by primary tumor site.

  6. Attenuation of cancer-initiating cells stemness properties by abrogating S100A4 calcium binding ability in head and neck cancers

    PubMed Central

    Cheng, Li-Hao; Hung, Kai-Feng; Huang, Tung-Fu; Hsieh, Hsin-Pei; Wang, Shu-Ying; Huang, Chih-Yang; Lo, Jeng-Fan

    2016-01-01

    S100A4 is a calcium-binding protein capable of promoting epithelial-mesenchymal transition. Previously, we have demonstrated that S100A4 is required to sustain the head and neck cancer-initiating cells (HN-CICs) subpopulation. In this study, to further investigate the molecular mechanism, we established the head and neck squamous cell carcinoma (HNSCC) cell lines stably expressing mutant S100A4 proteins with defective calcium-binding sites on either N-terminal (NM) or C-terminal (CM), or a deletion of the last 15 amino-acid residues (CD). We showed that the NM, CM and CD harboring sphere cells that were enriched with HN-CICs population exhibited impaired stemness and malignant properties in vitro, as well as reduced tumor growth ability in vivo. Mechanistically, we demonstrated that mutant S100A4 proteins decreased the promoter activity of Nanog, likely through inhibition of p53. Moreover, the biophysical analyses of purified recombinant mutant S100A4 proteins suggest that both NM and CM mutant S100A4 were very similar to the WT S100A4 with subtle difference on the secondary structure, and that the CD mutant protein displayed the unexpected monomeric form in the solution phase. Taken together, our results suggest that both the calcium-binding ability and the C-terminal region of S100A4 are important for HN-CICs to sustain its stemness property and malignancy, and that the mechanism could be mediated by repressing p53 and subsequently activating the Nanog expression. PMID:27793047

  7. Influence du débit et de la répartition de dose sur l'incidence des cancers pulmonaires après inhalation d'émetteurs

    NASA Astrophysics Data System (ADS)

    Fritsch, P.; Dudoignon, N.; Morlier, J. P.; Monchaux, G.; Morin, M.

    1998-04-01

    We have discussed experimental results reported on the influence of dose rate and dose distribution on the incidence of lung tumors after inhalation exposure to α emitters. New experiments have been carried out to characterize the range of tumor risk which could vary over more than a factor 20 depending on the α activity of the inhaled particles. Long term effects induced in rats after inhalation of poorly soluble 237NpO2 and industrial PuO2 with a similar granulometry will be compared, the specific activities of which varying within a factor 500. Nous avons rapporté les différentes données expérimentales de cancérogenèse pulmonaire qui montrent une variation du risque d'induction des tumeurs après inhalation de radionucléides émetteurs α selon le débit et la répartition de dose. De nouvelles expérimentations ont été initiées afin de préciser ces variations qui s'étalent sur plus d'un facteur 20. Elles consistent à comparer les effets induits chez le rat après exposition à des aérosols de 237NpO2 et de PuO2 d'origine industrielle peu solubles et de granulométrie analogue dont les activités spécifiques diffèrent d'un facteur 500.

  8. Post-diagnosis body mass index and mortality among women diagnosed with endometrial cancer: Results from the Women’s Health Initiative

    PubMed Central

    Arem, Hannah; Pfeiffer, Ruth M.; Moore, Steven C.; Irwin, Melinda L.; LaMonte, Michael J.; Sarto, Gloria E.; Nassir, Rami; Luo, Juhua; Chlebowski, Rowan T.; Brinton, Louise A.; Matthews, Charles E.

    2017-01-01

    Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women’s Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with <25 kg/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55–1.91). Our study does not support the hypothesis that higher BMI after endometrial cancer diagnosis is associated with poorer survival. PMID:28152055

  9. Microenvironment-Modulated Metastatic CD133+/CXCR4+/EpCAM- Lung Cancer-Initiating Cells Sustain Tumor Dissemination and Correlate with Poor Prognosis.

    PubMed

    Bertolini, Giulia; D'Amico, Lucia; Moro, Massimo; Landoni, Elena; Perego, Paola; Miceli, Rosalba; Gatti, Laura; Andriani, Francesca; Wong, Donald; Caserini, Roberto; Tortoreto, Monica; Milione, Massimo; Ferracini, Riccardo; Mariani, Luigi; Pastorino, Ugo; Roato, Ilaria; Sozzi, Gabriella; Roz, Luca

    2015-09-01

    Metastasis is the main reason for lung cancer-related mortality, but little is known about specific determinants of successful dissemination from primary tumors and metastasis initiation. Here, we show that CD133(+)/CXCR4(+) cancer-initiating cells (CIC) directly isolated from patient-derived xenografts (PDX) of non-small cell lung cancer are endowed with superior ability to seed and initiate metastasis at distant organs. We additionally report that CXCR4 inhibition successfully prevents the increase of cisplatin-resistant CD133(+)/CXCR4(+) cells in residual tumors and their metastatization. Immunophenotypic analysis of lung tumor cells intravenously injected or spontaneously disseminated to murine lungs demonstrated the survival advantage and increased colonization ability of a specific subset of CD133(+)/CXCR4(+) with reduced expression of epithelial cell adhesion molecule (EpCAM(-)), which also shows the greatest in vitro invasive potential. We next prove that recovered disseminated cells from lungs of PDX-bearing mice enriched for CD133(+)/CXCR4(+)/EpCAM(-) CICs are highly tumorigenic and metastatic. Importantly, microenvironment stimuli eliciting epithelial-to-mesenchymal transition, including signals from cancer-associated fibroblasts, are able to increase the dissemination potential of lung cancer cells through the generation of the CD133(+)/CXCR4(+)/EpCAM(-) subset. These findings also have correlates in patient samples where disseminating CICs are enriched in metastatic lymph nodes (20-fold, P = 0.006) and their detection in primary tumors is correlated with poor clinical outcome (disease-free survival: P = 0.03; overall survival: P = 0.05). Overall, these results highlight the importance of specific cellular subsets in the metastatic process, the need for in-depth characterization of disseminating tumor cells, and the potential of therapeutic strategies targeting both primary tumor and tumor-microenvironment interactions.

  10. Integrating cervical cancer prevention initiatives with HIV care in resource-constrained settings: A formative study in Durban, South Africa

    PubMed Central

    Ports, Katie A.; Haffejee, Firoza; Mosavel, Maghboeba; Rameshbabu, Anjali

    2015-01-01

    Cervical cancer screening rates remain suboptimal among women in South Africa (SA), where cervical cancer prevalence is high. The rollout of HIV-related services across SA may provide a means to deliver cervical cancer screening to populations with limited access to healthcare systems. In this mixed methods study, psychosocial factors influencing cervical cancer prevention and perceptions of the provision of Pap smears in HIV care settings were examined. Structured interviews were conducted with women (n=67) from a municipal housing estate in Durban, SA. Key informants (n=12) also participated in semi-structured interviews. Findings revealed that participants had low cervical cancer knowledge, but desired more information. Relevant themes included the normalization of HIV and beliefs that cervical cancer might be worse than HIV. A comprehensive community clinic was desired by most, even if HIV-positive patients were treated there. This study provides important insight into integrating cervical cancer screening with HIV clinics, which may increase cancer screening among South African women. PMID:25654190

  11. Skeletal muscle metastases as the initial manifestation of an unknown primary lung cancer detected on F-18 fluorodeoxyglucose positron emission tomography/computed tomography.

    PubMed

    Agrawal, Kanhaiyalal; Bhattacharya, Anish; Singh, Navneet; Harisankar, Chidambaram Natarajan Balasubramanian; Mittal, Bhagwant Rai

    2013-01-01

    Skeletal muscle metastasis as the initial presentation of the unknown primary lung cancer is unusual. A 65-year-old male patient presented with pain and swelling of the right forearm. Fine needle aspiration of the swelling revealed metastatic squamous cell carcinoma. The patient underwent whole body F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to identify the site of the primary malignancy. The authors present PET/CT images showing FDG-avid metastases to the skeletal muscles along with a previously unknown primary tumor in the right lung, in a patient presenting with initial muscular symptoms without any pulmonary manifestations.

  12. [Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

    PubMed

    Shimada, Yasuhiro

    2016-04-01

    The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

  13. 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

  14. KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer.

    PubMed

    Yu, T; Chen, X; Zhang, W; Liu, J; Avdiushko, R; Napier, D L; Liu, A X; Neltner, J M; Wang, C; Cohen, D; Liu, C

    2016-02-01

    Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifen-induced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras(LSL-G12D/+);Klf4(fl/fl) mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.

  15. Community-Campus Partnership in Action: Lessons Learned from the DuPage County Patient Navigation Collaborative

    PubMed Central

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

    2015-01-01

    Background 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. Objectives To discuss the facilitating factors and lessons learned in forging the DPNC. Methods A patient navigation collaborative was formed to guide medically underserved women through diagnostic resolution and if necessary, treatment, following an abnormal breast or cervical cancer screening. Lessons Learned 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. Conclusions By highlighting the strategies that contributed to DPNC success, we envision the DPNC to serve as a feasible model for future health interventions. PMID:24859105

  16. JianPi JieDu Recipe Inhibits Epithelial-to-Mesenchymal Transition in Colorectal Cancer through TGF-β/Smad Mediated Snail/E-Cadherin Expression

    PubMed Central

    Liu, Xuan; Deng, Wanli; Chai, Ni; Feng, Yuanyuan; Zhou, Lihong; Sui, Hua; Li, Chunpu; Sun, Xiaoting

    2017-01-01

    JPJD was an ideal alternative traditional Chinese medicine compound in the prevention and treatment of CRC, but its underlying mechanisms has not been fully elucidated. In this study, we demonstrated in vitro that TGF-β-induced EMT promoted the invasion and metastasis of CRC cells, reduced the expression of E-cadherin, and elevated the expression of Vimentin. However, JPJD could inhibit the invasive and migratory ability of TGF-β-stimulated CRC cells in a concentration-dependent manner through increasing the expression of E-cadherin and repressing the expression of Vimentin, as well as the inhibition of TGF-β/Smad signaling pathway. Meanwhile, JPJD reduced the transcriptional activities of EMT-associated factors Snail and E-cadherin during the initiation of TGF-β-induced EMT. In vivo, the results demonstrated that JPJD can significantly inhibit the liver and lung metastasis of orthotopic CRC tumor in nude mice, as well as significantly prolonging the survival time of tumor-bearing in a dose-dependent manner. Additionally, JPJD can upregulate the expression of E-cadherin and Smad2/3 in the cytoplasm and downregulate the expression of Vimentin, p-Smad2/3, and Snail in the orthotopic CRC tumor tissues. In conclusions, our new findings provided evidence that JPJD could inhibit TGF-β-induced EMT in CRC through TGF-β/Smad mediated Snail/E-cadherin expression. PMID:28299321

  17. A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression

    PubMed Central

    Casado-Medrano, Victoria; Barrio-Real, Laura; García-Rostán, Ginesa; Baumann, Matti; Rocks, Oliver; Caloca, María J.

    2016-01-01

    β2-chimaerin is a Rac1-specific negative regulator and a candidate tumor suppressor in breast cancer but its precise function in mammary tumorigenesis in vivo is unknown. Here, we study for the first time the role of β2-chimaerin in breast cancer using a mouse model and describe an unforeseen role for this protein in epithelial cell-cell adhesion. We demonstrate that expression of β2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of β2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between β2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low β2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of β2-chimaerin as tumor suppressor and provide the first in vivo evidence of a dual function in breast cancer, suppressing tumor initiation but favoring tumor progression. PMID:27058424

  18. Differences among college women for breast cancer prevention acquired information-seeking, desired apps and texts, and daughter-initiated information to mothers.

    PubMed

    Kratzke, Cynthia; Amatya, Anup; Vilchis, Hugo

    2014-04-01

    The purpose of this study was to examine among college women acquired breast cancer prevention information-seeking, desired apps and texts, and information given to mothers. Using a cross-sectional study, a survey was administered to college women at a southwestern university. College women (n = 546) used the Internet (44 %) for active breast cancer prevention information-seeking and used the Internet (74 %), magazines (69 %), and television (59 %) for passive information receipt. Over half of the participants desired breast cancer prevention apps (54 %) and texts (51 %). Logistic regression analyses revealed predictors for interest to receive apps were ethnicity (Hispanic), lower self-efficacy, actively seeking online information, and older age and predictors for interest to receive texts were lower self-efficacy and higher university level. Eighteen percent of college women (n = 99) reported giving information to mothers and reported in an open-ended item the types of information given to mothers. Predictors for giving information to mothers were actively and passively seeking online information, breast self-exam practice, and higher university level. Screenings were the most frequent types of information given to mothers. Breast cancer prevention information using apps, texts, or Internet and daughter-initiated information for mothers should be considered in health promotion targeting college students or young women in communities. Future research is needed to examine the quality of apps, texts, and online information and cultural differences for breast cancer prevention sources.

  19. Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of the Breast Health Global Initiative consensus, 2010.

    PubMed

    Anderson, Benjamin O; Cazap, Eduardo; El Saghir, Nagi S; Yip, Cheng-Har; Khaled, Hussein M; Otero, Isabel V; Adebamowo, Clement A; Badwe, Rajendra A; Harford, Joe B

    2011-04-01

    The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate prioritisation of breast cancer control programmes within the framework of existing, functional health

  20. Studying the capability of different cancer hallmarks to initiate tumor growth using a cellular automaton simulation. Application in a cancer stem cell context.

    PubMed

    Monteagudo, Ángel; Santos, José

    2014-01-01

    We used a cellular automaton model for cancer growth simulation at cellular level, based on the presence of different cancer hallmarks acquired by the cells. The presence of the hallmarks in each of the cells determines cell mitotic and apoptotic behaviors. Depending on the presence of the different hallmarks and some associated parameters of the hallmarks, the system can evolve to different dynamics. We used the cellular automaton model to inspect the capability of different hallmarks to generate tumor growth in different conditions, using this study in a cancer stem cell context to analyze the capability of the hallmarks to tumor regrowth in different circumstances.

  1. Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist's initiative.

    PubMed

    Landsbergen, K M; Prins, J B; Brunner, H G; van Duijvendijk, P; Nagengast, F M; van Krieken, J H; Ligtenberg, M; Hoogerbrugge, N

    2012-06-01

    According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second CRC has been diagnosed before the age of 70 years, owing to the high risk of Lynch syndrome (MIPA). The aim of the present MIPAPS study was to investigate general distress and cancer-specific distress following MSI testing. From March 2007 to September 2009, 400 patients who had been tested for MSI after newly diagnosed CRC were recruited from 30 Dutch hospitals. Levels of general distress (SCL-90) and cancer-specific distress (IES) were assessed immediately after MSI result disclosure (T1) and 6 months later (T2). Response rates were 23/77 (30%) in the MSI-positive patients and 58/323 (18%) in the MSI-negative patients. Levels of general distress and cancer-specific distress were moderate. In the MSI-positive group, 27% of the patients had high general distress at T1 versus 18% at T2 (p = 0.5), whereas in the MSI-negative group, these percentage were 14 and 18% (p = 0.6), respectively. At T1 and T2, cancer-specific distress rates in the MSI-positive group and MSI-negative group were 39 versus 27% (p = 0.3) and 38 versus 36% (p = 1.0), respectively. High levels of general distress were correlated with female gender, low social support and high perceived cancer risk. Moderate levels of distress were observed after MSI testing, similar to those found in other patients diagnosed with CRC. Immediately after result disclosure, high cancer-specific distress was observed in 40% of the MSI-positive patients.

  2. The Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Initially Clinically Node-Negative Breast Cancer after Neoadjuvant Chemotherapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Geng, Chong; Chen, Xiao; Pan, Xiaohua; Li, Jiyu

    2016-01-01

    Background With the increased use of neoadjuvant chemotherapy (NAC) in breast cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly important. In this study, we aimed to evaluate the feasibility and accuracy of SLNB for initially clinically node-negative breast cancer after NAC by conducting a systematic review and meta-analysis. Methods We searched PubMed, Embase, and the Cochrane Library from January 1, 1993 to November 30, 2015 for studies on initially clinically node-negative breast cancer patients who underwent SLNB after NAC followed by axillary lymph node dissection (ALND). Results A total of 1,456 patients from 16 studies were included in this review. The pooled identification rate (IR) for SLNB was 96% [95% confidence interval (CI): 95%-97%], and the false negative rate (FNR) was 6% (95% CI: 3%-8%). The pooled sensitivity, negative predictive value (NPV) and accuracy rate (AR) were 94% (95% CI: 92%-97%, I2 = 27.5%), 98% (95% CI: 98%-99%, I2 = 42.7%) and 99% (95% CI: 99%-100%, I2 = 32.6%), respectively. In the subgroup analysis, no significant differences were found in either the IR of an SLNB when different mapping methods were used (P = 0.180) or in the FNR between studies with and without immunohistochemistry (IHC) staining (P = 0.241). Conclusion Based on current evidence, SLNB is technically feasible and accurate enough for axillary staging in initially clinically node-negative breast cancer patients after NAC. PMID:27606623

  3. Accuracy of Computed Tomography for Predicting Pathologic Nodal Extracapsular Extension in Patients With Head-and-Neck Cancer Undergoing Initial Surgical Resection

    SciTech Connect

    Prabhu, Roshan S.; Magliocca, Kelly R.; Hanasoge, Sheela; Aiken, Ashley H.; Hudgins, Patricia A.; Hall, William A.; Chen, Susie A.; Eaton, Bree R.; Higgins, Kristin A.; Saba, Nabil F.; Beitler, Jonathan J.

    2014-01-01

    Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initial surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.

  4. Tumeur du sein révélée par une métastase gastrique découverte fortuitement

    PubMed Central

    Moussaoui, Aziz El; Assi, Fadi; Bental, Abdeslam

    2016-01-01

    Les métastases gastriques du cancer du sein sont rares, et leur découverte reste difficile, devant la symptomatologie qui est souvent non spécifique ou même absente. Nous rapportons une observation originale d'un carcinome canalaire du sein révélé par une métastase gastrique découverte de façon fortuite. PMID:28154673

  5. Early initiation of salvage hormone therapy influences survival in patients who failed initial radiation for locally advanced prostate cancer: A secondary analysis of RTOG protocol 86-10

    SciTech Connect

    Shipley, William U. . E-mail: wshipley@partners.org; DeSilvio, Michelle; Pilepich, Michael V.; Roach, Mack; Wolkov, Harvey B.; Sause, William T.; Rubin, Philip; Lawton, Colleen A.

    2006-03-15

    Purpose: We examined overall and disease-specific survival outcomes both from the time of initial treatment and from the start of salvage hormone therapy (HT), by the extent of disease progression at the time salvage HT was started in patients treated on RTOG Protocol 86-10. Methods and Materials: With a median follow-up of 9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall survival (OVS) and disease-specific survival (DSS) were compared by the extent of disease progression at the time salvage HT was started. Results: For those patients with distant metastases (DM) present at the start of salvage HT, the OVS and DSS were significantly reduced when compared with those with DM absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8 years, 38% vs. 65%). A statistically significant increase in DSS was observed among the 143 patients with DM absent when patients with prostate-specific antigen (PSA) less than 20 were compared with those with PSA greater than 20 at the time salvage HT was started. Conclusions: The DSS and the OVS of the relapsed patient are decreased in those with more extensive disease at the time of salvage HT. However, because this protocol could not evaluate the effect of posttreatment PSA velocity on outcomes, which is likely a better predictor of long-term success with salvage HT, these results cannot be taken to demonstrate that early salvage HT in patients with long posttreatment PSA doubling times is necessary for longer survival.

  6. COLORECTAL CANCER IN RELATION TO POSTMENOPAUSAL ESTROGEN AND ESTROGEN PLUS PROGESTIN IN THE WOMEN'S HEALTH INITIATIVE CLINICAL TRIAL AND OBSERVATIONAL STUDY

    PubMed Central

    Prentice, Ross L.; Pettinger, Mary; Beresford, Shirley A. A.; Wactawski-Wende, Jean; Hubbell, F. Allan; Stefanick, Marcia L.; Chlebowski, Rowan T.

    2009-01-01

    Background Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and Methods Postmenopausal women aged 50−79 at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were post-hysterectomy from the observational study and clinical trial respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. Results Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53 to 1.20) for estrogen and 1.15 (0.74 to 1.79) for estrogen plus progestin, with respectively 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. Conclusion Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7−8 years of treatment and follow-up. PMID:19423530

  7. Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study

    PubMed Central

    James, Benjamin; Nagar, Sapna; Kaplan, Sharone; Seng, Vanessa; Ahsan, Habibul; Angelos, Peter; Kaplan, Edwin L.; Guerrero, Marlon A.; Kuo, Jennifer H.; Lee, James A.; Mitmaker, Elliot J.; Moalem, Jacob; Ruan, Daniel T.; Shen, Wen T.; Grogan, Raymon H.

    2015-01-01

    Background: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. Methods: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. Results: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. Conclusion: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing. PMID:26431811

  8. Uterine Cancer

    MedlinePlus

    ... most common cancer in women in the United States and it is the most commonly diagnosed gynecologic cancer. Fallopian Tubes Ovaries Uterus Cervix Vagina Vulva www. cdc. gov/ cancer/ knowledge 800-CDC-INFO Inside Knowledge is an initiative ...

  9. Initial Evaluation of [18F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer

    PubMed Central

    Szabo, Zsolt; Mena, Esther; Rowe, Steven P.; Plyku, Donika; Nidal, Rosa; Eisenberger, Mario A.; Antonarakis, Emmanuel S.; Fan, Hong; Dannals, Robert F.; Chen, Ying; Mease, Ronnie C.; Vranesic, Melin; Bhatnagar, Akrita; Sgouros, George; Cho, Steve Y.; Pomper, Martin G.

    2015-01-01

    Purpose Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [18F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Procedures Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. Results No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUVmax up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [18F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi). Conclusions [18F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [18F]DCFPyL is similar to that from other PET radiotracers. PMID:25896814

  10. Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women’s Health Initiative: A Longitudinal Study from the United States

    PubMed Central

    Stefanick, Marcia L.; Johnson, Karen C.; Lane, Dorothy S.; LeBlanc, Erin S.; Prentice, Ross; Rohan, Thomas E.; Snively, Beverly M.; Vitolins, Mara; Zaslavsky, Oleg; Soerjomataram, Isabelle; Anton-Culver, Hoda

    2016-01-01

    Background High body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women. Methods and Findings Participants from the observational study of the Women’s Health Initiative (WHI) with BMI information from at least three occasions during follow-up, free of cancer at baseline, and with complete covariate information were included (n = 73,913). Trajectories of BMI across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years, which take into account the degree of overweight and obesity over time (a measure similar to pack-years of cigarette smoking), were calculated using predicted BMIs. Cox proportional hazard models were applied to determine the cancer risk associated with overweight and obesity duration. In secondary analyses, the influence of important effect modifiers and confounders, such as smoking status, postmenopausal hormone use, and ethnicity, was assessed. A longer duration of overweight was significantly associated with the incidence of all obesity-related cancers (hazard ratio [HR] per 10-y increment: 1.07, 95% CI 1.06–1.09). For postmenopausal breast and endometrial cancer, every 10-y increase in adulthood overweight duration was associated with a 5% and 17% increase in risk, respectively. On adjusting for intensity of overweight, these figures rose to 8% and 37%, respectively. Risks of postmenopausal breast and endometrial cancer related to overweight duration were much

  11. Circles of Care: Development and Initial Evaluation of a Peer Support Model for African Americans with Advanced Cancer

    ERIC Educational Resources Information Center

    Hanson, Laura C.; Armstrong, Tonya D.; Green, Melissa A.; Hayes, Michelle; Peacock, Stacie; Elliot-Bynum, Sharon; Goldmon, Moses V.; Corbie-Smith, Giselle; Earp, Jo Anne

    2013-01-01

    Peer support interventions extend care and health information to underserved populations yet rarely address serious illness. Investigators from a well-defined academic-community partnership developed and evaluated a peer support intervention for African Americans facing advanced cancer. Evaluation methods used the Reach, Efficacy, Adoption,…

  12. Nitric Oxide Inhibits Hetero-adhesion of Cancer Cells to Endothelial Cells: Restraining Circulating Tumor Cells from Initiating Metastatic Cascade

    NASA Astrophysics Data System (ADS)

    Lu, Yusheng; Yu, Ting; Liang, Haiyan; Wang, Jichuang; Xie, Jingjing; Shao, Jingwei; Gao, Yu; Yu, Suhong; Chen, Shuming; Wang, Lie; Jia, Lee

    2014-03-01

    Adhesion of circulating tumor cells (CTCs) to vascular endothelial bed becomes a crucial starting point in metastatic cascade. We hypothesized that nitric oxide (NO) may prevent cancer metastasis from happening by its direct vasodilation and inhibition of cell adhesion molecules (CAMs). Here we show that S-nitrosocaptopril (CAP-NO, a typical NO donor) produced direct vasorelaxation that can be antagonized by typical NO scavenger hemoglobin and guanylate cyclase inhibitor. Cytokines significantly stimulated production of typical CAMs by the highly-purified human umbilical vein endothelial cells (HUVECs). CAP-NO inhibited expression of the stimulated CAMs (particularly VCAM-1) and the resultant hetero-adhesion of human colorectal cancer cells HT-29 to the HUVECs in a concentration-dependent manner. The same concentration of CAP-NO, however, did not significantly affect cell viability, cell cycle and mitochondrial membrane potential of HT-29, thus excluding the possibility that inhibition of the hetero-adhesion was caused by cytotoxicity by CAP-NO on HT-29. Hemoglobin reversed the inhibition of CAP-NO on both the hetero-adhesion between HT-29 and HUVECs and VCAM-1 expression. These data demonstrate that CAP-NO, by directly releasing NO, produces vasorelaxation and interferes with hetero-adhesion of cancer cells to vascular endothelium via down-regulating expression of CAMs. The study highlights the importance of NO in cancer metastatic prevention.

  13. Lymphome malin non hodgkinien du cavum: protocoles thérapeutiques et facteurs pronostiques

    PubMed Central

    Ouraini, Saloua; Nakkabi, Ismail; Benariba, Fouad

    2015-01-01

    Le lymphome malin non hodgkinien est une entité histologique rare parmi les cancers du cavum, la plupart des tumeurs du nasopharynx étant des carcinomes indifférenciés ou Undifferencied Carcinoma of Nasopharyngeal Type (UCNT); Il pose souvent un problème de diagnostic positif clinique et histologique. La symptomatologie est généralement peu spécifique et la démarche étiologique repose sur la biopsie du cavum faite à l'examen endoscopique avec examen immuno-histochimique. Nous rapportons le cas d'un lymphome non hodgkinien avec atteinte du nasopharynx, l'analyse anatomopathologique est en faveur d'un lymphome malin non hodgkinien de phénotype B. Les aspects cliniques, radiologiques, histologiques et thérapeutiques sont décrits. PMID:26889334

  14. Supportive care after curative treatment for breast cancer (survivorship care): resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement.

    PubMed

    Ganz, Patricia A; Yip, Cheng Har; Gralow, Julie R; Distelhorst, Sandra R; Albain, Kathy S; Andersen, Barbara L; Bevilacqua, Jose Luiz B; de Azambuja, Evandro; El Saghir, Nagi S; Kaur, Ranjit; McTiernan, Anne; Partridge, Ann H; Rowland, Julia H; Singh-Carlson, Savitri; Vargo, Mary M; Thompson, Beti; Anderson, Benjamin O

    2013-10-01

    Breast cancer survivors may experience long-term treatment complications, must live with the risk of cancer recurrence, and often experience psychosocial complications that require supportive care services. In low- and middle-income settings, supportive care services are frequently limited, and program development for survivorship care and long-term follow-up has not been well addressed. As part of the 5th Breast Health Global Initiative (BHGI) Global Summit, an expert panel identified nine key resources recommended for appropriate survivorship care, and developed resource-stratified recommendations to illustrate how health systems can provide supportive care services for breast cancer survivors after curative treatment, using available resources. Key recommendations include health professional education that focuses on the management of physical and psychosocial long-term treatment complications. Patient education can help survivors transition from a provider-intense cancer treatment program to a post-treatment provider partnership and self-management program, and should include: education on recognizing disease recurrence or metastases; management of treatment-related sequelae, and psychosocial complications; and the importance of maintaining a healthy lifestyle. Increasing community awareness of survivorship issues was also identified as an important part of supportive care programs. Other recommendations include screening and management of psychosocial distress; management of long-term treatment-related complications including lymphedema, fatigue, insomnia, pain, and women's health issues; and monitoring survivors for recurrences or development of second primary malignancies. Where possible, breast cancer survivors should implement healthy lifestyle modifications, including physical activity, and maintain a healthy weight. Health professionals should provide well-documented patient care records that can follow a patient as they transition from active treatment

  15. Cri du Chat syndrome.

    PubMed

    Cerruti Mainardi, Paola

    2006-09-05

    The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-). The incidence ranges from 1:15,000 to 1:50,000 live-born infants. The main clinical features are a high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Malformations, although not very frequent, may be present: cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Molecular cytogenetic analysis has allowed a cytogenetic and phenotypic map of 5p to be defined, even if results from the studies reported up to now are not completely in agreement. Genotype-phenotype correlation studies showed a clinical and cytogenetic variability. The identification of phenotypic subsets associated with a specific size and type of deletion is of diagnostic and prognostic relevance. Specific growth and psychomotor development charts have been established. Two genes, Semaphorin F (SEMAF) and delta-catenin (CTNND2), which have been mapped to the "critical regions", are potentially involved in cerebral development and their deletion may be associated with mental retardation in CdCS patients. Deletion of the telomerase reverse transcriptase (hTERT) gene, localised to 5p15.33, could contribute to the phenotypic changes in CdCS. The critical regions were recently refined by using array comparative genomic hybridisation. The cat-like cry critical region was further narrowed using quantitative polymerase chain reaction (PCR) and three candidate genes were characterised in this region. The diagnosis is based on typical clinical manifestations. Karyotype analysis and, in doubtful cases, FISH analysis will confirm the diagnosis. There is no specific therapy for CdCS but early rehabilitative and educational interventions improve the prognosis and considerable progress has been made

  16. Cri du Chat syndrome

    PubMed Central

    Cerruti Mainardi, Paola

    2006-01-01

    The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-). The incidence ranges from 1:15,000 to 1:50,000 live-born infants. The main clinical features are a high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Malformations, although not very frequent, may be present: cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Molecular cytogenetic analysis has allowed a cytogenetic and phenotypic map of 5p to be defined, even if results from the studies reported up to now are not completely in agreement. Genotype-phenotype correlation studies showed a clinical and cytogenetic variability. The identification of phenotypic subsets associated with a specific size and type of deletion is of diagnostic and prognostic relevance. Specific growth and psychomotor development charts have been established. Two genes, Semaphorin F (SEMAF) and δ-catenin (CTNND2), which have been mapped to the "critical regions", are potentially involved in cerebral development and their deletion may be associated with mental retardation in CdCS patients. Deletion of the telomerase reverse transcriptase (hTERT) gene, localised to 5p15.33, could contribute to the phenotypic changes in CdCS. The critical regions were recently refined by using array comparative genomic hybridisation. The cat-like cry critical region was further narrowed using quantitative polymerase chain reaction (PCR) and three candidate genes were characterised in this region. The diagnosis is based on typical clinical manifestations. Karyotype analysis and, in doubtful cases, FISH analysis will confirm the diagnosis. There is no specific therapy for CdCS but early rehabilitative and educational interventions improve the prognosis and considerable progress has been made in

  17. Applications attract DuPont

    SciTech Connect

    Rotman, D.

    1996-08-07

    Scientists at DuPont say they have demonstrated the first chemical processing application for high-temperature superconducting (HTS) magnets. DuPont says the work, which uses a HTS magnet to separate mineral contaminants from kaolin, points to the feasibility of a range of HTS applications in industrial processing, including those involving polymerization. DuPont`s success comes after 10 years of work to commercialize high-temperature superconductors. And while superconductors have lost much of their luster since the late 1980s, the company says it is still bullish on their prospects. {open_quotes}At the moment, there`s no real market for superconductors,{close_quotes} says Alan Lauder, general manager/superconductivity. But, he says, several potentially lucrative applications could be commercialized within the next several years.

  18. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade.

    PubMed

    Momozono, Hiroyuki; Miyake, Hideaki; Tei, Hiromoto; Harada, Ken-Ichi; Fujisawa, Masato

    2016-05-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC.

  19. L'Aventure du LHC

    SciTech Connect

    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.

  20. Transforming Big Data into cancer-relevant insight: An initial, multi-tier approach to assess reproducibility and relevance | Office of Cancer Genomics

    Cancer.gov

    The Cancer Target Discovery and Development (CTD^2) Network was established to accelerate the transformation of "Big Data" into novel pharmacological targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding.

  1. A Tumor initiating cell-enriched prognostic signature for HER2+:ERα- breast cancer; rationale, new features, controversies and future directions.

    PubMed

    Liu, Jeff C; Egan, Sean E; Zacksenhaus, Eldad

    2013-08-01

    The high intra- and inter-tumor heterogeneity of many types of cancers, including breast cancer (BC), poses great challenge to development of subtype-specific prognosis. In BC, the classification of tumors as either ERα+ (Luminal A and Luminal B), HER2+ (ERα+ or ERα-) or triple-negative (TNBC)(Basal-like, claudin-low) guides both prognostication and therapy. Indeed, prognostic signatures for ERα+ BC are being incorporated into clinical use. However, these signatures distinguish between luminal A (low risk) and Luminal B (high risk) BC; signatures that identify low/high risk patients with luminal B BC are yet to be developed. Likewise, no signature is in clinical use for HER2+ or TNBC. The major obstacles to development of robust signatures stem from diversity of BC, clonal evolution and heterogeneity within each subtype. We have recently generated a prognostic signature for HER2+:ERα- BC based on the identification of genes that were differentially expressed in a tumor-initiating cell (TIC)-enriched fraction versus non-TIC fraction from a mouse model of HER2+ BC (MMTV-Hers/Neu). Here we describe the rationale behind development of this prognosticator, and present new features of the signature, including elevated PI3K pathway activity and low TNFalpha and IFNgamma signaling in high-risk tumors. In addition, we address controversies in the field such as whether random gene expression signatures significantly associate with cancer outcome. Finally, we suggest a guideline for development of prognostic signatures and discuss future directions.

  2. Targeting cancer initiating cells by promoting cell differentiation and restoring chemosensitivity via dual inactivation of STAT3 and Src activity using an active component of Antrodia cinnamomea mycelia

    PubMed Central

    Chan, Ik-On; Chen, Chin-Chu; Sheu, Sen-Je; Lin, Ting-wei; Chou, Shiu-Huey; Liu, Chung-Ji; Lee, Te-Chang; Lo, Jeng-Fan

    2016-01-01

    Cancer initiating cells (CICs) represent a subpopulation of cancer cells, which are responsible for tumor growth and resistance to chemotherapy. Herein, we first used a cell-based aldehyde dehydrogenase (ALDH) activity assay to identify that YMGKI-2 (also named as Ergone), an active component purified from Antrodia cinnamomea Mycelia extract (ACME), effectively abrogated the ALDH activity and abolished the CICs in head and neck squamous cell carcinoma cells (HNSCCs). Consequently, YMGKI-2 treatment suppressed self-renewal ability and expression of stemness signature genes (Oct-4 and Nanog) of sphere cells with enriched CICs. Moreover, YMGKI-2 treated sphere cells displayed reduction of CICs properties and promotion of cell differentiation, but not significant cytotoxicity. YMGKI-2 treatment also attenuated the tumorigenicity of HNSCC cells in vivo. Mechanistically, treatment of YMGKI-2 resulted in inactivation of STAT3 and Src. Lastly, combinatorial treatments with YMGKI-2 and standard chemotherapeutic drugs (cisplatin or Fluorouracil) restored the chemosensivity on sphere cells and cisplatin-resistant HNSCC cells. Together, we demonstrate that YMGKI-2 treatment effectively induces differentiation and reduces tumorigenicity of CICs. Further, combined treatment of YMGKI-2 and conventional chemotherapy can overcome chemoresistance. These results suggest that YMGKI-2 treatment may be used to improve future clinical responses in head and neck cancer treatment through targeting CICs. PMID:27682875

  3. Targeting Prostate Cancer with Multifunctional Nanoparticles

    DTIC Science & Technology

    2015-10-01

    4 Fig 1. Characterization of three prostate cancer cell lines by western blot. COXIV is used as a loading control...characterize our three prostate cancer cell lines , LNCaP, DU145 and PC3, which are being used in this project. We showed that prostate specific antigen...PSA) is expressed in the LNCaP cells, but absent in the DU145 cells whereas AMACR (P504S) is expressed in all prostate cancer cell lines (Fig 1

  4. Facial Layer-by-Layer Engineering of Upconversion Nanoparticles for Gene Delivery: Near-Infrared-Initiated Fluorescence Resonance Energy Transfer Tracking and Overcoming Drug Resistance in Ovarian Cancer.

    PubMed

    Lin, Min; Gao, Yan; Diefenbach, Thomas J; Shen, Jacson K; Hornicek, Francis J; Park, Yong Il; Xu, Feng; Lu, Tian Jian; Amiji, Mansoor; Duan, Zhenfeng

    2017-03-08

    Development of multidrug resistance (MDR) contributes to the majority of treatment failures in clinical chemotherapy. We report facial layer-by-layer engineered upconversion nanoparticles (UCNPs) for near-infrared (NIR)-initiated tracking and delivery of small interfering RNA (siRNA) to enhance chemotherapy efficacy by silencing the MDR1 gene and resensitizing resistant ovarian cancer cells to drug. Layer-by-layer engineered UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic interaction. The delivery vehicle enhances MDR1-siRNA cellular uptake, protects MDR1-siRNA from nuclease degradation, and promotes endosomal escape for silencing the MDR gene. The intrinsic photon upconversion of UCNPs provides an unprecedented opportunity for monitoring intracellular attachment and release of MDR1-siRNA by NIR-initiated fluorescence resonance energy transfer occurs between donor UCNPs and acceptor fluorescence dye-labeled MDR1-siRNA. Enhanced chemotherapeutic efficacy in vitro was demonstrated by cell viability assay. The developed delivery vehicle holds great potential in delivery and imaging-guided tracking of therapeutic gene targets for effective treatment of drug-resistant cancers.

  5. About the RAS Initiative

    Cancer.gov

    The RAS Initiative, a "hub and spoke" model, connects researchers to better understand and target the more than 30% of cancers driven by mutations in RAS genes. Includes oversight and contact information.

  6. RAS Initiative - Community Outreach

    Cancer.gov

    Through community and technical collaborations, workshops and symposia, and the distribution of reference reagents, the RAS Initiative seeks to increase the sharing of knowledge and resources essential to defeating cancers caused by mutant RAS genes.

  7. 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.

  8. 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.

  9. Poumon du puisatier

    PubMed Central

    Elidrissi, Amal Moustarhfir; Zaghba, Nahid; Benjelloun, Hanane; Yassine, Najiba

    2016-01-01

    Le puisatier a pour profession le creusement et l'entretien des puits pour fournir de l'eau. Il est au contact de divers minerais, particulièrement la silice, particule qui présente un risque certain de développement des maladies pulmonaires connues sous le nom de silicose. Le but de notre travail est de préciser le profil épidémiologique, clinique, radiologique et évolutif des patients puisatiers silicotiques. C'est une étude rétrospective concernant 54 cas de puisatiers ayant une silicose, colligés au service des maladies respiratoires du CHU Ibn Rochd de Casablanca, de Mars 1997 à Janvier 2016. Tous les malades étaient des puisatiers, de sexe masculin, avec une moyenne d'âge de 50 ans. Le tabagisme était retrouvé dans 36 cas et un antécédent de tuberculose était noté dans huit cas. La radiographie thoracique retrouvait des grandes opacités dans 39 cas, des petites opacités dans 15 cas, et un épaississement des septats dans 11 cas. Ce tableau de silicose s'était compliqué d'une surinfection bactérienne dans 37% des cas, d' un pneumothorax dans 4% des cas et d'une tuberculose dans 20% des cas. La prise en charge thérapeutique était celle des complications. La déclaration de la maladie professionnelle et de l'indemnisation était faite. L'évolution était bonne dans 12 cas, stationnaire dans 17 cas et mauvaise dans 16 cas. La silicose est une pneumoconiose fréquente chez les puisatiers. Elle retentit sur la fonction respiratoire. Nous soulignons l'association fréquente de tuberculose et nous insistons sur la prévention qui reste le meilleur traitement. PMID:28292119

  10. Excretory urography and computed tomography in the initial evaluation of patients with cervical cancer: are both examinations necessary

    SciTech Connect

    Goldman, S.M.; Fishman, E.K.; Rosenshein, N.B.; Gatewood, O.M.B.; Siegelman, S.S.

    1984-11-01

    One hundred ten patients with carcinoma of the cervix were studied to determine if both excretory urography and computed tomography are needed for routine evaluation. Computed tomography gave more information in 25 patients and the excretory urogram was more informative in 10 patients. Thirty-five hydroureters were detected by computed tomography, whereas excretory urography identified 21. It was concluded that routine use of both examinations is not indicated. Excretory urography is currently sufficient in evaluation of stage I and IIA lesions, while computed tomography obviates excretory urography in patients with advanced cervical cancer (IIB-IVB).

  11. Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells

    PubMed Central

    Gafar, Ahmed A.; Draz, Hossam M.; Goldberg, Alexander A.; Bashandy, Mohamed A.; Bakry, Sayed; Khalifa, Mahmoud A.; AbuShair, Walid; Titorenko, Vladimir I.

    2016-01-01

    Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells. LCA induced ER stress-related proteins, such as CCAAT-enhancer-binding protein homologous protein (CHOP), and the phosphorylation of eukaryotic initiation factor 2-alpha (p-eIF2α) and c-Jun N-terminal kinases (p-JNK) in both cancer cell-types. The p53 upregulated modulator of apoptosis (PUMA) and B cell lymphoma-like protein 11 (BIM) levels were decreased at overtly toxic LCA concentrations, although PUMA levels increased at lower LCA concentrations in both cell lines. LCA induced autophagy-related conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3BI–LC3BII), and autophagy-related protein ATG5 in PC-3 cells, but not in autophagy-deficient DU-145 cells. LCA (>10 µM) increased levels of reactive oxygen species (ROS) concentration-dependently in PC-3 cells, whereas ROS levels were not affected in DU-145 cells. Salubrinal, an inhibitor of eIF2α dephosphorylation and ER stress, reduced LCA-induced CHOP levels slightly in PC-3, but not DU-145 cells. Salubrinal pre-treatment increased the cytotoxicity of LCA in PC-3 and DU-145 cells and resulted in a statistically significant loss of cell viability at normally non-toxic concentrations of LCA. The late-stage autophagy inhibitor bafilomycin A1 exacerbated LCA toxicity at subtoxic LCA concentrations in PC-3 cells. The antioxidant α-tocotrienol strongly inhibited the toxicity of LCA in PC-3 cells, but not in DU-145 cells. Collectively

  12. Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells.

    PubMed

    Gafar, Ahmed A; Draz, Hossam M; Goldberg, Alexander A; Bashandy, Mohamed A; Bakry, Sayed; Khalifa, Mahmoud A; AbuShair, Walid; Titorenko, Vladimir I; Sanderson, J Thomas

    2016-01-01

    Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells. LCA induced ER stress-related proteins, such as CCAAT-enhancer-binding protein homologous protein (CHOP), and the phosphorylation of eukaryotic initiation factor 2-alpha (p-eIF2α) and c-Jun N-terminal kinases (p-JNK) in both cancer cell-types. The p53 upregulated modulator of apoptosis (PUMA) and B cell lymphoma-like protein 11 (BIM) levels were decreased at overtly toxic LCA concentrations, although PUMA levels increased at lower LCA concentrations in both cell lines. LCA induced autophagy-related conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3BI-LC3BII), and autophagy-related protein ATG5 in PC-3 cells, but not in autophagy-deficient DU-145 cells. LCA (>10 µM) increased levels of reactive oxygen species (ROS) concentration-dependently in PC-3 cells, whereas ROS levels were not affected in DU-145 cells. Salubrinal, an inhibitor of eIF2α dephosphorylation and ER stress, reduced LCA-induced CHOP levels slightly in PC-3, but not DU-145 cells. Salubrinal pre-treatment increased the cytotoxicity of LCA in PC-3 and DU-145 cells and resulted in a statistically significant loss of cell viability at normally non-toxic concentrations of LCA. The late-stage autophagy inhibitor bafilomycin A1 exacerbated LCA toxicity at subtoxic LCA concentrations in PC-3 cells. The antioxidant α-tocotrienol strongly inhibited the toxicity of LCA in PC-3 cells, but not in DU-145 cells. Collectively

  13. Rupture sous-cutanée du tendon long extenseur du pouce: à propos de 5 cas

    PubMed Central

    Abdelillah, Rachid; Abbassi, Najib; Erraji, Moncef; Abdeljawad, Najib; Yacoubi, Hicham; Daoudi, Abdelkrim

    2014-01-01

    La rupture spontanée du muscle long extenseur du pouce (EPL) du tendon au niveau du poignet est rare et principalement rapportés après fracture du radius distal à tubercule de Lister, dans la synovite, ténosynovite ou la polyarthrite rhumatoïde. Nous rapportons 5 cas de rupture spontanée du tendon long extenseur du pouce, traités par une greffe ou un transfert tendineux. PMID:25317233

  14. Regulatory role of zinc on the biokinetics and biodistribution of (65)Zn during the initiation of experimentally induced colon cancer.

    PubMed

    Chadha, Vijayta Dani; Goel, Ajay; Dhawan, D

    2011-01-01

    The present study was conducted to evaluate the kinetics of zinc utilization during the formation of colon carcinoma in an animal model of colon carcinogenesis. The rats were segregated into 4 groups: untreated control, 1,2-dimethylhydrazine (DMH) treated, zinc treated, and DMH+zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 wk. Zinc (in the form of zinc sulphate) was supplemented at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of study. Whole body (65)Zn kinetics followed two-compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The Tb(1) component showed a significant elevation while the Tb(2) component was significantly diminished in DMH-treated rats, which, however, got normalized following zinc supplementation. The biodistribution and subcellular distribution of (65)Zn was significantly affected in DMH-treated rats when compared to normal control rats. However, zinc significantly reversed the altered (65)Zn uptake in different organs and various fractions of colon. The present study for the first time demonstrated a faster mobilization of zinc during initiation of experimentally induced colon carcinoma and provides a physiological basis for the role of zinc in colon tumorigenesis.

  15. Cytochrome P450 1B1, a novel chemopreventive target for benzo[a]pyrene-initiated human esophageal cancer.

    PubMed

    Wen, Xia; Walle, Thomas

    2007-02-08

    Esophageal cancer is common worldwide, with poor prognosis. Smoking, including exposure to polyaromatic hydrocarbons like benzo[a]pyrene (BaP), is a major risk factor. In human esophageal HET-1A cells, we found that time-dependent BaP-DNA binding was associated with upregulation of CYP1B1, but not CYP1A1, mRNA and protein. The dietary flavonoid 5,7-dimethoxyflavone significantly inhibited BaP-DNA binding and down-regulated BaP-induced CYP1B1 mRNA and protein. 3',4'-Dimethoxyflavone was an even more potent inhibitor of CYP1B1 expression, while resveratrol had no effect. Thus, dietary methoxylated flavones inhibited BaP-induced CYP1B1 transcription in a cell-specific manner and hold promise as chemopreventive agents in esophageal carcinogenesis.

  16. Initial Study of Radiological and Clinical Efficacy Radioembolization Using 188Re-Human Serum Albumin (HSA) Microspheres in Patients with Progressive, Unresectable Primary or Secondary Liver Cancers

    PubMed Central

    Nowicki, Mirosław L.; Ćwikła, Jarosław B.; Sankowski, Artur J.; Shcherbinin, Sergey; Grimes, Josh; Celler, Anna; Buscombe, John R.; Bator, Andrzej; Pech, Maciej; Mikołajczak, Renata; Pawlak, Dariusz

    2014-01-01

    Background The aim of this initial study was to evaluate the clinical and radiological effectiveness of radioembolization (RE) using 188Re-Human Serum Albumin (HSA) microspheres in patients with advanced, progressive, unresectable primary or secondary liver cancers, not suitable to any other form of therapy. Material/Methods Overall, we included 13 patients with 20 therapy sessions. Clinical and radiological responses were assessed at 6 weeks after therapy, and then every 3 months. The objective radiological response was classified according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 by sequential MRI. Adverse events were evaluated using NCI CTCAE v.4.03. Results There were 4 patients with hepatocellular carcinoma (HCC), 6 with metastatic colorectal cancer (mCRC), 2 with neuroendocrine carcinoma (NEC), and 1 patient with ovarian carcinoma. Mean administered activity of 188Re HSA was 7.24 GBq (range 3.8–12.4) A high microspheres labeling efficacy of over 97±2.1% and low urinary excretion of 188Re (6.5±2.3%) during first 48-h follow-up. Median overall survival (OS) for all patients was 7.1 months (CI 6.2–13.3) and progression-free survival (PFS) was 5.1 months (CI 2.4–9.9). In those patients who had a clinical partial response (PR), stable disease (SD), and disease progression (DP) as assessed 6 weeks after therapy, the median OS was 9/5/4 months, respectively, and PFS was 5/2/0 months, respectively. The treatment adverse events (toxicity) were at an acceptable level. Initially and after 6 weeks, the CTC AE was grade 2, while after 3 months it increased to grade 3 in 4 subjects. This effect was mostly related to rapid cancer progression in this patient subgroup. Conclusions The results of this preliminary study indicate that RE using 188Re HSA is feasible and a viable option for palliative therapy in patients with extensive progressive liver cancer. It was well tolerated by most patients, with a low level of toxicity during the 3 months of

  17. Cancer

    MedlinePlus

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

  18. New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in 3D cancer spheroids induced by purified colon tumor-initiating cells

    PubMed Central

    2010-01-01

    Background Growing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs) responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133high/CD44high fraction of colon cancer cells is different from their bulk counterparts at the functional, morphological and genomic levels. In contrast to the majority of colon cancer cells expressing moderate levels of CD133, CD44 and CD166, cells with a high combined expression of CD133 and CD44 possessed several characteristic stem cell features, including profound self-renewal capacity in vivo and in vitro, and the ability to give rise to different cell phenotypes. The present study was undertaken for two aims: a) to determine stem cell-related genomic characteristics of floating 3D multicellular spheroids induced by CD133high/CD44high colon cancer cells; and b) to evaluate CSC-specific alterations induced by new-generation taxoid SB-T-1214. Results Selected CSC phenotype was isolated from three independent invasive colon cancer cell lines, HCT116, HT29 and DLD-1. A stem cell-specific PCR array assay (SABiosciences) revealed that colonospheres induced by purified CD133high/CD44high expressing cells display profound up-regulation of stem cell-related genes in comparison with their bulk counterparts. The FACS analysis has shown that the 3D colonospheres contained some minority cell populations with high levels of expression of Oct4, Sox2, Nanog and c-Myc, which are essential for stem cell pluripotency and self-renewal. Single administration of the SB-T-1214 at concentration 100 nM-1 μM for 48 hr not only induced growth inhibition and apoptotic cell death in these three types of colon cancer spheroids in 3D culture, but also mediated massive inhibition of the stem cell-related genes and significant down-regulation of the pluripotency gene expression. PCR array and FACS data were confirmed

  19. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

    PubMed

    Saloman, Jami L; Albers, Kathryn M; Li, Dongjun; Hartman, Douglas J; Crawford, Howard C; Muha, Emily A; Rhim, Andrew D; Davis, Brian M

    2016-03-15

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

  20. Readministration of EGFR Tyrosine Kinase Inhibitor in Non-small Cell Lung Cancer Patients after Initial Failure, What Affects its Efficacy?

    PubMed Central

    Zhao, Ze-Rui; li, Wei; Long, Hao

    2014-01-01

    Few therapeutic options are available for non-small cell lung cancer (NSCLC) after failure to primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Since TKI rechallenge is one of the most common salvage approaches in clinical practice, we sought to identify the independent factors that associated with 2nd progression progression-free survival (PFS) and overall survival (OS). Seventy-two consecutive EGFR-mutated NSCLC patients with TKI retreatment after initial failure were retrospectively analyzed in this study. Univariate survival analysis and Cox proportional hazards regression model was used to determine if EGFR-TKIs readministration is tolerable as well as efficacious for a certain group of patients. PMID:25104233

  1. The impact of the RBM4-initiated splicing cascade on modulating the carcinogenic signature of colorectal cancer cells

    PubMed Central

    Lin, Jung-Chun; Lee, Yuan-Chii; Liang, Yu-Chih; Fann, Yang C.; Johnson, Kory R.; Lin, Ying-Ju

    2017-01-01

    A growing body of studies has demonstrated that dysregulated splicing profiles constitute pivotal mechanisms for carcinogenesis. In this study, we identified discriminative splicing profiles of colorectal cancer (CRC) cells compared to adjacent normal tissues using deep RNA-sequencing (RNA-seq). The RNA-seq results and cohort studies indicated a relatively high ratio of exon 4-excluded neuro-oncological ventral antigen 1 (Nova1−4) and intron 2-retained SRSF6 (SRSF6+intron 2) transcripts in CRC tissues and cell lines. Nova1 variants exhibited differential effects on eliminating SRSF6 expression in CRC cells by inducing SRSF6+intron 2 transcripts which were considered to be the putative target of alternative splicing-coupled nonsense-mediated decay mechanism. Moreover, the splicing profile of vascular endothelial growth factor (VEGF)165/VEGF165b transcripts was relevant to SRSF6 expression, which manipulates the progression of CRC calls. These results highlight the novel and hierarchical role of an alternative splicing cascade that is involved in the development of CRC. PMID:28276498

  2. Tools for assessing the quality and accessibility of online health information: initial testing among breast cancer websites.

    PubMed

    Whitten, Pamela; Nazione, Samantha; Lauckner, Carolyn

    2013-12-01

    Health websites are used frequently, but there are many concerns about their value as information sources. Additionally, there are numerous personal barriers that prevent individuals from wholly benefitting from them. In order to assess the quality of health websites and their accessibility to users, we created tools based on previous research that examine design aspects, information validity, motivational health content and literacy content. To test these tools, we examined 155 breast cancer websites and created scores for each assessment tool to describe the percent of constructs on the average website. Results demonstrated that websites performed best on the design tool followed by the information validity, motivational health content and literacy assessment tools. The average website contained the majority of the design and information validity constructs, but only about a third of the motivational health or literacy constructs. Multiple items from the motivational health content and literacy assessment tools were not found on any of the websites, and many were only represented on a handful of sites. Overall, the assessment tools were useful in evaluating the quality of websites, and could serve as valuable resources for health website developers in the future.

  3. Breast cancer 1 (BRCA1)-deficient embryos develop normally but are more susceptible to ethanol-initiated DNA damage and embryopathies.

    PubMed

    Shapiro, Aaron M; Miller-Pinsler, Lutfiya; Wells, Peter G

    2016-04-01

    The breast cancer 1 (brca1) gene is associated with breast and ovarian cancers, and heterozygous (+/-) brca1 knockout progeny develop normally, suggesting a negligible developmental impact. However, our results show BRCA1 plays a broader biological role in protecting the embryo from oxidative stress. Sox2-promoted Cre-expressing hemizygous males were mated with floxed brca1 females, and gestational day 8 +/- brca1 conditional knockout embryos with a 28% reduction in protein expression were exposed in culture to the reactive oxygen species (ROS)-initiating drug ethanol (EtOH). Untreated +/- brca1-deficient embryos developed normally, but when exposed to EtOH exhibited increased levels of oxidatively damaged DNA, measured as 8-oxo-2'-deoxyguanosine, γH2AX, which is a marker of DNA double strand breaks that can result from 8-oxo-2'-deoxyguanosine, formation, and embryopathies at EtOH concentrations that did not affect their brca1-normal littermates. These results reveal that even modest BRCA1 deficiencies render the embryo more susceptible to drug-enhanced ROS formation, and corroborate a role for DNA oxidation in the mechanism of EtOH teratogenesis.

  4. Breast cancer 1 (BRCA1)-deficient embryos develop normally but are more susceptible to ethanol-initiated DNA damage and embryopathies☆

    PubMed Central

    Shapiro, Aaron M.; Miller-Pinsler, Lutfiya; Wells, Peter G.

    2015-01-01

    The breast cancer 1 (brca1) gene is associated with breast and ovarian cancers, and heterozygous (+/−) brca1 knockout progeny develop normally, suggesting a negligible developmental impact. However, our results show BRCA1 plays a broader biological role in protecting the embryo from oxidative stress. Sox2-promoted Cre-expressing hemizygous males were mated with floxed brca1 females, and gestational day 8 +/− brca1 conditional knockout embryos with a 28% reduction in protein expression were exposed in culture to the reactive oxygen species (ROS)-initiating drug ethanol (EtOH). Untreated +/− brca1-deficient embryos developed normally, but when exposed to EtOH exhibited increased levels of oxidatively damaged DNA, measured as 8-oxo-2'-deoxyguanosine, γH2AX, which is a marker of DNA double strand breaks that can result from 8-oxo-2'-deoxyguanosine, formation, and embryopathies at EtOH concentrations that did not affect their brca1-normal littermates. These results reveal that even modest BRCA1 deficiencies render the embryo more susceptible to drug-enhanced ROS formation, and corroborate a role for DNA oxidation in the mechanism of EtOH teratogenesis. PMID:26629949

  5. NKG2D initiates caspase-mediated CD3ζ degradation and lymphocyte receptor impairments associated with human cancer and autoimmune disease

    PubMed Central

    Hanaoka, Nobuyoshi; Jabri, Bana; Dai, Zhenpeng; Ciszewski, Cezary; Stevens, Anne M.; Yee, Cassian; Nakakuma, Hideki; Spies, Thomas; Groh, Veronika

    2011-01-01

    Deficiencies of the T cell and NK cell CD3ζ signaling adapter protein in cancer and autoimmune disease patients are well documented but mechanistic explanations are fragmentary. The stimulatory NKG2D receptor on T cells and NK cells mediates tumor immunity but can also promote local and systemic immune suppression in conditions of persistent NKG2D ligand induction that include cancer and certain autoimmune diseases. Here we provide evidence that establishes a causative link between CD3ζ impairment and chronic NKG2D stimulation due to pathological ligand expression. We describe a mechanism whereby NKG2D signaling in human T cells and NK cells initiates Fas ligand/Fas-mediated caspase-3/7 activation and resultant CD3ζ degradation. As a consequence, the functional capacities of the TCR, the low-affinity Fc receptor for IgG, and the NKp30 and NKp46 natural cytotoxicity receptors, which all signal through CD3ζ, are impaired. These findings are extended to ex vivo phenotypes of T cells and NK cells among tumor-infiltrating lymphocytes and in peripheral blood from juvenile-onset lupus patients. Collectively, these results indicate that pathological NKG2D ligand expression leads to simultaneous impairment of multiple CD3ζ-dependent receptor functions, thus offering an explanation that may be applicable to CD3ζ deficiencies associated with diverse disease conditions. PMID:20926796

  6. A high LDL-C to HDL-C ratio predicts poor prognosis for initially metastatic colorectal cancer patients with elevations in LDL-C.

    PubMed

    Liao, Fangxin; He, Wenzhuo; Jiang, Chang; Yin, Chenxi; Guo, Guifang; Chen, Xuxian; Qiu, Huijuan; Rong, Yuming; Zhang, Bei; Xu, Dazhi; Xia, Liangping

    2015-01-01

    Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.

  7. Evaluation of quality of life and anxiety and depression levels in patients receiving chemotherapy for colorectal cancer: impact of patient education before treatment initiation

    PubMed Central

    Polat, Ulku; Arpacı, Afey; Demir, Satı; Erdal, Sevgi; Yalcin, Şuayib

    2014-01-01

    Background As a consequence of the improved survival due to the availability of several treatment option cost-effectiveness and health-related quality of life (HRQoL) issues have gained increasing attention in colorectal cancer (CRC). In the present study, we aimed to evaluate quality of life, level of anxiety and depression before and after a 6-month follow-up period in chemotherapy receiving patients with CRC. Methods The study was conducted in 50 patients with colon or rectal cancer. All patients were informed and educated about their disease and treatment before getting the treatment and were followed for 6 months, during which they received chemotherapy. A “Questionnaire Form” to collect patient demographic characteristics; the “EORTC QLQ-C30 Scale” and “EQ-5D Scale” to evaluate patient’s quality of life; and the “Hospital Anxiety and Depression (HAD) Scale” to evaluate the level of anxiety and depression status of patients, were used as data collecting tools. Results Quality of life scores in all functional fields were high in the sixth course when compared to the first according to EORTC QLQ-C30 Scale, reaching to statistically significant level in emotional function score compared to the initial ones (P<0.05). Moreover quality of life score measured in the sixth month with EQ-5D was statistically significantly higher than the initial. Conclusions These data, shows that with proper patient management, quality of life score, and the anxiety and depression levels improve during the course of treatment. PMID:25083300

  8. Assessment of risk for asthma initiation and cancer and heart disease deaths among patrons and servers due to secondhand smoke exposure in restaurants and bars

    PubMed Central

    Liu, Ruiling; Bohac, David L; Gundel, Lara A; Hewett, Martha J; Apte, Michael G; Hammond, S Katharine

    2014-01-01

    Background Despite efforts to reduce exposure to secondhand smoke (SHS), only 5% of the world's population enjoy smoke-free restaurants and bars. Methods Lifetime excess risk (LER) of cancer death, ischaemic heart disease (IHD) death and asthma initiation among non-smoking restaurant and bar servers and patrons in Minnesota and the US were estimated using weighted field measurements of SHS constituents in Minnesota, existing data on tobacco use and multiple dose-response models. Results A continuous approach estimated a LER of lung cancer death (LCD) of 18×10−6(95% CI 13 to 23×10−6) for patrons visiting only designated non-smoking sections, 80×10−6(95% CI 66 to 95×10−6) for patrons visiting only smoking venues/sections and 802×10−6(95% CI 658 to 936×10−6) for servers in smoking-permitted venues. An attributable-risk (exposed/non-exposed) approach estimated a similar LER of LCD, a LER of IHD death about 10−2 for non-smokers with average SHS exposure from all sources and a LER of asthma initiation about 5% for servers with SHS exposure at work only. These risks correspond to 214 LCDs and 3001 IHD deaths among the general non-smoking population and 1420 new asthma cases among non-smoking servers in the US each year due to SHS exposure in restaurants and bars alone. Conclusions Health risks for patrons and servers from SHS exposure in restaurants and bars alone are well above the acceptable level. Restaurants and bars should be a priority for governments’ effort to create smoke-free environments and should not be exempt from smoking bans. PMID:23407112

  9. Proepithelin Regulates Prostate Cancer Cell Biology by Promoting Cell Growth, Migration, and Anchorage-Independent Growth

    PubMed Central

    Monami, Giada; Emiliozzi, Velia; Bitto, Alessandro; Lovat, Francesca; Xu, Shi-Qiong; Goldoni, Silvia; Fassan, Matteo; Serrero, Ginette; Gomella, Leonard G.; Baffa, Raffaele; Iozzo, Renato V.; Morrione, Andrea

    2009-01-01

    The growth factor proepithelin has recently emerged as an important regulator of transformation in several physiological and pathological systems. In this study, we determined the biological roles of proepithelin in prostate cancer cells using purified human recombinant proepithelin as well as proepithelin-depletion strategies. Proepithelin promoted the migration of androgen-dependent and -independent human prostate cancer cells; androgen-independent DU145 cells were the more responsive. In these cells, proepithelin additionally stimulated wound closure, invasion, and promotion of cell growth in vitro. These effects required the activation of both the Akt and mitogen-activated protein kinase pathways. We have analyzed proepithelin expression levels in different available prostate cancer microarray studies using the Oncomine database and found a statistically significant increase in proepithelin mRNA expression levels in prostate cancers compared with nonneoplastic controls. Notably, depletion of endogenous proepithelin by siRNA and antisense strategies impaired the ability of DU145 cells to grow and migrate after serum withdrawal and inhibited anchorage-independent growth. Our results provide the first evidence for a role of proepithelin in stimulating the migration, invasion, proliferation, and anchorage-independent growth of prostate cancer cells. This study supports the hypothesis that proepithelin may play a critical role as an autocrine growth factor in the establishment and initial progression of prostate cancer. Furthermore, proepithelin may prove to be a useful clinical marker for the diagnosis of prostate tumors. PMID:19179604

  10. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

    PubMed Central

    Saloman, Jami L.; Albers, Kathryn M.; Li, Dongjun; Hartman, Douglas J.; Crawford, Howard C.; Muha, Emily A.; Rhim, Andrew D.; Davis, Brian M.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations. PMID:26929329

  11. L'Aventure du LHC

    ScienceCinema

    None

    2016-07-12

    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.

  12. Evaluation of the cytotoxic effects of PLGA coated iron oxide nanoparticles as a carrier of 5- fluorouracil and mega-voltage X-ray radiation in DU145 prostate cancer cell line.

    PubMed

    Hajikarimi, Zahra; Khoei, Samideh; Khoee, Sepideh; Mahdavi, Seied Rabi

    2014-12-01

    The purpose of this study was to investigate the uptake and cytotoxic effects of magnetic poly lactic-co-glycolic acid (PLGA)-coated iron oxide nanoparticles as a carrier of 5-fluorouracil (5-FU) and X-ray on the level of proliferation capacity of DU145 prostate carcinoma cell line in monolayer culture. Following monolayer culture, DU 145 cells were treated with different concentrations of 5-FU or 5-FU loaded nanoparticles for 24 h and 2Gy X-ray (6 Mega-voltage (MV)). The rate of nanoparticles penetration was then measured using atomic adsorption spectroscopy (AAS). The cytotoxicity effect of these nanoparticles with/ without X-ray radiation was evaluated using colony formation assay. Spectroscopy results showed that iron content and therefore the cellular uptake of 5-FU loaded nanoparticles increased with increasing nanoparticle concentrations. Further, the proliferation capacity of the cells decreased with the increase of 5-FU and 5- FU loaded nanoparticle concentrations in combination with X-ray radiation. However the extent of reduction in colony number following treatment with 5-FU-loaded nanoparticles in combination with 2Gy of megavoltage X-ray radiation was significantly more than for free 5-FU. Thus, drug-loaded nanoparticles could deliver 5-FU more efficiently into the cells. PLGA coated iron oxide nanoparticles are therefore effective drug delivery vehicles for 5-FU. PLGA coated iron oxide nanoparticles are biocompatible and this coating is an appropriate surface that can penetrate into the cells.

  13. Recent innovations in the USA National Cancer Institute-sponsored investigator initiated Phase I and II anticancer drug development.

    PubMed

    Bando, Hideaki; Takebe, Naoko

    2015-11-01

    Exciting recent advancements in deep-sequencing technology have enabled a rapid and cost-effective molecular characterization of patient-derived tumor samples. Incorporating these innovative diagnostic technologies into early clinical trials could significantly propel implementation of precision medicine by identifying genetic markers predictive of sensitivity to agents. It may also markedly accelerate drug development and subsequent regulatory approval of novel agents. Particularly noteworthy, a high-response rate in a Phase II trial involving a biomarker-enriched patient cohort could result in a regulatory treatment approval in rare histologies, which otherwise would not be a candidate for a large randomized clinical trial. Furthermore, even if a trial does not meet its statistical endpoint, tumors from a few responders should be molecularly characterized as part of the new biomarker-mining processes. In order to accommodate patient screening and accelerate the accrual process, institutions conducting early clinical trials need to be a part of a multi-institution clinical trials network. Future clinical trial design will incorporate new biomarkers discovered by a 'phenotype-to-genotype' effort with an appropriate statistical design. To help advance such changes, the National Cancer Institute has recently reformed the existing early phase clinical trials network. A new clinical trial network, the Experimental Therapeutics Clinical Trials Network (ET-CTN), was begun and, in addition to its pre-existing infrastructure, an up-to-date clinical trial registration system, clinical trial monitoring system including electronic database and a central Institutional Review Board were formed. Ultimately, these reforms support identifying the most appropriate therapy for each tumor type by incorporating state-of-the-art molecular diagnostic tools into early clinical trials.

  14. Prognostic Factors for Survival and Resection in Patients With Initial Nonresectable Locally Advanced Pancreatic Cancer Treated With Chemoradiotherapy

    SciTech Connect

    Bjerregaard, Jon K.; Mortensen, Michael B.; Jensen, Helle A.; Nielsen, Morten; Pfeiffer, Per

    2012-07-01

    Background and Purpose: Controversies regarding the optimal therapy for patients with locally advanced pancreatic cancer (LAPC) exist. Although the prognosis as a whole remains dismal, subgroups are known to benefit from intensive therapy, including chemoradiotherapy (CRT). We describe the results in 178 patients treated from 2001 to 2010 and have developed a prognostic model for both survival and the possibility of a subsequent resection in these patients. Methods and Materials: From 2001 until 2010, 178 consecutive patients with LAPC were treated and included in the present study, with CRT consisting of 50 Gy in 27 fractions combined with tegafur-uracil(UFT)/folinic acid(FA). Results: The median survival from diagnosis was 11.5 months. Adverse events of Grade 3 or above were seen in 36% of the patients. Ninety-three percent of the patients completed all fractions. A Cox regression model for survival demonstrated resection (hazard ratio [HR] 0.12; 95% confidence interval [CI], 0.1-0.3) and pre-CRT gemcitabine-based therapy (HR 0.57; 95% CI, 0.4-0.9) as being associated with a favorable outcome, increasing gross tumor volume (HR 1.14; 95% CI, 1.0-1.3) was associated with shorter survival. A logistic regression model showed Stage III disease (odds ratio [OR] 0.16; 95% CI, 0.0-1.1) and abnormal hemoglobin (OR 0.26; 95% CI, 0.0-1.2) as being associated with lower odds of resection. Conclusion: This study confirms the favorable prognosis for patients receiving gemcitabine therapy before CRT and the poor prognosis associated with increasing tumor volume. In addition, CRT in patients with abnormal hemoglobin and Stage III disease rarely induced tumor shrinkage allowing subsequent resection.

  15. Recent innovations in the USA National Cancer Institute-sponsored investigator initiated Phase I and II anticancer drug development

    PubMed Central

    Bando, Hideaki; Takebe, Naoko

    2015-01-01

    Exciting recent advancements in deep-sequencing technology have enabled a rapid and cost-effective molecular characterization of patient-derived tumor samples. Incorporating these innovative diagnostic technologies into early clinical trials could significantly propel implementation of precision medicine by identifying genetic markers predictive of sensitivity to agents. It may also markedly accelerate drug development and subsequent regulatory approval of novel agents. Particularly noteworthy, a high-response rate in a Phase II trial involving a biomarker-enriched patient cohort could result in a regulatory treatment approval in rare histologies, which otherwise would not be a candidate for a large randomized clinical trial. Furthermore, even if a trial does not meet its statistical endpoint, tumors from a few responders should be molecularly characterized as part of the new biomarker-mining processes. In order to accommodate patient screening and accelerate the accrual process, institutions conducting early clinical trials need to be a part of a multi-institution clinical trials network. Future clinical trial design will incorporate new biomarkers discovered by a ‘phenotype-to-genotype’ effort with an appropriate statistical design. To help advance such changes, the National Cancer Institute has recently reformed the existing early phase clinical trials network. A new clinical trial network, the Experimental Therapeutics Clinical Trials Network (ET-CTN), was begun and, in addition to its pre-existing infrastructure, an up-to-date clinical trial registration system, clinical trial monitoring system including electronic database and a central Institutional Review Board were formed. Ultimately, these reforms support identifying the most appropriate therapy for each tumor type by incorporating state-of-the-art molecular diagnostic tools into early clinical trials. PMID:26423340

  16. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer

    PubMed Central

    Paller, CJ; Ye, X; Wozniak, PJ; Gillespie, BK; Sieber, PR; Greengold, RH; Stockton, BR; Hertzman, BL; Efros, MD; Roper, RP; Liker, HR; Carducci, MA

    2012-01-01

    BACKGROUND Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome. METHODS This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm. RESULTS: Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P<0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P =0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively. CONCLUSIONS POMx treatment was associated with ≥6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population. PMID:22689129

  17. P30 Cancer Center Support Grant Administrative Supplements to support NCI Approved Clinical Trial Proposals from NCI-designated Cancer Centers not affiliated with the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) for Investigator-Initiated Trials Utilizing CTEP IND agents in the ETCTN

    Cancer.gov

    P30 Cancer Center Support Grant Administrative Supplements to support NCI Approved Clinical Trial Proposals from NCI-designated Cancer Centers not affiliated with the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) for Investigator-Initiated Trials Utilizing CTEP IND agents in the ETCTN

  18. Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party

    PubMed Central

    Berghmans, T; Lafitte, J J; Lecomte, J; Alexopoulos, C G; Van Cutsem, O; Giner, V; Efremidis, A; Berchier, M C; Collon, T; Meert, A P; Scherpereel, A; Ninane, V; Leclercq, N; Paesmans, M; Sculier, J P

    2007-01-01

    In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08–2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08–2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26–2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy. PMID:17473825

  19. "A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies"

    PubMed Central

    2012-01-01

    Background The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis. Methods Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC). Results Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 103 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples. Conclusions

  20. Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

    PubMed Central

    Kang, Minyong; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2015-01-01

    Background The aim of this study was to investigate the effects of surgical castration, particularly delaying the time to entrance of systemic chemotherapy, in castration-resistant prostate cancer (CRPC) patients who were refractory to initial combination androgen deprivation therapy. Materials and methods We analyzed the clinical data of 14 CRPC patients diagnosed at Seoul National University Bundang Hospital (SNUBH) from November 2008 through May 2015. After exclusion of three patients, we finally analyzed the baseline characteristics of 11 CRPC patients. We also assessed the delaying time of docetaxel administration, which was defined as response duration, after surgical castration. Results After bilateral orchiectomy, the treatment response rate was 45.4% and the median duration of response was 9 months (range 4–48 mo). Responders had less aggressive biopsy Gleason scores compared to nonresponders. Notably, responders showed the reducing pattern of serum prostate specific antigen levels, while nonresponders demonstrated increasing tendency after surgical castration. Moreover, responders also presented with a reduction pattern of serum testosterone levels, whereas nonresponders showed an increasing pattern of testosterone levels after bilateral orchiectomy. Conclusions In summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy. PMID:26779458

  1. Initial Fludeoxyglucose (18F) Positron Emission Tomography-Computed Tomography (FDG-PET/CT) Imaging of Breast Cancer – Correlations with the Primary Tumour and Locoregional Metastases

    PubMed Central

    Ayaz, Sevin; Gültekin, Salih Sinan; Ayaz, Ümit Yaşar; Dilli, Alper

    2017-01-01

    Summary Backround We aimed to evaluate initial PET/CT features of primary tumour and locoregional metastatic lymph nodes (LNs) in breast cancer and to look for potential relationships between several parameters from PET/CT. Material/Methods Twenty-three women (mean age; 48.66±12.23 years) with a diagnosis of primary invasive ductal carcinoma were included. They underwent PET/CT imaging for the initial tumour staging and had no evidence of distant metastates. Patients were divided into two groups. The LABC (locally advanced breast cancer) group included 17 patients with ipsilateral axillary lymph node (LN) metastases. The Non-LABC group consisted of six patients without LN metastases. PET/CT parameters including tumour size, axillary LN size, SUVmax of ipsilateral axillary LNs (SUVmax-LN), SUVmax of primary tumour (SUVmax-T) and NT ratios (SUVmax-LN/SUVmax-T) were compared between the groups. Correlations between the above-mentioned PET/CT parameters in the LABC group as well as the correlation between tumour size and SUVmax-T within each group were evaluated statistically. Results The mean values of the initial PET/CT parameters in the LABC group were significantly higher than those of the non-LABC group (p<0.05). The correlation between tumour size and SUVmax-T value within both LABC and non-LABC groups was statistically significant (p<0.05). In the LABC group, the correlations between the size and SUVmax-LN values of metastatic axillary LNs, between tumour size and metastatic axillary LN size, between SUVmax-T values and metastatic axillary LN size, between SUVmax-T and SUVmax-LN values, and between tumour size and SUVmax-LN values were all significant (p<0.05). Conclusions We found significant correlations between PET/CT parameters of the primary tumour and those of metastatic axillary LNs. Patients with LN metastases had relatively larger primary tumours and higher SUVmax values. PMID:28105247

  2. Cigar Smoking and Cancer

    MedlinePlus

    ... Health Disparities Childhood Cancers Clinical Trials Global Health Key Initiatives The RAS Initiative NCI and the Precision ... Health Disparities Childhood Cancer Clinical Trials Global Health Key Initiatives Read about some of NCI's major research ...

  3. Cancer

    MedlinePlus

    ... Two kinds of lymphocytes can attack and kill cancer cells: T-cells and B-cells. Immunotherapy aims to boost the ability of the T-cell and B-cell lymphocytes to kill cancer. This kind of therapy can also be used ...

  4. Undergraduate cancer education in Spain: The debate, the opportunities and the initiatives of the University Forum of the Spanish Society of Radiation Oncology (SEOR)

    PubMed Central

    Lara, Pedro; Calvo, Felipe A.; Guedea, Ferran; Bilbao, Pedro; Biete, Alberto

    2013-01-01

    Most medical schools in Spain (80%) offer undergraduate training in oncology. This education is highly variable in terms of content (theory and practical training), number of credits, and the medical specialty and departmental affiliation of the professors. Much of this variability is due to university traditions in the configuration of credits and programmes, and also to the structure of the hospital-based practical training. Undergraduate medical students deserve a more coherent and modern approach to education with a strong emphasis on clinical practice. Oncology is an interdisciplinary science that requires the input of professors from multiple specialties to provide the primary body of knowledge and skills needed to obtain both a theoretical and clinical understanding of cancer. Clinical skills should be a key focus due to their importance in the current model of integrated medical management and care. Clinical radiation oncology is a traditional and comprehensive hospital-based platform for undergraduate education in oncology. In Spain, a significant number (n = 80) of radiation oncology specialists have a contractual relationship to teach university courses. Most Spanish universities (80%) have a radiation oncologist on staff, some of whom are department chairs and many others are full professors who have been hired and promoted under competitive conditions of evaluation as established by the National Agency for Quality Evaluation. The Spanish Society of Radiation Oncology (SEOR) has identified new opportunities to improve undergraduate education in oncology. In this article, we discuss proposals related to theoretical (20 items) and practical clinical training (9 items). We also describe the SEOR University Forum, which is an initiative to develop a strategic plan to implement and organize cancer education at the undergraduate level in an interdisciplinary teaching spirit and with a strong contribution from radiation oncologists. PMID:24416587

  5. MicroRNA-9 regulates non-small cell lung cancer cell invasion and migration by targeting eukaryotic translation initiation factor 5A2

    PubMed Central

    Xu, Guodong; Shao, Guofeng; Pan, Qiaoling; Sun, Lebo; Zheng, Dawei; Li, Minghui; Li, Ni; Shi, Huoshun; Ni, Yiming

    2017-01-01

    MicroRNAs (miRNAs) play a critical role in cancer development and progression. Bioinformatics analyses has identified eukaryotic translation initiation factor 5A2 (eIF5A2) as a target of miR-9. In this study, we attempted to determine whether miR-9 regulates non-small cell lung cancer (NSCLC) cell invasion and migration by targeting eIF5A2 We examined eIF5A2 expression using reverse transcription-quantitative PCR (RT-qPCR) and subsequently transfected A549 and NCI-H1299 NSCLC cells with a miR-9 mimic or miR-9 inhibitor to determine the migration and invasive capability of the cells via wound healing assay and Transwell invasion assay, respectively. E-cadherin and vimentin expression was detected with western blotting. The miR-9 mimic significantly reduced NSCLC cell invasive and metastatic ability, and the miR-9 inhibitor enhanced NSCLC cell migration activity, increasing the number of migrated cells. There was no significant difference between the negative control siRNA and miR-9 mimic groups after knockdown of eIF5A2; western blotting showed that miR-9 regulated E-cadherin and vimentin expression. These data show that miR-9 regulates NSCLC cell invasion and migration through regulating eIF5A2 expression. Taken together, our findings suggest that the mechanism of miR-9-regulated NSCLC cell invasion and migration may be related to epithelial-mesenchymal transition. PMID:28337276

  6. Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

    PubMed

    Overcash, Ryan F; Chappell, Vesna A; Green, Thomas; Geyer, Christopher B; Asch, Adam S; Ruiz-Echevarría, Maria J

    2013-01-01

    The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2), is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in prostate cancer, suggesting a role in this disease, but the molecular mechanism(s) involved in this effect are not clear. Although androgens promote tmeff2 transcription, androgen delivery to castrated animals carrying CWR22 xenografts increases TMEFF2 protein levels in the absence of mRNA changes, suggesting that TMEFF2 may also be post-transcriptionally regulated. Here we show that translation of TMEFF2 is regulated by androgens. Addition of physiological concentrations of dihydrotestosterone (DHT) to prostate cancer cell lines increases translation of endogenous TMEFF2 or transfected TMEFF2-Luciferase fusions, and this effect requires the presence of upstream open reading frames (uORFs) in the 5'-untranslated region (5'-UTR) of TMEFF2. Using chemical and siRNA inhibition of the androgen receptor (AR), we show that the androgen effect on TMEFF2 translation is mediated by the AR. Importantly, DHT also promotes phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α) in an AR-dependent manner, paralleling the effect on TMEFF2 translation. Moreover, endoplasmic reticulum (ER) stress conditions, which promote eIF2α phosphorylation, also stimulate TMEFF2 translation. These results indicate that androgen signaling promotes eIF2α phosphorylation and subsequent translation of TMEFF2 via a mechanism that requires uORFs in the 5'-UTR of TMEFF2.

  7. Carcinome neuroendocrine du sein: à propos d'un cas et revue de la littérature

    PubMed Central

    El Fatemi, Hinde; Hammas, Nawal; Moumna, Kaoutar; Bedahou, Mouhcine; Mellas, Nawfel; Mesbahi, Omar

    2012-01-01

    Le carcinome neuroendocrine primitif du sein est une tumeur rare qui a été reconnue par la dernière édition de la classification OMS du cancer du sein publiée en 2003. Le diagnostic est évoqué sur des critères morphologiques et confirmé par l'expression des marqueurs neuroendocrines (chromogranine et synaptophysine) par plus de 50% des cellules tumorales. Nous rapportons un nouveau cas de carcinome neuroendocrine primitif du sein, et à travers une revue de la littérature, nous détaillons les aspects épidémiologiques, morphologiques et immuno-histochimiques de cette tumeur rare. PMID:23330031

  8. 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

  9. Omega-3 fatty acids and other FFA4 agonists inhibit growth factor signaling in human prostate cancer cells.

    PubMed

    Liu, Ze; Hopkins, Mandi M; Zhang, Zhihong; Quisenberry, Chrystal B; Fix, Louise C; Galvan, Brianna M; Meier, Kathryn E

    2015-02-01

    Omega-3 fatty acids (n-3 FAs) are proposed to have many beneficial effects on human health. However, the mechanisms underlying their potential cancer preventative effects are unclear. G protein-coupled receptors (GPCRs) of the free fatty acid receptor (FFAR) family, FFA1/GPR40 and FFA4/GPR120, specifically bind n-3 FAs as agonist ligands. In this study, we examined the effects of n-3 FAs in human prostate cancer cell lines. Initial studies established that the long-chain n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid, inhibit proliferation of DU145 cells in response to lysophosphatidic acid (LPA), a mitogenic lipid mediator. When added alone to serum-starved DU145 cells, EPA transiently activates signaling events, including p70S6K phosphorylation. However, when added 15 minutes prior to LPA, EPA suppresses LPA-induced activating phosphorylations of ERK, FAK, and p70S6K, and expression of the matricellular protein CCN1. The rapid onset of the inhibitory action of EPA suggested involvement of a GPCR. Further studies showed that DU145 and PC-3 cells express mRNA and protein for both FFA4 and FFA1. TUG-891 (4-[(4-fluoro-4'-methyl[1,1'-biphenyl]-2-yl)methoxy]-benzenepropanoic acid), a selective agonist for FFA4, exerts inhibitory effects on LPA- and epidermal growth factor-induced proliferation and migration, similar to EPA, in DU145 and PC-3 cells. The effects of TUG-891 and EPA are readily reversible. The FFA1/FFA4 agonist GW9508 (4-[[(3-phenoxyphenyl)methyl]amino]-benzenepropranoic acid) likewise inhibits proliferation at doses that block FFA4. Knockdown of FFA4 expression prevents EPA- and TUG-891-induced inhibition of growth and migration. Together, these results indicate that activation of FFA4 initiates signaling events that can inhibit growth factor-induced signaling, providing a novel mechanism for suppression of cancer cell proliferation.

  10. Cancer

    MedlinePlus

    ... weaken. Talk with family, friends, or a support group about your feelings. Work with your health care providers throughout your treatment. Helping yourself can make you feel more in control. Support Groups The diagnosis and treatment of cancer often causes ...

  11. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells

    PubMed Central

    Riggi, Nicolò; Suvà, Mario-Luca; De Vito, Claudio; Provero, Paolo; Stehle, Jean-Christophe; Baumer, Karine; Cironi, Luisa; Janiszewska, Michalina; Petricevic, Tanja; Suvà, Domizio; Tercier, Stéphane; Joseph, Jean-Marc; Guillou, Louis; Stamenkovic, Ivan

    2010-01-01

    Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the mechanisms that underlie ESFT CSC development. We show that the EWS-FLI-1 fusion gene, associated with 85%–90% of ESFTs and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2, and NANOG in human pediatric MSCs (hpMSCs) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSCs expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWS-FLI-1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene, SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype. PMID:20382729

  12. Pancreatic cell plasticity and cancer initiation induced by oncogenic Kras is completely dependent on wild-type PI 3-kinase p110α

    PubMed Central

    Baer, Romain; Cintas, Célia; Dufresne, Marlène; Cassant-Sourdy, Stéphanie; Schönhuber, Nina; Planque, Laetitia; Lulka, Hubert; Couderc, Bettina; Bousquet, Corinne; Garmy-Susini, Barbara; Vanhaesebroeck, Bart; Pyronnet, Stéphane; Saur, Dieter; Guillermet-Guibert, Julie

    2014-01-01

    Increased PI 3-kinase (PI3K) signaling in pancreatic ductal adenocarcinoma (PDAC) correlates with poor prognosis, but the role of class I PI3K isoforms during its induction remains unclear. Using genetically engineered mice and pharmacological isoform-selective inhibitors, we found that the p110α PI3K isoform is a major signaling enzyme for PDAC development induced by a combination of genetic and nongenetic factors. Inactivation of this single isoform blocked the irreversible transition of exocrine acinar cells into pancreatic preneoplastic ductal lesions by oncogenic Kras and/or pancreatic injury. Hitting the other ubiquitous isoform, p110β, did not prevent preneoplastic lesion initiation. p110α signaling through small GTPase Rho and actin cytoskeleton controls the reprogramming of acinar cells and regulates cell morphology in vivo and in vitro. Finally, p110α was necessary for pancreatic ductal cancers to arise from Kras-induced preneoplastic lesions by increasing epithelial cell proliferation in the context of mutated p53. Here we identify an in vivo context in which p110α cellular output differs depending on the epithelial transformation stage and demonstrate that the PI3K p110α is required for PDAC induced by oncogenic Kras, the key driver mutation of PDAC. These data are critical for a better understanding of the development of this lethal disease that is currently without efficient treatment. PMID:25452273

  13. Essential oil of Cephalotaxus griffithii needle inhibits proliferation and migration of human cervical cancer cells: involvement of mitochondria-initiated and death receptor-mediated apoptosis pathways.

    PubMed

    Moirangthem, Dinesh Singh; Laishram, Surbala; Rana, Virendra Singh; Borah, Jagat Chandra; Talukdar, Narayan Chandra

    2015-01-01

    This study was conducted to determine the effect of Cephalotaxus griffithii needle essential oil (CGNO) on proliferation and migration of human cervical cancer (HCC) cells. CGNO treatment decreased the viability of all the tested HCC (HeLa, ME-180 and SiHa) cells. Morphological and DNA fragmentation analysis of CGNO-treated HeLa cells indicated the involvement of apoptosis in inducing HCC cell death. CGNO increased mitochondrial membrane depolarisation and upregulated the expression of caspase-9, caspase-8, caspase-3 and cleaved-PARP. The activity of caspase-8 and caspase-9 was also significantly increased. Wound healing and transwell migration assay demonstrated that CGNO significantly inhibited the migration of HeLa cells to close a scratched wound and also inhibited their migration through filter towards a chemotactic stimulus. Taken together, these results indicated that CGNO inhibited the proliferation and migration of HCC cells. Of note, CGNO induced HeLa cell death through mitochondria-initiated and death receptor-mediated apoptosis pathway.

  14. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.

    PubMed

    Riggi, Nicolò; Suvà, Mario-Luca; De Vito, Claudio; Provero, Paolo; Stehle, Jean-Christophe; Baumer, Karine; Cironi, Luisa; Janiszewska, Michalina; Petricevic, Tanja; Suvà, Domizio; Tercier, Stéphane; Joseph, Jean-Marc; Guillou, Louis; Stamenkovic, Ivan

    2010-05-01

    Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the mechanisms that underlie ESFT CSC development. We show that the EWS-FLI-1 fusion gene, associated with 85%-90% of ESFTs and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2, and NANOG in human pediatric MSCs (hpMSCs) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSCs expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWS-FLI-1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene, SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype.

  15. [Self-assessment of the effect of dysphagia on the quality of life in patients after partial laryngectomy for cancer initially located in the supraglottic area].

    PubMed

    Strek, Paweł; Hydzik-Sobocińtska, Karolina; Składzień, Jacek; Modrzejewski, Maciej; Zagólski, Olaf; Blaschke, Joanna; Najdzionek, Daniel; Kurzyński, Marian; Muszyński, Piotr; Gawlik, Jolanta; Dutsch-Wicherek, Magdalena

    2005-09-01

    Dysphagia is frequent in patients after partial laryngectomy for cancer initially located in the supraglottic area. To ensure the best quality of life, establishing how the patient feels after treatment is necessary. Therefore, a self-administered questionnaire was designed to evaluate the dysphagia. 95 patients (75 male and 20 women) who were operated in ENT Department CMUJ between 1998-2004 participated in this study. The MDADI questionnaire in the Polish version was used. The subjective evaluation by the patient of dysphagia is directly related to the size of the tumor and the extent of the partial laryngectomy treatment. Patients, whose tumor was located in supraglottic-glottic area, had subtotal laryngectomy m. Miodoński. Their quality of life was significantly worse due to dysphagia than those with tumors located only in the supraglottic area. Swallowing dysfunctionality was significantly greater after the resection of the hyoid bone. Reconstruction of the base of a tongue by a graft of angiopedunculated submandibular gland diminished the difficulties in swallowing. Moreover, the longer the period after treatment, the higher the quality of life becomes because of the improvement in the swallowing functionality.

  16. Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer

    DTIC Science & Technology

    2007-09-01

    androgen -insensitive prostate cancer patients based upon our work. 15. SUBJECT TERMS Prostate Cancer , Neuroendocrine, Progression...two androgen - ines PC-3 and DU-145 by examining the status of publication. a Src kinase inhibitor AZ independent prostate cancer cell l...differentiation in prostate cancer . AR activation. Together with our studies in the chimeric growth of androgen -sensitive and androgen -insensitive cells,

  17. The Establishment of the First Cancer Tissue Biobank at a Hispanic-Serving Institution: A National Cancer Institute–Funded Initiative between Moffitt Cancer Center in Florida and the Ponce School of Medicine and Health Sciences in Puerto Rico

    PubMed Central

    Flores, Idhaliz; Muñoz-Antonia, Teresita; Matta, Jaime; García, Miosotis; Fenstermacher, David; Gutierrez, Sylvia; Seijo, Edward; Torres-Ruiz, Jose’; Pledger, W. Jack

    2011-01-01

    Population-based studies are important to address emerging issues in health disparities among populations. The Partnership between the Moffitt Cancer Center (MCC) in Florida and the Ponce School of Medicine and Health Sciences (PSMHS) in Puerto Rico (the PSMHS-MCC Partnership) was developed to facilitate high-quality research, training, and community outreach focusing on the Puerto Rican population in the island and in the mainland, with funding from the National Cancer Institute. We report here the establishment of a Tissue Biobank at PSMHS, modeled after the MCC tissue biorepository, to support translational research projects on this minority population. This facility, the Puerto Rico Tissue Biobank, was jointly developed by a team of basic and clinical scientists from both institutions in close collaboration with the administrators and clinical faculty of the tissue accrual sites. The efforts required and challenges that needed to be overcome to establish the first functional, centralized cancer-related biobank in Puerto Rico, and to ensure that it continuously evolves to address new needs of this underserved Hispanic population, are described. As a result of the collaborative efforts between PSMHS and MCC, a tissue procurement algorithm was successfully established to acquire, process, store, and conduct pathological analyses of cancer-related biospecimens and their associated clinical-pathological data from Puerto Rican patients with cancer recruited at a tertiary hospital setting. All protocols in place are in accordance with standard operational procedures that ensure high quality of biological materials and patient confidentiality. The processes described here provide a model that can be applied to achieve the establishment of a functional biobank in similar settings. PMID:24836632

  18. 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.

  19. Les plaies du tendon patellaire

    PubMed Central

    Mechchat, Atif; Elidrissi, Mohammed; Mardy, Abdelhak; Elayoubi, Abdelghni; Shimi, Mohammed; Elibrahimi, Abdelhalim; Elmrini, Abdelmajid

    2014-01-01

    Les plaies du tendon patellaire sont peu fréquentes et sont peu rapportés dans la littérature, contrairement aux ruptures sous cutanées. Les sections du tendon patellaire nécessitent une réparation immédiate afin de rétablir l'appareil extenseur et de permettre une récupération fonctionnelle précoce. A travers ce travail rétrospectif sur 13 cas, nous analysons les aspects épidémiologiques, thérapeutiques et pronostiques de ce type de pathologie en comparant différents scores. L’âge moyen est de 25 ans avec une prédominance masculine. Les étiologies sont dominées par les accidents de la voie publique (68%) et les agressions par agent tranchant (26%) et contendant (6 %). Tous nos patients ont bénéficié d'un parage chirurgical avec suture tendineuse direct protégée par un laçage au fils d'aciers en légère flexion. La rééducation est débutée après sédation des phénomènes inflammatoires. Au dernier recul les résultats sont excellents et bon à 92%. Nous n'avons pas noté de différence de force musculaire et d'amplitude articulaire entre le genou sain et le genou lésé. Les lésions ouvertes du tendon patellaire est relativement rare. La prise en charge chirurgicale rapide donne des résultats assez satisfaisants. La réparation est généralement renforcée par un semi-tendineux, synthétique ou métallique en forme de cadre de renfort pour faciliter la réadaptation et réduire le risque de récidive après la fin de l'immobilisation. PMID:25170379

  20. Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer

    PubMed Central

    Stokum, Jesse A.; Schneider, Craig S.; Ozawa, Tatsuya; Xu, Su; Galisteo, Rebeca; Castellani, Rudolph J.; Kim, Anthony J.; Simard, J. Marc; Winkles, Jeffrey A.; Holland, Eric C.; Woodworth, Graeme F.

    2017-01-01

    Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS) virus / tumor virus receptor-A (tv-a) transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a) transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI) and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

  1. Initial Results of a Phase I Dose-Escalation Trial of Concurrent and Maintenance Erlotinib and Reirradiation for Recurrent and New Primary Head-and-Neck Cancer

    SciTech Connect

    Rusthoven, Kyle E.; Feigenberg, Steven J.; Raben, David; Kane, Madeleine; Song, John I.; Nicolaou, Nicos; Mehra, Ranee; Burtness, Barbara; Ridge, John; Swing, Robyn; Lango, Miriam; Cohen, Roger; Jimeno, Antonio; Chen Changhu

    2010-11-15

    Purpose: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). Methods and Materials: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinib started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. Results: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. Conclusions: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.

  2. Folate-mediated one-carbon metabolism genes and interactions with nutritional factors on colorectal cancer risk: Women’s Health Initiative Observational Study

    PubMed Central

    Cheng, Ting-Yuan David; Makar, Karen W.; Neuhouser, Marian L.; Miller, Joshua W.; Song, Xiaoling; Brown, Elissa C.; Beresford, Shirley A. A.; Zheng, Yingye; Poole, Elizabeth M.; Galbraith, Rachel L.; Duggan, David J.; Habermann, Nina; Bailey, Lynn B.; Maneval, David R.; Caudill, Marie A.; Toriola, Adetunji T.; Green, Ralph; Ulrich, Cornelia M.

    2015-01-01

    Background Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions in relation to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. We comprehensively investigated associations between genetic variants in FOCM and CRC risk, and whether FOCM nutrient status modified these associations. Methods We genotyped 288 candidate and tagging single nucleotide polymorphisms (SNPs) in 30 FOCM genes among 821 incident CRC case-control matched pairs in the Women’s Health Initiative Observational Study cohort. FOCM biomarkers (red blood cell [RBC] folate, plasma folate, pyridoxal-5’-phosphate [PLP], vitamin B12, and homocysteine) and self-reported alcohol consumption were measured at baseline. Conditional logistic regression was implemented; effect modification was examined based on known enzyme-nutrient relationships. Results We observed statistically significant associations between CRC risk and functionally defined candidate SNPs of MTHFD1 (K134R), MTRR (P450R), and PRDM2 (S450N), and a literature candidate SNP of TYMS (g.676789A>T) (nominal P<0.05). In addition we noted suggestive associations for tagSNPs in CBS, DHFR, DNMT3B, MAT1A, MTHFD1, and MTRR (nominal P<0.05; non-significant adjusted P). Significant interactions between nutrient biomarkers and candidate polymorphisms were observed for (i) plasma/RBC folate and FOLH1, PON1, TCN2, DNMT1, and DNMT3B; (ii) plasma PLP and TYMS TS3; (iii) plasma B12 and BHMT2; (iv) homocysteine and MTHFR and AARS. Conclusions Genetic variants in FOCM genes are associated with CRC risk among postmenopausal women. FOCM nutrients continue to emerge as effect modifiers of genetic influences on CRC risk. PMID:26108676

  3. Inhibitory effect of phytoglycoprotein on tumor necrosis factor-{alpha} and interleukin-6 at initiation stage of colon cancer in 1,2-dimethylhydrazine-treated ICR mice

    SciTech Connect

    Lee, Sei-Jung; Lim, Kye-Taek

    2007-12-01

    This study was carried out to investigate the chemopreventive potentials of plant originated glycoprotein (UDN glycoprotein, 116 kDa) isolated from the stems of Ulmus davidiana Nakai (UDN) on aberrant crypt foci (ACF) formation in 1,2-dimethylhydrazine (DMH)-treated ICR mice. UDN glycoprotein was administered to mice at 0.01% and 0.02% levels for 5 weeks. The mice were treated with 20 mg/kg DMH twice a week for 2 weeks in presence of UDN glycoprotein and killed at week 6. We found that UDN glycoprotein has inhibitory effects on the frequency of colonic aberrant crypt foci (ACF), activation of colonic proliferating cell nuclear antigen (PCNA), and release of plasma lactate dehydrogenase (LDH) in DMH-treated mice. In addition, UDN glycoprotein has anti-oxidative effects on the formation of plasma thiobarbituric acid reactive substances (TBARS) and the production of plasma inducible nitric oxide (NO) in DMH-treated mouse. Also, 0.02% UDN glycoprotein suppressed the DNA binding activities of nuclear factor-kappa B (NF-{kappa}B) and activator protein-1 (AP-1), accompanying the inhibitions of its subunits (p50, p65, c-Jun, and c-Fos), pro-inflammatory proteins [inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)], and pro-inflammatory cytokines [tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6] on DMH-stimulated ACF formation. On the basis of these results, we assume that UDN glycoprotein may be useful for colon cancer prevention at initiation stage.

  4. Learning about Cri du Chat Syndrome

    MedlinePlus

    ... chat syndrome - also known as 5p- syndrome and cat cry syndrome - is a rare genetic condition that ... du chat syndrome usually include a high-pitched cat-like cry, mental retardation, delayed development, distinctive facial ...

  5. Stem cell origin of cancer and differentiation therapy.

    PubMed

    Sell, Stewart

    2004-07-01

    Our forefathers in pathology, on observing cancer tissue under the microscope in the mid-19th century, noticed the similarity between embryonic tissue and cancer, and suggested that tumors arise from embryo-like cells [Recherches dur le Traitement du Cancer, etc. Paris. (1829); Editoral Archiv fuer pathologische Anatomie und Physiologie und fuer klinische Medizin 8 (1855) 23]. The concept that adult tissues contain embryonic remnants that generally lie dormant, but that could be activated to become cancer was later formalized by Cohnheim [Path. Anat. Physiol. Klin. Med. 40 (1867) 1-79; Virchows Arch. 65 (1875) 64] and Durante [Arch