lundi 31 décembre 2012

Focus: The ubiquitin-proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer.

Epithelial to Mesenchymal transition (EMT) in cancer, a process permitting cancer cells to become mobile and metastatic, has a signaling hardwire forged from development. Multiple signaling pathways that regulate carcinogenesis enabling characteristics in neoplastic cells such as proliferation, resistance to apoptosis and angiogenesis are also the main players in EMT. These pathways, as almost all cellular processes, are in their turn regulated by ubiquitination and the Ubiquitin-Proteasome System (UPS). Ubiquitination is the covalent link of target proteins with the small protein ubiquitin and serves as a signal to target protein degradation by the proteasome or to other outcomes such as endocytosis, degradation by the lysosome or specification of cellular localization. This paper reviews signal transduction pathways regulating EMT and being regulated by ubiquitination.

Source : The ubiquitin-proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer. Voutsadakis IA. J Biomed Sci. 2012 Jul 24;19:67.
Free paper available at:

Focus: Breast cancer chemoprevention: old and new approaches

In 1976, Sporn has defined chemoprevention as "the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred." Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected high-risk populations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused heavily on endocrine intervention using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Achieving much success in this particular setting and new approaches as low-dose administration are actually under investigations in several topics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing the risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this subgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the development of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy and provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ER-positive and ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and precancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations in breast cancer settings.

Source: Breast cancer chemoprevention: old and new approaches. Cazzaniga M, Bonanni B. J Biomed Biotechnol. 2012;2012:985620.
Free paper available at:

Focus : Endothelial cell metabolism and implications for cancer therapy.

Tumour tissue is characterised by fluctuating oxygen concentrations, decreased nutrient supply, and acidic pH. The primarily glycolytic metabolism of tumour cells contributes to this, with increased glucose consumption and increased lactate secretion. Endothelial cells are particularly challenged when recruited towards the tumour metabolic environment. They are required to proliferate and form functional networks in order to establish continuous blood flow. Considering that deregulated metabolism is an emerging hallmark of cancer and target of tumour therapy, it is of importance to incorporate the current knowledge about how the tumour metabolic environment, as a therapy target, can affect endothelial cell metabolism and the angiogenic response. Recent studies have shown differences in metabolic pathways in endothelial cells compared with other normal or tumour tissues. Therefore, we have reviewed relevant literature on endothelial metabolism and the response to angiogenic activation in conditions of metabolic stress.

Source: Endothelial cell metabolism and implications for cancer therapy. Harjes U, Bensaad K, Harris AL. Br J Cancer. 2012 Oct 9;107(8):1207-12.
Free paper available at:

vendredi 28 décembre 2012

Press Review (December 29, 2012) – Revue de presse (29 décembre 2012)

Elwood V. Jensen, Pioneer in Breast Cancer Treatment, Dies at 92
Elwood V. Jensen, a medical researcher whose studies of steroid hormones led to new treatments for breast cancer that have been credited with saving or extending hundreds of thousands of lives, died on Dec. 16 in Cincinnati. He was 92.
By Daniel E. Slotnik. In The New York Times

US cancer screening rates decline over the last 10 years, finds new study
The rate of people who seek preventive cancer screenings has fallen over the last ten years in the United States with wide variations between white-collar and blue-collar workers, according to a University of Miami Miller School of Medicine study published on December 27 in the open-access journal Frontiers in Cancer Epidemiology.
In EurekAlert (press release)

Anti-Androgen Therapies to Prevent Prostate Cancer Are Not One Size Fits All
A new study suggests that chemoprevention with anti-androgen therapies may not benefit all patients at risk for prostate cancer and could cause harm to some. Researchers at the Dana-Farber Cancer Institute and Harvard Medical School have identified a genetic mutation that actually results in a more robust transition from a precancerous to cancerous state when exposed to androgen deprivation.
By Anna Azvolinsky. In Cancer Network

Ability to Metabolize Tamoxifen Affects Breast Cancer Outcomes
For nearly a decade, breast cancer researchers studying the hormone therapy tamoxifen have been divided as to whether genetic differences in a liver enzyme affect the drug's effectiveness and the likelihood breast cancer will recur. A new study by researchers from the Mayo Clinic Cancer Center and the Austrian Breast and Colorectal Cancer Study Group provides evidence that genetic differences in the enzyme CYP2D6 play a key role in how well tamoxifen work.
In Science Daily (press release)

Breast cancer cells interact with non-cancerous tissue to drive metastasis
In addition to mutations, environmental conditions created by the tissues surrounding tumors (stroma) play a major role in cancer progression. Researchers led by Gregg Semenza at Johns Hopkins University examined the interactions between breast cancer cells and the stroma to identify underlying pro-metastatic molecular mechanisms.
In Science Codex

NIH study suggests gene variation may shape bladder cancer treatment
Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research at the National Institutes of Health.
In National Institutes of Health (press release)

Cyclin D1b is a genetic reprogrammer that drives cancer progression
Researchers led by Karen Knudsen at Thomas Jefferson University's Kimmel Cancer Center examined the role of cyclin D1b in prostate cancer.
In Science Codex

Bowel cancer gene discovery cracks mystery of families with a strong history of the disease
Cancer Research UK-funded scientists have discovered that two gene faults increase the risk of bowel cancer in families with a strong history of developing the disease, who, until now, had no explanation as to why their risk was greater. The research is published in Nature Genetics.
In Cancer Research UK

What Is a Meaningful Increased Survival?
In their quest for new agents, pharmaceutical researchers test millions of substances all over the world. They like using color-forming reactions to identify new molecules. However, in intensively colored solutions or in the case of mixtures with multiple substances these tests fail. As part of his doctoral thesis, Martin Stein, member of staff at the Chair of Biochemistry at the Technische Universitaet Muenchen, developed a testing reaction based on magnetic resonance data. It helps find a specific pharmaceutical molecule among hundreds of different substances even in the most turbid of bacterial brews
By Rebecca Bechhold. In Cancer Network (blog)

Découverte de deux gênes responsables du cancer de l'intestin
Des chercheurs britanniques pensent avoir trouvé pourquoi certaines familles sont très exposées au cancer de l’intestin. Deux gênes, transmis par les parents aux enfants, seraient en effet responsables de l’augmentation du risque de formation d'une tumeur.
Dans JOL Press

Cancer de la prostate: Un virus caché dans un macrophage pour tuer la tumeur
C’est à nouveau l’approche par virus oncolytique, un virus capable d’infecter uniquement les cellules cancéreuses et de les détruire, qui vient d’être testée pour le traitement du cancer avancé de la prostate chez l'homme.
Dans Santé.log

Le dépistage du cancer du col de l'utérus gratuit dès le 1er janvier
Le dépistage du cancer du col de l'utérus sera gratuit dans quelques jours. Les frottis (qui coûtent aujourd'hui 13 euros aux patientes) seront intégralement remboursés. C'est l'une des décisions prises vendredi soir lors du dernier Conseil des ministres de l'année.
Sur RTBF  

La cigarette affecterait les gènes du cancer‎
Le fait de fumer des cigarettes pourrait affecter les gènes du cancer dans l’ADN, montrant que la consommation de tabac altèrerait chimiquement l’activité des gènes faisant augmenter le risque de cancer.
Par Sandra Besson. Dans Actualités News Environnement

Cancer du sein en Algérie : 3 000 décès d'Algériennes par an
Environ 9 000 nouveaux cas de cancer du sein sont découverts chaque année en Algérie, et plus de 3000 victimes en meurent.
Par J Boukraa. Dans

Focus : Hope-based intervention for individuals susceptible to colorectal cancer: a pilot study

Individuals undergoing genetic testing for hereditary colorectal cancer (HCRC) are prone to develop psychological problems. This study investigated the short-term efficacy of a hope-based intervention program in increasing hope levels and decreasing psychopathology among HCRC genetic testing recipients. A longitudinal study was carried out on HCRC genetic testing recipients recruited by the Hereditary Gastrointestinal Cancer Registry. Participants joined a hope-based intervention program consisting of six sessions of weekly closed group therapy. Psychological questionnaires were administered immediately before the first and after the last sessions of the program measuring hope, anxiety and depression levels of the participants. There were 22 participants (7 men and 15 women) at a mean age of 49.4 ± 9.6 years. Women tended to have higher level of anxiety than men at pre-intervention. Paired sample t tests were conducted. Hope levels increased significantly from pre- to post-intervention (pre-total hope score = 5.56; post-total hope score = 6.07; t(1) = -0.281, p < 0.05). Anxiety level also decreased significantly from pre- to post-intervention (pre-anxiety score = 7.38; post-anxiety score = 5.90; t (1) = 2.35, p < 0.05). Our findings imply that hope-based intervention program would be effective in enhancing hope in HCRC genetic testing recipients. The program may also be more effective in alleviating anxiety than depression in these individuals.

Source: Hope-based intervention for individuals susceptible to colorectal cancer: a pilot study. Ho SM, Ho JW (, Pau BK, Hui BP, Wong RS, Chu AT. Fam Cancer. 2012 Dec;11(4):545-51.
Free paper available at:

jeudi 27 décembre 2012

Mutated genes in cancer (84) – BRIP1 (FANCJ)

BRIP1 (alias FANCJ)

In databases :

Ensembl ( ENSG00000136492
UniProt ( Q9BX63
GeneCards ( FANCJ
HGNC ( 20473 or BRIP1

Gene locus:


Protein name:

BRCA1 interacting protein C-terminal helicase 1 (BRIP1) or Fanconi anemia, complementation group J (FANCJ)

Protein Size:

1249 amino acids; about 141 Da


The protein encoded by BRIP1 is DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. It acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination (see Fanconi Anemia genes). It is involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1

Cancer-related alterations:

Defects in BRIP1 are a cause of low-risk susceptibility to breast cancer.

Defects in BRIP1 are the cause of Fanconi anemia complementation group J (FANCJ) (see Fanconi Anemia genes)

References (open access):

Pathology of hereditary breast cancer. van der Groep P, van der Wall E, van Diest PJ. Cell Oncol (Dordr). 2011 Apr;34(2):71-88.

Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass. Xie J, Litman R, Wang S, Peng M, Guillemette S, Rooney T, Cantor SB. Oncogene. 2010 Apr 29;29(17):2499-508.

Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers. Rebbeck TR, Mitra N, Domchek SM, Wan F, Chuai S, Friebel TM, Panossian S, Spurdle A, Chenevix-Trench G; kConFab, Singer CF, Pfeiler G, Neuhausen SL, Lynch HT, Garber JE, Weitzel JN, Isaacs C, Couch F, Narod SA, Rubinstein WS, Tomlinson GE, Ganz PA, Olopade OI, Tung N, Blum JL, Greenberg R, Nathanson KL, Daly MB. Cancer Res. 2009 Jul 15;69(14):5801-10.

Focus: Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations

Leukaemia-propagating cells are more frequent in high-risk acute B lymphoblastic leukaemia than in many malignancies that follow a hierarchical cancer stem cell model. It is unclear whether this characteristic can be more universally applied to patients from non-'high-risk' sub-groups and across a broad range of cellular immunophenotypes. Here, we demonstrate in a wide range of primary patient samples and patient samples previously passaged through mice that leukaemia-propagating cells are found in all populations defined by high or low expression of the lymphoid differentiation markers CD10, CD20 or CD34. The frequency of leukaemia-propagating cells and their engraftment kinetics do not differ between these populations. Transcriptomic analysis of CD34(high) and CD34(low) blasts establishes their difference and their similarity to comparable normal progenitors at different stages of B-cell development. However, consistent with the functional similarity of these populations, expression signatures characteristic of leukaemia propagating cells in acute myeloid leukaemia fail to distinguish between the different populations. Together, these findings suggest that there is no stem cell hierarchy in acute B lymphoblastic leukaemia.

Source: Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations. Rehe K, Wilson K, Bomken S, Williamson D, Irving J, den Boer ML, Stanulla M, Schrappe M, Hall AG, Heidenreich O, Vormoor J ( EMBO Mol Med. 2012 Dec 11.
Free paper available at:

Focus: Statins and the risk of gastric cancer in diabetes patients

BACKGROUND: Several studies have suggested a cancer risk reduction in statin users although the evidence remains weak for stomach cancer. The purpose of this study was to use an exact-matching case--control design to examine the risk of gastric cancer associated with the use of statins in a cohort of patients with diabetes.
Cases were defined as patients with incident gastric cancer identified by International Classification of Diseases 16.0 ~ 16.9 recorded at Samsung Medical Center database during the period of 1999 to 2008, at least 6 months after the entry date of diabetes code. Each gastric cancer case patient was matched with one control patient from the diabetes patient registry in a 1:1 fashion, blinded to patient outcomes.
A total of 983 cases with gastric cancer and 983 controls without gastric cancer, matched by age and sex, were included in the analysis. The presence of prescription for any statin was inversely associated with gastric cancer risk in the unadjusted conditional logistic regression model (OR: 0.18; 95% CI: 0.14 -- 0.24; P < .0001). Multivariate analysis using conditional logistic regression with Bonferroni's correction against aspirin indicated a significant reduction in the risk of gastric cancer in diabetes patients with statin prescriptions (OR: 0.21; 95% CI: 0.16 -- 0.28; P < .0001). After adjustment for aspirin use, a longer duration of statin use was associated with reduced risk of gastric cancer, with statistical significance (P<.0001).
A strong inverse association was found between the risk of gastric adenocarcinoma and statin use in diabetic patients.

Source: Statins and the risk of gastric cancer in diabetes patients. Lee J, Lee SH, Hur KY, Woo SY, Kim SW, Kang WK ( BMC Cancer. 2012 Dec 13;12(1):596.
Free paper available at:

mercredi 26 décembre 2012

Focus: JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer

Hyperactive PI3K/mTOR signaling is prevalent in human malignancies and its inhibition has potent antitumor consequences. Unfortunately, single-agent targeted cancer therapy is usually short-lived. We have discovered a JAK2/STAT5-evoked positive feedback loop that dampens the efficacy of PI3K/mTOR inhibition. Mechanistically, PI3K/mTOR inhibition increased IRS1-dependent activation of JAK2/STAT5 and secretion of IL-8 in several cell lines and primary breast tumors. Genetic or pharmacological inhibition of JAK2 abrogated this feedback loop and combined PI3K/mTOR and JAK2 inhibition synergistically reduced cancer cell number and tumor growth, decreased tumor seeding and metastasis, and also increased overall survival of the animals. Our results provide a rationale for combined targeting of the PI3K/mTOR and JAK2/STAT5 pathways in triple-negative breast cancer, a particularly aggressive and currently incurable disease.

Source: JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer. Britschgi A, Andraos R, Brinkhaus H, Klebba I, Romanet V, Müller U, Murakami M, Radimerski T, Bentires-Alj M ( Cancer Cell. 2012 Dec 11;22(6):796-811.
Free paper available at:

Focus: Effect of SMURF2 Targeting on Susceptibility to MEK Inhibitors in Melanoma

BackgroundThe mitogen-activated protein-kinase pathway consisting of the kinases RAF, MEK, and ERK is central to cell proliferation and survival and is deregulated in more than 90% of melanomas. MEK inhibitors are currently trialled in the clinic, but despite efficient target inhibition, cytostatic rather than cytotoxic activity limits their efficacy.MethodsWe assessed the cytotoxicity to MEK inhibitors (PD184352 and selumetinib) in melanoma cells by toluidine-blue staining, caspase 3 cleavage, and melanoma-sphere growth. Western blotting and quantitative real-time polymerase chain reaction were applied to determine SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2), PAX3, and MITF expression. Human melanoma samples (n = 77) from various stages were analyzed for SMURF2 and PAX3 expression. RNA interference was performed to target SMURF2 during MEK inhibition in vivo in melanoma xenografts in mice and zebrafish. All statistical tests were two-sided.ResultsActivation of transforming growth factor β (TGF-β) signalling sensitized melanoma cells to the cytotoxic effects of MEK inhibition. Melanoma cells resistant to the cytotoxic effects of MEK inhibitors counteracted TGF-β signalling through overexpression of the E3 ubiquitin ligase SMURF2, which resulted in increased expression of the transcription factors PAX3 and MITF. High MITF expression protected melanoma cells against MEK inhibitor cytotoxicity. Depleting SMURF2 reduced MITF expression and substantially lowered the threshold for MEK inhibitor-induced apoptosis. Moreover, SMURF2 depletion sensitized melanoma cells to the cytotoxic effects of selumetinib, leading to cell death at concentrations approximately 100-fold lower than the concentration required to induce cell death in SMURF2-expressing cells. Mice treated with selumetinib alone at a dosage of 10mg/kg body weight once daily produced no response, but in combination with SMURF2 depletion, selumetinib suppressed tumor growth by 97.9% (95% confidence interval = 38.65% to 155.50%, P = .005).ConclusionsTargeting SMURF2 may be a novel therapeutic approach for increasing the antitumor efficacy of MEK inhibitors.

Source: Effect of SMURF2 Targeting on Susceptibility to MEK Inhibitors in Melanoma. Smith MP, Ferguson J, Arozarena I, Hayward R, Marais R, Chapman A, Hurlstone A, Wellbrock C ( J Natl Cancer Inst. 2012 Dec 17.
Free paper available at:

mardi 25 décembre 2012

Anticancer molecules (103) – Molécules anticancéreuses (103) -VISMODEGIB


Name: vismodegib
Commercial name: Erivedge
Pharmacological class: hedgehog pathway inhibitor
Therapeutic class: antineoplastic
Action: vismodegib is an orally bioavailable small molecule with potential antineoplastic activity. Vismodegib targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO

In 2012, vismodegib is approved:

for the treatment of adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation


Nom: vismodegib
Nom commercial: Erivedge
Classe pharmacologique: inhibiteur de la voie de signalisation « Hedgehog »
Classe thérapeutique: antinéoplasiques
Action: biodisponible oralement, le vismodegib cible la voie de signalisation « Hedgehog », en bloquant les activités des récepteurs de surface cellulaire PTCH et / ou SMO liant Hedgehog. La voie de signalisation Hedgehog joue un rôle important dans la croissance et la réparation tissulaire; l’activation constitutive aberrante de cette voie de signalisation et la prolifération cellulaire incontrôlée qui l’accompagne peuvent être associées à des mutations dans les récepteurs PTCH et SMO.

En 2012, le vismodegib est approuvé:

Pour le traitement d’adultes ayant un carcinome à cellules basales métastatique ou un carcinome à cellules basales localement avancé récurrent après chirurgie ou qui ne sont pas candidats à la chirurgie, et qui ne sont pas candidats à la radiothérapie.

Focus: Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis

BACKGROUND: Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor beta. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC).
In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib.
Tumor growth and pulmonary metastasis were significantly suppressed in an orthotopic HCC model. Immunoblotting revealed that among known dovitinib targets, only PDGFR-beta was expressed in two HCC cell lines, while four of five endothelial lines expressed PDGFR-beta, FGFR-1, and VEGFR-2. Dovitinib inhibited endothelial cell proliferation and motility at 0.04 mumol/L, a pharmacologically relevant concentration; it was unable to inhibit the proliferation or motility of HCC cells at the same concentration. Immunohistochemical analyses showed that dovitinib significantly decreased the microvessel density of xenograft tumors, inhibiting proliferation and inducing apoptosis in HCC cells.
Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells.

Source: Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis. Chen ZY, Shi M, Peng LX, Wei W, Li XJ, Guo ZX, Li SH, Zhong C, Qian CN, Guo RP ( J Transl Med. 2012 Dec 10;10(1):245.
Free paper available at:

dimanche 23 décembre 2012

Focus: Advances in oncologic imaging: Update on 5 Common Cancers

Imaging has become a pivotal component throughout a patient's encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow-up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, and colorectal cancers, and lymphoma.

Source: Advances in oncologic imaging: Update on 5 Common Cancers. Akin O, Brennan SB, Dershaw DD, Ginsberg MS, Gollub MJ, Schöder H, Panicek DM, Hricak H. CA Cancer J Clin. 2012 Nov;62(6):364-93.
Free paper available at :

Focus: Removing barriers to participation in clinical trials, a conceptual framework and retrospective chart review study

BACKGROUND: Enrollment in interventional therapeutic clinical trials is a small fraction of all patients who might participate given reasonable access.
A hierarchical approach is utilized in measuring staged participation from trial availability to patient enrollment. Our framework suggests that concern for justice comes in the design and eligibility criteria for clinical trials; attention to beneficence is given in the eligibility and physician triage stages. The remaining four stages rely on respect for persons. An example is given where reasons for nonparticipation or barriers to participation in prostate cancer clinical trials are examined within the framework. In addition, medical oncology patients with an initial six month consultation are tracked from one stage to the next by race using the framework to assess participation comparability.
We illustrated seven transitions from being a patient to enrollment in a clinical trial in a small study of prostate cancer cases who consulted SKCCC Medical Oncology Department in early 2010. Pilot data suggest transition probabilities as follows: 65 % availability, 84 % eligibility, 92 % patient triage, 89 % trials discussed, 45 % patient interested, 63 % patient consented, and 92 % patient enrolled. The average transition probability was 77.7 %. The average transition probability, patient-trial-fit was 50 %; opportunity was 51 %, and acceptance was 66.7 %. Trial availability, patient interest and patient consented were three transitions that were below the average; none were statistically significant.
The framework may serve to streamline comprehensive reporting of clinical trial participation to the benefit of patients and the ethical conduct of clinical trials

Source: Removing barriers to participation in clinical trials, a conceptual framework and retrospective chart review study. Kanarek NF (, Kanarek MS, Olatoye D, Carducci MA. Trials. 2012 Dec 10;13(1):237.
Free paper available at:

Focus: Lung cancer risk at low cumulative asbestos exposure: meta-regression of the exposure-response relationship

Existing estimated lung cancer risks per unit of asbestos exposure are mainly based on, and applicable to, high exposure levels. To assess the risk at low cumulative asbestos exposure, we provide new evidence by fitting flexible meta-regression models, a notably new and more robust method.
Studies were selected if lung cancer risk per cumulative asbestos exposure in at least two exposure categories was reported. From these studies (n = 19), we extracted 104 risk estimates over a cumulative exposure range of 0.11-4,710 f-y/ml. We fitted linear and natural spline meta-regression models to these risk estimates. A natural spline allows risks to vary nonlinearly with exposure, such that estimates at low exposure are less affected by estimates in the upper exposure categories. Associated relative risks (RRs) were calculated for several low cumulative asbestos exposures.
A natural spline model fitted our data best. With this model, the relative lung cancer risk for cumulative exposure levels of 4 and 40 f-y/ml was estimated between 1.013 and 1.027, and 1.13 and 1.30, respectively. After stratification by fiber type, a non-significant three- to fourfold difference in RRs between chrysotile and amphibole fibers was found for exposures below 40 f-y/ml. Fiber-type-specific risk estimates were strongly influenced by a few studies.
The natural spline regression model indicates that at lower asbestos exposure levels, the increase in RR of lung cancer due to asbestos exposure may be larger than expected from previous meta-analyses. Observed potency differences between different fiber types are lower than the generally held consensus. Low-exposed industrial or population-based cohorts with quantitative estimates of asbestos exposure a required to substantiate the risk estimates at low exposure levels from our new, flexible meta-regression.

Source: Lung cancer risk at low cumulative asbestos exposure: meta-regression of the exposure-response relationship. van der Bij S (, Koffijberg H, Lenters V, Portengen L, Moons KG, Heederik D, Vermeulen RC. Cancer Causes Control. 2012
Free paper available at:

vendredi 21 décembre 2012

Press Review (December 22, 2012) – Revue de presse (22 décembre 2012)

Game changing diagnostic & prognostic prostate cancer genetic tests revealed by Jefferson
Researchers at the Kimmel Cancer Center at Jefferson have developed potentially game-changing diagnostic and prognostic genetic tests shown to better predict prostate cancer survival outcomes and distinguish clinically-relevant cancers.
In EurekAlert (press release)

Scientists Engineer Algae To Produce New Targeted Cancer Therapy
Next-generation cancer therapies are notoriously expensive. But maybe not for long.
By Emily Elert. In Popular Science

Cancer breakthrough: Disease depends on surrounding normal cells to spread, study finds
In a major breakthrough, Toronto scientists have discovered a new approach to cancer treatment that would target the “normal” cells embedded around tumours.
By Joseph Hall. In Toronto Star

Breast cancer photo projects on show at UAB Visual Arts Gallery
The University of Alabama at Birmingham (UAB) Visual Arts Gallery will present two powerful photographic projects on young women and breast cancer by fashion photographer David Jay Jan. 7-31, 2013.
By Shannon Thomason. In UAB News

Enzyme linked to prostate cancer may help identify lethal form of disease
Cancer researchers have identified an enzyme specifically linked to prostate cancer that they believe may help in early detection of an aggressive and deadly form of the disease.
By Noor Javed. In Toronto Star

MicroRNAs present exciting opportunities for cancer therapy and diagnosis
MicroRNA molecules potential biomarkers for early cancer detection, reports cancer biomarkers.
In EurekAlert (press release)

Coffee Drinking Linked With Lower Oral Cancer Death Risk: Study
As if there weren't already a host of other reasons to love coffee, a new study links drinking several cups a day with a decreased risk of dying from oral cancer.
In Huffington Post

Cancer News Blood cell gene fault linked to breast and ovarian cancer
Scientists have linked a rare genetic fault in the immune system to an increased risk of breast and ovarian cancers.
In Cancer Research UK

Poison for cancer cells: New method identifies active agents in mixtures of hundreds of substances
In their quest for new agents, pharmaceutical researchers test millions of substances all over the world. They like using color-forming reactions to identify new molecules. However, in intensively colored solutions or in the case of mixtures with multiple substances these tests fail. As part of his doctoral thesis, Martin Stein, member of staff at the Chair of Biochemistry at the Technische Universitaet Muenchen, developed a testing reaction based on magnetic resonance data. It helps find a specific pharmaceutical molecule among hundreds of different substances even in the most turbid of bacterial brews
In Medical XPress

Des boules de glace pour soigner le cancer du sein
Les patientes atteintes de cancer du sein pourraient être traitées sans chirurgie grâce au développement d'une technique qui détruit les tumeurs en les gelant.
Dans JOL Press (Blog)

Le café, un bon anti-cancer
Selon une récente étude américaine, boire régulièrement du café diminuerait considérablement le risque de développer des cancers de la bouche ou de la gorge.

Cancer : les cellules tumorales ne supportent pas la pression !
L'allongement de la durée du traitement par tamoxifène en adjuvant à 10 ans permet de réduire le risque de récidive tardive du cancer du sein avec expression des récepteurs aux estrogènes (ER+) et améliore la survie, selon l'étude ATLAS (Adjuvant Tamoxifen - Longer Against Shorter) présentée au San Antonio Breast Cancer Symposium (SABCS) et publiée simultanément dans le Lancet.
Par Janlou Chaput. Dans Futura-Sciences  

Aider les patients sous chimio qui sont « dans le brouillard »‎
La médecine s'intéresse de plus en plus aux troubles cognitifs qui touchent temporairement certaines personnes traitées pour un cancer.
Par Pauline Fréour. Dans Le Figaro-Santé 

Cancer : des médicaments fabriqués grâce à des algues
Traditionnellement dédiée à la production de biocarburants, l'algue microspique Chlamydomonas reinhardtii permet de produire à moindre coût des protéines complexes utilisées dans le traitement de certains cancers.
Par Marc Mennessier. Dans Le Figaro-Santé