vendredi 29 mars 2013

Press Review (March 30, 2013) – Revue de presse (30 mars 2013)

Scientists discover new DNA regions associated with three cancers
Researchers working on an international gene-hunting project identify new genetic markers linked with breast, ovarian and prostate cancer.
By Eryn Brown. In The Los Angeles Times

Cigarette labels may educate about bladder cancer
Graphic warning labels on packs of cigarettes may convince some people that smoking ups the risk of bladder cancer, says a new study from Canada.
By Andrew Seaman. Reuters

Cancer Drug That Shrinks All Tumors Set To Begin Human Clinical Trials
Researchers are one step closer to uncovering a cancer treatment that could be applicable across the board in killing every kind of cancer tumor.
By Sara Gates. In Huffington Post

Tumor DNA studies help explain cancer genetics
As it has become more efficient and less expensive to analyze the DNA in normal cells, it has also gotten a whole lot easier to analyze the mutated DNA in tumors — a project scientists hope will help explain why cancer behaves as it does and what new strategies oncologists might use to stop its growth.
By Eryn Brown. In The Los Angeles Times

18 Million Cancer Survivors Expected by 2022
An aging population coupled with improved treatment methods mean more people will survive cancer. But at what cost?
By Alexandra Sifferlin. In TIME

Cancer Biologists Find DNA-Damaging Toxins in Common Plant-Based Foods
In a laboratory study pairing food chemistry and cancer biology, scientists at the Johns Hopkins Kimmel Cancer Center tested the potentially harmful effect of foods and flavorings on the DNA of cells. They found that liquid smoke flavoring, black and green teas and coffee activated the highest levels of a well-known, cancer-linked gene called p53.
In Science Daily (press release)

What does the genetic markers study mean for cancer research? – video
Science correspondent Ian Sample discusses the findings of a medical study that identified genetic markers for breast, ovarian and prostate cancer. The study means it will soon be possible for patients to discover their risk of getting certain cancers in a £5 spit test at their GP. But what are the implications of these developments and what further possibilities will they open up?
By Leah Green. In The Guardian

Le vaccin contre le cancer du col de l'utérus est une évolution fantastique et efficace
Moins d'un tiers des adolescentes sont vaccinées contre le cancer du col de l'utérus. Comment expliquer cette faible couverture vaccinale alors qu'il s'agit de se prémunir contre le 12e cancer le plus fréquent chez les femmes ? Pourquoi les Français se méfient-ils du vaccin HPV ? Réponse de Jean-Charles Boulanger, gynécologue-obstétricien.
Par Jean-Charles Boulanger. Dans Le Nouvel Observateur

Weibo révèle le désastre des villages du cancer
Grâce à cet équivalent de Twitter, les citoyens lèvent le voile sur la crise environnementale qui ronge la Chine..
By Leslie Hook. Dans Courrier International

Un médicament ralentit le vieillissement et la progression du cancer
Des chercheurs de l'Université de Montréal ont découvert un nouveau mécanisme moléculaire qui peut possiblement ralentir le processus du vieillissement tout comme la progression de certaines formes de cancer. Ces chercheurs expliquent dans la sortie électronique du 23 mars de la revue Aging Cell comment ils ont trouvé qu'un antidiabétique, soit la metformine, réduit la production des cytokines inflammatoires qui normalement activent le système immunitaire, mais qui, en cas de surproduction, peuvent mener à une inflammation pathologique, une condition qui endommage les tissus dans le processus du vieillissement et qui favorise la croissance d'une tumeur cancéreuse.

CANCER du POUMON: Les isoflavones du soja prolongent la survie
Un apport alimentaire plus élevé en soja avant un diagnostic du cancer du poumon vient d’être associé à une survie prolongée chez les femmes, selon cette étude publiée dans l’édition du 25 mars du Journal of Clinical Oncology.
Dans Santé Log

L'algorithme de Google utilisé pour traquer le cancer du poumon
Dans une étude publiée dans la revue Cancer Research, on apprend que la lutte contre le cancer compte un nouvel atout: l'algorithme de Google.
Dans Huffington Post

jeudi 28 mars 2013

Focus: A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells

In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in invasive cell lines when compared to normal and less invasive cell lines. Transfection of miR-200c, miR-205, and miR-375 mimics into MDA-MB-231 cells led to the inhibition of in vitro cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that miR-200c plays a pivotal role in regulating the invasiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer invasiveness and ultimately lead to the identification of novel biomarkers associated with prognosis.

Source: A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells.   Luo D, Wilson JM, Harvel N, Liu J, Pei L, Huang S, Hawthorn L, Shi H ( J Transl Med. 2013 Mar 5;11:57.
Free paper available at:

mardi 26 mars 2013

Focus: Increased Sensitivity to Chemotherapy Induced by CpG-ODN Treatment Is Mediated by microRNA Modulation

We recently reported that peritumoral CpG-ODN treatment, activating TLR-9 expressing cells in tumor microenvironment, induces modulation of genes involved in DNA repair and sensitizes cancer cells to DNA-damaging cisplatin treatment. Here, we investigated whether this treatment induces modulation of miRNAs in tumor cells and their relevance to chemotherapy response. Array analysis identified 20 differentially expressed miRNAs in human IGROV-1 ovarian tumor cells from CpG-ODN-treated mice versus controls (16 down- and 4 up-regulated). Evaluation of the role of the 3 most differentially expressed miRNAs on sensitivity to cisplatin of IGROV-1 cells revealed significantly increased cisplatin cytotoxicity upon ectopic expression of hsa-miR-302b (up-modulated in our array), but no increased effect upon reduced expression of hsa-miR-424 or hsa-miR-340 (down-modulated in our array). Accordingly, hsa-miR-302b expression was significantly associated with time to relapse or overall survival in two data sets of platinum-treated ovarian cancer patients. Use of bio-informatics tools identified 19 mRNAs potentially targeted by hsa-miR-302b, including HDAC4 gene, which has been reported to mediate cisplatin sensitivity in ovarian cancer. Both HDAC4 mRNA and protein levels were significantly reduced in IGROV-1 cells overexpressing hsa-miR-302b. Altogether, these findings indicate that hsa-miR-302b acts as a "chemosensitizer" in human ovarian carcinoma cells and may represent a biomarker able to predict response to cisplatin treatment. Moreover, the identification of miRNAs that improve sensitivity to chemotherapy provides the experimental underpinning for their possible future clinical use.

Source: Increased Sensitivity to Chemotherapy Induced by CpG-ODN Treatment Is Mediated by microRNA Modulation. De Cecco L, Berardi M, Sommariva M, Cataldo A, Canevari S, Mezzanzanica D, Iorio MV, Tagliabue E, Balsari A ( PLoS One. 2013;8(3):e58849.
Free paper available at:

lundi 25 mars 2013

Focus : Cardiotoxicity of cancer therapeutics: current issues in screening, prevention, and therapy

In the context of modern cancer chemotherapeutics, cancer survivors are living longer and being exposed to potential comorbidities related to non-cancer side effects of such treatments. With close monitoring of cancer patients receiving potentially cardiotoxic medical therapies, oncologists, and cardiologists alike are identifying patients in both clinical and subclinical phases of cardiovascular disease related to such chemotherapies. Specifically, cardiotoxicity at the level of the myocardium and potential for the development of heart failure are becoming a growing concern with increasing survival of cancer patients. Traditional chemotherapeutic agents used commonly in the treatment of breast cancer and hematologic malignancies, such as anthracyclines and HER-2 antagonists, are well known to be associated with cardiovascular sequelae. Patients often present without symptoms and an abnormal cardiac imaging study performed as part of routine evaluation of patients receiving cardiotoxic therapies. Additionally, patients can present with signs and symptoms of cardiovascular disease months to years after receiving the chemotherapies. As the understanding of the physiology underlying the various cancers has grown, therapies have been developed that target specific molecules that represent key aspects of physiologic pathways responsible for cancer growth. Inhibition of these pathways, such as those involving tyrosine kinases, has lead to the potential for cardiotoxicity as well. In view of the potential cardiotoxicity of specific chemotherapies, there is a growing interest in identifying patients who are at risk of cardiotoxicity prior to becoming symptomatic or developing cardiotoxicity that may limit the use of potentially life-saving chemotherapy agents. Serological markers and novel cardiac imaging techniques have become the source of many investigations with the goal of screening patients for pre-clinical cardiotoxicity. Additionally, studies have been performed.

Source : Cardiotoxicity of cancer therapeutics: current issues in screening, prevention, and therapy. Sheppard RJ (, Berger J, Sebag IA. Front Pharmacol. 2013;4:19.
Free paper available at:

vendredi 22 mars 2013

Press Review (March 23, 2013) – Revue de presse (23 mars 2013)

Breast cancer drug does not provide value for money, regulator rules
Charity expresses disappointment after Nice rules everolimus should not be available for widespread NHS use.
In The Guardian

Gene Therapy Spurs Leukemia Hope
Researchers reported fresh evidence Wednesday that using gene therapy to manipulate the immune system is emerging as a promising new strategy in the fight against cancer.
By Ron Winslow. The Wall Street Journal

New Imaging Agent Enables Better Cancer Detection, More Accurate Staging
Researchers at the University of California, San Diego School of Medicine have shown that a new imaging dye, designed and developed at UC San Diego Moores Cancer Center, is an effective agent in detecting and mapping cancers that have reached the lymph nodes.
In UCSD Medical Center

Iraq War Anniversary: Birth Defects And Cancer Rates At Devastating High In Basra And Fallujah (VIDEO)
Ten years after the start of the U.S. invasion in Iraq, doctors in some of the Middle Eastern nation's cities are witnessing an abnormally high number of cases of cancer and birth defects. Scientists suspect the rise is tied to the use of depleted uranium and white phosphorus in military assaults.
By Eline Gordts. In Huffington Post

Cancer Research Technology and The Institute of Cancer Research enter collaboration with Janssen to discover multiple myeloma drug
Multiple myeloma is the third most common type of blood cancer, with around 4,700 new cases and around 2,600 deaths each year in the UK. It is often effectively treated initially but many patients become resistant to treatment, and there is an urgent need for new therapies.
In Cancer Research UK

Genetics May Be Tied to Breast Cancer Risk in Unexpected Ways
Scientists found new connections among genes, hormone sensitivity and fat.
In U.S. News & World Report

On Surviving a Brain Cancer Death Sentence
Valerie Harper received a death sentence. Just like my father. And while I hope that she lives as long as she can, comfortably and with dignity, "surviving" these types of cancer does not always mean what we would like it to.
By Davis Schneiderman. In Huffington Post

Dépister un cancer grâce à une prise de sang ?
Le dépistage précoce d’un cancer est fondamental dans le traitement de la maladie. Néanmoins, malgré les prouesses technologiques dans le domaine de l’imagerie médicale, la détection d’un cancer est parfois trop tardive. Une étude récente montre que l’on peut directement identifier des facteurs tumoraux dans le sang. Se dirige-t-on vers le dépistage grâce à une simple prise de sang ?
Par Agnès Roux. Dans Futura Sciences

Cancer du sein : mesdames, méfiez-vous du lait entier, il augmenterait les risques de mortalité
Selon une étude américaine, les femmes en rémission d'un cancer du sein doivent éviter de consommer trop de produits laitiers à base de lait entier.

CANCER: 7 règles de vie pour réduire son risque de 50%
Ces 7 mesures pourraient réduire de moitié le risque de développer un cancer, selon cette grande étude américaine.
Dans Santé Log

CANCER: Une protéine du poisson inhibe les métastases
Une protéine de poisson capable d’inhiber les métastases du cancer, c’est ce que viennent de découvrir ces chercheurs de l’Université du Maryland. Dérivé de la morue du Pacifique, ce composé naturel à l’activité anti-tumorale pourrait permettre de développer des aliments qui agissent comme des traitements complémentaires contre le cancer. Ces conclusions viennent d’être publiées dans l’édition des Actes de l’Académie des Science américaine (PNAS).
Dans Santé Log

Plus que jamais, le cancer appauvrit
Selon le constat alarmant de l'Observatoire sociétal des malades de la Ligue contre le cancer, "les malades n'arrivent plus à financer le quotidien".
Dans Le Point

jeudi 21 mars 2013

Anticancer molecules (105) – Molécules anticancéreuses (105) - CARFILZOMIB


Name: carfilzomib
Commercial name: Kyprolis
Pharmacological class: proteasome inhibitor
Therapeutic class: antineoplastic
Action: carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme that degrades unwanted cellular proteins. Inhibition of proteasome-mediated proteolysis results in a build-up of polyubiquinated proteins, which may cause cell cycle arrest, apoptosis, and inhibition of tumor growth.

In 2012, carfilzomib is approved:

for patients with multiple myeloma progression while on or after treatment with bortezomib and an immunomodulatory agent.


Nom: carfilzomib
Nom commercial: Kyprolis
Classe pharmacologique: inhibiteur du protéasome
Classe thérapeutique: antinéoplasiques
Action: le carfilzomib se lie de façon irréversible et inhibe l'activité de type chymotrypsine du protéasome 20S, une enzyme qui dégrade les protéines cellulaires indésirables. L'inhibition de la protéolyse médiée par le protéasome amène à une accumulation de protéines polyubiquitinées, ce qui peut entraîner un arrêt du cycle cellulaire, l'apoptose et l'inhibition de la croissance tumorale.
En 2012, le carfilzomib est approuvé:

chez les patients souffrant de myélome multiple en progression, pendant ou après le traitement par le bortézomib et un agent immunomodulateur.

Focus: Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1-BCR-ABL-JAK2 Complex

Imatinib mesylate (IM) induces clinical remission of chronic myeloid leukemia (CML). The Abelson helper integration site 1 (AHI-1) oncoprotein interacts with BCR-ABL and Janus kinase 2 (JAK2) to mediate IM response of primitive CML cells, but the effect of the interaction complex on the response to ABL and JAK2 inhibitors is unknown.

The AHI-1-BCR-ABL-JAK2 interaction complex was analyzed by mutational analysis and coimmunoprecipitation. Roles of the complex in regulation of response or resistance to ABL and JAK2 inhibitors were investigated in BCR-ABL + cells and primary CML stem/progenitor cells and in immunodeficient NSG mice. All statistical tests were two-sided.

The WD40-repeat domain of AHI-1 interacts with BCR-ABL, whereas the N-terminal region interacts with JAK2; loss of these interactions statistically significantly increased the IM sensitivity of CML cells. Disrupting this complex with a combination of IM and an orally bioavailable selective JAK2 inhibitor (TG101209 [TG]) statistically significantly induced death of AHI-1-overexpressing and IM-resistant cells in vitro and enhanced survival of leukemic mice, compared with single agents (combination vs TG alone: 63 vs 53 days, ratio = 0.84, 95% confidence interval [CI] = 0.6 to 1.1, P = .004; vs IM: 57 days, ratio = 0.9, 95% CI = 0.61 to 1.2, P = .003). Combination treatment also statistically significantly enhanced apoptosis of CD34+ leukemic stem/progenitor cells and eliminated their long-term leukemia-initiating activity in NSG mice. Importantly, this approach was effective against treatment-naive CML stem cells from patients who subsequently proved to be resistant to IM therapy.

Simultaneously targeting BCR-ABL and JAK2 activities in CML stem/progenitor cells may improve outcomes in patients destined to develop IM resistance.

Source: Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1-BCR-ABL-JAK2 Complex. Chen M, Gallipoli P, Degeer D, Sloma I, Forrest DL, Chan M, Lai D, Jorgensen H, Ringrose A, Wang HM, Lambie K, Nakamoto H, Saw KM, Turhan A, Arlinghaus R, Paul J, Stobo J, Barnett MJ, Eaves A, Eaves CJ, Holyoake TL, Jiang X ( J Natl Cancer Inst. 2013 Feb 27.
Free paper available at:

mercredi 20 mars 2013

Focus: Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis

BACKGROUND: Fascin-1 is an actin-bundling protein expressed in many human carcinomas, although absent from most normal epithelia. Fascin-1 promotes filopodia formation, migration and invasion in carcinoma cells; in mouse xenograft tumor models it contributes to metastasis. Fascin-1 is an interesting candidate biomarker for aggressive, metastatic carcinomas but data from individual studies of human tumors have not yet been pooled systematically.
This systematic review was conducted in accordance with PRISMA guidelines, using fixed and random effects models, as appropriate, to undertake meta-analysis.
A total of 26 immunohistochemical studies of 5 prevalent human carcinomas were identified for meta-analysis. Fascin-1 was associated with increased risk of mortality for breast (pooled hazard ratio, (HR) = 2.58; 95% confidence interval (CI) 1.48 to 4.52; P = 0.001), colorectal (HR = 1.60 (1.37 to 1.86; P <0.001) and esophageal carcinomas (HR = 1.35; CI 1.13 to 1.60; P = 0.001). There was no evidence of association of fascin-1 with mortality in gastric and lung carcinomas. Fascin-1 was associated with increased risk of disease progression in breast (HR = 2.48; CI 1.38 to 4.46; P = 0.002) and colorectal carcinomas (HR = 2.12; CI 1.00 to 4.47; P = 0.05), but not with progression of lung carcinomas (HR = 0.95; CI 0.49 to 1.85; P = 0.9). Fascin-1 was associated with increased risk of lymph node metastasis in colorectal (pooled risk ratio (RR) = 1.47; CI 1.26 to 1.71; P <0.001) and gastric carcinomas (RR = 1.43; CI 1.21 to 1.70; P <0.001). There was no evidence of association of fascin-1 with lymph node metastasis in lung or esophageal carcinomas. Fascin-1 was associated with increased risk of distant metastasis in colorectal (RR = 1.70; CI 1.18 to 2.45; P = 0.004) and gastric carcinomas (RR = 1.93; CI 1.21 to 3.33; P = 0.02). No association with distant metastasis in esophageal carcinomas was observed. Pooling across all the carcinomas provided strong evidence for association of fascin-1 with increased risk of mortality (HR = 1.44; CI 1.24 to 1.68; P <0.001; n = 3,645), lymph node metastasis (RR = 1.36; CI 1.18 to 1.55; P <0.001; n = 2,906) and distant metastasis (1.76; 1.34 to 2.32; P <0.001; n = 1,514).
Fascin-1 is associated consistently with increased risk of mortality in breast, colorectal and esophageal carcinomas and with metastasis in colorectal and gastric carcinomas. The results were stable to various sensitivity analyses and did not vary by predefined subgroups. These data will assist rational decision making for focusing investigations of fascin-1 as a biomarker or therapeutic target onto the most relevant carcinomas.

Source: Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis. Tan VY, Lewis SJ, Adams JC, Martin RM ( BMC Med. 2013 Feb 26;11(1):52.
Free paper available at :

mardi 19 mars 2013

lundi 18 mars 2013

FDA approves Lymphoseek to help locate lymph nodes in patients with certain cancers

The U.S. Food and Drug Administration recently approved Lymphoseek (technetium Tc 99m tilmanocept) Injection, a radioactive diagnostic imaging agent that helps doctors locate lymph nodes in patients with breast cancer or melanoma who are undergoing surgery to remove tumor-draining lymph nodes.

Lymph nodes filter lymphatic fluid that flows from the body’s tissues. This fluid may contain cancer cells, especially if the fluid drains a part of the body containing a tumor. By surgically removing and examining the lymph nodes that drain a tumor, doctors can sometimes determine if a cancer has spread.

Lymphoseek is an imaging drug that helps locate lymph nodes; it is not a cancer imaging drug. Lymphoseek is the first new drug used for lymph node mapping to be approved in more than 30 years. Other FDA-approved drugs used for lymph node mapping include sulfur colloid (1974) and isosulfan blue (1981).

More data at:

vendredi 15 mars 2013

Press Review (March 16, 2013) – Revue de presse (16 mars 2013)

Inadequate Treatment of Ovarian Cancer
A new study has found widespread failure among doctors to follow clinical guidelines for treating ovarian cancer, which kills 15,000 women a year in this country. This disturbing news shows the kind of challenge that health care reformers are up against in improving medical care — even when cost is not the issue.
In The New York Times

News Blood test tracks cancer
A blood test for DNA shed by dying tumour cells might one day be used to track a patient's response to therapy, results from a pilot study in breast cancer suggest. The technique would provide an alternative to invasive biopsies that retrieve tumour tissue for analysis.
By Heidi Ledford. In Nature

FDA approves imaging drug for cancer lymph nodes
The Food and Drug Administration has approved a new imaging drug to help doctors locate lymph nodes in patients with breast cancer and skin cancer.
In USA Today

Cancer costs
Educating patients is key, but the US National Cancer Institute must keep spending in check.
In Nature

New Monoclonal Antibody Developed That Can Target Proteins Inside Cancer Cells
Researchers have discovered a unique monoclonal antibody that can effectively reach inside a cancer cell, a key goal for these important anticancer agents, since most proteins that cause cancer or are associated with cancer are buried inside cancer cells. Scientists from Memorial Sloan-Kettering Cancer Center and Eureka Therapeutics have collaborated to create the new human monoclonal antibody, which targets a protein associated with many types of cancer and is of great interest to cancer researchers.
In Science Daily

Blood test reveals women's response to breast cancer treatment
Breast tumour DNA circulating in the bloodstream could be used to measure how well a woman’s cancer is responding to treatment, according to a new Cancer Research UK study published in the New England Journal of Medicine.
In Cancer Research UK

Heart disease risk after breast cancer radiotherapy smaller than previously thought
Researchers have for the first time calculated by how much radiotherapy for breast cancer increases the risk of heart disease and the findings can now be used by doctors to help treat patients more appropriately, according to a study published in the New England Journal of Medicine today (Wednesday).
In Cancer Research UK

En vidéo : comment faire pour éradiquer le cancer ?
Alors que le cancer a tué près de 150.000 Français en 2011, comment s’organiser pour faire encore reculer la mortalité de cette terrible maladie ? Futura-Sciences vous propose deux vidéos qui expliquent comment, jour après jour, la recherche progresse et s’équipe de nouvelles armes pour améliorer les soins et les traitements pour les patients.
Par Janlou Chaput. Dans Futura Sciences

La recherche sur le cancer, toujours une bonne affaire?
La médecine du cancer devrait devenir, selon des prévisions, le secteur industriel le plus lucratif de la santé au cours des prochaines années. Un secteur dominé par les géants pharmaceutiques suisses Roche et Novartis.
Par Chantal Britt. Dans

Prévenir le cancer et protéger les futures générations de femmes !
Chaque année en France, 1 000 femmes décèdent d'un cancer du col de l'utérus. Dans le monde, elles sont 275 000, c'est une femme qui meurt toutes les deux minutes, en majorité dans les pays en développement . Des cancers et des décès qui peuvent quasiment tous, être évités.
Par Seth Berkley et Jacqueline Godet. Dans Le Monde

Une piste génétique pour traiter le cancer colorectal
Une équipe anglaise a identifié trois gènes impliqués dans l'apparition de 60% des cancers colorectaux.
Par Aude Rambaud. Dans Le Figaro santé

Focus: Alcohol drinking cessation and the risk of laryngeal and pharyngeal cancers: a systematic review and meta-analysis

To evaluate the effect of alcohol cessation on the risk of developing laryngeal and pharyngeal cancers, combining available evidence in the scientific literature in a meta-analysis.
A systematic literature review was conducted, and a meta-analysis was applied on the retrieved studies. The generalised least squares method was used to estimate the trend from dose-response data to assess changes in the risks of laryngeal and pharyngeal cancers after drinking cessation.
A total of 9 case-control studies were included in the meta-analysis (4 and 8 estimates for laryngeal and pharyngeal cancers, respectively). On average, alcohol drinking cessation was associated with a 2% yearly reduction in the risk of developing laryngeal and pharyngeal cancers. There was a considerable heterogeneity between the studies of pharyngeal cancer, but this was mostly due to two studies. The increased risk of laryngeal and pharyngeal cancers caused by alcohol was reversible; the time periods until the risks became equal to those of never drinkers were 36 (95% CI 11-106) and 39 (95% CI 13-103) years, respectively. Moreover, 5 years of drinking cessation was associated with a reduction of around 15% in the alcohol-related elevated risk of laryngeal and pharyngeal cancers.
Although a long time period is required to completely eliminate the alcohol-related elevated risk of laryngeal and pharyngeal cancers, a substantial risk reduction can be seen in the short term (5-10 years), and drinking cessation should therefore be encouraged to reduce the incidence of these cancers.

Source: Alcohol drinking cessation and the risk of laryngeal and pharyngeal cancers: a systematic review and meta-analysis. Ahmad Kiadaliri A (, Jarl J, Gavriilidis G, Gerdtham UG. PLoS One. 2013;8(3):e58158.
Free paper available at :

jeudi 14 mars 2013

Focus: Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines

Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44) and a main population which was either weakly positive or negative for CD44 (CD44). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44CD90 sub-population. Moreover, these CD44CD90 cells revealed mesenchymal morphology, increased expression of mesenchymal markers and , increased mRNA levels of the embryonic stem cell related genes and and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44CD90 population a good candidate for the lung CSCs. Both CD44CD90 and CD44CD90 cells in the PLCCL derived from SCC formed spheroids, whereas the CD44 cells were lacking this potential. These results indicate that CD44CD90 sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44 sub-population.

Source: Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines. Wang P, Gao Q, Suo Z, Munthe E, Solberg S, Ma L, Wang M, Westerdaal NA, Kvalheim G, Gaudernack G ( PLoS One. 2013;8(3):e57020.
Free paper available at :

mercredi 13 mars 2013

FDA approves Stivarga for advanced gastrointestinal stromal tumors

            The U.S. Food and Drug Administration recently expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease.

            Stivarga, a multi-kinase inhibitor, blocks several enzymes that promote cancer growth. With this new approval, Stivarga is intended to be used in patients whose GIST cancer cannot be removed by surgery or has spread to other parts of the body (metastatic) and is no longer responding to Gleevec (imatinib) and Sutent (sunitinib), two other FDA-approved drugs to treat GIST.

mardi 12 mars 2013

Focus: Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress

We recently showed that differential expression of extracellular matrix (ECM) genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4) with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p=0.001). Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR=3.0, 95% CI=1.3-7.0, p=0.0098). Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT) genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III) phenotype. These findings support the key relevance of neoplastic and stroma interaction in breast cancer progression.

Source: Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress. Triulzi T, Casalini P, Sandri M, Ratti M, Carcangiu ML, Colombo MP, Balsari A, Ménard S, Orlandi R, Tagliabue E ( PLoS One. 2013;8(2):e56761.
Free paper available at: