mercredi 31 octobre 2012

Focus: Adherence evaluation of endocrine treatment in breast cancer: methodological aspects

BACKGROUND: Current studies on adherence to endocrine therapy in breast cancer patients suffer from methodological limitations due to a lack of well-validated methods for assessing adherence. There is no gold standard for measuring adherence. The aim of our study was to compare four different approaches for evaluating adherence to anastrozole therapy for breast cancer with regard to concordance between methods.
Outpatients with early breast cancer treated with anastrozole completed the multi-method assessment of adherence. We implemented a self-report scale (the Simplified Medication Adherence Questionnaire), physician- ratings, refill records and determination of anastrozole serum concentration.
Comparison of the four approaches using Spearman rank correlation revealed poor concordance across all methods reflecting weak correlations of 0.2-0.4. Considering this data incomparability across methods, we still observed high adherence rates of 78%-98% across measures.
Our findings contribute to the growing body of knowledge on the impact that methodological aspects exert on the results of adherence measurement in breast cancer patients receiving endocrine treatment. Our findings suggest that the development and validation of instruments specific to patients receiving endocrine agents is imperative in order to arrive at a more accurate assessment and to subsequently obtain more precise estimates of adherence rates in this patient population.

Source: Adherence evaluation of endocrine treatment in breast cancer: methodological aspects. Oberguggenberger AS, Sztankay M, Beer B, Schubert B, Meraner V, Oberacher H, Kemmler G, Giesinger J, Gamper E, Sperner-Unterweger B, Marth C, Holzner B, Hubalek M ( BMC Cancer. 2012 Oct 15;12(1):474.
Free paper available at:

mardi 30 octobre 2012

Focus: A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer

Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These datashow that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.

Source: A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer. Steve Goodison, Myron Chang, Yunfeng Dai, Virginia Urquidi, Charles J. Rosser. Plos One 7(10): e47469.
Free paper available at:

lundi 29 octobre 2012

FDA approves Synribo for chronic myelogenous leukemia

The U.S. Food and Drug Administration recently approved Synribo (omacetaxine mepesuccinate) to treat adults with chronic myelogenous leukemia (CML). Synribo is intended to be used in patients whose cancer progressed after treatment with at least two drugs from a class called tyrosine kinase inhibitors (TKIs), also used to treat CML.

Synribo is the second drug approved to treat CML in the past two months. On Sept. 4, 2012, the FDA approved Bosulif (bosutinib) to treat patients with chronic, accelerated or blast phase Philadelphia chromosome positive CML who are resistant to or who cannot tolerate other therapies.

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 Oct 15.
Free paper available at:

vendredi 26 octobre 2012

Press Review (October 27, 2012) – Revue de presse (27 octobre 2012)

Many Terminal Cancer Patients Put False Hope in Chemo, Study Finds
Doctors must improve their message, researchers say.
By Serena Gordon. In U.S. News & World Report

International Team Reports on Large-Scale Pancreatic Cancer Analysis‎
A whole-exome sequencing and copy number variation study of pancreatic cancer published online today in Nature suggests that the disease sometimes involves alterations to genes and pathways best known for their role in axon guidance during embryonic development.
In GenomeWeb

Acupuncture may ease dry mouth after cancer‎
People with chronic dry mouth related to cancer treatment reported some improvement in symptoms like sticky saliva and dry lips after eight weeks of group acupuncture, in a new study from the UK.
By Genevra Pittman. In Reuters

A Cancer Survivor's Reaction to Lance Armstrong's Downfall
I was half way through a course of chemotherapy when I learned Lance Armstrong was riding in a bike race in Manhattan. Lance had just won another Tour de France, and though I had never followed cycling before, I knew I had to see this post-cancer wonder.
By Emily Cousins. In Huffington Post

Targeted Radiation for Breast Cancer May Cause More Complications ‎
Study found brachytherapy had higher rates of wound, skin problems than whole-breast treatment in older women.
In U.S. News & World Report

Targeted breast cancer therapies coming to the forefront‎
Researchers uncovering more effective methods as they learn more about intricacies of disease.
By Scott Dance. In Baltimore Sun

Brain tumors may grow by causing brain cells to reset
A common type of brain tumor may be caused by mature adult cells being genetically "rewound" to a more immature state, according to a study in the journal Science.
By Jon Bardin. In Los Angeles Times

Les Français optimistes pour la lutte contre le cancer
Un sondage Ipsos pour la Fondation ARC montre que deux Français sur trois pensent en avoir un, un jour, mais 71% pensent aussi que le cancer sera vaincu dans vingt ans.
Par Damien Mascret. Dans Le Figaro

Cancer du sein : l'échographie plus efficaces chez les trentenaires que la mammographie
Chez les femmes de moins de 40 ans, les échographies mammaires seraient un outil de détection de cancer du sein plus efficace que les mammographies, selon une étude américaine publiée le 22 octobre dans la revue American Journal of Roentgenology.
Dans Le Parisien

Alimentation et cancers : des liens encore difficiles à démêler
L’alimentation est impliquée dans 30 à 35 % des cancers. Ça, les chercheurs en sont à peu près sûrs. Mais ils ont beaucoup de mal à identifier quels sont les aliments impliqués et par quels mécanismes ces aliments augmentent ou diminuent les risques de cancer.
Par Sylvie Montaron. Dans Le Progrès

Tester la rigidité des tissus pour estimer l'agressivité d'un cancer‎
Une équipe suisse de l'université de Bâle a démontré que la mesure de la dureté d'un tissu biologique permet d'identifier la nature de tumeurs, bénignes ou malignes.
Dans Le Monde

Un anticorps du lupus pour traiter le cancer ?
Un anticorps du lupus, maladie qui attaque les cellules et tissus sains du corps, rend les cellules cancéreuses plus sensibles à la chimiothérapie rapporte une nouvelle étude. Ce résultat est le premier à montrer que des anticorps du lupus pourraient être utilisés pour traiter le cancer.

Focus : Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events

Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and 3 lung tumor/normal pairs. Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Smoker and never-smoker cancer samples exhibit distinguishable patterns of mutations. A number of epigenetic regulators, including KDM6A, ASH1L, SMARCA4 and ATAD2, are frequently altered by mutations or copy number changes. A systematic survey of splice-site mutations identified 106 splice site mutations associated with cancer specific aberrant splicing, including mutations in several known cancer-related genes. RAC1b, an isoform of the RAC1 GTPase that includes one additional exon, was found to be preferentially up-regulated in lung cancer. We further show that its expression is significantly associated with sensitivity to a MAP2K (MEK) inhibitor PD-0325901. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer-specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers. The detailed characterizations of the lung cancer cell lines also provide genomic context to the vast amount of experimental data gathered for these lines over the decades, and represent highly valuable resources for cancer biology.

Source: Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Liu J, Lee W, Jiang Z, Chen Z, Jhunjhunwala S, Haverty PM, Gnad F, Guan Y, Gilbert H, Stinson J, Klijn C, Guillory J, Bhatt D, Vartanian S, Walter K, Chan J, Holcomb T, Dijkgraaf P, Johnson S, Koeman J, Minna JD, Gazdar AF, Stern HM, Hoeflich KP, Wu TD, Settleman J, de Sauvage FJ, Gentleman RC, Neve RM, Stokoe D, Modrusan Z, Seshagiri S, Shames DS, Zhang Z ( Genome Res. 2012 Oct 2.
Free paper available at:

jeudi 25 octobre 2012

Mutated genes in cancer (81) – SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127


In databases :

Ensembl ( ENSG00000073578;
UniProt ( P31040;
GeneCards ( SDHA ;
HGNC ( 10680 or SDHA;

Gene locus :


Protein name:

Succinate dehydrogenase complex, subunit A, flavoprotein variant

Protein Size:

664 amino acids; about 73 kDa


In databases :

Entrez ( SDHAF2 or 54949;
Ensembl ( ENSG000000167985;
UniProt ( Q9NX18;
GeneCards ( SDHAF2 ;
HGNC ( 26034 or SDHAF2;

Gene locus:


Protein name:

Succinate dehydrogenase complex assembly factor 2

Protein Size:

166 amino acids; about 20 kDa


In databases :

Ensembl ( ENSG00000117118;
UniProt ( P21912;
GeneCards ( SDHB ;
HGNC ( 10681 or SDHB ;

Gene locus:


Protein name:

Succinate dehydrogenase complex, subunit B, iron sulfur (Ip)

Protein size:

280 amino acids; about 32 kDa


In databases :

Ensembl ( ENSG00000143252;
UniProt ( Q99643;
GeneCards ( SDHC ;
HGNC ( 10682 or SDHC;

Gene locus :


Protein name:

Succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa

Protein size:

169 amino acids; about 19 kDa


In databases :

Ensembl ( ENSG00000204370;
UniProt ( O14521;
GeneCards ( SDHD;
HGNC ( 10683 or SDHD;

Gene locus :


Protein name :

Succinate dehydrogenase complex, subunit D, integral membrane protein

Protein Size :

159 amino acids; about 17 kDa


In databases :

Entrez ( TMEM127 or 55654;
Ensembl ( ENSG00000135956;
UniProt ( O75204;
GeneCards ( TMEM127 ;
HGNC ( 26038 or TMEM127;

Gene locus:


Protein name:

transmembrane protein 127

Protein Size:

238 amino acids; about 26 kDa


SDH is part of the mitochondrial electron transport chain (complex II, succinate-ubiquinone oxidoreductase) and catalyses the oxidation of succinate to fumarate in the Krebs cycle. Subunits A and B of this complex (SDHA, SDHB) constitute the catalytic core of the enzyme, while SDHC with SDHD anchor the complex to the matrix face of the mitochondrial inner membrane. SDHAF2 is an SDH cofactor that appears to be required for SDHA flavination, stability of the SDH complex, and therefore the function of the SDH enzyme. Abnormal SDH function due to mutations of nuclear DNA encoding for one of its subunits results in two completely different phenotypes. Defects in SDHA cause metabolic neurodegenerative disorders like congenital Leigh syndrome and late-onset optic atrophy, ataxia and myopathy, whereas SDHB, SDHC, and SDHD mutations predispose to familial PGL. The molecular and cellular mechanisms linking these latter SDHx mutations and tumorigenesis have not been fully elucidated. Also, the pathophysiology of distinct clinical phenotypes associated with abnormalities in different SDH subunits remains to be unraveled.
TMEM127 is a transmembrane protein that control cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1. It may act as a tumor suppressor. Relationships between SDH and TMEM127 poorly known.

Cancer-related alterations:

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare, usually benign tumors of the sympathetic or parasympathetic paraganglia. Pheochromocytoma is the tumor of the main sympathetic paraganglia, which is the adrenal medulla. The sympathetic paraganglioma secretes catecholamine while the parasympathetic do not. Both of them originate from neural crest cells and share similar mechanisms of tumor development. The same genetic alteration may predispose to the development of sympathetic and parasympathetic paraganglioma. Up to 35% of these tumors may be hereditary; they are associated with germline mutations in genes encoding subunits of the succinate dehydrogenase (SDH) enzyme complex in the context of the familial PGL syndromes, PGL1, 3 and 4 caused by mutations in the SDHD,SDHC and SDHB genes, respectively. Another familial PGL syndrome, PGL2, which is currently exclusively associated with head and neck paragangliomas, is caused by mutations in SDHAF2. Recently mutations were found in the SDHA subunit in a limited number of patients with PGL and/or PCC. Another gene found to predispose to PGL and/or PCC when mutated is TMEM127.
Less frequently, mutations in the genes responsible for Von Hippel Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN2), and neurofibromatosis type 1 (NF1) are also found in patients with hereditary PCC and PGL.

The SDHB, SDHC and SDHD gene mutations (but not SDHA) can also be found in patients with PGL and/or PCC and gastrointestinal stromal tumors (GISTs), also known as the Carney-Stratakis syndrome; SDHB mutations, in particular, may also predispose to thyroid and renal cancer, and possibly other tumors.

Mitochondrial dysfunction due to SDHx mutations have been linked to tumorigenesis by upregulation of hypoxic and angiogenesis pathways, apoptosis resistance and developmental culling of neuronal precursor cells. SDHB-, SDHC-, and SDHD-associated PGLs give rise to more or less distinct clinical phenotypes. SDHB mutations mainly predispose to extra-adrenal, and to a lesser extent, adrenal PGLs, with a high malignant potential, but also head and neck paragangliomas (HNPGL). SDHD mutations are typically associated with multifocal HNPGL and usually benign adrenal and extra-adrenal PGLs. SDHC mutations are a rare cause of mainly HNPGL. Most abdominal and thoracic SDHB-PGLs hypersecrete either norepinephrine or norepinephrine and dopamine.


Recent advances in the genetics of SDH-related paraganglioma and pheochromocytoma. Hensen EF, Bayley JP. Fam Cancer. 2011 Jun;10(2):355-63.

SDHA is a tumor suppressor gene causing paraganglioma. Burnichon N, Brière JJ, Libé R, Vescovo L, Rivière J, Tissier F, Jouanno E, Jeunemaitre X, Bénit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP. Hum Mol Genet. 2010 Aug 1;19(15):3011-20.

Hereditary Paraganglioma-Pheochromocytoma Syndromes. Klein RD, Lloyd RV, Young WF. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2008 May 21 [updated 2009 Sep 03].

The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. Stratakis CA, Carney JA. J Intern Med. 2009 Jul;266(1):43-52.

Focus: Adipocyte-derived endotrophin promotes malignant tumor progression

Adipocytes represent a major cell type in the mammary tumor microenvironment and are important for tumor growth. Collagen VI (COL6) is highly expressed in adipose tissue, upregulated in the obese state, and enriched in breast cancer lesions and is a stimulator of mammary tumor growth. Here, we have described a cleavage product of the COL6α3 chain, endotrophin (ETP), which serves as the major mediator of the COL6-mediated tumor effects. ETP augmented fibrosis, angiogenesis, and inflammation through recruitment of macrophages and endothelial cells. Moreover, ETP expression was associated with aggressive mammary tumor growth and high metastatic growth. These effects were partially mediated through enhanced TGF-β signaling, which contributes to tissue fibrosis and epithelial-mesenchymal transition (EMT) of tumor cells. Our results highlight the crucial role of ETP as an obesity-associated factor that promotes tumor growth in the context of adipocyte interactions with tumor and stromal cells.

Source: Adipocyte-derived endotrophin promotes malignant tumor progression. Park J, Scherer PE ( J Clin Invest. 2012 Oct 8.
Free paper available at:

mercredi 24 octobre 2012

Focus: The association between MTHFR 677C>T polymorphism and cervical cancer: evidence from a meta-analysis

BACKGROUND: MTHFR 677C>T polymorphism is a genetic alteration in an enzyme involved in folate metabolism, but its effect on host susceptibility to cervical cancer is still uncertain. The aim of this study was to investigate the association between MTHFR 677C>T polymorphism and cervical cancer by performing a meta-analysis.
Pubmed, Embase, Web of Science, and the Chinese Biomedical Database (CBM) databases were searched for case--control studies investigating the association between MTHFR 677C>T polymorphism and cervical cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess this possible association.
11 studies with a total of 1898 cervical cancer cases and 2678 controls were included. Meta-analyses of a total 11 studies showed no association between MTHFR 677C>T polymorphism and cervical cancer using all five genetic models (All P values > 0.05). However, subgroup analyses showed the odds of the homozygous TT genotype were much less in cervical cancer cases than in controls in Europeans, which implied an association between the homozygous TT genotype and cervical cancer in Europeans (For TT versus CC, fixed-effects OR = 0.65, 95%CI 0.45-0.93, P = 0.020, I2 = 0.0%). The odds for the homozygous TT genotype were greater in cervical cancer cases than in controls in East Asians, which also implied an association between the homozygous TT genotype and cervical cancer in East Asians (For TT versus CC, random-effects OR = 1.66, 95%CI 1.05-2.62, P = 0.029, I2 = 52.6%; For TT versus CT/CC, random-effects OR = 1.55, 95%CI 1.09-2.22, P = 0.016, I2 = 42.4%). Both subgroup analyses and meta-regression analyses suggested ethnicity was the major source of heterogeneity. Publication bias was not evident.
This meta-analysis supports an association between MTHFR 677C>T polymorphism and cervical cancer, and the effect of this association may be race specific. Further studies with large sample sizes and careful design are needed to identify this association more comprehensively.

Source: The association between MTHFR 677C>T polymorphism and cervical cancer: evidence from a meta-analysis. Mei Q, Zhou D, Gao J, Shen S, Wu J, Guo L, Liang Z ( ). BMC Cancer. 2012 Oct 11;12(1):467.
Free paper available at:

lundi 22 octobre 2012

Focus: TRIM59, a novel multiple cancer biomarker for immunohistochemical detection of tumorigenesis.

We identified a novel TRIM59 gene, as an early signal transducer in two (SV40Tag and Ras) oncogene pathways in murine prostate cancer (CaP) models. We explore its clinical applications as a multitumour marker detecting early tumorigenesis by immunohistochemistry (IHC).
88 CaP patients were from a tissue microarray (TMA) of radical prostatectomy specimen, 42 patients from a 35 multiple tumour TMA, 75 patients with renal cell carcinoma (RCC) and 92 patients from eight different tumour groups (breast, lung, parotid, gastrointestinal, female genital tract, bladder, kidney and prostate cancer).
TRIM59 upregulation specifically in tumour area was determined by IHC in 291 cases of 37 tumour types. To demonstrate that TRIM59 upregulation is 'tumour-specific', we characterised a significant correlation of TRIM59 IHC signals with tumorigenesis and progression, while in control and normal area, TRIM59 IHC signal was all negative or significantly low. TRIM59 protein upregulation in prostate and kidney cancers was detectable in both intensity and extent in early tumorigenesis of prostate intraepithelial neoplasia (p<0.05) and grade 1 of RCC (p<0.05), and stopped until high grades cancer. The results of the correlation in these two large cohorts of tumour types confirmed and repeated murine CaP model studies. Enhanced TRIM59 expression was identified in most of the 37 different tumours, while the highest intensities were in lung, breast, liver, skin, tongue and mouth (squamous cell cancer) and endometrial cancers. Multiple tumour upregulation was further confirmed by comparing relative scores of TRIM59 IHC signals in eight tumours with a larger patient population; and by a mouse whole-mount embryo (14.5 days post conception) test on the origin of TRIM59 upregulation in epithelial cells.
TRIM59 may be used a novel multiple tumour marker for immunohistochemical detecting early tumorigenesis and could direct a novel strategy for molecular-targeted diagnosis and therapy of cancer.

Source: TRIM59, a novel multiple cancer biomarker for immunohistochemical detection of tumorigenesis. Khatamianfar V, Valiyeva F, Rennie PS, Lu WY, Yang BB, Bauman GS, Moussa M, Xuan JW ( BMJ Open. 2012 Oct 8;2(5).
Free paper available at:

Recently adopted names for antitumoral compounds (October 2012) - Noms d’antitumoraux adoptés récemment (octobre 2012)

Name (nom)
Code name

Synthetic small molecule inhibitor
Monoclonal antibody
Insulin-like growth factor II
ON 01210
Chlorobenzylsulfone derivative