Focus: Tumor cells positive and negative for the common cancer stem cell markers are capable of initiating tumor growth and generating both progenies

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The cancer stem cell (CSC) model depicts that tumors are hierarchically organized and maintained by CSCs lying at the apex. CSCs have been "identified" in a variety of tumors through the tumor-forming assay, in which tumor cells distinguished by a certain cell surface marker (known as a CSC marker) were separately transplanted into immunodeficient mice. In such assays, tumor cells positive but not negative for the CSC marker (hereby defined as CSC(+) and CSC(-) cells, respectively) have the ability of tumor-forming and generating both progenies. However, here we show that CSC(+) and CSC(-) cells exhibit similar proliferation in the native states. Using a cell tracing method, we demonstrate that CSC(-) cells exhibit similar tumorigenesis and proliferation as CSC(+) cells when they were co-transplanted into immunodeficient mice. Through serial single-cell derived subline construction, we further demonstrated that CSC(+) and CSC(-) cells from CSC marker expressing tumors could invariably generate both progenies, and their characteristics are maintained among different generations irrespective of the origins (CSC(+)-derived or CSC(-)-derived). These findings demonstrate that tumorigenic cells cannot be distinguished by common CSC markers alone and we propose that cautions should be taken when using these markers independently to identify cancer stem cells due to the phenotypic plasticity of tumor cells.

Source: Tumor cells positive and negative for the common cancer stem cell markers are capable of initiating tumor growth and generating both progenies. Huang SD (huangsd@smmu.edu.cn), Yuan Y, Tang H, Liu XH, Fu CG, Cheng HZ, Bi JW, Yu YW, Gong DJ, Zhang W, Chen J, Xu ZY. PLoS One. 2013;8(1):e54579

Free paper available at:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054579

Focus: Matricellular proteins: priming the tumour microenvironment for cancer development and metastasis

Matricellular proteins have been classified as a family of non-structural matrix proteins capable of modulating a variety of biological processes within the extracellular matrix (ECM). These proteins are expressed dynamically and their cellular functions are highly dependent upon cues from the local environment. Recent studies have shown an increasing appreciation of the key roles these ECM proteins play within the tumour microenvironment. Induced by either tumour cells or tumour stromal components, matricellular proteins initiate downstream signalling events that lead to proliferation, invasion, matrix remodelling and dissemination to pre-metastatic niches in other organs. In this review, we summarise and discuss the current knowledge of the diverse roles these proteins play within the microenvironment that influences tumour progression and potential for future therapies targeting the tumour microenvironment.

Source: Matricellular proteins: priming the tumour microenvironment for cancer development and metastasis. Wong GS, Rustgi AK. Br J Cancer. 2013 Jan 15.

Free paper available at:

http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2012592a.pdf

Focus : The Cancer Stem Cell Marker CD133 Interacts with Plakoglobin and Controls Desmoglein-2 Protein Levels

Abstract

The pentaspan membrane glycoprotein CD133 (also known as prominin-1) has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin (also known as γ-catenin), a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi) results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.

Source: The Cancer Stem Cell Marker CD133 Interacts with Plakoglobin and Controls Desmoglein-2 Protein Levels. Koyama-Nasu R, Takahashi R, Yanagida S, Nasu-Nishimura Y, Oyama M, Kozuka-Hata H, Haruta R, Manabe E, Hoshino-Okubo A, Omi H, Yanaihara N, Okamoto A, Tanaka T, Akiyama T (akiyama@iam.u-tokyo.ac.jp). PLoS One. 2013;8(1):e53710.

Free paper available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542344/pdf/pone.0053710.pdf

FDA approves Gleevec for children with acute lymphoblastic leukemia

The U.S. Food and Drug Administration recently approved a new use of Gleevec (imatinib) to treat children newly diagnosed with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

ALL is the most common type of pediatric cancer and progresses quickly if untreated. Children with Ph+ ALL have a genetic abnormality that causes proteins called tyrosine kinases to stimulate the bone marrow to make too many immature white blood cells. This leaves less room for healthy white blood cells needed to fight infection.

Gleevec, a tyrosine kinase inhibitor, blocks the proteins that promote the development of cancerous cells. It should be used in combination with chemotherapy to treat children with Ph+ ALL.

Gleevec was granted accelerated approval in 2001 to treat patients with blast crisis, accelerated phase or chronic phase Ph+ chronic myeloid leukemia (CML) who have failed interferon-alpha therapy. It has since been approved to treat several conditions, most recently regular approval to treat children newly diagnosed with Ph+ CML (2011) and regular approval to treat adults whose Kit (CD117)-positive gastrointestinal stromal tumors (GIST) have been surgically removed (2012).

More information at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm336868.htm

Focus: Recent advances in the diagnosis and treatment of bladder cancer

ABSTRACT: Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/ blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/ or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed.

Source: Recent advances in the diagnosis and treatment of bladder cancer. Cheung G, Sahai A, Billlia M, Dasgupta P, Khan MS (shamim.khan@gstt.nhs.uk). BMC Med. 2013 Jan 17;11(1):13.

Free paper available at:

http://www.biomedcentral.com/content/pdf/1741-7015-11-13.pdf

Focus: Cancer statistics, 2013

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,660,290 new cancer cases and 580,350 cancer deaths are projected to occur in the United States in 2013. During the most recent 5 years for which there are data (2005-2009), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.5% per year in women. Overall, cancer death rates have declined 20% from their peak in 1991 (215.1 per 100,000 population) to 2009 (173.1 per 100,000 population). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate). Over the past 10 years of data (2000-2009), the largest annual declines in death rates were for chronic myeloid leukemia (8.4%), cancers of the stomach (3.1%) and colorectum (3.0%), and non-Hodgkin lymphoma (3.0%). The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of approximately 1.18 million deaths from cancer, with 152,900 of these deaths averted in 2009 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket and other underserved populations.

Source: Cancer statistics, 2013. Siegel R (Rebecca.siegel@cancer.org), Naishadham D, Jemal A. CA Cancer J Clin. 2013 Jan 17.

Free paper available at:

http://onlinelibrary.wiley.com/doi/10.3322/caac.21166/pdf

Focus : The Wnt Gatekeeper SFRP4 Modulates EMT, Cell Migration and Downstream Wnt Signalling in Serous Ovarian Cancer Cells

Aberrant Wnt signalling is implicated in numerous human cancers, and understanding the effects of modulation of pathway members may lead to the development of novel therapeutics. Expression of secreted frizzled related protein 4 (SFRP4), an extracellular modulator of the Wnt signalling pathway, is progressively lost in more aggressive ovarian cancer phenotypes. Here we show that recombinant SFRP4 (rSFRP4) treatment of a serous ovarian cancer cell line results in inhibition of β-catenin dependent Wnt signalling as measured by TOP/FOP Wnt reporter assay and decreased transcription of Wnt target genes, Axin2, CyclinD1 and Myc. In addition, rSFRP4 treatment significantly increased the ability of ovarian cancer cells to adhere to collagen and fibronectin, and decreased their ability to migrate across an inflicted wound. We conclude that these changes in cell behaviour may be mediated via mesenchymal to epithelial transition (MET), as rSFRP4 treatment also resulted in increased expression of the epithelial marker E-cadherin, and reduced expression of Vimentin and Twist. Combined, these results indicate that modulation of a single upstream gatekeeper of Wnt signalling can have effects on downstream Wnt signalling and ovarian cancer cell behaviour, as mediated through epithelial to mesenchymal plasticity (EMP). This raises the possibility that SFRP4 may be used both diagnostically and therapeutically in epithelial ovarian cancer.

Source: The Wnt Gatekeeper SFRP4 Modulates EMT, Cell Migration and Downstream Wnt Signalling in Serous Ovarian Cancer Cells. Ford CE (caroline.ford@unsw.edu.au), Jary E, Ma SS, Nixdorf S, Heinzelmann-Schwarz VA, Ward RL. PLoS One. 2013;8(1):e54362.

Free paper available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543420/pdf/pone.0054362.pdf

Press Review (January 26, 2013) – Revue de presse (26 janvier 2013)

Promising Prognostic Marker for Aggressive Breast Cancer

A team of researchers led by Goutham Narla, MD, PhD, at Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, and collaborators at the Mount Sinai School of Medicine and Erasmus Medical Center, have discovered a gene variant that drives the spread of breast cancer. Published in Science Translational Medicine, the study lays the early foundation for predicting which breast cancer patients may develop more aggressive disease and for designing more effective treatments.

In Science Daily

http://www.sciencedaily.com/releases/2013/01/130123195106.htm

Cancer expert remains to be convinced by breast screening review

Harms from breast cancer screening outweigh benefits if death caused by treatment is included.

In EurekAlert (press release)

http://www.eurekalert.org/pub_releases/2013-01/bmj-cer012413.php

SNPs Associated With Breast Cancer Risk Alter Binding Affinity for Pioneer Factor FOXA1

Dartmouth scientists showed that more than half of all the SNPs associated with breast cancer risk are located in distant regions and bound by FOXA1, a protein required for estrogen receptor-α (ER) function according to a paper published in the journal Nature Genetics in November.

In Science Daily (press release)

http://www.sciencedaily.com/releases/2013/01/130123165044.htm

Personal Epigenetic 'Signatures' Found Consistent in Prostate Cancer Patients' Metastases

In a genome-wide analysis of 13 metastatic prostate cancers, scientists at the Johns Hopkins Kimmel Cancer Center found consistent epigenetic "signatures" across all metastatic tumors in each patient. The discovery of the stable, epigenetic "marks" that sit on the nuclear DNA of cancer cells and alter gene expression, defies a prevailing belief that the marks vary so much within each individual's widespread cancers that they have little or no value as targets for therapy or as biomarkers for treatment response and predicting disease severity.

In Science Daily

http://www.sciencedaily.com/releases/2013/01/130123144041.htm

Researchers prevent cancer spread by blocking tissue scarring

Researchers at BRIC, University of Copenhagen have shown that the enzyme Lysyl Oxidase (LOX) can create a "scarred" microenvironment that enhances cancer spreading.

In Medical Xpress

http://medicalxpress.com/news/2013-01-cancer-blocking-tissue-scarring.html

Planning for Bacteria in Cancer Patients May Help Hospitals Fight Infections

What cancerous conditions lead to what kinds of bacterial infections? If doctors knew, they could predict which patients would likely benefit from pre-treatment with certain kinds of antibiotics. A University of Colorado Cancer Center study published in this month's issue of the International Journal of Infectious Diseases shows the answer: E. coli and Klebsiella pneumoniae are especially prevalent in patients with lung and GI cancers, more so for Klebsiella if these patients have been treated previously with aminopenicillins.

In Science Daily

http://www.sciencedaily.com/releases/2013/01/130123165105.htm

Research: Lupus drugs carry no significant cancer risk for patients

People who take immunosuppressive drugs to treat lupus do not necessarily increase their cancer risk according to new research led by scientists at the Research Institute of the McGill University Health Centre (RI-MUHC). This landmark study, which was published in Annals of the Rheumatic Diseases this month, addresses long-standing fears of a link between lupus medication and cancer.

In EurekAlert (press release)

http://www.eurekalert.org/pub_releases/2013-01/muhc-rld012413.php

Can Metastasis of Triple-Negative Breast Cancer Be Thwarted?

Researchers have demonstrated how a particularly aggressive type of breast cancer, triple-negative disease, spreads to other parts of the body. The results may lead to new therapies that could treat metastatic breast cancer. The findings are published in Cancer Cell.

By Anna Azvolinsky. In Cancer Network

http://www.cancernetwork.com/triple-negative-breast-cancer/content/article/10165/2124900

Informing women on breast cancer overdiagnosis

In a study exploring women's responses to being told about overdiagnosis in breast cancer screening, most women felt the information was important and could enable them to make choices.

In Medical Xpress

http://medicalxpress.com/news/2013-01-women-breast-cancer-overdiagnosis.html

Risque accru de cancer du poumon chez les fumeuses

Le risque de mourir d'un cancer du poumon a très fortement augmenté ces dernières décennies chez les femmes qui fument, selon une étude ayant porté sur plus de deux millions d'Américains, rendue publique mercredi.

Dans France24

http://www.france24.com/fr/20130124-risque-accru-cancer-poumon-fumeuses

Pourquoi les gros animaux sont-ils moins sujets au cancer que nous ?

Plus un animal est gros, plus il possède de cellules. Logiquement, on pourrait penser que plus il y a de cellules dans un organisme, plus il y a de risques de contracter un cancer. Pourtant, on constate le phénomène inverse. Cette contradiction, nommée paradoxe de Peto, vient d’être expliquée par un modèle mathématique. Une justification qui ne fait pas l’unanimité.

Par Janlou Chaput. Dans Futura-Sciences

http://www.futura-sciences.com/fr/news/t/biologie-3/d/pourquoi-les-gros-animaux-sont-ils-moins-sujets-au-cancer-que-nous_44182/

Cancer pancréatique stade IV : une association accroît la survie

Selon les résultats d’une étude multicentrique de phase III, l’association d’Abraxane (nab paclitaxel) et de gemcitabine majore la survie des patients atteints d’une forme avancée de cancer pancréatique.

Dans Le Quotidien du Médecin  

http://www.lequotidiendumedecin.fr/specialites/cancerologie/cancer-pancreatique-stade-iv-une-association-accroit-la-survie

Cancer: Une mortalité en baisse de 20% en 20 ans

C’est le rapport annuel encourageant de l’American Cancer Society, qui porte certes sur les Etats-Unis mais nous donne une tendance non négligeable. Car dans ce seul pays, ce sont en 20 années, 1,2 millions de décès par cancer qui ont été prévenus soit plus de 150.000 pour la seule année 2009. Les 4 cancers « les plus lourds » sont en régression, mais certains cancers poursuivent leur progression, comme le mélanome, le cancer de la thyroïde et du pancréas. Des indications précieuses pour l’ensemble des pays.

Dans Santé Log

http://www.santelog.com/news/cancerologie/cancer-une-mortalite-en-baisse-de-20-en-20-ans_9751_lirelasuite.htm

Calvitie précoce: Un indicateur de risque de cancer de la prostate?

La science nous livre parfois de curieuses associations mais elles trouvent toujours leur explication. Ici c’est la calvitie précoce, c’est-à-dire vers 40 ans qui est associée à un risque accru de cancer de la prostate. Cette étude australienne, présentée dans Cancer Epidemiology Biomarkers and Prevention qui, précisons-le n’a pas évalué les taux de mortalité, ne doit pas désespérer les hommes jeunes atteint d’alopécie androgénétique, en particulier, rappellent les auteurs, parce que de nombreux cas de cancer de la prostate ne sont pas agressifs.

Dans Santé Log

http://www.santelog.com/news/cancerologie/calvitie-precoce-un-indicateur-de-risque-de-cancer-de-la-prostate-_9791.htm

Focus : Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting

Background:Colorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-α (FRα) and endothelial growth factor receptor (EGFR).Methods:Marker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0-15). Matched positive and negative lymph nodes from 18 patients were also examined.Results:Markers were more highly expressed in tumour tissue than in matched normal tissue in 98.8%, 79.0%, 37.1% and 32.8% of cases for CEA, TAG-72, FRα and EGFR, respectively. Carcinoembryonic antigen showed the greatest differential expression, with tumours scoring a mean of 10.8 points higher than normal tissues (95% CI 10.31-11.21, P<0.001). Similarly, CEA showed the greatest differential expression between positive and negative lymph nodes. Receiver operating characteristic analyses showed CEA to have the best sensitivity (93.7%) and specificity (96.1%) for colorectal cancer detection.Conclusion:Carcinoembryonic antigen has the greatest potential to allow highly specific tumour imaging and drug delivery; future translational research should aim to exploit this.

Source: Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting. Tiernan JP, Perry SL, Verghese ET, West NP, Yeluri S, Jayne DG, Hughes TA. Br J Cancer. 2013 Jan 15.

Free paper available at:

http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2012605a.pdf

Focus : Transcriptional shift identifies a set of genes driving breast cancer chemoresistance

BACKGROUND:

Distant recurrences after antineoplastic treatment remain a serious problem for breast cancer clinical management, which threats patients' life. Systemic therapy is administered to eradicate cancer cells from the organism, both at the site of the primary tumor and at any other potential location. Despite this intervention, a significant proportion of breast cancer patients relapse even many years after their primary tumor has been successfully treated according to current clinical standards, evidencing the existence of a chemoresistant cell subpopulation originating from the primary tumor.

METHODS/FINDINGS:

To identify key molecules and signaling pathways which drive breast cancer chemoresistance we performed gene expression analysis before and after anthracycline and taxane-based chemotherapy and compared the results between different histopathological response groups (good-, mid- and bad-response), established according to the Miller & Payne grading system. Two cohorts of 33 and 73 breast cancer patients receiving neoadjuvant chemotherapy were recruited for whole-genome expression analysis and validation assay, respectively. Identified genes were subjected to a bioinformatic analysis in order to ascertain the molecular function of the proteins they encode and the signaling in which they participate. High throughput technologies identified 65 gene sequences which were over-expressed in all groups (P ≤ 0·05 Bonferroni test). Notably we found that, after chemotherapy, a significant proportion of these genes were over-expressed in the good responders group, making their tumors indistinguishable from those of the bad responders in their expression profile (P ≤ 0.05 Benjamini-Hochgerg`s method).

CONCLUSIONS:

These data identify a set of key molecular pathways selectively up-regulated in post-chemotherapy cancer cells, which may become appropriate targets for the development of future directed therapies against breast cancer.

Source: Transcriptional shift identifies a set of genes driving breast cancer chemoresistance. Vera-Ramirez L, Sanchez-Rovira P, Ramirez-Tortosa CL, Quiles JL, Ramirez-Tortosa M, Lorente JA (laura.vera@genyo.es). PLoS One. 2013;8(1):e53983.

Free paper available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542325/pdf/pone.0053983.pdf

Focus: The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3'-untranslated region (3'-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3'-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma.

Source: The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. Parker BC, Annala MJ, Cogdell DE, Granberg KJ, Sun Y, Ji P, Li X, Gumin J, Zheng H, Hu L, Yli-Harja O, Haapasalo H, Visakorpi T, Liu X, Liu CG, Sawaya R, Fuller GN, Chen K, Lang FL, Nykter M, Zhang W (wzhang@mdanderson.org). J Clin Invest. 2013 Jan 9.

Free paper available at:

https://www.jci.org/articles/view/67144

Focus: Higher levels of physical activity significantly increase survival in women with colorectal cancer

Source: Higher levels of physical activity significantly increase survival in women with colorectal cancer. Barton MK. CA Cancer J Clin. 2013 Jan 14.

Free paper available at:

http://onlinelibrary.wiley.com/doi/10.3322/caac.21175/pdf

Focus: Liver acid sphingomyelinase inhibits growth of metastatic colon cancer

Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate (S1P). These sphingolipids regulate carcinogenesis and proliferation, survival, and apoptosis of cancer cells. However, the role of ASM in host defense against liver metastasis remains unclear. In this study, the involvement of ASM in liver metastasis of colon cancer was examined using Asm-/- and Asm+/+ mice that were inoculated with SL4 colon cancer cells to produce metastatic liver tumors. Asm-/- mice demonstrated enhanced tumor growth and reduced macrophage accumulation in the tumor, accompanied by decreased numbers of hepatic myofibroblasts (hMFs), which express tissue inhibitor of metalloproteinase 1 (TIMP1), around the tumor margin. Tumor growth was increased by macrophage depletion or by Timp1 deficiency, but was decreased by hepatocyte-specific ASM overexpression, which was associated with increased S1P production. S1P stimulated macrophage migration and TIMP1 expression in hMFs in vitro. These findings indicate that ASM in the liver inhibits tumor growth through cytotoxic macrophage accumulation and TIMP1 production by hMFs in response to S1P. Targeting ASM may represent a new therapeutic strategy for treating liver metastasis of colon cancer.

Source: Liver acid sphingomyelinase inhibits growth of metastatic colon cancer. Osawa Y, Suetsugu A, Matsushima-Nishiwaki R, Yasuda I, Saibara T, Moriwaki H, Seishima M, Kozawa O (osawa-gif@umin.ac.jp). J Clin Invest. 2013 Jan 9.

Free paper available at:

http://www.jci.org/articles/view/65188

Focus: Cancer heterogeneity: implications for targeted therapeutics

Abstract

Developments in genomic techniques have provided insight into the remarkable genetic complexity of malignant tumours. There is increasing evidence that solid tumours may comprise of subpopulations of cells with distinct genomic alterations within the same tumour, a phenomenon termed intra-tumour heterogeneity. Intra-tumour heterogeneity is likely to have implications for cancer therapeutics and biomarker discovery, particularly in the era of targeted treatment, and evidence for a relationship between intra-tumoural heterogeneity and clinical outcome is emerging. Our understanding of the processes that exacerbate intra-tumoural heterogeneity, both iatrogenic and tumour specific, is likely to increase with the development and more widespread implementation of advanced sequencing technologies, and adaptation of clinical trial design to include comprehensive tissue collection protocols. The current evidence for intra-tumour heterogeneity and its relevance to cancer therapeutics will be presented in this mini-review.

Source: Cancer heterogeneity: implications for targeted therapeutics. Fisher R, Pusztai L, Swanton C (Charles.Swanton@cancer.org.uk). Br J Cancer. 2013 Jan 8.

Free paper available at:

http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2012581a.pdf

Focus: Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

ABSTRACT:

BACKGROUND: Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit.

METHODS:

In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes.

RESULTS:

Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05).

CONCLUSIONS:

Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology.

Source: Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series. Crispo A (anna.crispo@tin.it), Barba M, D Aiuto G, De Laurentiis M, Grimaldi M, Rinaldo M, Caolo G, D Aiuto M, Capasso I, Esposito E, Amore A, Di Bonito M, Botti G, Montella M. BMC Cancer. 2013 Jan 10;13(1):15.

Free paper available at:

http://www.biomedcentral.com/content/pdf/1471-2407-13-15.pdf

Press Review (January 19, 2013) – Revue de presse (19 janvier 2013)

Segregation Linked in Study With Lung Cancer Deaths

African-Americans who live in highly segregated counties are considerably more likely to die from lung cancer than those in counties that are less segregated, a new study has found.

By Sabrina Tavernise. In New York Times

http://www.nytimes.com/2013/01/17/health/study-links-segregation-and-lung-cancer-deaths-in-blacks.html?_r=0

Study calls for tobacco profits cap

Setting up an independent regulatory agency to cap cigarette manufacturers's profits would raise an extra £500 million a year, academics say.

In Cancer Research UK

http://www.cancerresearchuk.org/cancer-info/news/archive/cancernews/2013-01-17-Study-calls-for-tobacco-profits-cap?view=rss

New mechanism found on how a parasite leads to cancer

About 200 million people across 75 of the poorest countries in the world are now infected by the blood parasite Schistosoma haematobium (S. haematobium). The infection causes severe urogenital disease, but also causes bladder cancer in a number of patients and why this occurs is not clea

By Catarina Amorim. In Medical Xpress

http://medicalxpress.com/news/2013-01-mechanism-parasite-cancer.html

U.S. cancer death rates decline

The new year brings good news in the fight against cancer

By Kathryn Roethel. In San Francisco Chronicle

http://www.sfgate.com/health/article/U-S-cancer-death-rates-decline-4196561.php

Nobel laureate urges new direction for cancer research — and warns against antioxidant supplements

Anti-oxidative nutritional supplements “may have caused more cancers than they have prevented”.

By Susan Perry. In MinnPost.com

http://www.minnpost.com/second-opinion/2013/01/nobel-laureate-urges-new-direction-cancer-research-and-warns-against-antioxid

Scientists Seek out Cancer Cells Hiding from Treatment

Funding to improve leukemia treatment will investigate how cancer cells hide to avoid chemotherapy drugs.

In Science Daily (press release)

http://www.sciencedaily.com/releases/2013/01/130116090121.htm

Breast cancer mortality has not declined in women over 85

Since 1992 the number of deaths linked to breast cancer in Spain has decreased among young and middle aged patients but not among the elderly.

In EurekAlert (press release)

http://www.eurekalert.org/pub_releases/2013-01/f-sf-bcm011613.php

New treatment for bowel cancer

Researchers have found for the first time that a complex or proteins (mTorc1) promotes the growth of certain gastrointestinal cancers.

In ScienceAlert

http://www.sciencealert.com.au/news/20131701-23969.html

Cervical Cancer Awareness: Latinas At Greater Risk, 'Third Most Likely Group To Die Of The Disease'

Cervical cancer most commonly develops in women between the ages of 20 and 50, and according to the American Cancer Society, a low percentage of cases occur in women over the age of 50 and under the age of 65 (approximately 20 percent of cases).

By Hope Gillette. In Huffington Post

http://www.huffingtonpost.com/2013/01/14/latinas-at-greater-risk-for-cervical-cancer_n_2472472.html

Une piste pour évaluer le risque de cancer de la prostate

Des dosages répétés de PSA permettraient de déterminer les cancers de la prostate les plus dangereux.

Par Damien Mascret. Dans Le Figaro Santé

http://sante.lefigaro.fr/actualite/2013/01/16/19706-piste-pour-evaluer-risque-cancer-prostate

Le bilan en demi-teinte de l'Institut national du cancer

Le coût des soins se stabilise, la mortalité due à certaines tumeurs diminue, mais les inégalités ne cessent de se creuser.

Par Anne Jeanblanc. Dans Le Point

http://www.lepoint.fr/chroniqueurs-du-point/anne-jeanblanc/le-bilan-en-demi-teinte-de-l-institut-national-du-cancer-16-01-2013-1615643_57.php

MAUX CROISÉS – Un cruciverbiste dévoile son cancer dans les réponses à ses mots croisés

Le révérend John Galbraith Graham est une sommité du monde des mots croisés. Sous le pseudonyme d'Araucaria, il crée les grilles particulièrement compliquées qui apparaissent dans le Guardian, le Financial Times ou le magazine spécialisé 1 Across. Quand ses fidèles lecteurs ont commencé les mots croisés n° 25842 parus dans le Guardian en décembre, ils ont progressivement découvert que l'auteur souffrait d'un cancer.

Dans Le Monde  

http://bigbrowser.blog.lemonde.fr/2013/01/14/18-a-un-cruciverbiste-devoile-son-cancer-dans-les-reponses-a-ses-mots-croises/

Cancer de l’oesophage: la caméra-pilule qui pourrait reléguer l’endoscopie

Elle est décrite comme une technique d'imagerie rapide, simple et sans douleur que les patients pourraient largement préférer à l’endoscopie.

Dans Santé Log

http://www.santelog.com/news/diagnostic/cancer-de-l-oesophage-la-camera-pilule-qui-pourrait-releguer-l-endoscopie_9727.htm

Les bêtabloquants, nouvelle piste contre le cancer du poumon NPC ?

Des études prospectives sont nécessaires pour confirmer ces données et appellent à ne pas tirer de conclusions trop hâtives.

Par Zosia Chustecka, Aude Lecrubier. Dans Medscape France

http://www.medscape.fr/oncologie/articles/1494565/

Focus: Human endogenous retroviruses and cancer prevention: evidence and prospects

ABSTRACT:

BACKGROUND: Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections.

DISCUSSION:

Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues.Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system.HERV-K expression has been detected in different types of tumors.Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family.The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression.The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and breast cancer. An amino acid sequence similar to HERV-K-MEL, recognized to cause a significant protective effect against melanoma, is shared by the antigenic determinants expressed by some vaccines such as BCG, vaccinia virus and the yellow fever virus.HERV-K are also reactivated in the majority of human breast cancers. Monoclonal and single-chain antibodies against the HERV-K Env protein recently proved capable of blocking the proliferation of human breast cancer cells in vitro, inhibiting tumor growth in mice bearing xenograft tumors.

SUMMARY:

A recent epidemiological study provided provisional evidence of how melanoma risk could possibly be reduced if the yellow fever virus vaccine (YFV) were received at least 10 years before, possibly preventing tumor initiation rather than culling of melanoma cells already compromised. Further research is recommended to confirm the temporal pattern of this protection and eliminate/attenuate the potential role of relevant confounders as socio-economic status and other vaccinations.It appears also appropriate to examine the potential protective effect of YFV against other malignancies expressing high levels of HERV-K antigens, namely breast cancer, sarcoma, lymphoma and bladder cancer.Tumor immune-therapy, as described for the monoclonal antibodies against breast cancer, is indeed considered more complex and less advantageous than immune-prevention. Cellular immunity possibly triggered by vaccines as for YFV might also be involved in anti-cancer response, in addition to humoral immunity.

Source: Human endogenous retroviruses and cancer prevention: evidence and prospects. Cegolon L (l.cegolon@gmail.com), Salata C, Weiderpass E, Vineis P, Palù G, Mastrangelo G. BMC Cancer. 2013 Jan 3;13(1):4.

Free paper available at:

http://www.biomedcentral.com/content/pdf/1471-2407-13-4.pdf

LIST OF TUMOR MORPHOLOGIES (PART 10) - LISTE DE MORPHOLOGIES TUMORALES (PARTIE 10)

LIST OF TUMOR MORPHOLOGIES:

Tumor types are classified according to the International Classification of Diseases for Oncology (ICD-O), 3rd Edition, World Health Organization, Geneva, 2000. The ICD-O-3 is a dual classification and coding system for both morphology and topography of a neoplasm.

The MORPHOLOGY code (Mxxxx/x) indicates the specific histologic term.

The TOPOGRAPHY code (C00-C80) is occasionally mentioned here.

Abbreviation: NOS, not otherwise specified

LISTE DE MORPHOLOGIES TUMORALES

Les types de tumeurs sont classés en fonction de la « Classification Internationale des Maladies pour l'Oncologie (CIM-O), 3e édition, Organisation mondiale de la Santé, Genève, 2000. La CIM-O-3 est un système de classification et de codage pour la morphologie et la topographie d'une tumeur.

Le code de MORPHOLOGIE (Mxxxx/x) indique le terme spécifique histologique.

Le code de TOPOGRAPHIE (C00-C80) est occasionnellement mentionné ici.

Abréviation: SAI, sans autre indication

M850-M854 Néoplasmes canaliculaires, lobulaires et médullaires

M850	DUCT CARCINOMA	CARCINOME CANALAIRE
M8500/2	Intraductal carcinoma, noninfiltrating, NOS
	Carcinome intracanalaire non-infiltrant, SAI
M8500/3	Infiltrating duct carcinoma, NOS		C50._
	Carcinome canalaire infiltrant, SAI
M8501/2	Comedocarcinoma, noninfiltrating		C50._
	Comedocarcinome non infiltrant
M8501/3	Comedocarcinoma, NOS		C50._
	Comedocarcinome, SAI
M8502/3	Juvenile carcinoma of breast		C50._
	Carcinome juvénile du sein
M8503/2	Noninfiltrating intraductal papillary adenocarcinoma		C50._
	Adénocarcinome papillaire intracanaliculaire non infiltrant
M8503/3	Intraductal papillary adenocarcinoma with invasion		C50._
	Adénocarcinome papillaire intracanalaire
M8504/2	Noninfiltrating intracystic carcinoma
	Carcinome intrakystique non infiltrant
M8504/3	Intracystic carcinoma, NOS
	Carcinome intrakystique
M8507/2	Intraductal micropapillary carcinoma		C50._
	Carcinome intracanalaire micro-papillaire
M8508/3	Cystic hypersecretory carcinoma		C50._
	Carcinome hypersécrétoire kystique

           

M851	MEDULLARY CARCINOMA, NOS	CARCINOME MÉDULLAIRE, SAI
M8510/3	Medullary carcinoma, NOS
	Carcinome médullaire SAI
M8512/3	Medullary carcinoma with lymphoid stroma
	Carcinome médullaire à stroma lymphoïde
M8513/3	Atypical medullary carcinoma		C50._
	Carcinome médullaire atypique
M8514/3	Duct carcinoma, desmoplastic type
	Carcinome canalaire desmoplasique

M852	LOBULAR AND OTHER DUCTAL CARCINOMA	CARCINOME LOBULAIRE ET CANALAIRE (AUTRE)
M8520/2	Lobular carcinoma in situ, NOS		C50._
	Carcinome lobulaire in situ, SAI
M8520/3	Lobular carcinoma, NOS		C50._
	Carcinome lobulaire SAI
M8521/3	Infiltrating ductular carcinoma		C50._
	Carcinome canaliculaire infiltrant
M8522/2	Intraductal carcinoma and lobular carcinoma in situ		C50._
	Carcinome canalaire et lobulaire in situ
M8522/3	Infiltrating duct and lobular carcinoma		C50._
	Carcinome canalaire et lobulaire infiltrant
M8523/2	Infiltrating duct mixed with other types of carcinoma, in situ		C50._
	Carcinome canalaire infiltrant avec autres types de carcinomes, in situ
M8523/3	Infiltrating duct mixed with other types of carcinoma		C50._
	Carcinome canalaire infiltrant avec autres types de carcinomes
M8524/3	Infiltrating lobular mixed with other types of carcinoma		C50._
	Carcinome lobulaire infiltrant avec autres types de carcinomes
M8525/3	Polymorphous low grade adenocarcinoma
	Adénocarcinome polymorphe de bas grade

M853	INFLAMMATORY CARCINOMA	CARCINOME INFLAMMATOIRE
M8530/3	Inflammatory carcinoma		C50._
	Carcinome inflammatoire

M854	PAGET DISEASE, MAMMARY	MALADIE DE PAGET DU SEIN
M8540/3	Paget's disease, mammary		C50._
	Maladie de Paget du sein
M8541/3	Paget's disease and infiltrating duct carcinoma of breast		C50._
	Maladie de Paget, avec carcinome canaliculaire infiltrant du sein
M8542/3	Paget's disease, extramammary (except Paget's disease of bone)
	Maladie de Paget extramammaire (à l'exclusion de la maladie de Paget des os)
M8543/3	Paget's disease and intraductal carcinoma of breast		C50._
	Maladie de Paget et carcinome intracanalaire du sein