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Sweden: cancer statistics from IARC GlobalCan (2012)

Population in 2012: 9.5m
People newly diagnosed with cancer (excluding NMSC) / yr: 50,500
Age-standardised rate, incidence per 100,000 people/yr: 270.0
Risk of getting cancer before age 75:27.8%
People dying from cancer /yr: 22,100

Menu: Swedish Cancer Resources

Swedish Cancer Organisations
Cancer Centres in Sweden
Latest Research Publications from Sweden

Swedish Cancer Organisations (16 links)

Cancer Centres in Sweden (6 links)

Latest Research Publications from Sweden

Deperas-Kaminska M, Bajinskis A, Marczyk M, et al.
Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies.
Health Phys. 2014; 107(6):555-63 [PubMed] Related Publications
The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results indicate that the combined analysis of Apolipoprotein E, Factor X, and Pantothenate Kinase 4 allows discriminating between exposure to 2 Gy and lower and between 10 Gy and higher. The discrimination is possible up to 1 mo after exposure.

Related: Breast Cancer

Van Calster B, Van Hoorde K, Valentin L, et al.
Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.
BMJ. 2014; 349:g5920 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.
DESIGN: Observational diagnostic study using prospectively collected clinical and ultrasound data.
SETTING: 24 ultrasound centres in 10 countries.
PARTICIPANTS: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.
MAIN OUTCOME MEASURES: Histological classification and surgical staging of the mass.
RESULTS: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.
CONCLUSIONS: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Related: Ovarian Cancer

Fu YP, Kohaar I, Moore LE, et al.
The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.
Cancer Res. 2014; 74(20):5808-18 [PubMed] Article available free on PMC after 15/04/2015 Related Publications
A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.

Related: Chromosome 19 Bladder Cancer Bladder Cancer - Molecular Biology CCNE1 gene

Lauth M, Toftgard R
Think inside the BOCs: a mechanism underlying medulloblastoma progression.
Dev Cell. 2014; 31(1):1-2 [PubMed] Related Publications
Approximately one-third of medulloblastoma cases are associated with genetic lesions of Hedgehog (Hh) signaling pathway components. In this issue of Developmental Cell, Mille et al. (2014) show that the Hh coreceptor Boc functions specifically in the progression of early- to advanced-stage medulloblastoma by promoting Cyclin D1-dependent DNA damage and genomic instability.

Related: Childhood Medulloblastoma / PNET

Xiong A, Kundu S, Forsberg-Nilsson K
Heparan sulfate in the regulation of neural differentiation and glioma development.
FEBS J. 2014; 281(22):4993-5008 [PubMed] Related Publications
Heparan sulfate proteoglycans (HSPGs) are the main components of the extracellular matrix, where they interact with a large number of physiologically important macromolecules. The sulfation pattern of heparan sulfate (HS) chains determines the interaction potential of the proteoglycans. Enzymes of the biosynthetic and degradation pathways for HS chains are thus important regulators in processes ranging from embryonic development to tissue homeostasis, but also for tumor development. Formation of the nervous system is also critically dependent on intact HSPGs, and several studies have outlined the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common malignant primary brain tumor among adults, and the outcome is poor. Neural stem cells and glioma stem cells have several common traits, such as sustained proliferation and a highly efficient migratory capacity in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside, and the tumorigenic niche. These include interactions with the extracellular matrix, and many of the matrix components are deregulated in glioma, e.g. HSPGs and enzymes implementing the biosynthesis and modification of HS. In this article, we will present how HS-regulated pathways are involved in neural differentiation, and discuss their impact on brain development. We will also review and critically discuss the important role of structural modifications of HS in glioma growth and invasion. We propose that targeting invasive mechanisms of glioma cells through modulation of HS structure and HS-mediated pathways may be an attractive alternative to other therapeutic attempts, which so far have only marginally increased survival for glioma patients.

Related: Angiogenesis and Cancer Signal Transduction

Skibola CF, Berndt SI, Vijai J, et al.
Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
Am J Hum Genet. 2014; 95(4):462-71 [PubMed] Article available free on PMC after 02/04/2015 Related Publications
Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Cermignani L, Alberdi C, Demichelis S, et al.
Features related to breast cancer in an entire Argentine rural population.
Anticancer Res. 2014; 34(10):5537-42 [PubMed] Related Publications
AIM: A descriptive study was developed in an entire Argentine rural community considering breast cancer risk factors, preventive strategies and breast cancer incidence.
PATIENTS AND METHODS: the study comprised of 83 women. A questionnaire of 34 items was employed; a mammogram and a breast ultrasound were performed. ANOVA and Pearson correlation were employed.
RESULTS: Mean age was 54.5 years; 69% of women were postmenopausal; 96% had children; breastfeeding was X=10 months/child; Body Mass Index (BMI) was X=27.8 kg/m(2); 13% had first-degree relatives with breast cancer; 90% of women considered mammographic screening a necessary study. One woman had presented breast cancer. Argentine screening guidelines were not followed and an inverse relationship between education level and age of first mammogram was found (p<0.05). Mammographic and ultrasound studies did not reveal potential abnormalities.
CONCLUSION: Peculiar social and cultural characteristics may be relevant to evaluate breast cancer risk factors in Argentina.

Related: Breast Cancer Breast Cancer Screening Cancer Screening and Early Detection

Ansari D, Urey C, Hilmersson KS, et al.
Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression.
Anticancer Res. 2014; 34(10):5269-76 [PubMed] Related Publications
BACKGROUND/AIM: Mucin 4 (MUC4) has been linked to resistance to gemcitabine in pancreatic cancer cells. The aim of the present study was to assess whether epigenetic control of MUC4 expression can sensitize pancreatic cancer cells to gemcitabine treatment.
MATERIALS AND METHODS: A 76-member combined epigenetics and phosphatase small-molecule inhibitor library was screened for anti-proliferative activity against the MUC4(+) gemcitabine-resistant pancreatic cancer cell line Capan-1, followed by high-content screening of protein expression.
RESULTS: Apicidin, a histone deacetylase inhibitor, showed the greatest anti-proliferative activity with a lethal dose 50 (LD50) value of 5.17 μM. Apicidin significantly reduced the expression of MUC4 and its transcription factor hepatocyte nuclear factor 4α. Combined treatment with a sub-therapeutic concentration of apicidin and gemcitabine synergistically inhibited growth of Capan-1 cells.
CONCLUSION: Apicidin appears to be a novel anti-proliferative agent against pancreatic cancer cells that may reverse chemoresistance by epigenetically regulating MUC4 expression.

Related: MUC4 Cancer of the Pancreas Pancreatic Cancer Gemcitabine

Eggermont AM, Caldas C, Ringborg U, et al.
Cancer Core Europe: a consortium to address the cancer care-cancer research continuum challenge.
Eur J Cancer. 2014; 50(16):2745-6 [PubMed] Related Publications
European cancer research for a transformative initiative by creating a consortium of six leading excellent comprehensive cancer centres that will work together to address the cancer care-cancer research continuum. Prerequisites for joint translational and clinical research programs are very demanding. These require the creation of a virtual single 'e-hospital' and a powerful translational platform, inter-compatible clinical molecular profiling laboratories with a robust underlying computational biology pipeline, standardised functional and molecular imaging, commonly agreed Standard Operating Procedures (SOPs) for liquid and tissue biopsy procurement, storage and processing, for molecular diagnostics, 'omics', functional genetics, immune-monitoring and other assessments. Importantly also it requires a culture of data collection and data storage that provides complete longitudinal data sets to allow for: effective data sharing and common database building, and to achieve a level of completeness of data that is required for conducting outcome research, taking into account our current understanding of cancers as communities of evolving clones. Cutting edge basic research and technology development serve as an important driving force for innovative translational and clinical studies. Given the excellent track records of the six participants in these areas, Cancer Core Europe will be able to support the full spectrum of research required to address the cancer research- cancer care continuum. Cancer Core Europe also constitutes a unique environment to train the next generation of talents in innovative translational and clinical oncology.

Related: Cancer Prevention and Risk Reduction

Merid SK, Goranskaya D, Alexeyenko A
Distinguishing between driver and passenger mutations in individual cancer genomes by network enrichment analysis.
BMC Bioinformatics. 2014; 15:308 [PubMed] Article available free on PMC after 02/04/2015 Related Publications
BACKGROUND: In somatic cancer genomes, delineating genuine driver mutations against a background of multiple passenger events is a challenging task. The difficulty of determining function from sequence data and the low frequency of mutations are increasingly hindering the search for novel, less common cancer drivers. The accumulation of extensive amounts of data on somatic point and copy number alterations necessitates the development of systematic methods for driver mutation analysis.
RESULTS: We introduce a framework for detecting driver mutations via functional network analysis, which is applied to individual genomes and does not require pooling multiple samples. It probabilistically evaluates 1) functional network links between different mutations in the same genome and 2) links between individual mutations and known cancer pathways. In addition, it can employ correlations of mutation patterns in pairs of genes. The method was used to analyze genomic alterations in two TCGA datasets, one for glioblastoma multiforme and another for ovarian carcinoma, which were generated using different approaches to mutation profiling. The proportions of drivers among the reported de novo point mutations in these cancers were estimated to be 57.8% and 16.8%, respectively. The both sets also included extended chromosomal regions with synchronous duplications or losses of multiple genes. We identified putative copy number driver events within many such segments. Finally, we summarized seemingly disparate mutations and discovered a functional network of collagen modifications in the glioblastoma. In order to select the most efficient network for use with this method, we used a novel, ROC curve-based procedure for benchmarking different network versions by their ability to recover pathway membership.
CONCLUSIONS: The results of our network-based procedure were in good agreement with published gold standard sets of cancer genes and were shown to complement and expand frequency-based driver analyses. On the other hand, three sequence-based methods applied to the same data yielded poor agreement with each other and with our results. We review the difference in driver proportions discovered by different sequencing approaches and discuss the functional roles of novel driver mutations. The software used in this work and the global network of functional couplings are publicly available at http://research.scilifelab.se/andrej_alexeyenko/downloads.html.

Related: Ovarian Cancer

Wolff AS, Kärner J, Owe JF, et al.
Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors.
J Immunol. 2014; 193(8):3880-90 [PubMed] Article available free on PMC after 15/04/2015 Related Publications
Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism, and chronic mucocutaneous candidiasis plus autoantibodies neutralizing IL-17, IL-22, and type I IFNs. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG, thymoma, or both for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and we assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including chronic mucocutaneous candidiasis, AI, and asplenia, respectively, in 49 of 121 (40%) and 10 of 121 (8%) thymoma patients, but clinical features seldom occurred together with the corresponding autoantibodies. Both were rare in other MG subgroups (n = 126). In 38 patients with APS-I, by contrast, we observed neither autoantibodies against muscle Ags nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected underexpression in thymomas, levels were increased for four of the five TSAgs most frequently targeted by these patients' autoantibodies. Therefore, the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and hypoparathyroidism.

Related: Thymoma and Thymic Carcinoma

Al Olama AA, Kote-Jarai Z, Berndt SI, et al.
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Nat Genet. 2014; 46(10):1103-9 [PubMed] Related Publications
Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Related: Prostate Cancer

Azzi T, Lünemann A, Murer A, et al.
Role for early-differentiated natural killer cells in infectious mononucleosis.
Blood. 2014; 124(16):2533-43 [PubMed] Article available free on PMC after 16/10/2015 Related Publications
A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus.

Floodeen H, Lindgren R, Hallböök O, Matthiessen P
Evaluation of long-term anorectal function after low anterior resection: a 5-year follow-up of a randomized multicenter trial.
Dis Colon Rectum. 2014; 57(10):1162-8 [PubMed] Related Publications
BACKGROUND: Anorectal function after rectal surgery with low anastomosis is often impaired. Outcome of long-term anorectal function is poorly understood but may improve over time.
OBJECTIVE: We evaluated anorectal function 5 years after low anterior resection for cancer with regard to whether patients had a temporary stoma at initial resection. The objective of this study was to assess changes in anorectal function over time by comparing the results with anorectal function 1 year after rectal resection.
DESIGN: This study was a secondary end point of a randomized, multicenter controlled trial.
SETTINGS: The study was conducted at 21 Swedish hospitals performing rectal cancer surgery from 1999 to 2005.
PATIENTS: Patients included were those operated on with low anterior resection.
INTERVENTIONS: Patients were randomly assigned to receive or not receive a defunctioning stoma.
MAIN OUTCOME MEASURES: We evaluated anorectal function in patients who were initially randomly assigned to the defunctioning stoma or no stoma group, who had been free of stoma for 5 years, by means of using a standardized patient questionnaire. Questions addressed stool frequency, urgency, fragmentation of bowel movements, evacuation difficulties, incontinence, lifestyle alterations, and patient preference regarding permanent stoma formation. Results were compared with the same patient cohort at 1-year follow-up.
RESULTS: A total of 123 patients answered the bowel function questionnaire (65 in the no-stoma group and 58 in the stoma group). No differences were found between groups regarding the number of passed stools, need for medication to open the bowel, evacuation difficulties, incontinence, and urgency. General well-being was significantly better in the no-stoma group (p = 0.033). Comparison with anorectal function at 1 year showed no further changes over time.
LIMITATIONS: The study was based on a limited sample size (n = 123) and formed a secondary end point of a randomized trial.
CONCLUSIONS: Anorectal function was impaired for many patients, but the temporary presence of a defunctioning stoma after rectal resection did not affect long-term outcome. Anorectal function did not change between 1-year and 5-year follow-up.

Darlin L, Borgfeldt C, Widén E, Kannisto P
Elderly women above screening age diagnosed with cervical cancer have a worse prognosis.
Anticancer Res. 2014; 34(9):5147-51 [PubMed] Related Publications
AIM: To analyze the cervical screening history in women with cervical cancer and their outcome.
DESIGN: All women diagnosed with cervical cancer between January 2009 and December 2010 in the South Sweden region were included in the audit.
MATERIALS AND METHODS: Cervical cancer was registered in 165 women in 2009 and 2010. Their screening history was analyzed, and was classified as normal or imperfect. The method of discovering the cancer was either by symptoms or by screening. The main outcome measured was overall survival in cervical cancer related to cervical screening history.
RESULTS: Women above 65 years of age were more frequently diagnosed with advanced-stage disease (The International Federation of Gynecology and Obstetrics II-IV) (n=36 out of 43; 84%) compared to women below 65 years of age (n=35 out of 122; 29%) (p<0.001). All patients diagnosed by the cervical screening program were still alive (30/30) at the median follow-up time (36 months), showing better overall survival compared to women below screening age in whom cancer was discovered due to symptoms (68/98; p<0.001). Cox proportional hazards model showed that women beyond screening age (>65 years old) with normal screening history had a worse prognosis, with a hazard ratio of 4.8 (95% confidence interval=1.9-12.1, p=0.001), and women (>65 years old) who had not followed the screening program had a hazard ratio of 5.9 (95% confidence interval I 2.4-14.6, p<0.001), compared to women under 65 years old who had followed the screening program.
CONCLUSION: Cervical cancer in women above the age of 65 years is discovered at advanced stages of the disease and their prognosis is poor.

Related: Cancer Screening and Early Detection Cervical Cancer Cervical Cancer Screening

de Miranda NF, Georgiou K, Chen L, et al.
Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients.
Blood. 2014; 124(16):2544-53 [PubMed] Article available free on PMC after 16/10/2015 Related Publications
Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (≥10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents.

Related: Signal Transduction

Hoellein A, Fallahi M, Schoeffmann S, et al.
Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma.
Blood. 2014; 124(13):2081-90 [PubMed] Article available free on PMC after 25/09/2015 Related Publications
Myc oncogenic transcription factors (c-Myc, N-Myc, and L-Myc) coordinate the control of cell growth, division, and metabolism. In cancer, Myc overexpression is often associated with aggressive disease, which is in part due to the destruction of select targets by the ubiquitin-proteasome system (eg, SCF(Skp2)-directed destruction of the Cdk inhibitor p27(Kip1)). We reasoned that Myc would also regulate SUMOylation, a related means of posttranslational modification of proteins, and that this circuit would play essential roles in Myc-dependent tumorigenesis. Here, we report marked increases in the expression of genes that encode regulators and components of the SUMOylation machinery in mouse and human Myc-driven lymphomas, resulting in hyper-SUMOylation in these tumors. Further, inhibition of SUMOylation by genetic means disables Myc-induced proliferation, triggering G2/M cell-cycle arrest, polyploidy, and apoptosis. Using genetically defined cell models and conditional expression systems, this response was shown to be Myc specific. Finally, in vivo loss-of-function and pharmacologic studies demonstrated that inhibition of SUMOylation provokes rapid regression of Myc-driven lymphoma. Thus, targeting SUMOylation represents an attractive therapeutic option for lymphomas with MYC involvement.

Related: Signal Transduction

Zabriskie MS, Eide CA, Tantravahi SK, et al.
BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia.
Cancer Cell. 2014; 26(3):428-42 [PubMed] Article available free on PMC after 08/09/2015 Related Publications
Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph(+)) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph(+) leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.

Related: Chronic Myeloid Leukemia (CML) CML - Molecular Biology

Zamora-Ros R, Sacerdote C, Ricceri F, et al.
Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Br J Cancer. 2014; 111(9):1870-80 [PubMed] Related Publications
BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.
RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.
CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

Related: Bladder Cancer Bladder Cancer - Molecular Biology

Holme Ø, Løberg M, Kalager M, et al.
Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial.
JAMA. 2014; 312(6):606-15 [PubMed] Related Publications
IMPORTANCE: Colorectal cancer is a major health burden. Screening is recommended in many countries.
OBJECTIVE: To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 100,210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry.
INTERVENTIONS: Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp ≥10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention.
MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality.
RESULTS: A total of 98,792 participants were included in the intention-to-screen analyses, of whom 78,220 comprised the control group and 20,572 comprised the screening group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups.
CONCLUSIONS AND RELEVANCE: In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00119912.

Related: Colorectal (Bowel) Cancer Cancer Screening and Early Detection

Norström MM, Rådestad E, Stikvoort A, et al.
Novel method to characterize immune cells from human prostate tissue.
Prostate. 2014; 74(14):1391-9 [PubMed] Related Publications
BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common benign adenoma and prostate cancer is the most frequent malignancy in men over 50 years of age in the Western world, where it remains a significant health problem. Prostate lesions are known to contain immune cells, which may contribute to the immune control of tumor progression. However, due to their low numbers and restricted access to necessary material it is difficult to isolate immune cells from prostate tissue to characterize their immunological features.
METHODS: An efficient and robust method was developed to process prostate tissue and isolate immune cells for phenotypic analysis by multicolor flow cytometry as downstream application. Fresh prostate tissue from 11 patients undergoing surgery for bladder outlet obstruction due to BPH was processed to evaluate the number, viability, yield, and frequency of various immune cell types.
RESULTS: The presented method does not include enzymatic digestion nor incubation steps at 37 °C, increasing cellular viability and avoiding possible phenotypic modification. Various immune cell populations were detected in all patient samples and the median cellular viability was 90%. The number of detected events of individual cell populations varied between patients. The median frequency of different immune cell populations also varied, being 87% for the CD3- and 15% for the CD3+ cell population.
CONCLUSIONS: This novel method will allow the phenotypic characterization of immune cell populations present in tumor tissue of prostate cancer patients and promote development of novel approaches to immunotherapy of the disease.

Related: Prostate Cancer

Schröder FH, Hugosson J, Roobol MJ, et al.
Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.
Lancet. 2014; 384(9959):2027-35 [PubMed] Related Publications
BACKGROUND: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years.
METHODS: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736.
FINDINGS: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88).
INTERPRETATION: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.
FUNDING: Each centre had its own funding responsibility.

Related: Prostate Cancer

Chen T, Hemminki K, Kharazmi E, et al.
Multiple primary (even in situ) melanomas in a patient pose significant risk to family members.
Eur J Cancer. 2014; 50(15):2659-67 [PubMed] Related Publications
BACKGROUND: We aimed at assessing familial risk of melanoma by considering a detailed family history of multiple primary (invasive/in situ) melanomas (MPM), stratified by histology and location.
METHODS: Among 65,429 melanoma patients diagnosed in 1958-2010 in the Swedish Family-Cancer Database, there were 4248 patients with familial melanoma. A detailed family history of MPM was investigated by number of melanomas in one first-degree relative (FDR) and in ⩾2 FDRs. Familial melanoma risk was assessed by standardised incidence ratios (SIRs) comparing those with family history of melanoma to those without. Combining invasive/in situ melanoma was due to essentially identical familial risks.
RESULTS: For one affected FDR, familial risk increased from SIR=2.2 (95% confidence interval (CI)=2.2-2.3) for single melanoma to 16.3 (9.5-26.1) for ⩾5 melanomas, while for ⩾2 affected FDRs, the risk increased from 5.5 (4.8-6.2) for single melanoma to 23.9 (13.6-38.8) for ⩾2 melanomas. Significantly higher familial risks for superficial spreading melanoma (SSM) [2.5 (2.3-2.6)] than lentigo maligna melanoma (LMM) [1.8 (1.6-2.1)], and for multiple parts [5.3 (3.1-8.4)] and trunk [2.6 (2.5-2.8)] than head/neck [2.0 (1.8-2.2)] were observed. Only at head/neck, significantly higher risk for SSM [2.4 (1.9-3.0)] than LMM [1.6 (1.4-1.8)] was noted.
CONCLUSION: We found, for the first time, that familial risks were similar for two/three melanomas in one FDR or for a single melanoma in ⩾2 FDRs and, higher familial risks for SSM than LMM occurred only at head/neck. This study provides new evidence for genetic counselling in melanoma, suggesting the need for considering not only the number of affected family members but also the diagnosis of MPM (even in situ) in relatives.

Related: Melanoma Skin Cancer

Holm T
Ultra low resection versus abdomino-perineal excision in low rectal cancer.
Recent Results Cancer Res. 2014; 203:57-67 [PubMed] Related Publications
There have been several important improvements in the management of patients with rectal cancer during the recent 20 years. For more accurate local and distant tumour staging, introduction of neoadjuvant treatments, improved surgery, a more precise macroscopic and microscopic evaluation of the specimen and MDT discussions have all been crucial in improving local control and survival. However, the most important factor has been the TME technique with standardisation of the surgical procedure. For patients with low rectal cancer, the decision making is complex with several treatment options, including the choice between neoadjuvant treatment followed by surgery or surgery alone, restorative procedures or APE. If an APE is necessary, this must also be tailored to the individual patient based on patient's characteristics and the extent of local tumour growth.

Amin MB, Lin DW, Gore JL, et al.
The critical role of the pathologist in determining eligibility for active surveillance as a management option in patients with prostate cancer: consensus statement with recommendations supported by the College of American Pathologists, International Society of Urological Pathology, Association of Directors of Anatomic and Surgical Pathology, the New Zealand Society of Pathologists, and the Prostate Cancer Foundation.
Arch Pathol Lab Med. 2014; 138(10):1387-405 [PubMed] Related Publications
CONTEXT: Prostate cancer remains a significant public health problem. Recent publications of randomized trials and the US Preventive Services Task Force recommendations have drawn attention to overtreatment of localized, low-risk prostate cancer. Active surveillance, in which patients undergo regular visits with serum prostate-specific antigen tests and repeat prostate biopsies, rather than aggressive treatment with curative intent, may address overtreatment of low-risk prostate cancer. It is apparent that a greater awareness of the critical role of pathologists in determining eligibility for active surveillance is needed.
OBJECTIVES: To review the state of current knowledge about the role of active surveillance in the management of prostate cancer and to provide a multidisciplinary report focusing on pathologic parameters important to the successful identification of patients likely to succeed with active surveillance, to determine the role of molecular tests in increasing the safety of active surveillance, and to provide future directions.
DESIGN: Systematic review of literature on active surveillance for low-risk prostate cancer, pathologic parameters important for appropriate stratification, and issues regarding interobserver reproducibility. Expert panels were created to delineate the fundamental questions confronting the clinical and pathologic aspects of management of men on active surveillance.
RESULTS: Expert panelists identified pathologic parameters important for management and the related diagnostic and reporting issues. Consensus recommendations were generated where appropriate.
CONCLUSIONS: Active surveillance is an important management option for men with low-risk prostate cancer. Vital to this process is the critical role pathologic parameters have in identifying appropriate candidates for active surveillance. These findings need to be reproducible and consistently reported by surgical pathologists with accurate pathology reporting.

Related: Prostate Cancer USA Watchful Waiting - Prostate Cancer

Arab K, Park YJ, Lindroth AM, et al.
Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A.
Mol Cell. 2014; 55(4):604-14 [PubMed] Related Publications
DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.

Related: Cancer Prevention and Risk Reduction GADD45A

Tjörnstrand A, Gunnarsson K, Evert M, et al.
The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011.
Eur J Endocrinol. 2014; 171(4):519-26 [PubMed] Related Publications
OBJECTIVE: The number of studies on the incidence of pituitary adenomas (PAs) is limited. The aim of this study was to evaluate the standardised incidence rate (SIR) of PAs in western Sweden.
DESIGN, SUBJECTS AND METHODS: Data from adult patients diagnosed with PAs in 2001-2011, living in the Västra Götaland County, were collected from the Swedish Pituitary Registry (SPR). In addition, medical records on all patients diagnosed with PAs at the six hospitals in the region were reviewed. In total, 592 patients were included in the study.Age-SIR, given as rate/100 000 inhabitants (95% CI), was calculated using the WHO 2000 standard population as a reference.
RESULTS: The total SIR for PAs was 3.9/100 000 (3.6-4.3); 3.3/100 000 (2.9-3.7) for men and 4.7/100 000 (4.1-5.3) for women. In men, SIR increased with age, while in women SIR peaked at 25-34 years, mainly due to prolactinomas. Non-functioning PA (NFPA) was the most common PA (54%, 1.8/100 000 (1.6-2.0)) followed by prolactinomas (32%, 1.6/100 000 (1.3-1.9)), acromegaly (9%, 0.35/100 000 (0.25-0.45)), Cushing's disease (4%, 0.18/100 000 (0.11-0.25)) and TSH-producing PA (0.7%, 0.03/100 000 (0.00-0.05)). The proportion of macroadenomas for NFPA was 82%, prolactinomas 37%, GH-producing PA 77%, ACTH-producing PA 28% and TSH-producing PA 100%. The lifetime risk for PAs was 0.27% (0.24-0.31) in men and 0.29% (0.26-0.33) in women.
CONCLUSION: This study provides a reliable estimate on the overall incidence of PAs and confirms an increased incidence of PAs compared with studies conducted in the pre-magnetic resonance imaging era. The lower proportion of prolactinomas compared with previous studies is probably explained by the different criteria used.

Related: Pituitary Tumors

Boussemart L, Malka-Mahieu H, Girault I, et al.
eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies.
Nature. 2014; 513(7516):105-9 [PubMed] Related Publications
In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3)K-AKT-mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade. All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the 7-methylguanylate cap (m(7)G) at the 5' end of messenger RNA, thereby modulating the translation of specific mRNAs. Here we show that the persistent formation of the eIF4F complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and anti-BRAF plus anti-MEK drug combinations in BRAF(V600)-mutant melanoma, colon and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with one of three mechanisms: reactivation of MAPK signalling, persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 or increased pro-apoptotic BCL-2-modifying factor (BMF)-dependent degradation of eIF4G. The development of an in situ method to detect the eIF4E-eIF4G interactions shows that eIF4F complex formation is decreased in tumours that respond to anti-BRAF therapy and increased in resistant metastases compared to tumours before treatment. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A, synergizes with inhibiting BRAF(V600) to kill the cancer cells. eIF4F not only appears to be an indicator of both innate and acquired resistance but also is a promising therapeutic target. Combinations of drugs targeting BRAF (and/or MEK) and eIF4F may overcome most of the resistance mechanisms arising in BRAF(V600)-mutant cancers.

Related: EIF4E Melanoma BRAF gene Signal Transduction Thyroid Cancer Vemurafenib (Zelboraf)

Weller M, van den Bent M, Hopkins K, et al.
EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma.
Lancet Oncol. 2014; 15(9):e395-403 [PubMed] Related Publications
This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.

Ansari D, Bauden MP, Sasor A, et al.
Analysis of MUC4 expression in human pancreatic cancer xenografts in immunodeficient mice.
Anticancer Res. 2014; 34(8):3905-10 [PubMed] Related Publications
BACKGROUND/AIM: Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
MATERIALS AND METHODS: Pancreatic xenograft tumors were generated in immunodeficient mice (n=15) by subcutaneous injection of MUC4(+) human pancreatic cancer cell lines Capan-1, HPAF-II or CD18/HPAF. MUC4 immunoreactivity was compared between the cancer models. Alpha-smooth muscle actin (α-SMA) was used to identify cancer-associated fibroblasts and the amount of collagen fibers was quantified with sirius red.
RESULTS: Tumor incidence was 100%. Tumor size showed no difference across groups (p=0.796). The median MUC4 count was highest in Capan-1 tumors (p=0.002). α-SMA and collagen extent were also highest in Capan-1 tumors (p=0.018).
CONCLUSION: The Capan-1 xenograft model could serve as a valuable resource to test new therapeutic strategies targeting MUC4 in pancreatic cancer.

Related: MUC4 Cancer of the Pancreas Pancreatic Cancer

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