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Carcinomas mamários de tipo basal: perfil clínico-patológico e evolutivo; Basal-like breast cancers: clinicopathological features and outcome

DE BROT, Marina; SOARES, Fernando Augusto; STIEPCICH, Mônica Maria Ágata; CÚRCIO, Vinícius S.; GOBBI, Helenice
Fonte: Associação Médica Brasileira Publicador: Associação Médica Brasileira
Tipo: Artigo de Revista Científica
POR
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36.24%
OBJETIVO: Investigar a frequência de carcinomas mamários de fenótipo basal em uma série de tumores triplo-negativos (TTN), definidos pela negatividade para receptores de estrógeno (RE), de progesterona (RP) e HER2. MÉTODOS: Selecionamos 140 TTN, obtendo-se características clínico-patológicas e sobrevida. Microarranjo de tecido (2 cilindros de cada tumor) foi construído e submetido à imunoistoquímica para RE, RP, HER2, citoqueratinas (Cks) 5 e 14, EGFR, p63 e p53. Consideramos carcinomas de fenótipo basal os tumores negativos para RE, RP e HER2, e positivos para CK5. RESULTADOS: Encontramos 105 carcinomas de fenótipo basal entre 140 TTN (frequência=75%). A idade média das pacientes foi de 54,8 anos, sendo que 34,3% estavam na pré-menopausa. A maioria dos tumores foi classificada como carcinoma ductal invasor de alto grau. Os TTN exibiram positividade para CK5 (75,0%), CK14 (29%), EGFR (36,4%), p63 (28,6%) e p53 (67,1%). Estadiamento avançado da doença foi observado em 52 pacientes (50%), com diâmetro tumoral maior que 5 cm em 41 casos (39%) e metástases axilares em 61 casos (59,2%). Seguimento clínico foi obtido em 89 pacientes (média=51 meses). Destas, 45 pacientes (50,5%) evoluíram sem doença; 6 (6,7%) estavam vivas com doença e 38 (42...

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

MCKAY, James D.; Therese Truong; GABORIEAU, Valerie; CHABRIER, Amelie; CHUANG, Shu-Chun; BYRNES, Graham; ZARIDZE, David; SHANGINA, Oxana; SZESZENIA-DABROWSKA, Neonila; LISSOWSKA, Jolanta; RUDNAI, Peter; FABIANOVA, Eleonora; BUCUR, Alexandru; BENCKO, Vladi
Fonte: PUBLIC LIBRARY SCIENCE Publicador: PUBLIC LIBRARY SCIENCE
Tipo: Artigo de Revista Científica
ENG
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36.34%
Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5...

Allele loss, replication errors and loss of expression of E-cadherin in colorectal cancers.

Ilyas, M; Tomlinson, I P; Hanby, A; Talbot, I C; Bodmer, W F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1997 EN
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BACKGROUND: Loss of E-cadherin expression has been implicated in the development of invasive characteristics in colorectal carcinomas. Failure to express E-cadherin may result from mutations of the E-cadherin gene (HSECAD). AIMS: To examine the correlation between E-cadherin expression and genetic changes at HSECAD; and to examine differences in E-cadherin expression and genetic changes at HSECAD between three different groups of colorectal cancer--replication error positive (RER+) sporadic cancers, RER--sporadic cancers and ulcerative colitis associated cancers. SUBJECTS AND METHODS: Sixty eight colorectal cancers (22 RER+ sporadic cancers, 32 RER- sporadic cancers and 14 ulcerative colitis associated cancers) were studied using immunohistochemistry and for allele loss at the HSECAD locus. Exon 16 of HSECAD contains several mononucleotide repeat tracts which are very similar to microsatellite repeats and which may be susceptible to replication errors (manifest as new alleles). All cases were also examined for new alleles in exon 16. RESULTS: Absent or decreased E-cadherin protein expression was found in 27 (38%) of 68 colorectal cancers and the pattern of expression did not differ significantly among the three tumour groups. Allele loss occurred at HSECAD in four (10%) of 40 informative cancers and there were no differences between the three subgroups. New alleles at exon 16 were detected in three (14%) of 22 RER+ tumours; no new alleles were detected in RER- or ulcerative colitis associated cancers. Overall...

Features of Colorectal Cancers with High-Level Microsatellite Instability Occurring in Familial and Sporadic Settings : Parallel Pathways of Tumorigenesis

Young, Joanne; Simms, Lisa A.; Biden, Kelli G.; Wynter, Coral; Whitehall, Vicki; Karamatic, Rozemary; George, Jill; Goldblatt, Jack; Walpole, Ian; Robin, Sally-Anne; Borten, Michael M.; Stitz, Russell; Searle, Jeffrey; McKeone, Diane; Fraser, Leigh; Purdi
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /12/2001 EN
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26.6%
High-level microsatellite instability (MSI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting in the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might be discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of hMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant β-catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation...

Mammography screening interval and the frequency of interval cancers in a population-based screening.

Klemi, P. J.; Toikkanen, S.; Räsänen, O.; Parvinen, I.; Joensuu, H.
Fonte: Nature Publishing Group|1 Publicador: Nature Publishing Group|1
Tipo: Artigo de Revista Científica
Publicado em //1997 EN
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In a population-based mammography screening, 129,731 examinations were carried out among 36,000 women aged 40-74 in the city of Turku, Finland, in the period 1987-94. Women older than 50 were screened at 2-year intervals, and those younger than 50 at either 1-year or 3-year intervals, depending on their year of birth. Screen-detected breast cancers numbered 385 and, during the same time period, 154 women were diagnosed with breast cancer outside screening in the same age group in the same city, and 100 interval cancers were detected. Two hundred and fifty (67%) of the screen-detected cancers were of post-surgical stage I compared with 45 (45%) of the interval cancers and 52 (34%) of the cancers found outside screening (P<0.0001). However, among women aged 40-49 the frequency of stage I cancers did not differ significantly among screen-detected cancers, interval cancers and cancers found outside screening (50%, 42% and 44% respectively; P=0.73). Invasive interval cancers were more frequent among women aged 40-49 if screening was done at either 1-year (27%) or 3-year intervals (39%) than in older women screened at 2-year intervals (18%; P=0.08 and P=0.0009 respectively). Even if adjusted for the primary tumour size, screen-detected cancers had smaller S-phase fractions than interval cancers or control cancers (P=0.01)...

A comparison of axillary node status between cancers detected at the prevalence and first incidence breast screening rounds.

Holland, P. A.; Walls, J.; Boggis, C. R.; Knox, F.; Baildam, A. D.; Bundred, N. J.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em /11/1996 EN
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26.59%
Screen-detected breast cancers are smaller than those detected in symptomatic populations and, for any given size, they are associated with fewer lymph node metastases. The management of axillary lymph nodes in patients with screen-detected breast cancer remains controversial. We have previously reported that prevalence (initial screen)-detected cancers are associated with nodal metastases in 17.4% of cases overall. Cancers < or = 10 mm, of any grade, are associated with metastases in only 5% of cases, and grade I cancers <30 mm are not associated with metastases. This led to our recommendation that axillary surgery is unnecessary for these groups of women. The present study compared the nodal status of cancers detected at the prevalence and first incidence (second) screens in order to determine whether our recommendation is appropriate for cancers detected at the first incidence screen. Overall, 30.1% of cancers detected in the first incidence screen presented axillary nodal metastases. At all size ranges, cancers detected at the first incidence screen were associated with significantly more lymph node metastases than prevalence-detected cancers. In particular, cancers < or = 10 mm were associated with metastases in 14.3% of cases. With the possible exception of grade I cancers...

The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers

Lawes, D A; Pearson, T; SenGupta, S; Boulos, P B
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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There is increased incidence of microsatellite instability (MSI) in patients who develop multiple primary colorectal cancers (CRC), although the association with hereditary nonpolyposis colon cancer (HNPCC) is unclear. This study aims to evaluate the underlying genetic cause of MSI in these patients. Microsatellite instability was investigated in 111 paraffin-embedded CRCs obtained from 78 patients with metachronous and synchronous cancers, and a control group consisting of 74 cancers from patients with a single CRC. Tumours were classified as high level (MSI-H), low level (MSI-L) or stable (MSS). MLH1, MSH2 and MSH6 gene expression was measured by immunohistochemistry. Methylation of the MLH1 promoter region was evaluated in MSI-H cancers that failed to express MLH1, and mutational analysis performed in MSI-H samples that expressed MLH1, MSH2 and MSH6 proteins. The frequency of MSI-H was significantly greater in the multiple, 58 out of 111 (52%), compared to the single cancers, 10 out of 74 (13.5%), P<0.01. Of the 32 patients from whom two or more cancers were analysed, eight (25%) demonstrated MSI-H in both cancers, 13 (41%) demonstrated MSI-H in one cancer and 11 (34%) failed to demonstrate any MSI-H. MSI-H single cancers failed to express MLH1 or MSH2 in seven out of nine (78%) cases and MSI-L/MSS cancers failed to express MLH1 or MSH2 in one out of 45 (2.2%) cases...

Chromosomal Instability in BRAF Mutant, Microsatellite Stable Colorectal Cancers

Bond, Catherine E.; Umapathy, Aarti; Buttenshaw, Ron L.; Wockner, Leesa; Leggett, Barbara A.; Whitehall, Vicki L. J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 22/10/2012 EN
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The BRAF oncogene is mutated in 15% of sporadic colorectal cancers. Approximately half of these BRAF mutant cancers demonstrate frequent frameshift mutations termed microsatellite instability (MSI), but are diploid and chromosomally stable. BRAF wild type cancers are typically microsatellite stable (MSS) and instead acquire chromosomal instability (CIN). In these cancers, CIN is associated with a poor outcome. BRAF mutant cancers that are MSS, typically present at an advanced stage and have a particularly poor prognosis. We have previously demonstrated clinical and molecular similarities between MSS cancers with or without a BRAF mutation, and therefore hypothesised that CIN may also be frequent in BRAF mutant/MSS cancers. BRAF mutant/MSS (n = 60), and BRAF wild type/MSS CRCs (n = 90) were investigated for CIN using loss of heterozygosity analysis over twelve loci encompassing chromosomal regions 5q, 8p, 17p and 18q. CIN was frequent in BRAF mutant/MSS cancers (41/57, 72%), which was comparable to the rate found in BRAF wild type/MSS cancers (74/90, 82%). The greatest loss in BRAF mutant/MSS cancers occurred at 8p (26/44, 59%), and the least at 5q (19/49, 39%). CIN in BRAF mutant/MSS cancers correlated with advanced stage (AJCC III/IV: 15/17...

Microsatellite Stable Colorectal Cancers Stratified by the BRAF V600E Mutation Show Distinct Patterns of Chromosomal Instability

Bond, Catherine E.; Nancarrow, Derek J.; Wockner, Leesa F.; Wallace, Leanne; Montgomery, Grant W.; Leggett, Barbara A.; Whitehall, Vicki L. J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 20/03/2014 EN
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The BRAF (V600E) mutation in colorectal cancers that are microsatellite stable (MSS) confers a poor patient prognosis, whereas BRAF mutant microsatellite-unstable (MSI) colorectal cancers have an excellent prognosis. BRAF wild type cancers are typically MSS and display chromosomal instability (CIN). CIN has not been extensively studied on a genome-wide basis in relation to BRAF mutational status in colorectal cancer. BRAF mutant/MSS (BRAFmut/MSS) cancers (n = 33) and BRAF mutant/MSI (BRAFmut/MSI) cancers (n = 30) were compared for presence of copy number aberrations (CNAs) indicative of CIN, with BRAF wild type/MSS (BRAFwt/MSS) cancers (n = 18) using Illumina CytoSNP-12 arrays. BRAFmut/MSS and BRAFwt/MSS cancers showed comparable numbers of CNAs/cancer at 32.8 and 29.8 respectively. However, there were differences in patterns of CNA length between MSS cohorts, with BRAFmut/MSS cancers having significantly greater proportions of focal CNAs compared to BRAFwt/MSS cancers (p<0.0001); whereas whole chromosomal arm CNAs were more common in BRAFwt/MSS cancers (p<0.0001). This related to a reduced average CNA length in BRAFmut/MSS compared to BRAFwt/MSS cancers (20.7 Mb vs 33.4 Mb;p<0.0001); and a smaller average percent of CIN affected genomes in BRAFmut/MSS compared to BRAFwt/MSS cancers (23.9% vs 34.9% respectively). BRAFmut/MSI cancers were confirmed to have low CNA rates (5.4/cancer) and minimal CIN-affected genomes (average of 4.5%) compared to MSS cohorts (p<0.0001). BRAFmut/MSS cancers had more frequent deletion CNAs compared to BRAFwt/MSS cancers on 6p and 17q at loci not typically correlated with colorectal cancer...

Targeted Therapy in Biliary Tract Cancers

Merla, Amartej; Liu, Kenneth G.; Rajdev, Lakshmi
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
EN
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36.45%
A paradigm shift towards molecular-based, personalized cancer therapeutics has occurred in recent years and a number of targeted drugs have emerged. Various targeted therapies like erlotinib, trastuzumab, and cetuximab have been approved in lung, breast, and colon cancers, respectively. Numerous clinical trials involving targeted drugs in biliary tract cancers are currently in progress, though none have been approved for this disease. Biliary tract cancers are divided into separate entities both anatomically and in terms of pathogenesis but are grouped together in most trials given their rarity. Combination chemotherapy involving cisplatin and gemcitabine is the current standard of care in the metastatic setting. In this review, we will discuss the various molecular pathways implicated in biliary tract cancers and potential therapeutic targets.

Deregulation of MYCN, LIN28B and LET7 in a Molecular Subtype of Aggressive High-Grade Serous Ovarian Cancers

Anglesio, Michael S.; George, Joshy; Cowin, Prue A.; House, Colin M.; Sheppard, Karen E.; Etemadmoghadam, Dariush; Melnyk, Nataliya; Rustgi, Anil K.; Phillips, Wayne A.; Johnsen, Hilde; Holm, Ruth; Kristensen, Gunnar B.; Pearson, Richard B.; Huntsman, Dav
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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36.34%
Molecular subtypes of serous ovarian cancer have been recently described. Using data from independent datasets including over 900 primary tumour samples, we show that deregulation of the Let-7 pathway is specifically associated with the C5 molecular subtype of serous ovarian cancer. DNA copy number and gene expression of HMGA2, alleles of Let-7, LIN28, LIN28B, MYC, MYCN, DICER1, and RNASEN were measured using microarray and quantitative reverse transcriptase PCR. Immunohistochemistry was performed on 127 samples using tissue microarrays and anti-HMGA2 antibodies. Fluorescence in situ hybridisation of bacterial artificial chromosomes hybridized to 239 ovarian tumours was used to measure translocation at the LIN28B locus. Short interfering RNA knockdown in ovarian cell lines was used to test the functionality of associations observed. Four molecular subtypes (C1, C2, C4, C5) of high-grade serous ovarian cancers were robustly represented in each dataset and showed similar pattern of patient survival. We found highly specific activation of a pathway involving MYCN, LIN28B, Let-7 and HMGA2 in the C5 molecular subtype defined by MYCN amplification and over-expression, over-expression of MYCN targets including the Let-7 repressor LIN28B, loss of Let-7 expression and HMGA2 amplification and over-expression. DICER1...

Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers

Fetten, Katharina; Yassin, Yosuf; Buraimoh, Ayodele; Kim, Ji-Young; Legare, Robert D; Tung, Nadine Muskatel; Miron, Alexander; Schnitt, Stuart Jay; Gautam, Shiva Prasad; Kaplan, Jennifer; Szasz, Attila M.; Tian, Ruiyang; Wang, Zhigang C.; Collins, Laura C
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
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Introduction: The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to develop as BRCA1 carriers age, suggesting that they may be incidental and unrelated to BRCA1 deficiency. The purpose of this study was to compare the prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+ and ER- breast cancers that have occurred in BRCA1 carriers and to determine whether age at diagnosis or any pathologic features or biomarkers predict for loss of wt BRCA1 in these breast cancers. Methods: Relative amounts of mutated and wt BRCA1 DNA were measured by quantitative polymerase chain reaction performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER- invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation was determined on all cancers in which sufficient DNA was available. Immunostains for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53 were performed on paraffin sections from tissue microarrays containing these cancers. Results: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1-associated cancers (81.0% vs 88.6%...

Dietary Fibre Intake and Risks of Cancers of the Colon and Rectum in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Murphy, Neil; Norat, Teresa; Ferrari, Pietro; Jenab, Mazda; Bueno-de-Mesquita, Bas; Skeie, Guri; Dahm, Christina C.; Overvad, Kim; Olsen, Anja; Tjønneland, Anne; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Racine, Antoine; Kaaks, Rudolf
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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36.24%
Background: Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. Methodology/Principal Findings After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79–0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age...

Integrated Genomic Analysis of the 8q24 Amplification in Endometrial Cancers Identifies ATAD2 as Essential to MYC-Dependent Cancers

Raeder, Maria B.; Birkeland, Even; Trovik, Jone; Krakstad, Camilla; Shehata, Shyemaa; Schumacher, Steven; Zack, Travis Ian; Krohn, Antje; Werner, Henrica MJ.; Moody, Susan E; Wik, Elisabeth; Stefansson, Ingunn M.; Holst, Frederik; Oyan, Anne M.; Tamayo, P
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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Chromosome 8q24 is the most commonly amplified region across multiple cancer types, and the typical length of the amplification suggests that it may target additional genes to MYC. To explore the roles of the genes most frequently included in 8q24 amplifications, we analyzed the relation between copy number alterations and gene expression in three sets of endometrial cancers (N = 252); and in glioblastoma, ovarian, and breast cancers profiled by TCGA. Among the genes neighbouring MYC, expression of the bromodomain-containing gene ATAD2 was the most associated with amplification. Bromodomain-containing genes have been implicated as mediators of MYC transcriptional function, and indeed ATAD2 expression was more closely associated with expression of genes known to be upregulated by MYC than was MYC itself. Amplifications of 8q24, expression of genes downstream from MYC, and overexpression of ATAD2 predicted poor outcome and increased from primary to metastatic lesions. Knockdown of ATAD2 and MYC in seven endometrial and 21 breast cancer cell lines demonstrated that cell lines that were dependent on MYC also depended upon ATAD2. These same cell lines were also the most sensitive to the histone deacetylase (HDAC) inhibitor Trichostatin-A...

If You Don’t Find It Often, You Often Don’t Find It: Why Some Cancers Are Missed in Breast Cancer Screening

Evans, Karla K.; Birdwell, Robyn L.; Wolfe, Jeremy M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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36.48%
Mammography is an important tool in the early detection of breast cancer. However, the perceptual task is difficult and a significant proportion of cancers are missed. Visual search experiments show that miss (false negative) errors are elevated when targets are rare (low prevalence) but it is unknown if low prevalence is a significant factor under real world, clinical conditions. Here we show that expert mammographers in a real, low-prevalence, clinical setting, miss a much higher percentage of cancers than are missed when the mammographers search for the same cancers under high prevalence conditions. We inserted 50 positive and 50 negative cases into the normal workflow of the breast cancer screening service of an urban hospital over the course of nine months. This rate was slow enough not to markedly raise disease prevalence in the radiologists’ daily practice. Six radiologists subsequently reviewed all 100 cases in a session where the prevalence of disease was 50%. In the clinical setting, participants missed 30% of the cancers. In the high prevalence setting, participants missed just 12% of the same cancers. Under most circumstances, this low prevalence effect is probably adaptive. It is usually wise to be conservative about reporting events with very low base rates (Was that a flying saucer? Probably not.). However...

Distribution and pathological features of pancreatic, ampullary, biliary and duodenal cancers resected with pancreaticoduodenectomy

Chandrasegaram, M.D.; Chiam, S.C.; Chen, J.W.; Khalid, A.; Mittinty, M.L.; Neo, E.L.; Tan, C.P.; Dolan, P.M.; Brooke-Smith, M.E.; Kanhere, H.; Worthley, C.S.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
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26.61%
BACKGROUND: Pancreatic cancer (PC) has the worst survival of all periampullary cancers. This may relate to histopathological differences between pancreatic cancers and other periampullary cancers. Our aim was to examine the distribution and histopathologic features of pancreatic, ampullary, biliary and duodenal cancers resected with a pancreaticoduodenectomy (PD) and to examine local trends of periampullary cancers resected with a PD. METHODS: A retrospective review of PD between January 2000 and December 2012 at a public metropolitan database was performed. The institutional ethics committee approved this study. RESULTS: There were 142 PDs during the study period, of which 70 cases were pre-2010 and 72 post-2010, corresponding to a recent increase in the number of cases. Of the 142 cases, 116 were for periampullary cancers. There were also proportionately more PD for PC (26/60, 43% pre-2010 vs 39/56, 70% post-2010, P = 0.005). There were 65/116 (56%) pancreatic, 29/116 (25%), ampullary, 17/116 (15%) biliary and 5/116 (4%) duodenal cancers. Nodal involvement occurred more frequently in PC (78%) compared to ampullary (59%), biliary (47%) and duodenal cancers (20%), P = 0.002. Perineural invasion was also more frequent in PC (74%) compared to ampullary (34%)...

Improvements in progression-free and overall survival due to the use of anti-angiogenic agents in gynecologic cancers

Schmid, B.C.; Oehler, M.K.
Fonte: Springer Verlag Publicador: Springer Verlag
Tipo: Artigo de Revista Científica
Publicado em //2015 EN
Relevância na Pesquisa
36.24%
OPINION STATEMENT: In ovarian cancer (OC), the best established anti-angiogenic drug, bevacizumab, has demonstrated only modest prolonged progression free survival (PFS) and no increased overall survival (OS). The unanswered question is in which clinical situation bevacizumab might benefit ovarian cancer patients most. The cost-benefit analysis in the primary treatment was found not to be favorable but the use in the recurrent OC setting might be more compelling. Multi-targeted anti-angiogenic tyrosine kinase inhibitors (TKI) such as cediranib and pazopanib have shown some therapeutic benefits with improvements of PFS and OS in patients with platinum-sensitive as well as resistant OC, in whom there is a major need for novel therapies. Very promising is also the observed improvement of PFS in recurrent OC in patients when combining cediranib with the PARP inhibitor olaparib without giving additional chemotherapy. The anti-angiogenic agent trebananib has achieved similar results like TKI, but has a favorable toxicity profile which does not overlap with those of VEGF inhibitors. In cervical cancer the addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent or metastatic chemotherapy-naive disease results in a significant increase in OS. Considering the lack of therapeutic options in this difficult clinical setting...

Evaluation der Intervallkarzinome aus der Screening-Region Neckar-Alb vom 23.01.2008 bis 23.01.2011; Evaluation of the interval cancers from the screening area Neckar-Alb from 23.01.2008 to 23.01.2011

Stub, Sabine
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
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Intervallkarzinome sind Karzinome, die zwischen zwei Screening-Untersuchungen auftreten und auf der Vor-Mammographie entweder gar nicht sichtbar waren (no signs), retrospektiv mammographisch geringe Anzeichen aufwiesen (minimal signs) oder fälschlich als negativ befundet wurden (missed cancer). Die aufgetretenen Intervallkarzinome der ersten Screening-Runde aus dem Mammographie-Screening-Programm der Region Neckar-Alb wurden auf ihre Charakteristika untersucht und mit den im Screening entdeckten Karzinomen verglichen. Es wurde der Fragestellung nachgegangen, ob eine differierende Parenchymdichte zwischen der Intervallkarzinomgruppe und der Screening-Karzinomgruppe existiert. Es wurde geprüft, ob die europäischen Leitlinien eingehalten wurden und ob Intervallkarzinome als Qualitätsparameter zur Bewertung der Leistungsfähigkeit einer Screening-Einheit aussagekräftig sind. Abschließend wurden die Ergebnisse des Review-Prozesses der Intervallkarzinome evaluiert. Patientinnen, Material und Methode: Grundlage für diese Arbeit stellen die 70102 durchgeführten Mammographie-Untersuchungen, die 560 Screening-Karzinome, sowie die 49 Intervall-karzinome dar, die vom 23.01.2008 bis zum 23.01.2011 und bis zum Datenstand vom 01.03.2011 ermittelt wurden. Ergebnisse: Im Vergleich zu den Screening-Karzinomen gab bei den Intervallkarzinomen deutlich mehr invasive Karzinome...

Down regulation of gastric and intestinal phenotypic expression in Epstein-Barr virus-associated stomach cancers

Hirano, N.; Tsukamoto, T.; Mizoshita, T.; Koriyama, C.; Akiba, S.; Campos, F.; Carrasquilla, G.; Carrascal Marino, E.; Cao, X.; Toyoda, T.; Ban, H.; Miki, K.; Tatematsu, M.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
Relevância na Pesquisa
36.4%
importance of gastric and intestinal phenotypic expression for stomach carcinogenesis. In this study, we focused on Epstein-Barr virus (EBV)-associated stomach cancers, with special attention to Cdx2. Methods and Results: We evaluated the expression of gastric and intestinal phenotypic markers by immunohistochemistry in 35 EBV-positive [EBV (+)] and 75 EBV-negative [EBV (-)] stomach cancers in Colombia. The lesions were divided phenotypically into gastric (G), gastric-and-intestinal mixed (GI), intestinal (I), and null (N) phenotypes. In the EBV (+) cases, the lesions were divided phenotypically into 9 G (25.7%), 1 GI (2.9%), 3 I (8.6%), and 22 N (62.9%) types. Similarly, the EBV (-) lesions were also classified phenotypically as 15 G (20.0%), 19 GI (25.3%), 24 I (32.0%), and 17 N (22.7%) types. The proportion of N type EBV (+) lesions was higher than for their EBV (-) counterparts (P<0.0001). The expression of Cdx2 and MUC2 was also found to be significantly lower in EBV (+) than in EBV (-) stomach cancers (P=0.0001; P<0.0001). Cdx2 expression in the intestinal metaplastic glands present in non-neoplastic mucosa surrounding EBV (+) lesions was also significantly lower than in EBV (-) tumors (P=0.016) despite no evidence of EBV infection by low expression of intestinal phenotype markers...

Prevention of HPV-Related Cancers in Norway: Cost-Effectiveness of Expanding the HPV Vaccination Program to Include Pre-Adolescent Boys

Burger, Emily A.; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S.; Kim, Jane J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
36.34%
Background: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. Methods: A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. Results: Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However...