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Sample records for 1975-2004 featuring cancer

  1. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  2. Topological features in cancer gene expression data.

    PubMed

    Lockwood, S; Krishnamoorthy, B

    2015-01-01

    We present a new method for exploring cancer gene expression data based on tools from algebraic topology. Our method selects a small relevant subset from tens of thousands of genes while simultaneously identifying nontrivial higher order topological features, i.e., holes, in the data. We first circumvent the problem of high dimensionality by dualizing the data, i.e., by studying genes as points in the sample space. Then we select a small subset of the genes as landmarks to construct topological structures that capture persistent, i.e., topologically significant, features of the data set in its first homology group. Furthermore, we demonstrate that many members of these loops have been implicated for cancer biogenesis in scientific literature. We illustrate our method on five different data sets belonging to brain, breast, leukemia, and ovarian cancers. PMID:25592573

  3. Trends in nutrient concentrations, loads, and yields in streams in the Sacramento, San Joaquin, and Santa Ana Basins, California, 1975-2004

    USGS Publications Warehouse

    Kratzer, Charles R.; Kent, Robert; Seleh, Dina K.; Knifong, Donna L.; Dileanis, Peter D.; Orlando, James L.

    2011-01-01

    A comprehensive database was assembled for the Sacramento, San Joaquin, and Santa Ana Basins in California on nutrient concentrations, flows, and point and nonpoint sources of nutrients for 1975-2004. Most of the data on nutrient concentrations (nitrate, ammonia, total nitrogen, orthophosphate, and total phosphorus) were from the U.S. Geological Survey's National Water Information System database (35.2 percent), the California Department of Water Resources (21.9 percent), the University of California at Davis (21.6 percent), and the U.S. Environmental Protection Agency's STOrage and RETrieval database (20.0 percent). Point-source discharges accounted for less than 1 percent of river flows in the Sacramento and San Joaquin Rivers, but accounted for close to 80 percent of the nonstorm flow in the Santa Ana River. Point sources accounted for 4 and 7 percent of the total nitrogen and total phosphorus loads, respectively, in the Sacramento River at Freeport for 1985-2004. Point sources accounted for 8 and 17 percent of the total nitrogen and total phosphorus loads, respectively, in the San Joaquin River near Vernalis for 1985-2004. The volume of wastewater discharged into the Santa Ana River increased almost three-fold over the study period. However, due to improvements in wastewater treatment, the total nitrogen load to the Santa Ana River from point sources in 2004 was approximately the same as in 1975 and the total phosphorus load in 2004 was less than in 1975. Nonpoint sources of nutrients estimated in this study included atmospheric deposition, fertilizer application, manure production, and tile drainage. The estimated dry deposition of nitrogen exceeded wet deposition in the Sacramento and San Joaquin Valleys and in the basin area of the Santa Ana Basin, with ratios of dry to wet deposition of 1.7, 2.8, and 9.8, respectively. Fertilizer application increased appreciably from 1987 to 2004 in all three California basins, although manure production increased in the

  4. Features of triple-negative breast cancer

    PubMed Central

    Plasilova, Magdalena L.; Hayse, Brandon; Killelea, Brigid K.; Horowitz, Nina R.; Chagpar, Anees B.; Lannin, Donald R.

    2016-01-01

    Abstract The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57–0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases. PMID:27583878

  5. Recurrent thyroid cancer with changing histologic features

    PubMed Central

    Konduri, Kartik; Harshman, Leeanne K.; Welch, Brian J.; O'Brien, John C.

    2010-01-01

    We present the case of a 57-year-old woman diagnosed with breast cancer and a thyroid mass that was suspicious for cancer. The breast cancer was estrogen and progesterone receptor negative, HER2/neu borderline, with a high proliferative index. Treatment of this cancer took precedence. Nine months later, a total thyroidectomy was done for papillary thyroid cancer with metastases to 2 of 8 perithyroid lymph nodes. Postoperative radioactive iodine ablation was given. Recurrent thyroid disease was found in the right neck 1 year later and was resected; no radioactive iodine was given at that time. After 2½ years, the cancer recurred as a more highly aggressive, undifferentiated anaplastic thyroid carcinoma. Treatment is discussed. PMID:21240322

  6. feature - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    "Cancer is a disease of the genome," noted Lynda Chin, M.D., professor of dermatology, Harvard Medical School and Dana-Farber Cancer Institute. "And understanding the impact of genomic changes in the proteome is critically important for converting genomic knowledge into something that a clinician can use on their patients."

  7. Texture Features from Mammographic Images and Risk of Breast Cancer

    PubMed Central

    Manduca, Armando; Carston, Michael J.; Heine, John J.; Scott, Christopher G.; Pankratz, V. Shane; Brandt, Kathy R.; Sellers, Thomas A.; Vachon, Celine M.; Cerhan, James R.

    2009-01-01

    Mammographic percent density (PD) is a strong risk factor for breast cancer, but there has been relatively little systematic evaluation of other features in mammographic images that might additionally predict breast cancer risk. We evaluated the association of a large number of image texture features with risk of breast cancer using a clinic-based case-control study of digitized film mammograms, all with screening mammograms prior to breast cancer diagnosis. The sample was split into training (123 cases, 258 controls) and validation (123 cases, 264 controls) datasets. Age and body mass index (BMI)-adjusted Odds Ratios (ORs) per standard deviation change in the feature, 95% confidence intervals, and the area under the receiver operator characteristic curve (AUC) were obtained using logistic regression. A bootstrap approach was used to identify the strongest features in the training dataset, and results for features that validated in the second half of the sample were reported using the full dataset. The mean age at mammography was 64.0 ± 10.2 years, and the mean time from mammography to breast cancer was 3.7 ± 1.0 (range 2.0-5.9 years). PD was associated with breast cancer risk (OR=1.49; 1.25-1.78). The strongest features that validated from each of several classes (Markovian, run-length, Laws, wavelet and Fourier) showed similar ORs as PD and predicted breast cancer at a similar magnitude (AUC=0.58-0.60) as PD (AUC=0.58). All of these features were automatically calculated (unlike PD), and measure texture at a coarse scale. These features were moderately correlated with PD (r = 0.39-0.64), and after adjustment for PD, each of the features attenuated only slightly and retained statistical significance. However, simultaneous inclusion of these features in a model with PD did not significantly improve the ability to predict breast cancer. PMID:19258482

  8. Mueller matrix polarimetry for differentiating characteristic features of cancerous tissues

    NASA Astrophysics Data System (ADS)

    Du, E.; He, Honghui; Zeng, Nan; Sun, Minghao; Guo, Yihong; Wu, Jian; Liu, Shaoxiong; Ma, Hui

    2014-07-01

    Polarization measurements allow one to enhance the imaging contrast of superficial tissues and obtain new polarization sensitive parameters for better descriptions of the micro- and macro- structural and optical properties of complex tissues. Since the majority of cancers originate in the epithelial layer, probing the morphological and pathological changes in the superficial tissues using an expended parameter set with improved contrast will assist in early clinical detection of cancers. We carry out Mueller matrix imaging on different cancerous tissues to look for cancer specific features. Using proper scattering models and Monte Carlo simulations, we examine the relationship between the microstructures of the samples, which are represented by the parameters of the scattering model and the characteristic features of the Mueller matrix. This study gives new clues on the contrast mechanisms of polarization sensitive measurements for different cancers and may provide new diagnostic techniques for clinical applications.

  9. Predictive features of breast cancer on Mexican screening mammography patients

    NASA Astrophysics Data System (ADS)

    Rodriguez-Rojas, Juan; Garza-Montemayor, Margarita; Trevino-Alvarado, Victor; Tamez-Pena, José Gerardo

    2013-02-01

    Breast cancer is the most common type of cancer worldwide. In response, breast cancer screening programs are becoming common around the world and public programs now serve millions of women worldwide. These programs are expensive, requiring many specialized radiologists to examine all images. Nevertheless, there is a lack of trained radiologists in many countries as in Mexico, which is a barrier towards decreasing breast cancer mortality, pointing at the need of a triaging system that prioritizes high risk cases for prompt interpretation. Therefore we explored in an image database of Mexican patients whether high risk cases can be distinguished using image features. We collected a set of 200 digital screening mammography cases from a hospital in Mexico, and assigned low or high risk labels according to its BIRADS score. Breast tissue segmentation was performed using an automatic procedure. Image features were obtained considering only the segmented region on each view and comparing the bilateral di erences of the obtained features. Predictive combinations of features were chosen using a genetic algorithms based feature selection procedure. The best model found was able to classify low-risk and high-risk cases with an area under the ROC curve of 0.88 on a 150-fold cross-validation test. The features selected were associated to the differences of signal distribution and tissue shape on bilateral views. The model found can be used to automatically identify high risk cases and trigger the necessary measures to provide prompt treatment.

  10. Breast cancer detection in rotational thermography images using texture features

    NASA Astrophysics Data System (ADS)

    Francis, Sheeja V.; Sasikala, M.; Bhavani Bharathi, G.; Jaipurkar, Sandeep D.

    2014-11-01

    Breast cancer is a major cause of mortality in young women in the developing countries. Early diagnosis is the key to improve survival rate in cancer patients. Breast thermography is a diagnostic procedure that non-invasively images the infrared emissions from breast surface to aid in the early detection of breast cancer. Due to limitations in imaging protocol, abnormality detection by conventional breast thermography, is often a challenging task. Rotational thermography is a novel technique developed in order to overcome the limitations of conventional breast thermography. This paper evaluates this technique's potential for automatic detection of breast abnormality, from the perspective of cold challenge. Texture features are extracted in the spatial domain, from rotational thermogram series, prior to and post the application of cold challenge. These features are fed to a support vector machine for automatic classification of normal and malignant breasts, resulting in a classification accuracy of 83.3%. Feature reduction has been performed by principal component analysis. As a novel attempt, the ability of this technique to locate the abnormality has been studied. The results of the study indicate that rotational thermography holds great potential as a screening tool for breast cancer detection.

  11. Feature Extraction and Analysis of Breast Cancer Specimen

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Debnath; Robles, Rosslin John; Kim, Tai-Hoon; Bandyopadhyay, Samir Kumar

    In this paper, we propose a method to identify abnormal growth of cells in breast tissue and suggest further pathological test, if necessary. We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps. Normal ductal epithelial cells and ductal / lobular invasive carcinogenic cells also consider for comparison here in this paper. In fact, features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue. We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some greater extent.

  12. Lung cancer in central Tunisia: epidemiology and clinicopathological features.

    PubMed

    Missaoui, Nabiha; Hmissa, Sihem; Landolsi, Hanene; Korbi, Skander; Joma, Wafa; Anjorin, Affissath; Ben Abdelkrim, Soumaya; Beizig, Nadia; Mokni, Moncef

    2011-01-01

    Lung cancer is the most common cancer worldwide but data from Tunisia are limited. The aim of this research was to describe the epidemiology, pathology and clinical features of lung cancer in Central Tunisia. All lung cancer cases diagnosed during a 15-year period were analyzed based on the data of the Cancer Registry of the Center of Tunisia. Five-year age-specific rates, world age-standardized rates (ASR), and annual percent change were calculated using annual data on population size and the estimated age structure. A total of 1,882 incident cases of lung cancer were registered (1,782 males, 100 females). The median age at diagnosis was 64 years for males and 61 years for females, with ASRs of 35.2 per 100,000 among males and 1.5 among females. Over time, there were significant decreasing trends by -6.5% (95% CI: -12.9%; -0.2%) for females and a stable incidence for males at an annual rate of +0.2% (95% CI: -1.6%; +1.8%). The predominant histological type was squamous cell carcinoma in males (36.9%) and adenocarcinoma in females (52%). During 2003-2007, adenocarcinoma became the most frequent (33.7%) followed by squamous cell carcinoma (30.3%) in males. The majority of tumor cases were diagnosed at advanced stages (79.9%). In conclusion, lung cancer has remained the most common cancer diagnosed at advanced stages among Tunisian men. Our findings justify the need to plan and develop effective programs aiming at the control and prevention of the spread of lung cancer in Tunisia. PMID:22296375

  13. Signs and genetics of rare cancer syndromes with gastroenterological features.

    PubMed

    Bruno, William; Fornarini, Giuseppe; Ghiorzo, Paola

    2015-08-14

    Although the genetic bases of most hereditary cancer syndromes are known, and genetic tests are available for them, the incidence of the most rare of these syndromes is likely underestimated, partially because the clinical expression is neither fully understood nor easily diagnosed due to the variable and complex expressivity. The clinical features of a small pool of rare cancer syndromes include gastroenterological signs, though not necessarily tumors, that could require the intervention of a gastroenterologist during any of the phases of the clinical management. Herein we will attempt to spread the knowledge on these rare syndromes by summarizing the phenotype and genetic basis, and revising the peculiar gastroenterological signs whose underlying role in these rare hereditary cancer syndromes is often neglected. Close collaboration between geneticists and gastroenterologists could facilitate both the early identification of patients or relatives at-risk and the planning of multidisciplinary and tailored management of these subjects. PMID:26290627

  14. Signs and genetics of rare cancer syndromes with gastroenterological features

    PubMed Central

    Bruno, William; Fornarini, Giuseppe; Ghiorzo, Paola

    2015-01-01

    Although the genetic bases of most hereditary cancer syndromes are known, and genetic tests are available for them, the incidence of the most rare of these syndromes is likely underestimated, partially because the clinical expression is neither fully understood nor easily diagnosed due to the variable and complex expressivity. The clinical features of a small pool of rare cancer syndromes include gastroenterological signs, though not necessarily tumors, that could require the intervention of a gastroenterologist during any of the phases of the clinical management. Herein we will attempt to spread the knowledge on these rare syndromes by summarizing the phenotype and genetic basis, and revising the peculiar gastroenterological signs whose underlying role in these rare hereditary cancer syndromes is often neglected. Close collaboration between geneticists and gastroenterologists could facilitate both the early identification of patients or relatives at-risk and the planning of multidisciplinary and tailored management of these subjects. PMID:26290627

  15. Clinical Features of Liver Cancer with Cerebral Hemorrhage

    PubMed Central

    Lu, Qiuhong; Chen, Li; Zeng, Jinsheng; Huang, Gelun; Qin, Chao; Cheng, Daobin; Yu, Lixia; Liang, Zhijian

    2016-01-01

    Background Cerebral hemorrhage is common in patients with cancer, but the clinical features and pathogenesis of liver cancer patients with cerebral hemorrhage are not well known. Material/Methods Liver cancer patients who developed cerebral hemorrhage were recruited from the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014. We retrospectively analyzed clinical presentations, results of laboratory tests, and imaging examinations. The clinical features and pathogenesis were summarized. Results Among 11133 patients with liver cancer, 9 patients (0.08%), including 3 females and 6 males met the inclusion criteria. The age range was 48–73 years and the average age was 61.67±8.97 years. Five patients did not have traditional hemorrhage risk factors and 4s had the risk factors; however, all had developed hepatocellular carcinoma, and 3 had developed metastasis. All 9 patients showed elevated tumor markers: an increased AFP level was detected in 6 patients, coagulation dysfunctions in 8 patients, and abnormal liver functions in 6 patients. Five patients had developed cerebral hemorrhagic lesions in the lobes of their brains, while hemorrhagic lesions in the basal ganglia occurred in 3 patients and in the brainstem in only 1 patient. Four patients had clear consciousness, while 5 patients were in coma and showed poor prognosis. Conclusions Patients who have liver cancer complicated with cerebral hemorrhage usually lack traditional risk factors of cerebral hemorrhage. The site of cerebral hemorrhage is often detected in the lobes of the brain. Coagulation dysfunctions might be the main pathogenesis of liver cancer complicated with cerebral hemorrhage. PMID:27209058

  16. Clinical Features of Liver Cancer with Cerebral Hemorrhage.

    PubMed

    Lu, Qiuhong; Chen, Li; Zeng, Jinsheng; Huang, Gelun; Qin, Chao; Cheng, Daobin; Yu, Lixia; Liang, Zhijian

    2016-01-01

    BACKGROUND Cerebral hemorrhage is common in patients with cancer, but the clinical features and pathogenesis of liver cancer patients with cerebral hemorrhage are not well known. MATERIAL AND METHODS Liver cancer patients who developed cerebral hemorrhage were recruited from the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014. We retrospectively analyzed clinical presentations, results of laboratory tests, and imaging examinations. The clinical features and pathogenesis were summarized. RESULTS Among 11133 patients with liver cancer, 9 patients (0.08%), including 3 females and 6 males met the inclusion criteria. The age range was 48-73 years and the average age was 61.67±8.97 years. Five patients did not have traditional hemorrhage risk factors and 4s had the risk factors; however, all had developed hepatocellular carcinoma, and 3 had developed metastasis. All 9 patients showed elevated tumor markers: an increased AFP level was detected in 6 patients, coagulation dysfunctions in 8 patients, and abnormal liver functions in 6 patients. Five patients had developed cerebral hemorrhagic lesions in the lobes of their brains, while hemorrhagic lesions in the basal ganglia occurred in 3 patients and in the brainstem in only 1 patient. Four patients had clear consciousness, while 5 patients were in coma and showed poor prognosis. CONCLUSIONS Patients who have liver cancer complicated with cerebral hemorrhage usually lack traditional risk factors of cerebral hemorrhage. The site of cerebral hemorrhage is often detected in the lobes of the brain. Coagulation dysfunctions might be the main pathogenesis of liver cancer complicated with cerebral hemorrhage. PMID:27209058

  17. Clinical and molecular features of young-onset colorectal cancer

    PubMed Central

    Ballester, Veroushka; Rashtak, Shahrooz; Boardman, Lisa

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression. PMID:26855533

  18. Quantitative imaging features to predict cancer status in lung nodules

    NASA Astrophysics Data System (ADS)

    Liu, Ying; Balagurunathan, Yoganand; Atwater, Thomas; Antic, Sanja; Li, Qian; Walker, Ronald; Smith, Gary T.; Massion, Pierre P.; Schabath, Matthew B.; Gillies, Robert J.

    2016-03-01

    Background: We propose a systematic methodology to quantify incidentally identified lung nodules based on observed radiological traits on a point scale. These quantitative traits classification model was used to predict cancer status. Materials and Methods: We used 102 patients' low dose computed tomography (LDCT) images for this study, 24 semantic traits were systematically scored from each image. We built a machine learning classifier in cross validation setting to find best predictive imaging features to differentiate malignant from benign lung nodules. Results: The best feature triplet to discriminate malignancy was based on long axis, concavity and lymphadenopathy with average AUC of 0.897 (Accuracy of 76.8%, Sensitivity of 64.3%, Specificity of 90%). A similar semantic triplet optimized on Sensitivity/Specificity (Youden's J index) included long axis, vascular convergence and lymphadenopathy which had an average AUC of 0.875 (Accuracy of 81.7%, Sensitivity of 76.2%, Specificity of 95%). Conclusions: Quantitative radiological image traits can differentiate malignant from benign lung nodules. These semantic features along with size measurement enhance the prediction accuracy.

  19. [Feature extraction for breast cancer data based on geometric algebra theory and feature selection using differential evolution].

    PubMed

    Li, Jing; Hong, Wenxue

    2014-12-01

    The feature extraction and feature selection are the important issues in pattern recognition. Based on the geometric algebra representation of vector, a new feature extraction method using blade coefficient of geometric algebra was proposed in this study. At the same time, an improved differential evolution (DE) feature selection method was proposed to solve the elevated high dimension issue. The simple linear discriminant analysis was used as the classifier. The result of the 10-fold cross-validation (10 CV) classification of public breast cancer biomedical dataset was more than 96% and proved superior to that of the original features and traditional feature extraction method. PMID:25868233

  20. Specific gene hypomethylation and cancer: New insights into coding region feature trends

    PubMed Central

    Daura-Oller, Elias; Cabre, Maria; Montero, Miguel A; Paternain, Jose L; Romeu, Antoni

    2009-01-01

    Giving coding region structural features a role in the hypomethylation of specific genes, the occurrence of G+C content, CpG islands, repeat and retrotransposable elements in demethylated genes related to cancer has been evaluated. A comparative analysis among different cancer types has also been performed. In this work, the inter-cancer coding region features comparative analysis carried out, show insights into what structural trends/patterns are present in the studied cancers. PMID:19707296

  1. Features of ovarian cancer in Lynch syndrome (Review)

    PubMed Central

    NAKAMURA, KANAKO; BANNO, KOUJI; YANOKURA, MEGUMI; IIDA, MIHO; ADACHI, MASATAKA; MASUDA, KENTA; UEKI, ARISA; KOBAYASHI, YUSUKE; NOMURA, HIROYUKI; HIRASAWA, AKIRA; TOMINAGA, EIICHIRO; AOKI, DAISUKE

    2014-01-01

    Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9–2.7%. Lynch syndrome accounts for 10–15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65–75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome. PMID:25279173

  2. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

    PubMed Central

    Podolskiy, Dmitriy I.; Lobanov, Alexei V.; Kryukov, Gregory V.; Gladyshev, Vadim N.

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  3. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development.

    PubMed

    Podolskiy, Dmitriy I; Lobanov, Alexei V; Kryukov, Gregory V; Gladyshev, Vadim N

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  4. Feature selection using genetic algorithm for breast cancer diagnosis: experiment on three different datasets

    PubMed Central

    Aalaei, Shokoufeh; Shahraki, Hadi; Rowhanimanesh, Alireza; Eslami, Saeid

    2016-01-01

    Objective(s): This study addresses feature selection for breast cancer diagnosis. The present process uses a wrapper approach using GA-based on feature selection and PS-classifier. The results of experiment show that the proposed model is comparable to the other models on Wisconsin breast cancer datasets. Materials and Methods: To evaluate effectiveness of proposed feature selection method, we employed three different classifiers artificial neural network (ANN) and PS-classifier and genetic algorithm based classifier (GA-classifier) on Wisconsin breast cancer datasets include Wisconsin breast cancer dataset (WBC), Wisconsin diagnosis breast cancer (WDBC), and Wisconsin prognosis breast cancer (WPBC). Results: For WBC dataset, it is observed that feature selection improved the accuracy of all classifiers expect of ANN and the best accuracy with feature selection achieved by PS-classifier. For WDBC and WPBC, results show feature selection improved accuracy of all three classifiers and the best accuracy with feature selection achieved by ANN. Also specificity and sensitivity improved after feature selection. Conclusion: The results show that feature selection can improve accuracy, specificity and sensitivity of classifiers. Result of this study is comparable with the other studies on Wisconsin breast cancer datasets. PMID:27403253

  5. Automated colon cancer detection using hybrid of novel geometric features and some traditional features.

    PubMed

    Rathore, Saima; Hussain, Mutawarra; Khan, Asifullah

    2015-10-01

    Automatic classification of colon into normal and malignant classes is complex due to numerous factors including similar colors in different biological constituents of histopathological imagery. Therefore, such techniques, which exploit the textural and geometric properties of constituents of colon tissues, are desired. In this paper, a novel feature extraction strategy that mathematically models the geometric characteristics of constituents of colon tissues is proposed. In this study, we also show that the hybrid feature space encompassing diverse knowledge about the tissues׳ characteristics is quite promising for classification of colon biopsy images. This paper thus presents a hybrid feature space based colon classification (HFS-CC) technique, which utilizes hybrid features for differentiating normal and malignant colon samples. The hybrid feature space is formed to provide the classifier different types of discriminative features such as features having rich information about geometric structure and image texture. Along with the proposed geometric features, a few conventional features such as morphological, texture, scale invariant feature transform (SIFT), and elliptic Fourier descriptors (EFDs) are also used to develop a hybrid feature set. The SIFT features are reduced using minimum redundancy and maximum relevancy (mRMR). Various kernels of support vector machines (SVM) are employed as classifiers, and their performance is analyzed on 174 colon biopsy images. The proposed geometric features have achieved an accuracy of 92.62%, thereby showing their effectiveness. Moreover, the proposed HFS-CC technique achieves 98.07% testing and 99.18% training accuracy. The better performance of HFS-CC is largely due to the discerning ability of the proposed geometric features and the developed hybrid feature space. PMID:25819060

  6. Radiomic feature clusters and prognostic signatures specific for Lung and Head & Neck cancer.

    PubMed

    Parmar, Chintan; Leijenaar, Ralph T H; Grossmann, Patrick; Rios Velazquez, Emmanuel; Bussink, Johan; Rietveld, Derek; Rietbergen, Michelle M; Haibe-Kains, Benjamin; Lambin, Philippe; Aerts, Hugo J W L

    2015-01-01

    Radiomics provides a comprehensive quantification of tumor phenotypes by extracting and mining large number of quantitative image features. To reduce the redundancy and compare the prognostic characteristics of radiomic features across cancer types, we investigated cancer-specific radiomic feature clusters in four independent Lung and Head &Neck (H) cancer cohorts (in total 878 patients). Radiomic features were extracted from the pre-treatment computed tomography (CT) images. Consensus clustering resulted in eleven and thirteen stable radiomic feature clusters for Lung and H cancer, respectively. These clusters were validated in independent external validation cohorts using rand statistic (Lung RS = 0.92, p < 0.001, H RS = 0.92, p < 0.001). Our analysis indicated both common as well as cancer-specific clustering and clinical associations of radiomic features. Strongest associations with clinical parameters: Prognosis Lung CI = 0.60 ± 0.01, Prognosis H CI = 0.68 ± 0.01; Lung histology AUC = 0.56 ± 0.03, Lung stage AUC = 0.61 ± 0.01, H HPV AUC = 0.58 ± 0.03, H stage AUC = 0.77 ± 0.02. Full utilization of these cancer-specific characteristics of image features may further improve radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor phenotypic characteristics in clinical practice. PMID:26251068

  7. Radiomic feature clusters and Prognostic Signatures specific for Lung and Head & Neck cancer

    PubMed Central

    Parmar, Chintan; Leijenaar, Ralph T. H.; Grossmann, Patrick; Rios Velazquez, Emmanuel; Bussink, Johan; Rietveld, Derek; Rietbergen, Michelle M.; Haibe-Kains, Benjamin; Lambin, Philippe; Aerts, Hugo J.W.L.

    2015-01-01

    Radiomics provides a comprehensive quantification of tumor phenotypes by extracting and mining large number of quantitative image features. To reduce the redundancy and compare the prognostic characteristics of radiomic features across cancer types, we investigated cancer-specific radiomic feature clusters in four independent Lung and Head & Neck (H∓N) cancer cohorts (in total 878 patients). Radiomic features were extracted from the pre-treatment computed tomography (CT) images. Consensus clustering resulted in eleven and thirteen stable radiomic feature clusters for Lung and H & N cancer, respectively. These clusters were validated in independent external validation cohorts using rand statistic (Lung RS = 0.92, p < 0.001, H & N RS = 0.92, p < 0.001). Our analysis indicated both common as well as cancer-specific clustering and clinical associations of radiomic features. Strongest associations with clinical parameters: Prognosis Lung CI = 0.60 ± 0.01, Prognosis H & N CI = 0.68 ± 0.01; Lung histology AUC = 0.56 ± 0.03, Lung stage AUC = 0.61 ± 0.01, H & N HPV AUC = 0.58 ± 0.03, H & N stage AUC = 0.77 ± 0.02. Full utilization of these cancer-specific characteristics of image features may further improve radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor phenotypic characteristics in clinical practice. PMID:26251068

  8. Identification of cancerous gastric cells based on common features extracted from hyperspectral microscopic images

    PubMed Central

    Zhu, Siqi; Su, Kang; Liu, Yumeng; Yin, Hao; Li, Zhen; Huang, Furong; Chen, Zhenqiang; Chen, Weidong; Zhang, Ge; Chen, Yihong

    2015-01-01

    We construct a microscopic hyperspectral imaging system to distinguish between normal and cancerous gastric cells. We study common transmission-spectra features that only emerge when the samples are dyed with hematoxylin and eosin (H&E) stain. Subsequently, we classify the obtained visible-range transmission spectra of the samples into three zones. Distinct features are observed in the spectral responses between the normal and cancerous cell nuclei in each zone, which depend on the pH level of the cell nucleus. Cancerous gastric cells are precisely identified according to these features. The average cancer-cell identification accuracy obtained with a backpropagation algorithm program trained with these features is 95%. PMID:25909000

  9. [Particular features of lymph dissection in operations for gastric cancer].

    PubMed

    Iaitskiĭ, A N; Danilov, I N

    2008-01-01

    In order to optimize the technique of lymph dissection, a method of intraoperative mapping of lymph outflow tracts was used with a lymphotropic dye Blue patente V. It allowed better orientation during lymphodissection in operations for gastric cancer. The detection and investigation of the "signal" lymph node as the most probable object of lymphogenic metastazing can improve the accuracy of postoperative staging of gastric cancer. Visualization of the lymph nodes in the preparation made it possible to increase the number of lymph nodes sent for histological investigation. PMID:18522180

  10. [Cancer stem cells: Radiotherapeutic features and therapeutic targets].

    PubMed

    Méry, Benoîte; Rancoule, Chloé; Guy, Jean-Baptiste; Espenel, Sophie; Wozny, Anne-Sophie; Simonet, Stéphanie; Vallard, Alexis; Alphonse, Gersende; Ardail, Dominique; Rodriguez-Lafrasse, Claire; Magné, Nicolas

    2016-01-01

    Recent evidences suggest that many types of cancers contain a cell population presenting stem cell properties. While the great majority of tumor cells are destined to differentiate, and eventually stop dividing, only a minority population of cells, termed cancer stem cells (CSCs), possesses extensive self-renewal capability and can recapitulate tumor pathophysiology in an immune-compromised animal model. Tumor initiating cells have been identified and isolated in many tumor types including brain, colon and prostate. They are virtually resistant to radiation and may contribute to treatment resistance and recurrence. Therefore, therapies specifically targeting CSCs will likely be needed for complete tumor eradication. The present study reviews published reports identifying the mechanisms of radioresistance of CSCs and potential targets based on the pathways of self-renewal. Further elucidation of pathways that regulate CSCs may provide insights into the development of novel innovative therapies. PMID:26702506

  11. Chromosomal instability: A common feature and a therapeutic target of cancer.

    PubMed

    Tanaka, Kozo; Hirota, Toru

    2016-08-01

    Most cancer cells are aneuploid, containing abnormal numbers of chromosomes, mainly caused by elevated levels of chromosome missegregation, known as chromosomal instability (CIN). These well-recognized, but poorly understood, features of cancers have recently been studied extensively, unraveling causal relationships between CIN and cancer. Here we review recent findings regarding how CIN and aneuploidy occur, how they affect cellular functions, how cells respond to them, and their relevance to diseases, especially cancer. Aneuploid cells are under various kinds of stresses that result in reduced cellular fitness. Nevertheless, genetic heterogeneity derived from CIN allows the selection of cells better adapted to their environment, which supposedly facilitates generation and progression of cancer. We also discuss how we can exploit the properties of cancer cells exhibiting CIN for effective cancer therapy. PMID:27345585

  12. Stratification of Digestive Cancers with Different Pathological Features and Survival Outcomes by MicroRNA Expression

    PubMed Central

    Tang, Senwei; Wu, William K. K.; Li, Xiangchun; Wong, Sunny H.; Wong, Nathalie; Chan, Matthew T. V.; Sung, Joseph J. Y.; Yu, Jun

    2016-01-01

    MicroRNAs (miRNAs) are aberrantly expressed in virtually all cancer types, including digestive cancers. Herein, we aggregated and systematically analyzed miRNA expression profiles of 1765 tumor samples, including esophageal, gastric, liver, pancreatic, colon and rectal cancers, obtained through small RNA sequencing by The Cancer Genome Atlas. We found that digestive cancers of different tissue origins could be differentiated according to their miRNA expression profiles. In particular, esophageal squamous cell carcinoma and esophageal adenocarcinoma exhibited distinct miRNA expression patterns. Thirteen (e.g. miR-135b, miR-182) and sixteen (e.g. miR-139, miR-133a-1, miR-490) miRNAs were commonly upregulated and downregulated in more than four cancer types, respectively. Pertinent to pathological features, low miR-181d expression was associated with microsatellite instability in colon and gastric cancers whereas low miR-106a expression was associated with hepatitis B virus infection in hepatocellular carcinoma. Progression in colon cancer could also be predicted by low let-7f-2 and high miR-106a expression. Molecular subtypes with distinct prognostic outcomes independent of tumor-node-metastasis staging were identified in hepatocellular carcinoma and colon cancer. In total, 4 novel and 6 reported associations between specific miRNAs and patients’ survival were identified. Collectively, novel miRNA markers were identified to stratify digestive cancers with different pathological features and survival outcomes. PMID:27080237

  13. Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer

    PubMed Central

    Wei, You-Sheng; Yao, De-Sheng; Long, Ying

    2016-01-01

    Perineural invasion (PNI) has been investigated as a new prognostic factor in a number of carcinomas. However, studies on PNI in cervical cancer are limited, and inconsistent conclusions have been reported by different groups. The aim of the present study was to analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer, and to evaluate the clinical significance of PNI of cervical cancer. Retrospective review identified 206 patients with cervical cancer who underwent radical hysterectomy plus pelvic lymphadenectomy between December 2012 and August 2014. The association between PNI and clinical and histopathological features of cervical cancer and post-operative radiotherapy was evaluated based on univariate and multivariate analyses. PNI of cervical cancer was identified in 33 of 206 (16%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor grade, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age and histopathological types (P>0.05). Multivariate analysis suggests that LVSI and lymph node metastasis were associated with PNI of cervical cancer (P<0.05). In addition, post-operative radiotherapy was significantly more recommended for patients with PNI than those without PNI (P<0.001). In conclusion, PNI of cervical cancer is associated with LVSI and lymph node metastasis and can be used as an index for the determination of post-operative radiotherapy for cervical cancer patients. PMID:27588197

  14. Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

    PubMed Central

    Ward, R; Meagher, A; Tomlinson, I; O'Connor, T; Norrie, M; Wu, R; Hawkins, N

    2001-01-01

    BACKGROUND AND AIMS—In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice.
METHODS—DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53.
RESULTS—Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%.
CONCLUSIONS—We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.


Keywords: colorectal carcinoma; microsatellite instability; survival; MLH1; MSH2; immunohistochemistry PMID:11358903

  15. Microbiota organization is a distinct feature of proximal colorectal cancers.

    PubMed

    Dejea, Christine M; Wick, Elizabeth C; Hechenbleikner, Elizabeth M; White, James R; Mark Welch, Jessica L; Rossetti, Blair J; Peterson, Scott N; Snesrud, Erik C; Borisy, Gary G; Lazarev, Mark; Stein, Ellen; Vadivelu, Jamuna; Roslani, April C; Malik, Ausuma A; Wanyiri, Jane W; Goh, Khean L; Thevambiga, Iyadorai; Fu, Kai; Wan, Fengyi; Llosa, Nicolas; Housseau, Franck; Romans, Katharine; Wu, XinQun; McAllister, Florencia M; Wu, Shaoguang; Vogelstein, Bert; Kinzler, Kenneth W; Pardoll, Drew M; Sears, Cynthia L

    2014-12-23

    Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC. PMID:25489084

  16. Enhanced cancer recognition system based on random forests feature elimination algorithm.

    PubMed

    Ozcift, Akin

    2012-08-01

    Accurate classifiers are vital to design precise computer aided diagnosis (CADx) systems. Classification performances of machine learning algorithms are sensitive to the characteristics of data. In this aspect, determining the relevant and discriminative features is a key step to improve performance of CADx. There are various feature extraction methods in the literature. However, there is no universal variable selection algorithm that performs well in every data analysis scheme. Random Forests (RF), an ensemble of trees, is used in classification studies successfully. The success of RF algorithm makes it eligible to be used as kernel of a wrapper feature subset evaluator. We used best first search RF wrapper algorithm to select optimal features of four medical datasets: colon cancer, leukemia cancer, breast cancer and lung cancer. We compared accuracies of 15 widely used classifiers trained with all features versus to extracted features of each dataset. The experimental results demonstrated the efficiency of proposed feature extraction strategy with the increase in most of the classification accuracies of the algorithms. PMID:21567124

  17. Aspirin counteracts cancer stem cell features, desmoplasia and gemcitabine resistance in pancreatic cancer

    PubMed Central

    Zhang, Yiyao; Liu, Li; Fan, Pei; Bauer, Nathalie; Gladkich, Jury; Ryschich, Eduard; Bazhin, Alexandr V.; Giese, Nathalia A.; Strobel, Oliver; Hackert, Thilo; Hinz, Ulf; Gross, Wolfgang; Fortunato, Franco; Herr, Ingrid

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia, the selection of cancer stem-like cells (CSCs) and therapy resistance. The anti-inflammatory drug aspirin is suggested to lower the risk for PDA and to improve the treatment, although available results are conflicting and the effect of aspirin to CSC characteristics and desmoplasia in PDA has not yet been investigated. We characterized the influence of aspirin on CSC features, stromal reactions and gemcitabine resistance. Four established and 3 primary PDA cell lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal cultures and tissues from patients who did or did not receive aspirin before surgery were analyzed using MTT assays, flow cytometry, colony and spheroid formation assays, Western blot analysis, antibody protein arrays, electrophoretic mobility shift assays (EMSAs), immunohistochemistry and in vivo xenotransplantation. Aspirin significantly induced apoptosis and reduced the viability, self-renewal potential, and expression of proteins involved in inflammation and stem cell signaling. Aspirin also reduced the growth and invasion of tumors in vivo, and it significantly prolonged the survival of mice with orthotopic pancreatic xenografts in combination with gemcitabine. This was associated with a decreased expression of markers for progression, inflammation and desmoplasia. These findings were confirmed in tissue samples obtained from patients who had or had not taken aspirin before surgery. Importantly, aspirin sensitized cells that were resistant to gemcitabine and thereby enhanced the therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells, chick embryos or mice. These results highlight aspirin as an effective, inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia and CSC features PDA. PMID:25846752

  18. Classification of lung cancer using ensemble-based feature selection and machine learning methods.

    PubMed

    Cai, Zhihua; Xu, Dong; Zhang, Qing; Zhang, Jiexia; Ngai, Sai-Ming; Shao, Jianlin

    2015-03-01

    Lung cancer is one of the leading causes of death worldwide. There are three major types of lung cancers, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and carcinoid. NSCLC is further classified into lung adenocarcinoma (LADC), squamous cell lung cancer (SQCLC) as well as large cell lung cancer. Many previous studies demonstrated that DNA methylation has emerged as potential lung cancer-specific biomarkers. However, whether there exists a set of DNA methylation markers simultaneously distinguishing such three types of lung cancers remains elusive. In the present study, ROC (Receiving Operating Curve), RFs (Random Forests) and mRMR (Maximum Relevancy and Minimum Redundancy) were proposed to capture the unbiased, informative as well as compact molecular signatures followed by machine learning methods to classify LADC, SQCLC and SCLC. As a result, a panel of 16 DNA methylation markers exhibits an ideal classification power with an accuracy of 86.54%, 84.6% and a recall 84.37%, 85.5% in the leave-one-out cross-validation (LOOCV) and independent data set test experiments, respectively. Besides, comparison results indicate that ensemble-based feature selection methods outperform individual ones when combined with the incremental feature selection (IFS) strategy in terms of the informative and compact property of features. Taken together, results obtained suggest the effectiveness of the ensemble-based feature selection approach and the possible existence of a common panel of DNA methylation markers among such three types of lung cancer tissue, which would facilitate clinical diagnosis and treatment. PMID:25512221

  19. Detection and Classification of Cancer from Microscopic Biopsy Images Using Clinically Significant and Biologically Interpretable Features

    PubMed Central

    Kumar, Rajesh; Srivastava, Subodh

    2015-01-01

    A framework for automated detection and classification of cancer from microscopic biopsy images using clinically significant and biologically interpretable features is proposed and examined. The various stages involved in the proposed methodology include enhancement of microscopic images, segmentation of background cells, features extraction, and finally the classification. An appropriate and efficient method is employed in each of the design steps of the proposed framework after making a comparative analysis of commonly used method in each category. For highlighting the details of the tissue and structures, the contrast limited adaptive histogram equalization approach is used. For the segmentation of background cells, k-means segmentation algorithm is used because it performs better in comparison to other commonly used segmentation methods. In feature extraction phase, it is proposed to extract various biologically interpretable and clinically significant shapes as well as morphology based features from the segmented images. These include gray level texture features, color based features, color gray level texture features, Law's Texture Energy based features, Tamura's features, and wavelet features. Finally, the K-nearest neighborhood method is used for classification of images into normal and cancerous categories because it is performing better in comparison to other commonly used methods for this application. The performance of the proposed framework is evaluated using well-known parameters for four fundamental tissues (connective, epithelial, muscular, and nervous) of randomly selected 1000 microscopic biopsy images. PMID:27006938

  20. Mining featured micro ribonucleic acids associated with lung cancer based on bioinformatics

    PubMed Central

    Su, Lin; Li, Na; Huo, Xueyun

    2015-01-01

    Background Few genetic markers useful for the screening of lung cancer risk exist. Although related research has shown that certain expression profiles of micro ribonucleic acids (miRNAs) are different in lung cancer versus the normal lung, such as miR-29a and miR-29s, the precise molecular mechanism of lung cancer remains obscure. In order to get a better understanding of the pathogenetic mechanism of lung cancer, we analyzed the differentially expressed genes (DEGs) and identified featured miRNAs in lung cancer tissues. Methods We used the gene expression profile GSE10072, including 49 gene chips of non-tumor tissues and 58 gene chips of lung tumor specimens. The DEGs between these two groups were identified by Limma package in R language. The TarBase database was used to construct the networks of miRNA regulating DEGs related to lung cancer. After ordering miRNAs regulating DEGs, we further screened featured miRNAs combined with the miR2Disease database. Results A total of 5572 DEGs were obtained between lung cancer and control specimens. After constructing a miRNA regulatory network, a total of 398 regulations between 57 miRNAs and 321 target genes existed. By intergrating the miR2Disease database and using a sorting algorithm, a total of six featured miRNAs related to lung cancer were identified, including miR-520h, miR-133a, miR-34, miR-103, miR-370, and miR-148. They might be involved in lung cancer progression by regulating ABCG2, PKM2, VAMP2, GPD1, MAP3K8, and DNMT3B, respectively. Conclusion The top 10 significant miRNAs, such as miR-520h, miR-133a, miR-34, and miR-103 may be potential therapeutic targets for lung cancer. PMID:26273407

  1. Chromosomal changes in aggressive breast cancers with basal-like features

    PubMed Central

    Yu, Wayne; Kanaan, Yasmine; Bae, Young-Kyung; Gabrielson, Edward

    2009-01-01

    Using high-resolution oligonucleotide CGH arrays, we evaluated chromosomal copy number changes in a series of 16 breast cancers, selected on the basis of highly similar pathological and molecular features characteristic of the “basal-like” phenotype. Each of these cancers showed numerous gains and losses, reflecting multiple chromosomal rearrangements during the development of these high-grade cancers. Chromosomal losses were particularly prevalent on chromosomal arms 5q, 8p, 9q, 12q, 17p, 19p, and Xq, and gains were commonly seen on chromosomal arms 1q, 8q, and 17q. Particularly remarkable were regions of high-level amplification (> 8-fold copy number change) on 4q12, 8q23.3, 19p12, and 19q13.2. These regions included candidate oncogenes cKIT, JUND, and AKT2., and immunohistochemistry confirmed that these particular genes were highly expressed in the cancers harboring the specific amplifications. However, each of these amplifications was observed only in individual cases, and no particular chromosomal alteration appeared to generally characterize this group of cancers. Thus, genomic changes among breast cancers with basal-like features appear to be very heterogeneous. Distinct high-level amplifications may provide new targets for treating some of these cancers, but copy number changes do not reveal a distinctive genomic fingerprint for this proposed class of breast cancers. PMID:19602461

  2. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis

    PubMed Central

    Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh

    2015-01-01

    Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer. PMID:25797243

  3. Lowered circulating aspartate is a metabolic feature of human breast cancer

    PubMed Central

    Xie, Guoxiang; Zhou, Bingsen; Zhao, Aihua; Qiu, Yunping; Zhao, Xueqing; Garmire, Lana; Shvetsov, Yurii B.; Yu, Herbert; Yen, Yun; Jia, Wei

    2015-01-01

    Distinct metabolic transformation is essential for cancer cells to sustain a high rate of proliferation and resist cell death signals. Such a metabolic transformation results in unique cellular metabolic phenotypes that are often reflected by distinct metabolite signatures in tumor tissues as well as circulating blood. Using a metabolomics platform, we find that breast cancer is associated with significantly (p = 6.27E-13) lowered plasma aspartate levels in a training group comprising 35 breast cancer patients and 35 controls. The result was validated with 103 plasma samples and 183 serum samples of two groups of primary breast cancer patients. Such a lowered aspartate level is specific to breast cancer as it has shown 0% sensitivity in serum from gastric (n = 114) and colorectal (n = 101) cancer patients. There was a significantly higher level of aspartate in breast cancer tissues (n = 20) than in adjacent non-tumor tissues, and in MCF-7 breast cancer cell line than in MCF-10A cell lines, suggesting that the depleted level of aspartate in blood of breast cancer patients is due to increased tumor aspartate utilization. Together, these findings suggest that lowed circulating aspartate is a key metabolic feature of human breast cancer. PMID:26452258

  4. Prostate cancer multi-feature analysis using trans-rectal ultrasound images.

    PubMed

    Mohamed, S S; Salama, M M A; Kamel, M; El-Saadany, E F; Rizkalla, K; Chin, J

    2005-08-01

    This note focuses on extracting and analysing prostate texture features from trans-rectal ultrasound (TRUS) images for tissue characterization. One of the principal contributions of this investigation is the use of the information of the images' frequency domain features and spatial domain features to attain a more accurate diagnosis. Each image is divided into regions of interest (ROIs) by the Gabor multi-resolution analysis, a crucial stage, in which segmentation is achieved according to the frequency response of the image pixels. The pixels with a similar response to the same filter are grouped to form one ROI. Next, from each ROI two different statistical feature sets are constructed; the first set includes four grey level dependence matrix (GLDM) features and the second set consists of five grey level difference vector (GLDV) features. These constructed feature sets are then ranked by the mutual information feature selection (MIFS) algorithm. Here, the features that provide the maximum mutual information of each feature and class (cancerous and non-cancerous) and the minimum mutual information of the selected features are chosen, yielding a reduced feature subset. The two constructed feature sets, GLDM and GLDV, as well as the reduced feature subset, are examined in terms of three different classifiers: the condensed k-nearest neighbour (CNN), the decision tree (DT) and the support vector machine (SVM). The accuracy classification results range from 87.5% to 93.75%, where the performance of the SVM and that of the DT are significantly better than the performance of the CNN. PMID:16030375

  5. NOTE: Prostate cancer multi-feature analysis using trans-rectal ultrasound images

    NASA Astrophysics Data System (ADS)

    Mohamed, S. S.; Salama, M. M. A.; Kamel, M.; El-Saadany, E. F.; Rizkalla, K.; Chin, J.

    2005-08-01

    This note focuses on extracting and analysing prostate texture features from trans-rectal ultrasound (TRUS) images for tissue characterization. One of the principal contributions of this investigation is the use of the information of the images' frequency domain features and spatial domain features to attain a more accurate diagnosis. Each image is divided into regions of interest (ROIs) by the Gabor multi-resolution analysis, a crucial stage, in which segmentation is achieved according to the frequency response of the image pixels. The pixels with a similar response to the same filter are grouped to form one ROI. Next, from each ROI two different statistical feature sets are constructed; the first set includes four grey level dependence matrix (GLDM) features and the second set consists of five grey level difference vector (GLDV) features. These constructed feature sets are then ranked by the mutual information feature selection (MIFS) algorithm. Here, the features that provide the maximum mutual information of each feature and class (cancerous and non-cancerous) and the minimum mutual information of the selected features are chosen, yeilding a reduced feature subset. The two constructed feature sets, GLDM and GLDV, as well as the reduced feature subset, are examined in terms of three different classifiers: the condensed k-nearest neighbour (CNN), the decision tree (DT) and the support vector machine (SVM). The accuracy classification results range from 87.5% to 93.75%, where the performance of the SVM and that of the DT are significantly better than the performance of the CNN.

  6. Exploring new quantitative CT image features to improve assessment of lung cancer prognosis

    NASA Astrophysics Data System (ADS)

    Emaminejad, Nastaran; Qian, Wei; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin

    2015-03-01

    Due to the promotion of lung cancer screening, more Stage I non-small-cell lung cancers (NSCLC) are currently detected, which usually have favorable prognosis. However, a high percentage of the patients have cancer recurrence after surgery, which reduces overall survival rate. To achieve optimal efficacy of treating and managing Stage I NSCLC patients, it is important to develop more accurate and reliable biomarkers or tools to predict cancer prognosis. The purpose of this study is to investigate a new quantitative image analysis method to predict the risk of lung cancer recurrence of Stage I NSCLC patients after the lung cancer surgery using the conventional chest computed tomography (CT) images and compare the prediction result with a popular genetic biomarker namely, protein expression of the excision repair cross-complementing 1 (ERCC1) genes. In this study, we developed and tested a new computer-aided detection (CAD) scheme to segment lung tumors and initially compute 35 tumor-related morphologic and texture features from CT images. By applying a machine learning based feature selection method, we identified a set of 8 effective and non-redundant image features. Using these features we trained a naïve Bayesian network based classifier to predict the risk of cancer recurrence. When applying to a test dataset with 79 Stage I NSCLC cases, the computed areas under ROC curves were 0.77±0.06 and 0.63±0.07 when using the quantitative image based classifier and ERCC1, respectively. The study results demonstrated the feasibility of improving accuracy of predicting cancer prognosis or recurrence risk using a CAD-based quantitative image analysis method.

  7. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication.

    PubMed

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  8. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication

    PubMed Central

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  9. ERα-Negative and Triple Negative Breast Cancer: Molecular Features and Potential Therapeutic Approaches

    PubMed Central

    Chen, Jin-Qiang; Russo, Jose

    2010-01-01

    Triple negative breast cancer (TNBC) is a type of aggressive breast cancer lacking the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER-2). TNBC patients account for approximately 15% of total breast cancer patients and are more prevalent among young African, African-American and Latino women patients. The currently available ER-targeted and Her-2-based therapies are not effective for treating TNBC. Recent studies have revealed a number of novel features of TNBC. In the present work, we comprehensively addressed these features and discussed potential therapeutic approaches based on these features for TNBC, with particular focus on: 1) the pathological features of TNBC/basal-like breast cancer; 2) E2/ERβ – mediated signaling pathways; 3) G-protein coupling receptor-30/epithelial growth factor receptor (GPCR-30/EGFR) signaling pathway; 4) interactions of ERβ with breast cancer 1/2 (BRCA1/2); 5) chemokine CXCL8 and related chemokines; 6) altered microRNA signatures and suppression of ERα expression/ERα-signaling by micro-RNAs; 7) altered expression of several pro-oncongenic and tumor suppressor proteins; and 8) genotoxic effects caused by oxidative estrogen metabolites. Gaining better insights into these molecular pathways in TNBC may lead to identification of novel biomarkers and targets for development of diagnostic and therapeutic approaches for prevention and treatment of TNBC. PMID:19527773

  10. Identification and characterization of colorectal cancer using Raman spectroscopy and feature selection techniques.

    PubMed

    Li, Shaoxin; Chen, Gong; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Xu, Junfa; Li, Xueqiang; Lin, Lin

    2014-10-20

    This study aims to detect colorectal cancer with near-infrared Raman spectroscopy and feature selection techniques. A total of 306 Raman spectra of colorectal cancer tissues and normal tissues are acquired from 44 colorectal cancer patients. Five diagnostically important Raman bands in the regions of 815-830, 935-945, 1131-1141, 1447-1457 and 1665-1675 cm(-1) related to proteins, nucleic acids and lipids of tissues are identified with the ant colony optimization (ACO) and support vector machine (SVM). The diagnostic models built with the identified Raman bands provide a diagnostic accuracy of 93.2% for identifying colorectal cancer from normal Raman spectroscopy. The study demonstrates that the Raman spectroscopy associated with ACO-SVM diagnostic algorithms has great potential to characterize and diagnose colorectal cancer. PMID:25401621

  11. Aggressiveness features and outcomes of true interval cancers: comparison between screen-detected and symptom-detected cancers.

    PubMed

    Domingo, Laia; Blanch, Jordi; Servitja, Sònia; Corominas, Josep Maria; Murta-Nascimento, Cristiane; Rueda, Antonio; Redondo, Maximino; Castells, Xavier; Sala, Maria

    2013-01-01

    The question of whether screen detection confers an additional survival benefit in breast cancer is unclear and subject to several biases. Our aim was to examine the role of the diagnostic method (screen-detected, symptom-detected, and true interval cancers) and the clinical-pathological features in relapse-free survival and overall survival in breast cancer patients. We included 228 invasive breast cancers diagnosed in Barcelona from 1996 to 2008 among women aged 50-69 years. Ninety-seven patients were screen detected within the screening, 34 truly arose between 2-year screening mammograms (true interval cancers), and 97 were symptom detected outside the screening. The clinical-pathological features at diagnosis were compared. The overall and disease-free survival probabilities were computed using the Kaplan-Meier method. Cox proportional hazard models were applied, with adjustment by clinical-pathological variables. At diagnosis, symptom-detected and true interval cancers were in more advanced stages and were less differentiated. The highest proportion of triple-negative cancers was detected among true interval cancers (P=0.002). At 5 years of follow-up, the disease-free survival rates for screen-detected, true interval, and symptom-detected cancers were 87.5% (95% confidence interval, 80.5-95.2%), 64.1% (46.4-88.5%), and 79.4% (71.0-88.8%), respectively, and the overall survival rates were 94.5% (89.3-99.9%), 65.5% (47.1-91.2%), and 85.6% (78.3-93.6%), respectively. True interval cancers had the highest hazard ratio for relapse prediction (1.89; 0.67-5.31) and a hazard ratio of death of 5.55 (1.61-19.15) after adjustment for tumor-node-metastasis stage and phenotype. Clinically detected tumors, especially true interval cancers, more frequently showed biological features related to worse prognosis and were associated with poorer survival even after adjustment for clinical-pathological characteristics. PMID:22584215

  12. Modified Logistic Regression Models Using Gene Coexpression and Clinical Features to Predict Prostate Cancer Progression

    PubMed Central

    Zhao, Hongya; Logothetis, Christopher J.; Gorlov, Ivan P.; Zeng, Jia; Dai, Jianguo

    2013-01-01

    Predicting disease progression is one of the most challenging problems in prostate cancer research. Adding gene expression data to prediction models that are based on clinical features has been proposed to improve accuracy. In the current study, we applied a logistic regression (LR) model combining clinical features and gene co-expression data to improve the accuracy of the prediction of prostate cancer progression. The top-scoring pair (TSP) method was used to select genes for the model. The proposed models not only preserved the basic properties of the TSP algorithm but also incorporated the clinical features into the prognostic models. Based on the statistical inference with the iterative cross validation, we demonstrated that prediction LR models that included genes selected by the TSP method provided better predictions of prostate cancer progression than those using clinical variables only and/or those that included genes selected by the one-gene-at-a-time approach. Thus, we conclude that TSP selection is a useful tool for feature (and/or gene) selection to use in prognostic models and our model also provides an alternative for predicting prostate cancer progression. PMID:24367394

  13. Cuckoo search optimisation for feature selection in cancer classification: a new approach.

    PubMed

    Gunavathi, C; Premalatha, K

    2015-01-01

    Cuckoo Search (CS) optimisation algorithm is used for feature selection in cancer classification using microarray gene expression data. Since the gene expression data has thousands of genes and a small number of samples, feature selection methods can be used for the selection of informative genes to improve the classification accuracy. Initially, the genes are ranked based on T-statistics, Signal-to-Noise Ratio (SNR) and F-statistics values. The CS is used to find the informative genes from the top-m ranked genes. The classification accuracy of k-Nearest Neighbour (kNN) technique is used as the fitness function for CS. The proposed method is experimented and analysed with ten different cancer gene expression datasets. The results show that the CS gives 100% average accuracy for DLBCL Harvard, Lung Michigan, Ovarian Cancer, AML-ALL and Lung Harvard2 datasets and it outperforms the existing techniques in DLBCL outcome and prostate datasets. PMID:26547979

  14. Low-fidelity alternative DNA repair carcinogenesis theory may interpret many cancer features and anticancer strategies.

    PubMed

    Jiang, Chuo; Starr, Shane; Chen, Fuxue; Wu, Jiaxi

    2016-08-01

    We have proposed that the low-fidelity compensatory backup alternative DNA repair pathways drive multistep carcinogenesis. Here, we apply it to interpret the clinical features of cancer, such as mutator phenotype, tissue specificity, age specificity, diverse types of cancers originated from the same type of tissue, cancer susceptibility of patients with DNA repair-defective syndromes, development of cancer only for a selected number of individuals among those that share the same genetic defect, invasion and metastasis. Clinically, the theory predicts that to improve the efficacy of molecular targeted or synthetic lethal therapy, it may be crucial to inhibit the low-fidelity compensatory alternative DNA repair either directly or by blocking the signal transducers of the sustained microenvironmental stress. PMID:27166654

  15. Prediction of core cancer genes using a hybrid of feature selection and machine learning methods.

    PubMed

    Liu, Y X; Zhang, N N; He, Y; Lun, L J

    2015-01-01

    Machine learning techniques are of great importance in the analysis of microarray expression data, and provide a systematic and promising way to predict core cancer genes. In this study, a hybrid strategy was introduced based on machine learning techniques to select a small set of informative genes, which will lead to improving classification accuracy. First feature filtering algorithms were applied to select a set of top-ranked genes, and then hierarchical clustering and collapsing dense clusters were used to select core cancer genes. Through empirical study, our approach is capable of selecting relatively few core cancer genes while making high-accuracy predictions. The biological significance of these genes was evaluated using systems biology analysis. Extensive functional pathway and network analyses have confirmed findings in previous studies and can bring new insights into common cancer mechanisms. PMID:26345818

  16. [Clinical and prognostic features of surgical treatment in gastric cancer in aged patients].

    PubMed

    Lu, Sheng; Zhu, Zhenggang

    2016-05-25

    The incidence of gastric cancer in the elderly is increasing because of increased life expectancy and improved medical care. Gastric cancer in the elderly is characterized by specific clinicopathological features, including a male-predominance gender tendency, more comorbid diseases, more advanced clinical stage, distinct histopathological findings, absence of family history, etc. The incidence of surgery-related post-operative complication shows no significant difference between elderly and non-elderly patients. However, the incidence of non-surgery-related complications is relatively higher in elderly patients. Although the overall survival rate of elderly patients is lower, the disease-specific survival rate of elderly patients is comparable with non-elderly patients. Therefore, surgery is still an effective way to improve the prognosis of elderly gastric cancer patients, and care should be taken while dealing with the comorbid diseases in elderly gastric cancer patients to improve the survival. PMID:27215533

  17. Cancer Basics

    MedlinePlus

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  18. New Molecular Features of Colorectal Cancer Identified - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples

  19. Lung Cancer Prediction Using Neural Network Ensemble with Histogram of Oriented Gradient Genomic Features

    PubMed Central

    Adetiba, Emmanuel; Olugbara, Oludayo O.

    2015-01-01

    This paper reports an experimental comparison of artificial neural network (ANN) and support vector machine (SVM) ensembles and their “nonensemble” variants for lung cancer prediction. These machine learning classifiers were trained to predict lung cancer using samples of patient nucleotides with mutations in the epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene, and tumor suppressor p53 genomes collected as biomarkers from the IGDB.NSCLC corpus. The Voss DNA encoding was used to map the nucleotide sequences of mutated and normal genomes to obtain the equivalent numerical genomic sequences for training the selected classifiers. The histogram of oriented gradient (HOG) and local binary pattern (LBP) state-of-the-art feature extraction schemes were applied to extract representative genomic features from the encoded sequences of nucleotides. The ANN ensemble and HOG best fit the training dataset of this study with an accuracy of 95.90% and mean square error of 0.0159. The result of the ANN ensemble and HOG genomic features is promising for automated screening and early detection of lung cancer. This will hopefully assist pathologists in administering targeted molecular therapy and offering counsel to early stage lung cancer patients and persons in at risk populations. PMID:25802891

  20. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features.

    PubMed

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J; Altman, Russ B; Ré, Christopher; Rubin, Daniel L; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  1. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

    PubMed Central

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J.; Altman, Russ B.; Ré, Christopher; Rubin, Daniel L.; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  2. Imaging features of HER2 overexpression in breast cancer: a systematic review and meta-analysis.

    PubMed

    Elias, Sjoerd G; Adams, Arthur; Wisner, Dorota J; Esserman, Laura J; van't Veer, Laura J; Mali, Willem P Th M; Gilhuijs, Kenneth G A; Hylton, Nola M

    2014-08-01

    Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and human epidermal growth factor receptor type 2 (HER2) overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI), and/or [(18)F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 articles, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on five or more studies and robustness in subgroup analyses were as follows: the presence of microcalcifications on mammography [pooled odds ratio (pOR), 3.14; 95% confidence interval (CI), 2.46-4.00] or ultrasound (mass-associated pOR, 2.95; 95% CI, 2.34-3.71), branching or fine linear microcalcifications (pOR, 2.11; 95% CI, 1.07-4.14) or extremely dense breasts on mammography (pOR, 1.37; 95% CI, 1.07-1.76), and washout (pOR, 1.57; 95% CI, 1.11-2.21) or fast initial kinetics (pOR, 2.60; 95% CI, 1.43-4.73) on MRI all increased the chance of HER2 overexpression. Maximum [(18)F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference, +0.76; 95% CI, 0.10-1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up. PMID:24807204

  3. Association Between Changes in Mammographic Image Features and Risk for Near-Term Breast Cancer Development.

    PubMed

    Tan, Maxine; Zheng, Bin; Leader, Joseph K; Gur, David

    2016-07-01

    The purpose of this study is to develop and test a new computerized model for predicting near-term breast cancer risk based on quantitative assessment of bilateral mammographic image feature variations in a series of negative full-field digital mammography (FFDM) images. The retrospective dataset included series of four sequential FFDM examinations of 335 women. The last examination in each series ("current") and the three most recent "prior" examinations were obtained. All "prior" examinations were interpreted as negative during the original clinical image reading, while in the "current" examinations 159 cancers were detected and pathologically verified and 176 cases remained cancer-free. From each image, we initially computed 158 mammographic density, structural similarity, and texture based image features. The absolute subtraction value between the left and right breasts was selected to represent each feature. We then built three support vector machine (SVM) based risk models, which were trained and tested using a leave-one-case-out based cross-validation method. The actual features used in each SVM model were selected using a nested stepwise regression analysis method. The computed areas under receiver operating characteristic curves monotonically increased from 0.666±0.029 to 0.730±0.027 as the time-lag between the "prior" (3 to 1) and "current" examinations decreases. The maximum adjusted odds ratios were 5.63, 7.43, and 11.1 for the three "prior" (3 to 1) sets of examinations, respectively. This study demonstrated a positive association between the risk scores generated by a bilateral mammographic feature difference based risk model and an increasing trend of the near-term risk for having mammography-detected breast cancer. PMID:26886970

  4. Risk of Breast Cancer in Women with False-Positive Results according to Mammographic Features.

    PubMed

    Castells, Xavier; Torá-Rocamora, Isabel; Posso, Margarita; Román, Marta; Vernet-Tomas, Maria; Rodríguez-Arana, Ana; Domingo, Laia; Vidal, Carmen; Baré, Marisa; Ferrer, Joana; Quintana, María Jesús; Sánchez, Mar; Natal, Carmen; Espinàs, Josep A; Saladié, Francina; Sala, María

    2016-08-01

    Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26878225

  5. Prioritization of anticancer drugs against a cancer using genomic features of cancer cells: A step towards personalized medicine

    PubMed Central

    Gupta, Sudheer; Chaudhary, Kumardeep; Kumar, Rahul; Gautam, Ankur; Nanda, Jagpreet Singh; Dhanda, Sandeep Kumar; Brahmachari, Samir Kumar; Raghava, Gajendra P. S.

    2016-01-01

    In this study, we investigated drug profile of 24 anticancer drugs tested against a large number of cell lines in order to understand the relation between drug resistance and altered genomic features of a cancer cell line. We detected frequent mutations, high expression and high copy number variations of certain genes in both drug resistant cell lines and sensitive cell lines. It was observed that a few drugs, like Panobinostat, are effective against almost all types of cell lines, whereas certain drugs are effective against only a limited type of cell lines. Tissue-specific preference of drugs was also seen where a drug is more effective against cell lines belonging to a specific tissue. Genomic features based models have been developed for each anticancer drug and achieved average correlation between predicted and actual growth inhibition of cell lines in the range of 0.43 to 0.78. We hope, our study will throw light in the field of personalized medicine, particularly in designing patient-specific anticancer drugs. In order to serve the scientific community, a webserver, CancerDP, has been developed for predicting priority/potency of an anticancer drug against a cancer cell line using its genomic features (http://crdd.osdd.net/raghava/cancerdp/). PMID:27030518

  6. LETM1 overexpression is correlated with the clinical features and survival outcome of breast cancer

    PubMed Central

    Li, Nan; Zheng, Yahui; Xuan, Chouhui; Lin, Zhenhua; Piao, Longzhen; Liu, Shuangping

    2015-01-01

    Background: Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is a mitochondrial inner membrane protein that was first identified in Wolf-Hirschhorn syndrome. However, high-level expression of LETM1 has been correlated with multiple human malignancies, suggesting roles in carcinogenesis and tumor progression. This study is aimed to explore the clinicopathological characteristics and prognostic value of LETM1 overexpression in breast cancer. Methods: Immunohistochemical (IHC) staining, and immunofluorescence (IF) were performed to examine LETM1 expression in breast cancer cell line/tissues compared with adjacent normal tissues. Statistical analysis was applied to evaluate the correlation between LETM1 overexpression and the clinicopathological features of breast cancer. Survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was analyzed using the Cox proportional hazard models. Results: LETM1 protein showed cytoplasmic staining pattern in breast cancer. The strongly positive rate of LETM1 protein was 61.6% (98/159) in breast cancer, which was significantly higher than in DCIS (29.7%, 11/37), hyperplasia (16.7%, 3/18) and adjacent normal breast tissues (15.9%, 7/44). High-level expression of LETM1 protein was correlated with lymph node metastasis, poor differentiation, late clinical stage, disease-free survival (DFS) and overall survival (OS) rates in breast cancer. Moreover, multivariate analysis suggested that LETM1 emerged as a significant independent prognostic factor along with clinical stage of patients with breast cancer. Conclusions: LETM1 plays an important role in the progression of breast cancer. High level expression of LETM1 is an independent poor prognostic factor of breast cancer. PMID:26722481

  7. Flow Cytometry-Based Classification in Cancer Research: A View on Feature Selection

    PubMed Central

    Hassan, S. Sakira; Ruusuvuori, Pekka; Latonen, Leena; Huttunen, Heikki

    2015-01-01

    In this paper, we study the problem of feature selection in cancer-related machine learning tasks. In particular, we study the accuracy and stability of different feature selection approaches within simplistic machine learning pipelines. Earlier studies have shown that for certain cases, the accuracy of detection can easily reach 100% given enough training data. Here, however, we concentrate on simplifying the classification models with and seek for feature selection approaches that are reliable even with extremely small sample sizes. We show that as much as 50% of features can be discarded without compromising the prediction accuracy. Moreover, we study the model selection problem among the ℓ1 regularization path of logistic regression classifiers. To this aim, we compare a more traditional cross-validation approach with a recently proposed Bayesian error estimator. PMID:27081305

  8. Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study

    PubMed Central

    Jenkins, Mark A.; Hayashi, Shinichi; O’shea, Anne-Marie; Burgart, Lawrence J.; Smyrk, Tom C.; Shimizu, David; Waring, Paul M.; Ruszkiewicz, Andrew R.; Pollett, Aaron F.; Redston, Mark; Barker, Melissa A.; Baron, John A.; Casey, Graham R.; Dowty, James G.; Giles, Graham G.; Limburg, Paul; Newcomb, Polly; Young, Joanne P.; Walsh, Michael D.; Thibodeau, Stephen N.; Lindor, Noralane M.; Lemarchand, Loïc; Gallinger, Steven; Haile, Robert W.; Potter, John D.; Hopper, John L.; Jass, Jeremy R.

    2010-01-01

    Background & Aims The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H). Methods Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H. Results Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9 –14.1), proximal subsite (OR, 4.7; 95% CI, 3.1–7.3), mucinous histology (OR, 2.8; 95% CI, 1.7– 4.8), poor differentiation (OR, 1.9; 95% CI, 1.2–3.1), Crohn’s-like reaction (OR, 1.9; 95% CI, 1.2–2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3–2.9). MsPath score ≥ 1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H. Conclusions The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years. PMID:17631130

  9. Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database.

    PubMed

    Plasilova, Magdalena L; Hayse, Brandon; Killelea, Brigid K; Horowitz, Nina R; Chagpar, Anees B; Lannin, Donald R

    2016-08-01

    The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57-0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases. PMID:27583878

  10. CanDrA: cancer-specific driver missense mutation annotation with optimized features.

    PubMed

    Mao, Yong; Chen, Han; Liang, Han; Meric-Bernstam, Funda; Mills, Gordon B; Chen, Ken

    2013-01-01

    Driver mutations are somatic mutations that provide growth advantage to tumor cells, while passenger mutations are those not functionally related to oncogenesis. Distinguishing drivers from passengers is challenging because drivers occur much less frequently than passengers, they tend to have low prevalence, their functions are multifactorial and not intuitively obvious. Missense mutations are excellent candidates as drivers, as they occur more frequently and are potentially easier to identify than other types of mutations. Although several methods have been developed for predicting the functional impact of missense mutations, only a few have been specifically designed for identifying driver mutations. As more mutations are being discovered, more accurate predictive models can be developed using machine learning approaches that systematically characterize the commonality and peculiarity of missense mutations under the background of specific cancer types. Here, we present a cancer driver annotation (CanDrA) tool that predicts missense driver mutations based on a set of 95 structural and evolutionary features computed by over 10 functional prediction algorithms such as CHASM, SIFT, and MutationAssessor. Through feature optimization and supervised training, CanDrA outperforms existing tools in analyzing the glioblastoma multiforme and ovarian carcinoma data sets in The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia project. PMID:24205039

  11. Differentiating characteristic microstructural features of cancerous tissues using Mueller matrix microscope.

    PubMed

    Wang, Ye; He, Honghui; Chang, Jintao; Zeng, Nan; Liu, Shaoxiong; Li, Migao; Ma, Hui

    2015-12-01

    Polarized light imaging can provide rich microstructural information of samples, and has been applied to the detections of various abnormal tissues. In this paper, we report a polarized light microscope based on Mueller matrix imaging by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission optical microscope. The maximum errors for the absolute values of Mueller matrix elements are reduced to 0.01 after calibration. This Mueller matrix microscope has been used to examine human cervical and liver cancerous tissues with fibrosis. Images of the transformed Mueller matrix parameters provide quantitative assessment on the characteristic features of the pathological tissues. Contrast mechanism of the experimental results are backed up by Monte Carlo simulations based on the sphere-cylinder birefringence model, which reveal the relationship between the pathological features in the cancerous tissues at the cellular level and the polarization parameters. Both the experimental and simulated data indicate that the microscopic transformed Mueller matrix parameters can distinguish the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for liver cancer. With its simple structure, fast measurement and high precision, polarized light microscope based on Mueller matrix shows a good diagnosis application prospect. PMID:26280279

  12. Assessment of two mammographic density related features in predicting near-term breast cancer risk

    NASA Astrophysics Data System (ADS)

    Zheng, Bin; Sumkin, Jules H.; Zuley, Margarita L.; Wang, Xingwei; Klym, Amy H.; Gur, David

    2012-02-01

    In order to establish a personalized breast cancer screening program, it is important to develop risk models that have high discriminatory power in predicting the likelihood of a woman developing an imaging detectable breast cancer in near-term (e.g., <3 years after a negative examination in question). In epidemiology-based breast cancer risk models, mammographic density is considered the second highest breast cancer risk factor (second to woman's age). In this study we explored a new feature, namely bilateral mammographic density asymmetry, and investigated the feasibility of predicting near-term screening outcome. The database consisted of 343 negative examinations, of which 187 depicted cancers that were detected during the subsequent screening examination and 155 that remained negative. We computed the average pixel value of the segmented breast areas depicted on each cranio-caudal view of the initial negative examinations. We then computed the mean and difference mammographic density for paired bilateral images. Using woman's age, subjectively rated density (BIRADS), and computed mammographic density related features we compared classification performance in estimating the likelihood of detecting cancer during the subsequent examination using areas under the ROC curves (AUC). The AUCs were 0.63+/-0.03, 0.54+/-0.04, 0.57+/-0.03, 0.68+/-0.03 when using woman's age, BIRADS rating, computed mean density and difference in computed bilateral mammographic density, respectively. Performance increased to 0.62+/-0.03 and 0.72+/-0.03 when we fused mean and difference in density with woman's age. The results suggest that, in this study, bilateral mammographic tissue density is a significantly stronger (p<0.01) risk indicator than both woman's age and mean breast density.

  13. Immature truncated O-glycophenotype of cancer directly induces oncogenic features

    PubMed Central

    Radhakrishnan, Prakash; Dabelsteen, Sally; Madsen, Frey Brus; Francavilla, Chiara; Kopp, Katharina L.; Steentoft, Catharina; Vakhrushev, Sergey Y.; Olsen, Jesper V.; Hansen, Lars; Bennett, Eric P.; Woetmann, Anders; Yin, Guangliang; Chen, Longyun; Song, Haiyan; Bak, Mads; Hlady, Ryan A.; Peters, Staci L.; Opavsky, Rene; Thode, Christenze; Qvortrup, Klaus; Schjoldager, Katrine T.-B. G.; Clausen, Henrik; Hollingsworth, Michael A.; Wandall, Hans H.

    2014-01-01

    Aberrant expression of immature truncated O-glycans is a characteristic feature observed on virtually all epithelial cancer cells, and a very high frequency is observed in early epithelial premalignant lesions that precede the development of adenocarcinomas. Expression of the truncated O-glycan structures Tn and sialyl-Tn is strongly associated with poor prognosis and overall low survival. The genetic and biosynthetic mechanisms leading to accumulation of truncated O-glycans are not fully understood and include mutation or dysregulation of glycosyltransferases involved in elongation of O-glycans, as well as relocation of glycosyltransferases controlling initiation of O-glycosylation from Golgi to endoplasmic reticulum. Truncated O-glycans have been proposed to play functional roles for cancer-cell invasiveness, but our understanding of the biological functions of aberrant glycosylation in cancer is still highly limited. Here, we used exome sequencing of most glycosyltransferases in a large series of primary and metastatic pancreatic cancers to rule out somatic mutations as a cause of expression of truncated O-glycans. Instead, we found hypermethylation of core 1 β3-Gal-T-specific molecular chaperone, a key chaperone for O-glycan elongation, as the most prevalent cause. We next used gene editing to produce isogenic cell systems with and without homogenous truncated O-glycans that enabled, to our knowledge, the first polyomic and side-by-side evaluation of the cancer O-glycophenotype in an organotypic tissue model and in xenografts. The results strongly suggest that truncation of O-glycans directly induces oncogenic features of cell growth and invasion. The study provides support for targeting cancer-specific truncated O-glycans with immunotherapeutic measures. PMID:25118277

  14. Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

    PubMed Central

    Wrzeszczynski, Kazimierz O.; Varadan, Vinay; Byrnes, James; Lum, Elena; Kamalakaran, Sitharthan; Levine, Douglas A.; Dimitrova, Nevenka; Zhang, Michael Q.; Lucito, Robert

    2011-01-01

    The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates. PMID

  15. Mesenchymal traits are selected along with stem features in breast cancer cells grown as mammospheres

    PubMed Central

    Borgna, Silvia; Armellin, Michela; di Gennaro, Alessandra; Maestro, Roberta; Santarosa, Manuela

    2012-01-01

    Increasing evidence indicates that invasive properties of breast cancers rely on gain of mesenchymal and stem features, which has suggested that the dual targeting of these phenotypes may represent an appealing therapeutic strategy. It is known that the fraction of stem cells can be enriched by culturing breast cancer cells as mammospheres (MS), but whether these pro-stem conditions favor also the expansion of cells provided of mesenchymal features is still undefined. In the attempt to shed light on this issue, we compared the phenotypes of a panel of 10 breast cancer cell lines representative of distinct subtypes (luminal, HER2-positive, basal-like and claudin-low), grown in adherent conditions and as mammospheres. Under MS-proficient conditions, the increment in the fraction of stem-like cells was associated to upregulation of the mesenchymal marker Vimentin and downregulation of the epithelial markers expressed by luminal cells (E-cadherin, KRT18, KRT19, ESR1). Luminal cells tended also to upregulate the myoepithelial marker CD10. Taken together, our data indicate that MS-proficient conditions do favor mesenchymal/myoepithelial features, and indicate that the use of mammospheres as an in vitro tumor model may efficiently allow the exploitation of therapeutic approaches aimed at targeting aggressive tumors that have undergone epithelial-to-mesenchymal transition. PMID:23095640

  16. Prediction of near-term risk of developing breast cancer using computerized features from bilateral mammograms.

    PubMed

    Sun, Wenqing; Zheng, Bin; Lure, Fleming; Wu, Teresa; Zhang, Jianying; Wang, Benjamin Y; Saltzstein, Edward C; Qian, Wei

    2014-07-01

    Asymmetry of bilateral mammographic tissue density and patterns is a potentially strong indicator of having or developing breast abnormalities or early cancers. The purpose of this study is to design and test the global asymmetry features from bilateral mammograms to predict the near-term risk of women developing detectable high risk breast lesions or cancer in the next sequential screening mammography examination. The image dataset includes mammograms acquired from 90 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including image preprocessing, suspicious region segmentation, image feature extraction, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under curve (AUC) is 0.754±0.024 when applying the new computerized aided diagnosis (CAD) scheme to our testing dataset. The positive predictive value and the negative predictive value were 0.58 and 0.80, respectively. PMID:24725671

  17. Identifying ultrasound and clinical features of breast cancer molecular subtypes by ensemble decision.

    PubMed

    Zhang, Lei; Li, Jing; Xiao, Yun; Cui, Hao; Du, Guoqing; Wang, Ying; Li, Ziyao; Wu, Tong; Li, Xia; Tian, Jiawei

    2015-01-01

    Breast cancer is molecularly heterogeneous and categorized into four molecular subtypes: Luminal-A, Luminal-B, HER2-amplified and Triple-negative. In this study, we aimed to apply an ensemble decision approach to identify the ultrasound and clinical features related to the molecular subtypes. We collected ultrasound and clinical features from 1,000 breast cancer patients and performed immunohistochemistry on these samples. We used the ensemble decision approach to select unique features and to construct decision models. The decision model for Luminal-A subtype was constructed based on the presence of an echogenic halo and post-acoustic shadowing or indifference. The decision model for Luminal-B subtype was constructed based on the absence of an echogenic halo and vascularity. The decision model for HER2-amplified subtype was constructed based on the presence of post-acoustic enhancement, calcification, vascularity and advanced age. The model for Triple-negative subtype followed two rules. One was based on irregular shape, lobulate margin contour, the absence of calcification and hypovascularity, whereas the other was based on oval shape, hypovascularity and micro-lobulate margin contour. The accuracies of the models were 83.8%, 77.4%, 87.9% and 92.7%, respectively. We identified specific features of each molecular subtype and expanded the scope of ultrasound for making diagnoses using these decision models. PMID:26046791

  18. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features

    PubMed Central

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-01-01

    Abstract. Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the

  19. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features.

    PubMed

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-10-01

    Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance

  20. Selecting radiomic features from FDG-PET images for cancer treatment outcome prediction.

    PubMed

    Lian, Chunfeng; Ruan, Su; Denœux, Thierry; Jardin, Fabrice; Vera, Pierre

    2016-08-01

    As a vital task in cancer therapy, accurately predicting the treatment outcome is valuable for tailoring and adapting a treatment planning. To this end, multi-sources of information (radiomics, clinical characteristics, genomic expressions, etc) gathered before and during treatment are potentially profitable. In this paper, we propose such a prediction system primarily using radiomic features (e.g., texture features) extracted from FDG-PET images. The proposed system includes a feature selection method based on Dempster-Shafer theory, a powerful tool to deal with uncertain and imprecise information. It aims to improve the prediction accuracy, and reduce the imprecision and overlaps between different classes (treatment outcomes) in a selected feature subspace. Considering that training samples are often small-sized and imbalanced in our applications, a data balancing procedure and specified prior knowledge are taken into account to improve the reliability of the selected feature subsets. Finally, the Evidential K-NN (EK-NN) classifier is used with selected features to output prediction results. Our prediction system has been evaluated by synthetic and clinical datasets, consistently showing good performance. PMID:27236221

  1. Pathological features of localized prostate cancer in China: a contemporary analysis of radical prostatectomy specimens.

    PubMed

    Zhu, Yao; Yang, Xiao-Qun; Han, Cheng-Tao; Dai, Bo; Zhang, Hai-Liang; Shi, Guo-Hai; Wang, Chao-Fu; Ye, Ding-Wei

    2015-01-01

    There has been a rapid increase in the incidence of prostate cancer in China, especially in areas with boosted economic development. In this study, we analyzed the pathological features of a contemporary series of radical prostatectomy cases. A total of 230 consecutive, whole-mounted radical prostatectomy specimens collected from 2012 to 2014 were reviewed. The median age of the patients was 68 years, and 64.3% of patients presented with prostate specific antigen alone. Pathological examination indicated that a high proportion (77.4%) of patients had intermediate- or high-risk disease according to the Cancer of the Prostate Risk Assessment Post-Surgical score. After surgery, only 28 patients met the criteria for active surveillance (organ-confined Gleason ≥6 disease). The Prostate Cancer Research International Active Surveillance criteria achieved a sensitivity of 57.1% and a specificity of 98.0% for identifying candidates. The probability of Gleason score upgrading was 24.8% in the entire group and 59.0% in biopsy-confirmed Gleason ≥6 disease. The predominant tumor was located in the transition zone in 14.8% of cases, while only three patients (1.3%) had a predominant tumor located in the anterior region. Patients with transition zone-predominant tumor were likely to have been referred with urinary symptoms and high prostate specific antigen levels. The results of this study highlight the contemporary pathological features of localized prostate cancer in urban China. There was an increased trend towards asymptomatic cases, though most patients had intermediate- or high-risk disease and were suitable for definitive treatment. The low prevalence of dominant cancer in the anterior region may reflect race-based pathological differences. PMID:25799190

  2. pT0 Prostate Cancer: Predictive Clinicopathologic Features in an American Population

    PubMed Central

    Bream, Matthew J.; Dahmoush, Laila; Brown, James A.

    2013-01-01

    Introduction The pT0 stage of prostate cancer describes the radical prostatectomy (RP) specimen where no cancer can be identified. Given known racial and geographic differences in prostate cancer incidence and survival, we reviewed our experience with pT0 disease to determine applicability of these predictive features in an American population. Materials and Methods A retrospective chart review was conducted for all RPs at one state tertiary care institution during a 20-year period (1991-2011). Clinicopathologic features of pT0 patients were collected and their relevant pathologic material re-reviewed. Results Of a total of 1,635 RPs performed, 4 (0.2%) not receiving neoadjuvant therapy or other prior prostate surgeries were stage pT0. Biopsies from 3 of 4 patients were re-evaluated and confirmed a small focus, <1% of tissue, of Gleason score 3+3 adenocarcinoma; a fourth was not available for re-review. Our re-review of the RP slides identified small foci of cancer in two of the four, thus yielding a final true pT0 incidence of 0.1%. Preoperative prostate specific antigen ranged from 4.4 to 7.4 ng/ml, clinical stages were all T1c, and there was no evidence of recurrence at 3 months to 10 years of follow-up. Conclusions Stage pT0 prostate cancer is very uncommon, occurring with an incidence of 0.1%, and in our experience occurs only in clinical T1c patients with pre-biopsy prostate specific antigen < 7.5 ng/ml, with Gleason score 3 + 3 adenocarcinoma comprising < 1%, 1 mm of a single core biopsy, a stricter threshold than that seen in non-American populations. PMID:24917750

  3. Clinical features and overall survival among elderly cancer patients in a tertiary cancer center

    PubMed Central

    Antunes, Yuri Philippe Pimentel Vieira; Bugano, Diogo Diniz Gomes; del Giglio, Auro; Kaliks, Rafael Aliosha; Karnakis, Theodora; Pontes, Lucíola de Barros

    2015-01-01

    ABSTRACT Objective To evaluate the epidemiological profile and overall survival of a large population of elderly individuals diagnosed with solid tumors in a tertiary hospital. Methods This retrospective study included patients aged >65 years, diagnosed with solid tumors between January 2007 and December 2011, at Hospital Israelita Albert Einstein, São Paulo, Brazil. The medical records were reviewed to obtain information about clinical variables and overall survival. Results A total of 806 patients were identified, and 58.4% were male. Mean age was 74 years (65 to 99 years). The most common types were prostate (22%), colorectal (21%), breast (19%), and lung cancer (13%), followed by bladder (8%), pancreas (6%), and other types (11%). The majority of patients were diagnosed at early stage disease. After a median follow-up of 27 months (15 to 45 months), 29% of the patients (234/806) died, predominantly in the group older than 70 years. For the entire cohort, the median 2-year survival rate was 71%. Median overall survival was not reached within the study period. In a multivariate analysis, age (HR: 1.35; 95%CI: 1.25-1.45; p<0.001) and disease stage (HR: 1.93; 95%CI: 1.75-2.14; p<0.001) were independent negative predictors of poor survival. Conclusion The most prevalent tumors were prostate, colorectal, breast, and lung cancer, with the larger proportion diagnosed at initial stages, reflecting the great number of patients alive at last follow-up. PMID:26676269

  4. Automated detection of prostate cancer using wavelet transform features of ultrasound RF time series

    NASA Astrophysics Data System (ADS)

    Aboofazeli, Mohammad; Abolmaesumi, Purang; Moradi, Mehdi; Sauerbrei, Eric; Siemens, Robert; Boag, Alexander; Mousavi, Parvin

    2009-02-01

    The aim of this research was to investigate the performance of wavelet transform based features of ultrasound radiofrequency (RF) time series for automated detection of prostate cancer tumors in transrectal ultrasound images. Sequential frames of RF echo signals from 35 extracted prostate specimens were recorded in parallel planes, while the ultrasound probe and the tissue were fixed in position in each imaging plane. The sequence of RF echo signal samples corresponding to a particular spot in tissue imaging plane constitutes one RF time series. Each region of interest (ROI) of ultrasound image was represented by three groups of features of its time series, namely, wavelet, spectral and fractal features. Wavelet transform approximation and detail sequences of each ROI were averaged and used as wavelet features. The average value of the normalized spectrum in four quarters of the frequency range along with the intercept and slope of a regression line fitted to the values of the spectrum versus normalized frequency plot formed six spectral features. Fractal dimension (FD) of the RF time series were computed based on the Higuchi's approach. A support vector machine (SVM) classifier was used to classify the ROIs. The results indicate that combining wavelet coefficient based features with previously proposed spectral and fractal features of RF time series data would increase the area under ROC curve from 93.1% to 95.0%, respectively. Furthermore, the accuracy, sensitivity, and specificity increases to 91.7%, 86.6%, and 94.7%, from 85.7%, 85.2%, and 86.1%, respectively, using only spectral and fractal features.

  5. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer.

    PubMed

    Lesurf, Robert; Aure, Miriam Ragle; Mørk, Hanne Håberg; Vitelli, Valeria; Lundgren, Steinar; Børresen-Dale, Anne-Lise; Kristensen, Vessela; Wärnberg, Fredrik; Hallett, Michael; Sørlie, Therese

    2016-07-26

    Breast cancer consists of at least five main molecular "intrinsic" subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression. PMID:27396337

  6. Continuous wavelet transform-based feature selection applied to near-infrared spectral diagnosis of cancer.

    PubMed

    Chen, Hui; Lin, Zan; Mo, Lin; Wu, Hegang; Wu, Tong; Tan, Chao

    2015-12-01

    Spectrum is inherently local in nature since it can be thought of as a signal being composed of various frequency components. Wavelet transform (WT) is a powerful tool that partitions a signal into components with different frequency. The property of multi-resolution enables WT a very effective and natural tool for analyzing spectrum-like signal. In this study, a continuous wavelet transform (CWT)-based variable selection procedure was proposed to search for a set of informative wavelet coefficients for constructing a near-infrared (NIR) spectral diagnosis model of cancer. The CWT provided a fine multi-resolution feature space for selecting best predictors. A measure of discriminating power (DP) was defined to evaluate the coefficients. Partial least squares-discriminant analysis (PLS-DA) was used as the classification algorithm. A NIR spectral dataset associated to cancer diagnosis was used for experiment. The optimal results obtained correspond to the wavelet of db2. It revealed that on condition of having better performance on the training set, the optimal PLS-DA model using only 40 wavelet coefficients in 10 scales achieved the same performance as the one using all the variables in the original space on the test set: an overall accuracy of 93.8%, sensitivity of 92.5% and specificity of 96.3%. It confirms that the CWT-based feature selection coupled with PLS-DA is feasible and effective for constructing models of diagnostic cancer by NIR spectroscopy. PMID:26143320

  7. A new breast cancer risk analysis approach using features extracted from multiple sub-regions on bilateral mammograms

    NASA Astrophysics Data System (ADS)

    Sun, Wenqing; Tseng, Tzu-Liang B.; Zheng, Bin; Zhang, Jianying; Qian, Wei

    2015-03-01

    A novel breast cancer risk analysis approach is proposed for enhancing performance of computerized breast cancer risk analysis using bilateral mammograms. Based on the intensity of breast area, five different sub-regions were acquired from one mammogram, and bilateral features were extracted from every sub-region. Our dataset includes 180 bilateral mammograms from 180 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including sub-region segmentation, bilateral feature extraction, feature selection, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under the curve (AUC) is 0.763 ± 0.021 when applying the multiple sub-region features to our testing dataset. The positive predictive value and the negative predictive value were 0.60 and 0.73, respectively. The study demonstrates that (1) features extracted from multiple sub-regions can improve the performance of our scheme compared to using features from whole breast area only; (2) a classifier using asymmetry bilateral features can effectively predict breast cancer risk; (3) incorporating texture and morphological features with density features can boost the classification accuracy.

  8. CXCR7 mediates TGFβ1-promoted EMT and tumor-initiating features in lung cancer.

    PubMed

    Wu, Y-C; Tang, S-J; Sun, G-H; Sun, K-H

    2016-04-21

    In the tumor microenvironment, chemokine system has a critical role in tumorigenesis and metastasis. The acquisition of stem-like properties by cancer cells is involved in metastasis and drug resistance, which are pivotal problems that result in poor outcomes in patients with lung cancer. Patients with advanced lung cancer present high plasma levels of transforming growth factor-β1 (TGFβ1), which correlate with poor prognostic features. Therefore, TGFβ1 may be important in the tumor microenvironment, where chemokines are widely expressed. However, the role of chemokines in TGFβ1-induced tumor progression still remains unclear. In our study, TGFβ1 upregulated CXC chemokine receptor expression, migration, invasion, epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation in lung adenocarcinoma. We found that CXCR7 was the most upregulated chemokine receptor induced by TGFβ1. CXCR7 knockdown resulted in reduction of migration, invasion and EMT induced by TGFβ1, whereas CXCR4 knockdown did not reverse TGFβ1-promoted EMT. CXCR7 silencing significantly decreased cancer sphere-forming capacity, stem-like properties, chemoresistance and TGFβ1-induced CSC tumor initiation in vivo. In clinical samples, high TGFβ1 and CXCR7 expression was significantly associated with the late stages of lung adenocarcinoma. Moreover, TGFβ1 and CXCR7 coexpression was positively correlated with the CSC marker, CD44, which is associated with lymph node metastasis. Besides, patients with high expression of both CXCR7 and TGFβ1 presented a significantly worse survival rate. These results suggest that the TGFβ1-CXCR7 axis may be a prognostic marker and may provide novel targets for combinational therapies to be used in the treatment of advanced lung cancer in the future. PMID:26212008

  9. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer: Clinicoradiologic features and diagnostic implications.

    PubMed

    Hong, Su Jin; Kim, Tae Jung; Lee, Jae-Ho; Park, Jeong-Soo

    2016-06-01

    To describe the features and clinical implications of computed tomography (CT), positron emission tomography (PET), and percutaneous needle aspiration biopsy (PCNB) in pulmonary nontuberculous mycobacterial (NTM) disease manifesting as a solitary nodule, mass, or mass-like consolidation mimicking malignancy.Among a cohort of 388 patients with NTM pulmonary disease, 14 patients with clinically and radiologically suspected lung cancer were included in our study. Two chest radiologists evaluated CT features, including lesion type (nodule, mass, or mass-like consolidation), morphologic features (margin, degree of enhancement, calcification), and presence of accompanying findings suggestive of NTM pulmonary disease (bronchiectasis with clustered centrilobular nodules or upper-lobe cavitary lesions) by consensus. Diagnostic procedures for microbiologic diagnosis of NTM disease and clinical outcome were reviewed.Incidence of NTM pulmonary disease presenting as solitary nodule/mass (n = 8) or mass-like consolidation (n = 6) was 3.6% (14 of 388). Most lesions were detected incidentally during routine health check-up or evaluation of other disease (11 of 14, 79%). Lesions typically showed poor contrast-enhancement (9 of 12) and internal calcification (6 of 14). No lesions had CT features suggestive of NTM pulmonary disease. All 4 lesions for which PET/CT imaging was performed showed strong fluorodeoxyglucose uptake simulating malignant lesions (mean, 4.9; range, 3.6-7.8). PCNB revealed mycobacterial histology in 6 of 11 specimens and positive culture results were obtained for 7 of 7 specimens.NTM pulmonary disease may present as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. CT features and PCNB are important to diagnose NTM disease mimicking lung cancer to avoid unnecessary surgery. PMID:27367996

  10. Hypoxia-inducible factor 1–mediated characteristic features of cancer cells for tumor radioresistance

    PubMed Central

    Harada, Hiroshi

    2016-01-01

    Tumor hypoxia has been attracting increasing attention in the fields of radiation biology and oncology since Thomlinson and Gray detected hypoxic cells in malignant solid tumors and showed that they exert a negative impact on the outcome of radiation therapy. This unfavorable influence has, at least partly, been attributed to cancer cells acquiring a radioresistant phenotype through the activation of the transcription factor, hypoxia-inducible factor 1 (HIF-1). On the other hand, accumulating evidence has recently revealed that, even though HIF-1 is recognized as an important regulator of cellular adaptive responses to hypoxia, it may not become active and induce tumor radioresistance under hypoxic conditions only. The mechanisms by which HIF-1 is activated in cancer cells not only under hypoxic conditions, but also under normoxic conditions, through cancer-specific genetic alterations and the resultant imbalance in intermediate metabolites have been summarized herein. The relevance of the HIF-1–mediated characteristic features of cancer cells, such as the production of antioxidants through reprogramming of the glucose metabolic pathway and cell cycle regulation, for tumor radioresistance has also been reviewed. PMID:26983985

  11. Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer.

    PubMed

    Janecka, Anna; Kołodziej-Rzepa, Marta; Biesaga, Beata

    2016-01-01

    Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment. PMID:27381597

  12. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients*

    PubMed Central

    Huang, Yan-qin; Yuan, Ying; Ge, Wei-ting; Hu, Han-guang; Zhang, Su-zhan; Zheng, Shu

    2010-01-01

    Objective: The purpose of this study was to determine the unique and universal features of microsatellite instability-high (MSI-H) colorectal cancer (CRC) and MSI-H gastric cancer (GC) in the Chinese population. Methods: A new panel of mononucleotide MSI markers, BAT25, BAT26, NR21, NR24, and MONO-27, was used to define MSI status in 303 CRC and 288 GC subjects. Clinicopathological features of both types of MSI-H tumors were analyzed. Methylation analysis in the hMLH1 promoter region by methylation specific polymerase chain reaction (PCR) and mutation detection of hMSH2/hMLH1 genes by denaturing high-performance liquid chromatography (DHPLC) were carried out simultaneously. Results: MSI-H CRCs and MSI-H GCs account for 11.9% and 8.0% of unselected sporadic CRCs and GCs, respectively. MSI-H CRCs are strongly characterized by early onset, right-side location, low differentiation, mucinous tumor, less infiltration, less lymphatic metastasis, and more often familial tumor. MSI-H GCs only showed site preference for the antrum and less lymphatic metastasis. Genetic and epigenetic analyses were positive in 6/36 MSI-H CRCs and 0/23 MSI-H GCs with pathological mutation in major mismatch repair genes, and in 7/36 MSI-H CRCs and 18/23 MSI-H GCs with methylated hMLH1 promoter (P<0.01), respectively. Conclusions: Although there are many differences in the genetic basis and clinicopathological features between MSI-H CRC and MSI-H GC, when compared with their microsatellite stable (MSS) counterparts, site preference and lymphatic metastasis are features common to both types of MSI-H tumors. PMID:20803768

  13. A Comparative Analysis of Swarm Intelligence Techniques for Feature Selection in Cancer Classification

    PubMed Central

    Gunavathi, Chellamuthu; Premalatha, Kandasamy

    2014-01-01

    Feature selection in cancer classification is a central area of research in the field of bioinformatics and used to select the informative genes from thousands of genes of the microarray. The genes are ranked based on T-statistics, signal-to-noise ratio (SNR), and F-test values. The swarm intelligence (SI) technique finds the informative genes from the top-m ranked genes. These selected genes are used for classification. In this paper the shuffled frog leaping with Lévy flight (SFLLF) is proposed for feature selection. In SFLLF, the Lévy flight is included to avoid premature convergence of shuffled frog leaping (SFL) algorithm. The SI techniques such as particle swarm optimization (PSO), cuckoo search (CS), SFL, and SFLLF are used for feature selection which identifies informative genes for classification. The k-nearest neighbour (k-NN) technique is used to classify the samples. The proposed work is applied on 10 different benchmark datasets and examined with SI techniques. The experimental results show that the results obtained from k-NN classifier through SFLLF feature selection method outperform PSO, CS, and SFL. PMID:25157377

  14. A comparative analysis of swarm intelligence techniques for feature selection in cancer classification.

    PubMed

    Gunavathi, Chellamuthu; Premalatha, Kandasamy

    2014-01-01

    Feature selection in cancer classification is a central area of research in the field of bioinformatics and used to select the informative genes from thousands of genes of the microarray. The genes are ranked based on T-statistics, signal-to-noise ratio (SNR), and F-test values. The swarm intelligence (SI) technique finds the informative genes from the top-m ranked genes. These selected genes are used for classification. In this paper the shuffled frog leaping with Lévy flight (SFLLF) is proposed for feature selection. In SFLLF, the Lévy flight is included to avoid premature convergence of shuffled frog leaping (SFL) algorithm. The SI techniques such as particle swarm optimization (PSO), cuckoo search (CS), SFL, and SFLLF are used for feature selection which identifies informative genes for classification. The k-nearest neighbour (k-NN) technique is used to classify the samples. The proposed work is applied on 10 different benchmark datasets and examined with SI techniques. The experimental results show that the results obtained from k-NN classifier through SFLLF feature selection method outperform PSO, CS, and SFL. PMID:25157377

  15. Molecular Features and Survival Outcomes of the Intrinsic Subtypes Within HER2-Positive Breast Cancer

    PubMed Central

    Carey, Lisa A.; Adamo, Barbara; Vidal, Maria; Tabernero, Josep; Cortés, Javier; Parker, Joel S.; Perou, Charles M.; Baselga, José

    2014-01-01

    Background The clinical impact of the biological heterogeneity within HER2-positive (HER2+) breast cancer is not fully understood. Here, we evaluated the molecular features and survival outcomes of the intrinsic subtypes within HER2+ breast cancer. Methods We interrogated The Cancer Genome Atlas (n = 495) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets (n = 1730) of primary breast cancers for molecular data derived from DNA, RNA and protein, and determined intrinsic subtype. Clinical HER2 status was defined according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines or DNA copy-number aberration by single nucleotide polymorphism arrays. Cox models tested the prognostic significance of each variable in patients not treated with trastuzumab (n = 1711). Results Compared with clinically HER2 (cHER2)-negative breast cancer, cHER2+ breast cancer had a higher frequency of the HER2-enriched (HER2E) subtype (47.0% vs 7.1%) and a lower frequency of Luminal A (10.7% vs 39.0%) and Basal-like (14.1% vs 23.4%) subtypes. The likelihood of cHER2-positivity in HER2E, Luminal B, Basal-like and Luminal A subtypes was 64.6%, 20.0%, 14.4% and 7.3%, respectively. Within each subtype, only 0.3% to 3.9% of genes were found differentially expressed between cHER2+ and cHER2-negative tumors. Within cHER2+ tumors, HER2 gene and protein expression was statistically significantly higher in the HER2E and Basal-like subtypes than either luminal subtype. Neither cHER2 status nor the new 10-subtype copy number-based classification system (IntClust) added independent prognostic value to intrinsic subtype. Conclusions When the intrinsic subtypes are taken into account, cHER2-positivity does not translate into large changes in the expression of downstream signaling pathways, nor does it affect patient survival in the absence of HER2 targeting. PMID:25139534

  16. The growth regulatory fibroblast IK channel is the prominent electrophysiological feature of rat prostatic cancer cells.

    PubMed

    Rane, S G

    2000-03-16

    Physiological effectors for mitogenic cell growth control remain to be determined for mammalian tumor cells, particularly those derived from prostatic tissue. One such effector for mitogenic Ras/MAPK signaling in fibroblasts is an intermediate-conductance, calcium-activated potassium channel (FIK). In this study patch-clamp electrophysiology was used to show that both AT2.1 and MatLyLu rat prostate cancer cell lines express high levels of a current identified as FIK, based on the following criteria: activation by elevation of intracellular calcium, voltage independence, potassium selectivity, and block by charybdotoxin (ChTX) and the Stichodactyla helianthus potassium channel neurotoxin (StK). FIK current densities in AT2.1 and MatLyLu cells were comparable to the high levels seen in fibroblasts transfected with oncogenic Ras or Raf, suggesting hyperactivity of the Ras/MAPK pathway in prostatic cancer cells. Voltage-gated sodium current was present in most MatLyLu cells but absent from AT2.1 cells, and all AT2.1 cells had voltage-gated potassium currents. Thus, FIK is the main electrophysiological feature of rat prostatic cancer cells as it is for mitogenically active fibroblasts, suggesting it may play a similar growth regulatory role in both. PMID:10708575

  17. Multiple Adaptive Neuro-Fuzzy Inference System with Automatic Features Extraction Algorithm for Cervical Cancer Recognition

    PubMed Central

    Subhi Al-batah, Mohammad; Mat Isa, Nor Ashidi; Klaib, Mohammad Fadel; Al-Betar, Mohammed Azmi

    2014-01-01

    To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC)) to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE) algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS) is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy. PMID:24707316

  18. Multiple adaptive neuro-fuzzy inference system with automatic features extraction algorithm for cervical cancer recognition.

    PubMed

    Al-batah, Mohammad Subhi; Isa, Nor Ashidi Mat; Klaib, Mohammad Fadel; Al-Betar, Mohammed Azmi

    2014-01-01

    To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC)) to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE) algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS) is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy. PMID:24707316

  19. STAT3 Expression, Molecular Features, Inflammation Patterns and Prognosis in a Database of 724 Colorectal Cancers

    PubMed Central

    Morikawa, Teppei; Baba, Yoshifumi; Yamauchi, Mai; Kuchiba, Aya; Nosho, Katsuhiko; Shima, Kaori; Tanaka, Noriko; Huttenhower, Curtis; Frank, David A.; Fuchs, Charles S.; Ogino, Shuji

    2010-01-01

    Purpose STAT3 (signal transducer and activator of transcription 3) is a transcription factor that is constitutively activated in some cancers. STAT3 appears to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation and suppression of anti-tumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular or prognostic features of STAT3-activated colorectal cancer remain uncertain. Experimental Design Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical, pathologic and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q loss of heterozygosity, TP53 (p53), CTNNB1 (β-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations. Results Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer-specific mortality [log-rank p=0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative) 1.85, 95% confidence interval (CI) 1.30–2.63, Ptrend =0.0005; multivariate HR, 1.61, 95% CI 1.11–2.34, Ptrend =0.015). p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate odds ratio 3.23; 95% CI, 1.89–5.53; p<0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation. Conclusions STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. PMID:21310826

  20. Patient feature based dosimetric Pareto front prediction in esophageal cancer radiotherapy

    SciTech Connect

    Wang, Jiazhou; Zhao, Kuaike; Peng, Jiayuan; Xie, Jiang; Chen, Junchao; Zhang, Zhen; Hu, Weigang; Jin, Xiance; Studenski, Matthew

    2015-02-15

    Purpose: To investigate the feasibility of the dosimetric Pareto front (PF) prediction based on patient’s anatomic and dosimetric parameters for esophageal cancer patients. Methods: Eighty esophagus patients in the authors’ institution were enrolled in this study. A total of 2928 intensity-modulated radiotherapy plans were obtained and used to generate PF for each patient. On average, each patient had 36.6 plans. The anatomic and dosimetric features were extracted from these plans. The mean lung dose (MLD), mean heart dose (MHD), spinal cord max dose, and PTV homogeneity index were recorded for each plan. Principal component analysis was used to extract overlap volume histogram (OVH) features between PTV and other organs at risk. The full dataset was separated into two parts; a training dataset and a validation dataset. The prediction outcomes were the MHD and MLD. The spearman’s rank correlation coefficient was used to evaluate the correlation between the anatomical features and dosimetric features. The stepwise multiple regression method was used to fit the PF. The cross validation method was used to evaluate the model. Results: With 1000 repetitions, the mean prediction error of the MHD was 469 cGy. The most correlated factor was the first principal components of the OVH between heart and PTV and the overlap between heart and PTV in Z-axis. The mean prediction error of the MLD was 284 cGy. The most correlated factors were the first principal components of the OVH between heart and PTV and the overlap between lung and PTV in Z-axis. Conclusions: It is feasible to use patients’ anatomic and dosimetric features to generate a predicted Pareto front. Additional samples and further studies are required improve the prediction model.

  1. Focal Lymphocytic Thyroiditis Nodules Share the Features of Papillary Thyroid Cancer on Ultrasound

    PubMed Central

    Hwang, Sena; Shin, Dong Yeob; Kim, Eun Kyung; Yang, Woo Ick; Byun, Jung Woo; Lee, Su Jin; Kim, Gyuri; Im, Soo Jung

    2015-01-01

    Purpose It is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results. Materials and Methods We evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated. Results Of 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC. Conclusion Suspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US. PMID:26256977

  2. Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells

    PubMed Central

    Jacob-Hirsch, Jasmine; Amariglio, Ninette; Vlachos, George D.; Loutradis, Dimitrios; Anagnou, Nicholas P.

    2015-01-01

    Studies on individual types of gynecological cancers (GCs), utilizing novel expression technologies, have revealed specific pathogenetic patterns and gene markers for cervical (CC), endometrial (EC) and vulvar cancer (VC). Although the clinical phenotypes of the three types of gynecological cancers are discrete, the fact they originate from a common embryological origin, has led to the hypothesis that they might share common features reflecting regression to early embryogenesis. To address this question, we performed a comprehensive comparative analysis of their profiles. Our data identified both common features (pathways and networks) and novel distinct modules controlling the same deregulated biological processes in all three types. Specifically, four novel transcriptional modules were discovered regulating cell cycle and apoptosis. Integration and comparison of our data with other databases, led to the identification of common features among cancer types, embryonic stem (ES) cells and the newly discovered cell population of squamocolumnar (SC) junction of the cervix, considered to host the early cancer events. Conclusively, these data lead us to propose the presence of common features among gynecological cancers, other types of cancers, ES cells and the pre-malignant SC junction cells, where the novel E2F/NFY and MAX/CEBP modules play an important role for the pathogenesis of gynecological carcinomas. PMID:26559525

  3. Identifying Cancer Biomarkers From Microarray Data Using Feature Selection and Semisupervised Learning

    PubMed Central

    Maulik, Ujjwal

    2014-01-01

    Microarrays have now gone from obscurity to being almost ubiquitous in biological research. At the same time, the statistical methodology for microarray analysis has progressed from simple visual assessments of results to novel algorithms for analyzing changes in expression profiles. In a micro-RNA (miRNA) or gene-expression profiling experiment, the expression levels of thousands of genes/miRNAs are simultaneously monitored to study the effects of certain treatments, diseases, and developmental stages on their expressions. Microarray-based gene expression profiling can be used to identify genes, whose expressions are changed in response to pathogens or other organisms by comparing gene expression in infected to that in uninfected cells or tissues. Recent studies have revealed that patterns of altered microarray expression profiles in cancer can serve as molecular biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and prediction of therapeutic responses. Microarray data sets containing expression profiles of a number of miRNAs or genes are used to identify biomarkers, which have dysregulation in normal and malignant tissues. However, small sample size remains a bottleneck to design successful classification methods. On the other hand, adequate number of microarray data that do not have clinical knowledge can be employed as additional source of information. In this paper, a combination of kernelized fuzzy rough set (KFRS) and semisupervised support vector machine (S3VM) is proposed for predicting cancer biomarkers from one miRNA and three gene expression data sets. Biomarkers are discovered employing three feature selection methods, including KFRS. The effectiveness of the proposed KFRS and S3VM combination on the microarray data sets is demonstrated, and the cancer biomarkers identified from miRNA data are reported. Furthermore, biological significance tests are conducted for miRNA cancer biomarkers. PMID:27170887

  4. Total sacrectomy for recurrent rectal cancer – A case report featuring technical details and potential pitfalls

    PubMed Central

    Melich, George; Weber, Michael; Stein, Barry; Minutolo, Vincenzo; Arena, Manuel; Arena, Goffredo O.

    2014-01-01

    INTRODUCTION Total sacrectomy for recurrent rectal cancer is controversial. However, recent publications suggest encouraging outcomes with high sacral resections. We present the first case report describing technical aspects, potential pitfalls and treatment of complications associated with total sacrectomy performed as a treatment of recurrent rectal cancer. PRESENTATION OF CASE A fifty-three year old man was previously treated at another institution with a low anterior resection (LAR) followed by chemo-radiation and left liver tri-segmentectomy for metastatic rectal cancer. Three years following the LAR, the patient developed a recurrence at the site of colorectal anastomosis, manifesting clinically as a contained perforation, forming a recto-cutaneous fistula through the sacrum. Abdomino-perineal resection (APR) and complete sacrectomy were performed using an anterior–posterior approach with posterior spinal instrumented fusion and pelvic fixation using iliac crest bone graft. Left sided vertical rectus abdominis muscle flap and right sided gracilis muscle flap were used for hardware coverage and to fill the pelvic defect. One year after the resection, the patient remains disease free and has regained the ability to move his lower limbs against gravity. DISCUSSION The case described in this report features some formidable challenges due to the previous surgeries for metastatic disease, and the presence of a recto-sacral cutaneous fistula. An approach with careful surgical planning including considerationof peri-operative embolization is vital for a successful outcome of the operation. A high degree of suspicion for pseudo-aneurysms formation due infection or dislodgement of metallic coils is necessary in the postoperative phase. CONCLUSION Total sacrectomy for the treatment of recurrent rectal cancer with acceptable short-term outcomes is possible.A detailed explanation to the patient of the possible complications and expectations including the concept of a

  5. Breast Cancer With Brain Metastases: Clinicopathologic Features, Survival, and Paired Biomarker Analysis

    PubMed Central

    Shen, Qi; Hess, Kenneth R.; Suki, Dima; Aldape, Kenneth D.; Sawaya, Raymond; Ibrahim, Nuhad K.

    2015-01-01

    Background. The aim of this study was to describe clinicopathologic features of patients with breast cancer brain metastasis (BCBM); to evaluate survival after diagnosis of BCBM; and to compare estrogen receptor (ER), progesterone receptor (PR), and HER2 expression in the paired primary and brain tumors. Materials and Methods. We identified 140 consecutive patients who underwent craniotomy for BCBM (either for diagnostic purpose or with therapeutic intent) at the University of Texas MD Anderson Cancer Center between 2002 and 2009. Results. Most patients had invasive ductal histology (91%), grade 3 tumors (67%), and positive axillary lymph node (64%). Of the tumors, 56% were ER-negative, 62% were PR-negative, 44% were HER2-positive, and 28% were triple negative (TN). Brain metastasis (BM) was solitary in 51% of patients. Median interval from breast cancer diagnosis to BM was 46 months; median survival after BM was 14.1 months. In the univariate analysis, younger age, solitary brain metastasis, and ER or PR positivity in the breast tumors were associated with longer survival. There was a statistical trend toward increased survival in HER2-positive patients compared with HER2-negative patients (18 vs. 11 months). In the multivariate analysis, predictors for longer survival included younger age, solitary brain lesion, and HER2 positivity in the breast cancer. Biomarkers were evaluated in paired primary and brain tumors in 35 patients for ER status, 34 for PR status, and 36 for HER2 status. Discordant rates were 28% for ER, 20% for PR, and 3% for HER2. Conclusion. Compared with unselected breast cancer patients at the same institution, patients with breast cancer who had brain metastases had a higher proportion of hormone receptor-negative, HER2-positive, and TN tumors. Younger age, solitary brain lesion, and HER2 expression were independent predictors of better survival in patients with BCBM. HER2 status was highly concordant between the paired primary and brain tumors

  6. Radiogenomic analysis of breast cancer: dynamic contrast enhanced - magnetic resonance imaging based features are associated with molecular subtypes

    NASA Astrophysics Data System (ADS)

    Wang, Shijian; Fan, Ming; Zhang, Juan; Zheng, Bin; Wang, Xiaojia; Li, Lihua

    2016-03-01

    Breast cancer is one of the most common malignant tumor with upgrading incidence in females. The key to decrease the mortality is early diagnosis and reasonable treatment. Molecular classification could provide better insights into patient-directed therapy and prognosis prediction of breast cancer. It is known that different molecular subtypes have different characteristics in magnetic resonance imaging (MRI) examination. Therefore, we assumed that imaging features can reflect molecular information in breast cancer. In this study, we investigated associations between dynamic contrasts enhanced MRI (DCE-MRI) features and molecular subtypes in breast cancer. Sixty patients with breast cancer were enrolled and the MR images were pre-processed for noise reduction, registration and segmentation. Sixty-five dimensional imaging features including statistical characteristics, morphology, texture and dynamic enhancement in breast lesion and background regions were semiautomatically extracted. The associations between imaging features and molecular subtypes were assessed by using statistical analyses, including univariate logistic regression and multivariate logistic regression. The results of multivariate regression showed that imaging features are significantly associated with molecular subtypes of Luminal A (p=0.00473), HER2-enriched (p=0.00277) and Basal like (p=0.0117), respectively. The results indicated that three molecular subtypes are correlated with DCE-MRI features in breast cancer. Specifically, patients with a higher level of compactness or lower level of skewness in breast lesion are more likely to be Luminal A subtype. Besides, the higher value of the dynamic enhancement at T1 time in normal side reflect higher possibility of HER2-enriched subtype in breast cancer.

  7. Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features

    PubMed Central

    Koivunen, Peppi; Koivunen, Jussi P.

    2014-01-01

    Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can mediate adaptive resistance to oncogene ablative therapy. When pharmacological ablation of ALK oncogene was accompanied with PI3K inhibitor or salinomycin therapy, cancer stem-like cell features were reversed which was accompanied with decreased colony formation. Furthermore, co-targeting was able to block the formation of acquired resistance in H3122 line. The results suggest that cells with cancer stem-like cell features can mediate adaptive resistance to targeted therapies. Since these cells follow the stochastic model, concurrent therapy with an oncogene ablating agent and a stem-like cell-targeting drug is needed for maximal therapeutic efficiency. PMID:25238228

  8. SBRT for prostate cancer: Challenges and features from a physicist prospective.

    PubMed

    Mancosu, Pietro; Clemente, Stefania; Landoni, Valeria; Ruggieri, Ruggero; Alongi, Filippo; Scorsetti, Marta; Stasi, Michele

    2016-03-01

    Emerging data are showing the safety and the efficacy of Stereotactic Body Radiation Therapy (SBRT) in prostate cancer management. In this context, the medical physicists are regularly involved to review the appropriateness of the adopted technology and to proactively study new solutions. From the physics point of view there are two major challenges in prostate SBRT: (1) mitigation of geometrical uncertainty and (2) generation of highly conformal dose distributions that maximally spare the OARs. Geometrical uncertainties have to be limited as much as possible in order to avoid the use of large PTV margins. Furthermore, advanced planning and delivery techniques are needed to generate maximally conformal dose distributions. In this non-systematic review the technology and the physics aspects of SBRT for prostate cancer were analyzed. In details, the aims were: (i) to describe the rationale of reducing the number of fractions (i.e. increasing the dose per fraction), (ii) to analyze the features to be accounted for performing an extreme hypo-fractionation scheme (>6-7Gy), and (iii) to describe technological solutions for treating in a safe way. The analysis of outcomes, toxicities, and other clinical aspects are not object of the present evaluation. PMID:27061869

  9. Current composite-feature classification methods do not outperform simple single-genes classifiers in breast cancer prognosis

    PubMed Central

    Staiger, Christine; Cadot, Sidney; Györffy, Balázs; Wessels, Lodewyk F. A.; Klau, Gunnar W.

    2013-01-01

    Integrating gene expression data with secondary data such as pathway or protein-protein interaction data has been proposed as a promising approach for improved outcome prediction of cancer patients. Methods employing this approach usually aggregate the expression of genes into new composite features, while the secondary data guide this aggregation. Previous studies were limited to few data sets with a small number of patients. Moreover, each study used different data and evaluation procedures. This makes it difficult to objectively assess the gain in classification performance. Here we introduce the Amsterdam Classification Evaluation Suite (ACES). ACES is a Python package to objectively evaluate classification and feature-selection methods and contains methods for pooling and normalizing Affymetrix microarrays from different studies. It is simple to use and therefore facilitates the comparison of new approaches to best-in-class approaches. In addition to the methods described in our earlier study (Staiger et al., 2012), we have included two prominent prognostic gene signatures specific for breast cancer outcome, one more composite feature selection method and two network-based gene ranking methods. Employing the evaluation pipeline we show that current composite-feature classification methods do not outperform simple single-genes classifiers in predicting outcome in breast cancer. Furthermore, we find that also the stability of features across different data sets is not higher for composite features. Most stunningly, we observe that prediction performances are not affected when extracting features from randomized PPI networks. PMID:24391662

  10. Evolutionary features of thyroid cancer in patients with thyroidectomies from 2008 to 2013 in China.

    PubMed

    Liu, Xiaoyun; Zhu, Lijun; Wang, Zhixiao; Cui, Dai; Chen, Huanhuan; Duan, Yu; Shen, Meiping; Lu, Hui; Zhang, Zhihong; Chen, Jiawei; Alexander, Erik K; Yang, Tao; Wang, Xiaodong

    2016-01-01

    To evaluate the characteristics of thyroid carcinoma over time, we carried out a retrospective study to illustrate the evolutionary features of thyroid carcinoma. All records of thyroidectomies from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were obtained focusing on pathological diagnosis, size, local lymph node metastasis (LNM) of the tumors. The thyroid cancer detection rate increased from 24.6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance, and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years. PMID:27328631

  11. Evolutionary features of thyroid cancer in patients with thyroidectomies from 2008 to 2013 in China

    PubMed Central

    Liu, Xiaoyun; Zhu, Lijun; Wang, Zhixiao; Cui, Dai; Chen, Huanhuan; Duan, Yu; Shen, Meiping; Lu, Hui; Zhang, Zhihong; Chen, Jiawei; Alexander, Erik K.; Yang, Tao; Wang, Xiaodong

    2016-01-01

    To evaluate the characteristics of thyroid carcinoma over time, we carried out a retrospective study to illustrate the evolutionary features of thyroid carcinoma. All records of thyroidectomies from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were obtained focusing on pathological diagnosis, size, local lymph node metastasis (LNM) of the tumors. The thyroid cancer detection rate increased from 24.6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance, and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years. PMID:27328631

  12. Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

    PubMed

    De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Chang, Yu-Hui H

    2014-10-01

    Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues. PMID:24788529

  13. High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer

    PubMed Central

    LEBOK, PATRICK; ÖZTÜRK, MELIKE; HEILENKÖTTER, UWE; JAENICKE, FRITZ; MÜLLER, VOLKMAR; PALUCHOWSKI, PETER; GEIST, STEFAN; WILKE, CHRISTIAN; BURANDT, EICKE; LEBEAU, ANNETTE; WILCZAK, WALDEMAR; KRECH, TILL; SIMON, RONALD; SAUTER, GUIDO; QUAAS, ALEXANDER

    2016-01-01

    Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer. PMID

  14. Color edges extraction using statistical features and automatic threshold technique: application to the breast cancer cells

    PubMed Central

    2014-01-01

    Background Color image segmentation has been so far applied in many areas; hence, recently many different techniques have been developed and proposed. In the medical imaging area, the image segmentation may be helpful to provide assistance to doctor in order to follow-up the disease of a certain patient from the breast cancer processed images. The main objective of this work is to rebuild and also to enhance each cell from the three component images provided by an input image. Indeed, from an initial segmentation obtained using the statistical features and histogram threshold techniques, the resulting segmentation may represent accurately the non complete and pasted cells and enhance them. This allows real help to doctors, and consequently, these cells become clear and easy to be counted. Methods A novel method for color edges extraction based on statistical features and automatic threshold is presented. The traditional edge detector, based on the first and the second order neighborhood, describing the relationship between the current pixel and its neighbors, is extended to the statistical domain. Hence, color edges in an image are obtained by combining the statistical features and the automatic threshold techniques. Finally, on the obtained color edges with specific primitive color, a combination rule is used to integrate the edge results over the three color components. Results Breast cancer cell images were used to evaluate the performance of the proposed method both quantitatively and qualitatively. Hence, a visual and a numerical assessment based on the probability of correct classification (P C ), the false classification (P f ), and the classification accuracy (Sens(%)) are presented and compared with existing techniques. The proposed method shows its superiority in the detection of points which really belong to the cells, and also the facility of counting the number of the processed cells. Conclusions Computer simulations highlight that the proposed method

  15. Evaluation of correlation between CT image features and ERCC1 protein expression in assessing lung cancer prognosis

    NASA Astrophysics Data System (ADS)

    Tan, Maxine; Emaminejad, Nastaran; Qian, Wei; Sun, Shenshen; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin

    2014-03-01

    Stage I non-small-cell lung cancers (NSCLC) usually have favorable prognosis. However, high percentage of NSCLC patients have cancer relapse after surgery. Accurately predicting cancer prognosis is important to optimally treat and manage the patients to minimize the risk of cancer relapse. Studies have shown that an excision repair crosscomplementing 1 (ERCC1) gene was a potentially useful genetic biomarker to predict prognosis of NSCLC patients. Meanwhile, studies also found that chronic obstructive pulmonary disease (COPD) was highly associated with lung cancer prognosis. In this study, we investigated and evaluated the correlations between COPD image features and ERCC1 gene expression. A database involving 106 NSCLC patients was used. Each patient had a thoracic CT examination and ERCC1 genetic test. We applied a computer-aided detection scheme to segment and quantify COPD image features. A logistic regression method and a multilayer perceptron network were applied to analyze the correlation between the computed COPD image features and ERCC1 protein expression. A multilayer perceptron network (MPN) was also developed to test performance of using COPD-related image features to predict ERCC1 protein expression. A nine feature based logistic regression analysis showed the average COPD feature values in the low and high ERCC1 protein expression groups are significantly different (p < 0.01). Using a five-fold cross validation method, the MPN yielded an area under ROC curve (AUC = 0.669±0.053) in classifying between the low and high ERCC1 expression cases. The study indicates that CT phenotype features are associated with the genetic tests, which may provide supplementary information to help improve accuracy in assessing prognosis of NSCLC patients.

  16. mtDNA germ line variation mediated ROS generates retrograde signaling and induces pro-cancerous metabolic features

    PubMed Central

    Singh, Rajnish Kumar; Srivastava, Archita; Kalaiarasan, Ponnusamy; Manvati, Siddharth; Chopra, Rupali; Bamezai, Rameshwar N. K.

    2014-01-01

    mtDNA non-synonymous germ line variation (G10398A; p.A114T) has remained equivocal with least mechanistic understanding in showing an association with cancer. This has necessitated showing in-vitro how an over-expression within mitochondria of either of the variants produces higher intracellular ROS, resulting in differential anchorage dependent and independent growth. Both these features were observed to be relatively higher in ND3:114T variant. An elevated amount of intracellular carbonylated proteins and a reduced activity of a key glycolytic enzyme, Pyruvate kinase M2, along with high glucose uptake and lactate production were other pro-cancerous features observed. The retrograde signaling through surplus ROS was generated by post-ND3 over-expression regulated nuclear gene expression epigenetically, involving selectively the apoptotic-DDR-pathways. The feature of ND3 over-expression, inducing ROS mediated pro-cancerous features in the cells in in vitro, was replicated in a pilot study in a limited number of sporadic breast tumors, suggesting the importance of mitochondrial germ-line variant(s) in enabling the cells to acquire pro-cancerous features. PMID:25300428

  17. Primary oral cancer in a Turkish population sample: association with sociodemographic features, smoking, alcohol, diet and dentition.

    PubMed

    Güneri, Pelin; Cankaya, Hülya; Yavuzer, Atilla; Güneri, E Alpin; Erişen, Levent; Ozkul, Doğan; El, Sedef Nehir; Karakaya, Sibel; Arican, Armağan; Boyacioğlu, Hayal

    2005-11-01

    The aim of this multicentre case-control study was to investigate the association of a variety of factors with oral cancer in a group of Turkish patients. Questionnaires were used to investigate the sociodemographic features, smoking and alcohol consumptions, dietary habits and dental status of 79 primary oral cancer patients and 61 controls. Data were statistically analysed with Mann-Whitney U-test, Pearson Chi-square and binary logistic regression analyses to determine the odds ratios. Low level of education, gender, dietary habits, having poor oral hygiene and denture sores were associated with primary oral cancer in this patient sample; but eating salads and raw vegetables, fish, and drinking red wine were related with healthy status. Determination of the factors associated with oral cancer and of the high-risk groups would be beneficial to provide efficient screening protocols and prevention programmes for oral cavity cancers. PMID:16139559

  18. Regression-Based Approach For Feature Selection In Classification Issues. Application To Breast Cancer Detection And Recurrence

    NASA Astrophysics Data System (ADS)

    Belciug, Smaranda; Serbanescu, Mircea-Sebastian

    2015-09-01

    Feature selection is considered a key factor in classifications/decision problems. It is currently used in designing intelligent decision systems to choose the best features which allow the best performance. This paper proposes a regression-based approach to select the most important predictors to significantly increase the classification performance. Application to breast cancer detection and recurrence using publically available datasets proved the efficiency of this technique.

  19. Unsupervised feature construction and knowledge extraction from genome-wide assays of breast cancer with denoising autoencoders.

    PubMed

    Tan, Jie; Ung, Matthew; Cheng, Chao; Greene, Casey S

    2015-01-01

    Big data bring new opportunities for methods that efficiently summarize and automatically extract knowledge from such compendia. While both supervised learning algorithms and unsupervised clustering algorithms have been successfully applied to biological data, they are either dependent on known biology or limited to discerning the most significant signals in the data. Here we present denoising autoencoders (DAs), which employ a data-defined learning objective independent of known biology, as a method to identify and extract complex patterns from genomic data. We evaluate the performance of DAs by applying them to a large collection of breast cancer gene expression data. Results show that DAs successfully construct features that contain both clinical and molecular information. There are features that represent tumor or normal samples, estrogen receptor (ER) status, and molecular subtypes. Features constructed by the autoencoder generalize to an independent dataset collected using a distinct experimental platform. By integrating data from ENCODE for feature interpretation, we discover a feature representing ER status through association with key transcription factors in breast cancer. We also identify a feature highly predictive of patient survival and it is enriched by FOXM1 signaling pathway. The features constructed by DAs are often bimodally distributed with one peak near zero and another near one, which facilitates discretization. In summary, we demonstrate that DAs effectively extract key biological principles from gene expression data and summarize them into constructed features with convenient properties. PMID:25592575

  20. UNSUPERVISED FEATURE CONSTRUCTION AND KNOWLEDGE EXTRACTION FROM GENOME-WIDE ASSAYS OF BREAST CANCER WITH DENOISING AUTOENCODERS

    PubMed Central

    TAN, JIE; UNG, MATTHEW; CHENG, CHAO; GREENE, CASEY S

    2014-01-01

    Big data bring new opportunities for methods that efficiently summarize and automatically extract knowledge from such compendia. While both supervised learning algorithms and unsupervised clustering algorithms have been successfully applied to biological data, they are either dependent on known biology or limited to discerning the most significant signals in the data. Here we present denoising autoencoders (DAs), which employ a data-defined learning objective independent of known biology, as a method to identify and extract complex patterns from genomic data. We evaluate the performance of DAs by applying them to a large collection of breast cancer gene expression data. Results show that DAs successfully construct features that contain both clinical and molecular information. There are features that represent tumor or normal samples, estrogen receptor (ER) status, and molecular subtypes. Features constructed by the autoencoder generalize to an independent dataset collected using a distinct experimental platform. By integrating data from ENCODE for feature interpretation, we discover a feature representing ER status through association with key transcription factors in breast cancer. We also identify a feature highly predictive of patient survival and it is enriched by FOXM1 signaling pathway. The features constructed by DAs are often bimodally distributed with one peak near zero and another near one, which facilitates discretization. In summary, we demonstrate that DAs effectively extract key biological principles from gene expression data and summarize them into constructed features with convenient properties. PMID:25592575

  1. Clinical features and prognosis in colorectal cancer patients with different ethnicities in Northwest China

    PubMed Central

    Yusup, Akram; Wang, Hai-Jiang; Rahmutula, Azmat; Sayim, Parhat; Zhao, Ze-Liang; Zhang, Guo-Qing

    2013-01-01

    AIM: To compare the clinical factors and tumor characteristics that predict survival in colorectal cancer (CRC) patients with different ethnicities in Xin Jiang area. METHODS: A total of 1421 histopathologically confirmed sporadic CRC patients who were either Han/Chinese or Uyghur were identified and enrolled from a database of both diagnoses and operative procedures from Xin Jiang Tumor Hospital, which is affiliated to Xin Jiang Medical University between 2000 and 2007. Patients with family histories of CRC, hereditary nonpolyposis CRC, familial adenomatous polyposis, inflammatory bowel disease, carcinoid, squamous carcinoma or melanoma were excluded. The two ethnic groups were compared with regard to clinical features, tumor characteristics, disease stage, overall survival rate, disease-free survival rate and cancer-specific survival rate. The factors predicting long-term survival were assessed via both univariate and multivariate analysis. RESULTS: Among the 1421 patients with CRC enrolled in this study, 1210 patients were Han/Chinese (mean age, 62.3 ± 4.5 years; range, 19-92 years), while 211 patients were Uyghur (mean age, 52.4 ± 15.6 years; range, 17-87 years). There were significant differences in proportions of gender, age, blood type, occupation and histopathological type between the Han/Chinese and Uyghur patients (P < 0.05). The median overall, disease-free and cancer-specific survival time were 45, 62 and 65 mo for the Han/Chinese patients and 42, 49 and 61 mo for the Uyghur patients (P = 0.000, P = 0.005, P = 0.007). The cumulative 5-year survival of the Uyghur patients was significantly worse than that of the Han patients (P = 0.000). A multivariate analysis showed that age, ethnicity, histopathological type, differentiation, T (Infiltration depth), N (Lymph node metastasis), staging, postoperative metastasis and metastatic site (P < 0.05) were found to be the prognostic factors. CONCLUSION: The Uyghur CRC patients are associated with significantly

  2. Cancer of Unknown Primary in Adolescents and Young Adults: Clinicopathological Features, Prognostic Factors and Survival Outcomes

    PubMed Central

    Raghav, Kanwal; Mhadgut, Hemendra; McQuade, Jennifer L.; Lei, Xiudong; Ross, Alicia; Matamoros, Aurelio; Wang, Huamin; Overman, Michael J.; Varadhachary, Gauri R.

    2016-01-01

    Background Cancer in adolescents and young adults (AYAs) (15–39 years) is increasingly recognized as a distinct clinical and biological entity. Cancer of unknown primary (CUP), a disease traditionally presenting in older adults with a median age of 65 years, poses several challenges when diagnosed in AYA patients. This study describes clinicopathological features, outcomes and challenges in caring for AYA-CUP patients. Methods A retrospective review of 47 AYAs diagnosed with CUP at MD Anderson Cancer Center (6/2006–6/2013) was performed. Patients with favorable CUP subsets treated as per site-specific recommendations were excluded. Demographics, imaging, pathology and treatment data was collected using a prospectively maintained CUP database. Kaplan-Meier product limit method and log-rank test were used to estimate and compare overall survival. The cox-proportional model was used for multivariate analyses. Results Median age was 35 years (range 19–39). All patients underwent comprehensive workup. Adenocarcinoma was the predominant histology (70%). A median of 9 immunostains (range 2–29) were performed. The most common putative primary was biliary tract based on clinicopathological parameters as well as gene profiling. Patients presented with a median of 2 metastatic sites [lymph node (60%), lung (47%), liver (38%) and bone (34%)]. Most commonly used systemic chemotherapies included gemcitabine, fluorouracil, taxanes and platinum agents. Median overall survival for the entire cohort was 10.0 (95% confidence interval (CI): 6.7–15.4) months. On multivariate analyses, elevated lactate dehydrogenase (Hazard ratio (HR) 3.66; 95%CI 1.52–8.82; P = 0.004), ≥3 metastatic sites (HR 5.34; 95%CI 1.19–23.9; P = 0.029), and tissue of origin not tested (HR 3.4; 95%CI 1.44–8.06; P = 0.005) were associated with poor overall survival. Culine’s CUP prognostic model (lactate dehydrogenase, performance status, liver metastases) was validated in this cohort (median

  3. Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

    PubMed Central

    2014-01-01

    Background The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that two EGFR functional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism, R497K, may affect EGFR expression and breast cancer clinical profile. Methods The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the (CA)n and R497K polymorphisms, and the associations between (CA)n polymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed. Results (CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was (CA)16 (0.43; 95% CI = 0.40–0.46), which was set as the cut-off length to define the Short allele. Variant (CA)n genotypes had no significant effect in tumoral EGFR mRNA levels, but patients with two (CA)n Long alleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19–0.91). The evaluation of R497K polymorphism indicated a frequency of 0.21 (95% CI = 0.19 – 0.24) for the variant (Lys) allele. Patients with variant R497K genotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotype Arg/Arg (ORadjusted = 0.32; 95% CI = 0.17–0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of both EGFR polymorphisms (Lys allele of R497K and Long/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological

  4. Variability of Image Features Computed from Conventional and Respiratory-Gated PET/CT Images of Lung Cancer

    PubMed Central

    Oliver, Jasmine A.; Budzevich, Mikalai; Zhang, Geoffrey G.; Dilling, Thomas J.; Latifi, Kujtim; Moros, Eduardo G.

    2015-01-01

    Radiomics is being explored for potential applications in radiation therapy. How various imaging protocols affect quantitative image features is currently a highly active area of research. To assess the variability of image features derived from conventional [three-dimensional (3D)] and respiratory-gated (RG) positron emission tomography (PET)/computed tomography (CT) images of lung cancer patients, image features were computed from 23 lung cancer patients. Both protocols for each patient were acquired during the same imaging session. PET tumor volumes were segmented using an adaptive technique which accounted for background. CT tumor volumes were delineated with a commercial segmentation tool. Using RG PET images, the tumor center of mass motion, length, and rotation were calculated. Fifty-six image features were extracted from all images consisting of shape descriptors, first-order features, and second-order texture features. Overall, 26.6% and 26.2% of total features demonstrated less than 5% difference between 3D and RG protocols for CT and PET, respectively. Between 10 RG phases in PET, 53.4% of features demonstrated percent differences less than 5%. The features with least variability for PET were sphericity, spherical disproportion, entropy (first and second order), sum entropy, information measure of correlation 2, Short Run Emphasis (SRE), Long Run Emphasis (LRE), and Run Percentage (RPC); and those for CT were minimum intensity, mean intensity, Root Mean Square (RMS), Short Run Emphasis (SRE), and RPC. Quantitative analysis using a 3D acquisition versus RG acquisition (to reduce the effects of motion) provided notably different image feature values. This study suggests that the variability between 3D and RG features is mainly due to the impact of respiratory motion. PMID:26692535

  5. Comparative Analysis of Clinicopathologic Features of, Treatment in, and Survival of Americans with Lung or Bronchial Cancer

    PubMed Central

    Li, Dan; Du, Xianglin L.; Ren, Yinghong; Liu, Peijun; Li, Shuting; Yang, Jiao; Lv, Meng; Chen, Ling; Wang, Xin; Li, Enxiao; Yang, Jin; Yi, Min

    2016-01-01

    Ethnic disparities in lung and bronchial cancer diagnoses and disease-specific survival (DSS) rates in the United States are well known. However, few studies have specifically assessed these differences in Asian subgroups. The primary objectives of the retrospective analysis described herein were to identify any significant differences in clinicopathologic features, treatment, and survival rate between Asian lung cancer patients and lung cancer patients in other broad ethnic groups in the United States and to determine the reasons for these differences among subgroups of Asian patients with lung or bronchial cancer. We searched the Surveillance, Epidemiology, and End Results Program database to identify patients diagnosed with lung or bronchial cancer from 1990 to 2012. Differences in clinicopathologic features, treatment, and DSS rate in four broad ethnic groups and eight Asian subgroups were compared. The study population consisted of 849,088 patients, 5.2% of whom were of Asian descent. Female Asian patients had the lowest lung and bronchial cancer incidence rates, whereas male black patients had the highest rates. Asian patients had the best 5-year DSS rate. In our Asian subgroup analysis, Indian/Pakistani patients had the best 5-year DSS rate, whereas Hawaiian/Pacific Islander patients had the worst 5-year DSS rates. We found the differences in DSS rate among the four broad ethnic groups and eight Asian subgroups when we grouped patients by age and disease stage, as well. Asian patients had better DSS rates than those in the other three broad ethnic groups in almost every age and disease-stage group, especially in older patients and those with advanced-stage disease. In conclusion, we found that clinicopathologic features and treatment of lung and bronchial cancer differ by ethnicity in the United States, and the differences impact survival in each ethnic group. PMID:27244238

  6. Comparative Analysis of Clinicopathologic Features of, Treatment in, and Survival of Americans with Lung or Bronchial Cancer.

    PubMed

    Li, Dan; Du, Xianglin L; Ren, Yinghong; Liu, Peijun; Li, Shuting; Yang, Jiao; Lv, Meng; Chen, Ling; Wang, Xin; Li, Enxiao; Yang, Jin; Yi, Min

    2016-01-01

    Ethnic disparities in lung and bronchial cancer diagnoses and disease-specific survival (DSS) rates in the United States are well known. However, few studies have specifically assessed these differences in Asian subgroups. The primary objectives of the retrospective analysis described herein were to identify any significant differences in clinicopathologic features, treatment, and survival rate between Asian lung cancer patients and lung cancer patients in other broad ethnic groups in the United States and to determine the reasons for these differences among subgroups of Asian patients with lung or bronchial cancer. We searched the Surveillance, Epidemiology, and End Results Program database to identify patients diagnosed with lung or bronchial cancer from 1990 to 2012. Differences in clinicopathologic features, treatment, and DSS rate in four broad ethnic groups and eight Asian subgroups were compared. The study population consisted of 849,088 patients, 5.2% of whom were of Asian descent. Female Asian patients had the lowest lung and bronchial cancer incidence rates, whereas male black patients had the highest rates. Asian patients had the best 5-year DSS rate. In our Asian subgroup analysis, Indian/Pakistani patients had the best 5-year DSS rate, whereas Hawaiian/Pacific Islander patients had the worst 5-year DSS rates. We found the differences in DSS rate among the four broad ethnic groups and eight Asian subgroups when we grouped patients by age and disease stage, as well. Asian patients had better DSS rates than those in the other three broad ethnic groups in almost every age and disease-stage group, especially in older patients and those with advanced-stage disease. In conclusion, we found that clinicopathologic features and treatment of lung and bronchial cancer differ by ethnicity in the United States, and the differences impact survival in each ethnic group. PMID:27244238

  7. Bilateral image subtraction features for multivariate automated classification of breast cancer risk

    NASA Astrophysics Data System (ADS)

    Celaya-Padilla, Jose M.; Rodriguez-Rojas, Juan; Galván-Tejada, Jorge I.; Martínez-Torteya, Antonio; Treviño, Victor; Tamez-Peña, José G.

    2014-03-01

    Early tumor detection is key in reducing breast cancer deaths and screening mammography is the most widely available method for early detection. However, mammogram interpretation is based on human radiologist, whose radiological skills, experience and workload makes radiological interpretation inconsistent. In an attempt to make mammographic interpretation more consistent, computer aided diagnosis (CADx) systems has been introduced. This paper presents an CADx system aimed to automatically triage normal mammograms form suspicious mammograms. The CADx system co-reregister the left and breast images, then extracts image features from the co-registered mammographic bilateral sets. Finally, an optimal logistic multivariate model is generated by means of an evolutionary search engine. In this study, 440 subjects form the DDSM public data sets were used: 44 normal mammograms, 201 malignant mass mammograms, and 195 mammograms with malignant calci cations. The results showed a cross validation accuracy of 0.88 and an area under receiver operating characteristic (AUC) of 0.89 for the calci cations vs. normal mammograms. The optimal mass vs. normal mammograms model obtained an accuracy of 0.85 and an AUC of 0.88.

  8. Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers.

    PubMed

    Granados, D P; Rodenbrock, A; Laverdure, J-P; Côté, C; Caron-Lizotte, O; Carli, C; Pearson, H; Janelle, V; Durette, C; Bonneil, E; Roy, D C; Delisle, J-S; Lemieux, S; Thibault, P; Perreault, C

    2016-06-01

    Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients. PMID:26857467

  9. BioCAST/IFCT-1002: epidemiological and molecular features of lung cancer in never-smokers.

    PubMed

    Couraud, Sébastien; Souquet, Pierre-Jean; Paris, Christophe; Dô, Pascal; Doubre, Hélène; Pichon, Eric; Dixmier, Adrien; Monnet, Isabelle; Etienne-Mastroianni, Bénédicte; Vincent, Michel; Trédaniel, Jean; Perrichon, Marielle; Foucher, Pascal; Coudert, Bruno; Moro-Sibilot, Denis; Dansin, Eric; Labonne, Stéphanie; Missy, Pascale; Morin, Franck; Blanché, Hélène; Zalcman, Gérard

    2015-05-01

    Lung cancer in never-smokers (LCINS) (fewer than 100 cigarettes in lifetime) is considered as a distinct entity and harbours an original molecular profile. However, the epidemiological and molecular features of LCINS in Europe remain poorly understood. All consecutive newly diagnosed LCINS patients were included in this prospective observational study by 75 participating centres during a 14-month period. Each patient completed a detailed questionnaire about risk factor exposure. Biomarker and pathological analyses were also collected. We report the main descriptive overall results with a focus on sex differences. 384 patients were included: 65 men and 319 women. 66% had been exposed to passive smoking (significantly higher among women). Definite exposure to main occupational carcinogens was significantly higher in men (35% versus 8% in women). A targetable molecular alteration was found in 73% of patients (without any significant sex difference): EGFR in 51%, ALK in 8%, KRAS in 6%, HER2 in 3%, BRAF in 3%, PI3KCA in less than 1%, and multiple in 2%. We present the largest and most comprehensive LCINS analysis in a European population. Physicians should track occupational exposure in men (35%), and a somatic molecular alteration in both sexes (73%). PMID:25657019

  10. [Study on endoscopic features in responders to systemic chemotherapy in advanced gastric cancer].

    PubMed

    Yasutake, K; Tokisue, M; Masuda, T; Ono, S; Yoshimura, Y; Yasutake, K; Imamura, Y; Oya, M; Matsushita, K

    1990-10-20

    We studied the endoscopic features in 6 cases of advanced gastric cancer responded to chemotherapy. Patient characteristics were as follows. [table; see text] Age 43-77 (mean 63 years old) Endoscopic type Mean duration of PR was 26.6 weeks. The process of the improvement of primary lesion as judged by endoscopic findings were as follows. Firstly getting flat of wall, secondly reduction in size of ulcer, and lastly changing into scar. Number of reported cases including our case No. 6 which are diagnosed as scar endoscopically after chemotherapy and are operated successfully has been increasing. Most of them showed scar macroscopically with wide and irregular surface. Especially our case No. 6 showed keloidal scar. In these cases, the histological improvement into grade 2-3 was observed in scared tissue. Sooner or later, such a process of endoscopic improvement was observed 4-8 weeks after initiation of chemotherapy. Unless the endoscopic improvement was observed 8 weeks after initiation, regimen of chemotherapy should be changed into others. PMID:2148178

  11. DEMOGRAPHIC AND CLINICOPATHOLOGIC FEATURES OF PATIENTS WITH PRIMARY BREAST CANCER TREATED BETWEEN 1997 AND 2010: A SINGLE INSTITUTION EXPERIENCE.

    PubMed

    Žitnjak, Daniela; Soldić, Željko; Kust, Davor; Bolanća, Ante; Kusić, Zvonko

    2015-09-01

    Breast cancer accounted for 28% of all new cancers and 18% of female cancer deaths in Europe in 2010. It is the most common type of cancer in women in Croatia, with an incidence rate of 56.9/100 000 in the year 2010, and the highest number of newly diagnosed women aged between 60 and 64. Multiple factors are associated with an increased risk of breast cancer: advancing age, family history, exposure to endogenous and exogenous reproductive hormones, dietary factors, benign breast disease, and environmental factors. To assess demographic and clinicopathologic features of primary breast cancer, we retrospectively analyzed 870 patients treated in our institution between 1997 and 2010. Data were obtained from medical documentation and a printed questionnaire regarding life habits. Most of our patients presented with a breast lump and were self-diagnosed by breast examination. This fact highlights the need of regular breast self-examination, although it should also be taken into account that most of our patients did not attend regular mammography screening (only 31%). One of the most concerning facts is that the mean time from observing the first symptom to visiting a physician was 4 months. Previous studies have identified ignorance, fear and fatalistic attitudes, poor socioeconomic conditions, and illiteracy as important factors resulting in delay. Considering these facts, education and raising awareness about the disease in the general population is one of the key weapons for lowering breast cancer mortality. PMID:26666098

  12. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.

    PubMed

    Dong, Tieying; Kang, Xinmei; Liu, Zhaoliang; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Liu, Hang; Wang, Zhipeng; Zhang, Qingyuan

    2016-06-01

    Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic

  13. Quantitative identification of magnetic resonance imaging features of prostate cancer response following laser ablation and radical prostatectomy

    PubMed Central

    Litjens, Geert J. S.; Huisman, Henkjan J.; Elliott, Robin M.; Shih, Natalie Nc.; Feldman, Michael D.; Viswanath, Satish; Fütterer, Jurgen J.; Bomers, Joyce G. R.; Madabhushi, Anant

    2014-01-01

    Abstract. Laser interstitial thermotherapy (LITT) is a relatively new focal therapy technique for the ablation of localized prostate cancer. In this study, for the first time, we are integrating ex vivo pathology and magnetic resonance imaging (MRI) to assess the imaging characteristics of prostate cancer and treatment changes following LITT. Via a unique clinical trial, which gave us the availability of ex vivo histology and pre- and post-LITT MRIs, (1) we investigated the imaging characteristics of treatment effects and residual disease, and (2) evaluated treatment-induced feature changes in the ablated area relative to the residual disease. First, a pathologist annotated the ablated area and the residual disease on the ex vivo histology. Subsequently, we transferred the annotations to the post-LITT MRI using a semi-automatic elastic registration. The pre- and post-LITT MRIs were registered and features were extracted. A scoring metric based on the change in median pre- and post-LITT feature values was introduced, which allowed us to identify the most treatment responsive features. Our results show that (1) image characteristics for treatment effects and residual disease are different, and (2) the change of feature values between pre- and post-LITT MRIs can be a quantitative biomarker for treatment response. Finally, using feature change improved discrimination between the residual disease and treatment effects. PMID:26158070

  14. Features of Undiagnosed Breast Cancers at Screening Breast MR Imaging and Potential Utility of Computer-Aided Evaluation

    PubMed Central

    Seo, Mirinae; Bae, Min Sun; Koo, Hye Ryoung; Kim, Won Hwa; Lee, Su Hyun; Chu, Ajung

    2016-01-01

    Objective To retrospectively evaluate the features of undiagnosed breast cancers on prior screening breast magnetic resonance (MR) images in patients who were subsequently diagnosed with breast cancer, as well as the potential utility of MR-computer-aided evaluation (CAE). Materials and Methods Between March 2004 and May 2013, of the 72 consecutive pairs of prior negative MR images and subsequent MR images with diagnosed cancers (median interval, 32.8 months; range, 5.4-104.6 months), 36 (50%) had visible findings (mean size, 1.0 cm; range, 0.3-5.2 cm). The visible findings were divided into either actionable or underthreshold groups by the blinded review by 5 radiologists. MR imaging features, reasons for missed cancer, and MR-CAE features according to actionability were evaluated. Results Of the 36 visible findings on prior MR images, 33.3% (12 of 36) of the lesions were determined to be actionable and 66.7% (24 of 36) were underthreshold; 85.7% (6 of 7) of masses and 31.6% (6 of 19) of non-mass enhancements were classified as actionable lesions. Mimicking physiologic enhancements (27.8%, 10 of 36) and small lesion size (27.8%, 10 of 36) were the most common reasons for missed cancer. Actionable findings tended to show more washout or plateau kinetic patterns on MR-CAE than underthreshold findings, as the 100% of actionable findings and 46.7% of underthreshold findings showed washout or plateau (p = 0.008). Conclusion MR-CAE has the potential for reducing the number of undiagnosed breast cancers on screening breast MR images, the majority of which are caused by mimicking physiologic enhancements or small lesion size. PMID:26798217

  15. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    SciTech Connect

    Lee, Kang Nyeong; Choi, Ho Soon; Yang, Sun Young; Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo; Paik, Seung Sam

    2014-04-18

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.

  16. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  17. Association of mammographic image feature change and an increasing risk trend of developing breast cancer: an assessment

    NASA Astrophysics Data System (ADS)

    Tan, Maxine; Leader, Joseph K.; Liu, Hong; Zheng, Bin

    2015-03-01

    We recently investigated a new mammographic image feature based risk factor to predict near-term breast cancer risk after a woman has a negative mammographic screening. We hypothesized that unlike the conventional epidemiology-based long-term (or lifetime) risk factors, the mammographic image feature based risk factor value will increase as the time lag between the negative and positive mammography screening decreases. The purpose of this study is to test this hypothesis. From a large and diverse full-field digital mammography (FFDM) image database with 1278 cases, we collected all available sequential FFDM examinations for each case including the "current" and 1 to 3 most recently "prior" examinations. All "prior" examinations were interpreted negative, and "current" ones were either malignant or recalled negative/benign. We computed 92 global mammographic texture and density based features, and included three clinical risk factors (woman's age, family history and subjective breast density BIRADS ratings). On this initial feature set, we applied a fast and accurate Sequential Forward Floating Selection (SFFS) feature selection algorithm to reduce feature dimensionality. The features computed on both mammographic views were individually/ separately trained using two artificial neural network (ANN) classifiers. The classification scores of the two ANNs were then merged with a sequential ANN. The results show that the maximum adjusted odds ratios were 5.59, 7.98, and 15.77 for using the 3rd, 2nd, and 1st "prior" FFDM examinations, respectively, which demonstrates a higher association of mammographic image feature change and an increasing risk trend of developing breast cancer in the near-term after a negative screening.

  18. A new set of wavelet- and fractals-based features for Gleason grading of prostate cancer histopathology images

    NASA Astrophysics Data System (ADS)

    Mosquera Lopez, Clara; Agaian, Sos

    2013-02-01

    Prostate cancer detection and staging is an important step towards patient treatment selection. Advancements in digital pathology allow the application of new quantitative image analysis algorithms for computer-assisted diagnosis (CAD) on digitized histopathology images. In this paper, we introduce a new set of features to automatically grade pathological images using the well-known Gleason grading system. The goal of this study is to classify biopsy images belonging to Gleason patterns 3, 4, and 5 by using a combination of wavelet and fractal features. For image classification we use pairwise coupling Support Vector Machine (SVM) classifiers. The accuracy of the system, which is close to 97%, is estimated through three different cross-validation schemes. The proposed system offers the potential for automating classification of histological images and supporting prostate cancer diagnosis.

  19. A statistical feature selection method for lung cancer classification in CT scans

    NASA Astrophysics Data System (ADS)

    Al-Absi, Hamada R. H.; Samir, Brahim Belhaouari

    2013-10-01

    This paper presents a computer aided diagnosis for lung nodules in CT images. The system consists of feature extraction, feature selection and classification. A two-step feature selection process is introduced to reduce the number of coefficients produced in the feature extraction step. This helps in enhancing the classification performance as it removes unneeded and redundant information. The classification rate of the system reached 98.10 % with minimum false negatives and zero false positives.

  20. Computer extracted texture features on T2w MRI to predict biochemical recurrence following radiation therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Ginsburg, Shoshana B.; Rusu, Mirabela; Kurhanewicz, John; Madabhushi, Anant

    2014-03-01

    In this study we explore the ability of a novel machine learning approach, in conjunction with computer-extracted features describing prostate cancer morphology on pre-treatment MRI, to predict whether a patient will develop biochemical recurrence within ten years of radiation therapy. Biochemical recurrence, which is characterized by a rise in serum prostate-specific antigen (PSA) of at least 2 ng/mL above the nadir PSA, is associated with increased risk of metastasis and prostate cancer-related mortality. Currently, risk of biochemical recurrence is predicted by the Kattan nomogram, which incorporates several clinical factors to predict the probability of recurrence-free survival following radiation therapy (but has limited prediction accuracy). Semantic attributes on T2w MRI, such as the presence of extracapsular extension and seminal vesicle invasion and surrogate measure- ments of tumor size, have also been shown to be predictive of biochemical recurrence risk. While the correlation between biochemical recurrence and factors like tumor stage, Gleason grade, and extracapsular spread are well- documented, it is less clear how to predict biochemical recurrence in the absence of extracapsular spread and for small tumors fully contained in the capsule. Computer{extracted texture features, which quantitatively de- scribe tumor micro-architecture and morphology on MRI, have been shown to provide clues about a tumor's aggressiveness. However, while computer{extracted features have been employed for predicting cancer presence and grade, they have not been evaluated in the context of predicting risk of biochemical recurrence. This work seeks to evaluate the role of computer-extracted texture features in predicting risk of biochemical recurrence on a cohort of sixteen patients who underwent pre{treatment 1.5 Tesla (T) T2w MRI. We extract a combination of first-order statistical, gradient, co-occurrence, and Gabor wavelet features from T2w MRI. To identify which of these

  1. Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness

    NASA Astrophysics Data System (ADS)

    Vignati, A.; Mazzetti, S.; Giannini, V.; Russo, F.; Bollito, E.; Porpiglia, F.; Stasi, M.; Regge, D.

    2015-04-01

    To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean) -0.522, 0.821 (median) -0.569, 0.854 (10th percentile) -0.556, 0.854 (25th percentile) -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

  2. Can radiomics features be reproducibly measured from CBCT images for patients with non-small cell lung cancer?

    SciTech Connect

    Fave, Xenia Fried, David; Mackin, Dennis; Yang, Jinzhong; Zhang, Joy; Balter, Peter; Followill, David; Gomez, Daniel; Kyle Jones, A.; Stingo, Francesco; Fontenot, Jonas; Court, Laurence

    2015-12-15

    Purpose: Increasing evidence suggests radiomics features extracted from computed tomography (CT) images may be useful in prognostic models for patients with nonsmall cell lung cancer (NSCLC). This study was designed to determine whether such features can be reproducibly obtained from cone-beam CT (CBCT) images taken using medical Linac onboard-imaging systems in order to track them through treatment. Methods: Test-retest CBCT images of ten patients previously enrolled in a clinical trial were retrospectively obtained and used to determine the concordance correlation coefficient (CCC) for 68 different texture features. The volume dependence of each feature was also measured using the Spearman rank correlation coefficient. Features with a high reproducibility (CCC > 0.9) that were not due to volume dependence in the patient test-retest set were further examined for their sensitivity to differences in imaging protocol, level of scatter, and amount of motion by using two phantoms. The first phantom was a texture phantom composed of rectangular cartridges to represent different textures. Features were measured from two cartridges, shredded rubber and dense cork, in this study. The texture phantom was scanned with 19 different CBCT imagers to establish the features’ interscanner variability. The effect of scatter on these features was studied by surrounding the same texture phantom with scattering material (rice and solid water). The effect of respiratory motion on these features was studied using a dynamic-motion thoracic phantom and a specially designed tumor texture insert of the shredded rubber material. The differences between scans acquired with different Linacs and protocols, varying amounts of scatter, and with different levels of motion were compared to the mean intrapatient difference from the test-retest image set. Results: Of the original 68 features, 37 had a CCC >0.9 that was not due to volume dependence. When the Linac manufacturer and imaging protocol

  3. Histopathological Features of Non-Neoplastic Breast Parenchyma Do Not Predict BRCA Mutation Status of Patients with Invasive Breast Cancer

    PubMed Central

    Bayraktar, Soley; Qiu, Hongming; Liu, Diane; Shen, Yu; Gutierrez-Barrera, Angelica M; Arun, Banu K; Sahin, Aysegul A

    2015-01-01

    BACKGROUND Several studies have evaluated histologic features of non-neoplastic breast parenchyma in patients with BRCA1/2 mutations, but the results are conflicting. The limited data suggest a much higher prevalence of high-risk precursor lesions in BRCA carriers. Therefore, we designed this study to compare the clinicopathological characteristics of peritumoral benign breast tissue in patients with and without deleterious BRCA mutations. METHODS Women with breast cancer (BC) who were referred for genetic counseling and underwent BRCA genetic testing in 2010 and 2011 were included in the study. RESULTS Of the six benign histological features analyzed in this study, only stromal fibrosis grade 2/3 was found to be statistically different, with more BRCA noncarriers having stromal fibrosis grade 2/3 than BRCA1/2 carriers (P = 0.04). CONCLUSION There is no significant association between mutation risk and the presence of benign histologic features of peritumoral breast parenchyma. PMID:26327783

  4. Metastatic colon cancer, version 3.2013: featured updates to the NCCN Guidelines.

    PubMed

    Benson, Al B; Bekaii-Saab, Tanios; Chan, Emily; Chen, Yi-Jen; Choti, Michael A; Cooper, Harry S; Engstrom, Paul F; Enzinger, Peter C; Fakih, Marwan G; Fenton, Moon J; Fuchs, Charles S; Grem, Jean L; Hunt, Steven; Kamel, Ahmed; Leong, Lucille A; Lin, Edward; May, Kilian Salerno; Mulcahy, Mary F; Murphy, Kate; Rohren, Eric; Ryan, David P; Saltz, Leonard; Sharma, Sunil; Shibata, David; Skibber, John M; Small, William; Sofocleous, Constantinos T; Venook, Alan P; Willett, Christopher G; Gregory, Kristina M; Freedman-Cass, Deborah A

    2013-02-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy. PMID:23411381

  5. High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

    PubMed Central

    Wang, Ke; Li, Dan; Sun, Lu

    2016-01-01

    Purpose The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. Methods Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. Results EGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. Conclusion High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID:26855586

  6. Delayed perforation after endoscopic submucosal dissection for early gastric cancer: Clinical features and treatment

    PubMed Central

    Yano, Takafumi; Tanabe, Satoshi; Ishido, Kenji; Azuma, Mizutomo; Wada, Takuya; Suzuki, Mizuto; Kawanishi, Natsuko; Yamane, Sakiko; Sasaki, Tohru; Katada, Chikatoshi; Mikami, Tetsuo; Katada, Natsuya; Koizumi, Wasaburo

    2016-01-01

    Perforation is an important procedural complication of endoscopic submucosal dissection (ESD) for early gastric cancer. Although the incidence of delayed perforation after ESD is low, extreme caution is necessary because many cases require surgical intervention. Among 1984 lesions of early gastric cancer treated in our hospital by ESD in 1588 patients from September 2002 through March 2015, delayed perforation developed in 4 patients (4 lesions, 0.25%). A diagnosis of delayed perforation requires prompt action, including surgical intervention when required. PMID:27114751

  7. Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer.

    PubMed

    Silvers, Christopher R; Liu, Yu-Ru; Wu, Chia-Hao; Miyamoto, Hiroshi; Messing, Edward M; Lee, Yi-Fen

    2016-04-26

    Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high mortality, and heterogeneity in MIBC results in variable clinical outcomes, posing challenges for clinical management. Extracellular vesicles (EVs) derived from MIBC have been shown to promote cancer progression. EVs derived from bladder cell lines were subjected to proteomic analysis, and periostin was chosen for further characterization due to its stage-specific gene expression profile. Knockdown of periostin by RNA interference reduces invasiveness in vitro and produces a rounder morphology. Importantly, treating low grade BC cells with periostin-rich EVs promotes cell aggressiveness and activates ERK oncogenic signals, and periostin suppression reverses these effects. These data suggest that MIBC might transfer periostin in an EV-mediated paracrine manner to promote the disease. To determine the potential of periostin as a bladder cancer indicator, patient urinary EVs were examined and found to have markedly higher levels of periostin than controls. In addition, immunohistochemical staining of a bladder cancer tissue microarray revealed that the presence of periostin in MIBC cells is correlated with worse prognosis. In conclusion, periostin is a component of bladder cancer cells associated with poor clinical outcome, and EVs can transfer oncogenic molecules such as periostin to affect the tumor environment and promote cancer progression. PMID:26981774

  8. [Features of elderly patients over 75 years old with gastric cancer and surgical strategy].

    PubMed

    Chen, Lin; Cui, Jianxin

    2016-05-25

    The new cases and mortality of gastric cancer in the population aged over 75 years account for 21% and 30% of the cases in the whole population respectively. These elderly patients with gastric cancer are characteristic of nonspecific clinical manifestations, high proportion of upper gastric carcinoma, larger tumor size, advanced TNM stage, concomitant diseases, poor body function and high risk of complications. Specialists should pay more attention to the diagnosis and treatment of these patients. Comprehensive and systemic assessment should be performed, and concomitant diseases should be treated. Accurate preoperative staging should be accessed by EUS and CT. Individualized treatment according to the principle of precise surgery and enhanced recovery after surgery (ERAS) should be performed as follows. For early gastric cancer with low risk of lymph node metastasis, endoscopic submucosal dissection(ESD) is recommended for expanded indications. For resectable advanced gastric cancer, "downsizing" surgery obtaining ≥4 cm incisal margin is recommended, which must be based on accurate preoperative stage. And gasless laproscopy is applicable for these patients. For unresectable advanced gastric cancer, conversion therapy is not the priority unless patients with high response rate. Palliative chemotherapy, immunotherapy and best supportive care should be applied in turn. ERAS techniques application in elderly patients with gastric cancer requires careful selection. PMID:27215511

  9. Tracking the Correlation Between CpG Island Methylator Phenotype and Other Molecular Features and Clinicopathological Features in Human Colorectal Cancers: A Systematic Review and Meta-Analysis

    PubMed Central

    Zong, Liang; Abe, Masanobu; Ji, Jiafu; Zhu, Wei-Guo; Yu, Duonan

    2016-01-01

    Objectives: The controversy of CpG island methylator phenotype (CIMP) in colorectal cancers (CRCs) persists, despite many studies that have been conducted on its correlation with molecular and clinicopathological features. To drive a more precise estimate of the strength of this postulated relationship, a meta-analysis was performed. Methods: A comprehensive search for studies reporting molecular and clinicopathological features of CRCs stratified by CIMP was performed within the PubMed, EMBASE, and Cochrane Library. CIMP was defined by either one of the three panels of gene-specific CIMP markers (Weisenberger panel, classic panel, or a mixture panel of the previous two) or the genome-wide DNA methylation profile. The associations of CIMP with outcome parameters were estimated using odds ratio (OR) or weighted mean difference (WMD) or hazard ratios (HRs) with 95% confidence interval (CI) for each study using a fixed effects or random effects model. Results: A total of 29 studies involving 9,393 CRC patients were included for analysis. We observed more BRAF mutations (OR 34.87; 95% CI, 22.49–54.06) and microsatellite instability (MSI) (OR 12.85 95% CI, 8.84–18.68) in CIMP-positive vs. -negative CRCs, whereas KRAS mutations were less frequent (OR 0.47; 95% CI, 0.30–0.75). Subgroup analysis showed that only the genome-wide methylation profile-defined CIMP subset encompassed all BRAF-mutated CRCs. As expected, CIMP-positive CRCs displayed significant associations with female (OR 0.64; 95% CI, 0.56–0.72), older age at diagnosis (WMD 2.77; 95% CI, 1.15–4.38), proximal location (OR 6.91; 95% CI, 5.17–9.23), mucinous histology (OR 3.81; 95% CI, 2.93–4.95), and poor differentiation (OR 4.22; 95% CI, 2.52–7.08). Although CIMP did not show a correlation with tumor stage (OR 1.10; 95% CI, 0.82–1.46), it was associated with shorter overall survival (HR 1.73; 95% CI, 1.27–2.37). Conclusions: The meta-analysis highlights that CIMP-positive CRCs take their own

  10. Utilizing spatial and spectral features of photoacoustic imaging for ovarian cancer detection and diagnosis

    NASA Astrophysics Data System (ADS)

    Li, Hai; Kumavor, Patrick; Salman Alqasemi, Umar; Zhu, Quing

    2015-01-01

    A composite set of ovarian tissue features extracted from photoacoustic spectral data, beam envelope, and co-registered ultrasound and photoacoustic images are used to characterize malignant and normal ovaries using logistic and support vector machine (SVM) classifiers. Normalized power spectra were calculated from the Fourier transform of the photoacoustic beamformed data, from which the spectral slopes and 0-MHz intercepts were extracted. Five features were extracted from the beam envelope and another 10 features were extracted from the photoacoustic images. These 17 features were ranked by their p-values from t-tests on which a filter type of feature selection method was used to determine the optimal feature number for final classification. A total of 169 samples from 19 ex vivo ovaries were randomly distributed into training and testing groups. Both classifiers achieved a minimum value of the mean misclassification error when the seven features with lowest p-values were selected. Using these seven features, the logistic and SVM classifiers obtained sensitivities of 96.39±3.35% and 97.82±2.26%, and specificities of 98.92±1.39% and 100%, respectively, for the training group. For the testing group, logistic and SVM classifiers achieved sensitivities of 92.71±3.55% and 92.64±3.27%, and specificities of 87.52±8.78% and 98.49±2.05%, respectively.

  11. Association between dynamic contrast enhanced MRI imaging features and WHO histopathological grade in patients with invasive ductal breast cancer

    PubMed Central

    HUANG, JUAN; YU, JIANQUN; PENG, YULAN

    2016-01-01

    The present study aimed to investigate the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and World Health Organization (WHO) histopathological grade in patients with invasive ductal breast cancer. A retrospective analysis on the results of DCE-MRI of 92 patients, who were diagnosed with invasive ductal breast cancer following surgery or biopsy, and these results were correlated with WHO histopathological grade. The statistical analysis demonstrated that the tumor size, shape and characteristics of early enhancement were associated with the WHO histopathological grade: The larger the lesion's long diameter, the higher the WHO histopathological grade; the WHO histopathological grades of round and oval masses were relatively lower, while those of lobulated and irregular masses were higher; and tumors with heterogeneous and ring-like enhancement exhibited higher WHO histopathological grades, while those of homogeneous enhancement were lower. The lesion's margin shape was not associated with the WHO histopathological grade. The present study demonstrates that features of DCE-MRI and WHO histopathological grade in patients with invasive ductal breast cancer are correlated, and these MRI features could be used to evaluate the biological behavior and prognosis of lesions. PMID:27123145

  12. MicroRNAs As Biomarkers For Clinical Features Of Lung Cancer

    PubMed Central

    Hubaux, Roland; Becker-Santos, Daiana D.; Enfield, Katey S. S.; Lam, Stephen; Lam, Wan L.; Martinez, Victor D.

    2013-01-01

    Each year about 1.4 million people die from lung cancer worldwide. Despite efforts in prevention, diagnosis and treatment, survival rate remains poor for this disease. This unfortunate situation is largely due to the fact that a high proportion of cases are diagnosed at advanced stages, highlighting the great need for identifying new biomarkers in order to improve early diagnosis and treatment. Recent studies on microRNAs have not only shed light on their involvement in tumor development and progression, but also suggested their potential utility as biomarkers for subtype diagnostics, staging and prediction of treatment response. This review article summarizes the impact of microRNAs on lung cancer biology, and highlights their role in the detection and classification of lung cancer as well as direct targets for drug development. PMID:25221729

  13. A standardised protocol for texture feature analysis of endoscopic images in gynaecological cancer

    PubMed Central

    Neofytou, Marios S; Tanos, Vasilis; Pattichis, Marios S; Pattichis, Constantinos S; Kyriacou, Efthyvoulos C; Koutsouris, Dimitris D

    2007-01-01

    Background In the development of tissue classification methods, classifiers rely on significant differences between texture features extracted from normal and abnormal regions. Yet, significant differences can arise due to variations in the image acquisition method. For endoscopic imaging of the endometrium, we propose a standardized image acquisition protocol to eliminate significant statistical differences due to variations in: (i) the distance from the tissue (panoramic vs close up), (ii) difference in viewing angles and (iii) color correction. Methods We investigate texture feature variability for a variety of targets encountered in clinical endoscopy. All images were captured at clinically optimum illumination and focus using 720 × 576 pixels and 24 bits color for: (i) a variety of testing targets from a color palette with a known color distribution, (ii) different viewing angles, (iv) two different distances from a calf endometrial and from a chicken cavity. Also, human images from the endometrium were captured and analysed. For texture feature analysis, three different sets were considered: (i) Statistical Features (SF), (ii) Spatial Gray Level Dependence Matrices (SGLDM), and (iii) Gray Level Difference Statistics (GLDS). All images were gamma corrected and the extracted texture feature values were compared against the texture feature values extracted from the uncorrected images. Statistical tests were applied to compare images from different viewing conditions so as to determine any significant differences. Results For the proposed acquisition procedure, results indicate that there is no significant difference in texture features between the panoramic and close up views and between angles. For a calibrated target image, gamma correction provided an acquired image that was a significantly better approximation to the original target image. In turn, this implies that the texture features extracted from the corrected images provided for better approximations

  14. Molecular Features of Triple Negative Breast Cancer: Microarray Evidence and Further Integrated Analysis

    PubMed Central

    Chen, Weicai; Wu, Huisheng; Yuan, Zishan; Wang, Kun; Li, Guojin; Sun, Jie; Yu, Limin

    2015-01-01

    Purpose Breast cancer is a heterogeneous disease usually including four molecular subtypes such as luminal A, luminal B, HER2-enriched, and triple-negative breast cancer (TNBC). TNBC is more aggressive than other breast cancer subtypes. Despite major advances in ER-positive or HER2-amplified breast cancer, there is no targeted agent currently available for TNBC, so it is urgent to identify new potential therapeutic targets for TNBC. Methods We first used microarray analysis to compare gene expression profiling between TNBC and non-TNBC. Furthermore an integrated analysis was conducted based on our own and published data, leading to more robust, reproducible and accurate predictions. Additionally, we performed qRT-PCR in breast cancer cell lines to verify the findings in integrated analysis. Results After searching Gene Expression Omnibus database (GEO), two microarray studies were obtained according to the inclusion criteria. The integrated analysis was conducted, including 30 samples of TNBC and 77 samples of non-TNBC. 556 genes were found to be consistently differentially expressed (344 up-regulated genes and 212 down-regulated genes in TNBC). Functional annotation for these differentially expressed genes (DEGs) showed that the most significantly enriched Gene Ontology (GO) term for molecular functions was protein binding (GO: 0005515, P = 6.09E-21), while that for biological processes was signal transduction (GO: 0007165, P = 9.46E-08), and that for cellular component was cytoplasm (GO: 0005737, P = 2.09E-21). The most significant pathway was Pathways in cancer (P = 6.54E-05) based on Kyoto Encyclopedia of Genes and Genomes (KEGG). DUSP1 (Degree = 21), MYEOV2 (Degree = 15) and UQCRQ (Degree = 14) were identified as the significant hub proteins in the protein-protein interaction (PPI) network. Five genes were selected to perform qRT-PCR in seven breast cancer cell lines, and qRT-PCR results showed that the expression pattern of selected genes in TNBC lines and

  15. Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

    PubMed

    Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C; DeAngelis, Lisa M; Fenstermaker, Robert A; Friedman, Allan; Gilbert, Mark R; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Newton, Herbert B; Raizer, Jeffrey J; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tran, David; Tran, Nam; Vrionis, Frank D; Wen, Patrick Yung; McMillian, Nicole R; Ho, Maria

    2014-11-01

    The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. PMID:25361798

  16. The effect of HMGB1 on the clinicopathological and prognostic features of non-small cell lung cancer

    PubMed Central

    Yin, Bingjiao

    2016-01-01

    Several studies have assessed the diagnostic and prognostic values of high mobility group protein box 1 (HMGB1) expression in non-small cell lung cancer (NSCLC), but these results remain controversial. The purpose of this study was to perform a meta-analysis of the gene microarray analyses of datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to evaluate the association of HMGB1 expression with the clinicopathological and prognostic features of patients with NSCLC. Furthermore, we investigated the underlying molecular mechanisms by bioinformatics analysis. Twenty relevant articles involving 2651 patients were included in this meta-analysis; the HMGB1 expression in NSCLC tissues was significantly higher than that in the healthy non-cancer control tissues. We also found an indication by microarray analysis and meta-analysis that HMGB1 expression was associated with the cancer TNM Staging System. In terms of prognostic features, a survival analysis from KM-Plotter tool revealed that the high HMGB1 expression group exhibited poorer survival in lung adenocarcinoma (ADC) and overall NSCLC patients. The survival and disease-free analyses from TCGA datasets also showed that HMGB1 mainly affected the development of patients with ADC. Therefore, we focused on how HMGB1 affected the prognosis and development of ADC using bioinformatics analyses and detected that the mitogen-activated protein kinases (MAPK), apoptosis and cell cycle signaling pathways were the key pathways that varied during HMGB1 up-regulation in ADC. Moreover, various genes such as PLCG2, the phosphatidylinositol-4, 5-bisphosphate 3-kinase superfamily (PI3Ks), protein kinase C (PKC) and DGKZ were selected as hub genes in the gene regulatory network. Our results indicated that HMGB1 is a potential biomarker to predict progression and survival of NSCLC, especially of ADC types. PMID:26840258

  17. Expression of WASF3 in patients with non-small cell lung cancer: Correlation with clinicopathological features and prognosis

    PubMed Central

    WU, JIE; WANG, GUANG-CHUAN; CHEN, XUE-JUN; XUE, ZHAN-RUI

    2014-01-01

    Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis in different cancer cell types, and has been demonstrated to possess prognostic value in various types of human cancer. However, to the best of our knowledge, the expression profile of WASF3 and its correlations with the clinicopathological features of non-small cell lung cancer (NSCLC) have not yet been described. In the present study, the mRNA expression levels of WASF3, in 38 NSCLC patients and in matched normal tissues, were assessed using quantitative polymerase chain reaction and the protein expression in 96 specimens was analyzed using immunohistochemistry. In addition, patient survival data were collected retrospectively and the association between WASF3 expression and five-year overall survival was evaluated. The results demonstrated that the mRNA expression level of WASF3 in cancer tissues was markedly (approximately five times) higher compared with that of the normal tissues. The WASF3 protein expression profile in NSCLC was consistent with the mRNA expression result, which also correlated with the histological subtype and tumor stage. Furthermore, patients with WASF3-positive expression were associated with a poorer prognosis compared with those exhibiting WASF3-negative expression, and the five-year survival rate was 20.8 and 46.5%, respectively (Kaplan-Meier; log-rank, P=0.004). In the multivariate analysis, which included other clinicopathological features, WASF3 emerged as an independent prognostic factor (relative risk, 0.463; 95% CI, 0.271–0.792). These results indicate that WASF3 may be critical in the pathogenesis of NSCLC, in addition to being a valuable prognostic factor for NSCLC patients. Further investigations are required to identify the efficacy of WASF3 as a potential therapeutic target for the treatment of NSCLC. PMID:25120680

  18. Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers

    PubMed Central

    Lips, E H; Mulder, L; Oonk, A; van der Kolk, L E; Hogervorst, F B L; Imholz, A L T; Wesseling, J; Rodenhuis, S; Nederlof, P M

    2013-01-01

    Background: BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness characteristics frequencies in a large cohort of triple-negative breast cancers (TNBCs). Methods: As a measure of BRCAness, we determined a specific BRCA1-like pattern by array Comparative Genomic Hybridisation (aCGH), and BRCA1 promoter methylation in 377 TNBCs, obtained from 3 different patient cohorts. Clinicopathological data were available for all tumours, BRCA1-germline mutation status and chemotherapy response data were available for a subset. Results: Of the tumours, 66–69% had a BRCA1-like aCGH profile and 27–37% showed BRCA1 promoter methylation. BRCA1-germline mutations and BRCA1 promoter methylation were mutually exclusive events (P=1 × 10−5). BRCAness was associated with younger age and grade 3 tumours. Chemotherapy response was significantly higher in BRCA1-mutated tumours, but not in tumours with BRCAness (63% (12 out of 19) vs 35% (18 out of 52) pathological complete remission rate, respectively). Conclusion: The majority of the TNBCs show BRCAness, and those tumours share clinicopathological characteristics with BRCA1-mutated tumours. A better characterisation of TNBC and the presence of BRCAness could have consequences for both hereditary breast cancer screening and the treatment of these tumours. PMID:23558900

  19. Feature Selection and Cancer Classification via Sparse Logistic Regression with the Hybrid L1/2 +2 Regularization

    PubMed Central

    Huang, Hai-Hui; Liu, Xiao-Ying; Liang, Yong

    2016-01-01

    Cancer classification and feature (gene) selection plays an important role in knowledge discovery in genomic data. Although logistic regression is one of the most popular classification methods, it does not induce feature selection. In this paper, we presented a new hybrid L1/2 +2 regularization (HLR) function, a linear combination of L1/2 and L2 penalties, to select the relevant gene in the logistic regression. The HLR approach inherits some fascinating characteristics from L1/2 (sparsity) and L2 (grouping effect where highly correlated variables are in or out a model together) penalties. We also proposed a novel univariate HLR thresholding approach to update the estimated coefficients and developed the coordinate descent algorithm for the HLR penalized logistic regression model. The empirical results and simulations indicate that the proposed method is highly competitive amongst several state-of-the-art methods. PMID:27136190

  20. Feature Selection and Classification of MAQC-II Breast Cancer and Multiple Myeloma Microarray Gene Expression Data

    PubMed Central

    Liu, Qingzhong; Sung, Andrew H.; Chen, Zhongxue; Liu, Jianzhong; Huang, Xudong; Deng, Youping

    2009-01-01

    Microarray data has a high dimension of variables but available datasets usually have only a small number of samples, thereby making the study of such datasets interesting and challenging. In the task of analyzing microarray data for the purpose of, e.g., predicting gene-disease association, feature selection is very important because it provides a way to handle the high dimensionality by exploiting information redundancy induced by associations among genetic markers. Judicious feature selection in microarray data analysis can result in significant reduction of cost while maintaining or improving the classification or prediction accuracy of learning machines that are employed to sort out the datasets. In this paper, we propose a gene selection method called Recursive Feature Addition (RFA), which combines supervised learning and statistical similarity measures. We compare our method with the following gene selection methods: Support Vector Machine Recursive Feature Elimination (SVMRFE)Leave-One-Out Calculation Sequential Forward Selection (LOOCSFS)Gradient based Leave-one-out Gene Selection (GLGS) To evaluate the performance of these gene selection methods, we employ several popular learning classifiers on the MicroArray Quality Control phase II on predictive modeling (MAQC-II) breast cancer dataset and the MAQC-II multiple myeloma dataset. Experimental results show that gene selection is strictly paired with learning classifier. Overall, our approach outperforms other compared methods. The biological functional analysis based on the MAQC-II breast cancer dataset convinced us to apply our method for phenotype prediction. Additionally, learning classifiers also play important roles in the classification of microarray data and our experimental results indicate that the Nearest Mean Scale Classifier (NMSC) is a good choice due to its prediction reliability and its stability across the three performance measurements: Testing accuracy, MCC values, and AUC errors. PMID

  1. Clinical features and outcomes of patients with lung cancer as well as combined pulmonary fibrosis and emphysema

    PubMed Central

    Otsuka, Hajime; Sugino, Keishi; Hata, Yoshinobu; Makino, Takashi; Koezuka, Satoshi; Isobe, Kazutoshi; Tochigi, Naobumi; Shibuya, Kazutoshi; Homma, Sakae; Iyoda, Akira

    2016-01-01

    The syndrome of combined pulmonary fibrosis and emphysema (CPFE) has been characterized by severely impaired gas exchange and poor survival. However, the clinical features of patients with lung cancer plus CPFE have remained elusive. The present study performed a retrospective analysis to examine the clinical characteristics and outcome of surgically resected patients with lung cancer plus CPFE. Among 831 patients with primary lung cancer who underwent surgical resection, 23 patients (2.8%) were diagnosed with CPFE and 9 patients (1.1%) with solely idiopathic pulmonary fibrosis (IPF). Thirty-five patients were stratified as the solely emphysema group with adjustment of the pathological stage. The clinicopathological characteristics of patients in the CPFE group and their outcomes were evaluated and compared with those with the solely IPF or solely emphysema groups. Within the CPFE group, no significant differences in survival between patients with post-operative acute exacerbation (AE; n=3) and those without AE (n=20) were noted; however, in the solely IPF group, patients with post-operative AE (n=4) had a significantly shorter survival than those without AE (n=5; P=0.022). The 5-year survival rate of patients in the CPFE, solely IPF and solely emphysema groups was 22, 22 and 58%, respectively. Furthermore, the CPFE and solely IPF groups showed a significantly shorter survival than the solely emphysema group (P=0.001 and 0.011, respectively). In conclusion, surgically resected lung cancer patients with CPFE had poor survival, which was, in contrast to that of lung cancer patients with solely IPF, not affected by AE. PMID:27602222

  2. Thermography based breast cancer detection using texture features and minimum variance quantization

    PubMed Central

    Milosevic, Marina; Jankovic, Dragan; Peulic, Aleksandar

    2014-01-01

    In this paper, we present a system based on feature extraction techniques and image segmentation techniques for detecting and diagnosing abnormal patterns in breast thermograms. The proposed system consists of three major steps: feature extraction, classification into normal and abnormal pattern and segmentation of abnormal pattern. Computed features based on gray-level co-occurrence matrices are used to evaluate the effectiveness of textural information possessed by mass regions. A total of 20 GLCM features are extracted from thermograms. The ability of feature set in differentiating abnormal from normal tissue is investigated using a Support Vector Machine classifier, Naive Bayes classifier and K-Nearest Neighbor classifier. To evaluate the classification performance, five-fold cross validation method and Receiver operating characteristic analysis was performed. The verification results show that the proposed algorithm gives the best classification results using K-Nearest Neighbor classifier and a accuracy of 92.5%. Image segmentation techniques can play an important role to segment and extract suspected hot regions of interests in the breast infrared images. Three image segmentation techniques: minimum variance quantization, dilation of image and erosion of image are discussed. The hottest regions of thermal breast images are extracted and compared to the original images. According to the results, the proposed method has potential to extract almost exact shape of tumors. PMID:26417334

  3. Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features

    PubMed Central

    Dittmar, Yves; Settmacher, Utz

    2015-01-01

    Gastric cancer is one of the most common malignancies worldwide. The overall prognosis remains poor over the last decades even though improvements in surgical outcomes have been achieved. A better understanding of the molecular biology of gastric cancer and detection of eligible molecular targets might be of central interest to further improve clinical outcome. With this intention, first steps have been made in the research of growth factor signaling. Regarding morphogens, cell cycle and nuclear factor-κB signaling, a remarkable count of target-specific agents have been developed, nevertheless the transfer into the field of clinical routine is still at the beginning. The potential utility of epigenetic targets and the further evaluation of microRNA signaling seem to have potential for the development of novel treatment strategies in the future. PMID:26600929

  4. FDG and (82)Rb PET/MRI features of brain metastasis of breast cancer.

    PubMed

    Lu, Yang

    2015-06-01

    A 64-year-old woman with stage IV breast cancer underwent an FDG and Rb PET brain studies. The PET brain images were fused with MRI brain T1 post-contrast images. The known enhancing left superoposterior frontal brain metastasis is positive on both FDG Rb PET/MRI images. The Rb PET/MRI showed better target-to-noise ratio, but showed nonspecific uptake in the superior sagittal sinus. PMID:25674864

  5. Use of genetic algorithms for computer-aided diagnosis of breast cancers from image features

    NASA Astrophysics Data System (ADS)

    Floyd, Carey E., Jr.; Tourassi, Georgia D.; Baker, Jay A.

    1996-04-01

    In this investigation we explore genetic algorithms as a technique to train the weights in a feed forward neural network designed to predict breast cancer based on mammographic findings and patient history. Mammograms were obtained from 206 patients who obtained breast biopsies. Mammographic findings were recorded by radiologists for each patient. In addition, the outcome of the biopsy was recorded. Of the 206 cases, 73 were malignant while 133 were benign at the time of biopsy. A genetic algorithm (GA) was developed to adjust the weights of an artificial neural network (ANN) so that the ANN would output the outcome of the biopsy when the mammographic findings were given as inputs. The GA is a technique for function optimization that reflects biological genetic evolution. The ANN was a fully connected feed- forward network using a sigmoid activation with 11 inputs, one hidden layer with 10 nodes, and one output node (benign/malignant). The GA approach allows much flexibility in selecting the function to be optimized. In this work both mean-squared error (MSE) and receiver operating characteristic (ROC) curve area (Az) were explored as optimization criteria. The system was trained using a bootstrap sampling. Optimizing for the two criteria result in different solutions. The 'best' solution was obtained by minimizing a linear combination of MSE and (1-Az). ROC areas were 0.82 plus or minus 0.07, somewhat less than those obtained using backpropagation for ANN training: 0.90 plus or minus 0.05. This is the first description of a genetic algorithm for breast cancer diagnosis. The novel advantage of this technique is the ability to optimize the system for maximizing ROC area rather than minimizing mean squared error. A new technique for computer-aided diagnosis of breast cancer has been explored. The flexibility of the GA approach allows optimization of cost functions that have relevance to breast cancer prediction.

  6. Gene Expression Patterns Related to Vascular Invasion and Aggressive Features in Endometrial Cancer

    PubMed Central

    Mannelqvist, Monica; Stefansson, Ingunn M.; Bredholt, Geir; Hellem Bø, Trond; Øyan, Anne M.; Jonassen, Inge; Kalland, Karl-Henning; Salvesen, Helga B.; Akslen, Lars A.

    2011-01-01

    The presence of tumor cells entering vascular channels is a prognostic marker for many cancers, including endometrial carcinoma. Vascular invasion is considered to be an early step in the metastatic process and important for the progress of malignant tumors. Here, we investigated the gene expression patterns related to vascular involvement in 57 primary endometrial cancers, using DNA microarray and quantitative PCR techniques. A vascular invasion signature of 18 genes was significantly associated with patient survival and clinicopathological phenotype. Vascular involvement was also related to gene sets for epithelial-mesenchymal transition, wound response, endothelial cells, and vascular endothelial growth factor (VEGF) activity. With immunohistochemical validation, both collagen 8 and matrix metalloproteinase 3 (MMP3) were associated with vascular invasion, whereas ANGPTL4 and IL-8 were associated with patient survival. Our findings indicate that vascular involvement within primary tumors is associated with gene expression profiles related to angiogenesis and epithelial-mesenchymal transition. These data could contribute to an improved understanding of potential targets for metastatic spread and may provide clinically important information for better management of endometrial cancer. PMID:21281818

  7. Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain.

    PubMed

    Doré-Savard, Louis; Otis, Valérie; Belleville, Karine; Lemire, Myriam; Archambault, Mélanie; Tremblay, Luc; Beaudoin, Jean-François; Beaudet, Nicolas; Lecomte, Roger; Lepage, Martin; Gendron, Louis; Sarret, Philippe

    2010-01-01

    Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT). Bone metastases were visualized as early as day 8 by MRI (T(1)-Gd-DTPA) before pain detection. PET (Na(18)F) co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining). Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal) and ATF3 (DRG) neuronal activation, sustained by astrocyte (GFAP) and microglia (Iba1) reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future. PMID:21048940

  8. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer.

    PubMed

    Viljoen, Katie S; Dakshinamurthy, Amirtha; Goldberg, Paul; Blackburn, Jonathan M

    2015-01-01

    Various studies have presented clinical or in vitro evidence linking bacteria to colorectal cancer, but these bacteria have not previously been concurrently quantified by qPCR in a single cohort. We quantify these bacteria (Fusobacterium spp., Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Enteropathogenic Escherichia coli (EPEC), and afaC- or pks-positive E. coli) in paired tumour and normal tissue samples from 55 colorectal cancer patients. We further investigate the relationship between a) the presence and b) the level of colonisation of each bacterial species with site and stage of disease, age, gender, ethnicity and MSI-status. With the exception of S. gallolyticus, we detected all bacteria profiled here in both tumour and normal samples at varying frequencies. ETBF (FDR = 0.001 and 0.002 for normal and tumour samples) and afaC-positive E. coli (FDR = 0.03, normal samples) were significantly enriched in the colon compared to the rectum. ETBF (FDR = 0.04 and 0.002 for normal and tumour samples, respectively) and Fusobacterium spp. (FDR = 0.03 tumour samples) levels were significantly higher in late stage (III/IV) colorectal cancers. Fusobacterium was by far the most common bacteria detected, occurring in 82% and 81% of paired tumour and normal samples. Fusobacterium was also the only bacterium that was significantly higher in tumour compared to normal samples (p = 6e-5). We also identified significant associations between high-level colonisation by Fusobacterium and MSI-H (FDR = 0.05), age (FDR = 0.03) or pks-positive E. coli (FDR = 0.01). Furthermore, we exclusively identified atypical EPEC in our cohort, which has not been previously reported in association with colorectal cancer. By quantifying colorectal cancer-associated bacteria across a single cohort, we uncovered inter- and intra-individual patterns of colonization not previously recognized, as well as important associations with clinicopathological

  9. Primary hepatic cancers with multiple pathologic features in a patient with hepatitis C: report of a case.

    PubMed

    Oshima, Go; Shinoda, Masahiro; Tanabe, Minoru; Masugi, Yohei; Ueno, Akihisa; Takano, Kiminori; Kitago, Minoru; Itano, Osamu; Kawachi, Shigeyuki; Ohara, Kentaro; Oda, Masaya; Tanimoto, Akihiro; Sakamaoto, Michiie; Kitagawa, Yuko

    2012-01-01

    We report a case of multiple primary hepatic cancers exhibiting different pathologic features coexisting in a patient with chronic hepatitis C. Computed tomography showed 2 tumors in segment 8, 20 mm (S8-A) and 5 mm (S8-B) in diameter, and a 10-mm tumor in segment 6 (S6). Based on the images, the S8-A lesion was diagnosed as cholangiocellular carcinoma or combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC). The other 2 tumors were diagnosed as HCC. The patient underwent partial resections of segments 6 and 8. We found 2 more tumors (S8-C was 6 mm in diameter and S8-D was 4 mm) in the resected segment 8 specimen. Histopathologic examination revealed that the S8-A and S8-C tumors were combined HCC-CC, the S8-B and S6 lesions were scirrhous HCC, and the S8-D tumor was an early HCC. This is a very rare case in which different hepatic cancers with multiple pathologic features coexisted. PMID:23101996

  10. Metabolic Determinants and Anthropometric Indicators Impact Clinical-pathological Features in Epithelial Ovarian Cancer Patients

    PubMed Central

    Vici, Patrizia; Pizzuti, Laura; Di Lauro, Luigi; Conti, Laura; Mandoj, Chiara; Antenucci, Anna; Digiesi, Giovanna; Sergi, Domenico; Amodio, Antonella; Marchetti, Paolo; Sperati, Francesca; Valle, Mario; Garofalo, Alfredo; Vizza, Enrico; Corrado, Giacomo; Vincenzoni, Cristina; Tomao, Federica; Kayal, Ramy; Marsella, Annalise; Carosi, Mariantonia; Antoniani, Barbara; Giordano, Antonio; Maugeri-Saccà, Marcello; Barba, Maddalena

    2016-01-01

    Background: Over the last twenty years, the efforts of the scientific community devoted to the comprehension and treatment of ovarian cancer have remained poorly remunerative, with the case-fatality ratio of this disease remaining disappointedly high. Limited knowledge of the basic principles regulating ovarian carcinogenesis and factors impacting the course of disease may significantly impair our ability to intervene in early stages and lessen our expectations in terms of treatment outcomes. In the present study, we sought to assess whether metabolic factors and anthropometric indicators, i.e., pre-treatment fasting glucose and body mass index, are associated with renown cancer related prognostic factors such as tumour stage and grade at diagnosis. Materials and Methods: Study participants were 147 women diagnosed with epithelial ovarian cancer and treated with platinum based regimens and/or surgery at the Regina Elena National Cancer Institute of Rome, Italy. Glucose levels were assessed at the institutional laboratories on venous blood collected in overnight fasting conditions and prior to any therapeutic procedure. Stage was coded according to the FIGO staging system based on the results of the diagnostic workup, while tumour grade was locally assessed by an expert pathologist. Participants' characteristics were descriptively analyzed for the overall study population and in a subgroup of 70 patients for whom data on body mass index (BMI) were available. FIGO stage and grade were compared by categories of pre-treatment fasting glucose defined upon the median value, i.e., 89 mg/dl. The association of interest was tested in regression models including BMI. Results: For the overall study population, patients in the lowest category of fasting glucose were significantly more likely to exhibit a FIGO stage III-IV at diagnosis compared with their counterpart in the highest glucose category (81.3 vs 66.7%, p: 0.021). Subgroup analysis in 70 patients with BMI data

  11. Investigation of Endoscopic and Pathologic Features for Safe Endoscopic Treatment of Superficial Spreading Early Gastric Cancer.

    PubMed

    Lee, Kyong Joo; Pak, Kyung Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong Bai; Lee, Yong Chan; Kim, Hee Man; Lee, Sang Kil

    2016-04-01

    Superficial spreading early gastric cancer (EGC) is a rare disease that is treated mainly by surgery. There are few studies on the safety of endoscopic treatment for patients with superficial spreading EGC. The aims of this study were to (1) investigate the risk of lymph node metastasis of superficial spreading EGC and (2) investigate the potential criteria for endoscopic treatment of superficial spreading EGC using surgical specimens.Between 2000 and 2010, patients who received curative surgery of R0 resection at Severance Hospital (Seoul, Korea) for early gastric cancer were enrolled. The superficial spreading EGC was defined as cancer in which the longest tumor length was ≥6 cm. The medical records of the patients were reviewed retrospectively.Of the 3813 patients with EGC, 140 (3.7%) had lesions ≥ 6 cm, whereas 3673 (96.3%) had lesions < 6 cm. Patients with superficial spreading EGC had higher rates of submucosal cancer (59.3% vs 45.7%, P = 0.002), lymphovascular invasion (18.6% vs 9.8%, P < 0.001), and lymph node metastasis (15.7% vs 10.1%, P = 0.033) compared with patients with common EGC (< 6 cm). Multivariate analysis revealed that a tumor ≥ 6 cm was not strongly associated with lymph node metastasis in EGC, as compared with a tumor < 6 cm, but submucosal invasion and lymphovascular invasion were strongly associated with lymph node metastasis in EGC. In mucosal cancer without ulcers, tumors ≥ 6 cm had a higher rate of lymph node metastasis than tumors ≤ 2 cm; however, this trend was not significant (7.7% vs 5.3%, P = 0.455).Superficial spreading EGC was not associated with an increased risk of lymph node metastasis compared with common EGC. We suggest that differentiated intramucosal superficial spreading EGC without ulceration can be treated by endoscopic submucosal dissection. PMID:27057862

  12. Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system

    PubMed Central

    Liu, Li-Yu D; Chang, Li-Yun; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Lin, Yi-Shing; Jeng, Meei-Huey; Roth, Don A; Chang, King-Jen; Hsieh, Fon-Jou

    2014-01-01

    The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model. PMID:24526833

  13. Identification of hub subnetwork based on topological features of genes in breast cancer

    PubMed Central

    ZHUANG, DA-YONG; JIANG, LI; HE, QING-QING; ZHOU, PENG; YUE, TAO

    2015-01-01

    The aim of this study was to provide functional insight into the identification of hub subnetworks by aggregating the behavior of genes connected in a protein-protein interaction (PPI) network. We applied a protein network-based approach to identify subnetworks which may provide new insight into the functions of pathways involved in breast cancer rather than individual genes. Five groups of breast cancer data were downloaded and analyzed from the Gene Expression Omnibus (GEO) database of high-throughput gene expression data to identify gene signatures using the genome-wide global significance (GWGS) method. A PPI network was constructed using Cytoscape and clusters that focused on highly connected nodes were obtained using the molecular complex detection (MCODE) clustering algorithm. Pathway analysis was performed to assess the functional relevance of selected gene signatures based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Topological centrality was used to characterize the biological importance of gene signatures, pathways and clusters. The results revealed that, cluster1, as well as the cell cycle and oocyte meiosis pathways were significant subnetworks in the analysis of degree and other centralities, in which hub nodes mostly distributed. The most important hub nodes, with top ranked centrality, were also similar with the common genes from the above three subnetwork intersections, which was viewed as a hub subnetwork with more reproducible than individual critical genes selected without network information. This hub subnetwork attributed to the same biological process which was essential in the function of cell growth and death. This increased the accuracy of identifying gene interactions that took place within the same functional process and was potentially useful for the development of biomarkers and networks for breast cancer. PMID:25573623

  14. Diagnosis of breast cancer recurrence using a microfluidic device featuring tethered cationic polymers

    NASA Astrophysics Data System (ADS)

    Chen, Jem-Kun; Bai, Bing-Jun; Chang, Feng-Chih

    2011-07-01

    In this study, we grafted pH-responsive poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) onto a Si substrate as the medium in a microfluidic device to detect breast cancer recurrence DNA (bcrDNA584) and a control human genomic DNA (hgDNA528) at extremely low concentrations (down to 0.15 ng/μl). The quantities of these two DNAs obtained through the capture and release from tethered PDMAEMA brushes under pH tuning conditions were sufficient for them to be amplified recognizably, suggesting that this approach could be used in miniaturized lab-on-a-chip cartridges for rapid disease diagnosis.

  15. TU-C-17A-10: Patient Features Based Dosimetric Pareto Front Prediction In Esophagus Cancer Radiotherapy

    SciTech Connect

    Wang, J; Zhao, K; Peng, J; Hu, W; Jin, X

    2014-06-15

    Purpose: The purpose of this study is to study the feasibility of the dosimetric pareto front (PF) prediction based on patient anatomic and dosimetric parameters for esophagus cancer patients. Methods: Sixty esophagus patients in our institution were enrolled in this study. A total 2920 IMRT plans were created to generated PF for each patient. On average, each patient had 48 plans. The anatomic and dosimetric features were extracted from those plans. The mean lung dose (MLD), mean heart dose (MHD), spinal cord max dose and PTV homogeneous index (PTVHI) were recorded for each plan. The principal component analysis (PCA) was used to extract overlap volume histogram (OVH) features between PTV and other critical organs. The full dataset was separated into two parts include the training dataset and the validation dataset. The prediction outcomes were the MHD and MLD for the current study. The spearman rank correlation coefficient was used to evaluate the correlation between the anatomical features and dosimetric features. The PF was fit by the the stepwise multiple regression method. The cross-validation method was used to evaluation the model. Results: The mean prediction error of the MHD was 465 cGy with 100 repetitions. The most correlated factors were the first principal components of the OVH between heart and PTV, and the overlap between heart and PTV in Z-axis. The mean prediction error of the MLD was 195 cGy. The most correlated factors were the first principal components of the OVH between lung and PTV, and the overlap between lung and PTV in Z-axis. Conclusion: It is feasible to use patients anatomic and dosimetric features to generate a predicted PF. Additional samples and further studies were required to get a better prediction model.

  16. Association between bilateral asymmetry of kinetic features computed from the DCE-MRI images and breast cancer

    NASA Astrophysics Data System (ADS)

    Yang, Qian; Li, Lihua; Zhang, Juan; Zhang, Chengjie; Zheng, Bin

    2013-03-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast yields high sensitivity but relatively lower specificity. To improve diagnostic accuracy of DCE-MRI, we investigated the association between bilateral asymmetry of kinetic features computed from the left and right breasts and breast cancer detection with the hypothesis that due to the growth of angiogenesis associated with malignant lesions, the average dynamic contrast enhancement computed from the breasts depicting malignant lesions should be higher than negative or benign breasts. To test this hypothesis, we assembled a database involving 130 DCE-MRI examinations including 81 malignant and 49 benign cases. We developed a computerized scheme that automatically segments breast areas depicted on MR images and computes kinetic features related to the bilateral asymmetry of contrast enhancement ratio between two breasts. An artificial neural network (ANN) was then used to classify between malignant and benign cases. To identify the optimal approach to compute the bilateral kinetic feature asymmetry, we tested 4 different thresholds to select the enhanced pixels (voxels) from DCE-MRI images and compute the kinetic features. Using the optimal threshold, the ANN had a classification performance measured by the area under the ROC curve of AUC=0.79+/-0.04. The positive and negative predictive values were 0.75 and 0.67, respectively. The study suggested that the bilateral asymmetry of kinetic features or contrast enhancement of breast background tissue could provide valuable supplementary information to distinguish between the malignant and benign cases, which can be fused into existing computer-aided detection schemes to improve classification performance.

  17. In vivo relevant mixed urolithins and ellagic acid inhibit phenotypic and molecular colon cancer stem cell features: A new potentiality for ellagitannin metabolites against cancer.

    PubMed

    Núñez-Sánchez, María Ángeles; Karmokar, Ankur; González-Sarrías, Antonio; García-Villalba, Rocío; Tomás-Barberán, Francisco A; García-Conesa, María Teresa; Brown, Karen; Espín, Juan Carlos

    2016-06-01

    Colon cancer stem cells (CSCs) offer a novel paradigm for colorectal cancer (CRC) treatment and dietary polyphenols may contribute to battle these cells. Specifically, polyphenol-derived colon metabolites have the potential to interact with and affect colon CSCs. We herein report the effects against colon CSCs of two mixtures of ellagitannin (ET) metabolites, ellagic acid (EA) and the gut microbiota-derived urolithins (Uro) at concentrations detected in the human colon tissues following the intake of ET-containing products (pomegranate, walnuts). These mixtures reduce phenotypic and molecular features in two models of colon CSCs: Caco-2 cells and primary tumour cells from a patient with CRC. The mixture containing mostly Uro-A (85% Uro-A, 10% Uro-C, 5% EA) was most effective at inhibiting the number and size of colonospheres and aldehyde dehydrogenase activity (ALDH, a marker of chemoresistance) whereas the mixture containing less Uro-A but IsoUro-A and Uro-B (30% Uro-A, 50% IsoUro-A, 10% Uro-B, 5% Uro-C, 5% EA) had some effects on the number and size of colonospheres but not on ALDH. These data support a role for polyphenols metabolites in the control of colon cancer chemoresistance and relapse and encourage the research on the effects of polyphenols against CSCs. PMID:26995228

  18. Signet ring cell histology is associated with unique clinical features but does not affect gastric cancer survival.

    PubMed

    Theuer, C P; Nastanski, F; Brewster, W R; Butler, J A; Anton-Culver, H

    1999-10-01

    Signet ring cell histology is found in 3 to 39 per cent of gastric cancer cases and has been reported to be a feature of poor prognosis, although this issue has not been rigorously examined. The objective of this study was to determine those demographic and clinical variables associated with signet ring cell histology and to determine the effect of signet ring cell histology on survival using multivariate analyses. We studied a historical cohort of consecutive cases of gastric cancer reported to the population-based California Cancer Registries of Orange, San Diego, and Imperial Counties from 1984 through 1994. Factors associated with signet ring cell histology were assessed using chi2 and logistic regression. Life tables were constructed to assess unadjusted survival and survival differences in patient subgroups. Multivariate survival was determined using a Cox proportional hazards model. Of 3020 patients, 464 (15%) had signet ring cell histology. Patients with signet ring cell histology were more likely to be younger than 50 years (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.6-3.5), less likely to be male (OR = 0.49; 95% CI = 0.37-0.66), and more likely to have tumors of the distal stomach (OR = 2.0; 95% CI = 1.4-3.0). Signet ring cell histology did not adversely affect unadjusted overall survival, race-stratified survival, or stage-stratified survival. Multivariate analysis indicated that patients with signet ring cell histology had an insignificant increased risk of dying (relative risk = 1.027; P>0.10) in comparison with patients without signet ring cell histology. Patients with signet ring cell histology were more likely to be young women and to have tumors of the distal stomach. Signet ring cell histology did not impact survival in our group of largely advanced gastric cancer cases. PMID:10515534

  19. Breast cancer mitosis detection in histopathological images with spatial feature extraction

    NASA Astrophysics Data System (ADS)

    Albayrak, Abdülkadir; Bilgin, Gökhan

    2013-12-01

    In this work, cellular mitosis detection in histopathological images has been investigated. Mitosis detection is very expensive and time consuming process. Development of digital imaging in pathology has enabled reasonable and effective solution to this problem. Segmentation of digital images provides easier analysis of cell structures in histopathological data. To differentiate normal and mitotic cells in histopathological images, feature extraction step is very crucial step for the system accuracy. A mitotic cell has more distinctive textural dissimilarities than the other normal cells. Hence, it is important to incorporate spatial information in feature extraction or in post-processing steps. As a main part of this study, Haralick texture descriptor has been proposed with different spatial window sizes in RGB and La*b* color spaces. So, spatial dependencies of normal and mitotic cellular pixels can be evaluated within different pixel neighborhoods. Extracted features are compared with various sample sizes by Support Vector Machines using k-fold cross validation method. According to the represented results, it has been shown that separation accuracy on mitotic and non-mitotic cellular pixels gets better with the increasing size of spatial window.

  20. Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell features and sensitizes cells to radiotherapy

    PubMed Central

    Zhao, Xiaohui; Zhou, Yu; Zeng, Bing; Yu, Min; Zhou, Quanbo; Lin, Qing; Gao, Wenchao; Ye, Huilin; Zhou, Jiajia; Li, Zhihua; Liu, Yimin; Chen, Rufu

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) cells utilize a novel non-canonical pathway of glutamine metabolism that is essential for tumor growth and redox balance. Inhibition of this metabolic pathway in PDAC can potentially synergize with therapies that increase intracellular reactive oxygen species (ROS) such as radiation. Here, we evaluated the dependence of pancreatic cancer stem cells (PCSCs) on this non-canonical glutamine metabolism pathway and researched whether inhibiting this pathway can enhance radiosensitivity of PCSCs. We showed that glutamine deprivation significantly inhibited self-renewal, decreased expression of stemness-related genes, increased intracellular ROS, and induced apoptosis in PCSCs. These effects were countered by oxaloacetate, but not α-ketoglutarate. Knockdown of glutamic-oxaloacetic transaminase dramatically impaired PCSCs properties, while glutamate dehydrogenase knockdown had a limited effect, suggesting a dependence of PCSCs on non-canonical glutamine metabolism. Additionally, glutamine deprivation significantly increased radiation-induced ROS and sensitized PCSCs to fractionated radiation. Moreover, transaminase inhibitors effectively enhanced ROS generation, promoted radiation sensitivity, and attenuated tumor growth in nude mice following radiation exposure. Our findings reveal that inhibiting the non-canonical pathway of glutamine metabolism enhances the PCSC radiosensitivity and may be an effective adjunct in cancer radiotherapy. PMID:26439804

  1. CARM1 and PRMT1 are dysregulated in lung cancer without hierarchical features.

    PubMed

    Elakoum, Rania; Gauchotte, Guillaume; Oussalah, Abderrahim; Wissler, Marie-Pierre; Clément-Duchêne, Christelle; Vignaud, Jean-Michel; Guéant, Jean-Louis; Namour, Farès

    2014-02-01

    CARM1 and PRMT1 are 2 Protein Arginine Methyl Transferases (PRMT) dysregulated in cancer. CARM1 function is contradictory and depicted as facilitating proliferation or differentiation. PRMT1 is required for cell proliferation. CARM1 and PRMT1 cooperate for gene regulation. We report that CARM1 and PRMT1 are significantly overexpressed in 60 patients with Non-Small Cell Lung Carcinomas (NSCLC). CARM1 and PRMT1 correlated in healthy but not tumor tissue. Their levels of expression in tumor tissue were proportional to their levels of expression in the counterpart healthy tissue. Only CARM1 expression was found to be correlated with tumor differentiation and neither CARM1 nor PRMT1 expression was correlated with survival. Accordingly, CARM1 and PRMT1 are overexpressed in 2 NSCLC cell lines, A549 and H1299. Targeting PRMT1 with siRNA reduced proliferation, by decreasing cell growth and inhibiting soft agar colony formation, and promoted differentiation, by increasing the epithelial markers cytokeratin 7 and 8 and decreasing Neuromedin B receptor, which binds a mitogenic factor. siCARM1 yielded similar consequences but the conditions with siCARM1 reflected inhibition of both CARM1 and PRMT1. Together these results suggest that CARM1 and PRMT1 are involved in proliferation in lung cancer with no hierarchy of one protein over the other. The fact that CARM1 targeting suppresses PRMT1 in addition to CARM1 reinforces the functional importance of CARM1/PRMT1 interaction. PMID:24211191

  2. Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell features and sensitizes cells to radiotherapy.

    PubMed

    Li, Doudou; Fu, Zhiqiang; Chen, Ruiwan; Zhao, Xiaohui; Zhou, Yu; Zeng, Bing; Yu, Min; Zhou, Quanbo; Lin, Qing; Gao, Wenchao; Ye, Huilin; Zhou, Jiajia; Li, Zhihua; Liu, Yimin; Chen, Rufu

    2015-10-13

    Pancreatic ductal adenocarcinoma (PDAC) cells utilize a novel non-canonical pathway of glutamine metabolism that is essential for tumor growth and redox balance. Inhibition of this metabolic pathway in PDAC can potentially synergize with therapies that increase intracellular reactive oxygen species (ROS) such as radiation. Here, we evaluated the dependence of pancreatic cancer stem cells (PCSCs) on this non-canonical glutamine metabolism pathway and researched whether inhibiting this pathway can enhance radiosensitivity of PCSCs. We showed that glutamine deprivation significantly inhibited self-renewal, decreased expression of stemness-related genes, increased intracellular ROS, and induced apoptosis in PCSCs. These effects were countered by oxaloacetate, but not α-ketoglutarate. Knockdown of glutamic-oxaloacetic transaminase dramatically impaired PCSCs properties, while glutamate dehydrogenase knockdown had a limited effect, suggesting a dependence of PCSCs on non-canonical glutamine metabolism. Additionally, glutamine deprivation significantly increased radiation-induced ROS and sensitized PCSCs to fractionated radiation. Moreover, transaminase inhibitors effectively enhanced ROS generation, promoted radiation sensitivity, and attenuated tumor growth in nude mice following radiation exposure. Our findings reveal that inhibiting the non-canonical pathway of glutamine metabolism enhances the PCSC radiosensitivity and may be an effective adjunct in cancer radiotherapy. PMID:26439804

  3. Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis.

    PubMed

    Komatsu, Masato; Yoshimaru, Tetsuro; Matsuo, Taisuke; Kiyotani, Kazuma; Miyoshi, Yasuo; Tanahashi, Toshihito; Rokutan, Kazuhito; Yamaguchi, Rui; Saito, Ayumu; Imoto, Seiya; Miyano, Satoru; Nakamura, Yusuke; Sasa, Mitsunori; Shimada, Mitsuo; Katagiri, Toyomasa

    2013-02-01

    Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify the molecular mechanisms involved in the carcinogenesis of TNBC and to identify target molecules for novel anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 and 321 transcripts that were significantly upregulated and downregulated in TNBC, respectively. In particular, gene expression profile analyses of normal human vital organs allowed us to identify 104 cancer-specific genes, including those involved in breast carcinogenesis such as NEK2, PBK and MELK. Moreover, gene annotation enrichment analysis revealed prominent gene subsets involved in the cell cycle, especially mitosis. Therefore, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly-associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC. Small-interfering RNA-mediated knockdown of their expression significantly attenuated TNBC cell viability due to G1 and G2/M cell cycle arrest. Our data will provide a better understanding of the carcinogenesis of TNBC and could contribute to the development of molecular targets as a treatment for TNBC patients. PMID:23254957

  4. Prognostic Value and Reproducibility of Pretreatment CT Texture Features in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Fried, David V.; Tucker, Susan L.; Zhou, Shouhao; Liao, Zhongxing; Mawlawi, Osama; Ibbott, Geoffrey; Court, Laurence E.

    2014-11-15

    Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC). Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility. Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78

  5. Silencing of FGFR4 could influence the biological features of gastric cancer cells and its therapeutic value in gastric cancer.

    PubMed

    Ye, Yanwei; Jiang, Dongbao; Li, Jingjing; Wang, Min; Han, Chao; Zhang, Xiefu; Zhao, Chunlin; Wen, Jianguo; Kan, Quancheng

    2016-03-01

    To clarify the role of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the therapeutic value of BGJ398 targeted to FGFR4. We constructed lentivirus vectors to stably knockdown FGFR4 expression in GC cells. Function assays in vitro and in vivo, treated with 5-fluorouracil (5-Fu) and BGJ398, were performed to study the change of biological behaviors of GC cells and related mechanism. The proliferation and invasive ability of HGC27 and MKN45 significantly decreased while the apoptosis rate of GC cells obviously increased in shRNA group (P < 0.05). The expressions of Bcl-xl, FLIP, PCNA, vimentin, p-erk, and p-STAT3 significantly reduced while the expressions of caspase-3 and E-cadherin markly enhanced in shRNA group. The proliferation abilities of GC cells were more significantly inhibited by the combination of BGJ398 and 5-Fu in shRNA group (P < 0.05). Compared to negative control (NC), the single and combination of 5-Fu and BGJ398 all significantly increased the apoptosis rate of GC cells, especially in the combination group (P < 0.01). The single and combination of 5-Fu and BGJ398 decreased the expressions of PCNA, Bcl-xl, and FLIP while increased the expression of caspase-3 in GC cells, especially in shRNA groups. Furthermore, knockdown of FGFR4 expression might prevent the growth of GC in vivo. Silencing of FGFR4 expression could weaken the invasive ability, increase the apoptosis rate, and decrease the proliferation ability of GC cells in vitro and in vivo. Furthermore, the combination of 5-Fu and BGJ398 had synergy in inhibiting the proliferation ability and increasing apoptosis rate of GC cells, directing a new target drug in GC. PMID:26432329

  6. Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features.

    PubMed

    Alberti, C

    2010-01-01

    Genetic factors and their interactions with environmental conditions and internal microenvironment influence the prostate cancer (PC) development, so that gene expression couldn't strictly occur on the basis of reductionist determinisms of DNA causality but should also conform to multifactorial and stochastic events, moreover, considering the pre-RNA alternative splicing-mediated multi-protein assemblying mechanisms. Nevertheless, after age and ethnic background, the strongest epidemiological risk factor for PC is a positive family history. However, apart from RNaseL-, ElaC2-, MSR1-genes, there are not other identified high-risk genetic variants which might be considered responsible for hereditary PC, moreover suggesting that familial PC is a genetically heterogeneous disease, many gene loci rather than a specific major susceptibility gene predisposing to it. Gene-environment interactions play a crucial role in cancer development especially when low penetrance genes, such as in case of genetic polymorphisms, are the major players. Several epidemiological studies show, in some families, a possible, either syncronous or metachronous, association of other tumors (breast, brain, gastrointestinal tumors, lymphomas) with PC, thus suggesting a common genetic background. As far as the role of androgen metabolism and androgen receptor (AR)-related genes in the development of familial PC is concerned, a small number of either guanine-guanine-cytosine (< 16) or cytosine-adenine-guanine (< 18) repeats appears to increase the AR activity, resulting in a raising PC risk. Regarding the expression of both androgen and estrogen receptor-related genes in sporadic and hereditary PC, the immunohistochemistry findings show that the percentage of AR-positive cancer cells is higher in hereditary PC than in sporadic forms, whereas the mean number of estrogen-alpha-receptor-positive stromal cells is higher in sporadic PC rather than in that hereditary. As for 5-alpha-steroid-reductase-2

  7. On feature extraction and classification in prostate cancer radiotherapy using tensor decompositions.

    PubMed

    Fargeas, Auréline; Albera, Laurent; Kachenoura, Amar; Dréan, Gaël; Ospina, Juan-David; Coloigner, Julie; Lafond, Caroline; Delobel, Jean-Bernard; De Crevoisier, Renaud; Acosta, Oscar

    2015-01-01

    External beam radiotherapy is commonly prescribed for prostate cancer. Although new radiation techniques allow high doses to be delivered to the target, the surrounding healthy organs (rectum and bladder) may suffer from irradiation, which might produce undesirable side-effects. Hence, the understanding of the complex toxicity dose-volume effect relationships is crucial to adapt the treatment, thereby decreasing the risk of toxicity. In this paper, we introduce a novel method to classify patients at risk of presenting rectal bleeding based on a Deterministic Multi-way Analysis (DMA) of three-dimensional planned dose distributions across a population. After a non-rigid spatial alignment of the anatomies applied to the dose distributions, the proposed method seeks for two bases of vectors representing bleeding and non bleeding patients by using the Canonical Polyadic (CP) decomposition of two fourth order arrays of the planned doses. A patient is then classified according to its distance to the subspaces spanned by both bases. A total of 99 patients treated for prostate cancer were used to analyze and test the performance of the proposed approach, named CP-DMA, in a leave-one-out cross validation scheme. Results were compared with supervised (linear discriminant analysis, support vector machine, K-means, K-nearest neighbor) and unsupervised (recent principal component analysis-based algorithm, and multidimensional classification method) approaches based on the registered dose distribution. Moreover, CP-DMA was also compared with the Normal Tissue Complication Probability (NTCP) model. The CP-DMA method allowed rectal bleeding patients to be classified with good specificity and sensitivity values, outperforming the classical approaches. PMID:25443534

  8. Characterization of papillary thyroid microcarcinomas using sonographic features in malignant papillary thyroid cancer: a retrospective analysis.

    PubMed

    Gu, Wei-jun; Yan, Hui-xian; Luo, Yu-kun; Wang, Fu-lin; Yang, Guo-qing; Guo, Qing-hua; Jin, Nian; Zang, Li; Chen, Kang; Du, Jin; Wang, Xian-ling; Yang, Li-juan; Ba, Jian-ming; Dou, Jing-tao; Mu, Yi-ming; Pan, Chang-yu; Lv, Zhao-hui

    2015-05-01

    The diagnosis of malignant thyroid nodules is still a clinical challenge. This study aimed to determine the ultrasonographic characteristics of papillary thyroid carcinoma. The ultrasonographic and pathological data of 2453 thyroid nodules in a cohort of 1895 Chinese patients who underwent thyroidectomy from January 2010 to December 2012 were retrospectively reviewed. Anteroposterior and transversal (AP/TR) diameters ≥1, solid structure, infiltrative margins, hypoechoic appearance, and microcalcifications were more common in malignant nodules than in benign nodules (P < 0.01). These ultrasonographic features were independent risk factors of malignancy (P < 0.01) as determined by logistic regression analysis. Based on multivariate analysis, these characteristics were also present in large nodules (diameter >10 mm). However, in small nodules (diameter ≤10 mm), only AP/TR ≥1 and infiltrative margins were independent risk factors of malignancy (P < 0.01). Ultrasonography is of high diagnostic value for malignant thyroid nodules and may help to improve the differential diagnosis. Small and large nodules have distinct ultrasonographic features. PMID:26020388

  9. Skin cancer texture analysis of OCT images based on Haralick, fractal dimension and the complex directional field features

    NASA Astrophysics Data System (ADS)

    Raupov, Dmitry S.; Myakinin, Oleg O.; Bratchenko, Ivan A.; Kornilin, Dmitry V.; Zakharov, Valery P.; Khramov, Alexander G.

    2016-04-01

    Optical coherence tomography (OCT) is usually employed for the measurement of tumor topology, which reflects structural changes of a tissue. We investigated the possibility of OCT in detecting changes using a computer texture analysis method based on Haralick texture features, fractal dimension and the complex directional field method from different tissues. These features were used to identify special spatial characteristics, which differ healthy tissue from various skin cancers in cross-section OCT images (B-scans). Speckle reduction is an important pre-processing stage for OCT image processing. In this paper, an interval type-II fuzzy anisotropic diffusion algorithm for speckle noise reduction in OCT images was used. The Haralick texture feature set includes contrast, correlation, energy, and homogeneity evaluated in different directions. A box-counting method is applied to compute fractal dimension of investigated tissues. Additionally, we used the complex directional field calculated by the local gradient methodology to increase of the assessment quality of the diagnosis method. The complex directional field (as well as the "classical" directional field) can help describe an image as set of directions. Considering to a fact that malignant tissue grows anisotropically, some principal grooves may be observed on dermoscopic images, which mean possible existence of principal directions on OCT images. Our results suggest that described texture features may provide useful information to differentiate pathological from healthy patients. The problem of recognition melanoma from nevi is decided in this work due to the big quantity of experimental data (143 OCT-images include tumors as Basal Cell Carcinoma (BCC), Malignant Melanoma (MM) and Nevi). We have sensitivity about 90% and specificity about 85%. Further research is warranted to determine how this approach may be used to select the regions of interest automatically.

  10. Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases

    PubMed Central

    Lee, Taebum; Lee, Boram; Choi, Yoon-La; Han, Joungho; Ahn, Myung-Ju; Um, Sang-Won

    2016-01-01

    Background: Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy. Methods: In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features. Results: All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had KRAS mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation. Conclusions: EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response. PMID:27086595

  11. A New Combinatorial Optimization Approach for Integrated Feature Selection Using Different Datasets: A Prostate Cancer Transcriptomic Study

    PubMed Central

    Puthiyedth, Nisha; Riveros, Carlos; Berretta, Regina; Moscato, Pablo

    2015-01-01

    Background The joint study of multiple datasets has become a common technique for increasing statistical power in detecting biomarkers obtained from smaller studies. The approach generally followed is based on the fact that as the total number of samples increases, we expect to have greater power to detect associations of interest. This methodology has been applied to genome-wide association and transcriptomic studies due to the availability of datasets in the public domain. While this approach is well established in biostatistics, the introduction of new combinatorial optimization models to address this issue has not been explored in depth. In this study, we introduce a new model for the integration of multiple datasets and we show its application in transcriptomics. Methods We propose a new combinatorial optimization problem that addresses the core issue of biomarker detection in integrated datasets. Optimal solutions for this model deliver a feature selection from a panel of prospective biomarkers. The model we propose is a generalised version of the (α,β)-k-Feature Set problem. We illustrate the performance of this new methodology via a challenging meta-analysis task involving six prostate cancer microarray datasets. The results are then compared to the popular RankProd meta-analysis tool and to what can be obtained by analysing the individual datasets by statistical and combinatorial methods alone. Results Application of the integrated method resulted in a more informative signature than the rank-based meta-analysis or individual dataset results, and overcomes problems arising from real world datasets. The set of genes identified is highly significant in the context of prostate cancer. The method used does not rely on homogenisation or transformation of values to a common scale, and at the same time is able to capture markers associated with subgroups of the disease. PMID:26106884

  12. Multidetector computed tomography features of pancreatic metastases from leiomyosarcoma: Experience at a tertiary cancer center

    PubMed Central

    Suh, Chong Hyun; Keraliya, Abhishek; Shinagare, Atul B; Kim, Kyung Won; Ramaiya, Nikhil H; Tirumani, Sree Harsha

    2016-01-01

    AIM: To describe the multidetector computed tomography features of pancreatic metastasis from leiomyosarcoma (LMS). METHODS: Between January 1995 and December 2012, 13 consecutive patients (11 women, 2 men; mean age of 57 years; range, 38-78 years) with pancreatic metastases from LMS were included in our study. Imaging features including location, number, largest dimension, tumor attenuation and enhancement characteristics, presence of necrosis, pancreatic ductal dilatation, common bile duct (CBD) dilatation, presence of pancreatitis, and atrophy were documented. RESULTS: The most common site of origin of the pancreatic metastases from LMS was uterus (38.5%), followed by retroperitoneum (30.8%) and extremity (23.1%). None of the patients in our study had pancreas as the first site of metastasis. All patients developed pancreatic metastases at a median interval of 24 mo. Pancreatic metastases from LMS were solitary in 8/13 patients and multiple in 5/13 patients, had no predilection for any part of the pancreas, were hypovascular on arterial phase in 10/13 patients and associated with pancreatic duct dilatation in 3/13 patients. None had CBD dilatation. None of the pancreatic metastases in LMS cohort caused pancreatitis, and atrophy. Median duration of follow-up was 19 mo for LMS cohort during which two patients underwent resection of metastasis (median survival 45 mo) while the remaining underwent systemic therapy (median survival 13 mo). CONCLUSION: Pancreatic metastases from LMS are often solitary and hypovascular masses and less commonly associated with pancreatic ductal dilatation, CBD dilatation, pancreatitis or pancreatic atrophy. Surgical resection of solitary LMS pancreatic metastasis can be considered due to the long survival of these patients. PMID:27027985

  13. Breast Cancer-Specific Mortality Pattern and Its Changing Feature According to Estrogen Receptor Status in Two Time Periods

    PubMed Central

    Jiang, Yizhou; Shao, Zhimin

    2016-01-01

    Purpose To determine whether and how the patterns of breast cancer-specific mortality (BCSM) changed along with time periods. Methods We used the Surveillance, Epidemiology and End Results registry to identify 228209 female patients diagnosed with invasive breast cancer between 1990 and 2000 (cohort 1 [C1], 112981) and between 2001 and 2005 (cohort 2 [C2], 115228). BCSM was compared in two cohorts using Cox proportional hazard regression models. We analysed the relative hazard ratios (HRs) and absolute BCSM rates by flexible parametric survival modelling. Results The patterns of BCSM were similar between the two cohorts, with the peak of mortality presenting in the first 2–3 years after diagnosis, and mortality rate significantly decreased in C2 in all cases. In C2, the annual BCSM rate of all cases was 9.64 (per 1000 persons per year) in year 10 with a peak rate of 23.34 in year 2. In ER-negative and high-risk patients, marked survival improvements were achieved mostly in the first 5 years, while in ER-positive and low-risk patients, survival improvements were less but constant up to 10 years. Conclusion There has been a significant improvement of BCSM with substantially decreased mortality within 5 years. The current pattern of BCSM and its changing feature differs according to ER status. Our findings have some clinical implications both for treatment decisions and adjuvant treatment trial design. PMID:27299729

  14. Correlation of clinical features and genetic profiles of stromal interaction molecule 1 (STIM1) in colorectal cancers

    PubMed Central

    Wong, Henry Sung-Ching; Chang, Wei-Chiao

    2015-01-01

    STIM1 overexpression has been observed in a portion of colorectal cancer (CRC) patients and associated with cancer cell invasion and migration. To characterize the distinctive expression profiles associated with stromal interaction molecule 1 (STIM1) overexpression/low-expression between CRC subtypes, and further assess the divergence transcription regulation impact of STIM1 between colon (COADs) and rectum (READs) adenocarcinomas in order to depict the role of SOCE pathway in CRCs, we have conducted a comprehensive phenome-transcriptome-interactome analysis to clarify underlying molecular differences of COADs/READs contributed by STIM1. Results demonstrated that a number of novel STIM1-associated signatures have been identified in COADs but not READs. Specifically, the presence of STIM1 overexpression in COADs, which represented a disturbance of the SOCE pathway, was associated with cell migration and cell motility properties. We identified 11 prognostic mRNA/miRNA predictors associated with the overall survival of COAD patients, suggesting the correlation of STIM1-associated features to clinicopathological outcomes. These findings enhance our understanding on differences between CRC subtypes in panoramic view, and suggested STIM1 as a promising therapeutic biomarker in COADs. PMID:26543234

  15. Expression of PER, CRY, and TIM genes for the pathological features of colorectal cancer patients

    PubMed Central

    Wang, Yong; Cheng, Yunsheng; Yu, Gang; Jia, Benli; Hu, Zhihang; Zhang, Lijiu

    2016-01-01

    As typical clock gene machinery, period (PER1, PER2, and PER3), cryptochrome (CRY1 and CRY2), and timeless (TIM), could control proliferation, cellular metabolism, and many key functions, such as recognition and repair of DNA damage, dysfunction of the circadian clock could result in tumorigenesis of colorectal cancer (CRC). In this study, the expression levels of PER1, PER2, and PER3, as well as CRY1, CRY2, and TIM in the tumor tissue and apparently healthy mucosa from CRC patients were examined and compared via quantitative real-time polymerase chain reaction. Compared with the healthy mucosa from CRC patients, expression levels of PER1, PER2, PER3, and CRY2 in their tumor tissue are much lower, while TIM level was much enhanced. There was no significant difference in the CRY1 expression level. High levels of TIM mRNA were much prevalent in the tumor mucosa with proximal lymph nodes. CRC patients with lower expression of PER1 and PER3 in the tumor tissue showed significantly poorer survival rates. The abnormal expression levels of PER and TIM genes in CRC tissue could be related to the genesis process of the tumor, influencing host–tumor interactions. PMID:27103825

  16. Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms.

    PubMed

    Murtas, Corrado; Ghiggeri, Gian Marco

    2016-08-01

    Membranous nephropathy is a frequent cause of nephrotic syndrome in adults. In most patients, it appears as a primary renal disease but in about 20 % of cases membranous nephropathy is associated with systemic conditions such as systemic lupus erythematosus, infections or cancer, or with drug exposure. Reliable differentiation between primary and secondary membranous nephropathy has important implications for the patient, because of different therapeutic approaches between the different forms. The recent in vivo definition of glomerular targets of autoimmunity in idiopathic membranous nephropathy represented a real breakthrough and nowadays more than one podocyte antigen is considered in some way implicated in the pathogenesis of human membranous nephropathy. Specific antibodies against all these components have been detected in serum of patients and could become biomarkers of membranous nephropathy and/or of disease activity. In this brief review, we discuss the usefulness of newly described autoantibodies in the differential diagnosis of secondary membranous nephropathy. Histological clues for recognizing the two pathological entities are also analysed with regard to the available scientific evidence on this issue. Our evaluation shows that more research is needed to identify the best approach to reach a correct diagnosis of primary or secondary membranous nephropathy. PMID:26810113

  17. Microbiological and host features associated with corynebacteriosis in cancer patients: a five-year study.

    PubMed

    Martins, Cas; Faria, Lmd; Souza, Mc; Camello, Tcf; Velasco, E; Hirata, R; Thuler, Lcs; Mattos-Guaraldi, Al

    2009-09-01

    During a five-year period, 932 clinical isolates from cancer patients treated in a Brazilian reference centre were identified as corynebacteria; 86% of the cultures came from patients who had been clinically and microbiologically classified as infected and 77.1% of these patients had been hospitalised (71.1% from surgical wards). The adult solid tumour was the most common underlying malignant disease (66.7%). The univariate and multivariate analyses showed that hospitalised patients had a six-fold greater risk (OR = 5.5, 95% CI = 1.15-26.30 p = 0.033) related to 30-day mortality. The predominant species were Corynebacterium amycolatum (44.7%), Corynebacterium minutissimum (18.3%) and Corynebacterium pseudodiphtheriticum (8.5%). The upper urinary tracts, surgical wounds, lower respiratory tracts, ulcerated tumours and indwelling venous catheters were the most frequent sources of C. amycolatum strains. Corynebacterium jeikeium infection occurred primarily in neutropenic patients who have used venous catheters, while infection caused by C. amycolatum and other species emerged mainly in patients with solid tumours. PMID:19876565

  18. Biological Features of Human Papillomavirus-related Head and Neck Cancers Contributing to Improved Response.

    PubMed

    Cleary, C; Leeman, J E; Higginson, D S; Katabi, N; Sherman, E; Morris, L; McBride, S; Lee, N; Riaz, N

    2016-07-01

    Head and neck squamous cell carcinomas (HNSCC) are the sixth most common malignancy globally, and an increasing proportion of oropharyngeal HNSCCs are associated with the human papillomavirus (HPV). Patients with HPV-associated tumours have markedly improved overall and disease-specific survival compared with their HPV-negative counterparts when treated with chemoradiation. Although the difference in outcomes between these two groups is clearly established, the mechanism underlying these differences remains an area of investigation. Data from preclinical, clinical and genomics studies have started to suggest that an increase in radio-sensitivity of HPV-positive HNSCC may be responsible for improved outcomes, the putative mechanisms of which we will review here. The Cancer Genome Atlas and others have recently documented a multitude of molecular differences between HPV-positive and HPV-negative tumours. Preclinical investigations by multiple groups have explored possible mechanisms of increased sensitivity to therapy, including examining differences in DNA repair, hypoxia and the immune response. In addition to differences in the response to therapy, some groups have started to investigate phenotypic differences between the two diseases, such as tumour invasiveness. Finally, we will conclude with a brief review of ongoing clinical trials that are attempting to de-escalate treatment to minimise long-term toxicity while maintaining cure rates. New insights from preclinical and genomic studies may eventually lead to personalised treatment paradigms for HPV-positive patients. PMID:27052795

  19. Association of computerized texture features on MRI with early treatment response following laser ablation for neuropathic cancer pain: preliminary findings.

    PubMed

    Tiwari, Pallavi; Danish, Shabbar F; Jiang, Benjamin; Madabhushi, Anant

    2015-10-01

    was considered. Our quantitative approach first involved intensity standardization to allow for grayscale MR intensities acquired pre- and post-LITT to have a fixed tissue-specific meaning within the same imaging protocol, the same body region, and within the same patient. An affine registration was then performed on individual post-LITT MRI protocols to a reference MRI protocol pre-LITT. A total of 78 computerized texture features (co-occurrence matrix homogeneity, neighboring gray-level dependence matrix, Gabor) are then extracted from pre- and post-LITT MP-MRI on a per-voxel basis. Quantitative, voxelwise comparison of the changes in MRI texture features between pre- and post-LITT MRI indicate that (a) Gabor texture features at specific orientations were highly sensitive as well as specific in predicting subtle microarchitectural changes within and around the ablation zone pre- and post-LITT, (b) FLAIR was identified as the most sensitive MRI protocol in identifying early treatment changes yielding a normalized percentage change of 360% within the ablation zone relative to its pre-LITT value, and (c) GRE was identified as the most sensitive MRI protocol in quantifying changes outside the ablation zone post-LITT. Our preliminary results thus indicate potential for noninvasive computerized MP-MRI features over volumetric features in determining localized microarchitectural early focal treatment changes post-LITT for neuropathic cancer pain treatment. PMID:26870745

  20. Molecular characteristics and prognostic features of breast cancer in Nigerian compared with UK women.

    PubMed

    Agboola, A J; Musa, A A; Wanangwa, N; Abdel-Fatah, T; Nolan, C C; Ayoade, B A; Oyebadejo, T Y; Banjo, A A; Deji-Agboola, A M; Rakha, E A; Green, A R; Ellis, I O

    2012-09-01

    Although breast cancer (BC) incidence is lower in African-American women compared with White-American, in African countries such as Nigeria, BC is a common disease. Nigerian women have a higher risk for early-onset, with a high mortality rate from BC, prompting speculation that risk factors could be genetic and the molecular portrait of these tumours are different to those of western women. In this study, 308 BC samples from Nigerian women with complete clinical history and tumour characteristics were included and compared with a large series of BC from the UK as a control group. Immunoprofile of these tumours was characterised using a panel of 11 biomarkers of known relevance to BC. The immunoprofile and patients' outcome were compared with tumour grade-matched UK control group. Nigerian women presenting with BC were more frequently premenopausal, and their tumours were characterised by large primary tumour size, high tumour grade, advanced lymph node stage, and a higher rate of vascular invasion compared with UK women. In the grade-matched groups, Nigerian BC showed over representation of triple-negative and basal phenotypes and BRCA1 deficiency BC compared with UK women, but no difference was found regarding HER2 expression between the two series. Nigerian women showed significantly poorer outcome after development of BC compared with UK women. This study demonstrates that there are possible genetic and molecular differences between an indigenous Black population and a UK-based series. The basal-like, triple negative and BRCA1 dysfunction groups of tumours identified in this study may have implications in the development of screening programs and therapies for African patients and families that are likely to have a BRCA1 dysfunction, basal like and triple negative. PMID:22842985

  1. Clinicopathologic Features of Polypoid Lesions of the Gallbladder and Risk Factors of Gallbladder Cancer

    PubMed Central

    Kwon, Wooil; Lee, Seung Eun; Hwang, Dae Wook; Kim, Sun-Whe

    2009-01-01

    It is difficult to differentiate benign and malignancy in polypoid lesions of the gallbladder (PLG) by solely depending on imaging studies. Therefore clinicopathologic features of benign and malignant polyps are compared in an attempt to identify the risk factors of malignant polypoid lesions. The medical records of 291 patients who were confirmed to have PLG through cholecystectomy were reviewed and analyzed for age, sex, symptom, associated gallstone, morphology of PLG, size of PLG, number of PLG, and preoperative tumor markers. Benign PLG was found in 256 patients (88.0%) and malignant PLG in 35 patients (12.0%). Compared with benign group, the malignant group were older (61.1 yr vs. 47.1 yr, P<0.001), more often accompanied with symptoms (62.9% vs. 28.9%, P<0.001). Malignant PLG tended to be sessile (60.0% vs. 10.5%, P<0.001), larger (28.0 mm vs. 8.6 mm, P<0.001) and single lesion (65.7% vs. 44.1%, P<0.016). Age over 60 yr (P=0.021, odds ratio [OR], 8.16), sessile morphology (P<0.001, OR, 7.70), and size over 10 mm (P=0.009, OR, 8.87) were identified as risk factors for malignant PLG. Careful decision making on therapeutic plans should be made with consideration of malignancy for patients over 60 yr, with sessile morphology of PLG, and with PLG size of over 10 mm. PMID:19543513

  2. Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

    SciTech Connect

    Tan, Shan; Kligerman, Seth; Chen, Wengen; Lu, Minh; Kim, Grace; Feigenberg, Steven; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2013-04-01

    Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.

  3. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  4. Staging of cervical cancer based on tumor heterogeneity characterized by texture features on 18F-FDG PET images

    NASA Astrophysics Data System (ADS)

    Mu, Wei; Chen, Zhe; Liang, Ying; Shen, Wei; Yang, Feng; Dai, Ruwei; Wu, Ning; Tian, Jie

    2015-07-01

    The aim of the study is to assess the staging value of the tumor heterogeneity characterized by texture features and other commonly used semi-quantitative indices extracted from 18F-FDG PET images of cervical cancer (CC) patients. Forty-two patients suffering CC at different stages were enrolled in this study. Firstly, we proposed a new tumor segmentation method by combining the intensity and gradient field information in a level set framework. Secondly, fifty-four 3D texture features were studied besides of SUVs (SUVmax, SUVmean, SUVpeak) and metabolic tumor volume (MTV). Through correlation analysis, receiver-operating-characteristic (ROC) curves analysis, some independent indices showed statistically significant differences between the early stage (ES, stages I and II) and the advanced stage (AS, stages III and IV). Then the tumors represented by those independent indices could be automatically classified into ES and AS, and the most discriminative feature could be chosen. Finally, the robustness of the optimal index with respect to sampling schemes and the quality of the PET images were validated. Using the proposed segmentation method, the dice similarity coefficient and Hausdorff distance were 91.78   ±   1.66% and 7.94   ±   1.99 mm, respectively. According to the correlation analysis, all the fifty-eight indices could be divided into 20 groups. Six independent indices were selected for their highest areas under the ROC curves (AUROC), and showed significant differences between ES and AS (P  <  0.05). Through automatic classification with the support vector machine (SVM) Classifier, run percentage (RP) was the most discriminative index with the higher accuracy (88.10%) and larger AUROC (0.88). The Pearson correlation of RP under different sampling schemes is 0.9991   ±   0.0011. RP is a highly stable feature and well correlated with tumor stage in CC, which suggests it could differentiate ES and AS with high

  5. Staging of cervical cancer based on tumor heterogeneity characterized by texture features on (18)F-FDG PET images.

    PubMed

    Mu, Wei; Chen, Zhe; Liang, Ying; Shen, Wei; Yang, Feng; Dai, Ruwei; Wu, Ning; Tian, Jie

    2015-07-01

    The aim of the study is to assess the staging value of the tumor heterogeneity characterized by texture features and other commonly used semi-quantitative indices extracted from (18)F-FDG PET images of cervical cancer (CC) patients. Forty-two patients suffering CC at different stages were enrolled in this study. Firstly, we proposed a new tumor segmentation method by combining the intensity and gradient field information in a level set framework. Secondly, fifty-four 3D texture features were studied besides of SUVs (SUVmax, SUVmean, SUVpeak) and metabolic tumor volume (MTV). Through correlation analysis, receiver-operating-characteristic (ROC) curves analysis, some independent indices showed statistically significant differences between the early stage (ES, stages I and II) and the advanced stage (AS, stages III and IV). Then the tumors represented by those independent indices could be automatically classified into ES and AS, and the most discriminative feature could be chosen. Finally, the robustness of the optimal index with respect to sampling schemes and the quality of the PET images were validated. Using the proposed segmentation method, the dice similarity coefficient and Hausdorff distance were 91.78   ±   1.66% and 7.94   ±   1.99 mm, respectively. According to the correlation analysis, all the fifty-eight indices could be divided into 20 groups. Six independent indices were selected for their highest areas under the ROC curves (AUROC), and showed significant differences between ES and AS (P  <  0.05). Through automatic classification with the support vector machine (SVM) Classifier, run percentage (RP) was the most discriminative index with the higher accuracy (88.10%) and larger AUROC (0.88). The Pearson correlation of RP under different sampling schemes is 0.9991   ±   0.0011. RP is a highly stable feature and well correlated with tumor stage in CC, which suggests it could differentiate ES and AS with high

  6. Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging

    PubMed Central

    de Cobelli, Ottavio; Terracciano, Daniela; Tagliabue, Elena; Raimondi, Sara; Bottero, Danilo; Cioffi, Antonio; Jereczek-Fossa, Barbara; Petralia, Giuseppe; Cordima, Giovanni; Almeida, Gilberto Laurino; Lucarelli, Giuseppe; Buonerba, Carlo; Matei, Deliu Victor; Renne, Giuseppe; Di Lorenzo, Giuseppe; Ferro, Matteo

    2015-01-01

    Purpose The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy. Methods A total of 223 patients who fulfilled the criteria for “Prostate Cancer Research International: Active Surveillance”, were included. Mp–1.5 Tesla MRI examination staging with endorectal coil was performed at least 6–8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥0.5ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score. Results Multivariate analysis demonstrated the association of PIRADS score with upgrading (P<0.0001), ECE (P<0.0001), unfavorable prognosis (P<0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI. Conclusions mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS. PMID:26444548

  7. The proto-oncogene PBF binds p53 and is associated with prognostic features in colorectal cancer.

    PubMed

    Read, Martin L; Seed, Robert I; Modasia, Bhavika; Kwan, Perkin P K; Sharma, Neil; Smith, Vicki E; Watkins, Rachel J; Bansal, Sukhchain; Gagliano, Teresa; Stratford, Anna L; Ismail, Tariq; Wakelam, Michael J O; Kim, Dae S; Ward, Stephen T; Boelaert, Kristien; Franklyn, Jayne A; Turnell, Andrew S; McCabe, Christopher J

    2016-01-01

    The PTTG1-binding factor (PBF) is a transforming gene capable of eliciting tumor formation in xenograft models. However, the precise role of PBF in tumorigenesis and its prognostic value as a cancer biomarker remain largely uncharacterised, particularly in malignancies outside the thyroid. Here, we provide the first evidence that PBF represents a promising prognostic marker in colorectal cancer. Examination of a total of 39 patients demonstrated higher PBF expression at both the mRNA (P = 0.009) and protein (P < 0.0001) level in colorectal tumors compared to matched normal tissue. Critically, PBF was most abundant in colorectal tumors associated with Extramural Vascular Invasion (EMVI), increased genetic instability (GI) and somatic TP53 mutations, all features linked with recurrence and poorer patient survival. We further demonstrate by glutathione-S-transferase (GST) pull-down and coimmunoprecipitation that PBF binds to the tumor suppressor protein p53, as well as to p53 mutants (Δ126-132, M133K, V197E, G245D, I255F and R273C) identified in the colorectal tumors. Importantly, overexpression of PBF in colorectal HCT116 cells interfered with the transcriptional activity of p53-responsive genes such as mdm2, p21 and sfn. Diminished p53 stability (> 90%; P < 0.01) was also evident with a concurrent increase in ubiquitinated p53. Human colorectal tumors with wild-type TP53 and high PBF expression also had low p53 protein levels (P < 0.05), further emphasizing a putative interaction between these genes in vivo. Overall, these results demonstrate an emerging role for PBF in colorectal tumorigenesis through regulating p53 activity, with implications for PBF as a prognostic indicator for invasive tumors. PMID:25408419

  8. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    PubMed Central

    2013-01-01

    Background Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. Methods The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. Results The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Conclusions Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses. PMID:24209831

  9. Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

    PubMed Central

    2010-01-01

    Background Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400× magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of

  10. SU-E-J-270: Repeated 18F-FDG PET/CTs Based Feature Analysis for the Predication of Anal Cancer Recurrence

    SciTech Connect

    Wang, J; Chuong, M; Choi, W; Lu, W; Latifi, K; Saeed, N; Hoffe, S; Shridhar, R; Moros, E; Tan, S

    2015-06-15

    Purpose: To identify PET/CT based imaging predictors of anal cancer recurrence and evaluate baseline vs. mid-treatment vs. post-treatment PET/CT scans in the tumor recurrence prediction. Methods: FDG-PET/CT scans were obtained at baseline, during chemoradiotherapy (CRT, midtreatment), and after CRT (post-treatment) in 17 patients of anal cancer. Four patients had tumor recurrence. For each patient, the mid-treatment and post-treatment scans were respectively aligned to the baseline scan by a rigid registration followed by a deformable registration. PET/CT image features were computed within the manually delineated tumor volume of each scan to characterize the intensity histogram, spatial patterns (texture), and shape of the tumors, as well as the changes of these features resulting from CRT. A total of 335 image features were extracted. An Exact Logistic Regression model was employed to analyze these PET/CT image features in order to identify potential predictors for tumor recurrence. Results: Eleven potential predictors of cancer recurrence were identified with p < 0.10, including five shape features, five statistical texture features, and one CT intensity histogram feature. Six features were indentified from posttreatment scans, 3 from mid-treatment scans, and 2 from baseline scans. These features indicated that there were differences in shape, intensity, and spatial pattern between tumors with and without recurrence. Recurrent tumors tended to have more compact shape (higher roundness and lower elongation) and larger intensity difference between baseline and follow-up scans, compared to non-recurrent tumors. Conclusion: PET/CT based anal cancer recurrence predictors were identified. The post-CRT PET/CT is the most important scan for the prediction of cancer recurrence. The baseline and mid-CRT PET/CT also showed value in the prediction and would be more useful for the predication of tumor recurrence in early stage of CRT. This work was supported in part by the

  11. SU-E-J-243: Reproducibility of Radiomics Features Through Different Voxel Discretization Levels in F18-FDG PET Images of Cervical Cancer

    SciTech Connect

    Altazi, B; Fernandez, D; Zhang, G; Biagioli, M; Moros, E; Moffitt, H. Lee

    2015-06-15

    Purpose: Site-specific investigations of the role of Radiomics in cancer diagnosis and therapy are needed. We report of the reproducibility of quantitative image features over different discrete voxel levels in PET/CT images of cervical cancer. Methods: Our dataset consisted of the pretreatment PET/CT scans from a cohort of 76 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 31–76 years, treated with external beam radiation therapy to a dose range between 45–50.4 Gy (median dose: 45 Gy), concurrent cisplatin chemotherapy and MRI-based Brachytherapy to a dose of 20–30 Gy (median total dose: 28 Gy). Two board certified radiation oncologists delineated Metabolic Tumor volume (MTV) for each patient. Radiomics features were extracted based on 32, 64, 128 and 256 discretization levels (DL). The 64 level was chosen to be the reference DL. Features were calculated based on Co-occurrence (COM), Gray Level Size Zone (GLSZM) and Run-Length (RLM) matrices. Mean Percentage Differences (Δ) of features for discrete levels were determined. Normality distribution of Δ was tested using Kolomogorov - Smirnov test. Bland-Altman test was used to investigate differences between feature values measured on different DL. The mean, standard deviation and upper/lower value limits for each pair of DL were calculated. Interclass Correlation Coefficient (ICC) analysis was performed to examine the reliability of repeated measures within the context of the test re-test format. Results: 3 global and 5 regional features out of 48 features showed distribution not significantly different from a normal one. The reproducible features passed the normality test. Only 5 reproducible results were reliable, ICC range 0.7 – 0.99. Conclusion: Most of the radiomics features tested showed sensitivity to voxel level discretization between (32 – 256). Only 4 GLSZM, 3 COM and 1 RLM showed insensitivity towards mentioned discrete levels.

  12. Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway.

    PubMed

    Han, Dan; Wu, Gang; Chang, Chan; Zhu, Fang; Xiao, Yin; Li, Qiuhui; Zhang, Tao; Zhang, Liling

    2015-12-01

    Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-κB. NF-κB is involved in epithelial-mesenchymal transition (EMT) and self-renewal of breast cancer stem cells (CSCs). In this study, we treated MCF-7 and MDA-MB-231 breast cancer cells with TGF-β to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-β induced EMT in breast cancer cells in a dose-dependent manner. Also, DSF inhibited EMT-associated stem-like features, migration and invasion of tumor cells as well as tumor growth in xenograft model. The activation of NF-κB was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-κB activity and downregulate ERK/NF-κB/Snail pathway, leading to reverse EMT and stem-like features. Our data suggest that DSF inhibits EMT and stem-like properties in breast cancer cells associated with inhibition of the ERK/NF-κB/Snail pathway. PMID:26517513

  13. Testing Map Features Designed to Convey the Uncertainty of Cancer Risk: Insights Gained From Assessing Judgments of Information Adequacy and Communication Goals

    PubMed Central

    Severtson, Dolores J.

    2015-01-01

    Barriers to communicating the uncertainty of environmental health risks include preferences for certain information and low numeracy. Map features designed to communicate the magnitude and uncertainty of estimated cancer risk from air pollution were tested among 826 participants to assess how map features influenced judgments of adequacy and the intended communication goals. An uncertain versus certain visual feature was judged as less adequate but met both communication goals and addressed numeracy barriers. Expressing relative risk using words communicated uncertainty and addressed numeracy barriers but was judged as highly inadequate. Risk communication and visual cognition concepts were applied to explain findings. PMID:26412960

  14. Identification of More Feasible MicroRNA–mRNA Interactions within Multiple Cancers Using Principal Component Analysis Based Unsupervised Feature Extraction

    PubMed Central

    Taguchi, Y-h.

    2016-01-01

    MicroRNA(miRNA)–mRNA interactions are important for understanding many biological processes, including development, differentiation and disease progression, but their identification is highly context-dependent. When computationally derived from sequence information alone, the identification should be verified by integrated analyses of mRNA and miRNA expression. The drawback of this strategy is the vast number of identified interactions, which prevents an experimental or detailed investigation of each pair. In this paper, we overcome this difficulty by the recently proposed principal component analysis (PCA)-based unsupervised feature extraction (FE), which reduces the number of identified miRNA–mRNA interactions that properly discriminate between patients and healthy controls without losing biological feasibility. The approach is applied to six cancers: hepatocellular carcinoma, non-small cell lung cancer, esophageal squamous cell carcinoma, prostate cancer, colorectal/colon cancer and breast cancer. In PCA-based unsupervised FE, the significance does not depend on the number of samples (as in the standard case) but on the number of features, which approximates the number of miRNAs/mRNAs. To our knowledge, we have newly identified miRNA–mRNA interactions in multiple cancers based on a single common (universal) criterion. Moreover, the number of identified interactions was sufficiently small to be sequentially curated by literature searches. PMID:27171078

  15. Identification of More Feasible MicroRNA-mRNA Interactions within Multiple Cancers Using Principal Component Analysis Based Unsupervised Feature Extraction.

    PubMed

    Taguchi, Y-H

    2016-01-01

    MicroRNA(miRNA)-mRNA interactions are important for understanding many biological processes, including development, differentiation and disease progression, but their identification is highly context-dependent. When computationally derived from sequence information alone, the identification should be verified by integrated analyses of mRNA and miRNA expression. The drawback of this strategy is the vast number of identified interactions, which prevents an experimental or detailed investigation of each pair. In this paper, we overcome this difficulty by the recently proposed principal component analysis (PCA)-based unsupervised feature extraction (FE), which reduces the number of identified miRNA-mRNA interactions that properly discriminate between patients and healthy controls without losing biological feasibility. The approach is applied to six cancers: hepatocellular carcinoma, non-small cell lung cancer, esophageal squamous cell carcinoma, prostate cancer, colorectal/colon cancer and breast cancer. In PCA-based unsupervised FE, the significance does not depend on the number of samples (as in the standard case) but on the number of features, which approximates the number of miRNAs/mRNAs. To our knowledge, we have newly identified miRNA-mRNA interactions in multiple cancers based on a single common (universal) criterion. Moreover, the number of identified interactions was sufficiently small to be sequentially curated by literature searches. PMID:27171078

  16. Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

    PubMed Central

    Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

    2013-01-01

    Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

  17. Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer

    PubMed Central

    Meng, W.; Gu, T.; Gao, L. M.; Zong, Z. G.; Meng, L.; Fu, Z. Z.; Guo, L.

    2015-01-01

    This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival. PMID:26421870

  18. Association between BRAF and RAS mutations, and RET rearrangements and the clinical features of papillary thyroid cancer

    PubMed Central

    Ming, Jie; Liu, Zeming; Zeng, Wen; Maimaiti, Yusufu; Guo, Yawen; Nie, Xiu; Chen, Chen; Zhao, Xiangwang; Shi, Lan; Liu, Chunping; Huang, Tao

    2015-01-01

    Objective: To evaluate the significance of BRAF V600E and Ras mutations, and RET rearrangements in papillary thyroid cancer (PTC) in the South central region of China. Methods: We included patients from Union hospital’s pathology archive diagnosed with PTC and meeting the criteria for BRAF mutation, RAS mutation, and RET rearrangement testing. Medical records were analyzed for BRAF and RAS mutation status, RET rearrangements (positive or negative), and a list of standardized clinicopathologic features. Results: Positive BRAF mutation was found to be significantly associated with age and extrathyroidal extension (P=0.011 and P=0.013, respectively). However, there was no significant association between BRAF mutation and sex, tumor size, histological subtype, multifocality, or accompanying nodular goiter and Hashimoto’s. On the other hand, none of these characteristics of PTC were been found to be associated with RAS mutation. Additionally, the frequency of RET rearrangements was higher in patients ≤45 years old than that in patients >45 years old. Conclusions: We demonstrated that the BRAF V600E mutation slightly correlated with the clinicopathological characteristics of PTC in the Han population. Furthermore, neither RAS mutation nor RET rearrangements were found to be associated with the clinicopathological characteristics of PTCs. Our work provides useful information on somatic mutations to predict the risk of PTC in different ethnic groups. PMID:26823860

  19. SU-E-J-258: Prediction of Cervical Cancer Treatment Response Using Radiomics Features Based On F18-FDG Uptake in PET Images

    SciTech Connect

    Altazi, B; Fernandez, D; Zhang, G; Biagioli, M; Moros, E; Moffitt, H. Lee

    2015-06-15

    Purpose: Radiomics have shown potential for predicting treatment outcomes in several body sites. This study investigated the correlation between PET Radiomics features and treatment response of cervical cancer outcomes. Methods: our dataset consisted of a cohort of 79 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 25–86 years, (median age at diagnosis: 50 years) all treated between: 2009–14 with external beam radiation therapy to a dose range between: 45–50.4 Gy (median= 45 Gy), concurrent cisplatin chemotherapy and MRI-based brachytherapy to a dose of 20–30 Gy (median= 28 Gy). Metabolic Tumor Volume (MTV) in patient’s primary site was delineated on pretreatment PET/CT by two board certified Radiation Oncologists. The features extracted from each patient’s volume were: 26 Co-occurrence matrix (COM) Feature, 11 Run-Length Matrix (RLM), 11 Gray Level Size Zone Matrix (GLSZM) and 33 Intensity-based features (IBF). The treatment outcome was divided based on the last follow up status into three classes: No Evidence of Disease (NED), Alive with Disease (AWD) and Dead of Disease (DOD). The ability for the radiomics features to differentiate between the 3 treatments outcome categories were assessed by One-Way ANOVA test with p-value < 0.05 was to be statistically significant. The results from the analysis were compared with the ones obtained previously for standard Uptake Value (SUV). Results: Based on patients last clinical follow-up; 52 showed NED, 17 AWD and 10 DOD. Radiomics Features were able to classify the patients based on their treatment response. A parallel analysis was done for SUV measurements for comparison. Conclusion: Radiomics features were able to differentiate between the three different classes of treatment outcomes. However, most of the features were only able to differentiate between NED and DOD class. Also, The ability or radiomics features to differentiate types of response were more significant than SUV.

  20. Annual Report to the Nation on the Status of Cancer, 1975–2008, Featuring Cancers Associated With Excess Weight and Lack of Sufficient Physical Activity

    PubMed Central

    Eheman, Christie; Henley, S. Jane; Ballard-Barbash, Rachel; Jacobs, Eric J.; Schymura, Maria J.; Noone, Anne-Michelle; Pan, Liping; Anderson, Robert N.; Fulton, Janet E.; Kohler, Betsy A.; Jemal, Ahmedin; Ward, Elizabeth; Plescia, Marcus; Ries, Lynn A. G.; Edwards, Brenda K.

    2015-01-01

    BACKGROUND Annual updates on cancer occurrence and trends in the United States are provided through collaboration between the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This year’s report highlights the increased cancer risk associated with excess weight (overweight or obesity) and lack of sufficient physical activity (<150 minutes of physical activity per week). METHODS Data on cancer incidence were obtained from the CDC, NCI, and NAACCR; data on cancer deaths were obtained from the CDC’s National Center for Health Statistics. Annual percent changes in incidence and death rates (age-standardized to the 2000 US population) for all cancers combined and for the leading cancers among men and among women were estimated by joinpoint analysis of long-term trends (incidence for 1992–2008 and mortality for 1975–2008) and short-term trends (1999–2008). Information was obtained from national surveys about the proportion of US children, adolescents, and adults who are overweight, obese, insufficiently physically active, or physically inactive. RESULTS Death rates from all cancers combined decreased from 1999 to 2008, continuing a decline that began in the early 1990s, among men and among women in most racial and ethnic groups. Death rates decreased from 1999 to 2008 for most cancer sites, including the 4 most common cancers (lung, colorectum, breast, and prostate). The incidence of prostate and colorectal cancers also decreased from 1999 to 2008. Lung cancer incidence declined from 1999 to 2008 among men and from 2004 to 2008 among women. Breast cancer incidence decreased from 1999 to 2004 but was stable from 2004 to 2008. Incidence increased for several cancers, including pancreas, kidney, and adenocarcinoma of the esophagus, which are associated with excess weight. CONCLUSIONS Although improvements are reported in

  1. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    SciTech Connect

    Zhang, H; Chen, W; Kligerman, S; D’Souza, W; Suntharalingam, M; Lu, W; Tan, S; Kim, G

    2014-06-15

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features

  2. Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact

    PubMed Central

    Komura, Takuya; Sakai, Yoshio; Harada, Kenichi; Kawaguchi, Kazunori; Takabatake, Hisashi; Kitagawa, Hirohisa; Wada, Takashi; Honda, Masao; Ohta, Tetsuo; Nakanuma, Yasuni; Kaneko, Shuichi

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-γ-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis. We examined the inflammatory features of PDAC patients using the PDAC tissues, sera, and peripheral blood by immunohistochemical staining, measurement of cytokines/chemokines, gene expression analysis, and flow cytometry. We foundg that monocyte/macrophage cells and CD4+ T cells were highlighted immune-mediating cells in local cancer tissue as well as in peripheral blood of PDAC patients, among which the important subfraction with clinical impact influencing PDAC prognosis by chemotherapy

  3. Epigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines.

    PubMed

    Wang, Xiao Qi; Ng, Ray Kit; Ming, Xiaoyan; Zhang, Wu; Chen, Lin; Chu, Andrew C Y; Pang, Roberta; Lo, Chung Mau; Tsao, Sai Wah; Liu, Xuqing; Poon, Ronnie T P; Fan, Sheung Tat

    2013-01-01

    Activation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+(high) cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+(high) cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression. PMID:24023739

  4. The over-expression of FGFR4 could influence the features of gastric cancer cells and inhibit the efficacy of PD173074 and 5-fluorouracil towards gastric cancer.

    PubMed

    Li, Jingjing; Ye, Yanwei; Wang, Min; Lu, Lisha; Han, Chao; Zhou, Yubing; Zhang, Jingmin; Yu, Zujiang; Zhang, Xiefu; Zhao, Chunlin; Wen, Jianguo; Kan, Quancheng

    2016-05-01

    The aim was to investigate the function of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the treatment value of agent targeted to FGFR4. Function assays in vitro and in vivo were performed to investigate the discrepancy of biological features among the GC cells with different expression of FGFR4. GC cells were treated with the single and combination of PD173074 (PD, an inhibitor of FGFR4) and 5-fluorouracil (5-Fu). The invasion ability were stronger, and the apoptosis rates were lower in MGC803 and BGC823 cells treated with FGFR4-LV5 (over-expression of FGFR4 protein) (P < 0.05). The proliferation ability of GC cells is reduced when treated by the single and combination of 5-Fu and PD while that of the FGFR4-LV5 group was less inhibited compared with control group (P < 0.05). The apoptosis rates are remarkably increased in GC cells treated with the single and combination of 5-Fu and PD (P < 0.05). However, the apoptosis rate obviously is reduced in GC cells treated with FGFR4-LV5 compared with control group (P < 0.05). The expression of PCNA and Bcl-XL is remarkably decreased, and the expression of Caspase-3 and cleaved Caspase-3 is obviously increased in GC cells treated with the single and combination of 5-Fu and PD. The tumor volumes of nude mice in FGFR4-LV5 group were much more increased (P < 0.05). The over-expression of FGFR4 enhanced the proliferation ability of GC in vitro and in vivo. The combination of 5-Fu and PD exerted synergetic effect in weakening the proliferation ability and promoting apoptosis in GC cells, while the over-expression of FGFR4 might inhibit the efficacy of two drugs. PMID:26662569

  5. Nonlinear dimensionality reduction of CT histogram based feature space for predicting recurrence-free survival in non-small-cell lung cancer

    NASA Astrophysics Data System (ADS)

    Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

    2015-03-01

    Advantages of CT scanners with high resolution have allowed the improved detection of lung cancers. In the recent release of positive results from the National Lung Screening Trial (NLST) in the US showing that CT screening does in fact have a positive impact on the reduction of lung cancer related mortality. While this study does show the efficacy of CT based screening, physicians often face the problems of deciding appropriate management strategies for maximizing patient survival and for preserving lung function. Several key manifold-learning approaches efficiently reveal intrinsic low-dimensional structures latent in high-dimensional data spaces. This study was performed to investigate whether the dimensionality reduction can identify embedded structures from the CT histogram feature of non-small-cell lung cancer (NSCLC) space to improve the performance in predicting the likelihood of RFS for patients with NSCLC.

  6. Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State

    PubMed Central

    Sherman, Recinda L.; Howlader, Nadia; Jemal, Ahmedin; Ryerson, A. Blythe; Henry, Kevin A.; Boscoe, Francis P.; Cronin, Kathleen A.; Lake, Andrew; Noone, Anne-Michelle; Henley, S. Jane; Eheman, Christie R.; Anderson, Robert N.; Penberthy, Lynne

    2015-01-01

    Background: The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data. Methods: Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression. Results: Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. Overall mortality has been declining for both men and women since the early 1990’s and for children since the 1970’s. HR+/HER2- breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100000 non-Hispanic white women, respectively). HR+/HER2- breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P < .001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100000 non-Hispanic black women), which is reflected in high rates in southeastern states. Conclusions: Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk

  7. Le morte du tumour: histological features of tumor destruction in chemo-resistant cancers following intravenous infusions of pathotropic nanoparticles bearing therapeutic genes.

    PubMed

    Gordon, Erlinda M; Chan, Maria Teresa; Geraldino, Nelson; Lopez, Francisco F; Cornelio, Gerardo H; Lorenzo, Conrado C; Levy, John P; Reed, Rebecca A; Liu, Liqiong; Hall, Frederick L

    2007-06-01

    The pathotropic targeting of therapeutic nanoparticles to cancerous lesions is an innovative concept that has recently been reduced to practice in clinical trials for the treatment of metastatic cancer. Previously, we reported that intravenous infusions of Rexin-G, a pathotropic nanoparticle (or vector) bearing a cyto-ablative construct, induced tumor regression, reduced tumor burden, and improved survival, while enhancing the overall quality-of-life of patients with otherwise intractable chemotherapy-resistant cancers. In this report, we describe the major histopathological and radiologic features that are characteristic of solid tumors under the destructive influences of Rexin-G administered as a single therapeutic agent. To further promote tumor eradication and enhance cancer survival, we explored the potential of an auxiliary gene transfer strategy, specifically intended to induce a localized cancer auto-immunization in addition to assisting in acute tumor destruction. This immunization strategy uses Rexin-G in combination with Reximmune-C, a tumor targeted expression vector bearing a granulocyte macrophage-colony stimulating factor (GM-CSF) gene. Intravenous infusions of Rexin-G were given first to induce apoptosis and necrosis in the metastatic tumor nodules, thus exposing tumor neo-antigens, followed by Reximmune-C infusions, intended to recruit immune cells discretely into the same compartments (or lesions). The intent of this two-step approach is to bring a complement of cells involved in humoral and cell-mediated immunity in close proximity to the immunizing tumor antigens in a concerted effort to assist in tumor eradication and to promote a cancer vaccination in situ. Herein, we also describe the distinctive histopathologic and immunocytochemical features of tumors in terminal cancer patients who received Rexin-G infusions in combination with Reximmune-C. In addition to documenting the first histological indications of clinical efficacy achieved by this

  8. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

    SciTech Connect

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher

  9. Reduced NM23 Protein Level Correlates With Worse Clinicopathologic Features in Colorectal Cancers: A Meta-Analysis of Pooled Data.

    PubMed

    Yang, Tian; Chen, Bo-Zan; Li, Dan-Feng; Wang, Huai-Ming; Lin, Xiao-Sheng; Wei, Hong-Fa; Zeng, Yong-Ming

    2016-01-01

    The clinical value of a prominent metastasis suppressor, nonmetastatic protein 23 (NM23), remains controversial. In this study, we examined the correlation between NM23 protein levels and the clinicopathologic features of colorectal cancers (CRC), and assessed the overall prognostic value of NM23 for CRC. Embase, PubMed, Web of Science, and other scientific literature databases were exhaustively searched to identify relevant studies published prior to June 31, 2015. The methodological qualities of selected studies were scored based on the critical appraisal skills program (CASP) criteria, as independently assessed by 2 reviewers. NM23 protein levels in tumor tissues of CRC patients were examined in relation to Dukes stage, differentiation grade, T-stage, lymph node metastasis status, and overall survival (OS). STATA software version 12.0 (Stata Corp, College Station, TX) was used for statistical analysis of data pooled from selected studies. Nineteen cohort studies met the inclusion criteria for present study and contained a combined total of 2148 study subjects. Pooled odd ratios (ORs) for NM23 expression revealed that reduced NM23 protein levels in CRC tumor tissues correlated with Dukes stage C and D (OR = 1.89, 95% CI: 1.06-3.39, P = 0.032), poor differentiation grades (OR = 1.41, 95% CI: 1.03-1.94, P = 0.032), and positive lymph node metastasis status (OR = 3.21, 95% CI: 1.95-5.29, P < 0.001). On the other hand, no such correlations were evident with T-stage T3-4 (OR = 1.56, 95% CI: 0.60-4.06, P = 0.367) or OS (OR = 0.79, 95% CI: 0.58-1.08, P = 0.138). Our analysis of pooled data found that NM23 expression is reduced in CRC tissues and low NM23 levels tightly correlate with higher Dukes stages, poorer differentiation grade, and positive lymph node metastases. However, NM23 levels did not influence the OS in CRC patients. PMID:26825905

  10. Sparse representation of multi parametric DCE-MRI features using K-SVD for classifying gene expression based breast cancer recurrence risk

    NASA Astrophysics Data System (ADS)

    Mahrooghy, Majid; Ashraf, Ahmed B.; Daye, Dania; Mies, Carolyn; Rosen, Mark; Feldman, Michael; Kontos, Despina

    2014-03-01

    We evaluate the prognostic value of sparse representation-based features by applying the K-SVD algorithm on multiparametric kinetic, textural, and morphologic features in breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). K-SVD is an iterative dimensionality reduction method that optimally reduces the initial feature space by updating the dictionary columns jointly with the sparse representation coefficients. Therefore, by using K-SVD, we not only provide sparse representation of the features and condense the information in a few coefficients but also we reduce the dimensionality. The extracted K-SVD features are evaluated by a machine learning algorithm including a logistic regression classifier for the task of classifying high versus low breast cancer recurrence risk as determined by a validated gene expression assay. The features are evaluated using ROC curve analysis and leave one-out cross validation for different sparse representation and dimensionality reduction numbers. Optimal sparse representation is obtained when the number of dictionary elements is 4 (K=4) and maximum non-zero coefficients is 2 (L=2). We compare K-SVD with ANOVA based feature selection for the same prognostic features. The ROC results show that the AUC of the K-SVD based (K=4, L=2), the ANOVA based, and the original features (i.e., no dimensionality reduction) are 0.78, 0.71. and 0.68, respectively. From the results, it can be inferred that by using sparse representation of the originally extracted multi-parametric, high-dimensional data, we can condense the information on a few coefficients with the highest predictive value. In addition, the dimensionality reduction introduced by K-SVD can prevent models from over-fitting.

  11. Cancer

    MedlinePlus

    ... body. Cancerous cells are also called malignant cells. Causes Cancer grows out of cells in the body. Normal ... of many cancers remains unknown. The most common cause of cancer-related death is lung cancer. In the U.S., ...

  12. Association between Ultrasound Features and the 21-Gene Recurrence Score Assays in Patients with Oestrogen Receptor-Positive, HER2-Negative, Invasive Breast Cancer.

    PubMed

    Chae, Eun Young; Moon, Woo Kyung; Kim, Hak Hee; Kim, Won Hwa; Cha, Joo Hee; Shin, Hee Jung; Choi, Woo Jung; Han, Wonshik; Noh, Dong-Young; Lee, Sae Byul; Ahn, Sei Hyun

    2016-01-01

    A multigene expression assay corresponds to the likelihood of breast cancer recurrence after the initial diagnosis and can be used to guide the decision for additional chemotherapy. However, only few studies have investigated the associations between the imaging features of breast cancer and the results of multigene expression assays. Our study was to identify the relationship between imaging features on ultrasound (US) and the recurrence score (RS) on a 21-gene expression assay in patients with oestrogen receptor (ER)-positive, HER2-negative breast cancer. 267 patients with ER-positive, HER-negative invasive breast cancer who underwent examinations using US and Oncotype DX assay were included. US images were independently reviewed by dedicated breast radiologists who were blind to the RS. Tumour roundness was measured using a laboratory-developed software program. The pathological data were reviewed, including immunohistochemistry results. Univariate analysis was performed to assess the associations between the RS and each variable. Multiple logistic regression analysis was used to identify independent predictors of high RS. Of 267 patients, 147 (55%) had low, 96 (36%) intermediate, and 24 (9%) had high RS. According to the univariate analysis, parallel orientation, presence of calcification in the mass, and tumour roundness were positively associated with high RS. Multiple logistic regression analysis showed that parallel orientation (OR = 5.53) and tumour roundness (OR = 1.70 per 10 increase) were associated with high RS. Parallel orientation and tumour roundness are independent variables that may predict high RS in patients with ER-positive, HER2-negative breast cancer. PMID:27362843

  13. Association between Ultrasound Features and the 21-Gene Recurrence Score Assays in Patients with Oestrogen Receptor-Positive, HER2-Negative, Invasive Breast Cancer

    PubMed Central

    Chae, Eun Young; Kim, Won Hwa; Cha, Joo Hee; Shin, Hee Jung; Choi, Woo Jung; Han, Wonshik; Noh, Dong-Young; Lee, Sae Byul; Ahn, Sei Hyun

    2016-01-01

    A multigene expression assay corresponds to the likelihood of breast cancer recurrence after the initial diagnosis and can be used to guide the decision for additional chemotherapy. However, only few studies have investigated the associations between the imaging features of breast cancer and the results of multigene expression assays. Our study was to identify the relationship between imaging features on ultrasound (US) and the recurrence score (RS) on a 21-gene expression assay in patients with oestrogen receptor (ER)-positive, HER2-negative breast cancer. 267 patients with ER-positive, HER-negative invasive breast cancer who underwent examinations using US and Oncotype DX assay were included. US images were independently reviewed by dedicated breast radiologists who were blind to the RS. Tumour roundness was measured using a laboratory-developed software program. The pathological data were reviewed, including immunohistochemistry results. Univariate analysis was performed to assess the associations between the RS and each variable. Multiple logistic regression analysis was used to identify independent predictors of high RS. Of 267 patients, 147 (55%) had low, 96 (36%) intermediate, and 24 (9%) had high RS. According to the univariate analysis, parallel orientation, presence of calcification in the mass, and tumour roundness were positively associated with high RS. Multiple logistic regression analysis showed that parallel orientation (OR = 5.53) and tumour roundness (OR = 1.70 per 10 increase) were associated with high RS. Parallel orientation and tumour roundness are independent variables that may predict high RS in patients with ER-positive, HER2-negative breast cancer. PMID:27362843

  14. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    MedlinePlus

    ... please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer Past ... Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His Cancer / Prostate ...

  15. Vibrational biospectroscopy coupled with multivariate analysis extracts potentially diagnostic features in blood plasma/serum of ovarian cancer patients.

    PubMed

    Owens, Gemma L; Gajjar, Ketan; Trevisan, Júlio; Fogarty, Simon W; Taylor, Siân E; Da Gama-Rose, Bianca; Martin-Hirsch, Pierre L; Martin, Francis L

    2014-04-01

    Despite numerous advances in "omics" research, early detection of ovarian cancer still remains a challenge. The aim of this study was to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy could characterise alterations in the biomolecular signatures of human blood plasma/serum obtained from ovarian cancer patients compared to non-cancer controls. Blood samples isolated from ovarian cancer patients (n = 30) and healthy controls (n = 30) were analysed using ATR-FTIR spectroscopy. For comparison, a smaller cohort of samples (n = 8) were analysed using an InVia Renishaw Raman spectrometer. Resultant spectra were pre-processed prior to being inputted into principal component analysis (PCA) and linear discriminant analysis (LDA). Statistically significant differences (P < 0.001) were observed between spectra of ovarian cancer versus control subjects for both biospectroscopy methods. Using a support vector machine classifier for Raman spectra of blood plasma, a diagnostic accuracy of 74% was achieved, while the same classifier showed 93.3% accuracy for IR spectra of blood plasma. These observations suggest that a biospectroscopy approach could be applied to identify spectral alterations associated with the presence of insidious ovarian cancer. PMID:24259229

  16. Establishment of human colon cancer cell lines from fresh tumors versus xenografts: comparison of success rate and cell line features.

    PubMed

    Dangles-Marie, Virginie; Pocard, Marc; Richon, Sophie; Weiswald, Louis-Bastien; Assayag, Franck; Saulnier, Patrick; Judde, Jean-Gabriel; Janneau, Jean-Louis; Auger, Nathalie; Validire, Pierre; Dutrillaux, Bernard; Praz, Françoise; Bellet, Dominique; Poupon, Marie-France

    2007-01-01

    Obtaining representative human colon cancer cell lines from fresh tumors is technically difficult. Using 32 tumor fragments from patients with colon cancer, the present study shows that prior xenograft leads to more efficient cell line establishment compared with direct establishment from fresh tumors (P < 0.05). From 26 tumor specimens, we successfully established 20 tumor xenografts in nude mice (77%); among 19 of these xenografts, 9 (47%) led to cell lines, including four from liver metastases. Only 3 of 31 tumor specimens (9.7%) grew immediately in vitro, and all were derived from primary tumors. To compare major phenotypic and genotypic characteristics of human colon cancer cell lines derived from the same tumor fragment using two protocols, the two pairs of cell lines obtained from 2 of 32 tumor fragments were extensively studied. They displayed similar morphology and were able to form compact spheroids. Chemosensitivity to 5-fluorouracil, CPT11, and L-OHP differed between cell lines obtained from patient tumors and those derived from xenografts. Matched cell lines shared a common core of karyotype alterations and distinctive additional chromosomal aberrations. Expression levels of genes selected for their role in oncogenesis evaluated by real-time quantitative PCR were found to be statistically correlated whatever the in vitro culture model used. In conclusion, xenotransplantation in mice of tumor fragments before establishment of cell lines enables generation of more novel human cancer cell lines for investigation of colon cancer cell biology, opening up the opportunity of reproducing the diversity of this disease. PMID:17210723

  17. [Consensuses on lung cancer treatment by Chinese medicine experts from Beijing and Guangzhou and medication features in the North and South China].

    PubMed

    Wang, Shu-mei; Lin, Li-zhu; Nie, Hui

    2011-07-01

    To study the consensuses on lung cancer treatment by Chinese medicine experts from North China and South China, and to analyze their medication features from viewpoints such as the medication frequency, combination laws, medication classification by collecting 800 recipes on the treatment of lung cancer patients prescribed by 8 Chinese oncologists from Guanganmen Hospital of China Academy of Chinese Medical Sciences, the Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, and Guangdong Provincial Hospital of Traditional Chinese Medicine. Results showed that coix seed, poria, pinelliae tuber were the three herbs most commonly used in treatment of lung cancer by all experts. They generally accepted Pi invigorating and phlegm removing method as the basic treatment method for treating lung cancer. Secondly, they usually used white peony root, heterophylla falsestarwort root, and ophiopogonis tuber, etc. (with higher medication frequency) to nourish yin and moisten Fei. Thirdly, consistency was also shown in clearing heat, detoxication, and anticancer. Smilacis glabra, Rhizoma Smilacis Glabrae, Herba Hedyotis diffusae, Herba Scutellariae Barbatae were herbs used by all experts. However, there were differences between oncologists in North China and South China. Oncologists in South China paid more attention to heat toxin and blood stasis, while those in North China paid more attention to supplementing both qi and yin. PMID:21866673

  18. The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer

    PubMed Central

    Savina, Nataliya V.; Nikitchenko, Nataliya V.; Kuzhir, Tatyana D.; Rolevich, Alexander I.; Krasny, Sergei A.; Goncharova, Roza I.

    2016-01-01

    Genome instability and impaired DNA repair are hallmarks of carcinogenesis. The study was aimed at evaluating the DNA damage response in H2O2-treated lymphocytes using the alkaline comet assay in bladder cancer (BC) patients as compared to clinically healthy controls, elderly persons, and individuals with chronic inflammations. Polymorphism in DNA repair genes involved in nucleotide excision repair (NER) and base excision repair (BER) was studied using the PCR-RFLP method in the Belarusian population to elucidate the possible association of their variations with both bladder cancer risk and clinicopathological features of tumors. The increased level of H2O2-induced DNA damage and a higher proportion of individuals sensitive to oxidative stress were found among BC patients as compared to other groups under study. Heterozygosity in the XPD gene (codon 751) increased cancer risk: OR (95% CI) = 1.36 (1.03–1.81), p = 0.031. The frequency of the XPD 312Asn allele was significantly higher in T ≥ 2 high grade than in T ≥ 2 low grade tumors (p = 0.036); the ERCC6 1097Val/Val genotype was strongly associated with muscle-invasive tumors. Combinations of homozygous wild type alleles occurred with the increased frequency in patients with non-muscle-invasive tumors suggesting that the maintenance of normal DNA repair activity may prevent cancer progression. PMID:26649138

  19. [Specific features of gene amplification on the long arm of chromosome 17 in different molecular genetic subtypes of breast cancer].

    PubMed

    Zavalishina, L E; Danilova, N V; Matsionis, A E; Pavlenko, I A

    2014-01-01

    The frequency of gene amplification and coamplification of HER2/neu, TOP2A and the centromeric region of chromosome 17 (CEP17) was examined in 265 breast cancer (BC) cases belonging to different molecular genetic subgroups. Luminal B breast cancer was found to be characterized by the increased probability of coamplifications (CEP17 and HER/neu, HER2/neu, and TOP2A) on chromosome 17. At the same time, the amplification of just three loci on one chromosome is a rare event and encountered in 17% of luminal B breast cancer cases (or 1.1% of all BC cases). That of HER2/neu in conjunction with elevated CEP17 count is statistically significantly more rarely accompanied by deletion of TOP2A rather than its amplification. The findings suggest that there are different amplification mechanisms in different BC molecular genetic subgroups. PMID:25051718

  20. A New Biological Feature of Natural Killer Cells: The Recognition of Solid Tumor-Derived Cancer Stem Cells

    PubMed Central

    Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    Natural killer (NK) cells are classified as a member of the innate lymphoid cells (ILCs) group 1. ILCs have been recently identified and grouped on the basis of their phenotypical and functional characteristics. They are effectors of innate immunity and are involved in secondary lymphoid organ generation and tissue remodeling. NK cells are powerful cytotoxic lymphocytes able to recognize and eliminate tumor- and virus-infected cells by limiting their spread and tissue damage. The recognition of tumor cells is mediated by both activating and inhibitory receptors. While in hematological malignancies the role played by NK cells is widely known, their role in recognizing solid tumors remains unclear. Recently, tumor cell populations have been divided into two compartments: cancer-initiating cells (CICs) or cancer stem cells (CSCs) and senescent tumor cells. Here, CSC will be used. CSCs are a small subset of malignant cells with stem-like properties that are involved in tumor maintenance and recurrence due to their ability to survive to traditional therapies; they are, moreover, poorly recognized by T lymphocytes. Recent data showed that NK cells recognize in vitro cancer-initiating cells derived from colon cancer, glioblastoma, and melanoma. However, more in vivo studies are urgently required to fully understand whether these new antitumor NK cells with cytotoxic capability may be considered in the design of new immunotherapeutic interventions. PMID:27242786

  1. Triptolide reverses hypoxia-induced epithelial–mesenchymal transition and stem-like features in pancreatic cancer by NF-κB downregulation

    PubMed Central

    Liu, Li; Salnikov, Alexei V; Bauer, Nathalie; Aleksandrowicz, Ewa; Labsch, Sabrina; Nwaeburu, Clifford; Mattern, Jürgen; Gladkich, Jury; Schemmer, Peter; Werner, Jens; Herr, Ingrid

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies characterized by an intense tumor stroma with hypoperfused regions, a significant inflammatory response and pronounced therapy resistance. New therapeutic agents are urgently needed. The plant-derived agent triptolide also known as “thunder god vine” has a long history in traditional Chinese medicine for treatment of rheumatoid arthritis and cancer and is now in a clinical phase II trial for establishing the efficacy against a placebo. The authors mimicked the situation in patient tumors by induction of hypoxia in experimental models of pancreatic cancer stem cells (CSCs) and evaluated the therapeutic effect of triptolide. Hypoxia led to induction of colony and spheroid formation, aldehyde dehydrogenase 1 (ALDH1) and NF-κB activity, migratory potential and a switch in morphology to a fibroblastoid phenotype, as well as stem cell- and epithelial–mesenchymal transition-associated protein expression. Triptolide efficiently inhibited hypoxia-induced transcriptional signaling and downregulated epithelial–mesenchymal transition (EMT) and CSC features in established highly malignant cell lines, whereas sensitive cancer cells or nonmalignant cells were less affected. In vivo triptolide inhibited tumor take and tumor growth. In primary CSCs isolated from patient tumors, triptolide downregulated markers of CSCs, proliferation and mesenchymal cells along with upregulation of markers for apoptosis and epithelial cells. This study is the first to show that triptolide reverses EMT and CSC characteristics and therefore may be superior to current chemotherapeutics for treatment of PDA. What's new? Current treatment for pancreatic cancer does not directly target tumor hypoxia, a major mediator of aggressive growth, early metastasis, and therapy resistance. The plant-derived agent triptolide has a long history of use in rheumatoid arthritis and cancer in traditional Chinese medicine and has been

  2. The influence of uncertain map features on risk beliefs and perceived ambiguity for maps of modeled cancer risk from air pollution

    PubMed Central

    Myers, Jeffrey D.

    2012-01-01

    Maps are often used to convey information generated by models, for example, modeled cancer risk from air pollution. The concrete nature of images, such as maps, may convey more certainty than warranted for modeled information. Three map features were selected to communicate the uncertainty of modeled cancer risk: (a) map contours appeared in or out of focus, (b) one or three colors were used, and (c) a verbal-relative or numeric risk expression was used in the legend. Study aims were to assess how these features influenced risk beliefs and the ambiguity of risk beliefs at four assigned map locations that varied by risk level. We applied an integrated conceptual framework to conduct this full factorial experiment with 32 maps that varied by the three dichotomous features and four risk levels; 826 university students participated. Data was analyzed using structural equation modeling. Unfocused contours and the verbal-relative risk expression generated more ambiguity than their counterparts. Focused contours generated stronger risk beliefs for higher risk levels and weaker beliefs for lower risk levels. Number of colors had minimal influence. The magnitude of risk level, conveyed using incrementally darker shading, had a substantial dose-response influence on the strength of risk beliefs. Personal characteristics of prior beliefs and numeracy also had substantial influences. Bottom-up and top-down information processing suggest why iconic visual features of incremental shading and contour focus had the strongest visual influences on risk beliefs and ambiguity. Variations in contour focus and risk expression show promise for fostering appropriate levels of ambiguity. PMID:22985196

  3. The use of pathologic features in selecting the extent of surgical resection necessary for breast cancer patients treated by primary radiation therapy.

    PubMed

    Harris, J R; Connolly, J L; Schnitt, S J; Cady, B; Love, S; Osteen, R T; Patterson, W B; Shirley, R; Hellman, S; Cohen, R B

    1985-02-01

    The extent of the surgical resection necessary for breast cancer patients treated by primary radiation therapy is unknown. A simple gross excision of the tumor provides the best cosmetic result, but a wide local resection may be important to prevent local recurrence in some patients. In order to identify patients who are not adequately treated by gross excision of the tumor and radiation therapy, we performed a retrospective clinical-pathologic review of 221 treated women with infiltrating duct carcinoma. There were 53 cases in which the excision specimen showed a constellation of three pathologic features: prominent intraductal carcinoma in the tumor, intraductal carcinoma in the grossly-normal adjacent tissue, and poorly-differentiated nuclei. These cases had a 37% risk of a local recurrence at 6 years compared to eight per cent for all other cases (p less than 0.0001). In cases with all three features, the use of a supplemental dose of radiation to the primary site did not significantly reduce the risk of a local recurrence. Local recurrence at 6 years was 34% in cases with all three features, who received supplemental local radiation, compared to 49% in cases not receiving a supplemental dose (p = 0.28). Survival was also worse for patients with all three features compared to other cases (69% vs. 90% at 6 years, p = 0.002). These results indicate that patients with all three pathologic features have a high risk of local recurrence following gross excision of the tumor and radiation therapy. If primary radiation therapy is selected for these patients, they should first undergo a re-excision of the tumor site in order to be certain that areas of extensive intraductal carcinoma have been adequately resected. Patients whose tumors do not show all three features are adequately treated by gross excision of the tumor prior to radiation therapy. PMID:2982337

  4. Prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000380.htm Prostate cancer To use the sharing features on this page, please enable JavaScript. Prostate cancer is cancer that starts in the prostate gland. ...

  5. Significant differences in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

    PubMed Central

    Moyses, Raquel Ajub; López, Rossana Verónica Mendoza; Cury, Patrícia Maluf; Siqueira, Sheila Aparecida Coelho; Curioni, Otávio Alberto; de Gois Filho, José Francisco; Figueiredo, David Livingstone Alves; Head; GENCAPO, Neck Genome Project; Tajara, Eloiza Helena; Michaluart, Pedro

    2013-01-01

    OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project – Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation. PMID:23778492

  6. Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer

    PubMed Central

    Wen, Miaomiao; Wang, Xuejiao; Sun, Ying; Xia, Jinghua; Fan, Liangbo; Xing, Hao; Zhang, Zhipei; Li, Xiaofei

    2016-01-01

    Purpose Echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). Methods We enrolled 694 Chinese patients with NSCLC for analysis. EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. Results Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. In continuity correction χ2 test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. A total of 147 (21.18%) patients had EGFR mutations. In concordance with previous reports, EGFR mutation was correlated with age, smoking status, histology, and clinical stage, whereas patient age was not significantly associated with EGFR mutation. Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. Conclusion EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. The EGFR mutations and the EML4-ALK fusion genes are coexistent. PMID:27103824

  7. CD200 is related to cancer-stem-cell features and modulates response to chemoradiation in head and neck squamous cell carcinoma

    PubMed Central

    Jung, Yuh-S.; Vermeer, Paola D.; Vermeer, Daniel W.; Lee, Sang-Jin; Goh, Ah Ra; Ahn, Hyun-Joo; Lee, John H.

    2015-01-01

    Background We sought to characterize the expression of CD200, a membrane protein that functions in immune evasion, to examine its correlations with cancer stem cell-like features and analyze its response to chemotherapy and radiation, in human papillomavirus (HPV) positive and negative head and neck squamous cell carcinomas (HNSCCs). Methods CD200 expression was analyzed in several HNSCC cell lines. CD200 was over-expressed in HPV(+) murine tonsil epithelial cells, its effects on Shh and Bmi-1 examined in vitro, and tumor growth and response to chemoradiation analyzed in vitro and in vivo. Results CD200 was diversely expressed, consistently associated with expression of Bmi-1 and Shh. Overexpression of CD200 induced Bmi-1 and Shh. Tumor grew similarly between C57BL/6 and Rag1−/− C57BL6 mice. ,. CD200 expression enhanced the resistance to chemoradiation only in vivo. Conclusions CD200 was related to cancer-stem-cell features and modulates response to chemoradiation in vivo. Attenuating this might be a potential therapeutic strategy. PMID:24700450

  8. The fluorescent bioprobe with aggregation-induced emission features for monitoring to carbon dioxide generation rate in single living cell and early identification of cancer cells.

    PubMed

    Chen, Didi; Wang, Huan; Dong, Lichao; Liu, Pai; Zhang, Yahui; Shi, Jianbing; Feng, Xiao; Zhi, Junge; Tong, Bin; Dong, Yuping

    2016-10-01

    A novel fluorescent probe, tris (2-(dimethylamino) ethyl)-4,4',4″-(1H-pyrrole-1,2,5-triyl) tribenzoate (TPP-TMAE), with aggregation-enhanced emission (AEE) feature showed a simple, highly selective, specific, and instant response to trace amount carbon dioxide (CO2). Because of this special characteristic, TPP-TMAE is ideal to be a biomarker for in-situ monitoring of the CO2 generation rate during the metabolism of single living cell. The rates in single living HeLa cell, MCF-7 cell, and MEF cell were 6.40 × 10(-6)±6.0 × 10(-8) μg/h, 5.78 × 10(-6)±6.0 × 10(-8) μg/h, and 4.27 × 10(-7)±4.0 × 10(-9) μg/h, respectively. The distinct responses of TPP-TMAE to CO2 generated from cancer cells and normal cells suggested TPP-TMAE as a useful tool for deeper understanding metabolism process and distinguishing cancer cells from normal cells during the early diagnosis of cancers. PMID:27372422

  9. Activin Upregulation by NF-κB is Required to Maintain Mesenchymal Features of Cancer Stem-like Cells in Non-Small Cell Lung Cancer

    PubMed Central

    Wamsley, J. Jacob; Kumar, Manish; Allison, David F.; Clift, Sheena H.; Holzknecht, Caitlyn M.; Szymura, Szymon J.; Hoang, Stephen A.; Xu, Xiaojiang; Moskaluk, Christopher A.; Jones, David R.; Bekiranov, Stefan; Mayo, Marty W.

    2014-01-01

    Soluble growth factors and cytokines within the tumor microenvironment aid in the induction of the epithelial-to-mesenchymal transition (EMT). Although EMT promotes the development of cancer-initiating cells (CICs), cellular mechanisms by which cancer cells maintain mesenchymal phenotypes remain poorly understood. Work presented here indicates that induction of EMT stimulates non-small cell lung cancer (NSCLC) to secrete soluble factors that function in an autocrine fashion. Using gene expression profiling of all annotated and predicted secreted gene products, we find that NF-κB activity is required to upregulate INHBA/Activin, a morphogen in the TGFβ superfamily. INHBA is capable of inducing and maintaining mesenchymal phenotypes, including the expression of EMT master-switch regulators and self-renewal factors that sustain CIC phenotypes and promote lung metastasis. Our work demonstrates that INHBA mRNA and protein expression is commonly elevated in primary human NSCLC and provide evidence that INHBA is a critical autocrine factor that maintains mesenchymal properties of CICs to promote metastasis in NSCLC. PMID:25432175

  10. Expression of vimentin filaments in canine malignant mammary gland tumors: A simulation of clinicopathological features of human breast cancer

    PubMed Central

    RISMANCHI, SANAZ; YADEGAR, ORLY; MUHAMMADNEJAD, SAMAD; AMANPOUR, SAEID; TAGHIZADEH-JAHED, MASOUD; MUHAMMADNEJAD, AHAD

    2014-01-01

    Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies observed in females. Several biological similarities have been reported between CMMGTs and human breast cancer (HBC). The present study aimed to assess the correlation of vimentin filaments overexpression, as part of the process of epithelial-mesenchymal transition (EMT) and the clinicopathological characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs were collected. Paraffin-embedded blocks underwent immunohistochemistry staining, which was performed using vimentin (to assess the evolution of the EMT process), Ki-67 (for evaluation of tumor proliferation) and cluster of differentiation 34 (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade, vascular invasion, margin status, rate of expression of the vimentin filaments, microvessel density-CD34 and proliferation rate data were obtained. Finally, the association between the expression of the vimentin filaments and those parameters was resolved statistically. A significant association was shown between the overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin overexpression did not statistically correlate with the tumor stage or the margin status. Similar to the findings of the present study, certain recent studies have indicated that vimentin filament expression in HBC and CMMGTs is associated with the severity of cancer. Thus, spontaneous canine mammary tumor models appear to be an appropriate animal model for breast cancer research, and the results of the present study could aid to reinforce the association. PMID:25054018