Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features.

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Zlobec, Inti; Bihl, Michel; Foerster, Anja; Rufle, Alex; Lugli, Alessandro

2011-11-01

CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision-making. We report a comprehensive analysis of clinico-pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour- and host-related protein markers characterizing CIMP-high (CIMP-H), -low, and -negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP-H: ≥ 4/5 methylated genes), MSI (MSI-H: ≥ 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP-H was found in 24 cases (7.1%) and linked (p CIMP-low or -negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p CIMP-H, independently of MSI status. In addition to the expected clinico-pathological and molecular associations, CIMP-H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T-lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP-H in both microsatellite-stable (MSS) and MSI-H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP-H. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Associations between colorectal cancer molecular markers and pathways with clinicopathologic features in older women.

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Samadder, N Jewel; Vierkant, Robert A; Tillmans, Lori S; Wang, Alice H; Weisenberger, Daniel J; Laird, Peter W; Lynch, Charles F; Anderson, Kristin E; French, Amy J; Haile, Robert W; Potter, John D; Slager, Susan L; Smyrk, Thomas C; Thibodeau, Stephen N; Cerhan, James R; Limburg, Paul J

2013-08-01

Colorectal tumors have a large degree of molecular heterogeneity. Three integrated pathways of carcinogenesis (ie, traditional, alternate, and serrated) have been proposed, based on specific combinations of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in BRAF and KRAS. We used resources from the population-based Iowa Women's Health Study (n = 41,836) to associate markers of colorectal tumors, integrated pathways, and clinical and pathology characteristics, including survival times. We assessed archived specimens from 732 incident colorectal tumors and characterized them as microsatellite stable (MSS), MSI high or MSI low, CIMP high or CIMP low, CIMP negative, and positive or negative for BRAF and/or KRAS mutations. Informative marker data were collected from 563 tumors (77%), which were assigned to the following integrated pathways: traditional (MSS, CIMP negative, BRAF mutation negative, and KRAS mutation negative; n = 170), alternate (MSS, CIMP low, BRAF mutation negative, and KRAS mutation positive; n = 58), serrated (any MSI, CIMP high, BRAF mutation positive, and KRAS mutation negative; n = 142), or unassigned (n = 193). Multivariable-adjusted Cox proportional hazards regression models were used to assess the associations of interest. Patients' mean age (P = .03) and tumors' anatomic subsite (P = .0001) and grade (P = .0001) were significantly associated with integrated pathway assignment. Colorectal cancer (CRC) mortality was not associated with the traditional, alternate, or serrated pathways, but was associated with a subset of pathway-unassigned tumors (MSS or MSI low, CIMP negative, BRAF mutation negative, and KRAS mutation positive) (n = 96 cases; relative risk = 1.76; 95% confidence interval, 1.07-2.89, compared with the traditional pathway). We identified clinical and pathology features associated with molecularly defined CRC subtypes. However, additional studies are needed to determine how these features

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

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Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

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Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

2015-10-08

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

Biología molecular y cáncer de tiroides Molecular biology and thyroid cancer

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Juan Cassola Santana

2010-12-01

Full Text Available Se realiza una revisión actualizada sobre aspectos de biología molecular que servirán de base al cirujano actuante para un mejor conocimiento del cáncer tiroideo. El objetivo radica en alertar a los cirujanos sobre las nuevas evaluaciones a las que podrán someterse los tumores de la tiroides, que implicarán cambios en toda la gama de conductas actuales en estos casos. Se señalan aspectos que sin duda cambiarán los conceptos que se manejan hoy día.A updating review is carry out on the features of molecular biology as a basis for acting surgeon to a better knowledge of thyroid cancer. The objective is to alert surgeons on the new assessments for this type of cancer, implicating changes in all the range of current behaviors in these cases. The features that will change the nowadays concepts in this respect.

Molecular Imaging and Precision Medicine in Breast Cancer.

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Chudgar, Amy V; Mankoff, David A

2017-01-01

Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptomic and genomic features of invasive lobular breast cancer.

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Desmedt, Christine; Zoppoli, Gabriele; Sotiriou, Christos; Salgado, Roberto

2017-06-01

Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

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Xue, Yong; Chen, Shihui; Liu, Yong

2017-01-01

Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging. PMID:29114182

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.

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

2016-03-10

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. 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. 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). The meta-analysis highlights that CIMP-positive CRCs take their own molecular feature, especially overlapping with BRAF mutations

[{sup 18}F]FDG PET/CT features for the molecular characterization of primary breast tumors

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Antunovic, Lidija [Humanitas Research Hospital, Nuclear Medicine Department, Milan (Italy); Gallivanone, Francesca; Castiglioni, Isabella [National Research Council, Laboratory of Innovation and Integration in Molecular Medicine, Institute of Molecular Bioimaging and Physiology, Milan (Italy); Sollini, Martina; Kirienko, Margarita [Humanitas University, Department of Biomedical Sciences, Milan (Italy); Sagona, Andrea; Tinterri, Corrado [Humanitas Research Hospital, Breast Unit, Milan (Italy); Invento, Alessandra [Integrated University Hospital, Breast Unit, Verona (Italy); Manfrinato, Giulia [University of Milan, Residency Program in Nuclear Medicine, Milan (Italy); Chiti, Arturo [Humanitas Research Hospital, Nuclear Medicine Department, Milan (Italy); Humanitas University, Department of Biomedical Sciences, Milan (Italy)

2017-11-15

The aim of this study was to evaluate the role of imaging features derived from [{sup 18}F]FDG-PET/CT to provide in vivo characterization of breast cancer (BC). Images from 43 patients with a first diagnosis of BC were reviewed. Images were acquired before any treatment. Histological data were derived from pretreatment biopsy or surgical histological specimen; these included tumor type, grade, ER and PgR receptor status, lymphovascular invasion, Ki67 index, HER2 status, and molecular subtype. Standard parameters (SUV{sub mean}, TLG, MTV) and advanced imaging features (histogram-based and shape and size features) were evaluated. Univariate analysis, hierarchical clustering analysis, and exact Fisher's test were used for statistical analysis of data. Imaging-derived metrics were reduced evaluating the mutual correlation within group of features as well as the mutual correlation between groups of features to form a signature. A significant correlation was found between some advanced imaging features and the histological type. Different molecular subtypes were characterized by different values of two histogram-based features (median and energy). A significant association was observed between the imaging signature and luminal A and luminal B HER2 negative molecular subtype and also when considering luminal A, luminal B HER2-negative and HER2-positive groups. Similar results were found between the signature and all five molecular subtypes and also when considering the histological types of BC. Our results suggest a complementary role of standard PET imaging parameters and advanced imaging features for the in vivo biological characterization of BC lesions. (orig.)

Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

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Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

2014-11-01

Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

Cancer molecular markers: A guide to cancer detection and management.

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Nair, Meera; Sandhu, Sardul Singh; Sharma, Anil Kumar

2018-02-08

Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Recent advances in oncology have led to the discovery of cancer markers that has allowed early detection and targeted therapy of tumors. In this context, current review provides a detail outlook on various molecular markers for diagnosis, prognosis and management of therapeutic response in cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantitative diffusion weighted imaging parameters in tumor and peritumoral stroma for prediction of molecular subtypes in breast cancer

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He, Ting; Fan, Ming; Zhang, Peng; Li, Hui; Zhang, Juan; Shao, Guoliang; Li, Lihua

2018-03-01

Breast cancer can be classified into four molecular subtypes of Luminal A, Luminal B, HER2 and Basal-like, which have significant differences in treatment and survival outcomes. We in this study aim to predict immunohistochemistry (IHC) determined molecular subtypes of breast cancer using image features derived from tumor and peritumoral stroma region based on diffusion weighted imaging (DWI). A dataset of 126 breast cancer patients were collected who underwent preoperative breast MRI with a 3T scanner. The apparent diffusion coefficients (ADCs) were recorded from DWI, and breast image was segmented into regions comprising the tumor and the surrounding stromal. Statistical characteristics in various breast tumor and peritumoral regions were computed, including mean, minimum, maximum, variance, interquartile range, range, skewness, and kurtosis of ADC values. Additionally, the difference of features between each two regions were also calculated. The univariate logistic based classifier was performed for evaluating the performance of the individual features for discriminating subtypes. For multi-class classification, multivariate logistic regression model was trained and validated. The results showed that the tumor boundary and proximal peritumoral stroma region derived features have a higher performance in classification compared to that of the other regions. Furthermore, the prediction model using statistical features, difference features and all the features combined from these regions generated AUC values of 0.774, 0.796 and 0.811, respectively. The results in this study indicate that ADC feature in tumor and peritumoral stromal region would be valuable for estimating the molecular subtype in breast cancer.

Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach.

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Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

2018-01-01

In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident. Under this endogenous network hypothesis, we established a core working network of hepatocellular carcinoma (HCC) according to the hypothesis and quantified the working network by a nonlinear dynamical system. We showed that the two stable states of the working network reproduce the main known features of normal liver and HCC at both the modular and molecular levels. Using endogenous network hypothesis and validated working network, we explored genetic mutation pattern in cancer and potential strategies to cure or relieve HCC from a totally new perspective. Patterns of genetic mutations have been traditionally analyzed by posteriori statistical association approaches in light of traditional cancer mutation theory. One may wonder the possibility of a priori determination of any mutation regularity. Here, we found that based on the endogenous network theory the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. Normal hepatocyte and cancerous hepatocyte stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable

Cancer Stratification by Molecular Imaging

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Justus Weber

2015-03-01

Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

Clinicopathologic Features and Survival of Breast Cancer Subtypes in Northeast Iran

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Soodabeh Shahidsales

2018-01-01

Full Text Available Background: Breast cancer can be categorized into different histopathological subtypes based on gene expression profiles. This study aims to evaluate the clinicopathological features and overall survival of various subtypes of breast cancer to assist diagnosis and guide treatment. Methods: The clinicopathologic features of 1095 patients with breast cancer diagnosed over a 10–year period between 2001 and 2011 were analyzed. The Kaplan–Meier method was used to analyze disease-free survival and overall survival. Calculation of the hazard ratio was conducted by multivariate Cox regression. Results: According to the clinicopathologic characteristics of 1095 cases, there were 42% luminal A subtype, 19.2% luminal B, 23% triple negative, and 15% HER2+. The lowest (46.88±12.59 years and highest (50.54±12.32 years mean ages were in the triple negative and HER2+ groups, respectively. There was a significant correlation between histology subtype and age, BMI, lymph node, type of surgery, and stage of disease. There was significantly shorter overall survival and disease free survival in HER2+ breast cancer patients (P<0.001. Multivariate analysis showed that age had the highest hazard ratio of 2.481 (95% Confidence Interval: 1.375-4.477. Conclusion: The results of this study showed the importance of clinicopathological studies of molecular types which help early diagnosis and identification of the best strategy to treat breast cancer.

Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

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Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

2016-10-01

This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

Two dimensional molecular electronics spectroscopy for molecular fingerprinting, DNA sequencing, and cancerous DNA recognition.

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Rajan, Arunkumar Chitteth; Rezapour, Mohammad Reza; Yun, Jeonghun; Cho, Yeonchoo; Cho, Woo Jong; Min, Seung Kyu; Lee, Geunsik; Kim, Kwang S

2014-02-25

Laser-driven molecular spectroscopy of low spatial resolution is widely used, while electronic current-driven molecular spectroscopy of atomic scale resolution has been limited because currents provide only minimal information. However, electron transmission of a graphene nanoribbon on which a molecule is adsorbed shows molecular fingerprints of Fano resonances, i.e., characteristic features of frontier orbitals and conformations of physisorbed molecules. Utilizing these resonance profiles, here we demonstrate two-dimensional molecular electronics spectroscopy (2D MES). The differential conductance with respect to bias and gate voltages not only distinguishes different types of nucleobases for DNA sequencing but also recognizes methylated nucleobases which could be related to cancerous cell growth. This 2D MES could open an exciting field to recognize single molecule signatures at atomic resolution. The advantages of the 2D MES over the one-dimensional (1D) current analysis can be comparable to those of 2D NMR over 1D NMR analysis.

Molecular Cancer Prevention: Current Status & Future Directions

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Maresso, Karen Colbert; Tsai, Kenneth Y.; Brown, Powel H.; Szabo, Eva; Lippman, Scott; Hawk, Ernest

2016-01-01

The heterogeneity and complexity of advanced cancers strongly supports the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (e.g., aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the FDA for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, a number of challenges to the field must be addressed. Here we provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results of major randomized controlled trials. PMID:26284997

Molecular pathways and therapeutic targets in lung cancer

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Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

2014-01-01

Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

Molecular biology of gastric cancer.

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Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

2007-04-01

Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

Molecular biology-based diagnosis and therapy for pancreatic cancer

International Nuclear Information System (INIS)

Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

2011-01-01

Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

Molecular pathogenesis and mechanisms of thyroid cancer

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Xing, Mingzhao

2013-01-01

Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

Morphological and molecular features of oral fluid-derived exosomes: oral cancer patients versus healthy individuals.

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Zlotogorski-Hurvitz, Ayelet; Dayan, Dan; Chaushu, Gavriel; Salo, Tuula; Vered, Marilena

2016-01-01

Oral cancer (OC) patients are at high risk to develop recurrent disease or secondary primary cancers with no available biomarkers to detect these events until a visible lesion is readily present and diagnosed by biopsy. Exosomes secreted by cancer cells are involved in tumor growth, invasion and metastasis. We aimed to determine morphological and molecular differences between oral fluid (OF)-derived exosomes of OC patients and those isolated from healthy individuals (HI). OF from OC patients (n = 36) and HI (n = 25) was initially assessed by nanoparticle tracking analysis (NTA). Following ultracentrifugation, exosomal pellets of OC patients and HI were morphologically examined by transmission electron microscopy and atomic force microscopy (AFM). Enzyme-linked immunosorbent assay (ELISA) and western blotting (WB) were used to analyze the expression of exosomal markers--CD9, CD81 and CD63. NTA showed that OC samples of OF had a significantly higher concentration of nanoparticles/ml (p = 0.01) and modal nanoparticle size (p = 0.002) compared to HI. The difference in size was structurally highlighted by AFM three-dimensional images applied on exosomal pellets. ELISA and WB showed differential expression of exosomal markers in OC exosomes compared to HI: lower expression of CD81 and CD9 in contrast to a higher expression of CD63 (~53 kDa). OF-derived exosomes from OC patients differ both morphologically and molecularly from exosomes present in HI. This study is a baseline that provides a starting point for finding exosomal biomarkers for early detection of malignant changes in high-risk patients without overt clinical signs/lesions.

Molecular perspectives in differentiated thyroid cancer.

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Buffet, C; Groussin, L

2015-02-01

Progress in understanding the molecular genetics of thyroid cancer in the last 20 years has accelerated recently with the advent of high-throughput sequencing technologies known as Next-Generation Sequencing. Besides classical molecular abnormalities involving the MAPK (Mitogen Activated Protein Kinase) and PI3K (PhosphoInositide 3-Kinase) pathways that play a key role in follicular-derived thyroid tumorigenesis, new molecular abnormalities have been discovered. The major advances in recent years have been the discovery of new somatic driver gene point mutations (such as RASAL1 [RAS protein activator Like 1] mutations in follicular cancer) and/or mutations that have prognostic value (such as TERT [Telomerase reverse transcriptase] promoter mutations); new chromosomal rearrangements, usually having close connection with exposure to ionizing radiation (such as ALK [Anaplastic Lymphoma Kinase] rearrangements); and deregulation of some gene or microRNA expression representing a molecular signature. Progress made in understanding the molecular mechanisms of thyroid cancer offers new perspectives for the diagnosis of the benign or malignant status of a thyroid nodule, to refine prognosis and offer new perspectives of targeted therapy for radioiodine-refractory cancers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

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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. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives

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Yoon Young Choi

2016-01-01

Full Text Available Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

Science.gov (United States)

Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

2016-01-01

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

Ovarian and Breast Cancer Spheres Are Similar in Transcriptomic Features and Sensitive to Fenretinide

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Haiwei Wang

2013-01-01

Full Text Available Cancer stem cells (CSCs are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future.

Molecular biology of the lung cancer

International Nuclear Information System (INIS)

Panov, S.Z.

2005-01-01

Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the h allmarks of lung cancer . Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

Molecular imaging in cervical cancer

International Nuclear Information System (INIS)

KHAN, Sairah R.; ROCKALL, Andrea G.; BARWICK, Tara D.

2016-01-01

Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed.

Prostate cancer detection: Fusion of cytological and textural features.

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Nguyen, Kien; Jain, Anil K; Sabata, Bikash

2011-01-01

A computer-assisted system for histological prostate cancer diagnosis can assist pathologists in two stages: (i) to locate cancer regions in a large digitized tissue biopsy, and (ii) to assign Gleason grades to the regions detected in stage 1. Most previous studies on this topic have primarily addressed the second stage by classifying the preselected tissue regions. In this paper, we address the first stage by presenting a cancer detection approach for the whole slide tissue image. We propose a novel method to extract a cytological feature, namely the presence of cancer nuclei (nuclei with prominent nucleoli) in the tissue, and apply this feature to detect the cancer regions. Additionally, conventional image texture features which have been widely used in the literature are also considered. The performance comparison among the proposed cytological textural feature combination method, the texture-based method and the cytological feature-based method demonstrates the robustness of the extracted cytological feature. At a false positive rate of 6%, the proposed method is able to achieve a sensitivity of 78% on a dataset including six training images (each of which has approximately 4,000×7,000 pixels) and 1 1 whole-slide test images (each of which has approximately 5,000×23,000 pixels). All images are at 20X magnification.

Molecular Testing for Gastrointestinal Cancer

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Hye Seung Lee

2017-03-01

Full Text Available With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC and colorectal cancer (CRC. Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4. A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2 and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Prostate cancer detection: Fusion of cytological and textural features

Directory of Open Access Journals (Sweden)

Kien Nguyen

2011-01-01

Full Text Available A computer-assisted system for histological prostate cancer diagnosis can assist pathologists in two stages: (i to locate cancer regions in a large digitized tissue biopsy, and (ii to assign Gleason grades to the regions detected in stage 1. Most previous studies on this topic have primarily addressed the second stage by classifying the preselected tissue regions. In this paper, we address the first stage by presenting a cancer detection approach for the whole slide tissue image. We propose a novel method to extract a cytological feature, namely the presence of cancer nuclei (nuclei with prominent nucleoli in the tissue, and apply this feature to detect the cancer regions. Additionally, conventional image texture features which have been widely used in the literature are also considered. The performance comparison among the proposed cytological textural feature combination method, the texture-based method and the cytological feature-based method demonstrates the robustness of the extracted cytological feature. At a false positive rate of 6%, the proposed method is able to achieve a sensitivity of 78% on a dataset including six training images (each of which has approximately 4,000x7,000 pixels and 1 1 whole-slide test images (each of which has approximately 5,000x23,000 pixels. All images are at 20X magnification.

Clinicopathological and imaging features of breast cancer in Korean Women under 40 years of age

International Nuclear Information System (INIS)

Kim, Jun Woo; Jang, Mi Jung; Kim, Sun Mi; Yun, Bo La; Lee, Jong Yoon; Kim, Eun Kyu; Kang, Eun Young; Park, So Yeon

2017-01-01

To evaluate the clinicopathological and imaging features of mammography, ultrasonography, and magnetic resonance imaging (MRI) for breast cancer in Korean women under 40 years of age according to molecular subtypes. We included 183 breast cancers in 176 consecutive women under 40 years old who had been diagnosed with breast cancer between January 2012 and November 2014. The patients' clinical and pathologic records were available as electronic medical records. A retrospective review of the pre-operative imaging studies was performed with 177 mammographies, 183 ultrasonographies, and 178 MRIs. Eighty-six percent (158/183) of lesions were symptomatic, with masses (147/183) as the most common presentation. Eighty percent (22/25) of the asymptomatic lesions were diagnosed via screening ultrasonography. The luminal A subtype was the most common (n = 79, 43%), human epidermal growth factor receptor 2-enriched subtype showed indistinct margins on mammography (p = 0.006), the triple negative subtype depicted a posterior enhancement on ultrasonography (p < 0.001) and rim enhancement on MRI (p < 0.001). Breast cancers in Korean women under 40 years of age are commonly presented with a palpable mass, and luminal A is the most common molecular subtype. In our study, the imaging and pathologic characteristics of breast cancer in younger women were similar to those previously reported for older patients

Communication: Finding destructive interference features in molecular transport junctions

Energy Technology Data Exchange (ETDEWEB)

Reuter, Matthew G., E-mail: mgreuter@u.northwestern.edu [Department of Chemistry, Northwestern University, Evanston, Illinois 60208 (United States); Hansen, Thorsten [Department of Chemistry, H. C. Ørsted Institute, University of Copenhagen, DK 2100 Copenhagen (Denmark)

2014-11-14

Associating molecular structure with quantum interference features in electrode-molecule-electrode transport junctions has been difficult because existing guidelines for understanding interferences only apply to conjugated hydrocarbons. Herein we use linear algebra and the Landauer-Büttiker theory for electron transport to derive a general rule for predicting the existence and locations of interference features. Our analysis illustrates that interferences can be directly determined from the molecular Hamiltonian and the molecule–electrode couplings, and we demonstrate its utility with several examples.

Molecular basis of the triple negative breast cancer

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Ayse Feyda Nursal

2015-06-01

Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

TCGA study identifies genomic features of cervical cancer

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Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified novel genomic and molecular characteristics of cervical cancer that will aid in subclassification of the disease and may help target therapies that are most appropriate for each patient.

Radionuclide molecular target therapy for lung cancer

International Nuclear Information System (INIS)

Zhang Fuhai; Meng Zhaowei; Tan Jian

2012-01-01

Lung cancer harms people's health or even lives severely. Currently, the morbidity and mortality of lung cancer are ascending all over the world. Accounting for 38.08% of malignant tumor caused death in male and 16% in female in cities,ranking top in both sex. Especially, the therapy of non-small cell lung cancer has not been obviously improved for many years. Recently, sodium/iodide transporter gene transfection and the therapy of molecular target drugs mediated radionuclide are being taken into account and become the new research directions in treatment of advanced lung cancer patients with the development of technology and theory for medical molecular biology and the new knowledge of lung cancer's pathogenesis. (authors)

Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

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Roya Dolatkhah

2015-01-01

Full Text Available Purpose. The increasing incidence of colorectal cancer (CRC in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

International Nuclear Information System (INIS)

Dolatkhah, R.; Somi, M. H.; Dolatkhah, R.; Kermani, I. A.; Dastgiri, S.

2015-01-01

The increasing incidence of colorectal cancer (CRC) in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

Progress in molecular-based management of differentiated thyroid cancer

Science.gov (United States)

Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

2014-01-01

Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa.

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Hadgu, Endale; Seifu, Daniel; Tigneh, Wondemagegnhu; Bokretsion, Yonas; Bekele, Abebe; Abebe, Markos; Sollie, Thomas; Merajver, Sofia D; Karlsson, Christina; Karlsson, Mats G

2018-02-14

Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2). Limited data from East Africa including Ethiopia however shows hormone receptor negative tumors to account for a lower proportion of all breast cancers than has been reported from elsewhere in Africa. In this study from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed between 2012 and 2015 were enrolled. ER, PR, Ki67 and HER2 receptor status were assessed using immunohistochemistry from tissue microarrays. FISH was used for assessment of gene amplification in all equivocal tumor samples and for confirmation in HER2-enriched cases. The distribution of molecular subtypes was: Luminal A: 40%; Luminal B: 26%; HER2-enriched: 10%; TNBC: 23%. ER were positive in 65% of all tumors and 43% the cases were positive for PR. There was statistically significant difference in median age at diagnosis between the molecular subtypes (P molecular subtypes in different age ranges with Luminal B subtype being more common at younger ages (median = 36) and Luminal A subtype more prevalent at older ages (median = 42). There were no statistically significant differences in tumor grade, histology, and stage between the molecular subtypes of breast cancer. The present study detected Luminal A breast cancer to be the most common subtype and reveals a relatively low rate of hormone receptor negative and TNBC. Our findings and

Determination of morphological features and molecular interactions ...

African Journals Online (AJOL)

This research focused on identifying the morphological features and molecular interactions of the Nigerian Bentonitic clays using Scanning Electron Microscope (SEM) characterisation technique. The SEM microstructure images indicated that the bentonite samples are generally moderately dispersive to dispersive with ...

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.

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Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J

2016-01-01

The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the

Prognostic features and markers for testicular cancer management

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Eddy S Leman

2010-01-01

Full Text Available Testicular neoplasm accounts for about 1% of all cancers in men. Over the last 40 years, the incidence of testicular cancer has increased in northern European male populations for unknown reasons. When diagnosed at early stage, testicular cancer is usually curable with a high survival rate. In the past three decades, successful multidisciplinary approaches for the management of testicular cancer have significantly increased patient survival rates. Utilization of tumor markers and accurate prognostic classification has also contributed to successful therapy. In this article, we highlight the most commonly used tumor markers and several potential "novel" markers for testicular cancer as part of the ongoing effort in biomarker research and discovery. In addition, this article also identifies several key prognostic features that have been demonstrated to play a role in predicting relapse. These features include tumor size, rete testis invasion, lymphovascular invasion, and tumor histology. Together with tumor markers, these prognostic factors should be taken into account for risk-adapted management of testicular cancer.

Molecular subtyping of cancer: current status and moving toward clinical applications.

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Zhao, Lan; Lee, Victor H F; Ng, Michael K; Yan, Hong; Bijlsma, Maarten F

2018-04-12

Cancer is a collection of genetic diseases, with large phenotypic differences and genetic heterogeneity between different types of cancers and even within the same cancer type. Recent advances in genome-wide profiling provide an opportunity to investigate global molecular changes during the development and progression of cancer. Meanwhile, numerous statistical and machine learning algorithms have been designed for the processing and interpretation of high-throughput molecular data. Molecular subtyping studies have allowed the allocation of cancer into homogeneous groups that are considered to harbor similar molecular and clinical characteristics. Furthermore, this has helped researchers to identify both actionable targets for drug design as well as biomarkers for response prediction. In this review, we introduce five frequently applied techniques for generating molecular data, which are microarray, RNA sequencing, quantitative polymerase chain reaction, NanoString and tissue microarray. Commonly used molecular data for cancer subtyping and clinical applications are discussed. Next, we summarize a workflow for molecular subtyping of cancer, including data preprocessing, cluster analysis, supervised classification and subtype characterizations. Finally, we identify and describe four major challenges in the molecular subtyping of cancer that may preclude clinical implementation. We suggest that standardized methods should be established to help identify intrinsic subgroup signatures and build robust classifiers that pave the way toward stratified treatment of cancer patients.

[The molecular biology of epithelial ovarian cancer].

Science.gov (United States)

Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

2012-12-01

Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

Cancer diagnostics: The journey from histomorphology to molecular profiling.

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Ahmed, Atif A; Abedalthagafi, Malak

2016-09-06

Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

Breast Cancer Detection with Reduced Feature Set

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Ahmet Mert

2015-01-01

Full Text Available This paper explores feature reduction properties of independent component analysis (ICA on breast cancer decision support system. Wisconsin diagnostic breast cancer (WDBC dataset is reduced to one-dimensional feature vector computing an independent component (IC. The original data with 30 features and reduced one feature (IC are used to evaluate diagnostic accuracy of the classifiers such as k-nearest neighbor (k-NN, artificial neural network (ANN, radial basis function neural network (RBFNN, and support vector machine (SVM. The comparison of the proposed classification using the IC with original feature set is also tested on different validation (5/10-fold cross-validations and partitioning (20%–40% methods. These classifiers are evaluated how to effectively categorize tumors as benign and malignant in terms of specificity, sensitivity, accuracy, F-score, Youden’s index, discriminant power, and the receiver operating characteristic (ROC curve with its criterion values including area under curve (AUC and 95% confidential interval (CI. This represents an improvement in diagnostic decision support system, while reducing computational complexity.

Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

Science.gov (United States)

Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

2008-08-15

The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

Breast cancer features in women under the age of 40 years

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Deise Santiago Girão Eugênio

Full Text Available Summary Objective: To describe the clinical features, imaging findings and pathological aspects of breast cancer diagnosed in women under the age of 40 years. Method: A retrospective, descriptive study was performed through analysis of medical records between November 2008 and August 2012. One hundred and twenty (120 patients were included, of whom 112 underwent mammography, 113 underwent ultrasonography, and 105 underwent magnetic resonance imaging (MRI. The histopathological data was obtained in most cases from post-surgical analysis, which was available for 113 patients. Results: The mean age at diagnosis of primary breast cancer was 34 years. Only 11 patients (9.0% had a family history of breast or ovarian cancer in first-degree relative. Ninety-two (92 patients sought medical attention after showing breast symptoms, and the presence of a palpable nodule was the main complaint. One hundred and twenty-two (122 primary tumors were diagnosed, of which 112 were invasive (95%. The most common histological type was invasive ductal carcinoma (73.8%. Luminal B was the predominant molecular subtype (42.6%. Ultrasonography was positive in 94.5% of the cases and the most common finding were nodules (94.8%. At mammography, the malignancy was observed in 92.8% and the presence of suggestive calcifications was the dominant feature. The MRI was positive in 98% of patients, and mass lesions were the most common. Conclusion: Most cases of breast cancer diagnosed in patients under the age of 40 years, in our population, had symptoms at diagnosis and tumor with more aggressive biological behavior. Despite the ultrasound has been the most widely used method, we found improved characterization of breast lesions when also used mammography and MRI.

Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

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Huang Chi-Cheng

2012-09-01

Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

Molecular cytogenetic in the familial cancers

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Cermak, M.

2015-01-01

The development of cancer diseases is accompanied by number of genetic changes at different levels of the genome. Some of these changes are still subject of research but others are already known in such an extent that they are associated with a specific type of malignity, the development, or treatment possibilities. The cancer genetics dispose of wide range of techniques, with reliable detection of the causal changes. Starting the molecular cytogenetics has launched a new era in diagnostics of genetic aberrations. Fluorescence in situ hybridization (FISH) definitely changed cytogenetic world from black and white to color one and set the foundation of modern investigative methods such as M-FISH, CGH, array CGH and many others. Successively all these methodologies have become a part of routine cancer diagnostics thorough the world. Actually, when much attention is given mostly to submicroscopic changes in DNA supposed as predispositions to various malignancies, the molecular cytogenetics is trying to success in competition of modern highly sensitive molecular biology methods. (author)

Clinicopathological and imaging features of breast cancer in Korean Women under 40 years of age

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Kim, Jun Woo; Jang, Mi Jung; Kim, Sun Mi; Yun, Bo La; Lee, Jong Yoon; Kim, Eun Kyu; Kang, Eun Young; Park, So Yeon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

2017-06-15

To evaluate the clinicopathological and imaging features of mammography, ultrasonography, and magnetic resonance imaging (MRI) for breast cancer in Korean women under 40 years of age according to molecular subtypes. We included 183 breast cancers in 176 consecutive women under 40 years old who had been diagnosed with breast cancer between January 2012 and November 2014. The patients' clinical and pathologic records were available as electronic medical records. A retrospective review of the pre-operative imaging studies was performed with 177 mammographies, 183 ultrasonographies, and 178 MRIs. Eighty-six percent (158/183) of lesions were symptomatic, with masses (147/183) as the most common presentation. Eighty percent (22/25) of the asymptomatic lesions were diagnosed via screening ultrasonography. The luminal A subtype was the most common (n = 79, 43%), human epidermal growth factor receptor 2-enriched subtype showed indistinct margins on mammography (p = 0.006), the triple negative subtype depicted a posterior enhancement on ultrasonography (p < 0.001) and rim enhancement on MRI (p < 0.001). Breast cancers in Korean women under 40 years of age are commonly presented with a palpable mass, and luminal A is the most common molecular subtype. In our study, the imaging and pathologic characteristics of breast cancer in younger women were similar to those previously reported for older patients.

Molecular profiling of cancer--the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic.

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Stricker, Thomas; Catenacci, Daniel V T; Seiwert, Tanguy Y

2011-04-01

Cancers arise as a result of an accumulation of genetic aberrations that are either acquired or inborn. Virtually every cancer has its unique set of molecular changes. Technologies have been developed to study cancers and derive molecular characteristics that increasingly have implications for clinical care. Indeed, the identification of key genetic aberrations (molecular drivers) may ultimately translate into dramatic benefit for patients through the development of highly targeted therapies. With the increasing availability of newer, more powerful, and cheaper technologies such as multiplex mutational screening, next generation sequencing, array-based approaches that can determine gene copy numbers, methylation, expression, and others, as well as more sophisticated interpretation of high-throughput molecular information using bioinformatics tools like signatures and predictive algorithms, cancers will routinely be characterized in the near future. This review examines the background information and technologies that clinicians and physician-scientists will need to interpret in order to develop better, personalized treatment strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular biology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

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Nana-Sinkam, Serge Patrick; Powell, Charles A

2013-05-01

Based on recent bench and clinical research, the treatment of lung cancer has been refined, with treatments allocated according to histology and specific molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing. In this article, we review clinically relevant research directed toward understanding the biology of lung cancer. The clinical purposes of this research are (1) to identify susceptibility variants and field molecular alterations that will promote the early detection of tumors and (2) to identify tumor molecular alterations that serve as therapeutic targets, prognostic biomarkers, or predictors of tumor response. We focus on research developments in the understanding of lung cancer somatic DNA mutations, chromosomal aberrations, epigenetics, and the tumor microenvironment, and how they can advance diagnostics and therapeutics.

Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features.

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Teymouri, Manouchehr; Pirro, Matteo; Johnston, Thomas P; Sahebkar, Amirhosein

2017-05-06

Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively studied for its effects on human papilloma virus (HPV) infection as well as primary and malignant squamous cervical cancers. HPV infections, especially those related to HPV 16 and 18 types, have been established as the leading cause of cervical cancer; however, there are also additional contributory factors involved in the etiopathogenesis of cervical cancers. Curcumin has emerged as having promising chemopreventive and anticancer effects against both HPV-related and nonrelated cervical cancers. In this review, we first discuss the biological relevance of curcumin and both its pharmacological effects and pharmaceutical considerations from a chemical point of view. Next, the signaling pathways that are modulated by curcumin and are relevant to the elimination of HPV infection and treatment of cervical cancer are discussed. We also present counter arguments regarding the effects of curcumin on signaling pathways and molecular markers dysregulated by benzo(a)pyrene (Bap), a carcinogen found in pathological cervical lesions of women who smoke frequently, and estradiol, as two important risk factors involved in persistent HPV-infection and cervical cancer. Finally, various strategies to enhance the pharmacological activity and pharmacokinetic characteristics of curcumin are discussed with examples of studies in experimental models of cervical cancer. © 2016 BioFactors, 43(3):331-346, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors.

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Chad J Creighton

Full Text Available BACKGROUND: Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1 set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. METHODS AND RESULTS: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA, and incorporated all profiled features (not only the "best" predictive ones. As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser were used to "predict" the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas. Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers. CONCLUSIONS: Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of

Current and future molecular diagnostics in non-small-cell lung cancer.

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Li, Chun Man; Chu, Wing Ying; Wong, Di Lun; Tsang, Hin Fung; Tsui, Nancy Bo Yin; Chan, Charles Ming Lok; Xue, Vivian Wei Wen; Siu, Parco Ming Fai; Yung, Benjamin Yat Ming; Chan, Lawrence Wing Chi; Wong, Sze Chuen Cesar

2015-01-01

The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

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Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-01-01

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

Molecular biology of pancreatic cancer.

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Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

2011-06-28

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

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Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

Molecular alterations and biomarkers in colorectal cancer

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Grady, William M.; Pritchard, Colin C.

2013-01-01

The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

Genetics and molecular biology of breast cancer

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King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

1992-12-31

This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

[Molecular Biology for Surgical Treatment of Lung Cancer].

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Suda, Kenichi; Mitsudomi, Tetsuya

2017-01-01

Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis. As adjuvant settings, although biomarker-based cytotoxic therapies failed to show clinical efficacy, several trials are ongoing employing molecular targeted agents (EGFR-TKI or ALK-TKI) or immune checkpoint inhibitors. In clinical practice, mutational information is sometimes used to distinguish 2nd primary tumors from pulmonary metastases of previous cancers. Surgery also has important role for oligo-progressive disease during molecular targeted therapies.

Molecular Determinants of Colon Cancer Susceptibility in the East and West.

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Abdel-Rahman, W M; Faris, M E; Peltomaki, P

2017-01-01

The currently available knowledge of factors that dictate the development and progression as well as the clinical outcome of colorectal cancers (CRC) is mainly derived from Western countries. Considerable number of publications document different incidence rates and contrasting clinical features of CRC in various groups such as the differences between urban vs. rural areas, young vs. old age and the East vs. the West. In particular, Egyptian CRC is a surprisingly young age disease with higher proportion of poorly differentiated and advanced stage cancers as compared to the Western counterparts. Less number of publications addressed the molecular genetics and epigenetic basis of these differences. The available data on CRC and other cancers support a substantial role of several environmental risk factors which impinge on the epigenome and alter the overall cellular and tissue homeostasis. Thus, environmental factors could play a role in predisposition to CRC in general as well as in shaping distinct disease phenotypes in different settings. On the other hand, the environment offers a wide range of preventive modalities including a selection of dietary chemopreventive agents which could play a significant role in fighting cancer at early stages. We here compare the clinical and molecular characteristics of Eastern and Western CRC based on the latest literature. The genetic, epigenetic and environmental etiologies for the observed differences are discussed. Finally, prospects for cancer prevention in light of the increased etiologic understanding are outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report.

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Epplein, Meira; Bostick, Roberd M; Mu, Lina; Ogino, Shuji; Braithwaite, Dejana; Kanetsky, Peter A

2014-11-01

The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries. ©2014 American Association for Cancer Research.

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

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Willis, Rudolph E.

2016-01-01

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

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Abdollahi, H

2014-06-01

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

International Nuclear Information System (INIS)

Abdollahi, H

2014-01-01

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

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Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

Automated prostate cancer detection via comprehensive multi-parametric magnetic resonance imaging texture feature models

International Nuclear Information System (INIS)

Khalvati, Farzad; Wong, Alexander; Haider, Masoom A.

2015-01-01

Prostate cancer is the most common form of cancer and the second leading cause of cancer death in North America. Auto-detection of prostate cancer can play a major role in early detection of prostate cancer, which has a significant impact on patient survival rates. While multi-parametric magnetic resonance imaging (MP-MRI) has shown promise in diagnosis of prostate cancer, the existing auto-detection algorithms do not take advantage of abundance of data available in MP-MRI to improve detection accuracy. The goal of this research was to design a radiomics-based auto-detection method for prostate cancer via utilizing MP-MRI data. In this work, we present new MP-MRI texture feature models for radiomics-driven detection of prostate cancer. In addition to commonly used non-invasive imaging sequences in conventional MP-MRI, namely T2-weighted MRI (T2w) and diffusion-weighted imaging (DWI), our proposed MP-MRI texture feature models incorporate computed high-b DWI (CHB-DWI) and a new diffusion imaging modality called correlated diffusion imaging (CDI). Moreover, the proposed texture feature models incorporate features from individual b-value images. A comprehensive set of texture features was calculated for both the conventional MP-MRI and new MP-MRI texture feature models. We performed feature selection analysis for each individual modality and then combined best features from each modality to construct the optimized texture feature models. The performance of the proposed MP-MRI texture feature models was evaluated via leave-one-patient-out cross-validation using a support vector machine (SVM) classifier trained on 40,975 cancerous and healthy tissue samples obtained from real clinical MP-MRI datasets. The proposed MP-MRI texture feature models outperformed the conventional model (i.e., T2w+DWI) with regard to cancer detection accuracy. Comprehensive texture feature models were developed for improved radiomics-driven detection of prostate cancer using MP-MRI. Using a

Molecular imaging in the framework of personalized cancer medicine.

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Belkić, Dzevad; Belkić, Karen

2013-11-01

With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

Molecular profiling of childhood cancer: Biomarkers and novel therapies.

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Saletta, Federica; Wadham, Carol; Ziegler, David S; Marshall, Glenn M; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D; Byrne, Jennifer A

2014-06-01

Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

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Qingqing Meng

2013-01-01

Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer

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Stobiecki Maciej

2009-07-01

Full Text Available Abstract Background Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women. Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity. Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0

Molecular Concordance Between Primary Breast Cancer and Matched Metastases

DEFF Research Database (Denmark)

Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads

2016-01-01

Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both....... The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

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Manfred Beleut

Full Text Available Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

Image cytometric nuclear texture features in inoperable head and neck cancer: a pilot study

International Nuclear Information System (INIS)

Strojan-Flezar, Margareta; Lavrencak, Jaka; Zganec, Mario; Strojan, Primoz

2011-01-01

Image cytometry can measure numerous nuclear features which could be considered a surrogate end-point marker of molecular genetic changes in a nucleus. The aim of the study was to analyze image cytometric nuclear features in paired samples of primary tumor and neck metastasis in patients with inoperable carcinoma of the head and neck. Image cytometric analysis of cell suspensions prepared from primary tumor tissue and fine needle aspiration biopsy cell samples of neck metastases from 21 patients treated with concomitant radiochemotherapy was performed. Nuclear features were correlated with clinical characteristics and response to therapy. Manifestation of distant metastases and new primaries was associated (p<0.05) with several chromatin characteristics from primary tumor cells, whereas the origin of index cancer and disease response in the neck was related to those in the cells from metastases. Many nuclear features of primary tumors and metastases correlated with the TNM stage. A specific pattern of correlation between well-established prognostic indicators and nuclear features of samples from primary tumors and those from neck metastases was observed. Image cytometric nuclear features represent a promising candidate marker for recognition of biologically different tumor subgroups

Molecular biology of pancreatic cancer: how useful is it in clinical practice?

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Sakorafas, George H; Smyrniotis, Vasileios

2012-07-10

During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the

Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.

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Choi, Woonyoung; Ochoa, Andrea; McConkey, David J; Aine, Mattias; Höglund, Mattias; Kim, William Y; Real, Francisco X; Kiltie, Anne E; Milsom, Ian; Dyrskjøt, Lars; Lerner, Seth P

2017-09-01

Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA's bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Our observation showed that some of subtype-enriched mutations and copy number aberrations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Comparison of sonographic features in benign prostate hyperplasia and prostate cancer

International Nuclear Information System (INIS)

Choi, Won Young; Hong, Hyun Sook; Kang, Eun Young; Seol, Hae Young; Suh, Won Hyuck

1988-01-01

Transrectal sonography of prostate was sensitive to textural changes produced by both benign prostate hyperplasia (BPH) and prostate cancers. During recent 4 years, twenty cases of BPH and twenty cases of prostate cancers proven histologically were analyzed in their sonographic features, retrospectively, by using transrectal prostate sonography and suprapubic prostate sonography. The results were as follows: 1. Mean weights of BPH and prostate cancers was 40.4g and 47.6g, respectively. 2. Sonographic features of BPH revealed isoechogenecity in 11 cases, homogeneity in 18 cases, well defined capsular margins in 19 cases, and calcification in 16 cases. 3. Sonographic features of prostate cancers revealed mixed echogenecity in 14 cases, inhomogeneity in 15 cases, poorly defined capsular margin in 14 cases, and calcifications in 13 cases. 4. Authors concluded that prostate sonography were valuable diagnostic modality in the differentiation of BPH and prostate cancers.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

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Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

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Ilie, M; Hofman, P

2012-01-01

New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

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Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

2013-01-01

The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

T2-weighted MRI-derived textural features reflect prostate cancer aggressiveness: preliminary results.

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Nketiah, Gabriel; Elschot, Mattijs; Kim, Eugene; Teruel, Jose R; Scheenen, Tom W; Bathen, Tone F; Selnæs, Kirsten M

2017-07-01

To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. 3T multiparametric-MRI was performed on 23 prostate cancer patients prior to prostatectomy. Textural features [angular second moment (ASM), contrast, correlation, entropy], apparent diffusion coefficient (ADC), and DCE pharmacokinetic parameters (K trans and V e ) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. ASM and entropy correlated significantly (p textural features correlated insignificantly with K trans and V e . GS 4+3 cancers had significantly lower ASM and higher entropy than 3+4 cancers, but insignificant differences in median ADC, K trans , and V e . The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. • T2W MRI-derived textural features correlate significantly with Gleason score and ADC. • T2W MRI-derived textural features differentiate Gleason score 3+4 from 4+3 cancers. • T2W image textural features could augment tumour characterization.

Biomarkers of HIV-associated Cancer

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Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd

2014-01-01

Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of can...

Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

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Zardavas, Dimitrios; Piccart-Gebhart, Martine

2015-01-01

High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

Stress and its molecular consequences in cancer progression

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Magdalena Surman

2017-06-01

Full Text Available Stress, caused by psychological, physiological and physical factors has an adverse impact on human body homeostasis. There are two kind of stress: short-term and chronic. Cancer patients usually live under chronic stress, caused by diagnosis-related strong emotional experience and depression, resulting from various difficulties associated with disease progression and treatment. At the molecular level, stress factors induce production and secretion of stress-related hormones, such as catecholamines, glucocorticoids and dopamine (as a part of adaptational body response, which influence both normal and transformed cells through their specific receptors. The particular effects exerted by these molecules on cancer cells have been also observed in in vitro cultures and include changes in proliferation, apoptosis susceptibility and migration/invasion potential. As a result, it has been suggested that stress hormones may be responsible for progression of malignancy and thus accelerate the metastasis formation in cancer patients. However, the clinical data on correlation between stress and the patients survival, as well as the molecular analysis of stress hormone receptors expression and action in cancer cell, have not yet provided an unequivocal answer. For this reason, extensive studies, on molecular and clinical level are needed to fully determine stress impact on cancerprogression and on the effectiveness of anti-cancer treatment. Nowadays, it seems reasonable that the personalization of anti-cancer therapy should also focus on mental state of cancer patients, and provide them with psychological tools or techniques for stress management.

Molecular genetics of breast cancer

International Nuclear Information System (INIS)

Radice, P.; Pierotti, M. A.

1997-01-01

In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention

Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

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Rosa, Marilin

2015-04-01

Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

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Kenichi Konda

Full Text Available Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs.We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI] and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers alterations in 158 CRNs including 56 polypoid neoplasms (PNs, 25 granular type laterally spreading tumors (LST-Gs, 48 non-granular type LSTs (LST-NGs, 19 depressed neoplasms (DNs and 10 small flat-elevated neoplasms (S-FNs on the basis of macroscopic appearance.S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs (P<0.001. By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively (P<0.007. We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively (P<0.005. Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05. PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41.We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

Features of ovarian cancer in Lynch syndrome (Review).

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Nakamura, Kanako; Banno, Kouji; Yanokura, Megumi; Iida, Miho; Adachi, Masataka; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

2014-11-01

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.

Molecular mechanisms of cisplatin resistance in cervical cancer

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Zhu H

2016-06-01

Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

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Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

2017-02-01

The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Molecular Imaging of Breast Cancer: Present and future directions

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David eAlcantara

2014-12-01

Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database.

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Hwang, Ki-Tae; Noh, Woochul; Cho, Se-Heon; Yu, Jonghan; Park, Min Ho; Jeong, Joon; Lee, Hyouk Jin; Kim, Jongjin; Oh, Sohee; Kim, Young A

2017-10-01

This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.

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

International Nuclear Information System (INIS)

Crispo, Anna; Esposito, Emanuela; Amore, Alfonso; Di Bonito, Maurizio; Botti, Gerardo; Montella, Maurizio; Barba, Maddalena; D’Aiuto, Giuseppe; De Laurentiis, Michelino; Grimaldi, Maria; Rinaldo, Massimo; Caolo, Giuseppina; D’Aiuto, Massimiliano; Capasso, Immacolata

2013-01-01

Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology

Colorectal Cancers: An Update on Their Molecular Pathology.

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Inamura, Kentaro

2018-01-20

Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.

Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

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Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

2014-04-01

Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Can BI-RADS features on mammography be used as a surrogate for expensive genomic testing in breast cancer patients?

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Harowicz, Michael R.; Marks, Jeffrey R.; Marcom, P. Kelly; Mazurowski, Maciej A.

2017-03-01

Medical oncologists increasingly rely on expensive genomic analysis to stratify patients for different treatment. The genomic markers are able to divide patients into groups that behave differently in terms of tumor presentation, likelihood of metastatic spread, and response to chemotherapy and radiation therapy. In recent years there has been a rapid increase in the number of genomic tests available, like the Oncotype DX test, which provides the risk of cancer recurrence for a subset of patients. Radiogenomics, a new field that investigates the relationship between imaging phenotypes and genomic characteristics, may offer a less expensive and less invasive imaging surrogate for molecular subtype and Oncotype DX recurrence score (ODRS). This retrospective study analyzes the relationship between Breast Imaging-Reporting and Data System (BI-RADS) features as assessed by radiologists on mammograms with molecular subtype and ODRS. We used data from patients with BI-RADS features (shape or margin) and a genomic feature (subtype or ODRS) for the following cohort: shape vs. subtype (n=69), margin vs. subtype (n=78), shape vs. ODRS (n=20), and margin vs. ODRS (n=18). The association between features was assessed using a Fisher's exact test. Our results show that shape assessed by radiologists according to the BI-RADS lexicon is associated with molecular subtype (p=0.0171), while BI-RADS features of shape and margin were not significantly associated with ODRS (p=0.7839, p=0.6047 respectively).

18F-FDG PET radiomics approaches: comparing and clustering features in cervical cancer.

Science.gov (United States)

Tsujikawa, Tetsuya; Rahman, Tasmiah; Yamamoto, Makoto; Yamada, Shizuka; Tsuyoshi, Hideaki; Kiyono, Yasushi; Kimura, Hirohiko; Yoshida, Yoshio; Okazawa, Hidehiko

2017-11-01

The aims of our study were to find the textural features on 18 F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between 18 F-FDG PET textural features in cervical cancer. Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment 18 F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively. These features were compared between SCC and NSCC using a Bonferroni adjusted P value threshold of 0.0028 (0.05/18). To assess the association between PET features, a heat map analysis with hierarchical clustering, one of the radiomics approaches, was performed. Among 18 PET features, correlation, a second-order textural feature derived from NGLCM, was a stable parameter and it was the only feature which showed a robust trend toward significant difference between SCC and NSCC. Cervical SCC showed a higher correlation (0.70 ± 0.07) than NSCC (0.64 ± 0.07, P = 0.0030). The other PET features did not show any significant differences between SCC and NSCC. A higher correlation in SCC might reflect higher structural integrity and stronger spatial/linear relationship of cancer cells compared with NSCC. A heat map with a PET feature dendrogram clearly showed 5 distinct clusters, where correlation belonged to a cluster including MTV and TLG. However, the association between correlation and MTV/TLG was not strong. Correlation was a relatively independent PET feature in cervical cancer. 18 F-FDG PET textural features might reflect the

Clinical and Biological Features of Interval Colorectal Cancer

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Yu Mi Lee

2017-05-01

Full Text Available Interval colorectal cancer (I-CRC is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the “mean sojourn time.” It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

Cancer microarray data feature selection using multi-objective binary particle swarm optimization algorithm

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Annavarapu, Chandra Sekhara Rao; Dara, Suresh; Banka, Haider

2016-01-01

Cancer investigations in microarray data play a major role in cancer analysis and the treatment. Cancer microarray data consists of complex gene expressed patterns of cancer. In this article, a Multi-Objective Binary Particle Swarm Optimization (MOBPSO) algorithm is proposed for analyzing cancer gene expression data. Due to its high dimensionality, a fast heuristic based pre-processing technique is employed to reduce some of the crude domain features from the initial feature set. Since these pre-processed and reduced features are still high dimensional, the proposed MOBPSO algorithm is used for finding further feature subsets. The objective functions are suitably modeled by optimizing two conflicting objectives i.e., cardinality of feature subsets and distinctive capability of those selected subsets. As these two objective functions are conflicting in nature, they are more suitable for multi-objective modeling. The experiments are carried out on benchmark gene expression datasets, i.e., Colon, Lymphoma and Leukaemia available in literature. The performance of the selected feature subsets with their classification accuracy and validated using 10 fold cross validation techniques. A detailed comparative study is also made to show the betterment or competitiveness of the proposed algorithm. PMID:27822174

Breast Cancer Molecular Subtypes Among Moroccan Women

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Wissal Mahir

2016-12-01

Full Text Available Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors RE, the PR (progesterone receptors, the ((Human Epidermal Growth Factor Receptor-2, the Ki67 (proliferation marker HER2, CK5/6 has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment.Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors.Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative benefited from an additional marking with CK5/6 and EGFR to set the basal profile.Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS was

Automated Analysis and Classification of Histological Tissue Features by Multi-Dimensional Microscopic Molecular Profiling.

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Daniel P Riordan

Full Text Available Characterization of the molecular attributes and spatial arrangements of cells and features within complex human tissues provides a critical basis for understanding processes involved in development and disease. Moreover, the ability to automate steps in the analysis and interpretation of histological images that currently require manual inspection by pathologists could revolutionize medical diagnostics. Toward this end, we developed a new imaging approach called multidimensional microscopic molecular profiling (MMMP that can measure several independent molecular properties in situ at subcellular resolution for the same tissue specimen. MMMP involves repeated cycles of antibody or histochemical staining, imaging, and signal removal, which ultimately can generate information analogous to a multidimensional flow cytometry analysis on intact tissue sections. We performed a MMMP analysis on a tissue microarray containing a diverse set of 102 human tissues using a panel of 15 informative antibody and 5 histochemical stains plus DAPI. Large-scale unsupervised analysis of MMMP data, and visualization of the resulting classifications, identified molecular profiles that were associated with functional tissue features. We then directly annotated H&E images from this MMMP series such that canonical histological features of interest (e.g. blood vessels, epithelium, red blood cells were individually labeled. By integrating image annotation data, we identified molecular signatures that were associated with specific histological annotations and we developed statistical models for automatically classifying these features. The classification accuracy for automated histology labeling was objectively evaluated using a cross-validation strategy, and significant accuracy (with a median per-pixel rate of 77% per feature from 15 annotated samples for de novo feature prediction was obtained. These results suggest that high-dimensional profiling may advance the

The market trend analysis and prospects of cancer molecular diagnostics kits.

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Seo, Ju Hwan; Lee, Joon Woo; Cho, Daemyeong

2018-01-01

The molecular diagnostics market can be broadly divided into PCR (rt-PCR, d-PCR), NGS(Next Generation Sequencing), Microarray, FISH(Fluorescent in situ-hybridization) and other categories, based on the diagnostic technique. Also, depending on the disease being diagnosed, the market can also be divided into cancer, infectious diseases, HIV/STDs (herpes, syphilis), and women's health issues such as breast cancer, cervical cancer, ovarian cancer, HPV(human papillomavirus), and vaginitis.Chromosome analysis (including Fluorescent In-situ Hybridization) is one type of blood cancer diagnostic method, which involves the direct detection of individual cells with chromosomal translocation, but there have been problems of sensitivity when using this method. PCR targeting individual genes or the RT (reverse transcription)-PCR method offers outstanding sensitivity, but one drawback is the risk of false-positive reaction caused by contamination of samples, etc. Blood cancer molecular diagnostics kits allow us to overcome these shortcomings, and related products have been under development, with a focus on improving detection sensitivity, enabling multiple tests, and reducing the cost and diagnostic time. Blood cancer molecular diagnostics is usually performed based on platforms such as PCR. The global market for blood cancer molecular diagnostics kits is $ 335.9 million as of 2016 and is expected to reach $ 6980 million in 2026 with an average annual growth rate of 32.9%. The market in South Korea is anticipated to grow at an average annual rate of 28.9%, from $ 3.75 million as of 2016 to $ 60.89 million in 2026. The Market for blood cancer molecular diagnostics kits is judged to be higher in growth possibility due to the increase in the number of cancer patients.

Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer.

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Søreide, Kjetil; Sund, Malin

2015-01-28

Pancreatic cancer remains one of the deadliest human cancers with little progress made in survival over the past decades, and 5-year survival usually below 5%. Despite this dismal scenario, progresses have been made in understanding of the underlying tumor biology through among other definition of precursor lesions, delineation of molecular pathways, and advances in genome-wide technology. Further, exploring the relationship between epidemiological risk factors involving metabolic features to that of an altered cancer metabolism may provide the foundation for new therapies. Here we explore how nutrients and caloric intake may influence the KRAS-driven ductal carcinogenesis through mediators of metabolic stress, including autophagy in presence of TP53, advanced glycation end products (AGE) and the receptors (RAGE) and ligands (HMGB1), as well as glutamine pathways, among others. Effective understanding the cancer metabolism mechanisms in pancreatic cancer may propose new ways of prevention and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Self-renewal molecular mechanisms of colorectal cancer stem cells.

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Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

2017-01-01

Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer.

[Molecular biology of castration-resistant prostate cancer].

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Doucet, Ludovic; Terrisse, Safae; Gauthier, Hélène; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

2015-06-01

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Prostate cancer in Port Harcourt, Nigeria: features and outcome ...

African Journals Online (AJOL)

Background: To present the clinical features and outcome of management of patients with prostate cancer in Port Harcourt, Nigeria. Methods: A retrospective study of patients with prostate cancer managed in 14 years at the University of Port Harcourt Teaching Hospital. Results: Of 154,594 men above 40 years old who ...

Molecular concept in human oral cancer.

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Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U S

2015-01-01

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.

[Prognostic and predictive molecular markers for urologic cancers].

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Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

2014-04-01

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

Integrated Molecular Imaging and Therapy for Breast Cancer

National Research Council Canada - National Science Library

Panchapakesan, Balaji

2008-01-01

...) and NIR dosing of cancer cells using SWCNT. While previous studies have shown the transport of DNA into cells using nanotubes, in this study we show multi-component molecular targeting of both IGF1R and Her2 surface markers in cancer cells...

Molecular profiling of childhood cancer: Biomarkers and novel therapies

Directory of Open Access Journals (Sweden)

Federica Saletta

2014-06-01

General significance: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

A review of molecular biomarkers for bladder cancer | Miakhil ...

African Journals Online (AJOL)

Background: Numerous molecular markers for bladder cancer have been identified and investigated with various laboratory techniques. Molecular markers are isolated from tissue, serum and urine. They fall into proteomic, genetic and epigenetic categories. Some of molecular markers show promising results in terms of ...

Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

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Reuveni T

2011-11-01

Full Text Available Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.Keywords: functional computed tomography, molecular imaging, gold nanoparticles, biologically targeted in vivo imaging, contrast agents

Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

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Wu, Hua-Hsi; Lin, Wen-chang; Tsai, Kuo-Wang

2014-01-23

Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

Molecular Cochaperones: Tumor Growth and Cancer Treatment

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Stuart K. Calderwood

2013-01-01

Full Text Available Molecular chaperones play important roles in all cellular organisms by maintaining the proteome in an optimally folded state. They appear to be at a premium in cancer cells whose evolution along the malignant pathways requires the fostering of cohorts of mutant proteins that are employed to overcome tumor suppressive regulation. To function at significant rates in cells, HSPs interact with cochaperones, proteins that assist in catalyzing individual steps in molecular chaperoning as well as in posttranslational modification and intracellular localization. We review current knowledge regarding the roles of chaperones such as heat shock protein 90 (Hsp90 and Hsp70 and their cochaperones in cancer. Cochaperones are potential targets for cancer therapy in themselves and can be used to assess the likely prognosis of individual malignancies. Hsp70 cochaperones Bag1, Bag3, and Hop play significant roles in the etiology of some cancers as do Hsp90 cochaperones Aha1, p23, Cdc37, and FKBP1. Others such as the J domain protein family, HspBP1, TTC4, and FKBPL appear to be associated with more benign tumor phenotypes. The key importance of cochaperones for many pathways of protein folding in cancer suggests high promise for the future development of novel pharmaceutical agents.

Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

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Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

2015-01-01

The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

Cancer Stem Cells and Molecular Biology Test in Colorectal Cancer: Therapeutic Implications.

Science.gov (United States)

Effendi-Ys, Rustam

2017-10-01

Colorectal cancer (CRC) is the third most frequent cancer in males, the second in females, and is the second leading cause of cancer related death worldwide. Within Indonesia's 250 million population, the incidence rates for CRC per 100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500 cases per year.  More than 50% of colorectal cancer patients will develop metastasis. CRC is still the main cause of tumor-related death, and although most CRC patients are treated with surgery to remove the tumor tissue, some of the CRC patients recurred. Chemotherapy used as adjuvant or neoadjuvant therapy also has several problems, in which these treatments are useless in tumor cells with chemo-resistance. Molecular testing of CRC from tumor tissues has important implications for the selection of treatment. Biomarkers can be used as prognostic value, molecular predictive factors, and targeted therapy. Recent research reported that, cancer stem cells (CSCs) are considered as the origin of tumorigenesis, development, metastasis and recurrence. At present, it has been shown that CSCs existed in many tumors including CRC. This review aims to summarize the issue on CSCs, and the future development of drugs that target colorectal cancer stem cells.

Molecular markers in bladder cancer: Novel research frontiers.

Science.gov (United States)

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

Molecular Characterization of ERα-positive and Triple Negative Breast Cancer

NARCIS (Netherlands)

Severson, T.M.

2016-01-01

Breast cancer, one of the most common of all cancers, is diagnosed in over 1.5 million people world-wide each year. Overall, treatments for breast cancer are considered relatively successful, however recurrence is a clinical problem of paramount importance. Molecular subtypes of breast cancer,

[Fanconi anemia: cellular and molecular features].

Science.gov (United States)

Macé, G; Briot, D; Guervilly, J-H; Rosselli, F

2007-02-01

Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure. 11 among 12 FA gene have been isolated. The biochemical functions of the FANC proteins remain poorly understood. Anyhow, to cope with DNA crosslinks a cell needs a functional FANC pathway. Moreover, the FANC proteins appear to be involved in cell protection against oxidative damage and in the control of TNF-alpha activity. In this review, we describe the current understanding of the FANC pathway and we present how it may be integrated in the complex networks of proteins involved in maintaining the cellular homeostasis.

Molecular Classification and Correlates in Colorectal Cancer

OpenAIRE

Ogino, Shuji; Goel, Ajay

2008-01-01

Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

T2-weighted MRI-derived textural features reflect prostate cancer aggressiveness: preliminary results

Energy Technology Data Exchange (ETDEWEB)

Nketiah, Gabriel; Elschot, Mattijs; Kim, Eugene; Teruel, Jose R. [NTNU, Norwegian University of Science and Technology, Department of Circulation and Medical Imaging, Faculty of Medicine, Trondheim (Norway); Scheenen, Tom W. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Bathen, Tone F.; Selnaes, Kirsten M. [NTNU, Norwegian University of Science and Technology, Department of Circulation and Medical Imaging, Faculty of Medicine, Trondheim (Norway); St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway)

2017-07-15

To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. 3T multiparametric-MRI was performed on 23 prostate cancer patients prior to prostatectomy. Textural features [angular second moment (ASM), contrast, correlation, entropy], apparent diffusion coefficient (ADC), and DCE pharmacokinetic parameters (K{sup trans} and V{sub e}) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. ASM and entropy correlated significantly (p < 0.05) with both GS and median ADC. Contrast correlated moderately with median ADC. The textural features correlated insignificantly with K{sup trans} and V{sub e}. GS 4+3 cancers had significantly lower ASM and higher entropy than 3+4 cancers, but insignificant differences in median ADC, K{sup trans}, and V{sub e}. The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. (orig.)

Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

Directory of Open Access Journals (Sweden)

Giulia Magnani

2015-01-01

Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

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

International Nuclear Information System (INIS)

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

2005-01-01

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. (note)

ROLE OF MOLECULAR MARKERS IN THYROID NODULE MANAGEMENT: THEN AND NOW.

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Nikiforov, Yuri E

2017-08-01

To describe the evolution and clinical utility of molecular testing for thyroid nodules and cancer achieved over the last 2 decades. Scientific reports on thyroid cancer genetics and molecular diagnostics in thyroid nodules. Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded, such that most thyroid cancers now have known gene driver events. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer and for the introduction of new entities such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The progress with molecular tests for thyroid nodules started in the 1990s from demonstrating feasibility of detecting various molecular alterations in fine-needle aspiration (FNA) material collected from thyroid nodules. It was followed by the introduction of the first single-gene mutational markers, such as BRAF, and a small mutational panel into clinical practice in the mid 2000s. Currently, several more advanced molecular tests are available for clinical use. They are based on multiple molecular markers and have increasing impact on the clinical management of patients with thyroid nodules. The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA samples to inform more individualized management of these patients. FNA = fine-needle aspiration miRNA = micro RNA NGS = next-generation sequencing NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features NPV = negative predictive value PPV = positive predictive value PTC = papillary thyroid carcinoma RAI = radioactive iodine.

Molecular Biomarkers in the Clinical Management of Prostate Cancer.

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Udager, Aaron M; Tomlins, Scott A

2018-01-08

Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

UPAR targeted molecular imaging of cancers with small molecule-based probes.

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Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

2017-10-15

Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

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Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

2016-08-15

A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

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Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

2015-05-01

Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

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

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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.

Observations of the interstellar ice grain feature in the Taurus molecular clouds

International Nuclear Information System (INIS)

Whittet, D.C.B.; Longmore, A.J.; Baines, D.W.T.; Evans, A.

1984-01-01

Although water ice was originally proposed as a major constituent of the interstellar grain population, the advent of infrared astronomy has shown that the expected absorption due to O-H stretching vibrations at 3 μm is illusive. Observations have in fact revealed that the carrier of this feature is apparently restricted to regions deep within dense molecular clouds. However, the exact carrier of this feature is still controversial, and many questions remain as to the conditions required for its appearance. The Taurus molecular clouds were selected for observations, in the form of a preliminary survey in the 2-4 μm window. It is concluded that the carrier of the 3μm absorption feature appears to reside in the general cloud medium and is probably amorphous water ice. (author)

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

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Jácome, Alexandre Andrade Dos Anjos; Lima, Enaldo Melo de; Kazzi, Ana Izabela; Chaves, Gabriela Freitas; Mendonça, Diego Cavalheiro de; Maciel, Marina Mara; Santos, José Sebastião Dos

2016-04-01

Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Genetic, functional and molecular features of glucocorticoid receptor binding.

Directory of Open Access Journals (Sweden)

Francesca Luca

Full Text Available Glucocorticoids (GCs are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR, which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI and 4 Tuscans (TSI lymphoblastoid cell lines (LCLs, we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative depending on the presence of specific interacting transcription factors. Accordingly, when we performed ChIP-seq for GR and NF-κB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.

The hallmarks of premalignant conditions: a molecular basis for cancer prevention.

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Ryan, Bríd M; Faupel-Badger, Jessica M

2016-02-01

The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures. Published by Elsevier Inc.

Self-renewal molecular mechanisms of colorectal cancer stem cells

OpenAIRE

Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

2016-01-01

Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0737 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH...that there exist distinctive molecular correlates of PTEN loss in the context of ETS-negative versus ETS-positive human prostate cancers and that

Molecular mechanisms of cisplatin resistance in cervical cancer.

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Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

2016-01-01

Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer.

Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.

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Kryza, Thomas; Silva, Lakmali M; Bock, Nathalie; Fuhrman-Luck, Ruth A; Stephens, Carson R; Gao, Jin; Samaratunga, Hema; Lawrence, Mitchell G; Hooper, John D; Dong, Ying; Risbridger, Gail P; Clements, Judith A

2017-10-01

The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Mammographic features and misdiagnosed analysis on 92 cases with breast cancer

International Nuclear Information System (INIS)

Liu Mingjuan; Zhang Xiaoling; Guo Yan

2010-01-01

Objective: To investigate the atypical X-ray features in breast cancer and improve the accuracy of diagnosis. Methods: Mammographic features of 92 cases with pathologically confirmed breast cancer were analyzed retrospectively. Results: High-density mass with speculated margined, clusters of small calcification, stellate-like lesions were found in 51 cases, the rate of correct diagnosis was 96%-100%. Lobulated high-density mass were found in 17 cases, the correct diagnosis rate was about 88.3% cases with skin thickening were all correctly diagnosed. Round mass, focal parenchymal asymmetry and unidentified lesions were found in 20 cases, the diagnosing rate was less than 20%. Conclusion: Round mass, focal parenchymal asymmetry and unidentified lesions were atypical mammographic features of breast cancer. These lesions were misdiagnosed frequently. It is essential to find the indirect signs and associated finding to avoid misdiagnosis. On the other hand, further ultrasound or MRI were helpful to improve the diagnosis by detecting mass in breast, showing cystic lesions and blood supply. (authors)

Prognostic molecular markers in early breast cancer

International Nuclear Information System (INIS)

Esteva, Francisco J; Hortobagyi, Gabriel N

2004-01-01

A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D 1 and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

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Soumittra Nagasamy

2009-08-01

Full Text Available Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16% pathogenic mutations (12 in BRCA1 and 3 in BRCA2, of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free and with prognostic molecular markers (ER, PR, c-erbB2 and p53. Conclusion The stage of the disease at diagnosis was the only statistically significant (p

Scattering features for lung cancer detection in fibered confocal fluorescence microscopy images.

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Rakotomamonjy, Alain; Petitjean, Caroline; Salaün, Mathieu; Thiberville, Luc

2014-06-01

To assess the feasibility of lung cancer diagnosis using fibered confocal fluorescence microscopy (FCFM) imaging technique and scattering features for pattern recognition. FCFM imaging technique is a new medical imaging technique for which interest has yet to be established for diagnosis. This paper addresses the problem of lung cancer detection using FCFM images and, as a first contribution, assesses the feasibility of computer-aided diagnosis through these images. Towards this aim, we have built a pattern recognition scheme which involves a feature extraction stage and a classification stage. The second contribution relies on the features used for discrimination. Indeed, we have employed the so-called scattering transform for extracting discriminative features, which are robust to small deformations in the images. We have also compared and combined these features with classical yet powerful features like local binary patterns (LBP) and their variants denoted as local quinary patterns (LQP). We show that scattering features yielded to better recognition performances than classical features like LBP and their LQP variants for the FCFM image classification problems. Another finding is that LBP-based and scattering-based features provide complementary discriminative information and, in some situations, we empirically establish that performance can be improved when jointly using LBP, LQP and scattering features. In this work we analyze the joint capability of FCFM images and scattering features for lung cancer diagnosis. The proposed method achieves a good recognition rate for such a diagnosis problem. It also performs well when used in conjunction with other features for other classical medical imaging classification problems. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecularly targeted drugs for metastatic colorectal cancer

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Cheng YD

2013-11-01

Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

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Li, Xia; Yao, Xiaoping; Wang, Yibaina; Hu, Fulan; Wang, Fan; Jiang, Liying; Liu, Yupeng; Wang, Da; Sun, Guizhi; Zhao, Yashuang

2013-01-01

Purpose To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis. Methods A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. Results The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; PMLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; PMLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation. PMID:23555617

Animal models and therapeutic molecular targets of cancer: utility and limitations

Directory of Open Access Journals (Sweden)

Cekanova M

2014-10-01

Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

[Colorectal cancer (CCR): genetic and molecular alterations].

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Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

2014-01-01

The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

Unique molecular landscapes in cancer: implications for individualized, curated drug combinations.

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Wheler, Jennifer; Lee, J Jack; Kurzrock, Razelle

2014-12-15

With increasingly sophisticated technologies in molecular biology and "omic" platforms to analyze patients' tumors, more molecular diversity and complexity in cancer are being observed. Recently, we noted unique genomic profiles in a group of patients with metastatic breast cancer based on an analysis with next-generation sequencing. Among 57 consecutive patients, no two had the same molecular portfolio. Applied genomics therefore appears to represent a disruptive innovation in that it unveils a heterogeneity to metastatic cancer that may be ill-suited to canonical clinical trials and practice paradigms. Upon recognizing that patients have unique tumor landscapes, it is possible that there may be a "mismatch" between our traditional clinical trials system that selects patients based on common characteristics to evaluate a drug (drug-centric approach) and optimal treatment based on curated, individualized drug combinations for each patient (patient-centric approach). ©2014 American Association for Cancer Research.

Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

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Wu, Mingxiang; Ma, Jie

2017-04-01

Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

OpenAIRE

George H Sakorafas; Vasileios Smyrniotis

2012-01-01

Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

Mining genome sequencing data to identify the genomic features linked to breast cancer histopathology

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Ping, Zheng; Siegal, Gene P.; Almeida, Jonas S.; Schnitt, Stuart J.; Shen, Dejun

2014-01-01

Background: Genetics and genomics have radically altered our understanding of breast cancer progression. However, the genomic basis of various histopathologic features of breast cancer is not yet well-defined. Materials and Methods: The Cancer Genome Atlas (TCGA) is an international database containing a large collection of human cancer genome sequencing data. cBioPortal is a web tool developed for mining these sequencing data. We performed mining of TCGA sequencing data in an attempt to characterize the genomic features correlated with breast cancer histopathology. We first assessed the quality of the TCGA data using a group of genes with known alterations in various cancers. Both genome-wide gene mutation and copy number changes as well as a group of genes with a high frequency of genetic changes were then correlated with various histopathologic features of invasive breast cancer. Results: Validation of TCGA data using a group of genes with known alterations in breast cancer suggests that the TCGA has accurately documented the genomic abnormalities of multiple malignancies. Further analysis of TCGA breast cancer sequencing data shows that accumulation of specific genomic defects is associated with higher tumor grade, larger tumor size and receptor negativity. Distinct groups of genomic changes were found to be associated with the different grades of invasive ductal carcinoma. The mutator role of the TP53 gene was validated by genomic sequencing data of invasive breast cancer and TP53 mutation was found to play a critical role in defining high tumor grade. Conclusions: Data mining of the TCGA genome sequencing data is an innovative and reliable method to help characterize the genomic abnormalities associated with histopathologic features of invasive breast cancer. PMID:24672738

Mining genome sequencing data to identify the genomic features linked to breast cancer histopathology

Directory of Open Access Journals (Sweden)

Zheng Ping

2014-01-01

Full Text Available Background: Genetics and genomics have radically altered our understanding of breast cancer progression. However, the genomic basis of various histopathologic features of breast cancer is not yet well-defined. Materials and Methods: The Cancer Genome Atlas (TCGA is an international database containing a large collection of human cancer genome sequencing data. cBioPortal is a web tool developed for mining these sequencing data. We performed mining of TCGA sequencing data in an attempt to characterize the genomic features correlated with breast cancer histopathology. We first assessed the quality of the TCGA data using a group of genes with known alterations in various cancers. Both genome-wide gene mutation and copy number changes as well as a group of genes with a high frequency of genetic changes were then correlated with various histopathologic features of invasive breast cancer. Results: Validation of TCGA data using a group of genes with known alterations in breast cancer suggests that the TCGA has accurately documented the genomic abnormalities of multiple malignancies. Further analysis of TCGA breast cancer sequencing data shows that accumulation of specific genomic defects is associated with higher tumor grade, larger tumor size and receptor negativity. Distinct groups of genomic changes were found to be associated with the different grades of invasive ductal carcinoma. The mutator role of the TP53 gene was validated by genomic sequencing data of invasive breast cancer and TP53 mutation was found to play a critical role in defining high tumor grade. Conclusions: Data mining of the TCGA genome sequencing data is an innovative and reliable method to help characterize the genomic abnormalities associated with histopathologic features of invasive breast cancer.

When fear of cancer recurrence becomes a clinical issue: a qualitative analysis of features associated with clinical fear of cancer recurrence.

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Mutsaers, Brittany; Jones, Georden; Rutkowski, Nicole; Tomei, Christina; Séguin Leclair, Caroline; Petricone-Westwood, Danielle; Simard, Sébastien; Lebel, Sophie

2016-10-01

Fear of cancer recurrence (FCR) is a common experience for cancer survivors. However, it remains unclear what characteristics differentiate non-clinical from clinical levels of FCR. The goal of this study was to investigate the potential hallmarks of clinical FCR. A convenience sample of 40 participants (n = 19 female) was drawn from another study (Lebel et al. in Qual Life Res 25:311-321. doi: 10.1007/s11136-015-1088-2 , 2016). The semi-structured interview for fear of cancer recurrence (Simard and Savard in J Cancer Surviv 9:481-491. doi: 10.1007/s11764-015-0424-4 , 2015) was used to identify participants with non-clinical and clinical FCR and qualitative analysis of these interviews was performed. Individuals with clinical FCR reported the following features: death-related thoughts, feeling alone, belief that the cancer would return, experiencing intolerance of uncertainty, having cancer-related thoughts and imagery that were difficult to control, daily and recurrent, lasted 30 minutes or more, increased over time, caused distress and impacted their daily life. Triggers of FCR and coping strategies did not appear to be features of clinical FCR as they were reported by participants with a range of FCR scores. While features of clinical FCR found in this analysis such as intrusive thoughts, distress and impact on functioning confirmed previous FCR research, other features spontaneously emerged from the interviews including "death-related thoughts," "feeling alone," and "belief that the cancer will return." The participants' descriptions of cancer-specific fear and worry suggest that FCR is a distinct phenomenon related to cancer survivorship, despite similarities with psychological disorders (e.g., Anxiety Disorders). Future research investigating the construct of FCR, and the distinguishing features of clinical FCR across a range of cancer types and gender is required.

Molecular epidemiology, and possible real-world applications in breast cancer.

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Ito, Hidemi; Matsuo, Keitaro

2016-01-01

Gene-environment interaction, a key idea in molecular epidemiology, has enabled the development of personalized medicine. This concept includes personalized prevention. While genome-wide association studies have identified a number of genetic susceptibility loci in breast cancer risk, however, the application of this knowledge to practical prevention is still underway. Here, we briefly review the history of molecular epidemiology and its progress in breast cancer epidemiology. We then introduce our experience with the trial combination of GWAS-identified loci and well-established lifestyle and reproductive risk factors in the risk prediction of breast cancer. Finally, we report our exploration of the cumulative risk of breast cancer based on this risk prediction model as a potential tool for individual risk communication, including genetic risk factors and gene-environment interaction with obesity.

Molecular Imaging and Precision Medicine in Prostate Cancer.

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Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

2017-01-01

The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

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Ahn, Byeong-Cheol

2016-01-01

Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

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

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

2016-01-01

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. To

A COMPARATIVE ANALYSIS OF SINGLE AND COMBINATION FEATURE EXTRACTION TECHNIQUES FOR DETECTING CERVICAL CANCER LESIONS

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S. Pradeep Kumar Kenny

2016-02-01

Full Text Available Cervical cancer is the third most common form of cancer affecting women especially in third world countries. The predominant reason for such alarming rate of death is primarily due to lack of awareness and proper health care. As they say, prevention is better than cure, a better strategy has to be put in place to screen a large number of women so that an early diagnosis can help in saving their lives. One such strategy is to implement an automated system. For an automated system to function properly a proper set of features have to be extracted so that the cancer cell can be detected efficiently. In this paper we compare the performances of detecting a cancer cell using a single feature versus a combination feature set technique to see which will suit the automated system in terms of higher detection rate. For this each cell is segmented using multiscale morphological watershed segmentation technique and a series of features are extracted. This process is performed on 967 images and the data extracted is subjected to data mining techniques to determine which feature is best for which stage of cancer. The results thus obtained clearly show a higher percentage of success for combination feature set with 100% accurate detection rate.

Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases.

Science.gov (United States)

Ouaissi, Ali; Ouaissi, Mehdi

2005-01-01

A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.

Molecular imaging of cancer using PET and SPECT

DEFF Research Database (Denmark)

Kjaer, Andreas

2006-01-01

for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm......Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...

Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment

DEFF Research Database (Denmark)

Hojman, Pernille; Gehl, Julie; Christensen, Jesper F.

2018-01-01

The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. We propose...... that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications......, as this understanding may lead to changes in cancer treatment strategies. Hojman et al. discuss the role of exercise in controlling cancer progression through direct effects on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of cancer...

Molecular features of colorectal polyps presenting Kudo's type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis?

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Shinmura, Kensuke; Konishi, Kazuo; Yamochi, Toshiko; Kubota, Yutaro; Yano, Yuichiro; Katagiri, Atsushi; Muramoto, Takashi; Kihara, Toshihiro; Tojo, Masayuki; Konda, Kenichi; Tagawa, Teppei; Yanagisawa, Fumito; Kogo, Mari; Makino, Reiko; Takimoto, Masafumi; Yoshida, Hitoshi

2014-09-01

The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo's type II observed by chromoendoscopy, were evaluated. The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs.

A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

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Reinders Marcel JT

2009-11-01

Full Text Available Abstract Background Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the observed discrepancies are the measurement error associated with each feature and the choice of preprocessing method. Microarray data are known to be subject to technical variation and the confidence intervals around individual point estimates of expression levels can be wide. Furthermore, the estimated expression values also vary depending on the selected preprocessing scheme. In microarray breast cancer classification studies, however, these two forms of feature variability are almost always ignored and hence their exact role is unclear. Results We have performed a comprehensive sensitivity analysis of microarray breast cancer classification under the two types of feature variability mentioned above. We used data from six state of the art preprocessing methods, using a compendium consisting of eight diferent datasets, involving 1131 hybridizations, containing data from both one and two-color array technology. For a wide range of classifiers, we performed a joint study on performance, concordance and stability. In the stability analysis we explicitly tested classifiers for their noise tolerance by using perturbed expression profiles that are based on uncertainty information directly related to the preprocessing methods. Our results indicate that signature composition is strongly influenced by feature variability, even if the array platform and the stratification of patient samples are identical. In addition, we show that there is often a high level of discordance between individual class assignments for signatures constructed on data coming from different preprocessing schemes, even if the actual signature composition is identical

Feature Extraction and Analysis of Breast Cancer Specimen

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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.

Histomorphological features of combined forms of tuberculosis and lung cancer

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Savenkov Y.F.

2017-04-01

Full Text Available The were studied pathological features of combined forms of tuberculosis and non-small cell lung cancer in 72 patients who underwent radical surgical resection interventions from transsternal access with mediastinal lymph node dissection, with predominance of pneumonectomy - 63.9%. There were identified three main categories of pathological changes: cancer on the background of post-tuberculosis changes, cancer in tuberculoma, cancer in the wall of the active cavity. Post-tuberculosis changes were presented by dense centers, fibrosis, cirrhosis areas, sanitized cavities with histological predominance of coarse fiber connective tissue with giant cell granulomas, with areas characterized by the appearance of the lung tissue with atypical proliferation and metaplasia of bronchopulmonary epithelium, which is a precancerous condition. This malignant tumor process was presented mainly by adenocarcinomas and squamous cell cancer and differred by polymorphic macro- and microscopic picture. Cancer in tuberculoma and fibrous wall cavity differed by pronounced activity of tuberculosis process in the form of lymphohistiocytic infiltration, foci of caseous necrosis and presence of expressed granulation layer of Pirogov-Langhans’ cells. The basic morphological causes of carcinogenesis due to secondary changes of lung tissue in patients with tuberculosis were determined. The features of metastasis of malignant tumors on the background of specific tuberculous and post-tuberculosis changes in regional lymph nodes and the interrelation between the frequency of metastatic lesions with severity of tuberculosis and post-tuberculosis changes in them were studied; this has clinical significance in the surgical treatment of patients with concomitant forms of tuberculosis and lung cancer.

An expert support system for breast cancer diagnosis using color wavelet features.

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Issac Niwas, S; Palanisamy, P; Chibbar, Rajni; Zhang, W J

2012-10-01

Breast cancer diagnosis can be done through the pathologic assessments of breast tissue samples such as core needle biopsy technique. The result of analysis on this sample by pathologist is crucial for breast cancer patient. In this paper, nucleus of tissue samples are investigated after decomposition by means of the Log-Gabor wavelet on HSV color domain and an algorithm is developed to compute the color wavelet features. These features are used for breast cancer diagnosis using Support Vector Machine (SVM) classifier algorithm. The ability of properly trained SVM is to correctly classify patterns and make them particularly suitable for use in an expert system that aids in the diagnosis of cancer tissue samples. The results are compared with other multivariate classifiers such as Naïves Bayes classifier and Artificial Neural Network. The overall accuracy of the proposed method using SVM classifier will be further useful for automation in cancer diagnosis.

Quantitative imaging as cancer biomarker

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Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

Cancer Feature Selection and Classification Using a Binary Quantum-Behaved Particle Swarm Optimization and Support Vector Machine

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Maolong Xi

2016-01-01

Full Text Available This paper focuses on the feature gene selection for cancer classification, which employs an optimization algorithm to select a subset of the genes. We propose a binary quantum-behaved particle swarm optimization (BQPSO for cancer feature gene selection, coupling support vector machine (SVM for cancer classification. First, the proposed BQPSO algorithm is described, which is a discretized version of original QPSO for binary 0-1 optimization problems. Then, we present the principle and procedure for cancer feature gene selection and cancer classification based on BQPSO and SVM with leave-one-out cross validation (LOOCV. Finally, the BQPSO coupling SVM (BQPSO/SVM, binary PSO coupling SVM (BPSO/SVM, and genetic algorithm coupling SVM (GA/SVM are tested for feature gene selection and cancer classification on five microarray data sets, namely, Leukemia, Prostate, Colon, Lung, and Lymphoma. The experimental results show that BQPSO/SVM has significant advantages in accuracy, robustness, and the number of feature genes selected compared with the other two algorithms.

Cancer Feature Selection and Classification Using a Binary Quantum-Behaved Particle Swarm Optimization and Support Vector Machine

Science.gov (United States)

Sun, Jun; Liu, Li; Fan, Fangyun; Wu, Xiaojun

2016-01-01

This paper focuses on the feature gene selection for cancer classification, which employs an optimization algorithm to select a subset of the genes. We propose a binary quantum-behaved particle swarm optimization (BQPSO) for cancer feature gene selection, coupling support vector machine (SVM) for cancer classification. First, the proposed BQPSO algorithm is described, which is a discretized version of original QPSO for binary 0-1 optimization problems. Then, we present the principle and procedure for cancer feature gene selection and cancer classification based on BQPSO and SVM with leave-one-out cross validation (LOOCV). Finally, the BQPSO coupling SVM (BQPSO/SVM), binary PSO coupling SVM (BPSO/SVM), and genetic algorithm coupling SVM (GA/SVM) are tested for feature gene selection and cancer classification on five microarray data sets, namely, Leukemia, Prostate, Colon, Lung, and Lymphoma. The experimental results show that BQPSO/SVM has significant advantages in accuracy, robustness, and the number of feature genes selected compared with the other two algorithms. PMID:27642363

Using cell nuclei features to detect colon cancer tissue in hematoxylin and eosin stained slides.

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Jørgensen, Alex Skovsbo; Rasmussen, Anders Munk; Andersen, Niels Kristian Mäkinen; Andersen, Simon Kragh; Emborg, Jonas; Røge, Rasmus; Østergaard, Lasse Riis

2017-08-01

Currently, diagnosis of colon cancer is based on manual examination of histopathological images by a pathologist. This can be time consuming and interpretation of the images is subject to inter- and intra-observer variability. This may be improved by introducing a computer-aided diagnosis (CAD) system for automatic detection of cancer tissue within whole slide hematoxylin and eosin (H&E) stains. Cancer disrupts the normal control mechanisms of cell proliferation and differentiation, affecting the structure and appearance of the cells. Therefore, extracting features from segmented cell nuclei structures may provide useful information to detect cancer tissue. A framework for automatic classification of regions of interest (ROI) containing either benign or cancerous colon tissue extracted from whole slide H&E stained images using cell nuclei features was proposed. A total of 1,596 ROI's were extracted from 87 whole slide H&E stains (44 benign and 43 cancer). A cell nuclei segmentation algorithm consisting of color deconvolution, k-means clustering, local adaptive thresholding, and cell separation was performed within the ROI's to extract cell nuclei features. From the segmented cell nuclei structures a total of 750 texture and intensity-based features were extracted for classification of the ROI's. The nine most discriminative cell nuclei features were used in a random forest classifier to determine if the ROI's contained benign or cancer tissue. The ROI classification obtained an area under the curve (AUC) of 0.96, sensitivity of 0.88, specificity of 0.92, and accuracy of 0.91 using an optimized threshold. The developed framework showed promising results in using cell nuclei features to classify ROIs into containing benign or cancer tissue in H&E stained tissue samples. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

Molecular markers in breast cancer: new tools in imaging and prognosis

NARCIS (Netherlands)

Vermeulen, J.F.

2012-01-01

Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared

Molecular lipidomics of exosomes released by PC-3 prostate cancer cells

DEFF Research Database (Denmark)

Llorente, A.; Skotland, T.; Sylvanne, T.

2013-01-01

The molecular lipid composition of exosomes is largely unknown. In this study, sophisticated shotgun and targeted molecular lipidomic assays were performed for in-depth analysis of the lipidomes of the metastatic prostate cancer cell line, PC-3, and their released exosomes. This study, based...... in the quantification of approximately 280 molecular lipid species, provides the most extensive lipid analysis of cells and exosomes to date. Interestingly, major differences were found in the lipid composition of exosomes compared to parent cells. Exosomes show a remarkable enrichment of distinct lipids, demonstrating...... potentially be used as cancer biomarkers. (C) 2013 Elsevier B.V. All rights reserved....

CT features of lung cancer associated with idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Kim, Jun Hyoung; Song, Koun Sik; Lee, Deok Hee; Kim, Jin Suh; Lim, Tae Hwan

1996-01-01

It is well known that the incidence of lung cancer is high in patients with idiopathic pulmonary fibrosis(IPF). We analyzed the CT features of lung cancer associated with IPF. Retrospective analyzed the CT features of lung cancer associated with IPF. Retrospective analysis was performed in 23 patients with lung cancer(24 lung cancers) associated with IPF. The diagnosis of IPF was made by clinical and CT findings, and lung cancer was confirmed pathologically. We divided the location of lung cancer by lobar distribution and central or peripheral lung zone, and measured the size of mass. We classified the mediastinal lymph node enlargement by American Thoracic Society (ATS) mapping scheme. We evaluated the CT pattern of IPF. The subjects consisted of 6 cases of small cell carcinoma and 18 cases of non-small cell lung cancer. Non-small cell lung cancers were located in the right upper lobe in 5 cases, left upper lobe in 6 cases, right middle lobe in 1 case, right lower lobe in 9 cases, and left lower lobe in 3 cases. Twenty cancers(85%) were located in the peripheral lung zone. Eighteen cancers(73%) were surrounded by fibrotic lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3 cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung cancers. CT patterns of underlying IPF were honey-combing in 18 patients(78%) and mixed honey-combing and ground-glass opacity in 5 patients(22%). The lung cancer associated with IPF shows variable cell types. Most of the lung cancers were located peripherally, surrounded by end-stage fibrosis, and were associated with mediastinal lymph node enlargement

CT features of lung cancer associated with idiopathic pulmonary fibrosis

Energy Technology Data Exchange (ETDEWEB)

Kim, Jun Hyoung; Song, Koun Sik; Lee, Deok Hee; Kim, Jin Suh; Lim, Tae Hwan [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

1996-01-01

It is well known that the incidence of lung cancer is high in patients with idiopathic pulmonary fibrosis(IPF). We analyzed the CT features of lung cancer associated with IPF. Retrospective analyzed the CT features of lung cancer associated with IPF. Retrospective analysis was performed in 23 patients with lung cancer(24 lung cancers) associated with IPF. The diagnosis of IPF was made by clinical and CT findings, and lung cancer was confirmed pathologically. We divided the location of lung cancer by lobar distribution and central or peripheral lung zone, and measured the size of mass. We classified the mediastinal lymph node enlargement by American Thoracic Society (ATS) mapping scheme. We evaluated the CT pattern of IPF. The subjects consisted of 6 cases of small cell carcinoma and 18 cases of non-small cell lung cancer. Non-small cell lung cancers were located in the right upper lobe in 5 cases, left upper lobe in 6 cases, right middle lobe in 1 case, right lower lobe in 9 cases, and left lower lobe in 3 cases. Twenty cancers(85%) were located in the peripheral lung zone. Eighteen cancers(73%) were surrounded by fibrotic lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3 cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung cancers. CT patterns of underlying IPF were honey-combing in 18 patients(78%) and mixed honey-combing and ground-glass opacity in 5 patients(22%). The lung cancer associated with IPF shows variable cell types. Most of the lung cancers were located peripherally, surrounded by end-stage fibrosis, and were associated with mediastinal lymph node enlargement.

Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

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Metka Ravnik-Glavač

2005-07-01

Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

Molecular targeted therapies of aggressive thyroid cancer

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Silvia Martina eFerrari

2015-11-01

Full Text Available Differentiated thyroid carcinomas (DTC that arise from follicular cells account > 90% of thyroid cancer (TC [papillary thyroid cancer (PTC 90%, follicular thyroid cancer (FTC 10%], while medullary thyroid cancer (MTC accounts < 5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts towards the development of new drugs.Several genetic alterations in different molecular pathways in TC have been shown in the last decades, associated with TC development and progression. Rearranged during transfection (RET/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the above-mentioned molecular pathways involved in growth, angiogenesis, local and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC and anaplastic thyroid cancer (ATC, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds, and to personalize

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

Science.gov (United States)

Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

2018-01-01

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

Early Detection of Breast Cancer Using Molecular Beacons

National Research Council Canada - National Science Library

Yang, Lily

2008-01-01

.... We proposed to use molecular beacon technology to detect the level of expression of several biomarker genes that are highly expressed in breast cancer cells but not in normal breast epithelial cells...

Molecular and biological interactions in colorectal cancer

NARCIS (Netherlands)

Heer, Pieter de

2007-01-01

The current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell motility (non-receptor protein tyrosin adesion kinases, FAK, Src and paxillin, Apoptosis (caspase-3

Development of novel HER2 inhibitors against gastric cancer derived from flavonoid source of Syzygium alternifolium through molecular dynamics and pharmacophore-based screening

Directory of Open Access Journals (Sweden)

Babu TMC

2016-11-01

Full Text Available Tirumalasetty Muni Chandra Babu,1 Aluru Rammohan,2 Vijaya Bhaskar Baki,1 Savita Devi,3 Duvvuru Gunasekar,2 Wudayagiri Rajendra1 1Bioinformatics Center, Division of Molecular Biology, Department of Zoology, 2Natural Products Division, Department of Chemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 3Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India Abstract: Continuous usage of synthetic chemotherapeutic drugs causes adverse effects, which prompted for the development of alternative therapeutics for gastric cancer from natural source. This study was carried out with a specific aim to screen gastroprotective compounds from the fruits of Syzygium alternifolium (Myrtaceae. Three flavonoids, namely, 1 5-hydroxy-7,4'-dimethoxy-6,8-di-C-methylflavone, 2 kaempferol-3-O-β-D-glucopyranoside, and 3 kaempferol-3-O-α-L-rhamnopyranoside were isolated from the above medicinal plant by employing silica gel column chromatography and are characterized by NMR techniques. Antigastric cancer activity of these flavonoids was examined on AGS cell lines followed by cell cycle progression assay. In addition, pharmacophore-based screening and molecular dynamics of protein–ligand complex were carried out to identify potent scaffolds. The results showed that compounds 2 and 3 exhibited significant cytotoxic effect, whereas compound 1 showed moderate effect on AGS cells by inhibiting G2/M phase of cell cycle. Molecular docking analysis revealed that compound 2 has higher binding energies on human growth factor receptor-2 (HER2. The constructed pharmacophore models reveal that the compounds have more number of H-bond Acc/Don features which contribute to the inhibition of HER2 activity. By selecting these features, 34 hits were retrieved using the query compound 2. Molecular dynamic simulations (MDS of protein–ligand complexes demonstrated conspicuous

Inflammation to cancer: The molecular biology in the pancreas (Review)

OpenAIRE

LING, SUNBIN; FENG, TINGTING; JIA, KAIQI; TIAN, YU; LI, YAN

2014-01-01

Inflammatory responses are known to be correlated with cancer initiation and progression, and exploration of the route from inflammation to cancer makes a great contribution in elucidating the mechanisms underlying cancer development. Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and a poor prognosis. As chronic pancreatitis is considered to be a significant etiological factor for PC development, the current review aims to describe the molecular pathways from in...

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

Science.gov (United States)

Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

2018-03-26

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

Molecular prognostic markers in ovarian cancer : toward patient-tailored therapy

NARCIS (Netherlands)

Crijns, APG; Duiker, EW; de Jong, S; Willemse, PHB; van der Zee, AGJ; de Vries, EGE

2006-01-01

In ovarian cancer the ceiling seems to be reached with chemotherapeutic drugs. Therefore a paradigm shift is needed. Instead of treating all patients according to standard guidelines, individualized molecular targeted treatment should be aimed for. This means that molecular profiles of the distinct

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

Science.gov (United States)

Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

MLH1 promoter methylation frequency in colorectal cancer patients and related clinicopathological and molecular features.

Directory of Open Access Journals (Sweden)

Xia Li

Full Text Available To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC; to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR and 95% confidence intervals (95% CI were calculated.The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8-24.1%. They were 18.7% (95% CI: 14.7-23.6% and 16.4% (95% CI: 11.9-22.0% in sporadic and Lynch syndrome (LS CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215-2.215; P = 0.001, tumor location (pooled OR = 3.804, 95% CI: 2.715-5.329; P<0.001, tumor differentiation (pooled OR = 2.131, 95% CI: 1.464-3.102; P<0.001, MSI (OR: 27.096, 95% CI: 13.717-53.526; P<0.001. Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427-34.631; P<0.001 and 9.419 (95% CI: 2.613-33.953; P = 0.001, respectively.The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.

Analysis of the Clinicopathologic Features and Prognosis in Triple-Negative Breast Cancer

Institute of Scientific and Technical Information of China (English)

Dehong Yang; Hong Liu; Jing Zhao

2008-01-01

OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 treated in the Cancer Hospital of Tianjin Medical University were analyzed.The Her-2,ER and PR status was determined using immunohistochemistry.Of the total cases,one group was identified as triple negative breast cancer,ie defined as ER,PR and Her-2 negative.The other group was nontriple-negative breast cancer.Clinicopathologic features of the groups were compared and 5-year disease-free survival (DFS)analyzed by the Kaplan-Meier method.RESULTS Of the total cases,21.4% (109/509) of cases were found to be triple- negative while 78.6% (400/509) were non-triplenegative.The triple negative group had higher incidence rates than the non-triple-negative group of the medullary type and Grade Ⅲ tumors (P ＜ 0.05).There was no other difference in the clinicopathologic features between the 2 groups.From follow-up to June,2007,21.1% (23/109) of the triple-negative group and 12.7%(51/400) of the non-triple negative group had a local recurrence or distant metastasis,resulting in a significant difference (P ＜ 0.05).In the triple-negative group and non-triple-negative group,5-year DFS were 78.9% and 87.3% respectively.There was a statistically significant difference between the 2 groups (P = 0.031).CONCLUSION Compared with non-triple-negative breast cancer,triple-negative breast cancer patients have an increased likehood of a local recurrence or distant metastasis and a poorer prognosis.

Molecular and neuroendocrine mechanisms of cancer cachexia.

Science.gov (United States)

Mendes, Maria Carolina S; Pimentel, Gustavo D; Costa, Felipe O; Carvalheira, José B C

2015-09-01

Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment. © 2015 Society for Endocrinology.

Molecular biological features of male germ cell differentiation

Science.gov (United States)

HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

2007-01-01

Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

Molecular diagnosis of prostate cancer: Topical issues

Directory of Open Access Journals (Sweden)

E. N. Knyazev

2014-12-01

Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

Molecular features of colorectal polyps presenting Kudo’s type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis?

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Shinmura, Kensuke; Konishi, Kazuo; Yamochi, Toshiko; Kubota, Yutaro; Yano, Yuichiro; Katagiri, Atsushi; Muramoto, Takashi; Kihara, Toshihiro; Tojo, Masayuki; Konda, Kenichi; Tagawa, Teppei; Yanagisawa, Fumito; Kogo, Mari; Makino, Reiko; Takimoto, Masafumi; Yoshida, Hitoshi

2014-01-01

Background and study aims: The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo’s type II observed by chromoendoscopy, were evaluated. Methods: The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. Results: Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. Conclusions: Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs. PMID:26134964

Are clinicopathological features of colorectal cancers with methylation in half of CpG island methylator phenotype panel markers different from those of CpG island methylator phenotype-high colorectal cancers?

Science.gov (United States)

Bae, Jeong Mo; Rhee, Ye-Young; Kim, Kyung Ju; Wen, Xianyu; Song, Young Seok; Cho, Nam-Yun; Kim, Jung Ho; Kang, Gyeong Hoon

2016-01-01

CpG island methylator phenotype (CIMP)-high (CIMP-H) colorectal cancer (CRC) is defined when a tumor shows methylation at greater than or equal to 60% of CIMP panel markers. Although CRCs with methylation at 50% of panel markers are classified as CIMP-low/CIMP-0 tumors, little is known regarding the clinicopathological and molecular features of CRCs with methylation at 4/8 panel markers (4/8 methylated markers) and whether they are akin to CIMP-H or CIMP-low/CIMP-0 CRCs in terms of their clinicopathological or molecular features. A total of 1164 cases of surgically resected CRC were analyzed for their methylation status in 8 CIMP panel markers, and the frequencies of various clinicopathological and molecular features were compared between CRCs with 0/8, 1/8 to 3/8, 4/8, and 5/8 to 8/8 methylated markers. CRCs with 4/8 methylated markers were closer to CRCs with 5/8 to 8/8 methylated markers in terms of sex distribution, mucin production, serration, nodal metastasis, CK7 expression, CK20 loss, and CDX2 loss frequencies and overall survival rate. CRCs with methylation at 4/8 markers were closer to CRCs with 1/8 to 3/8 methylated markers in terms of less frequent right colon location and poor differentiation. CRCs with 4/8 methylated markers showed the shortest overall survival time compared with CRCs with 0/8, 1/8 to 3/8, 4/8, or 5/8 to 8/8 methylated markers. In terms of clinicopathological and molecular features, CRCs with 4/8 methylated markers appeared to be closer to CIMP-H than to CIMP-low/CIMP-0 and would thus be better classified as CIMP-H if the CRCs require classification into either CIMP-H or CIMP-low/CIMP-0. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular and genetic epidemiology of cancer in low- and medium-income countries.

Science.gov (United States)

Malhotra, Jyoti

2014-01-01

Genetic and molecular factors can play an important role in an individual's cancer susceptibility and response to carcinogen exposure. Cancer susceptibility and response to carcinogen exposure can be either through inheritance of high penetrance but rare germline mutations that constitute heritable cancer syndromes, or it can be inherited as common genetic variations or polymorphisms that are associated with low to moderate risk for development of cancer. These polymorphisms can interact with environmental exposures and can influence an individual's cancer risk through multiple pathways, including affecting the rate of metabolism of carcinogens or the immune response to these toxins. Thus, these genetic polymorphisms can account for some of the geographical differences seen in cancer prevalence between different populations. This review explores the role of molecular epidemiology in the field of cancer prevention and control in low- and medium-income countries. Using data from Human Genome Project and HapMap Project, genome-wide association studies have been able to identify multiple susceptibility loci for different cancers. The field of genetic and molecular epidemiology has been further revolutionized by the discovery of newer, faster, and more efficient DNA-sequencing technologies including next-generation sequencing. The new DNA-sequencing technologies can play an important role in planning and implementation of cancer prevention and screening strategies. More research is needed in this area, especially in investigating new biomarkers and measuring gene-environment interactions. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Molecular MR imaging of cancer gene therapy. Ferritin transgene reporter takes the stage

International Nuclear Information System (INIS)

Hasegawa, Sumitaka; Furukawa, Takako; Saga, Tsuneo

2010-01-01

Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic efficacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene. (author)

Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer

Science.gov (United States)

2017-07-01

AWARD NUMBER: W81XWH-16-1-0274 TITLE: Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0274 5c...organoid technology via collaboration with Dr. Mary Estes (Baylor College of Medicine ) and her lab, via one-on-one visits, has guided Dr. Alex Peniche with

Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

Science.gov (United States)

Papagiorgis, Petros Christakis

2016-05-01

Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study.

Science.gov (United States)

Holli-Helenius, Kirsi; Salminen, Annukka; Rinta-Kiikka, Irina; Koskivuo, Ilkka; Brück, Nina; Boström, Pia; Parkkola, Riitta

2017-12-29

The aim of this study was to use texture analysis (TA) of breast magnetic resonance (MR) images to assist in differentiating estrogen receptor (ER) positive breast cancer molecular subtypes. Twenty-seven patients with histopathologically proven invasive ductal breast cancer were selected in preliminary study. Tumors were classified into molecular subtypes: luminal A (ER-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67 MaZda. Texture parameters and tumour volumes were correlated with tumour prognostic factors. Textural differences were observed mainly in precontrast images. The two most discriminative texture parameters to differentiate luminal A and luminal B subtypes were sum entropy and sum variance (p = 0.003). The AUCs were 0.828 for sum entropy (p = 0.004), and 0.833 for sum variance (p = 0.003), and 0.878 for the model combining texture features sum entropy, sum variance (p = 0.001). In the LOOCV, the AUC for model combining features sum entropy and sum variance was 0.876. Sum entropy and sum variance showed positive correlation with higher Ki-67 index. Luminal B types were larger in volume and moderate correlation between larger tumour volume and higher Ki-67 index was also observed (r = 0.499, p = 0.008). Texture features which measure randomness, heterogeneity or smoothness and homogeneity may either directly or indirectly reflect underlying growth patterns of breast tumours. TA and volumetric analysis may provide a way to evaluate the biologic aggressiveness of breast tumours and provide aid in decisions regarding therapeutic efficacy.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

International Nuclear Information System (INIS)

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

Science.gov (United States)

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-04-14

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

From Molecular Biology to Clinical Trials: Toward Personalized Colorectal Cancer Therapy.

Science.gov (United States)

Palma, Sabina; Zwenger, Ariel O; Croce, María V; Abba, Martín C; Lacunza, Ezequiel

2016-06-01

During the past years, molecular studies through high-throughput technologies have led to the confirmation of critical alterations in colorectal cancer (CRC) and the discovery of some new ones, including mutations, DNA methylations, and structural chromosomal changes. These genomic alterations might act in concert to dysregulate specific signaling pathways that normally exert their functions on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Targeted therapy against key components of altered signaling pathways has allowed an improvement in CRC treatment. However, a significant percentage of patients with CRC and metastatic CRC will not benefit from these targeted therapies and will be restricted to systemic chemotherapy. Mechanisms of resistance have been associated with specific gene alterations. To fully understand the nature and significance of the genetic and epigenetic defects in CRC that might favor a tumor evading a given therapy, much work remains. Therefore, a dynamic link between basic molecular research and preclinical studies, which ultimately constitute the prelude to standardized therapies, is very important to provide better and more effective treatments against CRC. We present an updated revision of the main molecular features of CRC and their associated therapies currently under study in clinical trials. Moreover, we performed an unsupervised classification of CRC clinical trials with the aim of obtaining an overview of the future perspectives of preclinical studies. Copyright © 2015 Elsevier Inc. All rights reserved.

[Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

Science.gov (United States)

Hagymási, Krisztina; Tulassay, Zsolt

2008-03-23

Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

Molecular biomarkers to guide precision medicine in localized prostate cancer.

Science.gov (United States)

Smits, Minke; Mehra, Niven; Sedelaar, Michiel; Gerritsen, Winald; Schalken, Jack A

2017-08-01

Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer. Expert commentary: Active surveillance (AS) in localized prostate cancer is an accepted strategy in patients with very low-risk prostate cancer. Many more patients may benefit from watchful waiting, and include patients of higher clinical stage and grade, however selection criteria have to be optimized and early recognition of transformation from localized to lethal disease has to be improved by addition of molecular biomarkers. The role of non-invasive biomarkers is challenging the need for repeat biopsies, commonly performed at 1 and 4 years in men under AS programs.

Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

International Nuclear Information System (INIS)

Hendrix, Mary JC; Seftor, Elisabeth A; Kirschmann, Dawn A; Seftor, Richard EB

2000-01-01

During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

Incidence and histological features of colorectal cancer in the ...

African Journals Online (AJOL)

Incidence and histological features of colorectal cancer in the Northern Cape province, South Africa. ... This is a retrospective review of all cases of primary adenocarcinoma of the colon or rectum diagnosed by the two pathology laboratories operating in the Northern Cape between January 2002 and February 2009.

Clinicopathological Features and Management of Cancers in Lynch Syndrome

Directory of Open Access Journals (Sweden)

Markku Aarnio

2012-01-01

Full Text Available Lynch syndrome (LS is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

[Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

Science.gov (United States)

Maroto Rey, José Pablo; Cillán Narvaez, Elena

2013-06-01

There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

Molecular alterations in childhood thyroid cancer after Chernobyl accident and low-dose radiation risk

International Nuclear Information System (INIS)

Suzuki, Keiji; Mitsutake, Norisato; Yamashita, Shunichi

2012-01-01

The linear no-threshold (LNT) model of radiation carcinogenesis has been used for evaluating the risk from radiation exposure. While the epidemiological studies have supported the LNT model at doses above 100 mGy, more uncertainties are still existed in the LNT model at low doses below 100 mGy. Thus, it is urged to clarify the molecular mechanisms underlying radiation carcinogenesis. After the Chernobyl accident in 1986, significant amount of childhood thyroid cancer has emerged in the children living in the contaminated area. As the incidence of sporadic childhood thyroid cancer is very low, it is quite evident that those cancer cases have been induced by radiation exposure caused mainly by the intake of contaminated foods, such as milk. Because genetic alterations in childhood thyroid cancers have extensively been studied, it should provide a unique chance to understand the molecular mechanisms of radiation carcinogenesis. In a current review, molecular signatures obtained from the molecular studies of childhood thyroid cancer after Chernobyl accident have been overviewed, and new roles of radiation exposure in thyroid carcinogenesis will be discussed. (author)

The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses.

Science.gov (United States)

McAlpine, Jessica; Leon-Castillo, Alicia; Bosse, Tjalling

2018-04-01

Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

Science.gov (United States)

Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

2009-01-01

Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53). Conclusion The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers. PMID:19656415

Breast cancer Ki67 expression preoperative discrimination by DCE-MRI radiomics features

Science.gov (United States)

Ma, Wenjuan; Ji, Yu; Qin, Zhuanping; Guo, Xinpeng; Jian, Xiqi; Liu, Peifang

2018-02-01

To investigate whether quantitative radiomics features extracted from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are associated with Ki67 expression of breast cancer. In this institutional review board approved retrospective study, we collected 377 cases Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 53 low-Ki67 expression (Ki67 proliferation index less than 14%) and 324 cases with high-Ki67 expression (Ki67 proliferation index more than 14%). A binary-classification of low- vs. high- Ki67 expression was performed. A set of 52 quantitative radiomics features, including morphological, gray scale statistic, and texture features, were extracted from the segmented lesion area. Three most common machine learning classification methods, including Naive Bayes, k-Nearest Neighbor and support vector machine with Gaussian kernel, were employed for the classification and the least absolute shrink age and selection operator (LASSO) method was used to select most predictive features set for the classifiers. Classification performance was evaluated by the area under receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. The model that used Naive Bayes classification method achieved the best performance than the other two methods, yielding 0.773 AUC value, 0.757 accuracy, 0.777 sensitivity and 0.769 specificity. Our study showed that quantitative radiomics imaging features of breast tumor extracted from DCE-MRI are associated with breast cancer Ki67 expression. Future larger studies are needed in order to further evaluate the findings.

SU-D-207B-01: Radiomics Feature Reproducibility From Repeat CT Scans of Patients with Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Hu, P; Wang, J; Zhong, H; Zhou, Z; Shen, L; Hu, W; Zhang, Z [Fudan University Shanghai Cancer Center, Shanghai, Shanghai (China)

2016-06-15

Purpose: To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Methods: 40 rectal cancer patients were enrolled in this study, each of whom underwent two CT scans within average 8.7 days (5 days to 17 days), before any treatment was delivered. The rectal gross tumor volume (GTV) was distinguished and segmented by an experienced oncologist in both CTs. Totally, more than 2000 radiomics features were defined in this study, which were divided into four groups (I: GLCM, II: GLRLM III: Wavelet GLCM and IV: Wavelet GLRLM). For each group, five types of features were extracted (Max slice: features from the largest slice of target images, Max value: features from all slices of target images and choose the maximum value, Min value: minimum value of features for all slices, Average value: average value of features for all slices, Matrix sum: all slices of target images translate into GLCM and GLRLM matrices and superpose all matrices, then extract features from the superposed matrix). Meanwhile a LOG (Laplace of Gauss) filter with different parameters was applied to these images. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) were calculated to assess the reproducibility. Results: 403 radiomics features were extracted from each type of patients’ medical images. Features of average type are the most reproducible. Different filters have little effect for radiomics features. For the average type features, 253 out of 403 features (62.8%) showed high reproducibility (ICC≥0.8), 133 out of 403 features (33.0%) showed medium reproducibility (0.8≥ICC≥0.5) and 17 out of 403 features (4.2%) showed low reproducibility (ICC≥0.5). Conclusion: The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and

Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

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Luker, Gary D

2002-04-01

The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

[MRI findings and pathological features of occult breast cancer].

Science.gov (United States)

Zhang, J J; Yang, X T; Du, X S; Zhang, J X; Hou, L N; Niu, J L

2018-01-23

Objective: To investigate the magnetic resonance imaging (MRI) findings and clinicopathological features of primary lesions in patients with occult breast cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and Data System in 2013 were retrospectively analyzed to investigate the morphology and the time signal intensity curve (TIC) of breast lesions in patients with OBC. The clinical and pathological characteristics of these patients were also included. Results: A total of 34 patients were enrolled. Among these patients, 24 patients underwent modified radical mastectomy and 18 of them had primary breast carcinoma in pathological sections. MRI detected 17 cases of primary lesions, including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and 11 non-mass lesions with four linear distributions, three segmental distributions, three focal distributions, and one regions distribution. Five patients had TIC typeⅠprimary lesions, ten had TIC type Ⅱ primary lesions, and two had TIC type Ⅲ primary lesions. Among all 34 cases, 23 of them had complete results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%, type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER-2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC usually manifested as small mass lesions, or focal, linear or segmental distribution of non-mass lesions. The positive rate of ER and PR was low, but the positive rate of HER-2 and the proliferation index of Ki-67 was high. Type luminal B is the most common molecular subtype.

Clinical and Endoscopic Features of Undifferentiated Gastric Cancer in Patients with Severe Atrophic Gastritis.

Science.gov (United States)

Kishino, Maiko; Nakamura, Shinichi; Shiratori, Keiko

2016-01-01

Differentiated gastric cancer generally develops in the atrophic gastric mucosa, although undifferentiated cancer is sometimes encountered in patients with severe atrophic gastritis. We characterized the endoscopic features of undifferentiated gastric cancer in patients with severe atrophic gastritis. Stage IA early gastric cancer was diagnosed in 501 patients who were admitted to our hospital between April 2003 and March 2012. The endoscopic and pathological findings were compared among 29 patients with undifferentiated cancer and severe atrophic gastritis, 104 patients with undifferentiated cancer and mild/moderate atrophic gastritis and 223 patients with well-differentiated cancer and severe atrophic gastritis. Endoscopic atrophic gastritis was classified according to the Kimura-Takemoto classification as no gastritis, C-1 and C-2 (mild), C-3 and O-1 (moderate) or O-2 and O-3 (severe). The tumors were larger and showed deeper mural invasion in the patients with undifferentiated cancer and severe atrophic gastritis than in those with well-differentiated cancer and severe gastritis or undifferentiated cancer and mild/moderate gastritis. On endoscopy, undifferentiated cancer associated with severe gastritis was often red in color. It is often difficult to diagnose early undifferentiated gastric cancer, especially in patients with severe atrophic gastritis. The present study characterized the important endoscopic features of such tumors.

The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

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Sioshansi, Shirin [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, Providence, RI (United States); Huber, Kathryn E. [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Wazer, David E., E-mail: dwazer@tuftsmedicalcenter.org [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, Providence, RI (United States)

2011-06-28

The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

International Nuclear Information System (INIS)

Sioshansi, Shirin; Huber, Kathryn E.; Wazer, David E.

2011-01-01

The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

International Nuclear Information System (INIS)

Rafiei, Shahrzad; Komarova, Svetlana V

2013-01-01

Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

Directory of Open Access Journals (Sweden)

Hsu Hui-Chi

2011-04-01

Full Text Available Abstract Background Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Methods Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. Results We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was

Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

International Nuclear Information System (INIS)

Kao, Kuo-Jang; Chang, Kai-Ming; Hsu, Hui-Chi; Huang, Andrew T

2011-01-01

Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

Feature genes in metastatic breast cancer identified by MetaDE and SVM classifier methods.

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Tuo, Youlin; An, Ning; Zhang, Ming

2018-03-01

The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of PSVM) classifier training and verification. The accuracy of the SVM classifier was then evaluated using another independent dataset from The Cancer Genome Atlas database. Finally, function and pathway enrichment analyses for genes in the SVM classifier were performed. A total of 541 feature genes were identified between metastatic and non‑metastatic samples. The top 10 genes with the highest betweenness centrality values in the PPI network of feature genes were Nuclear RNA Export Factor 1, cyclin‑dependent kinase 2 (CDK2), myelocytomatosis proto‑oncogene protein (MYC), Cullin 5, SHC Adaptor Protein 1, Clathrin heavy chain, Nucleolin, WD repeat domain 1, proteasome 26S subunit non‑ATPase 2 and telomeric repeat binding factor 2. The cyclin‑dependent kinase inhibitor 1A (CDKN1A), E2F transcription factor 1 (E2F1), and MYC interacted with CDK2. The SVM classifier constructed by the top 30 feature genes was able to distinguish metastatic samples from non‑metastatic samples [correct rate, specificity, positive predictive value and negative predictive value >0.89; sensitivity >0.84; area under the receiver operating characteristic curve (AUROC) >0.96]. The verification of the SVM classifier in an independent dataset (35 metastatic samples and 143 non‑metastatic samples) revealed an accuracy of 94.38% and AUROC of 0.958. Cell cycle associated functions and pathways were the most significant terms of the 30 feature genes. A SVM classifier was constructed to assess the possibility of breast cancer metastasis, which presented high accuracy in several

Introduction to the cellular and molecular biology of cancer

National Research Council Canada - National Science Library

Selby, P. (Peter); Knowles, Margaret A

2005-01-01

... A. Prigent 186xii CONTENTS 12 Apoptosis: molecular physiology and significance for cancer therapeutics Dean A. Fennell 210 13 Mechanisms of viral carcinogenesis Paul Farrell 229 14 Cytokines and canc...

Inflammation to cancer: The molecular biology in the pancreas (Review).

Science.gov (United States)

Ling, Sunbin; Feng, Tingting; Jia, Kaiqi; Tian, Yu; Li, Yan

2014-06-01

Inflammatory responses are known to be correlated with cancer initiation and progression, and exploration of the route from inflammation to cancer makes a great contribution in elucidating the mechanisms underlying cancer development. Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and a poor prognosis. As chronic pancreatitis is considered to be a significant etiological factor for PC development, the current review aims to describe the molecular pathways from inflammation to pancreatic carcinogenesis, in support of the strategies for the prevention, diagnosis and treatment of PC.

Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment.

Science.gov (United States)

Polireddy, Kishore; Chen, Qi

2016-01-01

Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer.

Off-Center Rotation of CuPc Molecular Rotor on a Bi(111) Surface and the Chiral Feature.

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Sun, Kai; Tao, Min-Long; Tu, Yu-Bing; Wang, Jun-Zhong

2017-05-04

Molecular rotors with an off-center axis and the chiral feature of achiral CuPc molecules on a semi-metallic Bi(111) surface have been investigated by means of a scanning tunneling microscopy (STM) at liquid nitrogen (LN₂) temperature. The rotation axis of each CuPc molecular rotor is located at the end of a phthalocyanine group. As molecular coverage increases, the CuPc molecules are self-assembled into various nanoclusters and finally into two-dimensional (2D) domains, in which each CuPc molecule exhibits an apparent chiral feature. Such chiral features of the CuPc molecules can be attributed to the combined effect of asymmetric charge transfer between the CuPc and Bi(111) substrate, and the intermolecular van der Waals interactions.

[New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?].

Science.gov (United States)

Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry

2016-01-01

This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels

Directory of Open Access Journals (Sweden)

Tomoko Miyata

2015-01-01

Full Text Available Uterine leiomyosarcoma (LMS is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM, a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods.

Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence.

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Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L; Manson, JoAnn E; Qian, Zhi Rong; Ogino, Shuji

2016-05-01

In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.

Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

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Saba Garshasbi

2015-10-01

Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers

DEFF Research Database (Denmark)

Andersen, Lars Dyrskjøt; Zieger, Karsten; Ørntoft, Torben Falck

2007-01-01

individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here......Bladder cancer is the fifth most common neoplasm in industrialized countries. Due to frequent recurrences of the superficial form of this disease, bladder cancer ranks as one of the most common cancers. Despite the description of a large number of tumor markers for bladder cancers, none have......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction.

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Tan, Cong-Cong; Li, Gui-Xi; Tan, Li-Duan; Du, Xin; Li, Xiao-Qing; He, Rui; Wang, Qing-Shan; Feng, Yu-Mei

2016-11-29

Bone is one of the most common organs of breast cancer metastasis. Cancer cells that mimic osteoblasts by expressing bone matrix proteins and factors have a higher likelihood of metastasizing to bone. However, the molecular mechanisms of osteomimicry formation of cancer cells remain undefined. Herein, we identified a set of bone-related genes (BRGs) that are ectopically co-expressed in primary breast cancer tissues and determined that osteomimetic feature is obtained due to the osteoblast-like transformation of epithelial breast cancer cells that have undergone epithelial-mesenchymal transition (EMT) followed by bone morphogenetic protein-2 (BMP2) stimulation. Furthermore, we demonstrated that breast cancer cells that transformed into osteoblast-like cells with high expression of BRGs showed enhanced chemotaxis, adhesion, proliferation and multidrug resistance in an osteoblast-mimic bone microenvironment in vitro. During these processes, runt-related transcription factor 2 (RUNX2) functioned as a master mediator by suppressing or activating the transcription of BRGs that underlie the dynamic antagonism between the TGF-β/SMAD and BMP/SMAD signaling pathways in breast cancer cells. Our findings suggest a novel mechanism of osteomimicry formation that arises in primary breast tumors, which may explain the propensity of breast cancer to metastasize to the skeleton and contribute to potential strategies for predicting and targeting breast cancer bone metastasis and multidrug resistance.

Molecular Imaging and Precision Medicine in Head and Neck Cancer.

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Mena, Esther; Thippsandra, Shwetha; Yanamadala, Anusha; Redy, Siddaling; Pattanayak, Puskar; Subramaniam, Rathan M

2017-01-01

The concept of using tumor genomic profiling information has revolutionized personalized cancer treatment. Head and neck (HN) cancer management is being influenced by recent discoveries of activating mutations in epidermal growth factor receptor and related targeted therapies with tyrosine kinase inhibitors, targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular imaging using PET plays an important role in assessing the biologic behavior of HN cancer with the goal of delivering individualized cancer treatment. This review summarizes recent genomic discoveries in HN cancer and their implications for functional PET imaging in assessing response to targeted therapies, and drug resistance mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinicopathological features and prognosis of gastric cancer in young patients

International Nuclear Information System (INIS)

Liu, Shushang; Feng, Fan; Xu, Guanghui; Liu, Zhen; Tian, Yangzi; Guo, Man; Lian, Xiao; Cai, Lei; Fan, Daiming; Zhang, Hongwei

2016-01-01

The clinicopathological features and prognosis of gastric cancer in young patients are both limited and controversial. Therefore, the aim of this study was to define the clinicopathological features and prognosis of gastric cancer in young patients after curative resection. From May 2008 to December 2014, 198 young patients (age ≤ 40 years) and 1096 middle-aged patients (55 ≤ age ≤ 64 years) were enrolled in this study. The clinicopathological features and prognosis of gastric cancer in these patients were analyzed. Compared with middle-aged patients, the proportion of females, lower third tumors, tumor size less than 5 cm, poorly differentiated tumors and T1 tumors were significantly higher in young patients (all P < 0.05). The proportions of comorbidity, upper third tumors, well and moderately differentiated tumors, T4 tumors, and positive carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and carbohydrate antigen (CA) 19–9 were significantly lower in young patients (all P < 0.05). The distributions of N status and CA125 were comparable between young and middle-aged patients (all P > 0.05). The five-year overall survival rates were comparable between young patients and middle-aged patients (62.8 vs 54.7 %, P = 0.307). The tumor location, T status, N status and CA125 were independent predictors of prognosis in young patients. The overall survival of patients with tumors located in the upper or middle third was significantly lower than for those located in the lower third (60.8 vs 50.6 % vs 68.4 %, P = 0.016). The overall survival of CA125-positive patients was significantly lower than CA125-negative patients (49.0 vs 64.4 %, P = 0.001). The clinicopathological features were significantly different between young and middle-aged patients. The prognosis of gastric cancer in young patients was equivalent to that of middle-aged patients. Tumor location, T status, N status and CA125 were independent risk factors for prognosis in young patients. The online

Contour Propagation Using Feature-Based Deformable Registration for Lung Cancer

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Yuhan Yang

2013-01-01

Full Text Available Accurate target delineation of CT image is a critical step in radiotherapy treatment planning. This paper describes a novel strategy for automatic contour propagation, based on deformable registration, for CT images of lung cancer. The proposed strategy starts with a manual-delineated contour in one slice of a 3D CT image. By means of feature-based deformable registration, the initial contour in other slices of the image can be propagated automatically, and then refined by active contour approach. Three algorithms are employed in the strategy: the Speeded-Up Robust Features (SURF, Thin-Plate Spline (TPS, and an adapted active contour (Snake, used to refine and modify the initial contours. Five pulmonary cancer cases with about 400 slices and 1000 contours have been used to verify the proposed strategy. Experiments demonstrate that the proposed strategy can improve the segmentation performance in the pulmonary CT images. Jaccard similarity (JS mean is about 0.88 and the maximum of Hausdorff distance (HD is about 90%. In addition, delineation time has been considerably reduced. The proposed feature-based deformable registration method in the automatic contour propagation improves the delineation efficiency significantly.

The molecular biology of prostate cancer: current understanding and clinical implications.

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Gandhi, Jason; Afridi, Adil; Vatsia, Sohrab; Joshi, Gargi; Joshi, Gunjan; Kaplan, Steven A; Smith, Noel L; Khan, Sardar Ali

2018-04-01

With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the

Breast Cancer Detection with Gabor Features from Digital Mammograms

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Yufeng Zheng

2010-01-01

Full Text Available A new breast cancer detection algorithm, named the “Gabor Cancer Detection” (GCD algorithm, utilizing Gabor features is proposed. Three major steps are involved in the GCD algorithm, preprocessing, segmentation (generating alarm segments, and classification (reducing false alarms. In preprocessing, a digital mammogram is down-sampled, quantized, denoised and enhanced. Nonlinear diffusion is used for noise suppression. In segmentation, a band-pass filter is formed by rotating a 1-D Gaussian filter (off center in frequency space, termed as “Circular Gaussian Filter” (CGF. A CGF can be uniquely characterized by specifying a central frequency and a frequency band. A mass or calcification is a space-occupying lesion and usually appears as a bright region on a mammogram. The alarm segments (suspicious to be masses/calcifications can be extracted out using a threshold that is adaptively decided upon the histogram analysis of the CGF-filtered mammogram. In classification, a Gabor filter bank is formed with five bands by four orientations (horizontal, vertical, 45 and 135 degree in Fourier frequency domain. For each mammographic image, twenty Gabor-filtered images are produced. A set of edge histogram descriptors (EHD are then extracted from 20 Gabor images for classification. An EHD signature is computed with four orientations of Gabor images along each band and five EHD signatures are then joined together to form an EHD feature vector of 20 dimensions. With the EHD features, the fuzzy C-means clustering technique and k-nearest neighbor (KNN classifier are used to reduce the number of false alarms. The experimental results tested on the DDSM database (University of South Florida show the promises of GCD algorithm in breast cancer detection, which achieved TP (true positive rate = 90% at FPI (false positives per image = 1.21 in mass detection; and TP = 93% at FPI = 1.19 in calcification detection.

Shear-wave elastographic features of breast cancers: comparison with mechanical elasticity and histopathologic characteristics.

Science.gov (United States)

Lee, Su Hyun; Moon, Woo Kyung; Cho, Nariya; Chang, Jung Min; Moon, Hyeong-Gon; Han, Wonshik; Noh, Dong-Young; Lee, Jung Chan; Kim, Hee Chan; Lee, Kyoung-Bun; Park, In-Ae

2014-03-01

The objective of this study was to compare the quantitative and qualitative shear-wave elastographic (SWE) features of breast cancers with mechanical elasticity and histopathologic characteristics. This prospective study was conducted with institutional review board approval, and written informed consent was obtained. Shear-wave elastography was performed for 30 invasive breast cancers in 30 women before surgery. The mechanical elasticity of a fresh breast tissue section, correlated with the ultrasound image, was measured using an indentation system. Quantitative (maximum, mean, minimum, and standard deviation of elasticity in kilopascals) and qualitative (color heterogeneity and presence of signal void areas in the mass) SWE features were compared with mechanical elasticity and histopathologic characteristics using the Pearson correlation coefficient and the Wilcoxon signed rank test. Maximum SWE values showed a moderate correlation with maximum mechanical elasticity (r = 0.530, P = 0.003). There were no significant differences between SWE values and mechanical elasticity in histologic grade I or II cancers (P = 0.268). However, SWE values were significantly higher than mechanical elasticity in histologic grade III cancers (P masses were present in 43% of breast cancers (13 of 30) and were correlated with dense collagen depositions (n = 11) or intratumoral necrosis (n = 2). Quantitative and qualitative SWE features reflect both the mechanical elasticity and histopathologic characteristics of breast cancers.

Immature truncated O-glycophenotype of cancer directly induces oncogenic features

DEFF Research Database (Denmark)

Radhakrishnan, Prakash; Dabelsteen, Sally; Madsen, Frey Brus

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 s...

Genetic Fuzzy System (GFS based wavelet co-occurrence feature selection in mammogram classification for breast cancer diagnosis

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Meenakshi M. Pawar

2016-09-01

Full Text Available Breast cancer is significant health problem diagnosed mostly in women worldwide. Therefore, early detection of breast cancer is performed with the help of digital mammography, which can reduce mortality rate. This paper presents wrapper based feature selection approach for wavelet co-occurrence feature (WCF using Genetic Fuzzy System (GFS in mammogram classification problem. The performance of GFS algorithm is explained using mini-MIAS database. WCF features are obtained from detail wavelet coefficients at each level of decomposition of mammogram image. At first level of decomposition, 18 features are applied to GFS algorithm, which selects 5 features with an average classification success rate of 39.64%. Subsequently, at second level it selects 9 features from 36 features and the classification success rate is improved to 56.75%. For third level, 16 features are selected from 54 features and average success rate is improved to 64.98%. Lastly, at fourth level 72 features are applied to GFS, which selects 16 features and thereby increasing average success rate to 89.47%. Hence, GFS algorithm is the effective way of obtaining optimal set of feature in breast cancer diagnosis.

Molecular biology and riddle of cancer: the ‘Tom & Jerry’ show

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Md. Al Mamun

2011-11-01

Full Text Available From the conventional Bird’s eye, cancer initiation and metastasis are generally intended to be understood beneath the light of classical clonal genetic, epigenetic and cancer stem cell model. But inspite decades of investigation, molecular biology has shown hard success to give Eagle’s eye in unraveling the riddle of cancer. And it seems, tiring Tom runs in vague behind naughty Jerry.

Sputum-Based Molecular Biomarkers for the Early Detection of Lung Cancer: Limitations and Promise

Energy Technology Data Exchange (ETDEWEB)

Kim, Connie E. [Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine. 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine. 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

2011-07-19

Lung cancer is the leading cause of cancer deaths, with an overall survival of 15% at five years. Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung. Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers.

The implications of breast cancer molecular phenotype for radiation oncology

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Shirin eSioshansi

2011-06-01

Full Text Available The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence in the hormone receptor positive luminal subtypes compared to hormone receptor negative subtypes (triple negative and HER2-enriched. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of local recurrence. Unfortunately, no such remedy exists to address the increased risk of local recurrence for patients with triple negative tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and local recurrence following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased local recurrence in triple negative breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation and the appropriateness of accelerated partial breast irradiation.

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

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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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Baseline blood immunological profiling differentiates between Her2-breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response.

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Tudoran, Oana; Virtic, Oana; Balacescu, Loredana; Lisencu, Carmen; Fetica, Bogdan; Gherman, Claudia; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

2015-01-01

Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.

Shell feature: a new radiomics descriptor for predicting distant failure after radiotherapy in non-small cell lung cancer and cervix cancer

Science.gov (United States)

Hao, Hongxia; Zhou, Zhiguo; Li, Shulong; Maquilan, Genevieve; Folkert, Michael R.; Iyengar, Puneeth; Westover, Kenneth D.; Albuquerque, Kevin; Liu, Fang; Choy, Hak; Timmerman, Robert; Yang, Lin; Wang, Jing

2018-05-01

Distant failure is the main cause of human cancer-related mortalities. To develop a model for predicting distant failure in non-small cell lung cancer (NSCLC) and cervix cancer (CC) patients, a shell feature, consisting of outer voxels around the tumor boundary, was constructed using pre-treatment positron emission tomography (PET) images from 48 NSCLC patients received stereotactic body radiation therapy and 52 CC patients underwent external beam radiation therapy and concurrent chemotherapy followed with high-dose-rate intracavitary brachytherapy. The hypothesis behind this feature is that non-invasive and invasive tumors may have different morphologic patterns in the tumor periphery, in turn reflecting the differences in radiological presentations in the PET images. The utility of the shell was evaluated by the support vector machine classifier in comparison with intensity, geometry, gray level co-occurrence matrix-based texture, neighborhood gray tone difference matrix-based texture, and a combination of these four features. The results were assessed in terms of accuracy, sensitivity, specificity, and AUC. Collectively, the shell feature showed better predictive performance than all the other features for distant failure prediction in both NSCLC and CC cohorts.

Breast Cancer Arising Adjacent to an Involuting Fibroadenoma: Serial Changes in Radiologic Features

Science.gov (United States)

Park, Chae Jung; Kim, Eun-Kyung; Woo, Ha Young; Moon, Hee Jung; Yoon, Jung Hyun

2015-01-01

Fibroadenoma is a common benign breast lesion and its malignant transformation is rare. There have been several case reports and studies that retrospectively reviewed breast cancers that arose within fibroadenomas; however, none of these studies reported serial changes in radiologic features of the cancer, including findings from mammography and ultrasound (US). We report a case of breast cancer arising adjacent to an involuting fibro adenoma in a 39-year-old woman who was undergoing serial follow-up after her fibroadenoma was diagnosed. Seven years after her diagnosis, the lesion showed evidence of coarse calcifications, a typical sign of involution. Four years later, US revealed a newly developed hypoechoic lesion with irregular margins and peripherally located calcifications adjacent to the fibroadenoma. A core biopsy was performed, and histopathological examination resulted in a diagnosis of invasive ductal carcinoma. When new suspicious features are observed in a fibroadenoma, radiologists should raise the concern for breast cancer and proceed with diagnosis and treatment accordingly. PMID:26472981

Hereditary breast cancer

DEFF Research Database (Denmark)

Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

2014-01-01

Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

Infrared images of reflection nebulae and Orion's bar: Fluorescent molecular hydrogen and the 3.3 micron feature

International Nuclear Information System (INIS)

Burton, M.G.; Moorhouse, A.; Brand, P.W.J.L.; Roche, P.F.; Geballe, T.R.

1989-01-01

Images were obtained of the (fluorescent) molecular hydrogen 1-0 S(1) line, and of the 3.3 micron emission feature, in Orion's Bar and three reflection nebulae. The emission from these species appears to come from the same spatial locations in all sources observed. This suggests that the 3.3 micron feature is excited by the same energetic UV-photons which cause the molecular hydrogen to fluoresce

Molecular Characterization and Mortality From Breast Cancer in Men.

Science.gov (United States)

Massarweh, Suleiman Alfred; Sledge, George W; Miller, Dave P; McCullough, Debbie; Petkov, Valentina I; Shak, Steven

2018-05-10

Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor-positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer-specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

[Wolfram syndrome: clinical features, molecular genetics of WFS1 gene].

Science.gov (United States)

Tanabe, Katsuya; Matsunaga, Kimie; Hatanaka, Masayuki; Akiyama, Masaru; Tanizawa, Yukio

2015-02-01

Wolfram syndrome(WFS: OMIM 222300) is a rare recessive neuro-endocrine degenerative disorder, known as DIDMOAD(Diabetes Insipidus, early-onset Diabetes Mellitus, Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene(WFS1). The WFS1 protein is an endoplasmic reticulum(ER) embedded protein, which functions in ER calcium homeostasis and unfolded protein responses. Dysregulation of these cellular processes results in the development of ER stress, leading to apoptosis. In addition, abundantly present WFS1 protein in insulin secretory granules plays a role in the intra-granular acidification. However, the phenotypic pleiomorphism and molecular complexity of this disease limit the understanding of WFS. Here we review clinical features, molecular mechanisms and mutations of WFS1 gene that relate to this syndrome.

Management and performance features of cancer centers in Europe: A fuzzy-set analysis

NARCIS (Netherlands)

Wind, Anke; Lobo, Mariana Fernandes; van Dijk, Joris; Lepage-Nefkens, Isabelle; Laranja-Pontes, Jose; da Conceicao Goncalves, Vitor; van Harten, Willem H.; Rocha-Goncalves, Francisco Nuno

2016-01-01

The specific aim of this study is to identify the performance features of cancer centers in the European Union by using a fuzzy-set qualitative comparative analysis (fsQCA). The fsQCA method represents cases (cancer centers) as a combination of explanatory and outcome conditions. This study uses

Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

Science.gov (United States)

Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

2014-01-01

There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers. PMID:23094914

Fecal Molecular Markers for Colorectal Cancer Screening

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Rani Kanthan

2012-01-01

Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

Science.gov (United States)

Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

2016-01-01

This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

Science.gov (United States)

Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

2016-01-01

This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

Development and validation of risk models and molecular diagnostics to permit personalized management of cancer.

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Pu, Xia; Ye, Yuanqing; Wu, Xifeng

2014-01-01

Despite the advances made in cancer management over the past few decades, improvements in cancer diagnosis and prognosis are still poor, highlighting the need for individualized strategies. Toward this goal, risk prediction models and molecular diagnostic tools have been developed, tailoring each step of risk assessment from diagnosis to treatment and clinical outcomes based on the individual's clinical, epidemiological, and molecular profiles. These approaches hold increasing promise for delivering a new paradigm to maximize the efficiency of cancer surveillance and efficacy of treatment. However, they require stringent study design, methodology development, comprehensive assessment of biomarkers and risk factors, and extensive validation to ensure their overall usefulness for clinical translation. In the current study, the authors conducted a systematic review using breast cancer as an example and provide general guidelines for risk prediction models and molecular diagnostic tools, including development, assessment, and validation. © 2013 American Cancer Society.

Histological and molecular evaluation of patient-derived colorectal cancer explants.

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Joshua M Uronis

Full Text Available Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

Construction and analysis of circular RNA molecular regulatory networks in liver cancer.

Science.gov (United States)

Ren, Shuangchun; Xin, Zhuoyuan; Xu, Yinyan; Xu, Jianting; Wang, Guoqing

2017-01-01

Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. In this study, we used a systems biology approach to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network. We enriched the pathways and gene ontology items and determined their participation in cancer-related pathways such as p53 signaling pathway and pathways involved in angiogenesis and cell cycle. Quantitative real-time PCR was performed to verify the top-five circRNAs. ROC analysis showed circZFR, circFUT8, circIPO11 could significantly distinguish the cancer samples, with an AUC of 0.7069, 0.7575, and 0.7103, respectively. Our results suggest the circRNA-miRNA-mRNA network may help us further understand the molecular mechanisms of tumor progression in liver cancer, and reveal novel biomarkers and therapeutic targets.

Molecular analysis of precursor lesions in familial pancreatic cancer.

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Tatjana Crnogorac-Jurcevic

Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

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Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

2017-10-01

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; pmolecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Molecular features related to HIV integrase inhibition obtained from structure- and ligand-based approaches.

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Luciana L de Carvalho

Full Text Available Among several biological targets to treat AIDS, HIV integrase is a promising enzyme that can be employed to develop new anti-HIV agents. The aim of this work is to propose a mechanistic interpretation of HIV-1 integrase inhibition and to rationalize the molecular features related to the binding affinity of studied ligands. A set of 79 HIV-1 integrase inhibitors and its relationship with biological activity are investigated employing 2D and 3D QSAR models, docking analysis and DFT studies. Analyses of docking poses and frontier molecular orbitals revealed important features on the main ligand-receptor interactions. 2D and 3D models presenting good internal consistency, predictive power and stability were obtained in all cases. Significant correlation coefficients (r(2 = 0.908 and q(2= 0.643 for 2D model; r(2= 0.904 and q(2= 0.719 for 3D model were obtained, indicating the potential of these models for untested compounds. The generated holograms and contribution maps revealed important molecular requirements to HIV-1 IN inhibition and several evidences for molecular modifications. The final models along with information resulting from molecular orbitals, 2D contribution and 3D contour maps should be useful in the design of new inhibitors with increased potency and selectivity within the chemical diversity of the data.

Validation of a radiosensitivity molecular signature in breast cancer

NARCIS (Netherlands)

S.A. Eschrich (Steven); C. Fulp (Carl); Y. Pawitan (Yudi); J.A. Foekens (John); M. Smid (Marcel); J.W.M. Martens (John); M. Echevarria (Michelle); P.S. Kamath (Patrick); J.-H. Lee (Ji-Hyun); E.E. Harris (Eleanor); J. Bergh (Jonas); J.F. Torres-Roca (Javier)

2012-01-01

textabstractPurpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients.

Cisplatin in cancer therapy: molecular mechanisms of action

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Dasari, Shaloam; Tchounwou, Paul Bernard

2014-01-01

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is given to its molecular mechanisms of action, and its undesirable side effects. PMID:25058905

Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

International Nuclear Information System (INIS)

Mahajan, A.; Goh, V.; Basu, S.; Vaish, R.; Weeks, A.J.; Thakur, M.H.; Cook, G.J.

2015-01-01

Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure–function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [ 18 F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed “theranostics”. Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. -- Highlights: •Molecular functional imaging (MFI) gives insight into the tumor biology and intratumoral heterogeneity. •It has potential role in identifying radiomic signatures associated with underlying gene-expression. •Radiomics can be used to create a road map

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

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Guoli Chen

2016-01-01

Full Text Available Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional “one test-one drug” assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective.

Science.gov (United States)

Chen, Guoli; Yang, Zhaohai; Eshleman, James R; Netto, George J; Lin, Ming-Tseh

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

Imaging and Clinical Features of Thyroid Cancer in Children and Adolescents

International Nuclear Information System (INIS)

Lee, Kang Young; Hong, HyunSook; Lee, Eun Hye; Yi, Beom Ha; Lee, Hae Kyung; Lee, Yong Hwa; Koh, Eun Suk

2011-01-01

To evaluate clinical and imaging features of pediatric thyroid cancer, including BRAF'V 600E mutation status in papillary thyroid cancer (PTC). We evaluated clinical findings including BRAF''6 00E status, ultrasound (US), and CT features of 13 pediatric patients with thyroid cancer. US findings were retrospectively analyzed for location, presence of a nodule, echotexture, echogenicity, calcifications, margin, shape, intranodular vascularity and abnormal lymph nodes. CT characteristics of the lesions, including attenuation, calcification, and measured degree of enhancement, were assessed. The patients included three boys and ten girls with a mean age of 15.5 years (range 6-18 years). No patient was exposed to radiation. Palpable neck mass was the most common presentation. Eleven of 13 patients (84.6%) were diagnosed with PTC, and two (15.4%) had follicular thyroid cancer (FTC). Nine of 13 (69.2%) had high T-staging. BRAF V600E mutations were detected in 30.0% of PTC patients. A diffusely enlarged thyroid with calcifications (n = 2) or nodules (n = 7) was detected on US. All PTC nodules showed malignant US findings and one FTC displayed on indeterminate nodule. Nodules generally showed low attenuation on enhanced CT (n = 11/12). US demonstrated enlarged glands with calcifications or nodules. Diffusely enlarged thyroids with microcalcifications should be evaluated using fine-needle aspiration. A low attenuation nodule was a common finding on enhanced CT.

Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component.

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Qing Wei

Full Text Available We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.A slight male predominance was detected in these patients (59.0%. Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54 cases with KRAS mutations in 16.7% (9/54 cases and Nras mutations in 5.4%(3/54 cases. BRAF V600E mutation was detected in 3.7% (2/54 cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9% cases were composed of ≥50% signet-ring cells; 22 (36.1% cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of

Racial Disparities in the Molecular Landscape of Cancer.

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Heath, Elisabeth I; Lynce, Filipa; Xiu, Joanne; Ellerbrock, Angela; Reddy, Sandeep K; Obeid, Elias; Liu, Stephen V; Bollig-Fischer, Aliccia; Separovic, Duska; Vanderwalde, Ari

2018-04-01

African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing. Additionally, we evaluated protein expression using immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for known ethnicity associations. Considering only pathogenic or presumed pathogenic mutations, as determined by the American College of Medical Genetics and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections for multiple comparisons, we found that CRC tumors from AA patients harbored significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast, CRCs from AA patients were likely to carry fewer mutations of ataxia-telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF), including the V600E variant, than those from CC patients. Rates of immunohistochemical positivity for epidermal growth factor receptor (EGFR) and DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more frequent in the AA than in the CC cohort, whereas in squamous cell lung carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the AA than in CC group. Moreover

Exosomes in Cancer Liquid Biopsy: A Focus on Breast Cancer

OpenAIRE

Sina Halvaei; Shiva Daryani; Zahra Eslami-S; Tannaz Samadi; Narges Jafarbeik-Iravani; Tayebeh Oghabi Bakhshayesh; Keivan Majidzadeh-A; Rezvan Esmaeili

2018-01-01

The important challenge about cancer is diagnosis in primary stages and proper treatment. Although classical clinico-pathological features of the tumor have major prognostic value, the advances in diagnosis and treatment are indebted to discovery of molecular biomarkers and control of cancer in the pre-invasive state. Moreover, the efficiency of available therapeutic options is highly diminished, and chemotherapy is still the main treatment due to lack of enough specific targets. Accordingly,...

Molecular Imaging and Precision Medicine in Lung Cancer.

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Zukotynski, Katherine A; Gerbaudo, Victor H

2017-01-01

Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

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Storm, P; Aits, S; Puthia, M K; Urbano, A; Northen, T; Powers, S; Bowen, B; Chao, Y; Reindl, W; Lee, D Y; Sullivan, N L; Zhang, J; Trulsson, M; Yang, H; Watson, J D; Svanborg, C

2011-12-01

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

Science.gov (United States)

Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James; Svanborg, Catharina

2014-01-01

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic and metabolomic technology we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted the sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, the HAMLET sensitivity was modified by the glycolytic state of the tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen Hexokinase 1, PFKFB1 and HIF1α modified HAMLET sensitivity. Hexokinase 1 was shown to bind HAMLET in a protein array containing approximately 8000 targets and Hexokinase activity decreased within 15 minutes of HAMLET treatment, prior to morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. The glycolytic machinery was modified and glycolysis was shifted towards the pentose phosphate pathway. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 minutes. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene-addiction or the Warburg effect. PMID:21643007

Molecular Targets for Radiation Oncology in Prostate Cancer

International Nuclear Information System (INIS)

Wang, Tao; Languino, Lucia R.; Lian, Jane; Stein, Gary; Blute, Michael; FitzGerald, Thomas J.

2011-01-01

Recent selected developments of the molecular science of prostate cancer (PrCa) biology and radiation oncology are reviewed. We present potential targets for molecular integration treatment strategies with radiation therapy (RT), and highlight potential strategies for molecular treatment in combination with RT for patient care. We provide a synopsis of the information to date regarding molecular biology of PrCa, and potential integrated research strategy for improved treatment of PrCa. Many patients with early-stage disease at presentation can be treated effectively with androgen ablation treatment, surgery, or RT. However, a significant portion of men are diagnosed with advanced stage/high-risk disease and these patients progress despite curative therapeutic intervention. Unfortunately, management options for these patients are limited and are not always successful including treatment for hormone refractory disease. In this review, we focus on molecules of extracellular matrix component, apoptosis, androgen receptor, RUNX, and DNA methylation. Expanding our knowledge of the molecular biology of PrCa will permit the development of novel treatment strategies integrated with RT to improve patient outcome

Molecular subtypes and imaging phenotypes of breast cancer

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Nariya Cho

2016-10-01

Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

Molecular subtypes and imaging phenotypes of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

2016-08-15

During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

Molecular subtypes and imaging phenotypes of breast cancer

International Nuclear Information System (INIS)

Cho, Nariya

2016-01-01

During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics

Prostate cancer molecular profiling: the Achilles heel for the implementation of precision medicine.

Science.gov (United States)

Oliveira-Barros, Eliane Gouvêa; Nicolau-Neto, Pedro; Da Costa, Nathalia Meireles; Pinto, Luís Felipe Ribeiro; Palumbo, Antonio; Nasciutti, Luiz Eurico

2017-11-01

Cancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large-scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile. Cancer treatment personalized approaches rely on the premise that a well-defined panorama of tumor molecular alterations can help selecting new and specific therapeutic targets for its treatment and potentially discriminate tumors which behave differentially. Lately, molecular and genetic studies have been investigating PCa basis, revealing multiple recurrent genomic alterations that include mutations, DNA copy-number variations, rearrangements, and gene fusions, among others. In addition to the increment on PCa molecular biology knowledge, mapping the molecular alterations pattern of this neoplasia, especially the differences existent between tumors displaying distinct behaviors, could represent a great improvement concerning the identification of new targets, personalized medicine, and patients' management and prognosis. © 2017 International Federation for Cell Biology.

Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.

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Manning, H Charles; Buck, Jason R; Cook, Rebecca S

2016-02-01

Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A New Feature Ensemble with a Multistage Classification Scheme for Breast Cancer Diagnosis

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Idil Isikli Esener

2017-01-01

Full Text Available A new and effective feature ensemble with a multistage classification is proposed to be implemented in a computer-aided diagnosis (CAD system for breast cancer diagnosis. A publicly available mammogram image dataset collected during the Image Retrieval in Medical Applications (IRMA project is utilized to verify the suggested feature ensemble and multistage classification. In achieving the CAD system, feature extraction is performed on the mammogram region of interest (ROI images which are preprocessed by applying a histogram equalization followed by a nonlocal means filtering. The proposed feature ensemble is formed by concatenating the local configuration pattern-based, statistical, and frequency domain features. The classification process of these features is implemented in three cases: a one-stage study, a two-stage study, and a three-stage study. Eight well-known classifiers are used in all cases of this multistage classification scheme. Additionally, the results of the classifiers that provide the top three performances are combined via a majority voting technique to improve the recognition accuracy on both two- and three-stage studies. A maximum of 85.47%, 88.79%, and 93.52% classification accuracies are attained by the one-, two-, and three-stage studies, respectively. The proposed multistage classification scheme is more effective than the single-stage classification for breast cancer diagnosis.

Managing cancer-related venous thromboembolic disease: low-molecular-weight heparins and beyond.

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O'Connell, Casey L; Liebman, Howard A

2008-12-01

Venous thromboembolism is a major contributor to the morbidity and mortality of patients with cancer. For patients undergoing cancer surgery, several trials support the safety and efficacy of unfractionated heparin and of low-molecular-weight heparin for the prevention of venous thromboembolism, while data regarding the efficacy and safety of these agents in the setting of medical hospitalization is less definitive and must be extracted from trials including noncancer patients with different thrombotic risk factors. Randomized clinical studies confirm that patients with cancer who develop venous thromboembolism have superior outcomes when treated with long-term low-molecular-weight heparin as compared with warfarin. Novel anticoagulants that are orally bioavailable and function by directly inhibiting factor Xa or thrombin are entering the market. To date, data regarding the efficacy and safety of these novel anticoagulants as venous thromboembolism prophylaxis and treatment in cancer patients are not available and must be extracted from larger trials with heterogeneous patient populations.

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

International Nuclear Information System (INIS)

Osin, Pinchas P; Lakhani, Sunil R

1999-01-01

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

Vitamin D and Colorectal Cancer: Molecular, Epidemiological, and Clinical Evidence

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Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L.; Manson, JoAnn E.; Qian, Zhi Rong; Ogino, Shuji

2016-01-01

In many cells throughout the body, vitamin D is converted into its active form calcitriol, and binds to vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D metabolizing enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating effects of vitamin D. Preclinical and epidemiological studies provide evidence for anticancer effects of vitamin D (in particular, against colorectal cancer), though clinical trials have yet to prove its benefit. Additionally, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses, and clinical trials on vitamin D efficacy in colorectal cancer patients. Here we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies, and discuss the links and controversies within and between the two parts of evidence. PMID:27245104

Discrete Biogeography Based Optimization for Feature Selection in Molecular Signatures.

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Liu, Bo; Tian, Meihong; Zhang, Chunhua; Li, Xiangtao

2015-04-01

Biomarker discovery from high-dimensional data is a complex task in the development of efficient cancer diagnoses and classification. However, these data are usually redundant and noisy, and only a subset of them present distinct profiles for different classes of samples. Thus, selecting high discriminative genes from gene expression data has become increasingly interesting in the field of bioinformatics. In this paper, a discrete biogeography based optimization is proposed to select the good subset of informative gene relevant to the classification. In the proposed algorithm, firstly, the fisher-markov selector is used to choose fixed number of gene data. Secondly, to make biogeography based optimization suitable for the feature selection problem; discrete migration model and discrete mutation model are proposed to balance the exploration and exploitation ability. Then, discrete biogeography based optimization, as we called DBBO, is proposed by integrating discrete migration model and discrete mutation model. Finally, the DBBO method is used for feature selection, and three classifiers are used as the classifier with the 10 fold cross-validation method. In order to show the effective and efficiency of the algorithm, the proposed algorithm is tested on four breast cancer dataset benchmarks. Comparison with genetic algorithm, particle swarm optimization, differential evolution algorithm and hybrid biogeography based optimization, experimental results demonstrate that the proposed method is better or at least comparable with previous method from literature when considering the quality of the solutions obtained. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer: A Population-based Study.

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Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine; Pedersen, Lars; Vyberg, Mogens; Koeppe, Erika; Crockett, Seth D; Hamilton, Stanley R; Sørensen, Henrik T; Baron, John A

2016-11-01

Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy. We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%). In a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and

An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer.

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Cosgrove, Casey M; Tritchler, David L; Cohn, David E; Mutch, David G; Rush, Craig M; Lankes, Heather A; Creasman, William T; Miller, David S; Ramirez, Nilsa C; Geller, Melissa A; Powell, Matthew A; Backes, Floor J; Landrum, Lisa M; Timmers, Cynthia; Suarez, Adrian A; Zaino, Richard J; Pearl, Michael L; DiSilvestro, Paul A; Lele, Shashikant B; Goodfellow, Paul J

2018-01-01

The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods. Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status. A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular pathology and prostate cancer therapeutics: from biology to bedside.

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Rodrigues, Daniel Nava; Butler, Lisa M; Estelles, David Lorente; de Bono, Johann S

2014-01-01

Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Analysis on Clinical Features of 2168 Patients with Lung Cancer Diagnosed by Bronchoscope

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Yu Zhang

2013-06-01

Full Text Available Objective: To analyze the clinical features of lung cancer diagnosed by bronchoscopy. Methods: The clinical features of 2168 patients with lung cancer diagnosed by bronchoscopy were retrospectively analyzed, including gender, age, pathological type, diseased region, manifestations under bronchoscopy and methods of drawing materials. Results: The ratio of male/female was 4.8:1 and the peak onset age was 60 - 69 years old. The major pathological type was squamous cell carcinoma (44.5%, then adenocarcinoma (25.9% and small cell lung cancer (18.3%. The incidence of squamous cell carcinoma was the highest in males (50.6%, while that of adenocarcinoma in females (56.2%. The positive diagnostic rates of forceps biopsy, brush biopsy, bronchial alveolar lavage and transbronchial needle aspiration were 81.6%, 49.4%, 18.2% and 62.6%, respectively, whereas that of biopsy combined with brush biopsy came up to 89.0%. Conclusion: Bronchoscopy is an important method in diagnosis of lung cancer. Different ages and genders of patients with lung cancer have different onset, and the distribution of pathological types is diverse. Attaching more importance to bronchoscopy and improving biopsy technique can significantly improve the diagnostic rate and provide reliable evidences for clinical treatment.

Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations

DEFF Research Database (Denmark)

Visco, Carlo; Wang, Jinfen; Tisi, Maria Chiara

2017-01-01

apoptotic pathways, have higher proliferative index, and lack BCL2 translocations. CONCLUSIONS: HCV-positive DLBCL have distinct molecular and pathological features compared to the HCV-negative counterparts.British Journal of Cancer advance online publication, 26 September 2017; doi:10.1038/bjc.2017.345 www.bjcancer.com....... in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas. METHODS: We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1). Cases and controls were...... for MYC, BCL2 and BCL6, TP53 mutations, and diagnostic specimens reviewed to exclude transformation from low-grade lymphoma. RESULTS: Compared to the HCV-negative controls, patients with HCV-positive de novo DLBCL had differential expression of genes that regulate innate immune response and modulate...

Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine.

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Clark, Peter M; Ebiana, Victoria A; Gosa, Laura; Cloughesy, Timothy F; Nathanson, David A

2017-05-01

Comprehensive molecular analysis of individual tumors provides great potential for personalized cancer therapy. However, the presence of a particular genetic alteration is often insufficient to predict therapeutic efficacy. Drugs with distinct mechanisms of action can affect the biology of tumors in specific and unique ways. Therefore, assays that can measure drug-induced perturbations of defined functional tumor properties can be highly complementary to genomic analysis. PET provides the capacity to noninvasively measure the dynamics of various tumor biologic processes in vivo. Here, we review the underlying biochemical and biologic basis for a variety of PET tracers and how they may be used to better optimize cancer therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Cisplatin in cancer therapy: molecular mechanisms of action.

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Dasari, Shaloam; Tchounwou, Paul Bernard

2014-10-05

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

[Clinical and pathological features of breast cancer in a population of Mexico].

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Maffuz-Aziz, Antonio; Labastida-Almendaro, Sonia; Espejo-Fonseca, Aura; Rodríguez-Cuevas, Sergio

Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in México are described. A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures.

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Alessandro Furlan

Full Text Available The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by "RTK swapping" by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in

MOLECULAR BIOLOGICAL FACTORS IN THE PREDICTION OF PROSTATE CANCER

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S. V. Vtorushin

2017-01-01

Full Text Available Purpose: to review the available data on molecular-genetic diagnostic and prognostic markers in prostate cancer. Material and methods. The following electronic databases were used for our systematic review: Medline, Cochrane Library and Elibrary. Of 540 studies, 61 were used for our systematic review. Results. There are currently a variety of both prognostic and diagnostic markers used for diagnosis and treatment of prostate cancer. The review presents the classification of markers depending on the method and medium in which they were identified. The molecular mechanisms of participation of the different genes and proteins in the pathogenesis and progression of prostate carcinoma were analyzed and the potential importance of their use in clinical practice was provided. Conclusion. Many of the existing markers can be used for screening and early detection of tumors, and they have been proved to have a prognostic value. However, contradictory findings with regard to certain proteins and genes require further study, their validation with the subsequent implementation into clinical practice.

Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

International Nuclear Information System (INIS)

Stites, Edward C

2013-01-01

Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients. (paper)

The promise of molecular epidemiology in defining the association between radiation and cancer

International Nuclear Information System (INIS)

Neta, R.

2000-01-01

Molecular epidemiology involves the inclusion in epidemiologic studies of biologic measurements made at a genetic and molecular level and aims to improve the current knowledge of disease etiology and risk. One of the goals of molecular epidemiology studies of cancer is to determine the role of environmental and genetic factors in initiation and progression of malignancies and to use this knowledge to develop preventive strategies. This approach promises extraordinary opportunities for revolutionizing the practice of medicine and reducing risk. However, this will be accompanied by the need to address and resolve many challenges, such as ensuring the appropriate interpretation of molecular testing and resolving associated ethical, legal, and social issues. Traditional epidemiologic approaches determined that exposure to ionizing radiation poses significantly increased risk of leukemia and several other types of cancer. Such studies provided the basis for setting exposure standards to protect the public and the workforce from potentially adverse effects of ionizing radiation. These standards were set by using modeling approaches to extrapolate from the biological effects observed in high-dose radiation studies to predicted, but mostly immeasurable, effects at low radiation doses. It is anticipated that the addition of the molecular parameters to the population-based studies will help identify the genes and pathways characteristic of cancers due to radiation exposure of individuals, as well as identify susceptible or resistant subpopulations. In turn, the information about the molecular mechanisms should aid to improve risk assessment. While studies on radiogenic concerns are currently limited to only a few candidate genes, the exponential growth of scientific knowledge and technology promises expansion of knowledge about identity of participating genes and pathways in the future. This article is meant to provide an introductory overview of recent advances in

Diagnosis and management of differentiated thyroid cancer using molecular biology.

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Witt, Robert L; Ferris, Robert L; Pribitkin, Edmund A; Sherman, Steven I; Steward, David L; Nikiforov, Yuri E

2013-04-01

To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer. Ovid Medline 2006-2012 Manuscripts with clinical correlates. Papillary thyroid carcinomas harbor point mutations of the BRAF and RAS genes or RET/PTC rearrangements, all of which activate the mitogen-activated protein kinase pathway. These mutually exclusive mutations are found in 70% of PTC. BRAF mutation is found in 45% of papillary thyroid cancer and is highly specific. Follicular carcinomas are known to harbor RAS mutation or PAX8/PPARγ rearrangement. These mutations are also mutually exclusive and identified in 70% of follicular carcinomas. Molecular classifiers measure the expression of a large number of genes on a microarray chip providing a substantial negative predictive value pending further validation. 1) 20% to 30% of cytologically classified Follicular Neoplasms and Follicular Lesion of Undetermined Significance collectively are malignant on final pathology. Approximately 70% to 80% of thyroid lobectomies performed solely for diagnostic purposes are benign. Molecular alteration testing may reduce the number of unnecessary thyroid procedures, 2) may reduce the number of completion thyroidectomies, and 3) may lead to more individualized operative and postoperative management. Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ for follicular lesion of undetermined significance and follicular neoplasm improve specificity, whereas molecular classifiers may add negative predictive value to fine needle aspiration diagnosis. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

Molecular profiling in the treatment of colorectal cancer: focus on regorafenib

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Yan Y

2015-10-01

Full Text Available Yiyi Yan, Axel Grothey Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA Abstract: Metastatic colorectal cancer (mCRC is a highly heterogeneous disease. Its treatment outcome has been significantly improved over the last decade with the incorporation of biological targeted therapies, including anti-EGFR antibodies, cetuximab and panitumumab, and VEGF inhibitors, bevacizumab, ramucirumab, and aflibercept. The identification of predictive biomarkers has further improved the survival by accurately selecting patients who are most likely to benefit from these treatments, such as RAS mutation profiling for EGFR antibodies. Regorafenib is a multikinase inhibitor currently used as late line therapy for mCRC. The molecular and genetic markers associated with regorafenib treatment response are yet to be characterized. Here, we review currently available clinical evidence of mCRC molecular profiling, such as RAS, BRAF, and MMR testing, and its role in targeted therapies with special focus on regorafenib treatment. Keywords: metastatic colon cancer, targeted therapy, molecular profiling, regorafenib 

Progress in Molecular Imaging in Endoscopy and Endomicroscopy for Cancer Imaging

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Supang Khondee

2013-01-01

Full Text Available Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes.

A combination of molecular markers and clinical features improve the classification of pancreatic cysts.

Science.gov (United States)

Springer, Simeon; Wang, Yuxuan; Dal Molin, Marco; Masica, David L; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P; Wolfgang, Christopher L; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J; Klimstra, David S; Schattner, Mark A; Schmidt, C Max; Yip-Schneider, Michele; Cummings, Oscar W; Brand, Randall E; Zeh, Herbert J; Singhi, Aatur D; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J; Cameron, John; Pittman, Meredith; Eshleman, James R; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Karchin, Rachel; Hruban, Ralph H; Vogelstein, Bert; Lennon, Anne Marie

2015-11-01

The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Hereditary breast cancer: from molecular pathology to tailored therapies.

Science.gov (United States)

Tan, D S P; Marchiò, C; Reis-Filho, J S

2008-10-01

Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

Immunophenotyping invasive breast cancer: paving the road for molecular imaging

International Nuclear Information System (INIS)

Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

2012-01-01

Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

Directory of Open Access Journals (Sweden)

Cristina Trejo-Solís

2013-01-01

Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

Evaluation Methodology between Globalization and Localization Features Approaches for Skin Cancer Lesions Classification

Science.gov (United States)

Ahmed, H. M.; Al-azawi, R. J.; Abdulhameed, A. A.

2018-05-01

Huge efforts have been put in the developing of diagnostic methods to skin cancer disease. In this paper, two different approaches have been addressed for detection the skin cancer in dermoscopy images. The first approach uses a global method that uses global features for classifying skin lesions, whereas the second approach uses a local method that uses local features for classifying skin lesions. The aim of this paper is selecting the best approach for skin lesion classification. The dataset has been used in this paper consist of 200 dermoscopy images from Pedro Hispano Hospital (PH2). The achieved results are; sensitivity about 96%, specificity about 100%, precision about 100%, and accuracy about 97% for globalization approach while, sensitivity about 100%, specificity about 100%, precision about 100%, and accuracy about 100% for Localization Approach, these results showed that the localization approach achieved acceptable accuracy and better than globalization approach for skin cancer lesions classification.

[Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

Science.gov (United States)

Jono, Hirofumi

2018-01-01

　Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

Molecular Pathways: Cachexia Signaling-A Targeted Approach to Cancer Treatment.

Science.gov (United States)

Miyamoto, Yuji; Hanna, Diana L; Zhang, Wu; Baba, Hideo; Lenz, Heinz-Josef

2016-08-15

Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR. ©2016 American Association for Cancer Research.

Molecular imaging of apoptosis in cancer

International Nuclear Information System (INIS)

Hakumaeki, Juhana M.; Liimatainen, Timo

2005-01-01

Apoptosis plays an important role in cancer. Mechanisms hindering its action are implicated in a number of malignancies. Also, the induction of apoptosis plays a pivotal role in non-surgical cancer treatment regimes such as irradiation, chemotherapy, or hormones. Recent advanced in imaging science have made it now possible for us to detect and visualize previously inaccessible and even unrecognized biological phenomena in cells and tissue undergoing apoptosis in vivo. Not only are these imaging techniques painting an intriguing picture of the spatiotemporal characteristics and metabolic and biophysical of apoptosis in situ, but they are expected to have an ever increasing impact in preclinical testing and design of new anticancer agents as well. Rapid and accurate visualization of apoptotic response in the clinical settings can also be of significant diagnostic and prognostic worth. With the advent of molecular medicine and patient-tailored treatment options and therapeutic agents, such monitoring techniques are becoming paramount

Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

Science.gov (United States)

Subramaniam, Prasad

Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

Science.gov (United States)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

2015-08-01

Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

NARCIS (Netherlands)

Hoadley, Katherine A.; Yau, Christina; Hinoue, Toshinori; Wolf, Denise M.; Lazar, Alexander J.; Drill, Esther; Shen, Ronglai; Taylor, Alison M.; Cherniack, Andrew D.; Thorsson, Vésteinn; Akbani, Rehan; Bowlby, Reanne; Wong, Christopher K.; Wiznerowicz, Maciej; Sanchez-Vega, Francisco; Robertson, A. Gordon; Schneider, Barbara G.; Lawrence, Michael S.; Noushmehr, Houtan; Malta, Tathiane M.; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher C.; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, olanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, Jonathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Stuart, Joshua M.; Benz, Christopher C.; Laird, Peter W.

2018-01-01

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA

Molecular classification of gastric cancer: a new paradigm.

Science.gov (United States)

Shah, Manish A; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y; Klimstra, David S; Gerdes, Hans; Kelsen, David P

2011-05-01

Gastric cancer may be subdivided into 3 distinct subtypes--proximal, diffuse, and distal gastric cancer--based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. ©2011 AACR.

Genetic prognostic markers in colorectal cancer.

OpenAIRE

Houlston, R S; Tomlinson, I P

1997-01-01

The contribution of molecular genetics to colorectal cancer has been restricted largely to relatively rare inherited tumours and to the detection of germline mutations predisposing to these cancers. However, much is now also known about somatic events leading to colorectal cancer. A number of studies has been undertaken examining possible relations between genetic features and prognostic indices. While many of these studies are small and inconclusive, it is clear that a number of different pa...

Improving breast cancer survival analysis through competition-based multidimensional modeling.

Directory of Open Access Journals (Sweden)

Erhan Bilal

Full Text Available Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually. As with most cancers, it is a heterogeneous disease and different breast cancer subtypes are treated differently. Understanding the difference in prognosis for breast cancer based on its molecular and phenotypic features is one avenue for improving treatment by matching the proper treatment with molecular subtypes of the disease. In this work, we employed a competition-based approach to modeling breast cancer prognosis using large datasets containing genomic and clinical information and an online real-time leaderboard program used to speed feedback to the modeling team and to encourage each modeler to work towards achieving a higher ranked submission. We find that machine learning methods combined with molecular features selected based on expert prior knowledge can improve survival predictions compared to current best-in-class methodologies and that ensemble models trained across multiple user submissions systematically outperform individual models within the ensemble. We also find that model scores are highly consistent across multiple independent evaluations. This study serves as the pilot phase of a much larger competition open to the whole research community, with the goal of understanding general strategies for model optimization using clinical and molecular profiling data and providing an objective, transparent system for assessing prognostic models.

Guidance for laboratories performing molecular pathology for cancer patients

NARCIS (Netherlands)

Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

2014-01-01

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

Guidance for laboratories performing molecular pathology for cancer patients

NARCIS (Netherlands)

Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

Loss of heterozygosity in colorectal cancer

African Journals Online (AJOL)

STORAGESEVER

2009-12-29

Dec 29, 2009 ... and biological features of CRC, providing us much essential information about the pathogenesis of this disease. ... In all human cancers, the molecular genetic alte- .... Kras2 gene was detected in breast, rectum, stomach,.

Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.

Science.gov (United States)

Nemtsova, Marina V; Strelnikov, Vladimir V; Tanas, Alexander S; Bykov, Igor I; Zaletaev, Dmitry V; Rudenko, Viktoria V; Glukhov, Alexander I; Kchorobrich, Tatiana V; Li, Yi; Tarasov, Vadim V; Barreto, George E; Aliev, Gjumrakch

2017-10-01

We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.

The development of epidermal growth factor receptor molecular imaging in cancer

International Nuclear Information System (INIS)

Zhou Xiaoliang; Wang Hao; Shi Peiji; Liu Jianfeng; Meng Aimin

2013-01-01

In vivo epidermal growth factor receptor (EGFR) targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects. Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which could enable monitoring of receptor drug binding and receptor occupancy in vivo, and identification of the mutation in EGFR. PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders, predicting therapeutic outcome and monitoring EGFR-targeted treatment. This review analyzed the present situation and research progress of molecular imaging agents. (authors)

Molecular biology of breast cancer stem cells: potential clinical applications.

Science.gov (United States)

Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

2010-10-01

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

Science.gov (United States)

Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

2015-10-05

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed

Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

Directory of Open Access Journals (Sweden)

Zhao Y

2015-06-01

Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

Time-Trend in Epidemiological and Pathological Features of Schistosoma-Associated Bladder Cancer

International Nuclear Information System (INIS)

ZAGHLOUL, M.S.; EL-BARADIE, M.; NAZMY, M.; NOUH, A.; MONEER, M.; YOUNIS, A.

2008-01-01

To investigate the different emerging trends in the features of bladder cancer along 17 years. Patients and Methods: During a 17-year period (1988- 2004), 5071 epithelial bladder cancer patients underwent radical cystectomy at the National Cancer Institute (NCI), Cairo University, Egypt. The time was divided into 3 time periods to detect changes of the clinico pathologic features of patients in these periods. Results: There was a significant progressive increase in the patients' age with time and decrease in squamous/ transitional ratio, with transient increase in male predominance during the 2nd time period. Moreover, there was a decrease in the well differentiated (grade 1) tumor (p<0.001) and an increase in the frequency of pelvic nodal involvement (p<0.001). Transitional cell carcinoma (TCC) patients were significantly older than those with squamous cell carcinoma (SCC) (p<0.001). Progressive increase of age with time was evident in TCC, SCC and adenocarcinoma patients. Male to female ratio changed significantly in TCC and SCC. Conclusion: Time trend was confirmed with relative decrease in frequency of SCC and increase of TCC with changes in their pathological details. The differences between their characteristics and that of the Western countries are decreasing.

Identification of critical chemical features for Aurora kinase-B inhibitors using Hip-Hop, virtual screening and molecular docking

Science.gov (United States)

Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; John, Shalini; Lee, Keun Woo

2011-01-01

This study was performed to find the selective chemical features for Aurora kinase-B inhibitors using the potent methods like Hip-Hop, virtual screening, homology modeling, molecular dynamics and docking. The best hypothesis, Hypo1 was validated toward a wide range of test set containing the selective inhibitors of Aurora kinase-B. Homology modeling and molecular dynamics studies were carried out to perform the molecular docking studies. The best hypothesis Hypo1 was used as a 3D query to screen the chemical databases. The screened molecules from the databases were sorted based on ADME and drug like properties. The selective hit compounds were docked and the hydrogen bond interactions with the critical amino acids present in Aurora kinase-B were compared with the chemical features present in the Hypo1. Finally, we suggest that the chemical features present in the Hypo1 are vital for a molecule to inhibit the Aurora kinase-B activity.

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

Energy Technology Data Exchange (ETDEWEB)

Aulino, Paola [Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy and Interuniversity Institute of Myology (Italy); Faiola, Fabio [DVM Veterinarian chief, Health Status and Animal Welfare, Sapienza University of Rome, Via Scarpa 16, 00161 Rome (Italy); Adamo, Sergio; Coletti, Dario; Berardi, Emanuele; Cardillo, Veronica M; Rizzuto, Emanuele; Perniconi, Barbara; Ramina, Carla; Padula, Fabrizio [Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy and Interuniversity Institute of Myology (Italy); Spugnini, Enrico P [SAFU Department, Regina Elena Cancer Institute, Via delle Messi d' Oro 156, 00158 Rome (Italy); Baldi, Alfonso [Department Biochemistry, Section of Pathology, Second University of Naples, Via L. Armanni 5, 80138 Naples (Italy)

2010-07-08

The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

International Nuclear Information System (INIS)

Aulino, Paola; Faiola, Fabio; Adamo, Sergio; Coletti, Dario; Berardi, Emanuele; Cardillo, Veronica M; Rizzuto, Emanuele; Perniconi, Barbara; Ramina, Carla; Padula, Fabrizio; Spugnini, Enrico P; Baldi, Alfonso

2010-01-01

The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

Directory of Open Access Journals (Sweden)

Baldi Alfonso

2010-07-01

Full Text Available Abstract Background The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. Methods A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. Results We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. Conclusions We conclude, on the basis of the definition of

Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions

Directory of Open Access Journals (Sweden)

Romana Tomaszewska

1999-01-01

Full Text Available The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia and high‐grade proliferation (atypical papillary hyperplasia and carcinoma in situ. A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.

Familial Gastric Cancers.

Science.gov (United States)

Setia, Namrata; Clark, Jeffrey W; Duda, Dan G; Hong, Theodore S; Kwak, Eunice L; Mullen, John T; Lauwers, Gregory Y

2015-12-01

Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. ©AlphaMed Press.

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

Science.gov (United States)

Hu, Jieping; Wang, Gongxian; Sun, Ting

2017-05-01

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

Science.gov (United States)

Chu, Xin-Yi; Jiang, Ling-Han; Zhou, Xiong-Hui; Cui, Ze-Jia; Zhang, Hong-Yu

2017-07-14

The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Zhiwen Xiao

2014-01-01

Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

Science.gov (United States)

Ocak, S; Sos, M L; Thomas, R K; Massion, P P

2009-08-01

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer.

Science.gov (United States)

Chen, Xuesong; Sun, Lichun; Cong, Yingying; Zhang, Tingting; Lin, Qiushi; Meng, Qingwei; Pang, Hui; Zhao, Yanbin; Li, Yu; Cai, Li; Dong, Xiaoqun

2014-03-17

Bone scanning (BS), liver ultrasonography (LUS), and chest radiography (CXR) are commonly recommended for baseline staging in patients with newly diagnosed breast cancer. The purpose of this study is to demonstrate whether these tests are indicated for specific patient subpopulation based on clinical staging and molecular subtype. A retrospective study on 5406 patients with newly diagnosed breast cancer was conducted to identify differences in occurrence of metastasis based on clinical staging and molecular subtypes. All patients had been evaluated by BS, LUS and CXR at diagnosis. Complete information on clinical staging was available in 5184 patients. For stage I, II, and III, bone metastasis rate was 0%, 0.6% and 2.7%, respectively (P diagnosed breast cancer.

Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options

OpenAIRE

Tanna, P.; Strauss, R. W.; Fujinami, K.; Michaelides, M.

2017-01-01

Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular dystrophy and is associated with disease-causing sequence variants in the gene ABCA4 Significant advances have been made over the last 10 years in our understanding of both the clinical and molecular features of STGD1, and also the underlying pathophysiology, which has culminated in ongoing and planned human clinical trials of novel therapies. The aims of this review are to describe the detailed phenotypic and genot...

Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options

OpenAIRE

Tanna, Preena; Strauss, Rupert W; Fujinami, Kaoru; Michaelides, Michel

2016-01-01

Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular dystrophy and is associated with disease-causing sequence variants in the gene ABCA4. Significant advances have been made over the last 10?years in our understanding of both the clinical and molecular features of STGD1, and also the underlying pathophysiology, which has culminated in ongoing and planned human clinical trials of novel therapies. The aims of this review are to describe the detailed phenotypic and geno...

Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

Science.gov (United States)

Staquicini, Fernanda I; Qian, Ming D; Salameh, Ahmad; Dobroff, Andrey S; Edwards, Julianna K; Cimino, Daniel F; Moeller, Benjamin J; Kelly, Patrick; Nunez, Maria I; Tang, Ximing; Liu, Diane D; Lee, J Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R M; Lobb, Roy R; Edelman, Martin J; Sidman, Richard L; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

2015-03-20

Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Status and Advances of RGD Molecular Imaging in Lung Cancer

Directory of Open Access Journals (Sweden)

Ning YUE

2014-12-01

Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

Science.gov (United States)

2017-10-01

15.3%) NA 6 (6%) 6 (5.4%) Prostate - specific Antigen (PSA) ng/mL 76.7 (42.9) 78.2 (40.7) pTNM Stage T2 68 (67.3%) 48 (43.2%) T3 29 (28.7%) 58...Profiles Primary Aim #1: Determine if methylation profiles differ by race/ancestry Primary Aim #2: Identify ethnicity- specific markers of prostate ...by ethnicity and to identify ethnicity- specific methylation features of prostate cancer that could contribute the racial disparities that exist in

Molecular pathobiology of thyroid neoplasms.

Science.gov (United States)

Tallini, Giovanni

2002-01-01

Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

2011-02-24

Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

International Nuclear Information System (INIS)

Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

2011-01-01

Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

Molecular biology of prostate cancer progression

International Nuclear Information System (INIS)

Thompson, Timothy C.; Sehgal, I.; Timme, T.L.; Rn, C.; Yang, G.; Park, S.H.

1996-01-01

'control' gene in human prostate cancer was supported by studies using molecular biological and immunohistochemical techniques (Eastham et al, Clin Cancer Res 1:1111-1118, 1995 and Yang et al, Clin Cancer Res 2:399-401, 1996). Another possible ''control'' gene related to prostate cancer metastases may be the gene which encodes TGF-β1. We have previously shown that overexpression of TGF-β1 is associated with mouse and human prostate cancer and occurs predominantly in metastatic disease (Eastham et al, Lab Invest 73:628-635, 1995). To investigate a possible role of TGF-β1 in metastatic progression, we compared growth and extracellular matrix responses to TGF-β1 in six metastatic and six primary tumor cell lines derived from our metastatic mouse prostate cancer model system. The results indicated that tumor cell lines derived from focal pulmonary metastases secrete greater quantities of total TGF-β's and have lost most or all TGF-β1 growth inhibition, but respond to TGF-β1 through induction of type IV collagenase, matrix metalloproteinase-9. Cell lines derived from primary site tumors retain TGF-β1 growth inhibition, but lack TGF-β1-induced collagenase activity. Our results indicate that the elimination and/or subversion of TGF-β1 responsive pathways should be considered a mechanistic framework for metastatic events (Sehgal et al., Cancer Res 56:3359-3365, 1996). Both p53 and TGF-β1 can regulate the expression of downstream genetic targets, therefore, we are currently pursuing a strategy using differential display-polymerase chain reaction to elucidate additional changes in gene expression resulting from loss and/or subversion of function for these two putative ''control'' genes in prostate cancer metastasis. Hopefully, identification of these target genes will lead to greater understanding of the mechanisms of prostate cancer metastasis and possibly provide novel therapeutic targets

Dogs as a Model for Cancer.

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Gardner, Heather L; Fenger, Joelle M; London, Cheryl A

2016-01-01

Spontaneous cancers in client-owned dogs closely recapitulate their human counterparts with respect to clinical presentation, histological features, molecular profiles, and response and resistance to therapy, as well as the evolution of drug-resistant metastases. In several instances the incorporation of dogs with cancer into the preclinical development path of cancer therapeutics has influenced outcome by helping to establish pharmacokinetic/pharmacodynamics relationships, dose/regimen, expected clinical toxicities, and ultimately the potential for biologic activity. As our understanding regarding the molecular drivers of canine cancers has improved, unique opportunities have emerged to leverage this spontaneous model to better guide cancer drug development so that therapies likely to fail are eliminated earlier and therapies with true potential are optimized prior to human studies. Both pets and people benefit from this approach, as it provides dogs with access to cutting-edge cancer treatments and helps to insure that people are given treatments more likely to succeed.

Raman spectroscopic analysis for gastric and colorectal cancer in surgical treatment toward molecular-guided surgery

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Koga, Shigehiro; Watanabe, Yuji; Oshima, Yusuke

2018-02-01

Raman spectroscopy provides a wealth of diagnostic information to the surgeon with in situ cancer detection and label-free histopathology in intraoperative conditions. Raman spectroscopy is a promising optical technique which can analyze biological tissues with light scattering. The difference in frequencies between the incident light and the scattering light are called Raman shifts, which correspond to the vibrational energy of the molecular bonds. Raman spectrum gives information about the molecular structure and composition in biological specimens. We had been previously reported that Raman spectroscopy could distinguish various histological types of human lung cancer cells from normal cells in vitro, and also confirmed that Raman spectra obtained from cancer cells and their environment including other cells and extracellular matrix in xenograft models and spontaneous metastasis models were distinguishable using Raman spectroscopy combined with fluorescence microscopy and photoluminescence imaging. Malignancy can be characterized not only by the cancer cells but also by the environmental factors including immune cells, stroma cells, secretion vesicles and extracellular matrix, but to identify and detect cancer diagnostic biomarkers in vivo on Raman spectroscopy is still challenging. Here we investigate morphological and molecular dynamics in advanced cancer specimens obtained from patients. We are also constructing a customdesigned Raman spectral imaging system for both in vitro and in vivo assay of tumor tissues to reveal the metastasis process and to evaluate therapeutic effects of anti-cancer drugs and their drug delivery toward the clinical application of the technique.

From Molecular Classification to Targeted Therapeutics: The Changing Face of Systemic Therapy in Metastatic Gastroesophageal Cancer

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Adrian Murphy

2015-01-01

Full Text Available Histological classification of adenocarcinoma or squamous cell carcinoma for esophageal cancer or using the Lauren classification for intestinal and diffuse type gastric cancer has limited clinical utility in the management of advanced disease. Germline mutations in E-cadherin (CDH1 or mismatch repair genes (Lynch syndrome were identified many years ago but given their rarity, the identification of these molecular alterations does not substantially impact treatment in the advanced setting. Recent molecular profiling studies of upper GI tumors have added to our knowledge of the underlying biology but have not led to an alternative classification system which can guide clinician’s therapeutic decisions. Recently the Cancer Genome Atlas Research Network has proposed four subtypes of gastric cancer dividing tumors into those positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. Unfortunately to date, many phase III clinical trials involving molecularly targeted agents have failed to meet their survival endpoints due to their use in unselected populations. Future clinical trials should utilize molecular profiling of individual tumors in order to determine the optimal use of targeted therapies in preselected patients.

The CpG island methylator phenotype (CIMP) in colorectal cancer.

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Nazemalhosseini Mojarad, Ehsan; Kuppen, Peter Jk; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

2013-01-01

It is clear that colorectal cancer (CRC) develops through multiple genetic and epigenetic pathways. These pathways may be determined on the basis of three molecular features: (i) mutations in DNA mismatch repair genes, leading to a DNA microsatellite instability (MSI) phenotype, (ii) mutations in APC and other genes that activate Wnt pathway, characterized by chromosomal instability (CIN) phenotype, and (iii) global genome hypermethylation, resulting in switch off of tumor suppressor genes, indicated as CpG island methylator phenotype (CIMP). Each of these pathways is characterized by specific pathological features, mechanisms of carcinogenesis and process of tumor development. The molecular aspects of these pathways have been used clinically in the diagnosis, screening and management of patients with colorectal cancer. In this review we especially describe various aspects of CIMP, one of the important and rather recently discovered pathways that lead to colorectal cancer.

Immunophenotyping invasive breast cancer: paving the road for molecular imaging

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Vermeulen Jeroen F

2012-06-01

Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

[Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

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Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

2017-02-01

Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

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Reinhold, William C

2015-12-10

There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application.

Robustness of radiomic breast features of benign lesions and luminal A cancers across MR magnet strengths

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Whitney, Heather M.; Drukker, Karen; Edwards, Alexandra; Papaioannou, John; Giger, Maryellen L.

2018-02-01

Radiomics features extracted from breast lesion images have shown potential in diagnosis and prognosis of breast cancer. As clinical institutions transition from 1.5 T to 3.0 T magnetic resonance imaging (MRI), it is helpful to identify robust features across these field strengths. In this study, dynamic contrast-enhanced MR images were acquired retrospectively under IRB/HIPAA compliance, yielding 738 cases: 241 and 124 benign lesions imaged at 1.5 T and 3.0 T and 231 and 142 luminal A cancers imaged at 1.5 T and 3.0 T, respectively. Lesions were segmented using a fuzzy C-means method. Extracted radiomic values for each group of lesions by cancer status and field strength of acquisition were compared using a Kolmogorov-Smirnov test for the null hypothesis that two groups being compared came from the same distribution, with p-values being corrected for multiple comparisons by the Holm-Bonferroni method. Two shape features, one texture feature, and three enhancement variance kinetics features were found to be potentially robust. All potentially robust features had areas under the receiver operating characteristic curve (AUC) statistically greater than 0.5 in the task of distinguishing between lesion types (range of means 0.57-0.78). The significant difference in voxel size between field strength of acquisition limits the ability to affirm more features as robust or not robust according to field strength alone, and inhomogeneities in static field strength and radiofrequency field could also have affected the assessment of kinetic curve features as robust or not. Vendor-specific image scaling could have also been a factor. These findings will contribute to the development of radiomic signatures that use features identified as robust across field strength.

Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.

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Tomlins, Scott A; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B; Dicker, Adam P; Trock, Bruce J; DeMarzo, Angelo M; Ross, Ashley E; Schaeffer, Edward M; Klein, Eric A; Magi-Galluzzi, Cristina; Karnes, R Jeffrey; Jenkins, Robert B; Feng, Felix Y

2015-10-01

Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different among subtypes. A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes

Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review.

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Gan, Ren-You; Li, Hua-Bin; Sui, Zhong-Quan; Corke, Harold

2018-04-13

Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.

Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

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Park Hyung Seok

2012-01-01

Full Text Available Abstract Background Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. Methods In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR, and human epithelial receptor-2 (HER2 were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC according to ER, PR, and HER2 status. Results Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Conclusions Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

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2011-07-01