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Sample records for cancer molecular features

  1. Correlative Study on MRI Morphologic Features,Pathology, and Molecular Biology of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Rong Chen; Shuigen Gong; Weiguo Zhang; Jinhua Chen; Shuangwu He; Baohua Liu; Zengpeng Li

    2005-01-01

    OBJECTIVE To investigate the correlation among MRI morphologic features,pathology, and molecular biology of breast cancer.METHORDS MRI was used to analyze the morphologic features of breast cancers of 78 patients before operation. The mastectomy specimens of the breast neoplasms were immunohistochemically stained, and the expression of the estrogen (ER), progesterone receptor (PR), C-erbB-2, P53, and the distribution of microvessel density (MVD) measured. The pathologic results were compared with the MRI features.RESULTS Among the 80 breast cancers, ER positive expression was positively correlated with the spicular contour of breast cancers (P<0.01),while showing a significant inverse correlation with the T-stage (P<0.05). CerbB-2 and P53 positive expression were positively correlated with the necrotic center of the cancers (P<0.05). The expression of PR was not significantly correlated with the spicular contour, obscure margin, necrotic center, and T-stage of these cancers (P>0.05). Among 41 breast cancers examined with dynamic contrast enhanced MR, there was a positive correlation between the spatial distribution of the contrast agent and MVD(P<0.01).CONCLUSION To a certain extent there is some correlation among the MRI morphologic features, pathology, and molecular biological factors in breast cancer. The biological behavior and prognosis of breast cancer can be assessed based on MRI features.

  2. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Moira Ragazzi

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  3. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Anne Planche

    Full Text Available Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

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

    Science.gov (United States)

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

    2016-03-01

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

  5. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    International Nuclear Information System (INIS)

    Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Importance of Molecular Features of Non–Small Cell Lung Cancer for Choice of Treatment

    OpenAIRE

    Moran, Cesar

    2011-01-01

    Lung cancer is the leading cause of cancer-related deaths in the United States. Approximately 85% of lung cancer is categorized as non–small cell lung cancer, and traditionally, non–small cell lung cancer has been treated with surgery, radiation, and chemotherapy. Targeted agents that inhibit the epidermal growth factor receptor pathway have been developed and integrated into the treatment regimens in non–small cell lung cancer. Currently, approved epidermal growth factor receptor inhibitors ...

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

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    Lee, Kang Nyeong [Department of Internal Medicine, Hanyang University College of Medicine, Seoul (Korea, Republic of); Choi, Ho Soon, E-mail: hschoi96@hanyang.ac.kr [Department of Internal Medicine, Hanyang University College of Medicine, Seoul (Korea, Republic of); Yang, Sun Young [Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul (Korea, Republic of); Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo [Department of Internal Medicine, Hanyang University College of Medicine, Seoul (Korea, Republic of); Paik, Seung Sam [Pathology, Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2014-04-18

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

  10. 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.

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

    Science.gov (United States)

    Magnani, Giulia; Furlan, Daniela; Sahnane, Nora; Reggiani Bonetti, Luca; Domati, Federica; Pedroni, Monica

    2015-01-01

    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. PMID:26557847

  12. Molecular genetics of colorectal cancer.

    Science.gov (United States)

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  13. Analysis of normal-tumour tissue interaction in tumours: prediction of prostate cancer features from the molecular profile of adjacent normal cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    Full Text Available Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the tissue microenvironment in specifying tumour physiology. Because of the importance of normal cells in shaping the tissue microenvironment we formulate the hypothesis that molecular components of the profile of normal epithelial cells adjacent the tumour are predictive of tumour physiology. We addressed this hypothesis by developing statistical models that link gene expression profiles representing the molecular state of adjacent normal epithelial cells to tumour features in prostate cancer. Furthermore, network analysis showed that predictive genes are linked to the activity of important secreted factors, which have the potential to influence tumor biology, such as IL1, IGF1, PDGF BB, AGT, and TGFβ.

  14. Molecular imaging in cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Michalski, Mark H. [Stanford University School of Medicine, Stanford, CA (United States); Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States)

    2011-02-15

    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. (orig.)

  15. Molecular subtypes and clinicopathological features of breastcancer

    Directory of Open Access Journals (Sweden)

    Irianiwati Irianiwati

    2013-04-01

    Full Text Available Breast cancer is a heterogeneous disease with regard to morphological spectrum, clinical presentation and response to therapy. Based on immunohistochemistry detection of estrogen receptor, progesterone receptor, Her-2 status, proliferation rate and clusters of basal gene expression, breast cancers can be classified into luminal A, luminal B, basal-like/triple negative, and Her-2 positive. It was suggested that there was a close relationship between molecular subtypes and clinicopathological features of breast cancer, as they are very important to predict prognosis and therapeutic implications. Keywords: molecular subtypes - breast cancer- clinicopathological features -heterogeneity –theraputicimplications   Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  16. Breast Cancers Between Mammograms Have Aggressive Features

    Science.gov (United States)

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

  17. Analysis of Normal-Tumour Tissue Interaction in Tumours: Prediction of Prostate Cancer Features from the Molecular Profile of Adjacent Normal Cells

    OpenAIRE

    Trevino, Victor; Tadesse, Mahlet G.; Vannucci, Marina; Al-Shahrour, Fatima; Antczak, Philipp; Durant, Sarah; Bikfalvi, Andreas; Dopazo, Joaquin; Campbell, Moray J.; Falciani, Francesco

    2011-01-01

    Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the t...

  18. FEATURES OF BILATERAL BREAST CANCER NODAL METASTASIS

    Directory of Open Access Journals (Sweden)

    Ye. A. Fesik

    2014-01-01

    Full Text Available This article focuses on issues related to the identification and investigation of the lymph node metastases with bilateral breast cancer. The presence of metastases in the lymph nodes determines the stage of the disease, and introducing a form of tumor progression, characterizes the course and prognosis for the future in a specific patient. Thus, the identification of possible morphological and immunohistochemical characteristics of the tumor tissue and their comparison with the frequency and severity of regional lymph nodes would help to solve the problem of the identification of prognostic factors and markers associated with the risk of nodal metastasis in bilateral breast cancer. This work is relevant due to the fact that the literature on this issue to date are treated ambiguously, and answers to many questions, unfortunately, no.The authors performed a morphological study of the tumor tissue from 600 patients suffering from unilateral and bilateral breast cancer. To avoid false results were studied only cases corresponding to the histological type of invasive carcinoma of non-specific type. The study found that a greater number and a greater percentage of the affected lymph node metastases were observed in patients with bilaterally synchronous tumors. The patients of this group of metastatic lymph nodes was detected more frequently in the presence of infiltrative component of three or more types of structures with the presence of these discrete groups of tumor cells, and the observed maximum degree of inflammatory infiltration of the tumor stroma. In the group of patients with unilateral breast cancer nodal metastasis often detects when triple negative molecular genetic type of the lesion, with large amounts of tumor site, in the presence of infiltrative component of three or more types of structures with the obligatory presence of these microalveolar structures and discretely spaced groups of tumor cells and the highest severity of

  19. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  20. Molecular imaging in ovarian cancer.

    Science.gov (United States)

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  1. Molecular oncology of lung cancer.

    Science.gov (United States)

    Toyooka, Shinichi; Mitsudomi, Tetsuya; Soh, Junichi; Aokage, Keiju; Yamane, Masaomi; Oto, Takahiro; Kiura, Katsuyuki; Miyoshi, Shinichiro

    2011-08-01

    Progress in genetic engineering has made it possible to elucidate the molecular biological abnormalities in lung cancer. Mutations in KRAS and P53 genes, loss of specific alleles, and DNA methylation of the tumor suppressor genes were the major abnormalities investigated between 1980 and the 2000s. In 2004, mutations in the epidermal growth factor receptor (EGFR) gene that cause oncogene addiction were discovered in non-small-cell lung cancers (NSCLCs), especially in adenocarcinomas. Because they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), a great deal of knowledge has been acquired in regard to both EGFR and other genes in the EGFR family and their downstream genes. Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was discovered in NSCLC; and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers that have this translocation. These discoveries graphically illustrate that molecular biological findings are directly linked to the development of clinical oncology and to improving the survival rates of lung cancer patients. Here, we review the remarkable progress in molecular biological knowledge acquired thus far in regard to lung cancer, especially NSCLC, and the future possibilities. PMID:21850578

  2. Molecular classification of gastric cancer.

    Science.gov (United States)

    Chia, N-Y; Tan, P

    2016-05-01

    Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. PMID:26861606

  3. Topological Features In Cancer Gene Expression Data

    OpenAIRE

    Lockwood, Svetlana; Krishnamoorthy, Bala

    2014-01-01

    We present a new method for exploring cancer gene expression data based on tools from algebraic topology. Our method selects a small relevant subset from tens of thousands of genes while simultaneously identifying nontrivial higher order topological features, i.e., holes, in the data. We first circumvent the problem of high dimensionality by dualizing the data, i.e., by studying genes as points in the sample space. Then we select a small subset of the genes as landmarks to construct topologic...

  4. [Molecular diagnostics of lung cancer].

    Science.gov (United States)

    Ryska, A; Dziadziuszko, R; Olszewski, W; Berzinec, P; Öz, B; Gottfried, M; Cufer, T; Samarzija, M; Plank, L; Ostoros, Gy; Tímár, J

    2015-09-01

    Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.

  5. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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 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.

  6. 乳腺癌的分子分型与临床病理特征及预后的关系%Correlation of molecular subtypes with clinicopathologic features and prognosis in breast cancer

    Institute of Scientific and Technical Information of China (English)

    曹静; 吕志排; 雷冬梅; 楚天骄; 郝志伟

    2013-01-01

    Objective:To investigate the correlation between molecular subtypes,clinicopathologic features and prognosis in breast carcinoma.Methods:Data from 324 female patients with primary breast cancer admitted from Jan.2007 to Dec.2007 were retrospectively analyzed.According to immunohistochemical markers,324 cases of breast cancer were classified into four different subtypes:Luminal A,Luminal B,HER2/neu and basal-like subtype.Relationships between molecular subtypes and clinicopathological characteristics were analyzed,and the disease free survival (DFS) was studied.Results:Molecular subtypes had no correlation with age,tumors size,lymph node metastasis in patients with primary breast cancer (P>0.05).However,there was a correlation of molecular subtypes with histological grade (P<0.05).Patients were followed up for 11~72 months.DFS had a correlation with lymph node metastasis and molecular subtypes (P<0.05),and had no correlation with age,tumors size and histological grade (P>0.05).There was a significant difference in DFS between different molecular subtypes (,P<0.05).Conclusions:Molecular classification can predict the prognosis of patient.Luminal A had a better prognosis than the other three types,and HER2/neu was the worst.%目的:探讨乳腺癌分子分型与临床病理特征及预后之间的关系.方法:回顾性分析2007年我院324例原发性乳腺癌患者的临床病理资料.根据免疫组化结果,将乳腺癌分为Luminal A型、Luminal B型、HER2/neu型及basal-like型.观察乳腺癌分子分型与临床病理特征间的相互关系,比较各型患者术后的无病生存期.结果:乳腺癌的分子分型与年龄分组、肿瘤直径、淋巴结转移无关,与组织学分级相关(P<0.05).患者随访11~72个月,无病生存期与年龄分组、组织学分级无关,与淋巴结转移状态、分子分型相关.不同分子分型患者间的无病生存期存在统计学差异.结论:乳腺癌的分

  7. Molecular Epidemiology of Female Lung Cancer

    OpenAIRE

    Seon-Hee Yim; Yeun-Jun Chung

    2011-01-01

    Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differenc...

  8. The molecular biology of cancer.

    Science.gov (United States)

    Bertram, J S

    2000-12-01

    identifies key genes directly involved in carcinogenesis and demonstrates how mutations in these genes allow cells to circumvent cellular controls. This detailed understanding of the process of carcinogenesis at the molecular level has only been possible because of the advent of modern molecular biology. This new discipline, by precisely identifying the molecular basis of the differences between normal and malignant cells, has created novel opportunities and provided the means to specifically target these modified genes. Whenever possible this review highlights these opportunities and the attempts being made to generate novel, molecular based therapies against cancer. Successful use of these new therapies will rely upon a detailed knowledge of the genetic defects in individual tumors. The review concludes with a discussion of how the use of high throughput molecular arrays will allow the molecular pathologist/therapist to identify these defects and direct specific therapies to specific mutations.

  9. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. The consensus molecular subtypes of colorectal cancer.

    Science.gov (United States)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-11-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

  11. Main clinical epidemiological features of lung cancer

    International Nuclear Information System (INIS)

    A descriptive and cross-sectional study of 95 patients with lung cancer, discharged from Neumology Service at 'Dr Juan Bruno Zayas Alfonso' General Hospital in Santiago de Cuba, was carried out from January, 2008 to December, 2008 in order to identify the main clinical epidemiological features of the aforementioned disease. A malignancy predominance among men aged between 56 and 65 years old, belonging to urban areas and being heavy smoker (out of 30 cigarettes per day over 30 years ), was found. Those affected without a confirmed histological type and IV clinical stage epidermoid carcinoma were predominant. Most of them had the opportunity to be treated. Increasing and intensifying health promotion and disease prevention campaigns were recommended so as to achieve the population to avoid or quit the smoking habit. (author)

  12. Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies

    OpenAIRE

    Matsuoka, Tasuku; Yashiro, Masakazu

    2016-01-01

    Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the...

  13. Circadian molecular clocks and cancer.

    Science.gov (United States)

    Kelleher, Fergal C; Rao, Aparna; Maguire, Anne

    2014-01-01

    Physiological processes such as the sleep-wake cycle, metabolism and hormone secretion are controlled by a circadian rhythm adapted to 24h day-night periodicity. This circadian synchronisation is in part controlled by ambient light decreasing melatonin secretion by the pineal gland and co-ordinated by the suprachiasmatic nucleus of the hypothalamus. Peripheral cell autonomous circadian clocks controlled by the suprachiasmatic nucleus, the master regulator, exist within every cell of the body and are comprised of at least twelve genes. These include the basic helix-loop-helix/PAS domain containing transcription factors; Clock, BMal1 and Npas2 which activate transcription of the periodic genes (Per1 and Per2) and cryptochrome genes (Cry1 and Cry2). Points of coupling exist between the cellular clock and the cell cycle. Cell cycle genes which are affected by the molecular circadian clock include c-Myc, Wee1, cyclin D and p21. Therefore the rhythm of the circadian clock and cancer are interlinked. Molecular examples exist including activation of Per2 leads to c-myc overexpression and an increased tumor incidence. Mice with mutations in Cryptochrome 1 and 2 are arrhythmic (lack a circadian rhythm) and arrhythmic mice have a faster rate of growth of implanted tumors. Epidemiological finding of relevance include 'The Nurses' Health Study' where it was established that women working rotational night shifts have an increased incidence of breast cancer. Compounds that affect circadian rhythm exist with attendant future therapeutic possibilities. These include casein kinase I inhibitors and a candidate small molecule KL001 that affects the degradation of cryptochrome. Theoretically the cell cycle and malignant disease may be targeted vicariously by selective alteration of the cellular molecular clock. PMID:24099911

  14. Posterior breast cancer: Mammographic and ultrasonographic features

    Directory of Open Access Journals (Sweden)

    Janković Ana

    2013-01-01

    Full Text Available Background/Aim. Posterior breast cancers are located in the prepectoral region of the breast. Owing to this distinctive anatomical localization, physical examination and mammographic or ultrasonographic evaluation can be difficult. The purpose of the study was to assess possibilities of diagnostic mammography and breast ultrasonography in detection and differentiation of posterior breast cancers. Methods. The study included 40 women with palpable, histopathological confirmed posterior breast cancer. Mammographic and ultrasonographic features were defined according to Breast Imaging Reporting and Data System (BI-RADS lexicon. Results. Based on standard two-view mammography 87.5%, of the cases were classified as BI-RADS 4 and 5 categories, while after additional mammographic views all the cases were defined as BIRADS 4 and 5 categories. Among 96 mammographic descriptors, the most frequent were: spiculated mass (24.0%, architectural distortion (16.7%, clustered microcalcifications (12.6% and focal asymmetric density (12.6%. The differentiation of the spiculated mass was significantly associated with the possibility to visualize the lesion at two-view mammography (p = 0.009, without the association with lesion diameter (p = 0.083 or histopathological type (p = 0.055. Mammographic signs of invasive lobular carcinoma were significantly different from other histopathological types (architectural distortion, p = 0.003; focal asymmetric density, p = 0.019; association of four or five subtle signs of malignancy, p = 0.006. All cancers were detectable by ultrasonography. Mass lesions were found in 82.0% of the cases. Among 153 ultrasonographic descriptors, the most frequent were: irregular mass (15.7%, lobulated mass (7.2%, abnormal color Doppler signals (20.3%, posterior acoustic attenuation (18.3%. Ultrasonographic BI-RADS 4 and 5 categories were defined in 72.5% of the cases, without a significant difference among various histopathological types (p = 0

  15. Molecular Diagnostic Applications in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Laura Huth

    2014-06-01

    Full Text Available Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients.  Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC. Strategies for molecular analysis of single genes (as KRAS or TP53 as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  16. Molecular therapeutics in pancreas cancer.

    Science.gov (United States)

    Narayanan, Vignesh; Weekes, Colin D

    2016-04-15

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  17. Molecular pathogenesis ofsporadic colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    HidetsuguYamagishi; HajimeKuroda; YasuoImai; HideyukiHiraishi

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classiifed into three major groups according to frequently altered/mutated genes. These genes have been identiifed by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the ifrst half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a lim-ited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research ifeld and discuss its prospects.

  18. 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.

  19. Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

    Directory of Open Access Journals (Sweden)

    Kenichi Konda

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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

  20. DNA aptamers as molecular probes for colorectal cancer study.

    Directory of Open Access Journals (Sweden)

    Kwame Sefah

    Full Text Available BACKGROUND: Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development. METHODOLOGY AND RESULTS: Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh, nor do they recognize most other cancer cell lines tested. CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers.

  1. Hybrid Local Feature Selection In DNA Analysis Based Cancer Classification

    OpenAIRE

    Akila, M.; Mr.S.Senthamarai kannan

    2012-01-01

    Feature selection, as a preprocessing step to machine learning, is effective in reducing dimensionality, removing irrelevant data and increasing learning accuracy. The development of microarray dataset technology has supplied a large volume of data to many fields. In particular, it has been applied to prediction and diagnosis of cancer, so that it helps us to exactly predict and diagnose cancer. To precisely classify cancer we have to select genes related to cancer. The challenging task in ca...

  2. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider

    2004-01-01

    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  3. Integrated Molecular Profiling in Advanced Cancers Trial

    Science.gov (United States)

    2016-06-21

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  4. feature - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

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

  5. Molecular imaging of prostate cancer with PET.

    Science.gov (United States)

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  6. Genetic and molecular changes in ovarian cancer

    Science.gov (United States)

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  7. Molecular Profiling of Prostate Cancer Patients

    OpenAIRE

    Nna, Emmanuel Okechukwu

    2009-01-01

    In the UK, more than 30 000 men are diagnosed annually with prostate cancer (PCa) and about 10 000 men die from it each year. Although several molecular markers have been associated with prostate cancer development and/ or progression, only few of them are used in diagnostic pathology. The current standard tests include serum PSA test, digital rectal examination and histology of prostate biopsy. Recently the PCA-3 molecular test was approved in the European Union, and it is now...

  8. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing radiatio

  9. Expression of eag1 channel associated with the aggressive clinicopathological features and subtype of breast cancer

    OpenAIRE

    Liu, Guang-Xu; Yu, Yun-Cui; He, Xiang-ping; Ren, Sheng-Nan; Fang, Xue-Dong; Liu, Fen; He, Yan

    2015-01-01

    Backgrounds: Expression of eag1 channel (Eag1) is associated with cell malignant transformation, tumor cell metastasis and poor prognosis of the patient. This study aimed at examining whether expression of the Eag1 associated with aggressive clinicopathological feature and the molecular subtype of breast cancer. Materials and Methods: 109 patients who received breast cancer operation during January 2009 to December 2010 in Chinese-Japanese Friendship Hospital of Jilin University were recruite...

  10. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression

    OpenAIRE

    Sato, Katsuaki; Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein ...

  11. Molecular and genetic bases of pancreatic cancer.

    Science.gov (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  12. Molecular biology of the lung cancer

    International Nuclear Information System (INIS)

    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 hallmarks 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)

  13. Radionuclide molecular target therapy for lung cancer

    International Nuclear Information System (INIS)

    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)

  14. Exploiting novel molecular targets in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

  15. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev;

    2014-01-01

    with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer...... to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline...

  16. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Jenny-Maria Jönsson

    Full Text Available OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. RESULTS: 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and

  17. Clinicopathological features and prognosis of gastric cancer in young patients

    OpenAIRE

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

    2016-01-01

    Background 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. Methods 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 gast...

  18. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

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

    Science.gov (United States)

    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.

  20. Molecular markers for prostate cancer.

    NARCIS (Netherlands)

    Reynolds, M.A.; Kastury, K.; Groskopf, J.; Schalken, J.A.; Rittenhouse, H.G.

    2007-01-01

    Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non

  1. Molecular Mechanisms Underlying Psychological Stress and Cancer.

    Science.gov (United States)

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho

    2016-01-01

    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  2. New molecular targets against cervical cancer

    Directory of Open Access Journals (Sweden)

    Duenas-Gonzalez A

    2014-12-01

    Full Text Available Alfonso Duenas-Gonzalez,1,2 Alberto Serrano-Olvera,3 Lucely Cetina,4 Jaime Coronel4 1Unit of Biomedical Research in Cancer, Instituto de Investigaciones Biomedicas UNAM/Instituto Nacional de Cancerologia, Mexico City, 2ISSEMyM Cancer Center, Toluca, 3Medical Oncology Service, ABC Medical Center, Mexico City, 4Division of Clinical Research, Instituto Nacional de Cancerologia, Mexico City, Mexico On behalf of the Tumor Study Group Abstract: Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women. Major advances but still insufficient achievements in the treatment of locally advanced and high-risk early stage patients have occurred in the last decade with the incorporation of concurrent cisplatin with radiation and, lately, gemcitabine added to cisplatin chemoradiation. Despite a number of clinical studies incorporating molecular-targeted therapy as radiosensitizers being in progress, so far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and shown encouraging results in a Phase II study. In advanced disease, cisplatin doublets do not have a great impact on the natural history of the disease with median survival rates not exceeding 13 months. The first Phase III study of bevacizumab, added to cisplatin or a non-cisplatin-containing doublet, showed significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. Characterization of the mutational landscape of cervical cancer has already been initiated, indicating that, for now, few of these targetable alterations match with available agents. Progress in both the mutational landscape knowledge and developments of novel targeted therapies may result in more effective and individualized treatments for cervical cancer. The potential efficacy of

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Molecular markers for thyroid cancer

    International Nuclear Information System (INIS)

    The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more accessible and potentially usable from a methodological viewpoint for diagnosis of the thyroid nodule before surgery. The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more

  5. A refined molecular taxonomy of breast cancer. : molecular classification of breast cancer

    OpenAIRE

    Guedj, Michael; Marisa, Laëtitia; De Reynies, Aurélien; Orsetti, Béatrice; Schiappa, Renaud; Bibeau, Frédéric; MacGrogan, Gaëtan; Lerebours, Florence; Finetti, Pascal; Longy, Michel; Bertheau, Philippe; Bertrand, Françoise; Bonnet, Françoise; Martin, Anne-Laure; Feugeas, Jean-Paul

    2012-01-01

    International audience; The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. ...

  6. Genomics Study of Gastric Cancer and Its Molecular Subtypes.

    Science.gov (United States)

    Yuen, Siu Tsan; Leung, Suet Yi

    2016-01-01

    Gastric cancer is a heterogeneous disease encompassing diverse morphological (intestinal versus diffuse) and molecular subtypes (MSI, EBV, TP53 mutation). Recent advances in genomic technology have led to an improved understanding of the driver gene mutational profile, gene expression, and epigenetic alterations that underlie each of the subgroups, with therapeutic implications in some of these alterations. There have been attempts to classify gastric cancers based on these genomic features, with an aim to improve prognostication and predict responsiveness to specific drug therapy. The eventual aims of these genomic studies are to develop deep biological insights into the carcinogenic pathway in each of these subtypes. Future large-scale drug screening strategies may then be able to link these genomic features to drug responsiveness, eventually leading to genome-guided personalized medicine with improved cure rates. PMID:27573784

  7. [Molecular bases of cancer immunology].

    Science.gov (United States)

    Barrera-Rodríguez, R; Peralta-Zaragoza, O; Madrid-Marina, V

    1995-01-01

    The immune system is a tight network of different types of cells and molecules. The coordinated action of these elements mounts a precise immune response against tumor cells. However, these cells present several escape mechanisms, leading to tumor progression. This paper shows several cellular and molecular events involved in the regulation of the immune response against tumor cells. The interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and cytokines are discussed, as well as the most recent knowledge about escape mechanisms and immunotherapy. PMID:7502157

  8. Molecular subtyping of breast cancer: opportunities for new therapeutic approaches.

    Science.gov (United States)

    Mullan, P B; Millikan, R C

    2007-12-01

    Evidence is accumulating that breast cancer is not one disease but many separate diseases. DNA microarray-based gene expression profiling has demonstrated subtypes with distinct phenotypic features and clinical responses. Prominent among the new subtypes is 'basal-like' breast cancer, one of the 'intrinsic' subtypes defined by negativity for the estrogen, progesterone, and HER2/neu receptors and positivity for cytokeratins-5/6. Focusing on basal-like breast cancer, we discuss how molecular technologies provide new chemotherapy targets, optimising treatment whilst sparing patients from unnecessary toxicity. Clinical trials are needed that incorporate long-term follow-up of patients with well-characterised tumour markers. Whilst the absence of an obvious dominant oncogene driving basal-like breast cancer and the lack of specific therapeutic agents are serious stumbling blocks, this review will highlight several promising therapeutic candidates currently under evaluation. Thus, new molecular technologies should provide a fundamental foundation for better understanding breast and other cancers which may be exploited to save lives. (Part of a Multi-author Review). PMID:17957336

  9. Biomolecular features of clinical relevance in breast cancer

    NARCIS (Netherlands)

    Daidone, M.G.; Paradiso, A.; Gion, M.; Harbeck, N.; Sweep, C.G.J.; Schmitt, M.

    2004-01-01

    Breast cancer is a heterogeneous disease and its consequent complexity is a major challenge for physicians and biologists. Notwithstanding its potential curability due to the availability of treatment modalities which are effective in the presence of favourable clinical or pathobiological features,

  10. Gastric cancer-molecular and clinical dimensions.

    Science.gov (United States)

    Wadhwa, Roopma; Song, Shumei; Lee, Ju-Seog; Yao, Yixin; Wei, Qingyi; Ajani, Jaffer A

    2013-11-01

    Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer-differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

  11. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-01-01

    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.

  12. Molecular diagnosis of prostate cancer: Topical issues

    OpenAIRE

    E. N. Knyazev; K. A. Fomicheva; K. M. Nyushko; Kaprin, A. D.; B. Ya. Alekseev; M. Yu. Shkurnikov

    2014-01-01

    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 androge...

  13. 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.

  14. Integrating tumor microenvironment with cancer molecular classifications

    OpenAIRE

    Becht, Etienne; De Reyniès, Aurélien; Fridman, Wolf H.

    2015-01-01

    Editorial summary The composition of the tumor microenvironment is associated with a patient's prognosis and can be therapeutically targeted. A link between the cellular composition and genomic features of the tumor and its response to immunotherapy is beginning to emerge. Analyzing the microenvironment of tumor molecular subgroups can be a useful approach to tailor immunotherapies.

  15. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar

    2006-01-01

    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  16. Molecular Imaging of Pulmonary Cancer and Inflammation

    OpenAIRE

    Divgi, Chaitanya R.

    2009-01-01

    Molecular imaging (MI) may be defined as imaging in vivo using molecules that report on biologic function. This review will focus on the clinical use of radioactive tracers (nonpharmacologic amounts of compounds labeled with a radioactive substance) that permit external imaging using single photon emission computed tomography (planar, SPECT) or positron emission tomography (PET) imaging. Imaging of lung cancer has been revolutionized with the use of fluorine-18–labeled fluorodeoxyglucose (18F...

  17. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  18. [Basal cell carcinoma. Molecular genetics and unusual clinical features].

    Science.gov (United States)

    Reifenberger, J

    2007-05-01

    Basal cell carcinoma is the most common human cancer. Its incidence is steadily increasing. The development of basal cell carcinoma is linked to genetic factors, including the individual skin phototype, as well as the cumulative exposure to UVB. The vast majority of basal cell carcinomas are sporadic tumors, while familial cases associated with certain hereditary syndromes are less common. At the molecular level, basal cell carcinomas are characterized by aberrant activation of sonic hedgehog signaling, usually due to mutations either in the ptch or smoh genes. In addition, about half of the cases carry mutations in the tp53 tumor suppressor gene, which are often UVB-associated C-->T transition mutations. Clinically, basal cell carcinomas may show a high degree of phenotypical variability. In particular, tumors occurring in atypical locations, showing an unusual clinical appearance, or imitating other skin diseases may cause diagnostic problems. This review article summarizes the current state of the art concerning the etiology, predisposition and molecular genetics of basal cell carcinoma. In addition, examples of unusual clinical manifestations are illustrated. PMID:17440702

  19. CPFP Summer Curriculum: Molecular Prevention Course | Division of Cancer Prevention

    Science.gov (United States)

    This Cancer Prevention Fellowship Program (CPFP) one-week course on molecular aspects of cancer prevention follows the Principles and Practice of Cancer Prevention and Control course. It provides a strong background about molecular biology and genetics of cancer, and an overview of cutting-edge research and techniques in the fields of molecular epidemiology, biomarkers, multi-omic, and translational research. The following topics will be typically presented: |

  20. The correlations between the MRI features of breast cancer and molecular biological behavior%乳腺癌MRI特征与分子生物学行为的相关性研究

    Institute of Scientific and Technical Information of China (English)

    杨爱萍; 蔡忠刚

    2014-01-01

    目的:探讨乳腺癌MRI特征与ER、PR、Her-2、Ki-67表达及淋巴结转移的相关性,为乳腺癌的疗效评价提供依据。方法28例乳腺癌患者行MR平扫、MR动态增强( MR-DCE)及弥散加权成像( DWI),分析MRI成像特征(大小、边缘、强化、TIC类型、ADC值),并与肿瘤标记物( ER、PR、Her-2、Ki-67)表达、淋巴结转移进行相关性分析。结果①肿瘤标记物的表达及淋巴结转移:ER 阳性19例(67.86%)、PR 阳性18例(64.29%)、Her-2阳性15例(53.6%)、Ki-67阳性17例(60.71%)、淋巴结转移14例(50%)。②肿块型和非肿块型组、环形强化和非环形强化组与肿瘤标记物表达、淋巴结转移比较,差异无统计学意义。③肿瘤最大径>2 cm和≤2 cm组比较,Her-2阳性表达率差异有统计学意义(χ2=5.073,P<0.05);毛刺征和非毛刺征两组比较,PR阳性表达率差异有统计学意义(χ2=6.857, P<0.05)。④淋巴结转移率在TICⅡ型与Ⅲ型组比较,差异有统计学意义(χ2=7.337,P<0.05);ADC值在Her-2阳性和阴性组间比较,差异有统计学意义(t=5.624,P<0.01)。结论乳腺癌MRI征象(大小、毛刺征、TIC类型、ADC值)与肿瘤标记物(PR、Her-2)表达、淋巴结转移具有较高的相关性,分析MR征象有助于乳腺癌疗效的评价。%Objective To investigate the correlation between the MRI features of breast cancer and expression of ER, PR, HER-2, Ki-67 and lymph node metastasis, so as to provide basis for therapeutic evaluation of breast cancer.Methods We carried out MR plain scan, MR dynamic enhancement ( MR-DCE) and diffusion weighted imaging on 28 breast cancer patients;analyzed MRI ima-ging features ( size, edge, enhancement, TIC type and ADC value);and conducted correlation analysis with expression of tumor mark-ers ( ER, PR, Her-2, ki-67) and lymph node metastasis

  1. Molecular basis of the triple negative breast cancer

    OpenAIRE

    Ayse Feyda Nursal

    2015-01-01

    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-...

  2. Clinicopathological features of early gastric cancer with duodenal invasion

    Institute of Scientific and Technical Information of China (English)

    Tsutomu Namikawa; Kazuhiro Hanazaki

    2009-01-01

    The incidence of early gastric cancer (EGC) with duodenal invasion is ext remely low, al though advanced gastric cancer that arises in the antrum occasionally invades the duodenum. We investigated the clinicopathological features of EGC with duodenal invasion and provided strategies for clinical management. A Medline search was performed using the keyword "early gastric cancer" and "duodenal invasion". Additional articles were obtained from references within the papers identified by the Medline search. We revealed that EGC with duodenal invasion was of the superficial spreading type of tumor. Tumors > 60 mm in size invaded the duodenum more extensively, and the distance of duodenal invasion from the pyloric ring was further in the elevated type than in the depressed type of tumor. There was no significant difference between the length of duodenal invasion and the histological type of the tumor. Gastric cancer located adjacent to the pyloric ring, even if cancer invasion was confined to the mucosa or submucosa, was more likely to invade the duodenum. The present study reveals that the elevated type of EGC is associated with more extensive duodenal invasion when the tumor size is > 60 mm, thus highlighting the importance of identification of duodenal invasion in these cases. We also reveal that sufficient duodenal resection with a cancer-free distal surgical margin should be performed in cases of duodenal invasion.

  3. Molecular Features of Wheat Endosperm Arabinoxylan Inclusion in Functional Bread

    Directory of Open Access Journals (Sweden)

    Weili Li

    2013-06-01

    Full Text Available Arabinoxylan (AX is a major dietary fibre component found in a variety of cereals. Numerous health benefits of arabinoxylans have been reported to be associated with their solubility and molecular features. The current study reports the development of a functional bread using a combination of AX-enriched material (AEM and optimal commercial endoxylanase. The total AX content of bread was increased to 8.2 g per 100 g available carbohydrates. The extractability of AX in breads with and without endoxylanase was determined. The results demonstrate that water-extractable AX (WE-AX increased progressively through the bread making process. The application of endoxylanase also increased WE-AX content. The presence of 360 ppm of endoxylanase had positive effects on the bread characteristics in terms of bread volume and firmness by converting the water unextractable (WU-AX to WE-AX. In addition, the molecular weight (Mw distribution of the WE-AX of bread with and without endoxylanase was characterized by size-exclusion chromatography. The results show that as the portion of WE-AX increased, the amount of high Mw WE-AX (higher than 100 kDa decreased, whereas the amount of low Mw WE-AX (lower than 100 kDa increased from 33.2% to 44.2% through the baking process. The low Mw WE-AX further increased to 75.5% with the application of the optimal endoxylanase (360 ppm.

  4. The diagnostic value of transrectal ultrasonographic features in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoli Zou; Guang Yang; Hui Wang

    2012-01-01

    Objective: The aim of the study was to detect the valuable ultrasonographic features in diagnosing prostate cancer.Methods: The patients who underwent transrectal ultrasound in the period from May 2005 to October 2009 at the 1st Affiliated Hospital of Dalian Medical University, China, were included, with needle biopsy diagnosis for patients with the prostate cancer and prostatic hyperplasia.Seventy-four cases of prostate cancer were diagnosed as adenocarcinoma, compared with 51 cases diagnosed as prostatic hyperplasia.Retrospective analysis of patients with transrectal ultrasound were done, comparing the difference between the two groups in the echo level (hypoechogenic), outlines (ill-defined margin), posterior acoustic attenuation, periphery halo, microcalcification incidence, the blood supply level, peak systolic velocity (Vs) and resistance index (RI).Results: The ratios of hypoechogenic lesions in the prostate cancer group and prostatic hyperplasia group were 56.76% and 35.90%, respectively (P 0.05).Vs of the two groups were (44.00 ± 15.30) cm/s and (17.32 ± 4.65) cm/s, respectively (P < 0.05).RI of the two groups were 0.76 ± 0.10, and 0.51 ± 0.03 respectively (P < 0.05).The significant correlation was designated in the blood supply level between the prostate cancer group and prostatic hyperplasia group (r = -0.388, P < 0.01).Higher revascularization grade was seen in the prostate cancer group compared to benign prostatic hyperplasia group.Conclusion: (1) The significant roles for diagnosing prostate cancer are hypoechogenic, irregular outlines, spiculation, microcalcification, high revascularization grade, posterior acoustic attenuation, high Vs and high RI.(2) It could not help in diagnosing prostate cancer with ultrasonographic periphery halo or not.

  5. Clinical Features of Liver Cancer with Cerebral Hemorrhage.

    Science.gov (United States)

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

    2016-01-01

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

  6. Clinical Features of Liver Cancer with Cerebral Hemorrhage

    Science.gov (United States)

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

    2016-01-01

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

  7. Molecular imaging of apoptosis in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hakumaeki, Juhana M. [Cellular and Molecular Imaging Group, Department of Biomedical NMR, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland) and Department of Clinical Radiology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)]. E-mail: juhana.hakumaki@uku.fi; Liimatainen, Timo [Cellular and Molecular Imaging Group, Department of Biomedical NMR, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland)

    2005-11-01

    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.

  8. Molecular Taxonomy and Tumourigenesis of Colorectal Cancer.

    Science.gov (United States)

    Biswas, S; Holyoake, D; Maughan, T S

    2016-02-01

    Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

  9. Oral cancer: molecular technologies for risk assessment and diagnosis

    Institute of Scientific and Technical Information of China (English)

    Wan Tao Chen

    2008-01-01

    @@ Purpose: The effective biomarkers related to diagnosis, metastasis, drug resistance and irradiation sensitivity of oral cancers will help the pathologist and oncologist to determine the molecular taxonomy diagnosis and design the individualization treatment for the patients with oral cancers.

  10. Molecular Imaging of Biomarkers in Breast Cancer

    Science.gov (United States)

    Ulaner, Gary A.; Riedl, Chris C.; Dickler, Maura N.; Jhaveri, Komal; Pandit-Taskar, Neeta; Weber, Wolfgang

    2016-01-01

    The success of breast cancer therapy is ultimately defined by clinical endpoints such as survival. It is valuable to have biomarkers that can predict the most efficacious therapies or measure response to therapy early in the course of treatment. Molecular imaging has a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments. The potential advantages of imaging biomarkers are obvious and initial clinical studies have been promising, but proof of clinical utility still requires prospective multicenter clinical trials. PMID:26834103

  11. Overexpression of leptin and leptin receptors in breast cancer positively correlates with clinicopathological features

    Institute of Scientific and Technical Information of China (English)

    XIA Xiang-hou; GU Jun-chao; BAI Qing-yang; YU Wei

    2009-01-01

    @@ Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features.

  12. Molecular markers′ progress of breast cancer treatment efficacy

    OpenAIRE

    Dan Wang; Jingwei Xu; Guang Shi; Guanghao Yin

    2015-01-01

    Breast cancer is a famous malignant tumor which is caused by varieties of mutation in multiple genes. In order to detect breast cancer in an earlier time and take appropriate treatment which includes  predicting treatment efficacy, we need a more accurate method of discovering the occurrence of breast cancer. With the development of molecular biology and biological detection technologies continue to emerge, molecular markers of breast cancer have gaining more and more widespread attention, an...

  13. 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.

  14. Representation of Molecular Electrostatic Potentials of Biopolymer by Self-organizing Feature Map

    Institute of Scientific and Technical Information of China (English)

    QIAO,Xue-Bin(乔学斌); JIANG,Bo(姜波); HOU,Ting-Jun(侯廷军); XU,Xiao-Jie(徐筱杰)

    2001-01-01

    The Kohonen serf-organizing map was introduced to map theprotein molecular surface features.The protein or polypeptideproperties,such as shape and molecular electrostatic poten-rial,can be visualized by seff-organizing map,which wastrained by the 3D surface coordinates.Such maps allow thevisual comparison of molecular properties between proteinshaving common topological or chemical features.``

  15. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    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.

  16. Breast Cancer Detection with Gabor Features from Digital Mammograms

    Directory of Open Access Journals (Sweden)

    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.

  17. Molecular diagnosis for personalized target therapy in gastric cancer.

    Science.gov (United States)

    Cho, Jae Yong

    2013-09-01

    Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy. PMID:24156032

  18. Relationship between the expression of Ki-67 and molecular classification and clinical patho-logical features in breast cancer%Ki-67表达与乳腺癌分子分型及临床病理特征的关系

    Institute of Scientific and Technical Information of China (English)

    张莹; 任占平; 张芫

    2014-01-01

    目的:观察不同分子亚型乳腺癌中Ki-67的表达及其与乳腺癌临床病理特征的关系及意义。方法采用免疫组化En-Vision两步法检测245例乳腺癌组织中ER、PR、HER-2及Ki-67的表达,并比较Ki-67表达与乳腺癌临床病理参数的关系。结果不同分子分型乳腺癌中Ki-67的增殖指数差异有统计学意义( P50岁组的Ki-67增殖指数差异无统计学意义;患者按≤40岁及≥60岁分为年轻组及老年组时,年轻组Ki-67增殖指数明显高于老年组。结论 Ki-67在三阴型乳腺癌、年轻患者、伴腋窝淋巴结转移、肿块较大及ER、PR阴性组中的增殖指数较高。 Ki-67可作为判断乳腺癌预后的重要指标。%Purpose To study the expression of Ki-67 in breast cancer with different molecular classification, and to discuss the rela-tionship between the expression of Ki-67 and clinical pathological features in breast cancer. Methods All 245 patients with breast cancer were divided into different molecular classification through detecting the expression of ER, PR, HER-2 by immunohistochemical method. The expression of Ki-67 was also detected, and to study relationship between the expression and clinical pathological features. Results The difference of Ki-67 index was statistically significant in different molecular classification of breast cancer. Ki-67 index in patients with lymph node metastasis and larger tumor size were higher than that with no metastasis and smaller tumor size. Ki-67 index in patients with ER and PR positive were lower than that negative, the difference was statistically significant. Ki-67 expression differ-ence was not statistically significant between the two groups according to the median age (50 years old). But when patients were divid-ed into young and elderly groups by≤40 and≥60 years old, Ki-67 index in young group was more higher than that in elderly group. Conclusion Ki-67 index in patients with triple-negative breast cancer, young

  19. Lobular breast cancer: Clinical, molecular and morphological characteristics.

    Science.gov (United States)

    Christgen, Matthias; Steinemann, Doris; Kühnle, Elna; Länger, Florian; Gluz, Oleg; Harbeck, Nadia; Kreipe, Hans

    2016-07-01

    Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.

  20. Breast cancer. From molecular biology to personified therapy

    Directory of Open Access Journals (Sweden)

    Bondarenko I.N.

    2016-03-01

    Full Text Available Advances in molecular biology had changed approaches to systemic treatment of breast cancer. Clinical decisions on the choice of optimal treatment regimens are performing on the basis of immunohistochemical and molecular genetic classifications. Their increasing uses have contributed changes of paradigm for cancer treatment - from the empirical to the individualized and personalized. The basis for such approaches is knowledge of molecular epidemiology, heterogeneity of expression of molecular subtypes, prognostic and predictive biomarkers of breast cancer. Breast cancer is a widely heterogeneous disease with 20 histological types, 8, molecular-genetic, 6 genomic subtypes, which are characterized by specific molecular and biochemical properties, different clinical course and different outcomes. Molecular genetic classification, created not on the basis of clinical, anatomical and morphological heterogeneity of tumor cells, and on the basis of their molecular-genetic heterogeneity is widely used in clinical practice. This allowed to separate the patients with breast cancer to molecular 4 subtypes - luminal A, luminal B, HER / 2 positive and triple-negative. The significant role of immunohistochemical tissue tumor markers, estrogen and progesterone receptors, HER / 2-neu, Ki-67, p53 for selection the optimal treatment strategy is analyzing in this review. To increase the effectiveness of breast cancer treatment is possible, using a differentiated and personalized approach based on new molecular genetic classification of breast cancer (gene profiling or to its analogue - expression classification of breast cancer, based on the principle of diversity of immunohistochemical tumor tissue. Personification of cancer treatment involves a therapy based on the study of individual characteristics of tissue is not only the primary tumor but also its metastases. Citation: Bondarenko IN, Elhajj Mohammad H, Prokhach AV, Zavizion VF, Chebanov KO. [Breast cancer

  1. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus

    2006-01-01

    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g

  2. Hormonal and molecular aspects of endometrioid endometrial cancer

    NARCIS (Netherlands)

    Jongen, Vincentius Hubertus Willibrordus Maria

    2008-01-01

    This thesis concerns the expression and prognostic value of various hormones and molecular markers playing a role n endometrioid endometrial cancer. Especially we were interested in the enzyme aromatase, its expression and (prognostic) role in endometrioid endometrial cancer. Endometrial cancer is t

  3. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Alphy Rose-James

    2012-01-01

    Full Text Available Lung cancer accounts for the majority of cancer-related deaths worldwide of which non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based therapy is the stronghold for lung cancer at present. The discovery of various molecular alterations that underlie lung cancer has contributed to the development of specifically targeted therapies employing specific mutation inhibitors. Targeted chemotherapy based on molecular profiling has shown great promise in lung cancer treatment. Various molecular markers with predictive and prognostic significance in lung cancer have evolved as a result of advanced research. Testing of EGFR and Kras mutations is now a common practice among community oncologists, and more recently, ALK rearrangements have been added to this group. This paper discusses various predictive and prognostic markers that are being investigated and have shown significant relevance which can be exploited for targeted treatment in lung cancer.

  4. Molecular Pathways: Estrogen Pathway in Colorectal Cancer

    Science.gov (United States)

    Barzi, Afsaneh; Lenz, Annika Medea; Labonte, Melissa J.; Lenz, Heinz-Josef

    2013-01-01

    Worldwide colorectal cancer (CRC) has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data supports a role for estrogen and its receptors in the initiation and progression of CRC and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of CRC. In the Women’s Health Initiative (WHI) trial use of HRT in postmenopausal women reduced the risk of colon cancer by 56% (95% CI, 0.38 to 0.81; P=0.003). A recent meta-analysis showed that in females, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03 to 0.35; P=0.026). In this review, utilizing the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of CRC. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT or soy products, exerts its effects through preventing this loss. Thus in the adenoma to carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of CRC depends on identification of susceptible CRC population(s). Thus research to better understand the estrogen pathway is fundamental for clinical delivery of these agents. PMID:23965904

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

    Science.gov (United States)

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

    2016-03-01

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

  6. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis

    2008-01-01

    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  7. Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer

    DEFF Research Database (Denmark)

    Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine;

    2016-01-01

    BACKGROUND AND AIMS: 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....... METHODS: 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 (d......MMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. RESULTS: 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% CI, 1...

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

    Science.gov (United States)

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

    2015-01-01

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

  9. 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. PMID:26498010

  10. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression.

    Science.gov (United States)

    Sato, Katsuaki; Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  11. [Molecular biological predictors for kidney cancer].

    Science.gov (United States)

    Vtorushin, S V; Tarakanova, V O; Zavyalova, M V

    2016-01-01

    The paper considers the data available in the modern literature on studies of potential molecular predictors for renal cell carcinoma (RCC). Investigations of cell death markers, namely; Bcl-2 as an inhibitor of apoptosis, are of interest. Its high expression correlates with a more favorable prognosis. Inactivation of Berclin 1 that is an authophagy indicator in intact tissues gives rise to t high risk for tumorigenesis. At the same time, high Beclin 1 expression in the tissue of the tumor itself results in the lower efficiency of performed chemotherapy. Excess annexin A2 in the tumor promotes the growth and invasion of cancer cells. Patients with tumor over-expression of SAM68 protein involved in cell proliferation have a lower overall survival rate. The lifespan of patients without distinct metastases survive significantly longer in the overexpression of epithelial cell adhesion molecule (EpCAM). High PD-L1 protein expression on the cell membrane is considered to be a potential marker of effective immunotherapy for RCC. PMID:27077146

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

    International Nuclear Information System (INIS)

    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

  13. Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy

    OpenAIRE

    Pearson, Michele L.; Selby, Joseph V.; Katz, Kenneth A; Cantrell, Virginia; Braden, Christopher R.; Parise, Monica E.; Paddock, Christopher D.; Michael R Lewin-Smith; Kalasinsky, Victor F.; Goldstein, Felicia C.; Hightower, Allen W.; Papier, Arthur; Lewis, Brian; Motipara, Sarita; Eberhard, Mark L.

    2012-01-01

    Background Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. Methods A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006–2008. A case was defined as the self-reported emergence of fibers...

  14. Applications of molecular MRI and optical imaging in cancer

    OpenAIRE

    Penet, Marie-France; Mikhaylova, Maria; Li, Cong; Krishnamachary, Balaji; Glunde, Kristine; Pathak, Arvind P.; Bhujwalla, Zaver M.

    2010-01-01

    Some of the most exciting advances in molecular-functional imaging of cancer are occurring at the interface between chemistry and imaging. Several of these advances have occurred through the development of novel imaging probes that report on molecular pathways, the tumor micro-environment and the response of tumors to treatment; as well as through novel image-guided platforms such as nanoparticles and nanovesicles that deliver therapeutic agents against specific targets and pathways. Cancer c...

  15. The Utility of Molecular Imaging in Prostate Cancer.

    Science.gov (United States)

    Leiblich, Aaron; Stevens, Daniel; Sooriakumaran, Prasanna

    2016-03-01

    Prostate cancer is the commonest solid-organ cancer diagnosed in males and represents an important source of morbidity and mortality worldwide. Imaging plays a crucial role in diagnosing prostate cancer and informs the ongoing management of the disease at all stages. Several novel molecular imaging technologies have been developed recently that have the potential to revolutionise disease diagnosis and the surveillance of patients living with prostate cancer. These innovations include hyperpolarised MRI, choline PET/CT and PSMA PET/CT. The major utility of choline and PSMA PET/CT currently lies in their sensitivity for detecting early recurrence after radical treatment for prostate cancer and identifying discrete lesions that may be amenable to salvage therapy. Molecular imaging is likely to play a future role in characterising genetic and biochemical signatures in individual tumours, which may be of particular significance as cancer therapies move into an era of precision medicine. PMID:26894753

  16. Molecular mechanisms of tamoxifen-associated endometrial cancer (Review)

    OpenAIRE

    Hu, Rong; Hilakivi-Clarke, Leena; Clarke, Robert

    2015-01-01

    Tamoxifen has been prescribed to millions of females for breast cancer prevention or treatment. However, tamoxifen is known to significantly enhance the risk of developing endometrial lesions, including hyperplasia, polyps, carcinomas, and sarcoma. Notably, tamoxifen-associated endometrial cancer often has a poor clinical outcome. Understanding the molecular mechanism of tamoxifen-induced endometrial cancer is essential for developing strategies that minimize tamoxifen’s effects on the endome...

  17. Skeletal Muscle Laminopathies: A Review of Clinical and Molecular Features.

    Science.gov (United States)

    Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

    2016-01-01

    LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases. PMID:27529282

  18. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hiroaki; Itamochi

    2010-01-01

    Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

  19. Accurate molecular classification of cancer using simple rules

    OpenAIRE

    Gotoh Osamu; Wang Xiaosheng

    2009-01-01

    Abstract Background One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often ...

  20. New generation of breast cancer clinical trials implementing molecular profiling

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Zardavas; Martine Piccart-Gebhart

    2016-01-01

    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

  1. Molecular markers for detection, surveillance and prognostication of bladder cancer.

    NARCIS (Netherlands)

    Vrooman, O.P.; Witjes, J.A.

    2009-01-01

    Many markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular marker

  2. Molecular imaging of HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten

    2010-01-01

    HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate...... individual approaches to targeted therapy of HER2-positive breast cancers....

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

    Science.gov (United States)

    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. PMID:24704294

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

    Science.gov (United States)

    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.

  5. Novel approaches for the molecular classification of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Robert H. Getzenberg

    2010-01-01

    @@ Among the urologic cancers, prostate cancer is by far the most common, and it appears to have the potential to affect almost all men throughout the world as they age. A number of studies have shown that many men with prostate cancer will not die from their disease, but rather with the disease but from other causes. These men have a form of prostate cancer that is de-scribed as "very low risk" and has often been called indolent. There are however a group of men that have a form of prostate cancer that is much more aggressive and life threatening. Unlike other cancer types, we have few tools to provide for the molecular classification of prostate cancer.

  6. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

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

    2016-01-01

    . 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......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......, 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...

  7. How do patient and hospital features influence outcomes in small-cell lung cancer in England?

    OpenAIRE

    Rich, A L; Tata, L J; Free, C M; Stanley, R. A.; Peake, M D; Baldwin, D. R.; Hubbard , R B

    2011-01-01

    Background: Our aim was to systematically determine how features of patients and hospitals influence access to chemotherapy and survival for people with small-cell lung cancer in England. Methods: We linked the National Lung Cancer Audit and Hospital Episode Statistics and used multiple logistic and Cox regression analyses to assess the influence of patient and hospital features on small-cell lung cancer outcomes. Results: There were 7845 patients with histologically proven small-cell lung ca...

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

    OpenAIRE

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

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. C...

  9. Neuroblastoma: morphological pattern, molecular genetic features, and prognostic factors

    Directory of Open Access Journals (Sweden)

    A. M. Stroganova

    2016-01-01

    Full Text Available Neuroblastoma, the most common extracranial tumor of childhood, arises from the developing neurons of the sympathetic nervous system (neural cress stem cells and has various biological and clinical characteristics. The mean age at disease onset is 18 months. Neuroblastoma has a number of unique characteristics: a capacity for spontaneous regression in babies younger than 12 months even in the presence of distant metastases, for differentiation (maturation into ganglioneuroma in infants after the first year of life, and for swift aggressive development and rapid metastasis. There are 2 clinical classifications of neuroblastoma: the International neuroblastoma staging system that is based on surgical results and the International Neuroblastoma Risk Group Staging System. One of the fundamentally important problems for the clinical picture of neuroblastoma is difficulties making its prognosis. Along with clinical parameters (a patient’s age, tumor extent and site, some histological, molecular biochemical (ploidy and genetic (chromosomal aberrations, MYCN gene status, deletion of the locus 1p36 and 11q, the longer arm of chromosome 17, etc. characteristics of tumor cells are of considerable promise. MYCN gene amplification is observed in 20–30 % of primary neuroblastomas and it is one of the major indicators of disease aggressiveness, early chemotherapy resistance, and a poor prognosis. There are 2 types of MYCN gene amplification: extrachromosomal (double acentric chromosomes and intrachromosomal (homogenically painted regions. Examination of double acentric chromosomes revealed an interesting fact that it may be eliminated (removed from the nucleus through the formation of micronuclei. MYCN oncogene amplification is accompanied frequently by 1p36 locus deletion and longer 17q arm and less frequently by 11q23 deletion; these are poor prognostic factors for the disease. The paper considers in detail the specific, unique characteristics of the

  10. Structural Features and Molecular Evolution of Bowman-Birk Protease Inhibitors and Their Potential Application

    Institute of Scientific and Technical Information of China (English)

    Rui-Feng QI; Zhan-Wu SONG; Cheng-Wu CHI

    2005-01-01

    The Bowman-Birk inhibitors (BBIs) are well-studied serine protease inhibitors that are abundant in dicotyledonous and monocotyledonous plants. BBIs from dicots usually have a molecular weight of 8k and are double-headed with two reactive sites, whereas those from monocots can be divided into two classes, one approximately 8 kDa in size with one reactive site (another reactive site was lost) and the other approximately 16 kDa in size with two reactive sites. The reactive site is located at unique exposed surfaces formed by a disulfide-linked β-sheet loop that is highly conserved, rigid and mostly composed of nine residues. The structural features and molecular evolution of inhibitors are described, focusing on the conserved disulfide bridges. The sunflower trypsin inhibitor-1 (SFTI-1), with 14 amino acid residues, is a recently discovered bicyclic inhibitor, and is the most small and potent naturally occurring Bowman-Birk inhibitor.Recently, BBIs have become a hot topic because of their potential applications. BBIs are now used for defense against pathogens and insects in transgenic plants, which has advantages over using toxic and polluting insecticides. BBIs could also be applied in the prevention of cancer, Dengue fever, and inflammatory and allergic disorders, because of their inhibitory activity with respect to the serine proteases that play a pivotal role in the development and pathogenesis of these diseases. The canonical nine-residue loop of BBIs/STFI-1 provides an ideal template for drug design of specific inhibitors to target their respective proteases.

  11. Atrophy of the Tongue as the Presenting Feature of Metastatic Prostate Cancer

    OpenAIRE

    Abdullah, Zreik; Darrad, Maitrey; Pathak, Sanjeev

    2011-01-01

    Prostate cancer is the most frequently diagnosed solid organ cancer in men and is the second leading cause of cancer-related deaths in men in the United Kingdom. Commonly, it metastasizes to bones and lymph nodes, however, in advanced hormonerefractory disease it may involve the skull base leading to associated cranial nerve palsies. Cranial nerve palsy as the presenting feature of advanced hormone-sensitive prostate cancer is extremely rare. To the best of our knowledge, we report the first ...

  12. Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy.

    Directory of Open Access Journals (Sweden)

    Michele L Pearson

    Full Text Available BACKGROUND: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. METHODS: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. RESULTS: We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40 cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113. Case-patients had a median age of 52 years (range: 17-93 and were primarily female (77% and Caucasian (77%. Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9 and 35.45 (SD = 12.89, respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies; skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. CONCLUSIONS: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health

  13. [Matrix metalloproteases as molecular markers in gastric cancer].

    Science.gov (United States)

    de la Peña, Sol; Sampieri, Clara L; León-Córdoba, Kenneth

    2010-02-01

    Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis.

  14. 2. Molecular Biology as a Tool in Cancer Epidemiology

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@There can be little doubt that we are entering a new era in our understanding of the origins of human cancer. Unfortunately from the point of view of the cancer epidemiology community, some of the more recent advances in the molecular biology of cancer (once fully assimilated) will tend to make the talk of the up-to-date cancer epidemiologist a great deal less straightforward than many of us had previously envisaged it to be, There may still be a few cancers that will prove to result from only a few distinctive types of mutation in a relatively small number of genes, but I strongly suspect that the great majority of human cancers that we wish to study will prove to have their origins in a complex set of DNA changes whose precise

  15. Molecular genetics of breast cancer progression

    OpenAIRE

    Sigurður Ingvarsson 1956

    1999-01-01

    Somatic changes in the genome of breast cancer cells include amplifications, deletions and gene mutations. Several chromosome regions harboring known oncogenes are found amplified in breast tumors. Despite the high number of chromosome regions deleted in breast tumors the functional relationship to known genes at these locations and cancer growth is mainly undiscovered. Mutations in two tumor suppressor genes (TSG) have been described in a subset of breast carcinomas. These TSG are the TP53, ...

  16. Molecular targeted agents for gastric and gastroesophageal junction cancer.

    Science.gov (United States)

    Oshima, Takashi; Masuda, Munetaka

    2012-04-01

    Despite recent improvements in surgical techniques and chemotherapy, advanced cancers of the stomach and gastroesophageal junction (GEJ) continue to have poor clinical outcomes. However, molecules intimately related to cancer cell proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. Target molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways are considered to be promising candidates for molecular targeted therapy for gastric and GEJ cancer. In this review we focus on the recent developments in targeting relevant pathways in these types of cancer.

  17. Pathological Bases for a Robust Application of Cancer Molecular Classification

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2015-04-01

    Full Text Available Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes, and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors.

  18. Review on Feature Selection Techniques and the Impact of SVM for Cancer Classification using Gene Expression Profile

    CERN Document Server

    George, G Victo Sudha; 10.5121/ijcses.2011.2302

    2011-01-01

    The DNA microarray technology has modernized the approach of biology research in such a way that scientists can now measure the expression levels of thousands of genes simultaneously in a single experiment. Gene expression profiles, which represent the state of a cell at a molecular level, have great potential as a medical diagnosis tool. But compared to the number of genes involved, available training data sets generally have a fairly small sample size for classification. These training data limitations constitute a challenge to certain classification methodologies. Feature selection techniques can be used to extract the marker genes which influence the classification accuracy effectively by eliminating the un wanted noisy and redundant genes This paper presents a review of feature selection techniques that have been employed in micro array data based cancer classification and also the predominant role of SVM for cancer classification.

  19. REVIEW ON FEATURE SELECTION TECHNIQUES AND THE IMPACT OF SVM FOR CANCER CLASSIFICATION USING GENE EXPRESSION PROFILE

    Directory of Open Access Journals (Sweden)

    G.Victo Sudha George

    2011-09-01

    Full Text Available The DNA microarray technology has modernized the approach of biology research in such a way thatscientists can now measure the expression levels of thousands of genes simultaneously in a singleexperiment. Gene expression profiles, which represent the state of a cell at a molecular level, have greatpotential as a medical diagnosis tool. But compared to the number of genes involved, available trainingdata sets generally have a fairly small sample size for classification. These training data limitationsconstitute a challenge to certain classification methodologies. Feature selection techniques can be usedto extract the marker genes which influence the classification accuracy effectively by eliminating the unwanted noisy and redundant genes This paper presents a review of feature selection techniques that havebeen employed in micro array data based cancer classification and also the predominant role of SVMfor cancer classification.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Choline metabolism-based molecular diagnosis of cancer: an update

    OpenAIRE

    Glunde, Kristine; Penet, Marie-France; Jiang, Lu; Jacobs, Michael A.; Zaver M Bhujwalla

    2015-01-01

    Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholine-specific phospholipase C and -D and glycerophosphocholine phosphodiesterases, as well as several choline transporters. The net outcome of these enzymatic changes is an increase in phosphocholine and total choline (tCho) and, in some cancers, a relative decrease of glycerophosphocholine. The incre...

  2. Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

    OpenAIRE

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

    2013-01-01

    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...

  3. Integrated molecular portrait of non-small cell lung cancers

    OpenAIRE

    Lazar, Vladimir; Suo, Chen; Orear, Cedric; van den Oord, Joost; Balogh, Zsofia; Guegan, Justine; Job, Bastien; Meurice, Guillaume; Ripoche, Hugues; Calza, Stefano; Hasmats, Johanna; Lundeberg, Joakim; Lacroix, Ludovic; Vielh, Philippe; Dufour, Fabienne

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridiz...

  4. Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of de-veloping TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

  5. Senescent cells harbour features of the cancer epigenome

    OpenAIRE

    Cruickshanks, Hazel A; McBryan, Tony; Nelson, David M.; VanderKraats, Nathan D.; Shah, Parisha P.; van Tuyn, John; Rai, Taranjit Singh; Brock, Claire; Donahue, Greg; Dunican, Donncha S; Drotar, Mark E.; Meehan, Richard R.; Edwards, John R.; Berger, Shelley L.; Adams, Peter D.

    2013-01-01

    Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, l...

  6. Human prostate cancer stem cells: new features unveiled

    Institute of Scientific and Technical Information of China (English)

    Yuting Sun; Wei-Qiang Gao

    2011-01-01

    @@ Cancer stem cells (CSCs) are a rare sub-population of phenotypically distinct cancer cells exhibiting stem cell characteristics.They are tumourigenic, meanwhile capable of self-renewal and forming differentiated progenies.CSCs are believed to be resistant to the standard therapeutics, and provide the cell reservoir for tumour initiation.1 Understanding CSCs or in another word, tumour-initiating cells, is of critical therapeutic importance.

  7. [Molecular classification of bladder cancer. Possible similarities to breast cancer].

    Science.gov (United States)

    Wirtz, R M; Fritz, V; Stöhr, R; Hartmann, A

    2016-02-01

    Therapeutic decisions for breast cancer are increasingly becoming based on subtype-specific gene expression tests. For bladder cancer very similar subtypes have been identified by genome-wide mRNA analysis, which as for breast cancer differ with respect to the prognosis and response to therapy on the basis of their hormone dependency. At the DNA level, however, the type of mutations and their frequencies within the subtypes are strikingly different between bladder and breast cancers. It will be interesting to see whether possible driver mutations can serve as therapeutic targets in both indications. In contrast, the apparent hormone dependency of a substantial number of bladder carcinomas suggests that hormonal and anti-hormonal treatment can be valid therapy options similar to breast cancer. Moreover, gender-specific differences with respect to the incidence and aggressiveness of male compared to female bladder cancers can be explained by hormonal effects. Together with forthcoming immunomodulatory therapies these multiple therapy options raise and give new hope to efficiently combat this aggressive disease. PMID:26780243

  8. Colorectal Cancer & Molecular Mutations and Polymorphism

    Directory of Open Access Journals (Sweden)

    Aga Syed Sameer

    2013-05-01

    Full Text Available Colorectal cancer (CRC is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN or microsatellite instability (MIN or involving various proto-oncogenes, tumor suppressor genes and also epigenetic changes in the DNA. In this review I have focused on the mutations and polymorphisms of various important genes of the CIN and MIN pathways which have been implicated in the development of CRC.

  9. Colorectal cancer complicated by perforation. Specific features of surgical tactics

    Directory of Open Access Journals (Sweden)

    S. N. Shchaeva

    2015-01-01

    Full Text Available Objective: to assess the immediate results of surgical interventions for colorectal cancer complicated by perforation.Materials and methods. The immediate results of surgical treatment were retrospectively analyzed in 56 patients with colorectal cancer complicated by perforated colon cancer, who had been treated at Smolensk surgical hospitals in 2001 to 2013. Patients with diastatic perforation of the colon in the presence of decompensated obturation intestinal obstruction of tumor genesis were not included into this investigation.Results. The immediate results of uni- and multistage surgical interventions were analyzed in relation to the extent of peritonitis and the stage of colon cancer. More satisfactory immediate results were observed after multistage surgical treatment. Following these interventions, a fatal outcome of disseminated peritonitis in the presence of performed colorectal cancer was recorded in 8 (53.3 % cases whereas after symptomatic surgery there were 11 (67.8 % deaths. A fatal outcome was noted in 1 case (7.7 % after multistage surgery.Discussion. The results of surgical treatment in the patients with perforated colorectal cancer are directly related to the degree of peritonitis and the choice of surgical tactics.

  10. Molecular Concordance Between Primary Breast Cancer and Matched Metastases.

    Science.gov (United States)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads; Kruse, Torben A

    2016-07-01

    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 with respect to traditional clinical treatment targets and on the genomic and transcriptomic level. With the increasing use of molecularly targeted therapy, discordance of actionable molecular targets between primary tumors and recurrences can result in nonoptimal treatment or unnecessary side effects. 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 into the biology underlying metastatic progression and has the potential to identify novel, potentially druggable, drivers of progression. PMID:27089067

  11. Correlation of morphological and molecular parameters for colon cancer

    Science.gov (United States)

    Yuan, Shuai; Roney, Celeste A.; Li, Qian; Jiang, James; Cable, Alex; Summers, Ronald M.; Chen, Yu

    2010-02-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. There is great interest in studying the relationship among microstructures and molecular processes of colorectal cancer during its progression at early stages. In this study, we use our multi-modality optical system that could obtain co-registered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) images simultaneously to study CRC. The overexpressed carbohydrate α-L-fucose on the surfaces of polyps facilitates the bond of adenomatous polyps with UEA-1 and is used as biomarker. Tissue scattering coefficient derived from OCT axial scan is used as quantitative value of structural information. Both structural images from OCT and molecular images show spatial heterogeneity of tumors. Correlations between those values are analyzed and demonstrate that scattering coefficients are positively correlated with FMI signals in conjugated. In UEA-1 conjugated samples (8 polyps and 8 control regions), the correlation coefficient is ranged from 0.45 to 0.99. These findings indicate that the microstructure of polyps is changed gradually during cancer progression and the change is well correlated with certain molecular process. Our study demonstrated that multi-parametric imaging is able to simultaneously detect morphology and molecular information and it can enable spatially and temporally correlated studies of structure-function relationships during tumor progression.

  12. Accurate molecular classification of cancer using simple rules

    Directory of Open Access Journals (Sweden)

    Gotoh Osamu

    2009-10-01

    Full Text Available Abstract Background One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible. Methods We screened a small number of informative single genes and gene pairs on the basis of their depended degrees proposed in rough sets. Applying the decision rules induced by the selected genes or gene pairs, we constructed cancer classifiers. We tested the efficacy of the classifiers by leave-one-out cross-validation (LOOCV of training sets and classification of independent test sets. Results We applied our methods to five cancerous gene expression datasets: leukemia (acute lymphoblastic leukemia [ALL] vs. acute myeloid leukemia [AML], lung cancer, prostate cancer, breast cancer, and leukemia (ALL vs. mixed-lineage leukemia [MLL] vs. AML. Accurate classification outcomes were obtained by utilizing just one or two genes. Some genes that correlated closely with the pathogenesis of relevant cancers were identified. In terms of both classification performance and algorithm simplicity, our approach outperformed or at least matched existing methods. Conclusion In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction.

  13. Procathepsin D and cancer: From molecular biology to clinical applications

    OpenAIRE

    Vetvicka, Vaclav; Vashishta, Aruna; Saraswat-Ohri, Sujata; Vetvickova, Jana

    2010-01-01

    Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas. pCD affects multiple features of tumor cells including proliferation, invasion, metastases and apoptosis. Several laboratories have previously shown that the mitogenic effect of pCD on cancer cells is mediated via its propeptide part (APpCD). However, the exact mechanism of how pCD affects cancer cells has not been identified. Recent observations have also revealed the poss...

  14. Nasopharyngeal carcinoma: Imaging features of unusual cancer in children

    Directory of Open Access Journals (Sweden)

    Ayda A. Youssef

    2015-12-01

    Conclusion: Pediatric NPC is generally not suspected clinically until late into the disease process. Awareness that NPC can occur in children should prompt careful evaluation for distinctive radiographic features. Earlier diagnosis may then direct the patient to timely appropriate therapy when these key radiographic features are present and recognized.

  15. Endometrial cancer : from a molecular genetic perspective

    NARCIS (Netherlands)

    E. Smid-Koopman (Ellen)

    2002-01-01

    textabstractThe first observations indicative of a role of genetic factors in carcinogenesis were made as early as 1912, when Rous demonstrated that a filterable agent (i.e. virus) could induce cancer in chicken (Rous 1965). In 1914, Boveri postulated a "genetic" theory on carcinogenesis by hypothes

  16. Molecular pathology of colorectal cancer predisposing syndromes

    NARCIS (Netherlands)

    Puijenbroek, Marjo van

    2008-01-01

    Each year, approximately eleven thousand new colorectal cancer (CRC) patients are registered in the Netherlands. Half of these patients will eventually die of this disease. Consequently, it is of great importance to identify individuals with an increased risk for CRC. In this thesis, we evaluate the

  17. The consensus molecular subtypes of colorectal cancer

    NARCIS (Netherlands)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-01-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data shar

  18. Molecular-Genetic Aspects of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Krasteva M.

    2014-12-01

    Full Text Available Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.

  19. The epidemiology and molecular mechanisms linking obesity, diabetes, and cancer.

    Science.gov (United States)

    Ferguson, Rosalyn D; Gallagher, Emily J; Scheinman, Eyal J; Damouni, Rawan; LeRoith, Derek

    2013-01-01

    The worldwide epidemic of obesity is associated with increasing rates of the metabolic syndrome and type 2 diabetes. Epidemiological studies have reported that these conditions are linked to increased rates of cancer incidence and mortality. Obesity, particularly abdominal obesity, is associated with insulin resistance and the development of dyslipidemia, hyperglycemia, and ultimately type 2 diabetes. Although many metabolic abnormalities occur with obesity and type 2 diabetes, insulin resistance and hyperinsulinemia appear to be central to these conditions and may contribute to dyslipidemia and altered levels of circulating estrogens and androgens. In this review, we will discuss the epidemiological and molecular links between obesity, type 2 diabetes, and cancer, and how hyperinsulinemia and dyslipidemia may contribute to cancer development. We will discuss how these metabolic abnormalities may interact with estrogen signaling in breast cancer growth. Finally, we will discuss the effects of type 2 diabetes medications on cancer risk. PMID:23810003

  20. Molecular markers as therapeutic targets in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hsin-Hui Tseng; Biao He

    2013-01-01

    Lung cancer is responsible for 29% of cancer deaths in the United States and has very low 5-year survival rates of approximately 11% in men and 15% in women.Although the early diagnosis of lung cancer may increase the survival rate with adequate treatment,advanced lung cancers are often metastasized and receive limited benefit from therapeutic regimens.As conventional treatments for lung cancer reach their limitations,researchers have attempted to discover novel drug therapies aimed at specific targets contributing to the progression of tumorigenesis.Recent advances in systems biology have enabled the molecular biology of lung carcinogenesis to be elucidated.Our understanding of the physiologic processes of tumor development provide a means to design more effective and specific drugs with less toxicity,thereby accelerating the delivery of new drug therapies to the patient's bedside.

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

    Science.gov (United States)

    Iaitskiĭ, A N; Danilov, I N

    2008-01-01

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

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

    Science.gov (United States)

    Iaitskiĭ, A N; Danilov, I N

    2008-01-01

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

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

    NARCIS (Netherlands)

    Wind, Anke; Lobo, Mariana Fernandes; Dijk, van Joris; Lepage-Nefkens, Isabelle; Laranja-Pontes, Jose; Conceicao Goncalves, da Vitor; Harten, van Wim; 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 dat

  4. Inflammation, Autophagy, and Obesity: Common Features in the Pathogenesis of Pancreatitis and Pancreatic Cancer

    OpenAIRE

    Gukovsky, Ilya; Ning LI; Todoric, Jelena; Gukovskaya, Anna; Karin, Michael

    2013-01-01

    Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an env...

  5. TCGA divides gastric cancer into four molecular subtypes:implications for individualized therapeutics

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is chalenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especialy the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

  6. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    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.

  7. Molecular Imaging of Breast Cancer: Present and future directions

    Science.gov (United States)

    Alcantara, David; Pernia Leal, Manuel; Garcia, Irene; Garcia-Martin, Maria Luisa

    2014-12-01

    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.

  8. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    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 m

  9. X-ray features of pulmonary metastases of thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lutsenko, I.V. (Nauchno-Issledovatel' skij Onkologicheskij Inst., Moscow (USSR))

    Metastases of thyroid cancer to the chest cavity organs were detected in 19.4%. They were found most frequently in the pulmonary tissue (75.8%), in the mediastinal lymph nodes (57.9%), less frequently in the lymph nodes of the roots of the lungs (30.4%) and very rarely in the pleura (2.6%). X-ray signs of metastases are identical for all histological structures of thyroid cancer. The most typical are multiple lesions (91.8%). The nodular form is found in 74.5%, the nodal form in 17.2.%. Solitary metastases and cancerous lymphangitis are rarely noted (7.2 and 0.9% respectively. The regression of metastases, spontaneous pneumothorax and pneumonia are rarely observed as well (1.8, 0.9 and 1.8%) respectively). The doubling time of the size of metastatic tumors of thyroid cancer ranges from 52 to 379 days. The use of radioactive iodine and hormones inhibits their growth rates.

  10. X-ray features of pulmonary metastases of thyroid cancer

    International Nuclear Information System (INIS)

    Metastases of thyroid cancer to the chest cavity organs were detected in 19.4%. They were found most frequently in the pulmonary tissue (75.8%), in the mediastinal lymph nodes (57.9%), less frequently in the lymph nodes of the roots of the lungs (30.4%) and very rarely in the pleura (2.6%). X-ray signs of metastases are identical for all histological structures of thyroid cancer. The most typical are multiple lesions (91.8%). The nodular form is found in 74.5%, the nodal form in 17.2.%. Solitary metastases and cancerous lymphangitis are rarely noted (7.2 and 0.9% respectively. The regression of metastases, spontaneous pneumothorax and pneumonia are rarely observed as well (1.8, 0.9 and 1.8%) respectively). The doubling time of the size of metastatic tumors of thyroid cancer ranges from 52 to 379 days. The use of radioactive iodine and hormones inhibits their growth rates

  11. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    Science.gov (United States)

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  12. Identification of a novel luminal molecular subtype of breast cancer.

    Directory of Open Access Journals (Sweden)

    Anna Dvorkin-Gheva

    Full Text Available The molecular classification of human breast tumors has afforded insights into subtype specific biological processes, patient prognosis and response to therapies. However, using current methods roughly one quarter of breast tumors cannot be classified into one or another molecular subtype. To explore the possibility that the unclassifiable samples might comprise one or more novel subtypes we employed a collection of publically available breast tumor datasets with accompanying clinical information to assemble 1,593 transcript profiles: 25% of these samples could not be assigned to one of the current molecular subtypes of breast cancer. All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed "luminal-like". We also identified the luminal-like subtype in an independent collection of tumor samples (NKI295. We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors. Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.

  13. Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer.METHODS: We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer.Pathologic features were assessed on hematoxylin-eosinstained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis.RESULTS: Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (≥ 40), high lymphatic vessel density (≥ 9), high Ki-67 labeling index (≥ 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade,cathepsin D positivity, high lymphatic vessel density,superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers (microvessel density,cathepsin D, lymphatic vessel density, and MUC1)revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis.CONCLUSION: Analysis of a combination of immunohistochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.

  14. Application of Proteomics to Cancer Molecular Diagnostics

    Institute of Scientific and Technical Information of China (English)

    Sam HANASH

    2009-01-01

    @@ Strategies to achieve personalized medicine and improve public health encompass assessment of an individual's risk for disease, early detection and molecular classification of disease resulting in an informed choice of the most appropriate treatment instituted at an early stage of disease develop- ment. A major contribution of proteomics in this field is the development of blood based tests to achieve the goals of personalized medicine.

  15. Cancer metabolic reprogramming:impor tance, main features, and potentials for precise targeted anti-cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Liem Minh Phan; Sai-Ching Jim Yeung; Mong-Hong Lee

    2014-01-01

    Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warburg’s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. hTis review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this ifeld, and points out the potentials to translate these scientiifc ifndings into life-saving diagnosis and therapies to help cancer patients.

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

    Science.gov (United States)

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

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  17. Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer.

    Science.gov (United States)

    Latysheva, Natasha S; Oates, Matt E; Maddox, Louis; Flock, Tilman; Gough, Julian; Buljan, Marija; Weatheritt, Robert J; Babu, M Madan

    2016-08-18

    Gene fusions are common cancer-causing mutations, but the molecular principles by which fusion protein products affect interaction networks and cause disease are not well understood. Here, we perform an integrative analysis of the structural, interactomic, and regulatory properties of thousands of putative fusion proteins. We demonstrate that genes that form fusions (i.e., parent genes) tend to be highly connected hub genes, whose protein products are enriched in structured and disordered interaction-mediating features. Fusion often results in the loss of these parental features and the depletion of regulatory sites such as post-translational modifications. Fusion products disproportionately connect proteins that did not previously interact in the protein interaction network. In this manner, fusion products can escape cellular regulation and constitutively rewire protein interaction networks. We suggest that the deregulation of central, interaction-prone proteins may represent a widespread mechanism by which fusion proteins alter the topology of cellular signaling pathways and promote cancer. PMID:27540857

  18. Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

    International Nuclear Information System (INIS)

    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

  19. Dynamics of Molecular Emission Features from Nanosecond, Femtosecond Laser and Filament Ablation Plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Harilal, Sivanandan S.; Yeak, J.; Brumfield, Brian E.; Suter, Jonathan D.; Phillips, Mark C.

    2016-06-15

    The evolutionary paths of molecular species and nanoparticles in laser ablation plumes are not well understood due to the complexity of numerous physical processes that occur simultaneously in a transient laser-plasma system. It is well known that the emission features of ions, atoms, molecules and nanoparticles in a laser ablation plume strongly depend on the laser irradiation conditions. In this letter we report the temporal emission features of AlO molecules in plasmas generated using a nanosecond laser, a femtosecond laser and filaments generated from a femtosecond laser. Our results show that, at a fixed laser energy, the persistence of AlO is found to be highest and lowest in ns and filament laser plasmas respectively while molecular species are formed at early times for both ultrashort pulse (fs and filament) generated plasmas. Analysis of the AlO emission band features show that the vibrational temperature of AlO decays rapidly in filament assisted laser ablation plumes.

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

    Science.gov (United States)

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

    2016-08-01

    Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26878225

  1. ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome.

    Science.gov (United States)

    Riesco-Eizaguirre, Garcilaso; Santisteban, Pilar

    2016-11-01

    Thyroid cancer is the most common endocrine malignancy giving rise to one of the most indolent solid cancers, but also one of the most lethal. In recent years, systematic studies of the cancer genome, most importantly those derived from The Cancer Genome Altas (TCGA), have catalogued aberrations in the DNA, chromatin, and RNA of the genomes of thousands of tumors relative to matched normal cellular genomes and have analyzed their epigenetic and protein consequences. Cancer genomics is therefore providing new information on cancer development and behavior, as well as new insights into genetic alterations and molecular pathways. From this genomic perspective, we will review the main advances concerning some essential aspects of the molecular pathogenesis of thyroid cancer such as mutational mechanisms, new cancer genes implicated in tumor initiation and progression, the role of non-coding RNA, and the advent of new susceptibility genes in thyroid cancer predisposition. This look across these genomic and cellular alterations results in the reshaping of the multistep development of thyroid tumors and offers new tools and opportunities for further research and clinical development of novel treatment strategies. PMID:27666535

  2. Retinoic acid receptors: from molecular mechanisms to cancer therapy.

    Science.gov (United States)

    di Masi, Alessandra; Leboffe, Loris; De Marinis, Elisabetta; Pagano, Francesca; Cicconi, Laura; Rochette-Egly, Cécile; Lo-Coco, Francesco; Ascenzi, Paolo; Nervi, Clara

    2015-02-01

    Retinoic acid (RA), the major bioactive metabolite of retinol or vitamin A, induces a spectrum of pleiotropic effects in cell growth and differentiation that are relevant for embryonic development and adult physiology. The RA activity is mediated primarily by members of the retinoic acid receptor (RAR) subfamily, namely RARα, RARβ and RARγ, which belong to the nuclear receptor (NR) superfamily of transcription factors. RARs form heterodimers with members of the retinoid X receptor (RXR) subfamily and act as ligand-regulated transcription factors through binding specific RA response elements (RAREs) located in target genes promoters. RARs also have non-genomic effects and activate kinase signaling pathways, which fine-tune the transcription of the RA target genes. The disruption of RA signaling pathways is thought to underlie the etiology of a number of hematological and non-hematological malignancies, including leukemias, skin cancer, head/neck cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, renal cell carcinoma, pancreatic cancer, liver cancer, glioblastoma and neuroblastoma. Of note, RA and its derivatives (retinoids) are employed as potential chemotherapeutic or chemopreventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. In humans, retinoids reverse premalignant epithelial lesions, induce the differentiation of myeloid normal and leukemic cells, and prevent lung, liver, and breast cancer. Here, we provide an overview of the biochemical and molecular mechanisms that regulate the RA and retinoid signaling pathways. Moreover, mechanisms through which deregulation of RA signaling pathways ultimately impact on cancer are examined. Finally, the therapeutic effects of retinoids are reported. PMID:25543955

  3. Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

    Science.gov (United States)

    Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

    2016-06-01

    Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual

  4. [Development of molecular targeted therapies in lung cancers].

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2014-05-01

    Human cancers usually possess cumulative genetic aberrations. However, recent studies have revealed that the proliferation and survival of specific subsets of lung cancer depend on a few somatic mutation(s), so-called driver mutations. Representative driver mutations include the EGFR mutation and ALK translocation identified in about 40% and 3% of lung adenocarcinomas in Japan, respectively. These tumors are extremely sensitive to the respective tyrosine kinase inhibitors. This sensitivity has encouraged researchers and clinicians to explore novel driver mutations in lung cancers as future molecular targets. Driver mutations reported so far include the HER2 mutation, BRAF mutation, ROS1 translocation, RET translocation, and NTRK translocation in lung adenocarcinomas, and FGFR1 amplification, DDR2 mutation, and FGFR3 translocation in lung squamous cell carcinomas. However, despite initial dramatic responses, the acquisition of resistance to molecular targeted drugs is almost inevitable. Overcoming resistance to molecular targeted drugs, the key drugs at this time, is an urgent issue to improve the outcomes of lung cancer patients. PMID:24946519

  5. Non-invasive Optical Molecular Imaging for Cancer Detection

    Science.gov (United States)

    Luo, Zhen

    Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide

  6. Molecular markers and targets for colorectal cancer prevention

    Institute of Scientific and Technical Information of China (English)

    Naveena B JANAKIRAM; Chinthalapally V RAO

    2008-01-01

    Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from pro-moting/developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the bio-logical and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarkerin biomolecular pathwayare elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

  7. Computerized lung cancer malignancy level analysis using 3D texture features

    Science.gov (United States)

    Sun, Wenqing; Huang, Xia; Tseng, Tzu-Liang; Zhang, Jianying; Qian, Wei

    2016-03-01

    Based on the likelihood of malignancy, the nodules are classified into five different levels in Lung Image Database Consortium (LIDC) database. In this study, we tested the possibility of using threedimensional (3D) texture features to identify the malignancy level of each nodule. Five groups of features were implemented and tested on 172 nodules with confident malignancy levels from four radiologists. These five feature groups are: grey level co-occurrence matrix (GLCM) features, local binary pattern (LBP) features, scale-invariant feature transform (SIFT) features, steerable features, and wavelet features. Because of the high dimensionality of our proposed features, multidimensional scaling (MDS) was used for dimension reduction. RUSBoost was applied for our extracted features for classification, due to its advantages in handling imbalanced dataset. Each group of features and the final combined features were used to classify nodules highly suspicious for cancer (level 5) and moderately suspicious (level 4). The results showed that the area under the curve (AUC) and accuracy are 0.7659 and 0.8365 when using the finalized features. These features were also tested on differentiating benign and malignant cases, and the reported AUC and accuracy were 0.8901 and 0.9353.

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

    Science.gov (United States)

    Ozcift, Akin

    2012-08-01

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

  9. Breast imaging technology: Probing physiology and molecular function using optical imaging - applications to breast cancer

    International Nuclear Information System (INIS)

    The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring

  10. Intraoral sonographic features of tongue cancer after radical radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chikui, Toru E-mail: chikui@rad.dent.kyushu-u.ac.jp; Kawazu, Toshiyuki; Nakamura, Katsumasa; Urashima, Yuusuke; Yuasa, Kenji; Kanda, Shigenobu

    2004-12-01

    Purpose: The purpose was to illustrate the sonographic changes of tongue cancer after radical radiotherapy. Materials and methods: In 24 patients with tongue cancer treated by interstitial brachytherapy (BRT) (uneventful recovery n=16, recurrence n=5, severe soft tissue complication n=3), follow-up examination were performed and both the margin and the vascular pattern were retrospectively assessed. We basically performed US examination at least once every 3 months after BRT within 1 year during follow-up period. Results: In the healing process, intraoral sonography shows an unclear margin immediately after brachytherapy and a transient increase of the vascularity lasted within 6 months after BRT, followed by a decrease in the vascularity. The large difference in echogenicity between the primary site and the surrounding tissue and the increased difference suggested the possibility of either radiation ulceration or recurrence. Conclusion: Intraoral sonography could depict the sequence changes of the tongue after BRT, and it was thus useful to confirm the clinical findings of either radiation ulcers or recurrence.

  11. MicroRNAs as molecular markers in lung cancer

    Directory of Open Access Journals (Sweden)

    Javier Silva

    2013-10-01

    Full Text Available Lung cancer is the most common cause of cancer death in the western world for both men and women. Lung cancer appears to be a perfect candidate for a screening program, since it is the number one cancer killer, it has a long preclinical phase, curative treatment for the minority of patients who are diagnosed early and a target population at risk (smokers and it is also a major economic burden. The earliest approaches to identifying cancer markers were based on preliminary clinical or pathological observations, although molecular biology is a strong candidate for occupying a place among the set of methods. In search of markers, several alterations, such as mutations, loss of heterozygosity, microsatellite instability, DNA methylation, mitochondrial DNA mutations, viral DNA, modified expression of mRNA, miRNA and proteins, and structurally altered proteins have all been analysed. MicroRNAs (miRNA are small RNA molecules, about 19-25 nucleotides long and encoded in genomes of plants, animals, fungi and viruses. It has been reported that miRNAs may have multiple functions in lung development and that aberrant expression of miRNAs could induce lung tumorigenesis. We review here the role of miRNAs in lung tumorigenesis and also as a novel type of biomarker.-----------------------------------Cite this article as:Silva J, Garcia V, Lopez-Gonzalez A, Provencio M. MicroRNAs as molecular markers in lung cancer. Int J Cancer Ther Oncol 2013;1(1:010111. DOI: http://dx.doi.org/10.14319/ijcto.0101.11

  12. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    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.

  13. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    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

  14. A Retrospective Study on Pathologic Features and Racial Disparities in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Steven A. Bigler

    2011-01-01

    Full Text Available We reviewed more than 3,000 pathology reports on prostate cancer-related surgical specimens and analyzed racial disparities in histological and clinical features at the time of initial biopsy, diagnosis of prostate cancer, and prostatectomy, as well as in characteristics of tumor evolution between African American and Caucasian patients. As compared to Caucasians, African American patients had younger age, higher cancer detection rate, higher Gleason score of prostate cancer, and more bilateral involvement of the prostate. African Americans also had larger prostates, greater volume of tumor, and more positive margins. The diagnosis of HGPIN or ASAP in prostate biopsies and African American race conferred an increased risk of diagnosis of prostate cancer. The interval between prior noncancerous biopsy and the subsequent biopsy with diagnosis of prostate cancer was shorter in men with HGPIN, with ASAP, or of African American race.

  15. Molecular aspects of prostate cancer: implications for future directions

    Directory of Open Access Journals (Sweden)

    Etel R. P. Gimba

    2003-10-01

    Full Text Available Many studies have been developed trying to understand the complex molecular mechanisms involved in oncogenesis and progression of prostate cancer (PCa. Current biotechnological methodologies, especially genomic studies, are adding important aspects to this area. The construction of extensive DNA sequence data and gene expression profiles have been intensively explored to search for candidate biomarkers to evaluate PCa. The use of DNA micro-array robotic systems constitutes a powerful approach to simultaneously monitor the expression of a great number of genes. The resulting gene expressing profiles can be used to specifically describe tumor staging and response to cancer therapies. Also, it is possible to follow PCa pathological properties and to identify genes that anticipate the behavior of clinical disease. The molecular pathogenesis of PCa involves many contributing factors, such as alterations in signal transduction pathways, angiogenesis, adhesion molecules expression and cell cycle control. Also, molecular studies are making clear that many genes, scattered through several different chromosomal regions probably cause predisposition to PCa. The discovery of new molecular markers for PCa is another relevant advance resulting from molecular biology studies of prostate tumors. Interesting tissue and serum markers have been reported, resulting in many cases in useful novelties to diagnostic and prognostic approaches to follow-up PCa. Finally, gene therapy comes as an important approach for therapeutic intervention in PCa. Clinical trials for PCa have been demonstrating that gene therapy is relatively safe and well tolerated, although some improvements are yet to be developed.

  16. Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status.

    Science.gov (United States)

    Pais, Adi; Degani, Hadassa

    2016-01-01

    The estrogen receptor (ER) α is overexpressed in most breast cancers, and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) effects of two novel ER-targeted contrast agents (CAs), based on pyridine-tetra-acetate-Gd(III) chelate conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd). The experiments were conducted in solution, in human breast cancer cells, and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen-like agonistic activity, enhancing cell proliferation, as well as upregulating cMyc oncogene and downregulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast-enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd-specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors' ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also revealed that this

  17. Estrogen receptor targeted contrast agents for molecular magnetic resonance imaging of breast cancer hormonal status

    Directory of Open Access Journals (Sweden)

    Adi ePais

    2016-04-01

    Full Text Available The estrogen receptor α (ER is over expressed in most breast cancers and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer, as well as in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging effects of two novel ER- targeted contrast agents (CAs based on pyridine-tetra-acetate-Gd(III chelate conjugated to 17β-estradiol (EPTA-Gd or to tamoxifen (TPTA-Gd. The experiments were conducted in solution, in human breast cancer cells and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen like agonistic activity, enhancing cell proliferation, as well as up-regulating cMyc oncogene and down-regulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors’ ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also

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

    Directory of Open Access Journals (Sweden)

    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.

  19. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ~ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  20. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  1. Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features

    Institute of Scientific and Technical Information of China (English)

    Ming Gao; Xiu-Ju Liang; Zi-Sen Zhang; Wang Ma; Zhi-Wei Chang; Ming-Zhi Zhang

    2013-01-01

    Objective: To investigate the relationship between the expression of epidermal growth factor receptor (EGFR) in gastric cancer and the clinicopathological features and prognosis. Methods: A total of 78 paraffin specimens of gastric cancer operation were collected. The immunohistochemical method was used to detect the expression of EGFR in 78 cases of gastric cancer and 20 cases of adjacent normal tissue. The relationship between the high expression of EGFR and clinicopathological features was analyzed. Results: EGFR positive expression rate in the 78 cases of gastric cancer tissue was 57.7 %( 45/78), while EGFR was not expressed in 20 cases of adjacent normal tissue. The high EGFR expression was positively correlated with the position of gastric cancer, tumor size, cell differentiation, invasive depth, lymph node metastasis and TNM staging, yet having no obvious relation with gender or age. Conclusions: EGFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer, which can provide a theoretical basis for the targeted therapy for gastric cancer with EGFR as the target.

  2. Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype

    OpenAIRE

    Korenberg, Julie R; Kawashima, Hiroko; Pulst, Stefan-M.; Ikeuchi, T; Ogasawara, N; Yamamoto, K.; Schonberg, Steven A.; West, Ruth; Allen, Leland; Magenis, Ellen; Ikawa, K; Taniguchi, N; Epstein, Charles J.

    1990-01-01

    Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We now present evidence that significantly narrows the chromosomal region responsible for several of the phenotypic features of DS. We report a molecular and cytogenetic analysis of a three-generation family containing four individuals with clinical DS as manif...

  3. Clinical implications of the intrinsic molecular subtypes of breast cancer.

    Science.gov (United States)

    Prat, Aleix; Pineda, Estela; Adamo, Barbara; Galván, Patricia; Fernández, Aranzazu; Gaba, Lydia; Díez, Marc; Viladot, Margarita; Arance, Ana; Muñoz, Montserrat

    2015-11-01

    Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

  4. Molecular Targeted Therapies Using Botanicals for Prostate Cancer Chemoprevention

    OpenAIRE

    Kumar, Nagi; Chornokur, Ganna

    2012-01-01

    In spite of the large number of botanicals demonstrating promise as potential cancer chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving botanical agents to recommendation for clinical use include adopting a systematic, molecular-target based approach and utilizing the same ethical and rigorous methods that are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity...

  5. Diagnostic features of lung metastases differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    T. M. Geliashvili

    2015-01-01

    Full Text Available Background. The worldwide increasing incidence of thyroid cancer (TC is mainly due to a rise in its major form of differentiated TC (DTC: papillary. Most patients with DTC have a good prognosis; 10-year survival overall rates are as high as 85 %, but not greater than 40 % in a group of patients with distant metastases. At the same time, the lung is the most frequent target for distant metastases, accounting for 70 % of all sites.Objective: to estimate and compare the capabilities of different diagnostic techniques to detect lung metastases of DTC. Materials and methods. The results of diagnosing lung metastases were retrospectively analyzed in 36 patients (33 women and 3 men; mean age 53 years with DTC (29 patients with papillary TC and 7 with follicular TC treated at the department of radiotherapy with systemic therapy, Chelyabinsk Regional Clinical Oncology Center from 2011 to 2014.Results. Chest X-ray could reveal pulmonary metastases in 13 (36 % patients; lung pathology foci were absent in 23 (64 % patients. 131I whole-body scintigraphy (WBS proved to be of informative value in 24 (66.7 % patients, it displayed no increased accumulation of the radiopharmaceutical in the lung of 12 (33.3 % cases. Multislice spiral computed tomography (MSCT of the chest was carried out in 22 (61 % patients; out of them 21 (95.5 % were found to have 1.4-to-20-mm lung cancer foci. 18Fluorodeoxyglucose (18FDG positron emission tomography / computed tomography (PET / CT was performed in 18 (50 % patients, which showed 3–26-mm lung pathology foci in all the patents; out of them 16 (88.9 % were detected to have metastases owing to the CT component of this method. Thus, the highest sensitivity was exhibited by MSCT (95.5 %, 18FDG PET / CT (100 % due to its CT component, and 131I WBS (66.7 %.Conclusion. When lung metastases of DTC are suspected, 1 chest X-ray should be used as a screening test; 2 131I WBS should be performed in all patients; 3 MSCT of the chest is

  6. Relationship of carbohydrate molecular spectroscopic features in combined feeds to carbohydrate utilization and availability in ruminants

    Science.gov (United States)

    Zhang, Xuewei; Yu, Peiqiang

    To date, there is no study on the relationship between carbohydrate (CHO) molecular structures and nutrient availability of combined feeds in ruminants. The objective of this study was to use molecular spectroscopy to reveal the relationship between CHO molecular spectral profiles (in terms of functional groups (biomolecular, biopolymer) spectral peak area and height intensity) and CHO chemical profiles, CHO subfractions, energy values, and CHO rumen degradation kinetics of combined feeds of hulless barley with pure wheat dried distillers grains with solubles (DDGS) at five different combination ratios (hulless barley to pure wheat DDGS: 100:0, 75:25, 50:50, 25:75, 0:100). The molecular spectroscopic parameters assessed included: lignin biopolymer molecular spectra profile (peak area and height, region and baseline: ca. 1539-1504 cm-1); structural carbohydrate (STCHO, peaks area region and baseline: ca. 1485-1186 cm-1) mainly associated with hemi- and cellulosic compounds; cellulosic materials peak area (centered at ca. 1240 cm-1 with region and baseline: ca. 1272-1186 cm-1); total carbohydrate (CHO, peaks area region and baseline: ca. 1186-946 cm-1). The results showed that the functional groups (biomolecular, biopolymer) in the combined feeds are sensitive to the changes of carbohydrate chemical and nutrient profiles. The changes of the CHO molecular spectroscopic features in the combined feeds were highly correlated with CHO chemical profiles, CHO subfractions, in situ CHO rumen degradation kinetics and fermentable organic matter supply. Further study is needed to investigate possibility of using CHO molecular spectral features as a predictor to estimate nutrient availability in combined feeds for animals and quantify their relationship.

  7. Diffuse sclerosing variant of papillary thyroid carcinoma--an update of its clinicopathological features and molecular biology.

    Science.gov (United States)

    Pillai, Suja; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y

    2015-04-01

    Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma. The aim of this review is to critically analyse the features of this entity. A search of the literature revealed 25 clinicopathological studies with in-depth analysis of features of DSVPTC. Overall, the prevalence of DSVPTC varies from 0.7-6.6% of all papillary thyroid carcinoma. Higher prevalence of DSVPTC was noted in paediatric patients and in patients affected by irradiation. DSVPTC tends to occur more frequently in women and in patients in the third decade of life. Macroscopically, DSVPTC can involve the thyroid gland extensively without forming a dominant mass. Microscopic examination of DSVPTC revealed extensive fibrosis, squamous metaplasia and numerous psammoma bodies. The latter pathological feature can aid in the pre-operative diagnosis of the entity by fine needle aspiration and ultrasound. Compared to conventional papillary thyroid carcinoma, DSVPTC had a higher incidence of lymph node metastases at presentation. Distant metastases were noted in approximately 5% of the cases. Patients with DSVPTC were recommended to be managed by aggressive treatment protocols. It is likely that as a result of this, the prognosis of the patients with DSVPTC was noted to be similar to conventional papillary thyroid carcinoma. Overall, cancer recurrence and cancer related mortality have been reported in 14% and 3%, respectively, of patients with DSVPTC. In immunohistochemical studies, DSVPTC showed different expression patterns of epithelial membrane antigen, galectin 3, cell adhesion molecules, p53 and p63 when compared to conventional papillary thyroid carcinoma. On genetic analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC and activation of RET/PTC rearrangements are common. To conclude, DSVPTC has different clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

    2011-01-01

    Purpose Gastric cancer may be subdivided into three 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. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >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. Results 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 three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >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. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction 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. PMID:21430069

  12. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration.

    Science.gov (United States)

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

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

    Science.gov (United States)

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

    2005-08-01

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

  14. Mapping Drug Physico-Chemical Features to Pathway Activity Reveals Molecular Networks Linked to Toxicity Outcome

    OpenAIRE

    Philipp Antczak; Fernando Ortega; J Kevin Chipman; Francesco Falciani

    2010-01-01

    The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either compound features (i.e., QSAR), in vitro cell based assays or molecular profiling of target tissues (i.e., expression profiling). Although these approaches have already shown the potential of predictive toxicology, we still do not have a systematic approach to model the interaction between chemi...

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

    Directory of Open Access Journals (Sweden)

    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

  16. Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes

    Science.gov (United States)

    2016-01-01

    In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo. PMID:27267364

  17. Development of New Molecular EZH2 on Lung Cancer Invasion and Metastasis

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    Hui XIA

    2016-02-01

    Full Text Available Lung cancer is a serious threat to human health malignancies upward trend in morbidity and mortality. It is hot topic to investigate the molecular mechanisms of lung cancer development and explore the new therapeutic targets. The underlying mechanism of EZH2 on lung cancer development will demonstrate the new pathway of lung cancer development, invasion and metastasis. The exploration and application of new targeted molecular will improve the survival rate and living quality of lung cancer patients in future.

  18. Appraisal of progenitor markers in the context of molecular classification of breast cancers

    OpenAIRE

    Haviv, Izhak

    2011-01-01

    Clinical management of breast cancer relies on case stratification, which increasingly employs molecular markers. The motivation behind delineating breast epithelial differentiation is to better target cancer cases through innate sensitivities bequeathed to the cancer from its normal progenitor state. A combination of histopathological and molecular classification of breast cancer cases suggests a role for progenitors in particular breast cancer cases. Although a remarkable fraction of the re...

  19. Universal molecular features of refractory dissolved organic matter in fresh- and seawater

    Science.gov (United States)

    Dittmar, T.; Blasius, B.; Steinbrink, C.; Feenders, C.; Stumm, M.; Christoffers, J.; Niggemann, J.; Gerdts, G.; Osterholz, H.; Seibt, M.; Seidel, M.; Vähätalo, A.

    2012-04-01

    Dissolved organic matter (DOM) is among the largest pools of reduced carbon on Earth's surface. Its molecular structure and the reasons behind its stability in the aquatic environment are unknown. We present a mathematical model that predicts essential molecular features of refractory dissolved organic matter in fresh- and seawater. The model has only eight input variables and can accurately reproduce the presence and abundance of up to 10,000 molecular formulae in aquatic systems. The model was established with ultrahigh-resolution mass spectrometry data of North Pacific deep water (obtained on a 15 Tesla Fourier-transform ion cyclotron resonance mass spectrometer, FT-ICR-MS). We determined the molecular formulae of DOM with help of FT-ICR-MS in >1,000 samples from around the globe, covering a wide variety of open ocean, freshwater and coastal systems. The molecular formulae predicted from our North Pacific deep water model were present in all sea- and fresh water samples. In terrigenous DOM, we detected a second group of compounds that could also accurately be predicted with our model, by using a different set of eight input variables. This exclusively terrigenous compound group was more photo-reactive than the universal compound group. During a two-year sampling period at a continental shelf station, the universal DOM compounds were always present at their predicted abundance. During plankton blooms, additional compounds were produced that did not match our model and that did not persist on a longer term. The universal DOM pattern was also not observed in mesocosm experiments where algae and bacteria blooms were artificially induced. Refractory DOM in any aquatic system not only shares the same molecular formulae at the same relative abundance, but compounds with the same molecular formulae most likely have the same molecular structure, independent of the origin of DOM. Fragmentation experiments in the FT-ICR-MS on a wide range of molecular formulae revealed

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

    Directory of Open Access Journals (Sweden)

    Noriyuki Horiguchi

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    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. (orig.)

  2. Molecular profiling of indolent human prostate cancer:tackling technical challenges to achieve high-fidelity genome-wide data

    Institute of Scientific and Technical Information of China (English)

    Thomas A. Dunn; Helen L. Fedor; Angelo M. De Marzo; Jun Luo

    2012-01-01

    The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men,and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases.Since progressive acquisition and accumulation of genomic alterations,both genetic and epigenetic,is a defining feature of all human cancers at different stages of disease progression,it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer.Approaches capable of detecting such alterations on a genome-wide level are the most promising.Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression,and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment.However,defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge,particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens.Here,we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies,identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues,and highlight recent progresses in efforts to address these technical challenges.

  3. Xenogeneic homologous genes, molecular evolution and cancer therapy

    Institute of Scientific and Technical Information of China (English)

    田聆; 魏于全

    2001-01-01

    Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.

  4. Epigenetic: a molecular link between testicular cancer and environmental exposures?

    Directory of Open Access Journals (Sweden)

    Aurelie eVega

    2012-11-01

    Full Text Available In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters (EDs exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the Testicular Dysgenesis Syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Futhermore, infertility has been stated as a risk factor for testicular cancer. The incidence of testicular cancer has been increasing over the past decades. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS from fetal germ cells (primordial germ cell or gonocyte. During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications plays an important role in normal development as well as in various diseases, including testicular cancer.Here we will review chromatin modifications which can affect testicular physiology leading to the development of testicular cancer; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

  5. Molecular targets of cancer chemoprevention by garlic-derived organosulfides

    Institute of Scientific and Technical Information of China (English)

    Anna HERMAN-ANTOSIEWICZ; Anna A POWOLNY; Shivendra V SINGH

    2007-01-01

    The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables in-eluding garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer Cellsare frequently associated with perturbations in cell cycle progression and induc-tion of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bc1-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

  6. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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

  9. Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers

    Directory of Open Access Journals (Sweden)

    Clara L Sampieri

    2013-01-01

    Full Text Available Gastric cancer is a complex disease that involves a range of biological individuals and tumors with histopathological features. The pathogenesis of this disease is multi-factorial and includes the interaction of genetic predisposition with environmental factors. Gastric cancer is normally diagnosed in advanced stages where there are few alternatives to offer and the prognosis is difficult to establish. Metastasis is the leading cause of cancer deaths. Identification of key genes and signaling pathways involved in metastasis and recurrence could predict these events and thereby identify therapeutic targets. In this context, the extracellular matrix metalloproteinases (MMPs and their inhibitors (TIMPs represent a potential prognostic tool, because both genetic families regulate growth, angiogenesis, invasion, immune response, epithelial mesenchymal transition and cellular survival. Proteolytic parameters based on MMP/TIMP expression could be useful in the identification of patients with a high probability of developing distant metastases or peritoneal dissemination for each degree of histological malignancy. It is also probable that these parameters can allow improvement in the extent of surgery and dictate the most suitable therapy. We reviewed papers focused on human gastric epithelial cancer as a model and focus on the potential use of MMPs and TIMPs as molecular markers; also we include literature regarding gastric cancer risk factors, classification systems and MMP/TIMP regulation.

  10. Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers.

    Science.gov (United States)

    Sampieri, Clara L; León-Córdoba, Kenneth; Remes-Troche, Jos Maria

    2013-01-01

    Gastric cancer is a complex disease that involves a range of biological individuals and tumors with histopathological features. The pathogenesis of this disease is multi-factorial and includes the interaction of genetic predisposition with environmental factors. Gastric cancer is normally diagnosed in advanced stages where there are few alternatives to offer and the prognosis is difficult to establish. Metastasis is the leading cause of cancer deaths. Identification of key genes and signaling pathways involved in metastasis and recurrence could predict these events and thereby identify therapeutic targets. In this context, the extracellular matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) represent a potential prognostic tool, because both genetic families regulate growth, angiogenesis, invasion, immune response, epithelial mesenchymal transition and cellular survival. Proteolytic parameters based on MMP/TIMP expression could be useful in the identification of patients with a high probability of developing distant metastases or peritoneal dissemination for each degree of histological malignancy. It is also probable that these parameters can allow improvement in the extent of surgery and dictate the most suitable therapy. We reviewed papers focused on human gastric epithelial cancer as a model and focus on the potential use of MMPs and TIMPs as molecular markers; also we include literature regarding gastric cancer risk factors, classification systems and MMP/TIMP regulation.

  11. 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...

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

    OpenAIRE

    Jokinen, Elina; Laurila, Niina; Koivunen, Peppi; Koivunen, Jussi P

    2014-01-01

    Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can media...

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

    Science.gov (United States)

    Gunavathi, C; Premalatha, K

    2015-01-01

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

  14. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features.

    Science.gov (United States)

    Meini, María-Rocío; Tomatis, Pablo E; Weinreich, Daniel M; Vila, Alejandro J

    2015-07-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters.

  15. Quantitative Description of a Protein Fitness Landscape Based on Molecular Features

    Science.gov (United States)

    Meini, María-Rocío; Tomatis, Pablo E.; Weinreich, Daniel M.; Vila, Alejandro J.

    2015-01-01

    Understanding the driving forces behind protein evolution requires the ability to correlate the molecular impact of mutations with organismal fitness. To address this issue, we employ here metallo-β-lactamases as a model system, which are Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study of all the possible evolutionary pathways leading to a metallo-β-lactamase variant optimized by directed evolution. By studying the activity, stability and Zn(II) binding capabilities of all mutants in the preferred evolutionary pathways, we show that this local fitness landscape is strongly conditioned by epistatic interactions arising from the pleiotropic effect of mutations in the different molecular features of the enzyme. Activity and stability assays in purified enzymes do not provide explanatory power. Instead, measurement of these molecular features in an environment resembling the native one provides an accurate description of the observed antibiotic resistance profile. We report that optimization of Zn(II) binding abilities of metallo-β-lactamases during evolution is more critical than stabilization of the protein to enhance fitness. A global analysis of these parameters allows us to connect genotype with fitness based on quantitative biochemical and biophysical parameters. PMID:25767204

  16. Mapping drug physico-chemical features to pathway activity reveals molecular networks linked to toxicity outcome.

    Directory of Open Access Journals (Sweden)

    Philipp Antczak

    Full Text Available The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either compound features (i.e., QSAR, in vitro cell based assays or molecular profiling of target tissues (i.e., expression profiling. Although these approaches have already shown the potential of predictive toxicology, we still do not have a systematic approach to model the interaction between chemical features, molecular networks and toxicity outcome. Here, we describe a computational strategy designed to address this important need. Its application to a model of renal tubular degeneration has revealed a link between physico-chemical features and signalling components controlling cell communication pathways, which in turn are differentially modulated in response to toxic chemicals. Overall, our findings are consistent with the existence of a general toxicity mechanism operating in synergy with more specific single-target based mode of actions (MOAs and provide a general framework for the development of an integrative approach to predictive toxicology.

  17. Curcumin effectively inhibits oncogenic NF-kB signaling and restrains stemness features in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Gomez-Quiroz, Luis; Arreguin Camacho, Lucrecia O;

    2015-01-01

    BACKGROUND & AIMS: The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kB signaling. METHODS: We evaluated the CSCs-depleting potential of NF......-kB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of Side Population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western...... inhibition of NF-kB and HDAC signaling for treatment of liver cancer patients with poor prognosis....

  18. Cancer Basics

    Science.gov (United States)

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

  19. Molecular mechanisms of pharmacological doses of ascorbate on cancer cells.

    Science.gov (United States)

    Venturelli, Sascha; Sinnberg, Tobias W; Niessner, Heike; Busch, Christian

    2015-06-01

    Intravenous application of high-dose ascorbate (vitamin C) has been used in complementary medicine since the 1970s to treat cancer patients. In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. This anticancer effect is dose dependent, catalyzed by serum components and mediated by reactive oxygen species and ascorbyl radicals, making ascorbate a pro-oxidative pro-drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. It further depends on HIF-1 signaling and oxygen pressure, and shows a strong epigenetic signature (alteration of DNA-methylation and induction of tumor-suppressing microRNAs in cancer cells). The detailed understanding of ascorbate-induced antiproliferative molecular mechanisms warrants in-depth preclinical evaluation in cancer-bearing animal models for the optimization of an efficacious therapy regimen (e.g., combination with hyperbaric oxygen or O2-sensitizers) that subsequently need to be evaluated in clinical trials. PMID:26065536

  20. 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.

  1. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Pierre Cordelier

    2011-02-01

    Full Text Available 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.

  2. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    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

  3. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  4. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    International Nuclear Information System (INIS)

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed

  5. 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.

  6. Pharmacophore modeling and molecular dynamics simulation to identify the critical chemical features against human sirtuin 2 inhibitors

    Science.gov (United States)

    Sakkiah, Sugunadevi; Baek, Ayoung; Lee, Keun Woo

    2012-03-01

    Sirtuin 2 (SIRT2) is one of the emerging targets in chemotherapy field and mainly associated with many diseases such as cancer and Parkinson's. Hence, quantitative hypothesis was developed using Discovery Studio v2.5. Top ten resultant hypotheses were generated, among them Hypo1 was selected as a best hypothesis based on the statistical parameters like high cost difference (52), lowest RMS (0.71), and good correlation coefficient (0.96). Hypo1 has been validated by using well known methodologies such as Fischer's randomization method (95% confidence level), test set which has shown the correlation coefficient of 0.93 as well as the goodness of hit (0.65), and enrichment factor (8.80). All the above statistical validations confirm that the chemical features in Hypo1 (1 hydrogen bond acceptor, 1 hydrophobic, and 2 ring aromatic features) was able to inhibit the function of SIRT2. Hence, Hypo1 was used as a query in virtual screening to find a novel scaffolds by screening the various chemical databases. The screened molecules from the databases were checked for the ADMET as well as the drug-like properties. Due to the lack of SIRT2-ligand complex structure in PDB, molecular docking and molecular dynamics (MD) simulation was carried out to find the suitable orientation of ligand in the active site. The representative structure from MD simulations was used as a receptor to dock the molecules which passed the drug-like properties from the virtual screening. Finally, 29 compounds were selected as a potent candidate leads based on the interactions with the active site residues of SIRT2. Thus, the resultant pharmacophore can be used to discover and design the SIRT2 inhibitors with desired biological activity.

  7. 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, defin

  8. Comparative Analysis of Feature Extraction Methods for the Classification of Prostate Cancer from TRUS Medical Images

    Directory of Open Access Journals (Sweden)

    Manavalan Radhakrishnan

    2012-01-01

    Full Text Available Diagnosing Prostate cancer is a challenging task for Urologists, Radiologists, and Oncologists. Ultrasound imaging is one of the hopeful techniques used for early detection of prostate cancer. The Region of interest (ROI is identified by different methods after preprocessing. In this paper, DBSCAN clustering with morphological operators is used to extort the prostate region. The evaluation of texture features is important for several image processing applications. The performance of the features extracted from the various texture methods such as histogram, Gray Level Cooccurrence Matrix (GLCM, Gray-Level Run-Length Matrix (GRLM, are analyzed separately. In this paper, it is proposed to combine histogram, GLRLM and GLCM in order to study the performance. The Support Vector Machine (SVM is adopted to classify the extracted features into benign or malignant. The performance of texture methods are evaluated using various statistical parameters such as sensitivity, specificity and accuracy. The comparative analysis has been performed over 5500 digitized TRUS images of prostate.

  9. Ensemble based system for whole-slide prostate cancer probability mapping using color texture features.

    LENUS (Irish Health Repository)

    DiFranco, Matthew D

    2011-01-01

    We present a tile-based approach for producing clinically relevant probability maps of prostatic carcinoma in histological sections from radical prostatectomy. Our methodology incorporates ensemble learning for feature selection and classification on expert-annotated images. Random forest feature selection performed over varying training sets provides a subset of generalized CIEL*a*b* co-occurrence texture features, while sample selection strategies with minimal constraints reduce training data requirements to achieve reliable results. Ensembles of classifiers are built using expert-annotated tiles from training images, and scores for the probability of cancer presence are calculated from the responses of each classifier in the ensemble. Spatial filtering of tile-based texture features prior to classification results in increased heat-map coherence as well as AUC values of 95% using ensembles of either random forests or support vector machines. Our approach is designed for adaptation to different imaging modalities, image features, and histological decision domains.

  10. Molecular biology of testicular germ cell tumors: unique features awaiting clinical application.

    Science.gov (United States)

    Boublikova, Ludmila; Buchler, Tomas; Stary, Jan; Abrahamova, Jitka; Trka, Jan

    2014-03-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men characterized by distinct biologic features and clinical behavior. Both genetic predispositions and environmental factors probably play a substantial role in their etiology. TGTCs arise from a malignant transformation of primordial germ cells in a process that starts prenatally, is often associated with a certain degree of gonadal dysgenesis, and involves the acquirement of several specific aberrations, including activation of SCF-CKIT, amplification of 12p with up-regulation of stem cell genes, and subsequent genetic and epigenetic alterations. Their embryonic and germ origin determines the unique sensitivity of TGCTs to platinum-based chemotherapy. Contrary to the vast majority of other malignancies, no molecular prognostic/predictive factors nor targeted therapy is available for patients with these tumors. This review summarizes the principal molecular characteristics of TGCTs that could represent a potential basis for development of novel diagnostic and treatment approaches. PMID:24182421

  11. Molecular pathways: targeting ETS gene fusions in cancer.

    Science.gov (United States)

    Feng, Felix Y; Brenner, J Chad; Hussain, Maha; Chinnaiyan, Arul M

    2014-09-01

    Rearrangements, or gene fusions, involving the ETS family of transcription factors are common driving events in both prostate cancer and Ewing sarcoma. These rearrangements result in pathogenic expression of the ETS genes and trigger activation of transcriptional programs enriched for invasion and other oncogenic features. Although ETS gene fusions represent intriguing therapeutic targets, transcription factors, such as those comprising the ETS family, have been notoriously difficult to target. Recently, preclinical studies have demonstrated an association between ETS gene fusions and components of the DNA damage response pathway, such as PARP1, the catalytic subunit of DNA protein kinase (DNAPK), and histone deactylase 1 (HDAC1), and have suggested that ETS fusions may confer sensitivity to inhibitors of these DNA repair proteins. In this review, we discuss the role of ETS fusions in cancer, the preclinical rationale for targeting ETS fusions with inhibitors of PARP1, DNAPK, and HDAC1, as well as ongoing clinical trials targeting ETS gene fusions.

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

    OpenAIRE

    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 fluorescent labeled (NIRF) tracers for detection of breast cancer. Thus far, only a few molecular imaging tracers have been taken to the clinic of which most are suitable for PET. My thesis describes the e...

  13. Efficient molecular subtype classification of high-grade serous ovarian cancer.

    Science.gov (United States)

    Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David

    2015-07-01

    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. PMID:25810134

  14. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

    Science.gov (United States)

    Budinska, Eva; Popovici, Vlad; Tejpar, Sabine; D'Ario, Giovanni; Lapique, Nicolas; Sikora, Katarzyna Otylia; Di Narzo, Antonio Fabio; Yan, Pu; Hodgson, John Graeme; Weinrich, Scott; Bosman, Fred; Roth, Arnaud; Delorenzi, Mauro

    2013-09-01

    The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http

  15. Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy.

    Science.gov (United States)

    Sherbet, G V

    2009-07-18

    The growth, invasion and metastatic spread of cancer have been identified with the deregulation of cell proliferation, altered intercellular and cell-substratum adhesion and enhanced motility and the deposition of disseminated cancer cells at distant sites. The identification of therapeutic targets for cancer is crucial to human welfare. Drug development, molecular modelling and design of effective drugs greatly depend upon the identification of suitable therapeutic targets. Several genetic determinants relating to proliferation and growth, invasion and metastasis have been identified. S100A4 appears to be able to activate and integrate pathways to generate the phenotypic responses that are characteristic of cancer. S100A4 signalling can focus on factors associated with normal and aberrant proliferation, apoptosis and growth, and differentiation. It is able to activate signalling pathways leading to the remodelling of the cell membrane and the extracellular matrix; modulation of cytoskeletal dynamics, acquisition of invasiveness and induction of angiogenesis. Therefore S100A4 is arguably a molecular target of considerable potential possessing a wide ranging biological activity that can alter and regulate the major phenotypic features of cancer. The evolution of an appropriate strategy that permits the identification of therapeutic targets most likely to be effective in the disease process without unduly affecting normal biological processes and function is an incontrovertible imperative. By virtue of its ability to activate interacting and multi-functional signalling systems, S100A4 appears to offer suitable targets for developing new therapeutic procedures. Some effectors of the S100A4-activated pathways might also lend themselves as foci of therapeutic interest.

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

    Science.gov (United States)

    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.

  17. Breast cancer molecular subtypes: from TNBC to QNBC

    Science.gov (United States)

    Hon, Jane Date C; Singh, Baljit; Sahin, Aysegul; Du, Gang; Wang, Jinhua; Wang, Vincent Y; Deng, Fang-Ming; Zhang, David Y; Monaco, Marie E; Lee, Peng

    2016-01-01

    Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

  18. SPARCoC: a new framework for molecular pattern discovery and cancer gene identification.

    Directory of Open Access Journals (Sweden)

    Shiqian Ma

    Full Text Available It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust, which is based on a novel Common-background and Sparse-foreground Decomposition (CSD model and the Maximum Block Improvement (MBI co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust and nonnegative matrix factorization (NMF. We apply SPARCoC to the study of lung adenocarcinoma (ADCA, an extremely heterogeneous histological type, and a significant challenge for molecular subtyping. For testing and verification, we use high quality gene expression profiling data of lung ADCA patients, and identify prognostic gene signatures which could cluster patients into subgroups that are significantly different in their overall survival (with p-values < 0.05. Our results are only based on gene expression profiling data analysis, without incorporating any other feature selection or clinical information; we are able to replicate our findings with completely independent datasets. SPARCoC is broadly applicable to large-scale genomic data to empower pattern discovery and cancer gene identification.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    Zhang Yu; Yu Like; Xie Haiyan; Hu Weihua; Hao Keke; Xia Ning

    2013-01-01

    Objective: To analyze the clinical features of lung cancer diagnosed by bronchoscopy. Methods:The clinical features of2168 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 signiifcantly improve the diagnostic rate and provide reliable evidences for clinical treatment.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. An Approach with Support Vector Machine using Variable Features Selection on Breast Cancer Prognosis

    Directory of Open Access Journals (Sweden)

    Sandeep Chaurasia

    2013-09-01

    Full Text Available Cancer diagnosis and clinical outcome prediction are among the most important emerging applications of machine learning. In this paper we have used an approach by using support vector machine classifier to construct a model that is useful for the breast cancer survivability prediction. We have used both 5 cross and 10 cross validation of variable selection on input feature vectors and the performance measurement through bio-learning class performance while measuring AUC, specificity and sensitivity. The performance of the SVM is much better than the other machine learning classifier.

  4. Extending pathways and processes using molecular interaction networks to analyse cancer genome data

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    Krasnogor Natalio

    2010-12-01

    Full Text Available Abstract Background Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways. Results We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes. Conclusions The proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data.

  5. 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

  6. Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker.

    Directory of Open Access Journals (Sweden)

    Saleh M Rachidi

    Full Text Available BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2 is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only

  7. Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features.

    Science.gov (United States)

    Rosty, Christophe; Young, Joanne P; Walsh, Michael D; Clendenning, Mark; Walters, Rhiannon J; Pearson, Sally; Pavluk, Erika; Nagler, Belinda; Pakenas, David; Jass, Jeremy R; Jenkins, Mark A; Win, Aung Ko; Southey, Melissa C; Parry, Susan; Hopper, John L; Giles, Graham G; Williamson, Elizabeth; English, Dallas R; Buchanan, Daniel D

    2013-06-01

    KRAS-mutated carcinomas comprise 35-40% of all colorectal carcinomas but little is known about their characteristics. The aim of this study was to examine the pathological and molecular features of KRAS-mutated colorectal carcinomas and to compare them with other carcinoma subgroups. KRAS mutation testing was performed in 776 incident tumors from the Melbourne Collaborative Cohort Study. O(6)-methylguanine DNA methyltransferase (MGMT) status was assessed using both immunohistochemistry and MethyLight techniques. Microsatellite instability (MSI) phenotype and BRAF V600E mutation status were derived from earlier studies. Mutation in KRAS codon 12 or codon 13 was present in 28% of colorectal carcinomas. Compared with KRAS wild-type carcinomas, KRAS-mutated carcinomas were more frequently observed in contiguity with a residual polyp (38 vs 21%; Pcarcinomas showed more frequent location in the proximal colon (41 vs 27%; P=0.001), mucinous differentiation (46 vs 25%; Pcarcinomas were distributed in a bimodal pattern along the proximal-distal axis of the colorectum. Compared with male subjects, female subjects were more likely to have KRAS-mutated carcinoma in the transverse colon and descending colon (39 vs 15%; P=0.02). No difference in overall survival was observed in patients according to their tumor KRAS mutation status. In summary, KRAS-mutated carcinomas frequently develop in contiguity with a residual polyp and show molecular features distinct from other colorectal carcinomas, in particular from tumors with neither BRAF nor KRAS mutation.

  8. Molecular targeted treatment and radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  9. Molecular targeted treatment and radiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marquardt, Friederike; Roedel, Franz; Capalbo, Gianni; Weiss, Christian; Roedel, Claus [Dept. of Radiation Therapy, Univ. of Frankfurt/Main (Germany)

    2009-06-15

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  10. Clinicopathological features and surgical safety of gastric cancer in elderly patients.

    Science.gov (United States)

    Lim, Joo Hyun; Lee, Dong Ho; Shin, Cheol Min; Kim, Nayoung; Park, Young Soo; Jung, Hyun Chae; Song, In Sung

    2014-12-01

    Gastric cancer is one of the most common cancers, especially among the elderly. However little is known about gastric cancer in elderly patients. This study was designed to evaluate the specific features of gastric cancer in elderly patients. Medical records of 1,107 patients who had radical gastrectomy for gastric cancer between June 2005 and December 2009 were reviewed. They were divided into young (CA 19-9 (5.6%, 13.4%, 14.6%, P=0.001), advanced diseases (42.5%, 47.0%, and 57.6, P=0.014), and node metastasis (37.6%, 38.9%, 51.5%, P=0.029) were more common in the young-old and old-old age groups. There were no significant differences in Helicobacter pylori status (63.6%, 56.7%, 61.2%, P=0.324) between the three groups. Surgery-related complication rates were similar in the three groups (5.3%, 5.1%, 8.1%, P=0.497). Microsatellite instability (Pcancer without significant risk of complications. However, considering the more advanced disease and synchronous tumors among the elderly, care should be taken while deciding the extent of surgery for elderly gastric cancer.

  11. Clinical features and prognosis of obese breast cancer patients:a retrospective study*

    Institute of Scientific and Technical Information of China (English)

    Zhendong Zheng; Heng Cao; Shuxian Qu; Yongye Liu; Ying Piao; Xiaodong Xie

    2013-01-01

    Objective:The aim of our study was to investigate the prognosis of obese breast cancer patients. Methods:This study was conducted on a total of 317 breast cancer patients who were histopathological y and clinical y diagnosed at the General Hospital of Shenyang Military Region (China) from 2004 to 2006. Clinical data including height, weight, age at diagnosis, tumor size, lymph node status, menopausal status, family history of cancer and hormone receptor status were col-lected. Log-rank test was performed to compare the disease free survival (DFS) and overal survival (OS). Cox proportional hazards regression analysis was conducted to make multivariate analysis. The Chi square test was used to compare the clinical features among normal weight group, overweight group, and obese group. Results:Obesity was an independent prognostic factor for DFS (P=0.022) and OS (P=0.032) in breast cancer patients. In the stratified analysis based on the hormone receptor status, obesity was independently associated with OS in patients with negative ER/PR (P=0.002), but such association was not observed in patients with positive hormone receptors. Obesity was also associated with lymph node status (P=0.001) and smoking (P=0.009). Conclusion:Obesity is associated with poor DFS and OS in patients with breast cancer. Therefore, maintaining normal weight may benefit breast cancer patients.

  12. Genomic Characterization of High-Grade Serous Ovarian Cancer: Dissecting Its Molecular Heterogeneity as a Road Towards Effective Therapeutic Strategies.

    Science.gov (United States)

    Mittempergher, Lorenza

    2016-07-01

    High-grade serous ovarian carcinoma (HGSOC) accounts for the majority of the ovarian cancer deaths, but over the last years little improvement in overall survival has been achieved. HGSOC is a molecularly and clinically heterogeneous disease. At genomic level, it represents a C-class malignancy having frequent gene losses (NF1, RB1, PTEN) and gains (CCNE1, MYC). HGSOC shows a simple mutational profile with TP53 nearly always mutated and with other genes mutated at low frequency. Importantly, 50 % of all HGSOCs have genetic features indicating a homologous recombination (HR) deficiency. HR deficient tumors are highly sensitive to PARP inhibitor anticancer agents, which exhibit synthetic lethality with a defective HR pathway. Transcriptionally, HGSOCs can be grouped into different molecular subtypes with distinct biology and prognosis. Molecular stratification of HGSOC based on these genomic features may result in improved therapeutic strategies. PMID:27241520

  13. 月经初潮年龄对中国女性乳腺癌临床病理特征及分子表型的影响%Influence of age at menarche on clinical pathological features and molecular phenotype in Chinese female breast cancer

    Institute of Scientific and Technical Information of China (English)

    孙刚; 王珂

    2015-01-01

    目的:探索中国女性月经初潮年龄对乳腺癌临床病理特征及分子表型的影响。方法:收集本院收治的女性乳腺癌临床资料共210例,按月经初潮年龄分为≤13岁组和>13岁组,采用卡方检验分别比较各组间临床病理特征及分子表型的差异。结果:月经初潮年龄越早(≤13岁),腋窝淋巴结转移几率越高,同时肿瘤分期越晚(P <0.05);初潮年龄越早,非 Luminal 型出现的比例越高(P <0.05)。结论:月经初潮越早,乳腺癌的恶性程度越高并且多呈现出非 Luminal 型的分子表型。%Objective:To investigate the influence of age at menarche on tumor clinical characteristics and molec-ular subtypes in Chinese females with breast cancer.Methods:The clinical findings of 2 1 0 Chinese females with breast cancer were divided into 2 groups:≤13 years old and >13 years old,then analyzed as age at menarche retro-spectively.Results:The age of menarche ≤13 years old was a higher risk factor of axillary lymph nodes metastasis, later TNMstaging and non -Luminal subtype than that of >13 years old(P <0.05).Conclusion:Earlier age at menarche might be related to higher grade malignancy,TNMstaging and appearance of non -Luminal subtype in Chi-nese females with breast cancer.

  14. Imaging and Clinical Features of Thyroid Cancer in Children and Adolescents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Young; Hong, HyunSook; Lee, Eun Hye; Yi, Beom Ha; Lee, Hae Kyung [Dept. of Radiology, Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheonl (Korea, Republic of); Lee, Yong Hwa [Dept. of Labortory Medicine and Genetics, Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheonl (Korea, Republic of); Koh, Eun Suk [Dept. of Pathology, Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheonl (Korea, Republic of)

    2011-08-15

    To evaluate clinical and imaging features of pediatric thyroid cancer, including BRAF'V{sup 600E} mutation status in papillary thyroid cancer (PTC). We evaluated clinical findings including BRAF''6{sup 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{sup 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.

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

    Science.gov (United States)

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

    2012-02-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  17. Book Review of "The Molecular Biology of Cancer" by Stella Pelengaris, Michael Khan (Editors

    Directory of Open Access Journals (Sweden)

    Schmidt Christian

    2007-11-01

    Full Text Available Abstract Here, a review of "The Molecular Biology of Cancer" (Stella Pelengaris and Michael Khan [Editors] is given. The detailed description of the book is provided here: Pelengaris S, Khan M (Eds: The Molecular Biology of Cancer; Blackwell Publishing, Oxford (U.K.; 2006. 531 pages, 214 illustrations, ISBN 9-78140-511-814-9, £31.99.

  18. Unveiling atomic-scale features of inherent heterogeneity in metallic glass by molecular dynamics simulations

    Science.gov (United States)

    Hu, Y. C.; Guan, P. F.; Li, M. Z.; Liu, C. T.; Yang, Y.; Bai, H. Y.; Wang, W. H.

    2016-06-01

    Heterogeneity is commonly believed to be intrinsic to metallic glasses (MGs). Nevertheless, how to distinguish and characterize the heterogeneity at the atomic level is still debated. Based on the extensive molecular dynamics simulations that combine isoconfigurational ensemble and atomic pinning methods, we directly reveal that MG contains flow units and the elastic matrix which can be well distinguished by their distinctive atomic-level responsiveness and mechanical performance. The microscopic features of the flow units, such as the shape, spatial distribution dimensionality, and correlation length, are characterized from atomic position analyses. Furthermore, the correlation between the flow units and the landscape of energy state, free volume, atomic-level stress, and especially the local bond orientational order parameter is discussed.

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

    Science.gov (United States)

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

    2014-10-01

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

  20. Molecular application of spectral photoacoustic imaging in pancreatic cancer pathology

    Science.gov (United States)

    Lakshman, Minalini; Hupple, Clinton; Lohse, Ines; Hedley, David; Needles, Andrew; Theodoropoulos, Catherine

    2012-12-01

    Spectral imaging is an advanced photo-acoustic (PA) mode that can discern optical absorption of contrast agent(s) in the tissue micro-environment. This advancement is made possible by precise control of optical wavelength using a tunable pulsed laser, ranging from 680-970 nm. Differential optical absorption of blood oxygenation states makes spectral imaging of hemoglobin ideal to investigate remodeling of the tumor microenvironment- a molecular change that renders resistance to standard cancer treatment. Approach: Photo-acoustic imaging was performed on the Vevo® LAZR system (VisualSonics) at 5-20 Hz. Deep abdominal imaging was accomplished with a LZ250D probe at a center frequency of 21MHz and an axial resolution of 75 μm. The tumor model was generated in an immune compromised mouse by surgical implantation of primary patient derived tumors, in the pancreas. Results: Spectral imaging for oxygen saturation at 750 nm and 850 nm characterized this tumor with a poorly oxygenated core surrounded by a well oxygenated periphery. Multispectral imaging identified a sub region in the core with a four-fold signal exclusively at 750 and 800 nm. A co-registered 2D image of this region was shown to be echogenic and calcification was suspected. Perfusion imaging with contrast enhanced ultrasound using microbubbles (Vevo MicroMarker® contrast agents, VisualSonics) identified functional vessels towards this sub region. Histology confirmed calcification and vascularization in the tumor core. Taken together, non-invasive characterization of the tumor microenvironment using photo-acoustics rendered spectral imaging a sensitive tool to monitor molecular changes representative of progression of pancreatic cancer that kills within 6 months of diagnosis.

  1. Molecular advances to treat cancer of the brain.

    Science.gov (United States)

    Fathallah-Shaykh, H M; Zhao, L J; Mickey, B; Kafrouni, A I

    2000-06-01

    Malignant primary and metastatic brain tumours continue to be associated with poor prognosis. Nevertheless, recent advances in molecular medicine, specifically in the strategies of gene therapy, targeting tumour cells, anti-angiogenesis and immunotherapy, have created novel tools that may be of therapeutic value. To date, gene therapy trials have not yet demonstrated clinical efficacy because of inherent defects in vector design. Despite this, advances in adenoviral technology, namely the helper-dependent adenoviral constructs (gutless) and the uncovering of brain parenchymal cells as effective and necessary targets for antitumour benefits of adenoviral-mediated gene transfer, suggest that developments in vector design may be approaching the point of clinical utility. Targeting tumour cells refers to strategies that destroy malignant but spare normal cells. A new assortment of oncolytic viruses have emerged, capable of specific lysis of cancer tissue while sparing normal cells and propagating until they reach the tumour borders. Furthermore, peptides have been transformed into bullets that specifically seek and destroy cancer cells. The concept of tumour angiogenesis has been challenged by new but still very controversial findings that tumour cells themselves may form blood channels. These results may lead to the redirecting of the molecular targets toward anti-angiogenesis in some tumours including glioblastoma multiform. Unfortunately, our knowledge regarding the immunological ignorance of the tumour is still limited. Even so, newly discovered molecules have shed light on novel pathways leading to the escape of the tumour from the immune system. Finally, significant limitations in our current experimental tumour models may soon be overcome by firstly, the development of models of reproducible organ-specific tumours in non-inbred animals and secondly applying genomics to individualize therapy for a particular tumour in a specific patient.

  2. 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 fluoresc

  3. Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer

    OpenAIRE

    Wu, Xueming; Burden-Gulley, Susan M.; Yu, Guan-Ping; Tan, Mingqian; Lindner, Daniel; Brady-Kalnay, Susann M.; Lu, Zheng-Rong

    2012-01-01

    Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecula...

  4. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Directory of Open Access Journals (Sweden)

    Maria Victoria Maliandi

    2011-01-01

    Full Text Available The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  5. Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran

    Directory of Open Access Journals (Sweden)

    Geramizadeh

    2015-10-01

    Full Text Available Context Colorectal cancer is one of the most common cancers worldwide (the third most common cancer in the world and is especially more common in Western countries; however, its incidence has been increased significantly during the last few years in Eastern countries such as Iran and considered as one of the five common cancers in this country. According to molecular pathways, numerous biomarkers have been identified for colorectal cancers which help patients’ management. Evidence aquisition In this study, we tried to review published articles about the molecular biomarkers of colorectal cancer from Iran. We searched medical databases such as google scholar, Scopus, PubMed, Magiran, SID and Iran Medex for keywords of “colon cancer, KRAS, BRAF, mismatch repair gene, Microsatellite instability, molecular genetics, molecular pathogenesis, biomarker and Iran” to find studies published about colorectal cancers from Iran regarding molecular biomarkers. Conclusion This study showed that molecular biomarkers in colorectal cancer of Iranian patients are not so different from Western population.

  6. MOLECULAR GENETIC MARKERS AS PREDICTORS OF SUPERFICIAL BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Babayan

    2009-01-01

    Full Text Available A system of clinical and morphological criteria is currently used to determine the pattern of superficial bladder cancer (SBC. However, this system does not completely reflect the clinical potential of SBC and needs additional markers. The purpose of this study was to search for and evaluate molecular genetic disorders as additional markers of the course of SBC. The diagnostic panel included the deletion of the loci 3р14, 9р21, 9q34, 17р13 (ТР53, mutations of exon 7 of the FGFR3 gene, and hypermethylation of the promoter regions of the RASSF1, RARB, p16, p14, CDH1 genes. The study was made on 108 matched samples (tumor/peripheral blood obtained from patients with SBC. The deletions of the loci 3р14, 9р21 and anomalous methylation of the RARb and p16 genes are markers of the worse course of SBC while FGFR3 gene mutation is a marker of better prognosis. In the context of estimation of the relapsing potential of a primary tumor, the 9p21 locus deletion is a marker associated with recurrence within the first year after malignancy resection. The group of molecular genetic markers determined by the authors for poor prognosis in combination with classical clinical and morphological criteria will specify the pattern of the course of the disease and its prognosis.

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

    OpenAIRE

    Sakorafas, George H; 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...

  8. Exploring the role of molecular biomarkers as a potential weapon against gastric cancer: A review of the literature

    Science.gov (United States)

    Matboli, Marwa; El-Nakeep, Sarah; Hossam, Nourhan; Habieb, Alaa; Azazy, Ahmed E M; Ebrahim, Ali E; Nagy, Ziad; Abdel-Rahman, Omar

    2016-01-01

    Gastric cancer (GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging II-IV. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.

  9. Exploring the role of molecular biomarkers as a potential weapon against gastric cancer: A review of the literature.

    Science.gov (United States)

    Matboli, Marwa; El-Nakeep, Sarah; Hossam, Nourhan; Habieb, Alaa; Azazy, Ahmed E M; Ebrahim, Ali E; Nagy, Ziad; Abdel-Rahman, Omar

    2016-07-14

    Gastric cancer (GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging II-IV. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management. PMID:27468184

  10. The Morphologic Features and Accuracy of Preoperative T-Staging in Resected Gallbladder Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Ehn; Kim, Mi Young; Kim, Jong Bum; Kim, Youn Jeong; Kang, Young Hye; Suh, Chang Hae [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of); Lee, Kun Yong [Dept. of General Surgery, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of); Cho, Suk Jin [Dept. of Pathology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2012-04-15

    To assess the morphological features and the accuracy of T staging images in surgically- proven gallbladder cancers, retrospectively. Images of 59 surgically-proven gallbladder cancers were reviewed. Morphologic features, shape, size of tumors and the presence of stones or sludge within the images were evaluated and correlated with surgicopathologic findings. Polypoid masses were shown in 49 cases (83%). The sizes of tumors were well correlated with surgicopathologic T-stage. With ROC evaluation, the size cutoff point to differentiate the {<=} T1 versus {>=} T2 lesions was 2.4 cm. Stones or sludge were found in 25 cases (42%). The positive predictive value, negative predictive value, sensitivities, specificities, and accuracy of the ability to differentiate the {<=} T1 versus {>=} T2 lesions were 75%, 86%, 46%, 96%, 85% and those of the ability to differentiate {<=} T2 versus {>=} T3 lesions were 89%, 49%, 45%, 90%, and 61%, respectively. Image analysis showed that polypoid mass and wall thickening were major findings. With this in mind, polypoid mass shows the possibility of gallbladder cancer originating from adenoma, even if the size is larger than 2 or 2.4 cm, the surgicopathologic stage could be low. Moreover, the accuracy of image based T stage on pericholecystic infiltration and wall thickening was low.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2015-03-01

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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    George H Sakorafas

    2012-07-01

    Full Text Available 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 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. Results 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. Conclusion 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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

    2011-01-01

    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 ...

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

    Science.gov (United States)

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

    2016-06-01

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

  19. Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer

    OpenAIRE

    Jonathan Ma; Sadhika Malladi; Beck, Andrew H.

    2016-01-01

    Though patient sex influences response to cancer treatments, little is known of the molecular causes, and cancer therapies are generally given irrespective of patient sex. We assessed transcriptomic differences in tumors from men and women spanning 17 cancer types, and we assessed differential expression between tumor and normal samples stratified by sex across 7 cancers. We used the LincsCloud platform to perform Connectivity Map analyses to link transcriptomic signatures identified in male ...

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

    International Nuclear Information System (INIS)

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

  1. Breast Cancer with Neoductgenesis: Histopathological Criteria and Its Correlation with Mammographic and Tumour Features

    Directory of Open Access Journals (Sweden)

    Wenjing Zhou

    2014-01-01

    Full Text Available Introduction. Breast cancer with mammographic casting type calcifications, high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction, lymphocyte infiltration, and tenascin-C (TN-C overexpression has been proposed to represent a more aggressive form of breast cancer and has been denominated as breast cancer with neoductgenesis. We developed histopathological criteria for neoductgenesis in order to study reproducibility and correlation with other tumour markers. Methods. 74 cases of grades 2 and 3 DCIS, with or without an invasive component, were selected. A combined score of the degree(s of concentration of ducts, lymphocyte infiltration, and periductal fibrosis was used to classify cases as showing neoductgenesis, or not. Diagnostic reproducibility, correlation with tumour markers, and mammographic features were studied. Results. Twenty-three of 74 cases were diagnosed with neoductgenesis. The kappa value between pathologists showed moderate reproducibility (0.50 (95% CI; 0.41–0.60. Neoductgenesis correlated significantly with malignant type microcalcifications and TN-C expression (P=0.008 and 0.04 and with ER, PR, and HER2 status (P<0.00001 for all three markers. Conclusions. We developed histological criteria for breast cancer with neoductgenesis. Neoductgenesis, by our applied histopathological definition was related to more aggressive tumour biology and malignant mammographic calcifications.

  2. Molecular voting for glioma classification reflecting heterogeneity in the continuum of cancer progression.

    Science.gov (United States)

    Fuller, Gregory N; Mircean, Cristian; Tabus, Ioan; Taylor, Ellen; Sawaya, Raymond; Bruner, Janet M; Shmulevich, Ilya; Zhang, Wei

    2005-09-01

    Gliomas, the most common brain tumors, are generally categorized into two lineages (astrocytic and oligodendrocytic) and further classified as low-grade (astrocytoma and oligodendroglioma), mid-grade (anaplastic astrocytoma and anaplastic oligodendroglioma), and high-grade (glioblastoma multiforme) based on morphological features. A strict classification scheme has limitations because a specific glioma can be at any stage of the continuum of cancer progression and may contain mixed features. Thus, a more comprehensive classification based on molecular signatures may reflect the biological nature of specific tumors more accurately. In this study, we used microarray technology to profile the gene expression of 49 human brain tumors and applied the k-nearest neighbor algorithm for classification. We first trained the classification gene set with 19 of the most typical glioma cases and selected a set of genes that provide the lowest cross-validation classification error with k=5. We then applied this gene set to the 30 remaining cases, including several that do not belong to gliomas such as atypical meningioma. The results showed that not only does the algorithm correctly classify most of the gliomas, but the detailed voting results also provide more subtle information regarding the molecular similarities to neighboring classes. For atypical meningioma, the voting was equally split among the four classes, indicating a difficulty in placement of meningioma into the four classes of gliomas. Thus, the actual voting results, which are typically used only to decide the winning class label in k-nearest neighbor algorithms, provide a useful method for gaining deeper insight into the stage of a tumor in the continuum of cancer development.

  3. Molecular approach to genetic and epigenetic pathogenesisof early-onset colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancertype and the incidence of this disease is increasinggradually per year in individuals younger than 50 yearsold. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population thatincludes both hereditary and sporadic forms of theCRC. Although EOCRC cases have some distinguishingclinical and pathological features than elder age CRC,the molecular mechanism underlying the EOCRC ispoorly clarified. Given the significance of CRC in theworld of medicine, the present review will focus on therecent knowledge in the molecular basis of genetic andepigenetic mechanism of the hereditary forms of EOCRC,which includes Lynch syndrome, Familial CRC type X,Familial adenomatous polyposis, MutYH-associatedpolyposis, Juvenile polyposis syndrome, Peutz-JeghersSyndrome and sporadic forms of EOCRC. Recent findingsabout molecular genetics and epigenetic basis of EOCRCgave rise to new alternative therapy protocols. Althoughexact diagnosis of these cases still remains complicated,the present review paves way for better predictions andcontributes to more accurate diagnostic and therapeuticstrategies into clinical approach.

  4. Molecular markers in prostate cancer.Part I:predicting lethality

    Institute of Scientific and Technical Information of China (English)

    Sachin Agrawal; William D.Dunsmuir

    2009-01-01

    Assessing the lethality of 'early,' potentially organ-confined prostate cancer (PCa) is one of the central controversies in moderu-day urological clinical practice.Such cases are often considered for radical 'curative' treatment,although active surveillance may be equally appropriate for many men.Moreover,the balance between judicious intervention and overtreatment can be difficult to judge.The patient's age,comorbidities,family history and philosophy of self-health care can be weighed against clinical features such as the palpability of disease,the number and percentage of biopsy cores involved with the disease,histological grade,presenting prostate-specific antigen (PSA) and possible previous PSA kinetics.For many years,scientists and physicians have sought additional molecular factors that may be predictive for disease stage,progression and lethality.Usually,claims for a 'new' unique marker fall short of true clinical value.More often than not,such molecular markers are useful only in multivariate models.This review summarizes relevant molecular markers and models reported up to and including 2008.

  5. Comparison of MRI of liver cancer (preoperative and resected liver specimen) and pathological feature

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Toshihiko (Kurume Univ., Fukuoka (Japan). School of Medicine)

    1990-10-01

    Twenty-one nodules of hepatocellular carcinoma (HCC) and eighteen nodules of liver metastasis, which were confirmed pathologically, were investigated by MRI before operation and MRI of resected liver specimen. Pre-operative MRI pointed out all HCCs and seventeen metastases. STIR method was most useful for detection of HCCs. T2WI and STIR method were most useful for detection of liver metastases. Pre-operative MRI also revealed 93% of capsule formation, 29% of septal formation, 75% of fatty metamorphosis of HCC and 75% of necrosis of liver metastasis, and post-operative MRI of resected specimens revealed 100% of capsule formation, 71% of septal formation, 75% of fatty metamorphosis of HCC and 88% of necrosis of liver metastasis. T1WI showed a high intensity halo surrounding metastasis. This characteristic peripheral halo was seen in 22% of metastases. These findings corresponded to pathological feature of liver cancer. MRI was thought to be useful diagnostic modality of liver cancer. (author).

  6. Beyond breast cancer: mammographic features and mortality risk in a population of healthy women.

    Directory of Open Access Journals (Sweden)

    Rachel A Murphy

    Full Text Available BACKGROUND: Breast fibroglandular (dense tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features. METHODS: We evaluated relationships between nondense (fatty breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs and 95% confidence intervals (CIs were estimated by Cox proportional hazards regression. RESULTS: In age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference. Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram, smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference. CONCLUSIONS: These data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk.

  7. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

    International Nuclear Information System (INIS)

    Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features. In 40 cases of invasive breast cancer, BNIP3 mRNA in situ hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α) and its downstream targets Glucose Transporter 1 (Glut-1) and Carbonic Anhydrase (CAIX) by immunohistochemistry. BNIP3 mRNA was expressed in 16/40 (40%) of the cases and correlated with BNIP3 protein expression (p = 0.0218). Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010) and showed a higher mitotic activity index (p = 0.027). BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells. BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response

  8. Correlation of primary tumor FDG uptake with histopathologic features of advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Won; Won, Kyoung Sook; Song, Bong Il; Kang, Yu Na [Keimyung University Dongsan Medical Center, Daegu (Korea, Republic of)

    2015-06-15

    Histopathologic features could affect the FDG uptake of primary gastric cancer and detection rate on FDG PET/CT. The aim of this study was to evaluate the FDG uptake of primary gastric cancer by correlating it with the histopathologic features of the tumors. Fifty patients with locally advanced gastric adenocarcinoma who were referred for preoperative FDG-PET/CT scans were enrolled in this study. The detection rate of PET/CT and maximum standardized uptake values (SUV{sub max}) of the primary tumor were compared using the WHO, Lauren, Ming and Borrmann classifications and tumor size and location. In 45 of the 50 patients (90 %), the primary gastric tumors were detected by FDG PET/CT. On comparison using the WHO classification, the detection rate and SUV{sub max} of the tubular type were significantly higher than those of the poorly cohesive type. On comparison using the Lauren and Ming classifications, the SUV{sub maxs} of the intestinal type and expanding type were significantly higher than those of the diffuse and infiltrative type, respectively. On comparison using the Borrmann classification and tumor size and location, there was no significant difference in the detection rate and SUV{sub max} of primary gastric tumors. This study demonstrates that the poorly cohesive type according to the WHO classification, diffuse type according to the Lauren classification and infiltrative type according to the Ming classification have low FDG uptake in patients with locally advanced gastric carcinoma. Understanding the relationship between primary tumor FDG uptake and histopathologic features would be helpful in detecting the primary tumor by FDG PET/CT in patients with gastric cancer.

  9. Features of exciton dynamics in molecular nanoclusters (J-aggregates): Exciton self-trapping (Review Article)

    Science.gov (United States)

    Malyukin, Yu. V.; Sorokin, A. V.; Semynozhenko, V. P.

    2016-06-01

    We present thoroughly analyzed experimental results that demonstrate the anomalous manifestation of the exciton self-trapping effect, which is already well-known in bulk crystals, in ordered molecular nanoclusters called J-aggregates. Weakly-coupled one-dimensional (1D) molecular chains are the main structural feature of J-aggregates, wherein the electron excitations are manifested as 1D Frenkel excitons. According to the continuum theory of Rashba-Toyozawa, J-aggregates can have only self-trapped excitons, because 1D excitons must adhere to barrier-free self-trapping at any exciton-phonon coupling constant g = ɛLR/2β, wherein ɛLR is the lattice relaxation energy, and 2β is the half-width of the exciton band. In contrast, very often only the luminescence of free, mobile excitons would manifest in experiments involving J-aggregates. Using the Urbach rule in order to analyze the low-frequency region of the low-temperature exciton absorption spectra has shown that J-aggregates can have both a weak (g 1) exciton-phonon coupling. Moreover, it is experimentally demonstrated that under certain conditions, the J-aggregate excited state can have both free and self-trapped excitons, i.e., we establish the existence of a self-trapping barrier for 1D Frenkel excitons. We demonstrate and analyze the reasons behind the anomalous existence of both free and self-trapped excitons in J-aggregates, and demonstrate how exciton-self trapping efficiency can be managed in J-aggregates by varying the values of g, which is fundamentally impossible in bulk crystals. We discuss how the exciton-self trapping phenomenon can be used as an alternate interpretation of the wide band emission of some J-aggregates, which has thus far been explained by the strongly localized exciton model.

  10. Oral cancer: Deregulated molecular events and their use as biomarkers.

    Science.gov (United States)

    Sinevici, Nicoleta; O'sullivan, Jeff

    2016-10-01

    Oral Cancer (OC) is a subset of head and neck cancer (HNC) with an annual worldwide incidence of 275,000 cases. OC remains a significant burden worldwide in terms of diagnosis, treatment and prognosis. Despite desirable outcomes in early diagnosed OCs and treatment advances most OCs are detected in advanced stages. The 5-year survival rate of early-stage disease is ∼80% and that of late-stage disease is only ∼20%. Recurrence and chemoresistance from a treatment point of view and pain and disfiguration are important factors contributing to the high morbidity and mortality of OC. Furthermore the process of oral carcinogenesis is complex and not yet fully understood. Consequently numerous potential biomarkers have been hypothesised though controversial results across the board hamper their clinical implementation. Of greatest advantage would be biomarkers signalling early events preceeding OC. Biomarker targets predominately involve deregulated molecular events that participate in cell signalling, growth, survival, motility, angiogenesis and cell cycle control but can also use changes in metabolic genes to discriminate healthy form disease state. Promising potential biomarkers include the growth signalling oncogenes, Epidermal Growth Factor Receptor and Cyclin D1, the anti-growth signalling components p53 and p21, apoptotic effectors such as Bcl-2 and also components involved in immortalisation, angiogenesis, invasion and metastasis processes. Translation of these potential biomakers to the patients is closer than ever though few issues remain to be resolved. Firstly large clinical trials are needed to validate their clinical applicability but also standardised methods of collection, storage and processing methods are needed to minimise variability. PMID:27688099

  11. Evaluating stability of histomorphometric features across scanner and staining variations: predicting biochemical recurrence from prostate cancer whole slide images

    Science.gov (United States)

    Leo, Patrick; Lee, George; Madabhushi, Anant

    2016-03-01

    Quantitative histomorphometry (QH) is the process of computerized extraction of features from digitized tissue slide images. Typically these features are used in machine learning classifiers to predict disease presence, behavior and outcome. Successful robust classifiers require features that both discriminate between classes of interest and are stable across data from multiple sites. Feature stability may be compromised by variation in slide staining and scanning procedures. These laboratory specific variables include dye batch, slice thickness and the whole slide scanner used to digitize the slide. The key therefore is to be able to identify features that are not only discriminating between the classes of interest (e.g. cancer and non-cancer or biochemical recurrence and non- recurrence) but also features that will not wildly fluctuate on slides representing the same tissue class but from across multiple different labs and sites. While there has been some recent efforts at understanding feature stability in the context of radiomics applications (i.e. feature analysis of radiographic images), relatively few attempts have been made at studying the trade-off between feature stability and discriminability for histomorphometric and digital pathology applications. In this paper we present two new measures, preparation-induced instability score (PI) and latent instability score (LI), to quantify feature instability across and within datasets. Dividing PI by LI yields a ratio for how often a feature for a specific tissue class (e.g. low grade prostate cancer) is different between datasets from different sites versus what would be expected from random chance alone. Using this ratio we seek to quantify feature vulnerability to variations in slide preparation and digitization. Since our goal is to identify stable QH features we evaluate these features for their stability and thus inclusion in machine learning based classifiers in a use case involving prostate cancer

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

    Directory of Open Access Journals (Sweden)

    Chellamuthu Gunavathi

    2014-01-01

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

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

    Science.gov (United States)

    Gunavathi, Chellamuthu; Premalatha, Kandasamy

    2014-01-01

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

  14. Physiological and Molecular Features of Puccinellia tenuiflora Tolerating Salt and Alkaline-Salt Stress

    Institute of Scientific and Technical Information of China (English)

    Xia Zhang; Liqin Wei; Zizhang Wang; Tai Wang

    2013-01-01

    Saline-alkali soil seriously threatens agriculture productivity; therefore,understanding the mechanism of plant tolerance to alkaline-salt stress has become a major challenge.Halophytic Puccinellia tenuiflora can tolerate salt and alkaline-salt stress,and is thus an ideal plant for studying this tolerance mechanism.In this study,we examined the salt and alkaline-salt stress tolerance of P.tenuiflora,and analyzed gene expression profiles under these stresses.Physiological experiments revealed that P.tenuiflora can grow normally with maximum stress under 600 mmol/L NaCl and 150 mmol/L Na2CO3 (pH 11.0)for 6 d.We identified 4,982 unigenes closely homologous to rice and barley.Furthermore,1,105 genes showed differentially expressed profiles under salt and alkaline-salt treatments.Differentially expressed genes were overrepresented in functions of photosynthesis,oxidation reduction,signal transduction,and transcription regulation.Almost all genes downregulated under salt and alkaline-salt stress were related to cell structure,photosynthesis,and protein synthesis.Comparing with salt stress,alkaline-salt stress triggered more differentially expressed genes and significantly upregulated genes related to H+ transport and citric acid synthesis.These data indicate common and diverse features of salt and alkalinesalt stress tolerance,and give novel insights into the molecular and physiological mechanisms of plant salt and alkaline-salt tolerance.

  15. 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

  16. Bases moleculares de la cancerización de cavidad oral Molecular basis on oral cavity cancerization

    Directory of Open Access Journals (Sweden)

    M.A. González-Moles

    2008-02-01

    Full Text Available Se presenta una revisión bibliográfica breve sobre los principales aspectos moleculares de interés en la cancerización de cavidad oral. Se hace referencia a los conocimientos más recientes sobre las aberraciones cromosómicas más comunes y las alteraciones de los oncogenes y genes supresores tumorales que están implicados en la carcinogénesis oral. Así mismo, se resume la teoría molecular actual que explica el proceso de cancerización de campo.A review about the main molecular aspects on oral cavity cancerization is presented, with special reference to the common chromosomal aberration, oncogenes and tumour suppressor genes implied in oral carcinogenesis. A summary about molecular theory explaining the field cancerization process is also presented.

  17. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

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

    Science.gov (United States)

    Xi, Maolong; 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Mohammad Subhi Al-batah

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  2. Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview.

    Science.gov (United States)

    Zhao, Ming; He, Xiang-Lei; Teng, Xiao-Dong

    2016-02-01

    The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.

  3. Comparative Analysis of Clinical Features of Lung Cancer in West China Hospital in 2000 and 2010

    Directory of Open Access Journals (Sweden)

    Xiaojun YAO

    2012-06-01

    Full Text Available Background and objective Primary lung cancer is one of the most common malignant tumors. The aim of the current study is to retrospectively analyze the clinical features variation of patients with primary bronchogenic carcinoma in West China Hospital Sichuan University to provide information for early detection and treatment of lung cancer. Methods We collected data of patients of permanent population in Sichuan province who diagnosed primary bronchogenic carcinoma in 2000 and 2010 in West China Hospital Sichuan University respectively for comparative analysis of reasons to visit the doctor, duration from symptom onset to visit the doctor, combined diseases, incidences of bi-primary carcinoma, family history of malignant tumor, sites of tumors, grade of differentiation, tumor staging and initial treatment modalities. Results A total of 2,167 cases (616 cases in 2000 and 1,551 cases in 2010 met inclusion criteria were retrieved for analysis. In 2010, compared with data of 2000, the rate of patients who visit the doctors because abnormalities were detected by health examination elevated remarkably (5.2% vs 16.7%, P<0.001, the duration from symptom onset to visit the doctor abridged significantly (P<0.001, patients with family history of malignant tumor increased significantly (3.9% vs 13.7%, P<0.001, the constituent ratio of poorly differentiated adenocarcinoma decreased (72.3% vs 51.8%, P=0.002 accompanied with low differentiated squamous cell carcinoma increased (59.4% vs 76.7%, P=0.002. For NSCLC staging, there is a notably increase of rate of stage Ia (1.0% vs 4.5%, P< 0.001 and stage IV (30.4% vs 37.8%, P<0.001 while decrease of stage IIIa (26.6% vs 14.8%, P=0.002. For initial treatment modalities, there is markedly increased chemotherapy rate of non-small cell lung cancer (NSCLC patients (41.8% vs 63.4%, P=0.002 while remarkably increased surgery rate of stage IIIa patients (41.8% vs 63.4%, P=0.002 and decreased surgery rate of stage IV

  4. Automated oral cancer identification using histopathological images: a hybrid feature extraction paradigm.

    Science.gov (United States)

    Krishnan, M Muthu Rama; Venkatraghavan, Vikram; Acharya, U Rajendra; Pal, Mousumi; Paul, Ranjan Rashmi; Min, Lim Choo; Ray, Ajoy Kumar; Chatterjee, Jyotirmoy; Chakraborty, Chandan

    2012-02-01

    Oral cancer (OC) is the sixth most common cancer in the world. In India it is the most common malignant neoplasm. Histopathological images have widely been used in the differential diagnosis of normal, oral precancerous (oral sub-mucous fibrosis (OSF)) and cancer lesions. However, this technique is limited by subjective interpretations and less accurate diagnosis. The objective of this work is to improve the classification accuracy based on textural features in the development of a computer assisted screening of OSF. The approach introduced here is to grade the histopathological tissue sections into normal, OSF without Dysplasia (OSFWD) and OSF with Dysplasia (OSFD), which would help the oral onco-pathologists to screen the subjects rapidly. The biopsy sections are stained with H&E. The optical density of the pixels in the light microscopic images is recorded and represented as matrix quantized as integers from 0 to 255 for each fundamental color (Red, Green, Blue), resulting in a M×N×3 matrix of integers. Depending on either normal or OSF condition, the image has various granular structures which are self similar patterns at different scales termed "texture". We have extracted these textural changes using Higher Order Spectra (HOS), Local Binary Pattern (LBP), and Laws Texture Energy (LTE) from the histopathological images (normal, OSFWD and OSFD). These feature vectors were fed to five different classifiers: Decision Tree (DT), Sugeno Fuzzy, Gaussian Mixture Model (GMM), K-Nearest Neighbor (K-NN), Radial Basis Probabilistic Neural Network (RBPNN) to select the best classifier. Our results show that combination of texture and HOS features coupled with Fuzzy classifier resulted in 95.7% accuracy, sensitivity and specificity of 94.5% and 98.8% respectively. Finally, we have proposed a novel integrated index called Oral Malignancy Index (OMI) using the HOS, LBP, LTE features, to diagnose benign or malignant tissues using just one number. We hope that this OMI can

  5. Molecular genetic, diagnosis, prevention and gene therapy in prostatic cancer: review article

    Directory of Open Access Journals (Sweden)

    Noori Daloii MR

    2009-04-01

    Full Text Available "nThe prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer, and also the second leading cause of cancer death (after lung cancer among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

  6. Finding Combination of Features from Promoter Regions for Ovarian Cancer-related Gene Group Classification

    KAUST Repository

    Olayan, Rawan S.

    2012-12-01

    In classification problems, it is always important to use the suitable combination of features that will be employed by classifiers. Generating the right combination of features usually results in good classifiers. In the situation when the problem is not well understood, data items are usually described by many features in the hope that some of these may be the relevant or most relevant ones. In this study, we focus on one such problem related to genes implicated in ovarian cancer (OC). We try to recognize two important OC-related gene groups: oncogenes, which support the development and progression of OC, and oncosuppressors, which oppose such tendencies. For this, we use the properties of promoters of these genes. We identified potential “regulatory features” that characterize OC-related oncogenes and oncosuppressors promoters. In our study, we used 211 oncogenes and 39 oncosuppressors. For these, we identified 538 characteristic sequence motifs from their promoters. Promoters are annotated by these motifs and derived feature vectors used to develop classification models. We made a comparison of a number of classification models in their ability to distinguish oncogenes from oncosuppressors. Based on 10-fold cross-validation, the resultant model was able to separate the two classes with sensitivity of 96% and specificity of 100% with the complete set of features. Moreover, we developed another recognition model where we attempted to distinguish oncogenes and oncosuppressors as one group from other OC-related genes. That model achieved accuracy of 82%. We believe that the results of this study will help in discovering other OC-related oncogenes and oncosuppressors not identified as yet.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiazhou; Zhao, Kuaike; Peng, Jiayuan; Xie, Jiang; Chen, Junchao; Zhang, Zhen; Hu, Weigang, E-mail: jackhuwg@gmail.com [Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Jin, Xiance [The 1st Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000 (China); Studenski, Matthew [Department of Radiation Oncology, University of Miami-Miller School of Medicine, Miami, Florida 33136 (United States)

    2015-02-15

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

  8. [Venous thrombo-embolic disease in cancer. Low molecular weight heparin indications].

    Science.gov (United States)

    Nou, M; Laroche, J-P

    2016-05-01

    Cancer and venous thrombo-embolic disease (VTE) are closely related. Indeed, cancer can reveal VTE and VTE can be the first sign of cancer. Low molecular weight heparin (LWMH) is now the first line treatment in cancer patients. Compliance with marketing authorizations and guidelines are crucial for patient-centered decision-making. This work deals with the prescription of LWMH in patients who develop VTE during cancer in order to better recognize what should or should not be done. The patient's wishes must be taken into consideration when making the final therapeutic decision. The other treatments are discussed: vitamin K antagonists and direct oral anticoagulants (DOACs) may be useful. PMID:27146099

  9. Cancer Research from Molecular Discovery to Global Health

    Science.gov (United States)

    A science writers' seminar to discuss the latest research in cancer genetics and global health efforts, including talks from leaders of NCI’s new centers of cancer genomics and global health will be held Dec. 13, 2011, at NCI.

  10. Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years

    Science.gov (United States)

    Hong, Ji Hyung; Ha, Kyung Sun; Jung, Yun Hwa; Won, Hye Sung; An, Ho Jung; Lee, Guk Jin; Kang, Donghoon; Park, Ji Chan; Park, Sarah; Byun, Jae Ho; Suh, Young Jin; Kim, Jeong Soo; Park, Woo Chan; Jung, Sang Seol; Park, Il Young; Chung, Su-Mi; Woo, In Sook

    2016-01-01

    Purpose Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. Materials and Methods Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. Results Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. Conclusion Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted

  11. Molecular biomarker set for early detection of ovarian cancer

    KAUST Repository

    Bajic, Vladimir B.

    2015-06-16

    Embodiments of the present invention concern methods and compositions related to detection of ovarian cancer, including detection of the stage of ovarian cancer, in some cases. In particular, the invention encompasses use of expression of TFAP2A and in some embodiments CA125 and/or E2F5 to identify ovarian cancer, including detecting mRNA and/or protein levels of the respective gene products. Kits for detection of ovarian cancer are also described.

  12. Molecular Diagnosis for Personalized Target Therapy in Gastric Cancer

    OpenAIRE

    Cho, Jae Yong

    2013-01-01

    Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathway...

  13. A good molecular target for prostate cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Sidney R Grimes

    2011-01-01

    @@ An exciting new basic medical research study shows that inhibition of the activity of the kinesin spindle protein Eg5 effectively blocks cell division and induces cell death in prostate cancer cells.1 The potent anticancer drug S-(methoxytrityl)-L-cysteine(S(MeO)TLC)spe-cifically blocks activity of Eg5 in prostate cancer cells, arrests cell division, induces cell death during mitosis and inhibits prostate cancer cells in a mouse model of prostate cancer.

  14. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    OpenAIRE

    Bruna Karina Banin Hirata; Julie Massayo Maeda Oda; Roberta Losi Guembarovski; Carolina Batista Ariza; Carlos Eduardo Coral de Oliveira; Maria Angelica Ehara Watanabe

    2014-01-01

    Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical m...

  15. Lipocalin 2 expression is associated with aggressive features of endometrial cancer

    International Nuclear Information System (INIS)

    . Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer

  16. Relationship between COX-2 expression and clinicopathological features of colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    詹俊; 刘建平; 朱兆华; 姚和瑞; 陈春燕

    2004-01-01

    Background Cyclo-oxgenase 2 (COX-2) is involved in prostaglandin synthesis in central nervous system, and it also plays a role in human carcinogenesis. Our purpose of this study is to investigate the COX-2 expression in different development stages of colorectal cancer, and to discuss the relationship between the gene expression and clinicopathological features of the cancer.Methods COX-2 expression was examined by immunohistochemical staining in 76 surgical specimens of colorectal cancer (44 of advanced stage and 32 of early stage), thirty-three adenomas and 18 normal colonic mucosal tissues taken by endoscopic biopsy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to evaluate the relation of COX-2 to prognosis.Results COX-2 expression, divided into 4 grades from "-" to"+++", is respectively 83.3%, 16.7%, 0% and 0% in normal colonic mucosal tissues; 12.1%, 42.4%, 36.4% and 9.1% in adenomas; 6.3%, 28.1%, 46.9% and 18.7% in early colorectal cancers (ECCs), and 6.8%, 20.5%, 18.2% and 54.5% in advanced colorectal cancers (CRCs). The differences in COX-2 expression between advanced CRCs and early colorectal cancers (ECCs) as well as between the advanced CRCs and adenomas were statistically significant (P<0.01); but there was no significant difference between ECCs and adenomas. Kaplan-Meier survival analysis showed a significant difference in the survival curves between low high COX-2 groups (P<0.05). Cox proportional hazards regression showed that COX-2 expression was related to poorer long-term outcome with a hazard ratio of 2.665 unadjusted for other variables (P<0.05), and COX-2 expression was an independent risk factor of poor prognosis.Conclusions COX-2 expression is gradually up-regulated in the development from normal epithelium to adenomas and from ECCs to advanced CRCs. Alhough the COX-2 protein can not be regarded as a tumor marker to diagnose CRCs early, COX-2 expression can be regarded as an independent risk factor of poor

  17. Study of the Molecular Recognition of Aptamers Selected through Ovarian Cancer Cell-SELEX

    OpenAIRE

    Dimitri Van Simaeys; Dalia López-Colón; Kwame Sefah; Rebecca Sutphen; Elizabeth Jimenez; Weihong Tan

    2010-01-01

    BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy, and the ovarian clear cell carcinoma subtype (OCCA) demonstrates a particularly poor response to standard treatment. Improvements in ovarian cancer outcomes, especially for OCCA, could be expected from a clearer understanding of the molecular pathology that might guide strategies for earlier diagnosis and more effective treatment. METHODOLOGY/PRINCIPAL FINDINGS: Cell-SELEX technology was employed to develop new molecular ...

  18. Characterization of molecular subtypes of Korean breast cancer: An ethnically and clinically distinct population

    OpenAIRE

    Han, Wonshik; Nicolau, Monica; Noh, Dong-Young; Jeffrey, Stefanie S.

    2010-01-01

    We aimed to investigate the molecular characteristics of Korean breast cancer. A cDNA microarray study (>42k clones) was performed on 69 breast cancers and three normal breast tissues. The subjects had a high percentage of HER-2 expression, hormone receptor negativity, and young onset. Molecular subtypes according to gene expression profiles were determined and their correlations to the clinicopathologic characteristics and patients outcome were analyzed. The tumors were subdivided into lumin...

  19. Lobular breast cancer : molecular basis, mouse and cellular models

    NARCIS (Netherlands)

    Christgen, Matthias; Derksen, Patrick W B

    2015-01-01

    Infiltrating lobular breast cancer (ILC) is the most common special breast cancer subtype. With mutational or epigenetic inactivation of the cell adhesion molecule E-cadherin (CDH1) being confined almost exclusively to ILC, this tumor entity stands out from all other types of breast cancers. The mol

  20. Investigation on the isoform selectivity of novel kinesin-like protein 1 (KIF11) inhibitor using chemical feature based pharmacophore, molecular docking, and quantum mechanical studies.

    Science.gov (United States)

    Karunagaran, Subramanian; Subhashchandrabose, Subramaniyan; Lee, Keun Woo; Meganathan, Chandrasekaran

    2016-04-01

    Kinesin-like protein (KIF11) is a molecular motor protein that is essential in mitosis. Removal of KIF11 prevents centrosome migration and causes cell arrest in mitosis. KIF11 defects are linked to the disease of microcephaly, lymph edema or mental retardation. The human KIF11 protein has been actively studied for its role in mitosis and its potential as a therapeutic target for cancer treatment. Pharmacophore modeling, molecular docking and density functional theory approaches was employed to reveal the structural, chemical and electronic features essential for the development of small molecule inhibitor for KIF11. Hence we have developed chemical feature based pharmacophore models using Discovery Studio v 2.5 (DS). The best hypothesis (Hypo1) consisting of four chemical features (two hydrogen bond acceptor, one hydrophobic and one ring aromatic) has exhibited high correlation co-efficient of 0.9521, cost difference of 70.63 and low RMS value of 0.9475. This Hypo1 is cross validated by Cat Scramble method; test set and decoy set to prove its robustness, statistical significance and predictability respectively. The well validated Hypo1 was used as 3Dquery to perform virtual screening. The hits obtained from the virtual screening were subjected to various scrupulous drug-like filters such as Lipinski's rule of five and ADMET properties. Finally, six hit compounds were identified based on the molecular interaction and its electronic properties. Our final lead compound could serve as a powerful tool for the discovery of potent inhibitor as KIF11 agonists. PMID:26815769

  1. Multi-channels statistical and morphological features based mitosis detection in breast cancer histopathology.

    Science.gov (United States)

    Irshad, Humayun; Roux, Ludovic; Racoceanu, Daniel

    2013-01-01

    Accurate counting of mitosis in breast cancer histopathology plays a critical role in the grading process. Manual counting of mitosis is tedious and subject to considerable inter- and intra-reader variations. This work aims at improving the accuracy of mitosis detection by selecting the color channels that better capture the statistical and morphological features having mitosis discrimination from other objects. The proposed framework includes comprehensive analysis of first and second order statistical features together with morphological features in selected color channels and a study on balancing the skewed dataset using SMOTE method for increasing the predictive accuracy of mitosis classification. The proposed framework has been evaluated on MITOS data set during an ICPR 2012 contest and ranked second from 17 finalists. The proposed framework achieved 74% detection rate, 70% precision and 72% F-Measure. In future work, we plan to apply our mitosis detection tool to images produced by different types of slide scanners, including multi-spectral and multi-focal microscopy.

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

    Directory of Open Access Journals (Sweden)

    Alexandre Andrade dos Anjos Jácome

    2016-04-01

    Full Text Available Abstract: 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.

  3. Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human.

    Science.gov (United States)

    Shepelin, Denis; Korzinkin, Mikhail; Vanyushina, Anna; Aliper, Alexander; Borisov, Nicolas; Vasilov, Raif; Zhukov, Nikolay; Sokov, Dmitry; Prassolov, Vladimir; Gaifullin, Nurshat; Zhavoronkov, Alex; Bhullar, Bhupinder; Buzdin, Anton

    2016-01-01

    Melanoma is the most aggressive and dangerous type of skin cancer, but its molecular mechanisms remain largely unclear. For transcriptomic data of 478 primary and metastatic melanoma, nevi and normal skin samples, we performed high-throughput analysis of intracellular molecular networks including 592 signaling and metabolic pathways. We showed that at the molecular pathway level, the formation of nevi largely resembles transition from normal skin to primary melanoma. Using a combination of bioinformatic machine learning algorithms, we identified 44 characteristic signaling and metabolic pathways connected with the formation of nevi, development of primary melanoma, and its metastases. We created a model describing formation and progression of melanoma at the level of molecular pathway activation. We discovered six novel associations between activation of metabolic molecular pathways and progression of melanoma: for allopregnanolone biosynthesis, L-carnitine biosynthesis, zymosterol biosynthesis (inhibited in melanoma), fructose 2, 6-bisphosphate synthesis and dephosphorylation, resolvin D biosynthesis (activated in melanoma), D-myo-inositol hexakisphosphate biosynthesis (activated in primary, inhibited in metastatic melanoma). Finally, we discovered fourteen tightly coordinated functional clusters of molecular pathways. This study helps to decode molecular mechanisms underlying the development of melanoma.

  4. 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.

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

    International Nuclear Information System (INIS)

    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

  6. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Directory of Open Access Journals (Sweden)

    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.

  7. [Usefulness of the oncogenetic molecular counselling in adults whith familial cancer].

    Science.gov (United States)

    Valdespino-Gómez, Víctor M; Valdespino-Castillo, Víctor E

    2016-01-01

    More than 200 cancer susceptibility syndromes (CSS) have been recognized through performing classic epidemiologic studies and genetic linkage analysis. In most CSSs clinical conditions of the patients have been identified as well as their hereditary patterns and the predisponent genes to cancer development. Cancer hereditary identification is a useful condition, since cancer family integrants may benefit of efficient strategies in early screening and in tumor prevention strategies; this consultation is performed by oncogenetic molecular medical consultants who must be scientifically competent for Human Genetics and Cancer molecular biology domains. The oncogenetic molecular consult of patients and family relatives of cancer predisposition families is a medical service in health programs of developed and developing countries; in our country this type of medical service needs to be organized and settled to be part of the integral oncology medical service. The oncogenetic molecular consultation is a structural process of assessment and communication of the associated integral problems of the cancer inherited susceptibility in familial cancer. PMID:27100983

  8. Molecular targeted therapy in gastrointestinal cancer%胃肠癌分子靶向治疗

    Institute of Scientific and Technical Information of China (English)

    Miao Xiang; Ximing Xu

    2011-01-01

    Gastrointestinal cancer is one of the highly prevalent malignant diseases worldwide which is a major cause of morbidity and mortality. Gastric cancer is the second leading cause of cancer mortality in the world and its management,especially in advanced stages, has evolved relatively little [1]. Colorectal cancer (CRC) remains the third most common malignancy and the third leading cause of cancer death worldwide [2]. The surgical treatment is still the most effective therapy for the gastrointestinal cancer. However, the majority of the patients had lost the opporunity of surgical therapy when it was detected at advanced stage, so to seek means other than surgical treatment of gastrointestinal cancer metastasis and recurrence also has an important significance. With the deeping research of the molecular biology, molecular targeted therapy has become the hotspot and focus of comprehensive treatment of gastrointestinal cancer which is proposed against the molecular biological targets such as tumor cell growth, apoptosis, cell cycle, invasion and angiogenesis. Molecular targeted therapy can be grouped into six main areas: the epidermal growth factor receptor (EGFR) inhibitors, anti-angiogenic factors, cell cycle inhibitors, apoptosis promoters and matrix metalloproteinase innhibitors, cyclooxygenase inhibitors. The review of the progress are as follows.

  9. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Frolich, Camilla; Albrechtsen, Reidar; Andersen, Lars Dyrskjøt;

    2006-01-01

    staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...... could be detected in the urine by Western blotting; ADAM12 was present in higher levels in the urine from patients with bladder cancer compared with urine from healthy individuals. Significantly, following removal of tumor by surgery, in most bladder cancer cases examined, the level of ADAM12...

  10. Clinical features, outcome and risk factors in cervical cancer patients after surgery for chronic radiation enteropathy

    International Nuclear Information System (INIS)

    Radical hysterectomy and radiotherapy have long been mainstays of cervical cancer treatment. Early stage cervical cancer (FIGO stage IB1–IIA) is traditionally treated using radical surgery combined with radiotherapy, while locally advanced cervical cancer is treated using radiotherapy alone or chemoradiotherapy. In this retrospective study, we describe and analyse the presenting clinical features and outcomes in our cohort and evaluate possible risk factors for postoperative morbidity in women who underwent surgery for chronic radiation enteropathy (CRE). One hundred sixty-six eligible cervical cancer patients who underwent surgery for CRE were retrospectively identified between September 2003 and July 2014 in a prospectively maintained database. Among them, 46 patients received radical radiotherapy (RRT) and 120 received radical surgery plus radiotherapy (RS + RT). Clinical features, postoperative morbidity and mortality, and risk factors for postoperative morbidity were analysed. RS + RT group patients were more likely to present with RTOG/EORTC grade III late morbidity (76.1 % vs 92.5 %; p = 0.004), while RRT group patients tended to show RTOG/EORTC grade IV late morbidity (23.9 % vs 7.5 %; p = 0.004). One hundred forty patients (84.3 %) were treated with aggressive resection (anastomosis 57.8 % and stoma 26.5 %). Overall and major morbidity, mortality and incidence of reoperation in the RRT and RS + RT groups did not differ significantly (63 % vs 64.2 % [p = 1.000], 21.7 % vs 11.7 % [p = 0.137], 6.5 % vs 0.8 % [p = 0.065] and 6.5 % vs 3.3 % [p = 0.360], respectively). However, incidence of permanent stoma and mortality during follow-up was higher in the RRT group than in the RS + RT group (44.2 % vs 12.6 % [p = 0.000] and 16.3 % vs 3.4 % [p = 0.004], respectively). In multivariate analysis, preoperative anaemia was significantly associated with overall morbidity (p = 0.015), while severe intra-abdominal adhesion (p = 0.017), ASA grades III–V (P = 0

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Intracellular Trafficking Considerations in the Development of Natural Ligand-Drug Molecular Conjugates for Cancer

    OpenAIRE

    Yoon, Dennis J.; Liu, Christina T.; Quinlan, Devin S.; Nafisi, Parsa M.; Kamei, Daniel T.

    2011-01-01

    Overexpressed receptors, characteristic of many cancers, have been targeted by various researchers to achieve a more specific treatment for cancer. A common approach is to use the natural ligand for the overexpressed receptor as a cancer-targeting agent which can deliver a chemically or genetically conjugated toxic molecule. However, it has been found that the therapeutic efficacy of such ligand-drug molecular conjugates can be limited, since they naturally follow the intracellular traffickin...

  13. Molecular Markers for Prostate Cancer in Formalin-Fixed Paraffin-Embedded Tissues

    OpenAIRE

    Tamara Sequeiros; Marta García; Melania Montes; Mireia Oliván; Marina Rigau; Eva Colás; Inés de Torres; Juan Morote; Jaume Reventós; Andreas Doll

    2013-01-01

    Prostate cancer (PCa) is the most frequently diagnosed type of cancer in developed countries. The decisive method of diagnosis is based on the results of biopsies, morphologically evaluated to determine the presence or absence of cancer. Although this approach leads to a confident diagnosis in most cases, it can be improved by using the molecular markers present in the tissue. Both miRNAs and proteins are considered excellent candidates for biomarkers in formalin-fixed paraffin-embedded (FFPE...

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

    Science.gov (United States)

    Miyata, Tomoko; Sonoda, Kenzo; Tomikawa, Junko; Tayama, Chiharu; Okamura, Kohji; Maehara, Kayoko; Kobayashi, Hiroaki; Wake, Norio; Kato, Kiyoko; Hata, Kenichiro; Nakabayashi, Kazuhiko

    2015-01-01

    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. PMID:27057136

  15. Imaging Features for the Prediction of Extensive Intraductal Components in Invasive Cancer in Addition to the Histopathologic Grades

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hye Yoen; Kim, Keum Won; Park, Yong Sung; Cho, Yong Jun; Hwang, Cheol Mog; Kim, Hyun Jin; Sul, Hae Jung; Yoon, Dae Sung [Konyang University, College of Medicine, Nonsan (Korea, Republic of); Kim, Gyu Soon [Eulji University, College of Medicine, Daejeon (Korea, Republic of)

    2009-12-15

    To evaluate the usefulness of US and mammography in detecting extensive intraductal component (EIC) in invasive cancer and correlating the results with the histopathologic grade. We retrospectively reviewed the mammographic and sonographic features of 125 invasive breast cancers, classified as 'invasive cancer with EIC' (n=57) and 'invasive cancer without EIC' (n=68). The mammographic features are classified as microcalcifications only, microcalcifications beyond the soft tissue density, soft tissue density without microcalcification, and sonographic features classified according to ten sonographic suspicious features for malignancy by Stavros. We calculated sensitivities, specificities, positive predictive value, negative predictive value, and accuracy to correlate them with histologic grade. Microcalcifications on mammography, calcification, duct extension, and a branching pattern on sonography were found to be statistically significant predictors of EIC. Also, a thick echogenic halo, angular margin, microlobuation, taller than wide feature on sonography, and soft tissue shadow without microcalcification on mammography showed a decreased risk of EIC. In addition, the presence of a branching pattern is an indicator of high histologic grade (p<0.05). Microcalcification on mammography, calcification, duct extension, and branching pattern on sonography are an indicator of the presence of EIC in invasive cancer. In addition, when a branching pattern is present, the tumor tends to have a high histologic grade.

  16. Interaction of pathology and molecular characterization of thyroid cancers

    International Nuclear Information System (INIS)

    This paper presents the results of joint studies of thyroid cancer in children under 15 years of age between departments in Cambridge, Brussels, Naples and Munich in the European Union, and departments in Minsk, Kiev and Obninsk in the newly independent states of Eastern Europe. The pathology of 264 cases of childhood thyroid cancer out of 430 that have occurred since 1990 in the 3 countries in which high levels of fallout from the Chernobyl accident occurred has been restudied by NIS and EU pathologists. The overall level of agreement reached was about 97%. The diagnosis was supported by immunocytochemistry and ISH for the differentiation markers, thyroglobulin and calcitonin, and the tumors were classified according to the WHO, with papillary carcinomas being further subclassified. 99% of the 134 Belarussian cases were papillary carcinomas, as were 94% of the 114 Ukrainian tumors. All 9 of the Russian cases available for study were papillary in type. 76 of 154 cases of childhood thyroid cancer reviewed over a 30 year period in England and Wales and were also studied, 68% of these were papillary carcinoma. Histological study showed that a subtype of papillary carcinoma, rarely found in adults, with a solid/follicular architecture occurred in children. It was found in 72% of the Belarussian papillary carcinomas, 76% of the Ukrainian cases, but only 40% of the England and Wales cases. Molecular biological studies showed that the proportion of cases of papillary carcinoma expressing the ret gene was not significantly different in the exposed and the unexposed tumors, studies of the type of translocation leading to ret gene expression are not yet conclusive. Ras gene mutations were found as expected in follicular carcinoma, but were absent from any papillary carcinoma, whether from exposed or unexposed cases. TSH receptor mutations, normally found in follicular tumors were not found in any papillary carcinomas, nor were any p53 mutations identified. All these results

  17. FBXW7 mutations in patients with advanced cancers: clinical and molecular characteristics and outcomes with mTOR inhibitors.

    Directory of Open Access Journals (Sweden)

    Denis L Jardim

    Full Text Available PURPOSE: FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes. Preclinical data suggest that FBXW7 mutations sensitize cells to mTOR inhibitors. Clinicopathologic characteristics of cancer patients with FBXW7 mutations and their responses to mTOR inhibitors remain unknown. METHODS: Using multiplex gene panels we evaluated how the FBXW7 mutation affected the cancer phenotype of patients referred to a phase I clinic starting January 2012. Whenever possible patients positive for FBXW7 mutation were treated with regimens containing an mTOR inhibitors and their outcomes were reviewed. RESULTS: FBXW7 mutations were detected in 17 of 418 patients (4.0%. Among tumor types with more than 10 patients tested, FBXW7 mutations occurred in colorectal cancer (7/49; 14.3%, squamous cell cancer of head and neck (2/18; 11.1%, liver (1/13; 7.7%, and ovarian cancers (1/40; 2.5%. No one clinical, pathological or demographic feature was characteristic of the FBXW7-mutated patient population. The mutation occurred in isolation in only 2/17 (12% patients, and KRAS was frequently found as a concomitant mutation, especially in patients with colorectal cancer (6/7; 86%. Ten patients were treated on a protocol containing an mTOR inhibitor, with a median time to treatment failure of 2.8 months (range, 1.3-6.8. One patient with liver cancer (fibrolamellar subtype continues to have a prolonged stable disease for 6.8+ months. CONCLUSION: In patients with advanced cancers, somatic mutations in FBXW7 usually occur with other simultaneous molecular aberrations, which can contribute to limited therapeutic efficacy of mTOR inhibitors.

  18. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Directory of Open Access Journals (Sweden)

    Tamer M Fouad

    2011-01-01

    Full Text Available

    The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate

  19. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Directory of Open Access Journals (Sweden)

    Ola Khorshid

    2011-12-01

    Full Text Available The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate, toxicity and OS.

  20. Molecular markers for urothelial bladder cancer prognosis: Toward implementation in clinical practice

    NARCIS (Netherlands)

    Rhijn, B.W. van; Catto, J.W.; Goebell, P.J.; Knuchel, R.; Shariat, S.F.; Poel, H.G. van der; Sanchez-Carbayo, M.; Thalmann, G.N.; Schmitz-Drager, B.J.; Kiemeney, L.A.L.M.

    2014-01-01

    OBJECTIVES: To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to

  1. 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......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

  2. Tobacco and Cancer

    Science.gov (United States)

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

  3. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

    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...

  4. High-throughput genomic technology in research and clinical management of breast cancer. Molecular signatures of progression from benign epithelium to metastatic breast cancer

    OpenAIRE

    Rennstam, Karin; Hedenfalk, Ingrid

    2006-01-01

    It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease progression in breast cancer remains poorly understood. High-throughput molecular profiling techniques are excellent tools for the study of complex molecular alterations. By accurate...

  5. Biologia molecular do câncer cervical Molecular biology of cervical cancer

    Directory of Open Access Journals (Sweden)

    Waldemar Augusto Rivoire

    2006-01-01

    Full Text Available A carcinogênese é um processo de múltiplas etapas. Alterações no equilíbrio citogenético ocorrem na transformação do epitélio normal a câncer cervical. Numerosos estudos apoiam a hipótese de que a infecção por HPV está associada com o desenvolvimento de alterações malignas e pré-malignas do trato genital inferior. Neste trabalho são apresentadas as bases para a compreensão da oncogênese cervical. O ciclo celular é controlado por proto-oncogenes e genes supressores. Quando ocorrem mutações, proto-oncogenes tornam-se oncogenes, que são carcinogênicos e causam multiplicação celular excessiva. A perda da ação de genes supressores funcionais pode levar a célula ao crescimento inadequado. O ciclo celular também pode ser alterado pela ação de vírus, entre eles o HPV (Human Papiloma Virus, de especial interesse na oncogênese cervical. Os tipos de HPV 16 e 18 são os de maior interesse, freqüentemente associados a câncer cervical e anal. O conhecimento das bases moleculares que estão envolvidas na oncogênese cervical tem sido possível devido a utilização de técnicas avançadas de biologia molecular. A associação destas técnicas aos métodos diagnósticos clássicos, poderão levar a uma melhor avaliação das neoplasias cervicais e auxiliar no desenvolvimento de novas terapias, talvez menos invasivas e mais efetivas.Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18

  6. Associations between body mass index and molecular subtypes as well as other clinical characteristics of breast cancer in Chinese women

    Directory of Open Access Journals (Sweden)

    Chen FY

    2013-03-01

    Full Text Available Fei-Yu Chen, Hui-Ying Ou, Shou-Man Wang, Yu-Hui Wu, Guo-Jiao Yan, Li-Li Tang Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha City, Hunan Province, People's Republic of China Background: Several studies have shown a positive association between body mass index (BMI and the development of hormone receptor-positive breast cancer in postmenopausal women; however, the associations between BMI groups and molecular subtypes have yet to be well defined in premenopausal breast cancer patients. Methods: A total of 2465 female breast cancer patients diagnosed at our institution were recruited for this study. Clinicopathologic information (including age, body height and weight, as well as tumor subtypes and stages was collected; analyses of these characteristics and the associations between them were performed. Results: A total of 1951 cases were included in the study. The mean age was 47.3 years, the majority of patients were of normal weight, premenopausal, had stage 2 cancer, and did not present with positive nodes. The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2+, and triple-negative subtypes were 57.8%, 11.6%, 6.1%, and 24.5%, respectively. There were significant differences in the clinicopathologic features among BMI groups in premenopausal patients. The case-only odds ratio (OR analysis revealed that normal weight patients tended to have luminal B cancer (OR = 1.4, P = 0.206, and overweight and obese patients tended to have triple-negative cancer in premenopausal patients (OR = 2.8, OR = 3.7, respectively; P < 0.001. Conclusion: In Chinese women, breast cancer came with these characteristics: young mean age (premenopause, luminal A subtype, and the majority of them were within a normal weight range. In premenopausal patients, underweight patients tended to have luminal A, lower human epidermal growth factor receptor 2+ expression, stage 1 and no positive node cancer. However

  7. Correlation between smoking history and molecular pathways in sporadic colorectal cancer: a meta-analysis

    OpenAIRE

    Chen, Ke; Xia, Guanggai; Zhang, Changhua; Sun, Yunwei

    2015-01-01

    Background: Epidemiological studies have shown that smoking increases the risk for colorectal cancer (CRC). Evidence of the guiding significance of smoking history for molecular classification and molecular targeted anti-tumor therapy is not well established. Aims: To provide indirectly evidence, we conducted a systematic meta-analysis of association between smoking history and different molecular classification. Methods: We searched in multiple databases up to January 2014, and identified 27...

  8. [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.

  9. Basic research and clinical application of optical molecular imaging in breast cancer

    International Nuclear Information System (INIS)

    As a rapidly developing biomedical imaging technology,in vivo optical molecular imaging has been widely applied in various research fields owing to its unique real-time, quantitative and noninvasive characteristics. The applications of in vivo optical imaging technology in the basic and clinical research of breast cancer were reviewed, including detection of distant metastasis,tumor apoptosis, cell cycle, hypoxia and angiogenesis, ER-mediated molecular pathway, breast cancer stem cells, early diagnosis, sentinel node biopsy, evaluation of drug efficacy and detection of human epidermal growth factor receptor-2 (HER-2) expression. They all seem to have a promising potential in in vivo optical molecular imaging. (authors)

  10. Molecularly Characterised Xenograft Tumour Mouse Models: Valuable Tools for Evaluation of New Therapeutic Strategies for Secondary Liver Cancers

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available To develop and evaluate new therapeutic strategies for the treatment of human cancers, well-characterised preclinical model systems are a prerequisite. To this aim, we have established xenotransplantation mouse models and corresponding cell cultures from surgically obtained secondary human liver tumours. Established xenograft tumours were patho- and immunohistologically characterised, and expression levels of cancer-relevant genes were quantified in paired original and xenograft tumours and the derivative cell cultures applying RT-PCR-based array technology. Most of the characteristic morphological and immunohistochemical features of the original tumours were shown to be maintained. No differences were found concerning expression of genes involved in cell cycle regulation and oncogenesis. Interestingly, cytokine and matrix metalloproteinase encoding genes appeared to be expressed differentially. Thus, the established models are closely reflecting pathohistological and molecular characteristics of the selected human tumours and may therefore provide useful tools for preclinical analyses of new antitumour strategies in vivo.

  11. Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells.

    Science.gov (United States)

    Somasagara, Ranganatha R; Deep, Gagan; Shrotriya, Sangeeta; Patel, Manisha; Agarwal, Chapla; Agarwal, Rajesh

    2015-04-01

    Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcitabine-resistant (GR) and gemcitabine-sensitive (GS) PanC cells and underlying molecular mechanisms, together with efficacy of a natural agent bitter melon juice (BMJ). GR PanC cells showed distinct morphological features including spindle-shaped morphology and a decrease in E-cadherin expression. GR cells also showed higher ATP production with an increase in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Molecular studies showed higher expression of glucose transporters (GLUT1 and 4) suggesting an increase in glucose uptake by GR cells. Importantly, GR cells showed a significant increase in Akt and ERK1/2 phosphorylation and their inhibition decreased cell viability, suggesting their role in survival and drug resistance of these cells. Recently, we reported strong efficacy of BMJ against a panel of GS cells in culture and nude mice, which we expanded here and found that BMJ was also effective in decreasing both Akt and ERK1/2 phosphorylation and viability of GR PanC cells. Overall, we have identified novel mechanisms of gemcitabine resistance in PanC cells which are targeted by BMJ. Considering the short survival in PanC patients, our findings could have high translational potential in controlling this deadly malignancy. PMID:25672620

  12. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal

    2014-03-01

    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  13. Pathological Features of Gastric Cancer in Zhuanghe High-risk Area in China during 1992-2005

    Institute of Scientific and Technical Information of China (English)

    GONG Yue-hua; SUN Li-ping; LIU Yan-hou; HUANG he; SUN Guo-peng; WANG Quan-gang; YIN Yuan-jun; YUAN Yuan

    2008-01-01

    Objective:To investigate the pathological features and chronological changes of 1003 cases with gastric cancer in Zhuanghe high-risk area during 1992-2005 and the relationship between the changes and etiology factors in order tO make a clue for gastric cancer prevention. Methods:A total of 1003 gastric cancer specimens resected surgically between 1992-2005 in Zhuanghe Center Hospital were studied.The specimens were fixed in formalin and diagnosed by routine pathology. Results:The incidence of patients with gastric cancer was highest at age of 60-69,the next high was at age of 50-59 and it was significantly higher in male than in female(P<0.001),the ratio was 3.0∶1.During the past 14 years,there were 159(15.9%)EGC,195(19.4%)moderate and 649(64.7%)advanced gastric cancer detected.In macroscopical features,type Ⅲ remained dominant in EGC,the next was mixed type in EGC.In advanced gastric cancer the Borrmann's type Ⅲ remained the dominant,the next was type Ⅱ.For nodal metastasis,positive cases were decreasing and negative were increasing in EGC,moreover negative cases were higher than positive ones each year.There was no obvious trend in advanced cancer but positive cases were higher than negative ones each year.In histological features,papillary,moderately and poorly differentiated tubular adenocarcinoma remained downtrend,mucus adenocarcinoma and undifferentiation cancer remained uptrend year after year.The radio of intestinal to diffuse type decreased from 0.78 to 0.62 during the past 14 years. Conclusion:There were significant chorological trends of pathological characteristic of gastric cancer in Zhuanghe high-risk area during the past 14 years.

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

    Science.gov (United States)

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

    2014-03-01

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

  15. NIH scientists identify molecular link between metabolism and breast cancer

    Science.gov (United States)

    A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings by researchers at the National Cancer Institute (NCI), part of th

  16. Molecular genetics of cancer and tumorigenesis: Drosophila models

    Institute of Scientific and Technical Information of China (English)

    Wu-Min Deng

    2011-01-01

    Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

  17. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery (pancr

  18. From molecular imaging to personalized radionuclide therapy of cancer

    International Nuclear Information System (INIS)

    Full text of publication follows. 68Gallium is a positron emitter (t1/2 68 min) which can be produced from a generator in a convenient, 'in-house' preparation and used for labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 7700 68Ga PET/CT studies in patients with neuroendocrine tumors (NET) and have established SSTR PET/CT as the new gold standard for imaging G1 and G2 NET (staging, re-staging, therapy response evaluation and detection of unknown primary NET). The same peptides can be labeled with 177Lutetium or 90Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRNT is based on the receptor-mediated internalization of SA. Several clinical trials indicate that PRRNT can deliver effective radiation doses to tumors. A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective therapy for patients with G1-2 neuroendocrine tumors, irrespective of previous therapies, with a survival advantage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NET was 39 mo. Similar results were obtained for NET of unknown primary (median PFS: 38 mo) whereas NET of small bowel had a median PFS of 51 months. Side effects like 3-4 NEThro- or hemato-toxicity were observed in only 0.2% and 2% of patients respectively. PRRNT is highly effective in the management of NET, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept using sequential (DUO) PRRNT) results in excellent therapeutic responses. By

  19. In search of molecular approaches to improving cancer therapy efficacy.

    Science.gov (United States)

    Cherepenko, E; Telegeev, G

    2014-03-01

    The study of genome rearrangement sites using full genome sequences is an important approach to revealing the nature of cancer and finding effective ways for cancer treatment. The progress in DNA sequencing could make the procedure of whole genome reading close to routine procedure of lower cost. The personal analysis of rearranged ends (PARE) method used for rearrangement study is reviewed. PARE allows identifying of individual cancer biomarkers making personal medicine possible. Also, the progress in "liquid biopsy" technology based on detection of circulating tumor cells in the patient's blood is shortly summarized. Another important approach is the discovered phenomenon of synthetic lethality causing cancer cell death due to appropriate combination of mutations in different genes or inhibitors of their protein products. Studies of genome rearrangements and synthetic lethality are considered promising for the development of effective cancer treatment approaches.

  20. Molecular imaging of cancer: MR spectroscopy and beyond

    International Nuclear Information System (INIS)

    Proton magnetic resonance spectroscopic imaging is a non-invasive diagnostic tool for the investigation of cancer metabolism. As an adjunct to morphologic and dynamic magnetic resonance imaging, it is routinely used for the staging, assessment of treatment response, and therapy monitoring in brain, breast, and prostate cancer. Recently, its application was extended to other cancerous diseases, such as malignant soft-tissue tumours, gastrointestinal and gynecological cancers, as well as nodal metastasis. In this review, we discuss the current and evolving clinical applications of proton magnetic resonance spectroscopic imaging. In addition, we will briefly discuss other evolving techniques, such as phosphorus magnetic resonance spectroscopic imaging, sodium imaging and diffusion-weighted imaging in cancer assessment.

  1. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...... by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...

  2. Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging.

    Science.gov (United States)

    Yang, Yaliang; Li, Fuhai; Gao, Liang; Wang, Zhiyong; Thrall, Michael J; Shen, Steven S; Wong, Kelvin K; Wong, Stephen T C

    2011-08-01

    We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer.

  3. Lung cancer in never smokers: change of a mindset in the molecular era.

    Science.gov (United States)

    Lee, Young Joo; Kim, Joo-Hang; Kim, Se Kyu; Ha, Sang-Jun; Mok, Tony S; Mitsudomi, Tetsuya; Cho, Byoung Chul

    2011-04-01

    Lung cancer is a leading cause of cancer-related mortality across the world. Although the majority of lung cancer is attributed to tobacco smoke, approximately 25% of lung cancers worldwide occur in lifelong never smokers. Over the past decades, the bulk of research on this disease suggested that several genetic, environmental, hormonal, and viral factors might increase the risk of lung cancer among never smokers. However, there has been no dominant risk factor whose significance has been validated across racial and ethnic groups. However, this subset of lung cancers has received renewed attention due to the introduction of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors showing the dramatic therapeutic response on selected patients with activating EGFR mutations which occur more commonly in never smokers. The treatment strategy blocking EGFR pathway in EGFR-mutant lung cancer represents a remarkable example of molecular targeted therapies which completely repress tumor by inhibition of driving oncogenes. More recently, a surprising positive effect of an ALK inhibitor on EML4-ALK-positive lung cancer has been suggested that lung cancer in never smokers is likely to be an assemblage of molecularly defined subsets which would be a good candidate for personalized diagnostic and therapeutic approaches. PMID:21272954

  4. Telomerase promoter mutations in cancer: an emerging molecular biomarker?

    Science.gov (United States)

    Vinagre, João; Pinto, Vasco; Celestino, Ricardo; Reis, Marta; Pópulo, Helena; Boaventura, Paula; Melo, Miguel; Catarino, Telmo; Lima, Jorge; Lopes, José Manuel; Máximo, Valdemar; Sobrinho-Simões, Manuel; Soares, Paula

    2014-08-01

    Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target. PMID:25048572

  5. Small interfering RNA-based molecular therapy of cancers

    Institute of Scientific and Technical Information of China (English)

    Wei Guo; Wangbing Chen; Wendan Yu; Wenlin Huang; Wuguo Deng

    2013-01-01

    RNA interference (RNAi) has become a gold standard for validating gene function in basic life science research and provides a promising therapeutic modality for cancer and other diseases. This mini-review focuses on the potential of smal interfering RNAs (siRNAs) in anticancer treatment, including the establishment and screening of cancer-associated siRNA libraries and their applications in anticancer drug target discovery and cancer therapy. This article also describes the current delivery approaches of siRNAs using lipids, polymers, and, in particular, gold nanoparticles to induce significant gene silencing and tumor growth regression.

  6. Aspectos moleculares dos esteroides sexuais sobre a cartilagem e os ossos Molecular features of sexual steroids on cartilage and bone

    Directory of Open Access Journals (Sweden)

    Roberta Bastos Wolff

    2012-08-01

    Full Text Available No Brasil, o crescimento dos casos registrados de doenças degenerativas das cartilagens articulares por ano é de 20%, o que representa, anualmente, que mais de 200 mil brasileiros desenvolvem doenças degenerativas das articulações e, com repercussões negativas sobre a massa óssea. Este trabalho mostra evidências que a produção hormonal de esteroides sexuais (estrogênios, progestagênios e androgênios têm influência na qualidade da cartilagem, bem como na massa óssea. Portanto, o objetivo dessa revisão foi o de analisar os dados da literatura sobre a ação molecular e gênica dos esteroides sexuais na fisiologia da cartilagem hialina e do osso, bem como a interferência da osteoartrite na qualidade dessas estruturas.In Brazil, the increase in the reported cases of degenerative diseases of articular cartilage is 20% per year, meaning that 200,000 Brazilians develop degenerative joint diseases every year, which have a negative impact on bone mass. This study shows evidence that hormone production of sexual steroids (estrogens, progestogens, and androgens have an influence on cartilage quality, as well as on bone mass. Therefore, this review aimed to analyze literature data on the molecular and genic action of sexual steroids on hyaline cartilage and bone physiology, as well as osteoarthritis interference on the quality of these structures.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  9. Cellular and Molecular Mechanisms of 3,3'-Diindolylmethane in Gastrointestinal Cancer.

    Science.gov (United States)

    Kim, Soo Mi

    2016-01-01

    Studies in humans have shown that 3,3'-diindolylmethane (DIM), which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER) stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers. PMID:27447608

  10. Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells

    OpenAIRE

    Buchholz Thomas A; Lacerda Lara; Xu Wei; Robertson Fredika; Ueno Naoto T; Lucci Anthony; Landis Melissa D; Rodriguez Angel A; Li Li; Cohen Evan; Gao Hui; Krishnamurthy Savitri; Zhang Xiaomei; Debeb Bisrat G; Cristofanilli Massimo

    2010-01-01

    Abstract Background Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced b...

  11. Splicing Regulation: A Molecular Device to Enhance Cancer Cell Adaptation

    Directory of Open Access Journals (Sweden)

    Vittoria Pagliarini

    2015-01-01

    Full Text Available Alternative splicing (AS represents a major resource for eukaryotic cells to expand the coding potential of their genomes and to finely regulate gene expression in response to both intra- and extracellular cues. Cancer cells exploit the flexible nature of the mechanisms controlling AS in order to increase the functional diversity of their proteome. By altering the balance of splice isoforms encoded by human genes or by promoting the expression of aberrant oncogenic splice variants, cancer cells enhance their ability to adapt to the adverse growth conditions of the tumoral microenvironment. Herein, we will review the most relevant cancer-related splicing events and the underlying regulatory mechanisms allowing tumour cells to rapidly adapt to the harsh conditions they may face during the occurrence and development of cancer.

  12. New Molecular Tools for Efficient Screening of Cervical Cancer

    OpenAIRE

    Magnus von Knebel Doeberitz

    2001-01-01

    Cytological screening using the Pap-smear led to a remarkable reduction of the mortality of cervical cancer. However, due to subjective test criteria it is hampered by poor inter- and intra-observer agreement. More reproducible assays are expected to improve the current screening and avoid unnecessary medical intervention and psychological distress for the affected women. Cervical cancer arises as consequence of persistent high risk papillomavirus (HR-HPV) infections. Expression of two viral ...

  13. Molecular mechanisms of cisplatin resistance in cervical cancer

    OpenAIRE

    Zhu, Xueqiong

    2016-01-01

    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 tr...

  14. Molecular mechanisms of cisplatin resistance in cervical cancer

    OpenAIRE

    Zhu H; Luo H; Zhang W; Shen Z; Hu X; Zhu X

    2016-01-01

    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 ...

  15. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  16. Correlation of pretreatment hemoglobin and platelet counts with clinicopathological features in colorectal cancer in Saudi population

    Directory of Open Access Journals (Sweden)

    Eyad F Al-Saeed

    2014-01-01

    Full Text Available Background/Aims: In Saudi Arabia, colorectal cancers (CRCs are registered as the second most common cancers. However, no data has been reported about correlation of the severity of the anemia and pretreatment platelets level with clinicopathological features of CRCs. We aimed to evaluate the association between pretreatment hemoglobin and platelets level and the clinicopathological features of CRC patients in Saudi Arabia. Materials and Methods: Between September 2005 and November 2011, One hundred and fifty-four confirmed CRC patients underwent thorough physical examination, blood investigations, endoscopic ultrasonography (EUS, and computed tomography (CT for staging before surgery. Findings of physical assessment, EUS, CT, and pathological specimens were correlated with pretreatment hemoglobin and platelets levels the Pearson-Kendall tau correlative coefficients. Results: The mean age of cohort was 56.6 years (range: 26-89. Left-sided CRC were predominant (97 patients; 63%. Mean size of primary tumor was 6 cms (1-18 SD ± 3.55. Mean values of hemoglobin, red blood cells, hematocrit, white blood cells, and platelets were 11.9 SD ± 2.3, 35.5 SD ± 5.7, 4.43 × 10 6 /mL SD ± 0.6, 7.67 10 6 /mL SD ± 2.44, and 343 × 10 3 /mL SD ± 164.4, respectively. Pretreatment hemoglobin was inversely correlated with primary tumor size (R: 0.71, R2: 1.55, P = 0.0001 and nodal status (R: 0.02, R2: 0.05, P = 0.01. Right-sided CRC had significantly low pretreatment hemoglobin levels ( P = 0.001. Interestingly, pretreatment thrombocytosis was seen only in right-sided CRC (P = 0.0001. Conclusion: Pretreatment anemia and thrombocytosis were found mainly in right-sided CRCs and advanced primary and nodal stages. Pretreatment hemoglobin and thrombocytosis can be considered as useful prognostic markers in CRC patients.

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

    International Nuclear Information System (INIS)

    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- [18F]-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

  18. Feature activated molecular dynamics: an efficient approach for atomistic simulation of solid-state aggregation phenomena.

    Science.gov (United States)

    Prasad, Manish; Sinno, Talid

    2004-11-01

    An efficient approach is presented for performing efficient molecular dynamics simulations of solute aggregation in crystalline solids. The method dynamically divides the total simulation space into "active" regions centered about each minority species, in which regular molecular dynamics is performed. The number, size, and shape of these regions is updated periodically based on the distribution of solute atoms within the overall simulation cell. The remainder of the system is essentially static except for periodic rescaling of the entire simulation cell in order to balance the pressure between the isolated molecular dynamics regions. The method is shown to be accurate and robust for the Environment-Dependant Interatomic Potential (EDIP) for silicon and an Embedded Atom Method potential (EAM) for copper. Several tests are performed beginning with the diffusion of a single vacancy all the way to large-scale simulations of vacancy clustering. In both material systems, the predicted evolutions agree closely with the results of standard molecular dynamics simulations. Computationally, the method is demonstrated to scale almost linearly with the concentration of solute atoms, but is essentially independent of the total system size. This scaling behavior allows for the full dynamical simulation of aggregation under conditions that are more experimentally realizable than would be possible with standard molecular dynamics.

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

    Directory of Open Access Journals (Sweden)

    Kanwal Raghav

    Full Text Available Cancer in adolescents and young adults (AYAs (15-39 years is increasingly recognized as a distinct clinical and biological entity. Cancer of unknown primary (CUP, a disease traditionally presenting in older adults with a median age of 65 years, poses several challenges when diagnosed in AYA patients. This study describes clinicopathological features, outcomes and challenges in caring for AYA-CUP patients.A retrospective review of 47 AYAs diagnosed with CUP at MD Anderson Cancer Center (6/2006-6/2013 was performed. Patients with favorable CUP subsets treated as per site-specific recommendations were excluded. Demographics, imaging, pathology and treatment data was collected using a prospectively maintained CUP database. Kaplan-Meier product limit method and log-rank test were used to estimate and compare overall survival. The cox-proportional model was used for multivariate analyses.Median age was 35 years (range 19-39. All patients underwent comprehensive workup. Adenocarcinoma was the predominant histology (70%. A median of 9 immunostains (range 2-29 were performed. The most common putative primary was biliary tract based on clinicopathological parameters as well as gene profiling. Patients presented with a median of 2 metastatic sites [lymph node (60%, lung (47%, liver (38% and bone (34%]. Most commonly used systemic chemotherapies included gemcitabine, fluorouracil, taxanes and platinum agents. Median overall survival for the entire cohort was 10.0 (95% confidence interval (CI: 6.7-15.4 months. On multivariate analyses, elevated lactate dehydrogenase (Hazard ratio (HR 3.66; 95%CI 1.52-8.82; P = 0.004, ≥3 metastatic sites (HR 5.34; 95%CI 1.19-23.9; P = 0.029, and tissue of origin not tested (HR 3.4; 95%CI 1.44-8.06; P = 0.005 were associated with poor overall survival. Culine's CUP prognostic model (lactate dehydrogenase, performance status, liver metastases was validated in this cohort (median overall survival: good-risk 25.2 months vs

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

    International Nuclear Information System (INIS)

    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

  1. Strain measurement by cardiovascular magnetic resonance in pediatric cancer survivors: validation of feature tracking against harmonic phase imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jimmy C. [C.S. Mott Children' s Hospital, University of Michigan Congenital Heart Center, Ann Arbor, MI (United States); University of Michigan, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); University of Michigan, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Connelly, James A. [University of Michigan, Department of Pediatrics and Communicable Diseases, Division of Hematology-Oncology, Ann Arbor, MI (United States); Zhao, Lili [University of Michigan, Department of Biostatistics, Ann Arbor, MI (United States); Agarwal, Prachi P. [University of Michigan, Department of Radiology, Division of Cardiothoracic Radiology, Ann Arbor, MI (United States); Dorfman, Adam L. [University of Michigan, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); University of Michigan, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States)

    2014-09-15

    Left ventricular strain may be a more sensitive marker of left ventricular dysfunction than ejection fraction in pediatric cancer survivors after anthracycline therapy, but there is limited validation of strain measurement by feature tracking on cardiovascular magnetic resonance (MR) images. To compare left ventricular circumferential and radial strain by feature tracking vs. harmonic phase imaging analysis (HARP) in pediatric cancer survivors. Twenty-six patients (20.2 ± 5.6 years old) underwent cardiovascular MR at least 5 years after completing anthracycline therapy. Circumferential and radial strain were measured at the base, midventricle and apex from short-axis myocardial tagged images by HARP, and from steady-state free precession images by feature tracking. Left ventricular ejection fraction more closely correlated with global circumferential strain by feature tracking (r = -0.63, P = 0.0005) than by HARP (r = -0.39, P = 0.05). Midventricular circumferential strain did not significantly differ by feature tracking or HARP (-20.8 ± 3.4 vs. -19.5 ± 2.5, P = 0.07), with acceptable limits of agreement. Midventricular circumferential strain by feature tracking strongly correlated with global circumferential strain by feature tracking (r = 0.87, P < 0.0001). Radial strain by feature tracking had poor agreement with HARP, particularly at higher values of radial strain. Intraobserver and interobserver reproducibility was excellent for feature tracking circumferential strain, but reproducibility was poor for feature tracking radial strain. Midventricular circumferential strain by feature tracking is a reliable and reproducible measure of myocardial deformation in patients status post anthracycline therapy, while radial strain measurements are unreliable. Further studies are necessary to evaluate potential relation to long-term outcomes. (orig.)

  2. Multiple Features Based Approach to Extract Bio-molecular Event Triggers Using Conditional Random Field

    Directory of Open Access Journals (Sweden)

    Amit Majumder

    2012-11-01

    Full Text Available The purpose of Biomedical Natural Language Processing (BioNLP is to capture biomedical phenomena from textual data by extracting relevant entities, information and relations between biomedical entities (i.e. proteins and genes. In general, in most of the published papers, only binary relations were extracted. In a recent past, the focus is shifted towards extracting more complex relations in the form of bio-molecular events that may include several entities or other relations. In this paper we propose an approach that enables event trigger extraction of relatively complex bio-molecular events. We approach this problem as a detection of bio-molecular event trigger using the well-known algorithm, namely Conditional Random Field (CRF. We apply our experiments on development set. It shows the overall average recall, precision and F-measure values of 64.27504%, 69.97559% and 67.00429%, respectively for the event detection.

  3. Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy?

    Science.gov (United States)

    Gonda, Tamas A; Varro, Andrea; Wang, Timothy C; Tycko, Benjamin

    2010-02-01

    It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.

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

    Science.gov (United States)

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

    2016-07-01

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

  5. A Health Services Research Agenda for Cellular, Molecular and Genomic Technologies in Cancer Care

    Science.gov (United States)

    Wideroff, Louise; Phillips, Kathryn A.; Randhawa, Gurvaneet; Ambs, Anita; Armstrong, Katrina; Bennett, Charles L.; Brown, Martin L.; Donaldson, Molla S.; Follen, Michele; Goldie, Sue J.; Hiatt, Robert A.; Khoury, Muin J.; Lewis, Graham; McLeod, Howard L.; Piper, Margaret; Powell, Isaac; Schrag, Deborah; Schulman, Kevin A.; Scott, Joan

    2009-01-01

    Background In recent decades, extensive resources have been invested to develop cellular, molecular and genomic technologies with clinical applications that span the continuum of cancer care. Methods In December 2006, the National Cancer Institute sponsored the first workshop to uniquely examine the state of health services research on cancer-related cellular, molecular and genomic technologies and identify challenges and priorities for expanding the evidence base on their effectiveness in routine care. Results This article summarizes the workshop outcomes, which included development of a comprehensive research agenda that incorporates health and safety endpoints, utilization patterns, patient and provider preferences, quality of care and access, disparities, economics and decision modeling, trends in cancer outcomes, and health-related quality of life among target populations. Conclusions Ultimately, the successful adoption of useful technologies will depend on understanding and influencing the patient, provider, health care system and societal factors that contribute to their uptake and effectiveness in ‘real-world’ settings. PMID:19367091

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

    Science.gov (United States)

    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.

  7. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

    International Nuclear Information System (INIS)

    We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

  8. THE SIGNIFICANCE OF FORM FACTOR IN THE QUANTITATIVE ANALYSIS OF THE MORPHOLOGICAL FEATURES OF BREAST CANCER NUCLEI

    Institute of Scientific and Technical Information of China (English)

    杨建茹; 管增伟; 刘长安

    2001-01-01

    Objective In the present study, an important aspect in medical image analysis, quantification of form factor was investigated. It is suggested that nuclear form of both normal and cancer cells of the same tissue should be taken into account when FF( form factor) is analyzed.The value of FF can’t be independently used to serve as evidence. Because breast tissue is complex, breast cancer cells take on diverse and complicated morphological features.Methods Slides of the tissue sections of breast cancer were pathologically confirmed and analyzed in terms of the morphological parameters using DMRXA full-automatic bio-fluorescent microscope and Q550IW computer(Leica, Germany). Of the samples examined, there were 9 cases of adenocarcinoma and 6 normal controls.Results Statistical analysis was performed using SAS software. The results are listed in Table Ⅰ. We found that the nuclear area, perimeter, length and breadth of breast cancer cells were significantly higher than those of normal breast cells(P<0.01). From the data given in the paper it can be seen that FF in the control is significantly higher than that in breast cancer.Conclusion Breast tissue is complicated, consisting of simple cubiodal epithelium, simple columnar epithelium and multiple columnar epithelium, etc. These different cells may have round or ovoid nuclei. Breast cancer cells take on diverse and complicated morphological features. They are classified as duct, lobular and special carcinoma according to their histogenesis and morphological structures. Their nuclear morphological features are diverse as well. Therefore, nuclear form of both normal and cancer cells of the same tissue should be taken into account when form factor is analyzed, nuclear FF alone is not reliable enough to distinguish normal from malignant breast cells.

  9. Genomic analysis and selected molecular pathways in rare cancers

    International Nuclear Information System (INIS)

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer. (paper)

  10. New Molecular Tools for Efficient Screening of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Magnus von Knebel Doeberitz

    2001-01-01

    Full Text Available Cytological screening using the Pap-smear led to a remarkable reduction of the mortality of cervical cancer. However, due to subjective test criteria it is hampered by poor inter- and intra-observer agreement. More reproducible assays are expected to improve the current screening and avoid unnecessary medical intervention and psychological distress for the affected women. Cervical cancer arises as consequence of persistent high risk papillomavirus (HR-HPV infections. Expression of two viral oncogenes, E6 and E7, in epithelial stem cells is required to initiate and maintain cervical carcinogenesis and results in significant overexpression of the cellular p16INK4a protein. Since this protein is not expressed in normal cervical squamous epithelia, screening for p16INK4a over-expressing cells allows to specifically identify dysplastic lesions, and significantly reduces the inter-observer disagreement of the conventional cytological or histological tests. Progression of preneoplastic lesions to invasive cancers is associated with extensive recombination of viral and cellular genomes which can be monitored by detection of papillomavirus oncogene transcripts (APOT assay derived from integrated viral genome copies. Detection of integrated type oncogene transcripts points to far advanced dysplasia or invasive cancers and thus represents a progression marker for cervical lesions. These new assays discussed here will help to improve current limitations in cervical cancer screening, diagnosis, and therapy control.

  11. Molecular markers for tumor cell dissemination in female cancers

    International Nuclear Information System (INIS)

    In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author)

  12. Clinical features and prognostic factors for patients with bone metastases from prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jian He; Zhao-Chong Zeng; Ping Yang; Bing Chen; We Jiang; Shi-Suo Du

    2012-01-01

    To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer (PCa).We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009.The overall survival rate after bone metastases was calculated using the Kaplan-Meier method.The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models.The follow-up rate was 100%,the follow-up cases during 1,3 and 5 years were 103,79 and 55,respectively.The 1-,3- and 5-year survival rates were 89.1%,60.9% and 49.8%,respectively,with a median survival time of 48.5 months for patients with bone metastases from PCa.In univariate analysis,age,Gleason score,clinical stage,the number of bone lesions,alkaline phosphatase (ALP) level,invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis.By multivariate analysis using Cox regression,ALP level,Gleason score and non-regional lymph node metastases were independent prognostic factors.These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.

  13. Analysis on the childhood and adolescent differentiated thyroid cancer: clinical features and radioiodine treatment

    International Nuclear Information System (INIS)

    Objective: Children with differentiated thyroid cancer (DTC) frequently present with more extensive disease than adults. The aim of this study was to characterize the clinical features of child-hood and adolescent DTC and evaluate the outcome and safety of radioiodine treatment. Methods: The records of 38 childhood and adolescent DTC cases, with 28 females and 10 males (mean age: 16.4 years) were reviewed. At diagnosis, all had metastatic lesions with 38 at regional lymph nodes, 15 at lung, 2 at brain and bone. Twenty-three had a total thyroidectomy, 7 had subtotal thyroidectomy, 5 had lobectomy, and 3 had other treatment. All received post-operative radioiodine therapy. All had follow-up for at least one year. Results: At the time of follow-up, all were survive (with a median follow-up of 5.13 years). Four-teen patients had no evidence of disease, 16 had partial remission, and 8 were stable disease. Conclusions: DTC of the thyroid in childhood and adolescent has high risks of residual/recurrence and metastasis. Post-thyroidectomy oral administration of radioiodine was an effective and safety adjuvant therapy for outcomes. (authors)

  14. Relationship between H.Pylori infection and clinicopathological features and prognosis of gastric cancer

    International Nuclear Information System (INIS)

    Aimed to assess the relationship between H.Pylori and the clinicopathological features and prognosis of gastric cancer by quantitative detection of H.Pylori. 157 patients were enrolled, all patients had a record of clinicopathological parameters. Specimens including the tumor and non-neoplastic were detected for H.Pylori by Real-Time PCR and analyzed clinical data retrospectively. Variables independently affecting prognosis were investigated by means of multivariate analysis using the Cox proportional hazards model. H.Pylori infection was greater in non-neoplastic tissue than the tumor tissue (p < 0.05), H.Pylori infection and its copies were related to the tumor site and N staging (p < 0.05). Overall survival (OS) in all 157 patients has no correlation with the H.Pylori infection status (p = 0.715). As to the patients who underwent a curative surgery, relapse-free survival (RFS) has no correlation with the H.Pylori infection status (p = 0.639). Among the H.Pylori positive patients, OS and RFS of those with higher copies were longer than in patients with low copies, but there was no significant statistical difference. H.Pylori infection status and its copies were related to N staging. The OS and RFS in patients with positive H.Pylori status has no significant difference from the patients with negative H.Pylori status

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

    Science.gov (United States)

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

    2014-03-01

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

  16. DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes

    OpenAIRE

    Santarpia, Libero; Iwamoto, Takayuki; Di Leo, Angelo; Hayashi, Naoki; Bottai, Giulia; Stampfer, Martha; André, Fabrice; Turner, Nicholas C.; Symmans, W Fraser; Hortobágyi, Gabriel N.; Pusztai, Lajos; Bianchini, Giampaolo

    2013-01-01

    DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. In this study, the authors sought to assess the differential expression, bimodal distribution, and prognostic and predictive role of DNA repair genes in individual breast cancer molecular subtypes including estrogen receptor-positive/ HER2-negative, estrogen receptor-negative/HER2-negative, and HER2-positive cancers. The predictive value of DNA repair g...

  17. 2007 EORTC-NCI-ASCO Annual Meeting: Molecular Markers in Cancer

    OpenAIRE

    Lukan, C

    2008-01-01

    The recent EORTC-NCI-ASCO Annual Meeting on ‘Molecular Markers in Cancer’ was held on 15–17 November 2007 in Brussels, Belgium. It was the largest meeting to date and marked the first year in which the American Association of Clinical Oncology (ASCO) joined in the efforts of the European Organisation for Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) in organizing this annual event. More than 300 clinicians, pathologists, laboratory scientists and representat...

  18. Peptide-Targeted Nanoglobular Gd-DOTA Monoamide Conjugates for Magnetic Resonance Cancer Molecular Imaging

    OpenAIRE

    Tan, Mingqian; Wu, Xueming; Jeong, Eun-Kee; Chen, Qianjin; Lu, Zheng-Rong

    2010-01-01

    Effective imaging of cancer molecular biomarker is critical for accurate cancer diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the fibrin-fibronectin complexes presented in tumor extracellular matrix. In this study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance (MR) imaging of the fibrin-fibronectin complexes in tumor. The targeted nanoglobular contrast agents were prepared by conjugating peptide...

  19. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer

    OpenAIRE

    Budinska, Eva; Popovici, Vlad; Tejpar, Sabine; d'Ario, Giovanni; Lapique, Nicolas; Sikora, Katarzyna Otylia; Di Narzo, Antonio Fabio; Yan, Pu; Hodgson, John Graeme; Weinrich, Scott; Bosman, Fred; Roth, Arnaud; Delorenzi, Mauro

    2013-01-01

    The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defi...

  20. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

    OpenAIRE

    Budinska E.; Popovici V.; Tejpar S; D' Ario G.; Lapique N.; Sikora K.O.; Di Narzo A.F.; Yan P.; Hodgson J.G.; Weinrich S.; Bosman F.; Roth A.; Delorenzi M.

    2013-01-01

    The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defi...

  1. Early Cancer Detection and Targeted Therapy by Magnetic Resonance Molecular Imaging and Nano Medicine

    OpenAIRE

    Li, Zhao

    2015-01-01

    The common theme of my 5-year PhD research is to channel progress in spin physics and nano-bio-materials into meaningful improvements in the theoretical studies, methodological developments, and advanced applications of magnetic resonance (MR) to: 1) MR Molecular Imaging: to detect lesions (especially cancers) at early stages through imaging the existence and locations of physiologically important biomarkers; and2) MR Nano Medicine: to cure diseases (especially cancers) by targeted therapy th...

  2. The molecular biology of cancer and its diagnostic implications.

    Science.gov (United States)

    Aw, S E

    1981-07-01

    The origin of cancer is discussed from the view of the two-stage model of malignant transformation. Environmental carcinogens play an integral part in the process. When the cell is transformed, cell surface changes are found for such components as fibronectin, collagen, actin, myosin, glycopeptides and enzyme activities. Hormone receptors are a fruitful line for research. Both qualitative and quantitative alterations are also seen with cancer cell enzymes. Among enzymes that can be used as markers of malignancy are the protease. A group of oncodevelopmental proteins, hormonal and non-hormonal, are in regular service for the management of cancer. Improvements in diagnostic specificity can be expected as the newer technologies are harnessed for medical use.

  3. MicroRNAs and cancer resistance: A new molecular plot.

    Science.gov (United States)

    Fanini, F; Fabbri, M

    2016-05-01

    The most common cause of cancer relapse is drug resistance, acquired or intrinsic, which strongly limits the efficacy of both conventional and new targeted chemotherapy. MicroRNAs (miRNAs) are a growing, large family of short noncoding RNAs frequently dysregulated in malignancies. Although the mechanism of miRNA-mediated drug resistance is not fully understood, an increasing amount of evidence suggests their involvement in the acquisition of tumor cell drug resistance, pointing towards the need for novel and more innovative therapeutic approaches. Use of antagomiRs or mimics can modulate specific miRNAs in order to restore gene networks and signaling pathways, perhaps optimizing chemotherapies by increasing cancer cell sensitivity to drugs. The aim of this review is to provide a state-of-the-art scenario with regard to the most recent discoveries in the field of miRNAs involved in the process of resistance to cancer therapy.

  4. The molecular and cellular origin of human prostate cancer.

    Science.gov (United States)

    Packer, John R; Maitland, Norman J

    2016-06-01

    Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs.

  5. Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly

    DEFF Research Database (Denmark)

    Miller, Bryan W; Morton, Jennifer P; Pinese, Mark;

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility...

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

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Bishnu P. [Division of Gastroenterology, Department of Medicine, University of Michigan, School of Medicine, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109 (United States); Wang, Thomas D., E-mail: thomaswa@umich.edu [Division of Gastroenterology, Department of Medicine, University of Michigan, School of Medicine, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109 (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2010-06-11

    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.

  7. Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin.

    Science.gov (United States)

    Drew, Janice E

    2012-02-01

    Obesity is linked to increased risk of colon cancer, currently the third most common cancer. Consequently rising levels of obesity worldwide are likely to significantly impact on obesity-related colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases colon cancer risk is thus a focus for research to inform strategies to prevent the increasing trend in obesity-related cancers. This review will consider research on deregulation of adipokine signalling, a consequence of altered adipokine hormone secretion from excess adipose tissue, with a focus on leptin, which has been studied extensively as a potential mediator of obesity-related colon cancer. Numerous investigations using colon cell lines in vitro, in vivo studies in rodents and investigations of colon cancer patients illuminate the complexity of the interactions of leptin with colon tissues via leptin receptors expressed by the colon epithelium. Although evidence indicates a role for leptin in proliferation of colon epithelial cells in vitro, this has been contradicted by studies in rodent models. However, recent studies have indicated that leptin may influence inflammatory mediators linked with colon cancer and also promote cell growth dependent on genotype and is implicated in growth promotion of colon cancer cells. Studies in human cancer patients indicate that there may be different tumour sub-types with varying levels of leptin receptor expression, indicating the potential for leptin to induce variable responses in the different tumour types. These studies have provided insights into the complex interplay of adipokines with responsive tissues prone to obesity-related colon cancer. Deregulation of adipokine signalling via adipokine receptors located in the colon appears to be a significant factor in obesity-related colon cancer. Molecular profiling of colon tumours will be a useful tool in future strategies to characterise the influence that adipokines may have

  8. Male breast cancer: An update in diagnosis, treatment and molecular profiling

    OpenAIRE

    Onami, Susan; Ozaki, Melanie; Mortimer, Joanne E; Pal, Sumanta Kumar

    2010-01-01

    Significant advances have been made in the diagnosis and treatment of female breast cancer, resulting in a decline in incidence and a global improvement in clinical outcome. The statistics for male breast cancer (MBC) stand in sharp contrast – over the past several decades, there has been a steady rise in the incidence of this disease, and clinical outcome has improved at a much slower pace. In the current review, the clinicopathologic features of MBC are described in detail. An emphasis is p...

  9. Inferences of drug responses in cancer cells from cancer genomic features and compound chemical and therapeutic properties

    Science.gov (United States)

    Wang, Yongcui; Fang, Jianwen; Chen, Shilong

    2016-01-01

    Accurately predicting the response of a cancer patient to a therapeutic agent is a core goal of precision medicine. Existing approaches were mainly relied primarily on genomic alterations in cancer cells that have been treated with different drugs. Here we focus on predicting drug response based on integration of the heterogeneously pharmacogenomics data from both cell and drug sides. Through a systematical approach, named as PDRCC (Predict Drug Response in Cancer Cells), the cancer genomic alterations and compound chemical and therapeutic properties were incorporated to determine the chemotherapeutic response in cancer patients. Using the Cancer Cell Line Encyclopedia (CCLE) study as the benchmark dataset, all pharmacogenomics data exhibited their roles in inferring the relationships between cancer cells and drugs. When integrating both genomic resources and compound information, the prediction coverage was significantly increased. The validity of PDRCC was also supported by its effective in uncovering the unknown cell-drug associations with database and literature evidences. It set the stage for clinical testing of novel therapeutic strategies, such as the sensitive association between cancer cell ‘A549_LUNG’ and compound ‘Topotecan’. In conclusion, PDRCC offers the possibility for faster, safer, and cheaper the development of novel anti-cancer therapeutics in the early-stage clinical trails. PMID:27645580

  10. Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus.

    Science.gov (United States)

    Byun, Haewon; Kwon, Soohyun; Ahn, Hee-Jeong; Liu, Hong; Forrest, Douglas; Demb, Jonathan B; Kim, In-Jung

    2016-08-01

    The superior colliculus (SC) is a midbrain center involved in controlling head and eye movements in response to inputs from multiple sensory modalities. Visual inputs arise from both the retina and visual cortex and converge onto the superficial layer of the SC (sSC). Neurons in the sSC send information to deeper layers of the SC and to thalamic nuclei that modulate visually guided behaviors. Presently, our understanding of sSC neurons is impeded by a lack of molecular markers that define specific cell types. To better understand the identity and organization of sSC neurons, we took a systematic approach to investigate gene expression within four molecular families: transcription factors, cell adhesion molecules, neuropeptides, and calcium binding proteins. Our analysis revealed 12 molecules with distinct expression patterns in mouse sSC: cadherin 7, contactin 3, netrin G2, cadherin 6, protocadherin 20, retinoid-related orphan receptor β, brain-specific homeobox/POU domain protein 3b, Ets variant gene 1, substance P, somatostatin, vasoactive intestinal polypeptide, and parvalbumin. Double labeling experiments, by either in situ hybridization or immunostaining, demonstrated that the 12 molecular markers collectively define 10 different sSC neuronal types. The characteristic positions of these cell types divide the sSC into four distinct layers. The 12 markers identified here will serve as valuable tools to examine molecular mechanisms that regulate development of sSC neuronal types. These markers could also be used to examine the connections between specific cell types that form retinocollicular, corticocollicular, or colliculothalamic pathways. J. Comp. Neurol. 524:2300-2321, 2016. © 2016 Wiley Periodicals, Inc. PMID:26713509

  11. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

    OpenAIRE

    Mario Orozco-Morales; Giovanny Soca-Chafre; Pedro Barrios-Bernal; Norma Hernández-Pedro; Oscar Arrieta

    2016-01-01

    Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical ...

  12. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer.

    Science.gov (United States)

    Orozco-Morales, Mario; Soca-Chafre, Giovanny; Barrios-Bernal, Pedro; Hernández-Pedro, Norma; Arrieta, Oscar

    2016-01-01

    Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use. PMID:26941482

  13. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mario Orozco-Morales

    2016-01-01

    Full Text Available Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs, the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs. Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use.

  14. Nuclear EGFR as a molecular target in cancer

    International Nuclear Information System (INIS)

    The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell’s nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future

  15. Molecular Response to Hypoxia; from C. elegans to cancer

    NARCIS (Netherlands)

    Gort, E.H.

    2008-01-01

    Oncogenesis is governed by genetic and epigenetic events that co-opt to malignant progression. The role of the microenvironment in tumorigenesis and maintenance is increasingly appreciated. Oxygen supply is one of the rate limiting microenvironmental factors. Like healthy cells, cancer cells rely on

  16. Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

  17. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning.

  18. Sphingosine kinase 1 is a relevant molecular target in gastric cancer

    DEFF Research Database (Denmark)

    Fuereder, Thorsten; Hoeflmayer, Doris; Jaeger-Lansky, Agnes;

    2011-01-01

    Sphingosine kinase 1 (Sphk1), a lipid kinase implicated in cell transformation and tumor growth, is overexpressed in gastric cancer and is linked with a poor prognosis. The biological relevance of Sphk1 expression in gastric cancer is unclear. Here, we studied the functional significance of Sphk1...... as a novel molecular target for gastric cancer by using an antisense oligonucleotide approach in vitro and in vivo. Gastric cancer cell lines (MKN28 and N87) were treated with Sphk1 with locked nucleic acid-antisense oligonucleotides (LNA-ASO). Sphk1 target regulation, cell growth, and apoptosis were...... assessed for single-agent Sphk1 LNA-ASO and for combinations with doxorubicin. Athymic nude mice xenografted with gastric cancer cells were treated with Sphk1 LNA and assessed for tumor growth and Sphk1 target regulation, in vivo. In vitro, nanomolar concentrations of Sphk1 LNA-ASO induced an approximately...

  19. CD24 as a Molecular Marker in Ovarian Cancer: A Literature Review

    Directory of Open Access Journals (Sweden)

    Lu Huang

    2016-01-01

    Full Text Available Ovarian cancer is the most lethal gynecologic cancer, with a mortality rate of > 60%. Cancer stem cell (CSC hypothesis offers an attractive explanation of chemoresistance, metastasis, etc., associated with the disease. However, there are still controversy and limitation in defining the CSC markers. CD24 is a mucin-type glycosyl-phosphatidylinositol-linked glycoprotein, expressed on the surface of cells, which serves as a normal receptor for P-selectin and is found involved in molecular adhesion and metastatic tumor spread. Expression rate of CD24 has been associated with progression of various cancers and poor survival rates. In this review, the function of CD24 in ovarian cancer, especially in ovarian CSC system, was discussed in an effort to broaden the interpretation of potential mechanism.

  20. Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein

    Directory of Open Access Journals (Sweden)

    Moon Sung-Pyo

    2004-10-01

    Full Text Available Abstract Background Heptaplatin is a new platinum derivative with anticancer activity against various cancer cell lines, including cisplatin-resistant cancer cell lines (Cancer Chemother Pharmacol 1995; 35: 441. Methods Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines has been investigated in connection with metallothionein (MT. Cytotoxicity was determined by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was carried out to examine the function of MT. Results Of various gastric cancer cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA, respectively, showing 80-fold difference. The IC50 values of SNU-638 to cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold greater than those of SNU-601, respectively. Heptaplatin was more effective against cisplatin-resistant and MT-transfected gastric cancer sublines than cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but not zinc, induction of MT. Conclusion These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction.

  1. Sentinel lymph node detection in breast cancer patients using surgical navigation system based on fluorescence molecular imaging technology

    Science.gov (United States)

    Chi, Chongwei; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Tian, Jie

    2015-03-01

    Introduction: Precision and personalization treatments are expected to be effective methods for early stage cancer studies. Breast cancer is a major threat to women's health and sentinel lymph node biopsy (SLNB) is an effective method to realize precision and personalized treatment for axillary lymph node (ALN) negative patients. In this study, we developed a surgical navigation system (SNS) based on optical molecular imaging technology for the precise detection of the sentinel lymph node (SLN) in breast cancer patients. This approach helps surgeons in precise positioning during surgery. Methods: The SNS was mainly based on the technology of optical molecular imaging. A novel optical path has been designed in our hardware system and a feature-matching algorithm has been devised to achieve rapid fluorescence and color image registration fusion. Ten in vivo studies of SLN detection in rabbits using indocyanine green (ICG) and blue dye were executed for system evaluation and 8 breast cancer patients accepted the combination method for therapy. Results: The detection rate of the combination method was 100% and an average of 2.6 SLNs was found in all patients. Our results showed that the method of using SNS to detect SLN has the potential to promote its application. Conclusion: The advantage of this system is the real-time tracing of lymph flow in a one-step procedure. The results demonstrated the feasibility of the system for providing accurate location and reliable treatment for surgeons. Our approach delivers valuable information and facilitates more detailed exploration for image-guided surgery research.

  2. Automated Breast Cancer Diagnosis based on GVF-Snake Segmentation, Wavelet Features Extraction and Neural Network Classification

    Directory of Open Access Journals (Sweden)

    Abderrahim Sebri

    2007-01-01

    Full Text Available Breast cancer accounts for the second most cancer diagnoses among women and the second most cancer deaths in the world. In fact, more than 11000 women die each year, all over the world, because this disease. The automatic breast cancer diagnosis is a very important purpose of medical informatics researches. Some researches has been oriented to make automatic the diagnosis at the step of mammographic diagnosis, some others treated the problem at the step of cytological diagnosis. In this work, we describes the current state of the ongoing the BC automated diagnosis research program. It is a software system that provides expert diagnosis of breast cancer based on three step of cytological image analysis. The first step is based on segmentation using an active contour for cell tracking and isolating of the nucleus in the studied image. Then from this nucleus, have been extracted some textural features using the wavelet transforms to characterize image using its texture, so that malign texture can be differentiated from benign on the assumption that tumoral texture is different from the texture of other kinds of tissues. Finally, the obtained features will be introduced as the input vector of a Multi-Layer Perceptron (MLP, to classify the images into malign and benign ones.

  3. Features of undiagnosed breast cancers at screening breast MR imaging and potential utility of computer-aided evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Mirinae; Cho, Nariya; Bea, Min Sun; Koo, Hye Ryoung; Kim, Won Hwa; Lee, Su Hyun; Chu, A Jung [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-02-15

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

  4. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs.

  5. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. PMID:26454049

  6. Leishmania (Viannia panamensis expresses a nuclease with molecular and biochemical features similar to the Endonuclease G of higher eukaryotes*

    Directory of Open Access Journals (Sweden)

    Miguel A Toro-Londoño

    2011-06-01

    Full Text Available Objective: To characterize the molecular and biochemical features of the Endonuclease G of Leishmania (Viannia panamensis. Methods: The gene of the putative L. (V. panamensis Endonuclease G was amplified, cloned, and sequenced. The recombinant protein was produced in a heterologous expression system and biochemical assays were run to determine its ion, temperature, and pH preferences. Results: The L. (V. panamensis rENDOG has biochemical features similar to those found in other trypanosomatids and higher eukaryotes. In addition, phylogenetic analysis revealed a possible evolutionary relationship with metazoan ENDOG. Conclusions: L. (V. panamensis has a gene that codifies an ENDOG homologous to those of higher organisms. This enzyme can be produced in Escherichia coli and is able to degrade covalently closed circular double-stranded DNA. It has a magnesium preference, can be inhibited by potassium, and is able to function within a wide temperature and pH range.

  7. Leishmania (Viannia panamensis expresses a nuclease with molecular and biochemical features similar to the Endonuclease G of higher eukaryotes

    Directory of Open Access Journals (Sweden)

    Miguel A. Toro-Londoño

    2011-06-01

    Full Text Available Objective: To characterize the molecular and biochemical features of the Endonuclease G of Leishmania (Viannia panamensis.Methods: The gene of the putative L. (V. panamensis Endonuclease G was amplified, cloned, and sequenced. The recombinant protein was produced in a heterologous expression system and biochemical assays were run to determine its ion, temperature, and pH preferences.Results: The L. (V. panamensis rENDOG has biochemical features similar to those found in other trypanosomatids and higher eukaryotes. In addition, phylogenetic analysis revealed a possible evolutionary relationship with metazoan ENDOG.Conclusions: L. (V. panamensis has a gene that codifies an ENDOG homologous to those of higher organisms. This enzyme can be produced in Escherichia coli and is able to degrade covalently closed circular double-stranded DNA. It has a magnesium preference, can be inhibited by potassium, and is able to function within a wide temperature and pH range.

  8. Studies on the Conformational Features of Neomycin-B and its Molecular Recognition by RNA and Bacterial Defense Proteins

    Science.gov (United States)

    Asensio, Juan Luis; Bastida, Agatha; Jiménez-Barbero, Jesús

    According to NMR and molecular dynamics simulations, the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. Very probably, this feature allows the adaptation of these ligands to the spatial and electronic requirements of different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the distinct enzymes involved in bacterial resistance are consistent with this view. This conformational diversity can, in certain favorable cases, be exploited in the design of new antibiotic derivatives not susceptible to enzymatic inactivation, by designing tailor-made conformationally locked aminoglycosides.

  9. Differential CT features between malignant mesothelioma and pleural metastasis from lung cancer or extra thoracic primary tumor mimicking malignant mesothelioma

    International Nuclear Information System (INIS)

    To evaluate the differential CT features found among malignant mesothelioma and pleural metastasis from lung cancer and from extra-thoracic primary tumor which on CT mimic malignant mesothelioma. Forty-four patients who on chest CT scans showed pleural thickening suggesting malignant pleural disease and in whom this condition was pathologically confirmed were included in this study. On the basis of their pathologically proven primary disease (malignant mesothelioma (n=3D14), pleural metastasis of lung cancer (n=3D18), extra thoracic primary tumor (n=3D12). They were divided into three groups. Cases of lung which on CT showed a primary lung nodule or endobronchial mass with pleural lesion, or manifested only pleural effusion, were excluded. The following eight CT features were retrospectively analyzed: 1) configuration of pleural lesion (type I, single or multiple separate nodules, type II, localized flat pleural thickening, type III, diffuse flat pleural thickening; type IV, type III with pleural nodules superimposed; type V, mass filling the hemithorax), 2) the presence of pleural effusion, 3) chest wall or rib invasion, 4) the involvement of a major fissure, 5) extra-pleural fat proliferation, 6) calcified plaque, 7) metastatic lymph nodes, 8) metastatic lung modules. In malignant mesothelioma, type IV (8/14) or II (4/14) pleural thickening was relatively frequent. Pleural metastasis of lung cancer favored type IV (8/18) or I (6/18) pleural thickening, while pleural metastasis from extrathoracic primary tumor showed a variable thickening configuration, except type V. Pleural metastasis from lung cancer and extrapleural primary tumor more frequently showed type I configuration than did malignant mesothelioma, and there were significant differences among the three groups. Fissural involvement, on the other hand, was significantly more frequent in malignant mesothelioma than in pleural metastasis from lung cancer or extrapleural primary tumor. Metastatic lymph nodes

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

    Science.gov (United States)

    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.

  11. Comparison of Radiologic Features of Triple-Negative and Estrogen Receptor/Progesteron Receptor Positive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Joong; Kim, Keum Won; Kim, Dae Ho; Cho, Yong Jun; Hwang, Cheol Mog; Seo, Jae Young; Kim, Jin Suk; Yoon, Dae Sung [Dept. of Konyang University College of Medicine, Konyang University Hospital, Daejeon (Korea, Republic of); Kim, Gyu Soon [Dept. of Radiology, Eulji University College of Medicine, Eulji University Hospital, Daejeon (Korea, Republic of)

    2013-06-15

    To retrospectively investigate the imaging [mammographic, ultrasonographic (US), magnetic resonance (MR) imaging] features and standardized uptake values (SUV) in positron emission tomography (PET)/computed tomography (CT) of triple-negative breast cancers (TNBC) and to compare them with breast cancers that are either estrogen receptor (ER) positive or progesteron receptor (PR) positive. 155 breast cancers cases were identified in 134 women (mean age, 51 years; range, 31-86 years). Surgically confirmed TNBC (n = 27) and ER-positive/PR-positive breast cancers (n = 81) were included among them. Cancers were investigated with mammography (n = 81), US (n = 106), MR imaging (n = 34) and PET-CT (n = 59). Mammographic findings are identified by detection of characteristic masses and microcalcifications. US findings included tumor size, margin, tumor shape, calcification and posterior shadowing. MR findings included tumor size, shape, margin, internal enhancement, intratumoral signal intensity and kinetics. Peak SUVs (p-SUV) of breast cancers were evaluated in PET/CT. These findings were compared with TNBC and ER/PR positive groups. Mammographic findings had no significant association with the TNBC. High pathological grade (p < 0.05), larger than 2 cm in size, well-marginal mass, and round or oval-shaped (p < 0.05) is US were significantly associated with TNBC. In MR imaging, round mass shape (p < 0.05), well-circumscribed mass margin (p < 0.05), rim enhancement (p < 0.05), were significantly associated with TNBC. The peak SUV of TNBC tend to be higher than that of ER-positive/PR-positive breast cancer (7.95 {+-} 5.50 vs. 4.91 {+-} 3.00, p < 0.05). TNBC tend to have high pathological grade, are of a large, round and smooth mass with rim enhancement on MR and US. In addition to above features, PET-CT with SUV estimation can improve the accuracy of test through the evaluation of TNBC.

  12. Covalent features in the hydrogen bond of a water dimer: molecular orbital analysis

    CERN Document Server

    Wang, Bo; Dai, Xing; Gao, Yang; Wang, Zhigang; Zhang, Rui-Qin

    2015-01-01

    The covalent-like characteristics of hydrogen bonds offer a new perspective on intermolecular interactions. Here, using density functional theory and post-Hartree-Fock methods, we reveal that there are two bonding molecular orbitals (MOs) crossing the O and H atoms of the hydrogen-bond in water dimer. Energy decomposition analysis also shows a non-negligible contribution of the induction term. These results illustrate the covalent-like character of the hydrogen bond between water molecules, which contributes to the essential understanding of ice, liquid water, related materials, and life sciences.

  13. Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells.

    Science.gov (United States)

    Clapéron, A; Guedj, N; Mergey, M; Vignjevic, D; Desbois-Mouthon, C; Boissan, M; Saubaméa, B; Paradis, V; Housset, C; Fouassier, L

    2012-03-15

    Scaffold proteins form multiprotein complexes that are central to the regulation of intracellular signaling. The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is highly expressed at the plasma membrane of normal biliary epithelial cells and binds epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with oncogenic properties. This study investigated EBP50-EGFR interplay in biliary cancer. We report that in a collection of 106 cholangiocarcinomas, EBP50 was delocalized to the cytoplasm of tumor cells in 66% of the cases. Ectopic expression of EBP50 was correlated with the presence of satellite nodules and with the expression of EGFR, which was at the plasma membrane, implying a loss of interaction with EBP50 in these cases. In vitro, loss of interaction between EBP50 and EGFR was mimicked by EBP50 depletion using a small interfering RNA approach in human biliary carcinoma cells co-expressing the two proteins at their plasma membrane, and in which interaction between EBP50 and EGFR was validated. EBP50 depletion caused an increase in EGFR expression at their surface, and a sustained activation of the receptor and of its downstream effectors (extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3) in both basal and EGF-stimulated conditions. Cells lacking EBP50 showed epithelial-to-mesenchymal transition-associated features, including reduction in E-cadherin and cytokeratin-19 expression, induction of S100A4 and of the E-cadherin transcriptional repressor, Slug, and loss of cell polarity. Accordingly, depletion of EBP50 induced the disruption of adherens junctional complexes, the development of lamellipodia structures and the subsequent acquisition of motility properties. All these phenotypic changes were prevented upon inhibition of EGFR tyrosine kinase by gefitinib. These findings indicate that loss of EBP50 at the plasma membrane in tumor cells may contribute to biliary carcinogenesis

  14. Curcumin: a Polyphenol with Molecular Targets for Cancer Control.

    Science.gov (United States)

    Qadir, Muhammad Imran; Naqvi, Syeda Tahira Qousain; Muhammad, Syed Aun

    2016-01-01

    Curcumin, is a polyphenol from Curcuma longa (turmeric plant), is a polyphenol that belongs to the ginger family which has long been used in Ayurveda medicines to treat various diseases such as asthma, anorexia, coughing, hepatic diseases, diabetes, heart diseases, wound healing and Alzheimer's. Various studies have shown that curcumin has anti-infectious, anti-inflammatory, anti-oxidant, hepatoprotective, thrombosuppressive, cardio protective, anti-arthritic, chemo preventive and anti-carcinogenic activities. It may suppress both initiation and progression stages of cancer. Anticancer activity of curcumin is due to negative regulation of inflammatory cytokines, transcription factors, protein kinases, reactive oxygen species (ROS) and oncogenes. This review focuses on the different targets of curcumin to treat cancer. PMID:27356682

  15. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    International Nuclear Information System (INIS)

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[11C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

  16. Hyperpolarized 13C MR for Molecular Imaging of Prostate Cancer

    OpenAIRE

    Wilson, David M.; Kurhanewicz, John

    2014-01-01

    Hyperpolarization using dissolution dynamic nuclear polarization has emerged as a versatile method to dramatically improve the MR signal of low-sensitivity nuclei. This technique facilitates the study of real-time metabolism in vitro and in vivo using 13C-enriched substrates and has been applied to numerous models of human disease. In particular, several mechanisms underlying prostate cancer have been interrogated using hyperpolarized 13C MR spectroscopy. This review highlights key metabolic ...

  17. Modeling emission features of salicylidene aniline molecular crystals: A QM/QM' approach.

    Science.gov (United States)

    Presti, Davide; Labat, Frédéric; Pedone, Alfonso; Frisch, Michael J; Hratchian, Hrant P; Ciofini, Ilaria; Cristina Menziani, Maria; Adamo, Carlo

    2016-04-01

    A new computational protocol relying on the use of electrostatic embedding, derived from QM/QM' ONIOM calculations, to simulate the effect of the crystalline environment on the emission spectra of molecular crystals is here applied to the β-form of salicylidene aniline (SA). The first singlet excited states (S1 ) of the SA cis-keto and trans-keto conformers, surrounded by a cluster of other molecules representing the crystalline structure, were optimized by using a QM/QM' ONIOM approach with and without electronic embedding. The model system consisting of the central salicylidene aniline molecule was treated at the DFT level by using either the B3LYP, PBE0, or the CAM-B3LYP functional, whereas the real system was treated at the HF level. The CAM-B3LYP/HF level of theory provides emission energies in good agreement with experiment with differences of -20/-32 nm (cis-keto form) and -8/-14 nm (trans-keto form), respectively, whereas notably larger differences are obtained using global hybrids. Though such differences on the optical properties arise from the density functional choice, the contribution of the electronic embedding is rather independent of the functional used. This plays in favor of a more general applicability of the present protocol to other crystalline molecular systems. PMID:26919703

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 乳腺癌的分子分型%Molecular classification of breast cancer

    Institute of Scientific and Technical Information of China (English)

    张百红; 岳红云

    2014-01-01

    乳腺癌是一种分子水平异质性很高的疾病,分子分型可为乳腺癌的个体化治疗提供一个新视野.在分子病理学、分子生物学和系统生物学指导下,乳腺癌经历了4类分型、70种和21种基因蛋白谱以及基因组整合分类等不同分型.这些分型将为乳腺癌的精确治疗提供指导.%Breast cancer is a group of heterogeneous diseases.Molecular portraits provide a new insight for personalized cancer management in breast cancer.According to the molecular pathology,molecular biology and system biology,breast cancer goes through different typing methods,including four subclasses,geneexpression signature and integrated genomic classification.These major subtypes of breast cancer may provide guidance for precise therapeutics.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. MOLECULAR MARKERS OF BLADDER CANCER: FROM THE PARTICULAR TO THE GENERAL

    Directory of Open Access Journals (Sweden)

    A. A. Zabolotneva

    2014-08-01

    Full Text Available Bladder cancer (BC is the second most common urinary tract malignancy. Early diagnosis of BC generally increases the probability of successful treatment in a patient. The paper considers noninvasive diagnosis methods for BC and gives a database of the known molecular markers of this disease.

  2. MOLECULAR MARKERS OF BLADDER CANCER: FROM THE PARTICULAR TO THE GENERAL

    OpenAIRE

    A. A. Zabolotneva; N. M. Gaifullin; A. A. Buzdin; B. Ya. Alekseyev; Yu. Yu. Andreyeva; P. V. Shegai; D. G. Sokov; I. G. Rusakov

    2011-01-01

    Bladder cancer (BC) is the second most common urinary tract malignancy. Early diagnosis of BC generally increases the probability of successful treatment in a patient. The paper considers noninvasive diagnosis methods for BC and gives a database of the known molecular markers of this disease.

  3. Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer.

    Science.gov (United States)

    Ross, A E; D'Amico, A V; Freedland, S J

    2016-03-01

    An increased molecular understanding of localized prostate cancer and the improved ability for molecular testing of pathologic tissue has led to the development of multiple clinical assays. Here we review the relevant molecular biology of localized prostate cancer, currently available tissue-based tests and describe which is best supported for use in various clinical scenarios. Literature regarding testing of human prostate cancer tissue with Ki-67, PTEN (by immunohistochemistry (IHC) or fluroescence in situ hybridization (FISH)), ProMark, Prolaris, OncotypeDX Prostate and Decipher was reviewed to allow for generation of expert opinions. At diagnosis, evaluation of PTEN status, use of ProMark or OncotypeDX Prostate in men with Gleason 6 or 3+4=7 disease may help guide the use of active surveillance. For men with Gleason 7 or above disease considering watchful waiting, Ki-67 and Prolaris add independent prognostic information. For those men who have undergone prostatectomy and have adverse pathology, Decipher testing may aid in the decision to undergo adjuvant radiation. Newly available molecular tests bring opportunities to improve decision making for men with localized prostate cancer. A review of the currently available data suggests clinical scenarios for which each of these tests may have the greatest utility. PMID:26123120

  4. Molecular prognostic factors in locally irresectable rectal cancer treated preoperatively by chemo-radiotherapy

    NARCIS (Netherlands)

    Reerink, O; Karrenbeld, Arend; Plukker, JTM; Verschueren, Rene; Szabo, BG; Sluiter, WJ; Hospers, GAP; Mulder, NH

    2004-01-01

    PURPOSE: The aim of this study was to determine the relationship between survival and value of molecular markers in the primary tumour in a group of patients with irresectable rectal cancer, treated with preoperative chemo-radiotherapy. MATERIALS AND METHODS: Immunohistochemistry for p53, p21, bcl-2

  5. From molecular classification to targeted therapeutics: the changing face of systemic therapy in metastatic gastroesophageal cancer.

    Science.gov (United States)

    Murphy, Adrian; Kelly, Ronan J

    2015-01-01

    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.

  6. Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer

    NARCIS (Netherlands)

    E. Hoekstra (Elmer); L.L. Kodach (Liudmila L.); A. Mooppilmadham Das (Asha); R.R. Ruela-de-Sousa (Roberta); C.V. Ferreira (Carmen); J.C. Hardwick (James); C.J. van der Woude (Janneke); M.P. Peppelenbosch (Maikel); T.L.M. ten Hagen (Timo); G.M. Fuhler (Gwenny)

    2015-01-01

    textabstractPhosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influ

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

    Science.gov (United States)

    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. PMID:26677427

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

    Science.gov (United States)

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

    2015-03-01

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

  9. Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors.

    Directory of Open Access Journals (Sweden)

    Teresa Mairal

    Full Text Available The thyroid hormone and retinol transporter protein known as transthyretin (TTR is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis.

  10. Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors.

    Science.gov (United States)

    Mairal, Teresa; Nieto, Joan; Pinto, Marta; Almeida, Maria Rosário; Gales, Luis; Ballesteros, Alfredo; Barluenga, José; Pérez, Juan J; Vázquez, Jesús T; Centeno, Nuria B; Saraiva, Maria Joao; Damas, Ana M; Planas, Antoni; Arsequell, Gemma; Valencia, Gregorio

    2009-01-01

    The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis. PMID:19125186

  11. Immunoregulatory network and cancer-associated genes: molecular links and relevance to aging

    Directory of Open Access Journals (Sweden)

    Robi Tacutu

    2011-09-01

    Full Text Available Although different aspects of cancer immunity are a subject of intensive investigation, an integrative view on the possible molecular links between immunoregulators and cancer-associated genes has not yet been fully considered. In an attempt to get more insights on the problem, we analyzed these links from a network perspective. We showed that the immunoregulators could be organized into a miRNA-regulated PPI network-the immunoregulatory network. This network has numerous links with cancer, including (i cancerassociated immunoregulators, (ii direct and indirect protein-protein interactions (through the common protein partners, and (iii common miRNAs. These links may largely determine the interactions between the host's immunity and cancer, supporting the possibility for co-expression and post-transcriptional co-regulation of immunoregulatory and cancer genes. In addition, the connection between immunoregulation and cancer may lie within the realm of cancer-predisposing conditions, such as chronic inflammation and fibroproliferative repair. A gradual, age-related deterioration of the integrity and functionality of the immunoregulaory network could contribute to impaired immunity and generation of cancer-predisposing conditions.

  12. Facial Nerve Palsy: An Unusual Presenting Feature of Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ozcan Yildiz

    2011-01-01

    Full Text Available Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in men and women; it is responsible for 1.3 million deaths annually worldwide. It can metastasize to any organ. The most common site of metastasis in the head and neck region is the brain; however, it can also metastasize to the oral cavity, gingiva, tongue, parotid gland and lymph nodes. This article reports a case of small cell lung cancer presenting with metastasis to the facial nerve.

  13. 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.

  14. Maintenance of radiation-induced intestinal fibrosis: Cellular and molecular features

    Institute of Scientific and Technical Information of China (English)

    Valérie Haydont; Marie-Catherine Vozenin-Brotons

    2007-01-01

    Recent advances in cell and molecular radiobiology clearly showed that tissue response to radiation injury cannot be restricted to a simple cell-killing process, but depends upon continuous and integrated pathogenic processes, involving cell differentiation and crosstalk between the various cellular components of the tissue within the extracellular matrix. Thus, the prior concept of primary cell target in which a single-cell type (whatever it's epithelial or endothelial cells) dictates the whole tissue response to radiation injury has to be replaced by the occurrence of coordinated multicellular response that may either lead to tissue recovery or to sequel development. In this context, the present review will focus on the maintenance of the radiation-induced wound healing and fibrogenic signals triggered by and through the microenvironment toward the mesencnymal cell compartment, and will highlight how sequential and sustained modifications in cell phenotypes will in cascade modify cell-to-cell interactions and tissue composition.

  15. The Immunohistochemical Assessment of ALDH1 Activity in Breast Cancer and it’s Correlation With Pathologic Features

    Directory of Open Access Journals (Sweden)

    Molanae S

    2011-12-01

    Full Text Available Background: Aldehyde dehydrogenase 1 (ALDH1 is a marker of normal and malignant human mammary stem cells that has been reported to be associated with poor prognosis. Studies on the detection of ALDH1+ cells can help the treatment of patients with breast cancer. The aim of this study was to determine the activity of ALDH1 in breast cancer and its relationship with the pathological features of the tumors.Methods: ALDH1 activity was studied by immunohistochemistry in 121 paraffin-embedded histological samples of breast cancer patients from Department of Pathology of Milad Hospital, Tehran, Iran during 2006-2007. The relationship of ALDH1 with the pathological features of the tumors (size, grade, lymph node metastasis and vascular invasion was also investigated.Results: Eighty-five percent of breast cancer samples expressed ALDH1 in their cytoplasm with a wide range of intensity (weak, moderate and strong, while 18 samples (14.9% were completely negative. The majority of cases (97.1% showed ALDH1 positivity in the stroma of tumors which varied from weak (2.9% to strong (73.5%. ALDH1 H-score (ALDH1% × intensity of tumor cells varied from 0 to 240 (mean= 80. ALDH1 H-score was ≤80 in 62 (51.2% and >80 in 59 (48.8% samples. There was no statistically significant relationship between ALDH1 H-score and age (P=0.358, tumor size (P=0.375, tumor grade (P=0.207, lymph node metastasis (P=0.125 or vascular invasion (P=0.190.Conclusion: ALDH1 activity was demonstrated in 85.1% of breast cancer samples although its level of expression was not correlated with the pathologic features of breast tumors.

  16. Cross-cancer profiling of molecular alterations within the human autophagy interaction network.

    Science.gov (United States)

    Lebovitz, Chandra B; Robertson, A Gordon; Goya, Rodrigo; Jones, Steven J; Morin, Ryan D; Marra, Marco A; Gorski, Sharon M

    2015-01-01

    Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival.

  17. Quantum Interactomics and Cancer Molecular Mechanisms: I. Report Outline

    CERN Document Server

    Baianu, I C

    2004-01-01

    Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quant...

  18. Serum high mobility group box-1 (HMGB1 is closely associated with the clinical and pathologic features of gastric cancer

    Directory of Open Access Journals (Sweden)

    Chung Jae

    2009-05-01

    Full Text Available Abstract Background High mobility group box-1 (HMGB1 is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer. Methods A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA method. Clinical parameters, International Union Against Cancer (UICC TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables. Results The serum HMGB1 levels were significantly different among disease groups (ANOVA, p and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p . However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05. The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA (30–40% of sensitivity. Conclusion HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.

  19. The Correlation between Microsatellite Instability and the Features of Sporadic Colorectal Cancer in the North Part of Iran

    Directory of Open Access Journals (Sweden)

    Masoumeh Faghani

    2012-01-01

    Full Text Available Background. The aim of this study was to determine the correlation between MSI and sporadic colorectal cancer in Guilan province, North part of Iran. Materials and Methods. A total of 96 patients who underwent resection for sporadic colorectal cancer in Guilan province were studied. No patients had positive family history of cancers. The frequencies of MSI were analyzed by testing the BAT-26 and BAT-25 markers. Results. MSI analysis revealed that 22.9% of the tumors (22 patients were microsatellite instability positive and 77.1% (74 patients were microsatellite instability negative. The highest rate of MSI (40.9% was found in the rectal region. MSI-H status was seen more frequently in distal tumors (P=0.04, odds ratio = 3.13, 0.96–10.14. Conclusions. Distal tumor location and MSI may associate with special clinicopathological features. It seems that there may be correlation with underlying genetic and immunologic mechanisms.

  20. The development of low-molecular weight hydrogels for applications in cancer therapy

    Science.gov (United States)

    Tian, Ran; Chen, Jin; Niu, Runfang

    2014-03-01

    To improve the anti-cancer efficacy and to counteract the side effects of chemotherapy, a variety of drug delivery systems have been invented in past decades, but few of these systems have succeeded in clinical trials due to their respective inherent shortcomings. Recently, low-molecular weight hydrogels of peptides that self-assemble via non-covalent interactions have attracted considerable attention due to their good biocompatibility, low toxicity, inherent biodegradability as well as their convenience of design. Low-molecular weight hydrogels have already shown promise in biomedical applications as diverse as 3D-cell culture, enzyme immobilization, controllable MSC differentiation, wound healing, drug delivery etc. Here we review the recent development in the use of low-molecular weight hydrogels for cancer therapy, which may be helpful in the design of soft materials for drug delivery.

  1. Prevailing features of X-ray induced molecular electron spectra revealed with fullerenes

    CERN Document Server

    Garibay, Abraham Camacho; Rost, Jan M

    2014-01-01

    Intense X-ray photo-absorption from short and intense pulses by a molecule triggers complicated electron and subsequently ion dynamics leading to photo-electron spectra which are difficult to interpret. Illuminating fullerenes offers a way to separate out the electron dynamics. Moreover, the fullerene cage confines spatially the origin of photo and Auger electrons. Together with the sequential nature of the photo processes at intensities available at X-ray free electron lasers, this allows for a remarkably detailed interpretation of the photo-electron spectra as we will demonstrate. The general features derived can serve as a paradigm for less well-defined situations in other large molecules or clusters.

  2. Molecular imaging of cancer with radiolabeled peptides and PET.

    Science.gov (United States)

    Vāvere, Amy L; Rossin, Raffaella

    2012-06-01

    Radiolabeled peptides hold promise for diagnosis and therapy of cancer as well as for early monitoring of therapy outcomes, patient stratification, etc. This manuscript focuses on the development of peptides labeled with 18F, 64Cu, 68Ga and other positron-emitting radionuclides for PET imaging. The major techniques for radionuclide incorporation are briefly discussed. Then, examples of positron-emitting peptides targeting somatostatin receptors, integrins, gastrin-releasing peptide receptors, vasointestinal peptide receptors, melanocortin 1 receptors and others are reviewed. PMID:22292762

  3. Synemin: Molecular Features and the Use of Proximity Ligation Assay to Study Its Interactions.

    Science.gov (United States)

    Paul, Madhumita; Skalli, Omar

    2016-01-01

    Synemin has three splice variants (α, β, and L) with identical head and rod domains but with tail domains of varying size. α- and β-Synemin are larger than most intermediate filament proteins (1565 and 1253 amino acids, respectively) but L-synemin is shorter (339 amino acids). Synemin isoforms do not self-assemble into filaments but can copolymerize with vimentin and desmin. Synemin is present in all muscle cell types, in a few neural cell types, and in various other nonepithelial cell types. Synemin expression is regulated, sometimes in an isoform-specific manner, during development of the nervous system, in brain and breast cancer cells and during injuries to the brain and liver. Mice-lacking synemin develop a myopathic phenotype, possibly due to synemin role in linking desmin filaments to costameres and sarcomeres. Synemin may play this role through its demonstrated binding to costameric and sarcolemmal proteins, such as α-actinin, vinculin, and members of the dystroglycan complex. In astrocytoma cells, synemin regulates proliferation by interacting with PP2A to modulate Akt phosphorylation status. Methods to identify synemin binding partners are central to understand the roles of this protein in diverse cell types. Here, we describe how to use proximal ligation assays (PLA) for this purpose. PLA complement biochemical methods such as immunoprecipitation by relying on the use of antibodies conjugated to oligonucleotide probes to visualize by fluorescence microscopy protein-protein interactions in cells and tissues.

  4. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  5. Nanoscale/Molecular analysis of Fecal Colonocytes for Colorectal Cancer Screening | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Existing guidelines recommend colorectal cancer (CRC) screening for all patients over age 50. However, CRC remains the second leading cause of cancer death among Americans largely because colonoscopic screening of all the >100 million Americans over age 50 is unfeasible for both patient-related (non-compliance) and societal (inadequate endoscopic capacity and funding) reasons. |

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

    Science.gov (United States)

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

    2014-03-01

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

  7. New Targeted Molecular Therapies for Dedifferentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Alessandro Antonelli

    2010-01-01

    Full Text Available Dedifferentiated thyroid cancer (DeTC derived from follicular epithelium is often incurable because it does not respond to radioiodine, radiotherapy, or chemotherapy. In cases, RET/PTC rearrangements are found in 30%–40%, RAS mutations in about 10%, and BRAF mutations in around 40%–50%, with no overlap between these mutations results in papillary thyroid cancer, while a higher prevalence of BRAF mutations (up to 70% has been observed in DeTC. The identification of these activating mutations in DeTC makes this malignancy an excellent model to examine the effect of tyrosine kinase inhibitors (TKIs. Clinical trials with several TKIs targeting RET, and to a lesser extent BRAF, and other TKRs have shown positive results, with about one-third of DeTC showing a reduction in tumor size up to 50%, with the longest treatment duration of approximately three-four years. Angiogenesis inhibitors have also shown promising activity in DeTC. Progress is being made toward effective targeted DeTC therapy. The possibility of testing the sensitivity of primary DeTC cells from each subject to different TKIs could increase the effectiveness of the treatment.

  8. Using large-scale genome variation cohorts to decipher the molecular mechanism of cancer.

    Science.gov (United States)

    Habermann, Nina; Mardin, Balca R; Yakneen, Sergei; Korbel, Jan O

    2016-01-01

    Characterizing genomic structural variations (SVs) in the human genome remains challenging, and there is a growing interest to understand somatic SVs occurring in cancer, a disease of the genome. A havoc-causing SV process known as chromothripsis scars the genome when localized chromosome shattering and repair occur in a one-off catastrophe. Recent efforts led to the development of a set of conceptual criteria for the inference of chromothripsis events in cancer genomes and to the development of experimental model systems for studying this striking DNA alteration process in vitro. We discuss these approaches, and additionally touch upon current "Big Data" efforts that employ hybrid cloud computing to enable studies of numerous cancer genomes in an effort to search for commonalities and differences in molecular DNA alteration processes in cancer. PMID:27342254

  9. Using large-scale genome variation cohorts to decipher the molecular mechanism of cancer.

    Science.gov (United States)

    Habermann, Nina; Mardin, Balca R; Yakneen, Sergei; Korbel, Jan O

    2016-01-01

    Characterizing genomic structural variations (SVs) in the human genome remains challenging, and there is a growing interest to understand somatic SVs occurring in cancer, a disease of the genome. A havoc-causing SV process known as chromothripsis scars the genome when localized chromosome shattering and repair occur in a one-off catastrophe. Recent efforts led to the development of a set of conceptual criteria for the inference of chromothripsis events in cancer genomes and to the development of experimental model systems for studying this striking DNA alteration process in vitro. We discuss these approaches, and additionally touch upon current "Big Data" efforts that employ hybrid cloud computing to enable studies of numerous cancer genomes in an effort to search for commonalities and differences in molecular DNA alteration processes in cancer.

  10. 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.

  11. Molecular and genetic features of zinc transporters in physiology and pathogenesis.

    Science.gov (United States)

    Fukada, Toshiyuki; Kambe, Taiho

    2011-07-01

    Zinc (Zn) is a vital element. It plays indispensable roles in multifarious cellular processes, affecting the expression and activity of a variety of molecules, including transcription factors, enzymes, adapters, channels, growth factors, and their receptors. A disturbance in Zn homeostasis due to Zn deficiency or an excess of Zn absorption can therefore impair the cellular machinery and exert various influences on physiological programs, such as systemic growth, morphogenetic processes, and immune responses, as well as neuro-sensory and endocrine functions. Thus, Zn imbalance becomes pathogenic in humans. Zn homeostasis is controlled by the coordinated actions of Zn transporters, which are responsible for Zn influx and efflux, and intricately regulate the intracellular and extracellular Zn concentration and distribution. In this review, we describe crucial roles of Zn transporters in biological phenomena, focusing in particular on how Zn transporters contribute to cellular events at the molecular, biochemical, and genetic level, with recent progress uncovering the roles of Zn transporters in physiology and pathogenesis. PMID:21566827

  12. Physiological and Molecular Features of the Pathosystem Arabidopsis thaliana L.-Sclerotinia sclerotiorum Libert

    Institute of Scientific and Technical Information of China (English)

    Fu-Ming Dai; Tong Xu; Gerhard A. Wolf; Zu-Hua He

    2006-01-01

    The fungal pathogen Sclerotinia sclerotiorum Libert causes rot diseases on many crops worldwide and large economic losses occur frequently because of a lack of resistant varieties. The pathogenesis of S. sclerotiorum and the molecular basis of plant responses to the pathogen are poorly understood. In the present investigation,the process of S. sclerotiorum infection in Arabidopsis thaliana L., a plant that is highly susceptible to this fungus, was analysed. In addition, the defense activation in the host was investigated. A convenient inoculation method using millet grain was developed for S. sclerotiorum in Arabidopsis. The fungus rapidly infected the plants, probably through ball- or cushion-like infection structures. Visible symptoms developed within 24h and plants were killed 72 h after inoculation. Cellulase, the main enzyme that caused host tissues to rot,was secreted by S. sclerotiorum in a pH-dependent manner. Oxalic acid, another pathogenic factor secreted by the fungus, induced necrotic lesions on the leaves. Infection with S. sclerotiorum strongly induced the production of the pathogenesis-related (PR) proteins β-1,3-glucanase and chitinase in Arabidopsis.Furthermore, the PR gene PDF. 1 was induced, but not PR1, indicating that the pathogen activated basal defense of jasmonic acid/ethylene dependence, which is consistent with its necrotrophic characteristics.This pathosystem for Arabidopsis-S. sclerotiorum could provide an approach for the analysis of the interactions between S. sclerotiorum and other crops, thereby facilitating genetic manipulation techniques for controlling this pathogen.

  13. Unraveling the distinctive features of hemorrhagic and non-hemorrhagic snake venom metalloproteinases using molecular simulations.

    Science.gov (United States)

    de Souza, Raoni Almeida; Díaz, Natalia; Nagem, Ronaldo Alves Pinto; Ferreira, Rafaela Salgado; Suárez, Dimas

    2016-01-01

    Snake venom metalloproteinases are important toxins that play fundamental roles during envenomation. They share a structurally similar catalytic domain, but with diverse hemorrhagic capabilities. To understand the structural basis for this difference, we build and compare two dynamical models, one for the hemorrhagic atroxlysin-I from Bothrops atrox and the other for the non-hemorraghic leucurolysin-a from Bothrops leucurus. The analysis of the extended molecular dynamics simulations shows some changes in the local structure, flexibility and surface determinants that can contribute to explain the different hemorrhagic activity of the two enzymes. In agreement with previous results, the long Ω-loop (from residue 149 to 177) has a larger mobility in the hemorrhagic protein. In addition, we find some potentially-relevant differences at the base of the S1' pocket, what may be interesting for the structure-based design of new anti-venom agents. However, the sharpest differences in the computational models of atroxlysin-I and leucurolysin-a are observed in the surface electrostatic potential around the active site region, suggesting thus that the hemorrhagic versus non-hemorrhagic activity is probably determined by protein surface determinants. PMID:26676823

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

    Science.gov (United States)

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

    2015-04-01

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

  15. Patient-derived xenografts recapitulate molecular features of human uveal melanomas.

    Science.gov (United States)

    Laurent, Cécile; Gentien, David; Piperno-Neumann, Sophie; Némati, Fariba; Nicolas, André; Tesson, Bruno; Desjardins, Laurence; Mariani, Pascale; Rapinat, Audrey; Sastre-Garau, Xavier; Couturier, Jérôme; Hupé, Philippe; de Koning, Leanne; Dubois, Thierry; Roman-Roman, Sergio; Stern, Marc-Henri; Barillot, Emmanuel; Harbour, J William; Saule, Simon; Decaudin, Didier

    2013-06-01

    We have previously developed a new method for the development and maintenance of uveal melanoma (UM) xenografts in immunodeficient mice. Here, we compare the genetic profiles of the primary tumors to their corresponding xenografts that have been passaged over time. The study included sixteen primary UMs and corresponding xenografts at very early (P1), early (P4), and late (P9) in vivo passages. The tumors were analyzed for mutation status of GNAQ, GNA11, GNAS, GNA15, BAP1, and BRAF, chromosomal copy number alterations using Affymetrix GeneChip(®) Genome-Wide Human SNP6.0 arrays, gene expression profiles using GeneChip(®) Human Exon 1.0 ST arrays, BAP1 mRNA and protein expression, and MAPK pathway status using Reverse Phase Protein Arrays (RPPA). The UM xenografts accurately recapitulated the genetic features of primary human UMs and they exhibited genetic stability over the course of their in vivo maintenance. Our technique for establishing and maintaining primary UMs as xenograft tumors in immunodeficient mice exhibit a high degree of genetic conservation between the primary tumors and the xenograft tumors over multiple passages in vivo. These models therefore constitute valuable preclinical tool for drug screening in UM.

  16. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach.

    Science.gov (United States)

    Platania, Chiara B M; Di Paola, Luisa; Leggio, Gian M; Romano, Giovanni L; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio

    2015-01-01

    Anti-angiogenic agents are biological drugs used for treatment of retinal neovascular degenerative diseases. In this study, we aimed at in silico analysis of interaction of vascular endothelial growth factor A (VEGFA), the main mediator of angiogenesis, with binding domains of anti-angiogenic agents used for treatment of retinal diseases, such as ranibizumab, bevacizumab and aflibercept. The analysis of anti-VEGF/VEGFA complexes was carried out by means of protein-protein docking and molecular dynamics (MD) coupled to molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculation. Molecular dynamics simulation was further analyzed by protein contact networks. Rough energetic evaluation with protein-protein docking scores revealed that aflibercept/VEGFA complex was characterized by electrostatic stabilization, whereas ranibizumab and bevacizumab complexes were stabilized by Van der Waals (VdW) energy term; these results were confirmed by MM-PBSA. Comparison of MM-PBSA predicted energy terms with experimental binding parameters reported in literature indicated that the high association rate (Kon) of aflibercept to VEGFA was consistent with high stabilizing electrostatic energy. On the other hand, the relatively low experimental dissociation rate (Koff) of ranibizumab may be attributed to lower conformational fluctuations of the ranibizumab/VEGFA complex, higher number of contacts and hydrogen bonds in comparison to bevacizumab and aflibercept. Thus, the anti-angiogenic agents have been found to be considerably different both in terms of molecular interactions and stabilizing energy. Characterization of such features can improve the design of novel biological drugs potentially useful in clinical practice. PMID:26578958

  17. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach

    Directory of Open Access Journals (Sweden)

    Chiara Bianca Maria Platania

    2015-10-01

    Full Text Available Anti-angiogenic agents are biological drugs used for treatment of retinal neovascular degenerative diseases. In this study, we aimed at in-silico analysis of interaction of vascular endothelial growth factor A (VEGFA, the main mediator of angiogenesis, with binding domains of anti-angiogenic agents used for treatment of retinal diseases, such as ranibizumab, bevacizumab and aflibercept. The analysis of anti-VEGF/VEGFA complexes was carried out by means of protein-protein docking and molecular dynamics (MD coupled to molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA calculation. Molecular dynamics simulation was further analyzed by protein contact networks. Rough energetic evaluation with protein-protein docking scores revealed that aflibercept/VEGFA complex was characterized by electrostatic stabilization, whereas ranibizumab and bevacizumab complexes were stabilized by Van der Waals (VdW energy term; these results were confirmed by MM-PBSA. Comparison of MM-PBSA predicted energy terms with experimental binding parameters reported in literature indicated that the high association rate (Kon of aflibercept to VEGFA was consistent with high stabilizing electrostatic energy. On the other hand, the relatively low experimental dissociation rate (Koff of ranibizumab may be attributed to lower conformational fluctuations of the ranibizumab/VEGFA complex, higher number of contacts and hydrogen bonds in comparison to bevacizumab and aflibercept. Thus, the anti-angiogenic agents have been found to be considerably different both in terms of molecular interactions and stabilizing energy. Characterization of such features can improve the design of novel biological drugs potentially useful in clinical practice.

  18. miR-126-3p and miR-451a correlate with clinicopathological features of lung adenocarcinoma: The underlying molecular mechanisms.

    Science.gov (United States)

    Chen, Qingyong; Hu, Huizhen; Jiao, Demin; Yan, Jie; Xu, Wei; Tang, Xiali; Chen, Jun; Wang, Jian

    2016-08-01

    Lung cancer is the most common malignancy worldwide. This study aimed to identify miRNA biomarkers of lung adenocarcinoma and to investigate their molecular mechanisms. miRNA expression profiling of tumor tissues and adjacent normal tissues from 10 patients were detected using microarray. Differentially expressed miRNAs (DEMs) were identified, and were verified using quantitative reverse transcription-PCR. Thereafter, correlations between DEM expression and clinicopathological features were determined in 49 patients. Furthermore, Targetscan was utilized to predict target genes, among which transcription factors (TFs) were identified. The interactions among miRNAs, TFs and target genes were used to construct an miRNA-TF-target network. Totally, 11 DEMs were identified, among which two downregulated miRNAs (miR-126-3p and miR-451a) were validated. Low levels of miR-126-3p and miR-451a were associated with poor pathological stage, large tumor diameter and lymph node metastasis (P0.65, P<0.05). For miR-126-3p, 154 target genes were predicted (e.g., PLXNB2), which were enriched in 29 pathways mainly concerning apoptosis and cancer. For miR‑451a, 397 target genes were predicted, which were enriched in 5 pathways including 'PPAR signaling pathway'. Ten genes were co-regulated by miR-126-3p and miR-451a, e.g., TSC1. Furthermore, an miRNA-TF-target network was constructed, and a sub-network was identified, including 2 miRNAs, 15 targets, and 7 TFs. In conclusion, miR-126-3p and miR-451a predicted the severity of lung adenocarcinoma. However, the possible mechanisms explored by bioinformatics need to be further validated. PMID:27277197

  19. Natural Products as Promising Antitumoral Agents in Breast Cancer: Mechanisms of Action and Molecular Targets.

    Science.gov (United States)

    Bonofiglio, Daniela; Giordano, Cinzia; De Amicis, Francesca; Lanzino, Marilena; Andò, Sebastiano

    2016-01-01

    Extensive research over the past several decades has identified numerous dietary and phytochemical compounds that have chemopreventive potential and could represent an important source of anti-cancer lead molecules. In this scenario several nutritional factors have attracted considerable attention as modifiable risk factor in the prevention of breast cancer, the most frequently diagnosed cancer and a major cause of death among women worldwide. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for breast cancers able also to counteract the recurrent phenomenon of resistance to hormonal and targeted therapy that represent the first-line treatment in the management of breast cancer patients. The present review focuses on chemopreventive and anti-cancer activities of different bioactive compounds obtained from dietary sources such as Omega-3 fatty acids, naturally present in fish, Resveratrol (3,5,40-trihydroxy-transstilbene), a phytoalexin found in grapes and Epigallocatechin Gallate, a polyphenolic compound found in green tea, or purified from medicinal plant (Oldenlandia Diffusa) and fruits (Ziziphus Jujube) highlighting their potential use in breast cancer treatment. Herein, we discuss the molecular mechanisms by which the bioactive compounds can inhibit carcinogenesis by regulating antioxidant enzyme activities, and inducing antiproliferative and apoptotic effects in different breast cancer cell lines. Understanding the mechanism of action of dietary compounds or traditionally used herbs having potential preventive and therapeutic effects on cancer may provide a rationale for further translational studies. This review emphasizes the importance, in the next future, of a proper scientific validation of these natural bioactive compounds for clinical use in the therapeutic portfolio for breast cancer. PMID:26156544

  20. Molecular profiling of breast cancer: transcriptomic studies and beyond.

    Science.gov (United States)

    Culhane, A C; Howlin, J

    2007-12-01

    Utilisation of 'omics' technologies, in particular gene expression profiling, has increased dramatically in recent years. In basic research, high-throughput profiling applications are increasingly used and may now even be considered standard research tools. In the clinic, there is a need for better and more accurate diagnosis, prognosis and treatment response indicators. As such, clinicians have looked to omics technologies for potential biomarkers. These prediction profiling studies have in turn attracted the attention of basic researchers eager to uncover biological mechanisms underlying clinically useful signatures. Here we highlight some of the seminal work establishing the arrival of the omics, in particular transcriptomics, in breast cancer research and discuss a sample of the most current applications. We also discuss the challenges of data analysis and integrated data analysis with emphasis on utilising the current publicly available gene expression datasets. (Part of a Multi-author Review). PMID:17957338