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Sample records for cancer tissues insight

  1. Mathematical modeling of cancer cell invasion of tissue: biological insight from mathematical analysis and computational simulation.

    Science.gov (United States)

    Andasari, Vivi; Gerisch, Alf; Lolas, Georgios; South, Andrew P; Chaplain, Mark A J

    2011-07-01

    The ability of cancer cells to break out of tissue compartments and invade locally gives solid tumours a defining deadly characteristic. One of the first steps of invasion is the remodelling of the surrounding tissue or extracellular matrix (ECM) and a major part of this process is the over-expression of proteolytic enzymes, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), by the cancer cells to break down ECM proteins. Degradation of the matrix enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body, a process known as metastasis. In this paper we undertake an analysis of a mathematical model of cancer cell invasion of tissue, or ECM, which focuses on the role of the urokinase plasminogen activation system. The model consists of a system of five reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, uPA, uPA inhibitors, plasmin and the host tissue. Cancer cells react chemotactically and haptotactically to the spatio-temporal effects of the uPA system. The results obtained from computational simulations carried out on the model equations produce dynamic heterogeneous spatio-temporal solutions and using linear stability analysis we show that this is caused by a taxis-driven instability of a spatially homogeneous steady-state. Finally we consider the biological implications of the model results, draw parallels with clinical samples and laboratory based models of cancer cell invasion using three-dimensional invasion assay, and go on to discuss future development of the model.

  2. Framework of collagen type I - vasoactive vessels structuring invariant geometric attractor in cancer tissues: insight into biological magnetic field.

    Directory of Open Access Journals (Sweden)

    Jairo A Díaz

    Full Text Available In a previous research, we have described and documented self-assembly of geometric triangular chiral hexagon crystal-like complex organizations (GTCHC in human pathological tissues. This article documents and gathers insights into the magnetic field in cancer tissues and also how it generates an invariant functional geometric attractor constituted for collider partners in their entangled environment. The need to identify this hierarquic attractor was born out of the concern to understand how the vascular net of these complexes are organized, and to determine if the spiral vascular subpatterns observed adjacent to GTCHC complexes and their assembly are interrelational. The study focuses on cancer tissues and all the macroscopic and microscopic material in which GTCHC complexes are identified, which have been overlooked so far, and are rigorously revised. This revision follows the same parameters that were established in the initial phase of the investigation, but with a new item: the visualization and documentation of external dorsal serous vascular bed areas in spatial correlation with the localization of GTCHC complexes inside the tumors. Following the standard of the electro-optical collision model, we were able to reproduce and replicate collider patterns, that is, pairs of left and right hand spin-spiraled subpatterns, associated with the orientation of the spinning process that can be an expansion or contraction disposition of light particles. Agreement between this model and tumor data is surprisingly close; electromagnetic spiral patterns generated were identical at the spiral vascular arrangement in connection with GTCHC complexes in malignant tumors. These findings suggest that the framework of collagen type 1 - vasoactive vessels that structure geometric attractors in cancer tissues with invariant morphology sets generate collider partners in their magnetic domain with opposite biological behavior. If these principles are incorporated

  3. Signalling networks associated with urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer tissues: new insights from protein microarray analysis.

    Science.gov (United States)

    Wolff, Claudia; Malinowsky, Katharina; Berg, Daniela; Schragner, Kerstin; Schuster, Tibor; Walch, Axel; Bronger, Holger; Höfler, Heinz; Becker, Karl-Friedrich

    2011-01-01

    The urokinase-type plasminogen activator (uPA) and the main uPA inhibitor PAI-1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node-negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer-related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA- and PAI-1-associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI-1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI-1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER-receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI-1 expression was correlated with nodal stage. Network monitoring for uPA and PAI-1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development.

  4. Adipose Tissue Immunity and Cancer

    Directory of Open Access Journals (Sweden)

    Victoria eCatalan

    2013-10-01

    Full Text Available Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete proinflammatory adipokines and cytokines providing a microenvironment favourable for tumour growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching towards M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumour growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumour cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumour microenvironment with more sophisticated and selective anti-tumoural drugs.

  5. A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk

    OpenAIRE

    Campbell, Kristin L.; Makar, Karen W.; Kratz, Mario; Foster-Schubert, Karen E.; McTiernan, Anne; Ulrich, Cornelia M.

    2009-01-01

    Examination of adipose tissue biology may provide important insight into mechanistic links for the observed association between higher body fat and risk of several types of cancer, in particular colorectal and breast cancer. We tested two different methods of obtaining adipose tissue from healthy individuals.

  6. Diagnosis of breast cancer by tissue analysis

    Institute of Scientific and Technical Information of China (English)

    Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

    2013-01-01

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

  7. Zinc isotopic compositions of breast cancer tissue.

    Science.gov (United States)

    Larner, Fiona; Woodley, Laura N; Shousha, Sami; Moyes, Ashley; Humphreys-Williams, Emma; Strekopytov, Stanislav; Halliday, Alex N; Rehkämper, Mark; Coombes, R Charles

    2015-01-01

    An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.

  8. Dynamics of cancerous tissue correlates with invasiveness

    Science.gov (United States)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-01-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion. PMID:28262796

  9. Dynamics of cancerous tissue correlates with invasiveness

    Science.gov (United States)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-03-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

  10. Disrupting Ovarian Cancer Metastatic Colonization: Insights from Metastasis Suppressor Studies

    Directory of Open Access Journals (Sweden)

    Shaheena Khan

    2010-01-01

    Full Text Available Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.

  11. Oestrone sulphate, adipose tissue, and breast cancer.

    Science.gov (United States)

    Hawkins, R A; Thomson, M L; Killen, E

    1985-01-01

    Oestrone sulphate, the oestrogen in highest concentration in the plasma, may play a role in the induction and growth of breast cancers. By enzymolysis and radioimmunoassay, oestrone sulphate concentrations were measured in 3 biological fluids. High concentrations of the conjugate (up to 775 nmol/l) were detected in breast cyst fluids from some premenopausal women, the concentrations in blood plasma (0.91-4.45 nmol/l) being much lower. Concentrations in the plasmas from postmenopausal women with (0.23-4.63 nmol/l) or without (0.18-1.27 nmol/l) breast cancer were still lower. Oestrone sulphate concentration in cow's milk or cream (0.49-0.67 nmol/l) was also low: dietary intake in these fluids is probably of little consequence. The capacity of breast tissues for hydrolysis of oestrone sulphate was examined in two ways: In tissue slices incubated with 85 pM (3H) oestrone sulphate solution at 37 degrees C, cancers (131-412 fmol/g tissue/hr) and adipose tissues (23-132 fmol/g tissue/hr) hydrolysed significantly more sulphate than did benign tissues (1-36 fmol/g tissue/hr). In tissue homogenates incubated with 5-25 microM [3H] oestrone sulphate at 37 degrees much higher capacities for hydrolysis (nmol/g tissue/hr) were demonstrated with a Km of 2-16.5 microM: cancers (34-394) and benign tissues (9-485) had significantly higher sulphatase activities than adipose tissues (9-39). On a protein basis, however, the sulphatase activities in the 3 tissues were comparable. It is concluded that oestrone sulphate is present in breast cysts and blood plasma and that in vitro, the conjugated hormone can be hydrolysed by breast tissues. The biological significance of these findings in vivo remains to be established.

  12. Adipogenesis: new insights into brown adipose tissue differentiation.

    Science.gov (United States)

    Carobbio, Stefania; Rosen, Barry; Vidal-Puig, Antonio

    2013-12-01

    Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models both in vivo and in vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.

  13. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  14. Lung Cancer Presenting as a Soft-Tissue Metastasis

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    Candice Baldeo

    2015-04-01

    Full Text Available Soft-tissue metastasis refers to the growth of cancer cells, originating from internal cancer, in soft tissues. In most cases, soft-tissue metastases develop after initial diagnosis of the primary internal malignancy and late in the course of the disease. In very rare cases, they may occur at the same time or before the primary cancer has been detected. In our cases, the soft-tissue metastases and the primary lung cancer were diagnosed at the same time.

  15. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of allcancers, with almost uniform lethality despite aggressivetreatment. Recently, there have been important advancesin the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recentnew targeted agents and the use of multiple therapeuticcombinations, no treatment option is viable in patients withadvanced cancer. Developing novel strategies to targetprogression of PC is of intense interest. A small populationof pancreatic cancer stem cells (CSCs) has been foundto be resistant to chemotherapy and radiation therapy.CSCs are believed to be responsible for tumor initiation,progression and metastasis. The CSC research has recentlyachieved much progress in a variety of solid tumors,including pancreatic cancer to some extent. This leads tofocus on understanding the role of pancreatic CSCs. Thefocus on CSCs may offer new targets for prevention andtreatment of this deadly cancer. We review the most salientdevelopments in important areas of pancreatic CSCs. Here,we provide a review of current updates and new insightson the role of CSCs in pancreatic tumor progression withspecial emphasis on DclK1 and Lgr5, signaling pathwaysaltered by CSCs, and the role of CSCs in prevention andtreatment of PC.

  16. When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer.

    Science.gov (United States)

    Lapeire, Lore; Denys, Hannelore; Cocquyt, Véronique; De Wever, Olivier

    2015-07-01

    Since the discovery of leptin in 1994, our vision of adipose tissue as a static organ regulating mainly lipid storage and release has been completely overthrown, and adipose tissue is now seen as an active and integral organ in human physiology. In the past years, extensive research has tremendously given us more insights in the mechanisms and pathways involved not only in normal but also in 'sick' adipose tissue, for example, in obesity and lipodystrophy. With growing evidence of a link between obesity and several types of cancer, research focusing on the interaction between adipose tissue and cancer has begun to unravel the interesting but complex multi-lateral communication between the different players. With breast cancer as one of the first cancer types where a positive correlation between obesity and breast cancer incidence and prognosis in post-menopausal women was found, we have focused this review on the paracrine and endocrine role of adipose tissue in breast cancer initiation and progression. As important inter-species differences in adipose tissue occur, we mainly selected human adipose tissue- and breast cancer-based studies with a short reflection on therapeutic possibilities. This review is part of the special issue on "Adiposopathy in Cancer and (Cardio)Metabolic Diseases".

  17. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the differ

  18. Big Data-Led Cancer Research, Application, and Insights.

    Science.gov (United States)

    Brown, James A L; Ni Chonghaile, Triona; Matchett, Kyle B; Lynam-Lennon, Niamh; Kiely, Patrick A

    2016-11-01

    Insights distilled from integrating multiple big-data or "omic" datasets have revealed functional hierarchies of molecular networks driving tumorigenesis and modifiers of treatment response. Identifying these novel key regulatory and dysregulated elements is now informing personalized medicine. Crucially, although there are many advantages to this approach, there are several key considerations to address. Here, we examine how this big data-led approach is impacting many diverse areas of cancer research, through review of the key presentations given at the Irish Association for Cancer Research Meeting and importantly how the results may be applied to positively affect patient outcomes. Cancer Res; 76(21); 6167-70. ©2016 AACR.

  19. Obesity and cancer: mechanistic insights from transdisciplinary studies.

    Science.gov (United States)

    Allott, Emma H; Hursting, Stephen D

    2015-12-01

    Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie-restriction studies in mouse models that support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link.

  20. Cancer stem cells: an insight and future perspective.

    Science.gov (United States)

    Kaur, Sandeep; Singh, Gurdeep; Kaur, Kirandeep

    2014-01-01

    The cancer stem cell (CSC) concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are typically rare. Rare CSCs have been isolated from a number of human tumors, including hematopoietic, brain, colon, and breast cancer. With the growing evidence that CSCs exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. Understanding the biology of CSCs will contribute to the identification of molecular targets important for future therapies.

  1. Nanoscale insights into ion-beam cancer therapy

    CERN Document Server

    2017-01-01

    This book provides a unique and comprehensive overview of state-of-the-art understanding of the molecular and nano-scale processes that play significant roles in ion-beam cancer therapy. It covers experimental design and methodology, and reviews the theoretical understanding of the processes involved. It offers the reader an opportunity to learn from a coherent approach about the physics, chemistry and biology relevant to ion-beam cancer therapy, a growing field of important medical application worldwide. The book describes phenomena occurring on different time and energy scales relevant to the radiation damage of biological targets and ion-beam cancer therapy from the molecular (nano) scale up to the macroscopic level. It illustrates how ion-beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal tissue whilst maximizing cell-killing within the tumour, offering a significant development in cancer therapy. The full potential ...

  2. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    Science.gov (United States)

    2015-08-01

    oncogenes; inactivation of tumor suppression genes; and interaction between cancer cells and tumor-associated stroma and tumor- associated macrophages ...into inflamed tissue and dif- ferentiate into macrophages , which coordinate inflammatory re- sponses by producing chemokines and clearing debris by...AWARD NUMBER: W81XWH-10-1-0275 TITLE: Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions PRINCIPAL INVESTIGATOR

  3. Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues

    Institute of Scientific and Technical Information of China (English)

    Mehmet Yaman; Gokce Kaya; Hayrettin Yekeler

    2007-01-01

    AIM: To assess whether trace metal concentrations (which influence metabolism as both essential and non-essential elements) are increased or decreased in cancerous tissues and to understand the precise role of these metals in carcinogenesis.METHODS: Concentrations of trace metals including Cd,Ni, Cu, Zn, Fe, Mg and Ca in both cancerous and noncancerous stomach tissue samples were determined by atomic absorption spectrometry (AAS). Tissue samples were digested using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame AAS determinations.RESULTS: From the obtained data in this study,the concentrations of nickel, copper and iron in the cancerous human stomach were found to be significantly higher than those in the non-cancerous tissues, by using t-test for the paired samples. Furthermore, the average calcium concentrations in the cancerous stomach tissue samples were found to be significantly lower than those in the non-cancerous stomach tissue samples by using t-test. Exceedingly high Zn concentrations (207-826 mg/kg) were found in two paired stomach tissue samples from both cancerous and non-cancerous parts.CONCLUSION: In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples.

  4. EXPRESSION MECHANISM AND CLINICAL SIGNIFICANCE OF NOB1 IN GASTRIC CANCER TISSUE AND ADJACENT NORMAL TISSUE.

    Science.gov (United States)

    Zhou, W-P; Liu, X; Yang, Y; Liu, Y-F

    2015-01-01

    This paper studies the effect and relationship of NOB1 in the development of gastric cancer, based on an analysis of NOB1expression in gastric cancer tissue and adjacent tissue. Thirty gastric cancer tissue samples taken during surgery with complete pathological data and their related adjacent normal tissue were examined in this study. NOB1 protein expression in gastric cancer tissue and adjacent normal tissue was detected by immunohistochemistry (IHC). Real-time PCR was used to detect NOB1 mRNA expression, which provided a basis on which to explore the clinical pathological characteristics for patients with gastric cancer. Results show that NOB1 protein in gastric cancer tissue and adjacent normal tissue were diffusely expressed both in the cytoplasm and nucleus. The positive expression rate in gastric cancer tissue was 73%, higher than that in adjacent normal tissue (47%). Both the reference NAPDH and NOB1 amplification are reflected in the amplification curve in standard S-shape and the unimodal solubility curve which was not altered by non-specific amplification and primer dimer. NOB1 mRNA relative expression in cancer tissue was 4.899∓1.412. NOB1 expression had no direct relationship with the patients’ age, gender, tumor differentiation or infiltration degree, lymphatic metastasis, distant metastasis nor pTNM periodization, but was directly related to the size of the tumor. All the findings in this paper suggest that NOB1 can be one of the focuses for diagnosing and treating gastric cancer and that its protein expression is likely to increase with the growth of tumor, thus playing a great role in the incidence and development of gastric cancer.

  5. [Studies on trace elements in cancerous stomach tissue of the patients with stomach cancer].

    Science.gov (United States)

    Kobayashi, M

    1990-05-01

    This study was performed to find out whether copper, zinc, manganese, selenium and iron concentrations in the cancerous and normal stomach tissues of the patients with stomach cancer vary within the malignant stages and Borrmann classification or not, and to investigate the interaction of copper, zinc, manganese, selenium and iron concentrations in blood of these patients. Copper concentration in cancerous tissues was not statistically significant as compared with normal tissues. Plasma and whole blood copper concentration of Stage IV showed a significant higher level than that of stage I. Zinc concentration in cancerous tissues was not statistically significant as compared with normal tissues. Selenium concentration in cancerous tissues showed a statistically significant high level as compared with that in normal tissues. Plasma selenium concentration of Stage III showed a significant lower level than that of stage I. Iron concentration in cancerous tissues showed a significantly lower level than that in normal tissues at stage IV. Whole blood iron concentration was low levels in proportion to the progress of stomach cancer. The correlation of selenium concentration between in cancerous tissues and in whole blood of these patients was significant with the correlation coefficient of 0.340. The correlation of iron concentration between in cancerous tissues and in whole blood of these patients was significant with the correlation coefficient of 0.423. The correlation between iron concentration in cancerous tissues and hemoglobin concentration in whole blood of these patients was significant with the correlation coefficient of 0.361.

  6. New Insights into Fe Localization in Plant Tissues

    Directory of Open Access Journals (Sweden)

    Hannetz eRoschzttardtz

    2013-09-01

    Full Text Available Deciphering cellular iron (Fe homeostasis requires having access to both quantitative and qualitative information on the subcellular pools of Fe in tissues and their dynamics within the cells. We have taken advantage of the Perls/DAB Fe staining procedure to perform a systematic analysis of Fe distribution in roots, leaves and reproductive organs of the model plant Arabidopsis thaliana, using wild-type and mutant genotypes affected in iron transport and storage. Roots of soil-grown plants accumulate iron in the apoplast of the central cylinder, a pattern that is strongly intensified when the citrate effluxer FRD3 is not functional, thus stressing the importance of citrate in the apoplastic movement of Fe. In leaves, Fe level is low and only detected in and around vascular tissues. In contrast, Fe staining in leaves of iron-treated plants extends in the surrounding mesophyll cells where Fe deposits, likely corresponding to Fe-ferritin complexes, accumulate in the chloroplasts. The loss of ferritins in the fer1,3,4 triple mutant provoked a massive accumulation of Fe in the apoplastic space, suggesting that in the absence of iron buffering in the chloroplast, cells activate iron efflux and/or repress iron influx to limit the amount of iron in the cell. In flowers, Perls/DAB staining has revealed a major sink for Fe in the anthers. In particular, developing pollen grains accumulate detectable amounts of Fe in small-size intracellular bodies that aggregate around the vegetative nucleus at the binuclear stage and that were identified as amyloplasts. In conclusion, using the Perls/DAB procedure combined to selected mutant genotypes, this study has established a reliable atlas of Fe distribution in the main Arabidopsis organs, proving and refining long-assumed intracellular locations and uncovering new ones. This iron map of Arabidopsis will serve as a basis for future studies of possible actors of iron movement in plant tissues and cell compartments.

  7. Adolescents and cancer: discrepancy between untroubled appearance and insight disturbance.

    Science.gov (United States)

    Massimo, L M; Caprino, D

    2011-04-01

    The care of adolescents suffering from high risk disease is a demanding challenge. At times, adolescents may well be too old for the pediatrician and Pediatric Units, and yet too young for the adult practitioner. A dedicated approach that builds on the insight deriving from special attention to, and reflection on the adolescent patient's true desire to share feelings is pivotal to the efforts that must be made to improve the perceived quality of life. The specific age class of adolescence is the focus of few papers, and we feel that a broader discussion of the subject would be useful. In our short article we report the pieces written by three very positive-minded girls suffering from cancer for the journal of our Department. They show deep and severe insight disturbance.

  8. Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues.

    Science.gov (United States)

    Hwang, S-I; Thumar, J; Lundgren, D H; Rezaul, K; Mayya, V; Wu, L; Eng, J; Wright, M E; Han, D K

    2007-01-01

    Successful treatment of multiple cancer types requires early detection and identification of reliable biomarkers present in specific cancer tissues. To test the feasibility of identifying proteins from archival cancer tissues, we have developed a methodology, termed direct tissue proteomics (DTP), which can be used to identify proteins directly from formalin-fixed paraffin-embedded prostate cancer tissue samples. Using minute prostate biopsy sections, we demonstrate the identification of 428 prostate-expressed proteins using the shotgun method. Because the DTP method is not quantitative, we employed the absolute quantification method and demonstrate picogram level quantification of prostate-specific antigen. In depth bioinformatics analysis of these expressed proteins affords the categorization of metabolic pathways that may be important for distinct stages of prostate carcinogenesis. Furthermore, we validate Wnt-3 as an upregulated protein in cancerous prostate cells by immunohistochemistry. We propose that this general strategy provides a roadmap for successful identification of critical molecular targets of multiple cancer types.

  9. Tissue and serum sialidase levels in breast cancer.

    Science.gov (United States)

    Sönmez, H; Süer, S; Güngör, Z; Baloglu, H; Kökoglu, E

    1999-02-08

    Breast cancer is both one of the most common and one of the most treatable of all human malignancies. It has been suggested by various investigators that sialic acid increases in the sera of cancerous patients. In cancer patients, an increase in the levels of serum sialic acid may also be due to an increase in the activity of serum or tissue sialidase. The purpose of the present investigation was to determine whether the concentration of sialidase in serum and breast tissue could be used as a tumor marker in breast cancer. In this study; serum sialidase levels in 26 patient with breast cancer and 31 controls were found to be 77.04+/-25.07 U/l and 55.56+/-7.50 U/l, respectively. The mean tissue sialidase levels in 26 breast cancer patients and 13 controls were 39.76+/-17.03 U/g protein and 14.30+/-7.09 U/g protein, respectively. Serum and tissue sialidase levels in breast cancer were significantly higher than those found in the control group (P breast cancer patients were found to be 67.73+/-11.87 U/l and 33.41+/-12.17 U/g protein and 87.89+/-31.94 U/l and 47.17+/-19.30 U/g protein, respectively. Also we found a significant difference between the levels of serum and tissue sialidase in Grade I-II and III (P < 0.05).

  10. Breast cancer screening in Korean woman with dense breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-11-15

    Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

  11. Synchrotron refractive-index microradiography of human liver cancer tissue

    Institute of Scientific and Technical Information of China (English)

    TONG Yongpeng; ZHANG Guilin; LI Yan; HWU Yeukuang; TSAI Wenli; JE Jung Ho; Margaritondo G.; YUAN Dong

    2005-01-01

    Three human liver tissue samples (~5 mm × 40 mm × 20 mm) were excised from a cancer patient's liver during surgery. The microradiology analysis was performed with a non-standard approach on a synchrotron. High-resolution refractive-index edge-enhanced microradiographs that cover a larger volume of the liver tissue sample were obtained. The cancer tissue and normal tissue could be clearly identified and distinguished based on their different textures. Furthermore, new blood vessel hyperplasia was found near the cancer area. Blood vessels with a diameter smaller than 20 μm could be identified. These findings were fully consistent with the histopathological examination of the same area. Microradiographs of the newly formed blood vessels at different angles were also obtained. This result shows that it is possible to further develop this approach into a technique of microradiographic imaging for clinic diagnosis of liver cancer at the early stage.

  12. Preventing clonal evolutionary processes in cancer: Insights from mathematical models.

    Science.gov (United States)

    Rodriguez-Brenes, Ignacio A; Wodarz, Dominik

    2015-07-21

    Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze treatment responses, and aid in the design of treatment strategies to combat the emergence of drug-resistant cells. The discussion will be done in the context of specific examples. Among defense mechanisms, we explore how replicative limits and cellular senescence induced by telomere shortening can influence the emergence and evolution of tumors. Among treatment approaches, we consider the targeted treatment of chronic lymphocytic leukemia (CLL) with tyrosine kinase inhibitors. We illustrate how basic evolutionary mathematical models have the potential to make patient-specific predictions about disease and treatment outcome, and argue that evolutionary models could become important clinical tools in the field of personalized medicine.

  13. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    Science.gov (United States)

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-09-08

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA).

  14. Gene expression profiles in liver cancer and normal liver tissues

    Institute of Scientific and Technical Information of China (English)

    Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu

    2000-01-01

    AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.

  15. Tissue-specificity of proteoglycans expression in different cancers

    Directory of Open Access Journals (Sweden)

    A. V. Suhovskih

    2016-01-01

    Full Text Available Background. Proteoglycans (PGs are complex glycosylated molecules playing an important role in cell-cell and cell-matrix interactions and signaling. Expression of PGs and their expression pattern change considerably during malignant transformation of mammalian cells and tissues.Objective. The aim of our work was to investigate tissue-specificity of main PGs expression (glypican-1, perlecan, syndecan-1, aggrecan, versican, CSPG4/NG2, brevican, decorin, lumican in normal cells (fibroblasts and normal epithelial prostate cells PNT2 and in different human cancer cell lines (prostate, breast, lung, brain, kidney. Expression patterns of main PGs were determined in these cells using reverse transcription polymerase chain reaction analysis and immunocytochemical staining.Results. It was shown that fibroblasts actively expressed PGs, and PNT2 cells had lower (5–6-fold expression levels of a limited set of PG. In different cancer cell lines, overall transcriptional activities of PGs varied up to 10-fold, although their expression patterns had tissue-specific properties (for example, expression of syndecan-1 is more specific for prostate cancer cells, while perlecan is typical for lung cancer cell lines.Conclusions. Along with this, variability of the PG expression patterns in cell lines of the same tissue of origin was shown, suggesting a possible contribution of the variable PGs expression to intratumoural heterogeneity of cancer cells and their potential as perspective biomarker (s for personalised cancer diagnostics.

  16. Adipose tissue, obesity and adipokines: role in cancer promotion.

    Science.gov (United States)

    Booth, Andrea; Magnuson, Aaron; Fouts, Josephine; Foster, Michelle

    2015-01-01

    Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose - elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of well-characterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

  17. Interleukin 18 expression in the primary breast cancer tumour tissue

    Directory of Open Access Journals (Sweden)

    Nahida Srabović

    2011-02-01

    Full Text Available Aim To investigate the presence and expression levels of the IL-18 in the primary breast cancer tissue in relation to the unchangedbreast tissue in same patients and the breast tissue in patients withbenign breast disease, as well as the correlation between the IL-18 expression levels and pathohistological factors, including thecorrelation between IL-18 expression and the estrogens and progesterone receptor status. Methods This prospective randomized study was conducted at the Policlinic for Laboratory Diagnostics of the University Clinical Centre of Tuzla. 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in the study. The tree-step immunohistochemical staining was used for testing the levels of IL-18 expression and hormone receptor status. Results IL-18 was present in the breast cancer tumour, in the surrounding unchanged tissue of the same patients and in the breast tissue of patients with benign breast tumour and other benign breast disease. The expression of this interleukin was signiicantly higher in breast cancer tumour tissue as compared to its expression in surrounding unchanged tissue of the same patients (p<0,05, whereas IL-18 expression was not signiicantly higher in breast cancer tumours compared to its expression in breast tissue of the patients with benign breast diseases (p=0,057. There was no signiicant correlation between IL-18 expression and the lymph node status, and between IL-18 expression and the pathohistological factors. Conclusion The results suggest possible involvement of IL-18 in complex mechanisms of breast carcinogenesis.

  18. Expression of a novel immunoglobulin gene SNC73 in humar cancer and non-cancerous tissues

    Institute of Scientific and Technical Information of China (English)

    Jian-Bin Hu; Shu Zheng; Yong-Chuan Deng

    2003-01-01

    AIM: To investigate the expression of immunoglobulin gene SNC73 in malignant tumors and non-cancerous normal tissues.METHODS: Expression level of SNC73 in tumors and noncancerous tissues from the same patient was determined by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (RT-PCR-ELISA) in 90cases of malignant tumors, including colorectal cancer, gastric cancer, breast cancer, lung cancer and liver cancer. Analysis on the correlation of SNC73 expression with sex, age, site,grade of differentiation, depth of invasion, and metastases in colorectal cancer patients was made.RESULTS: Expression level of SNC73 in non-cancerous colorectal mucosa and colorectal cancerous tissues was 1.234±0.842 and 0.737±0.731, respectively (P<0.01), with the mean ratio of 7.134±14.092 (range, 0.36-59.54).Expression of SNC73 showed no significant difference among gastric cancer, breast cancer, lung cancer and liver cancer when compared with non-cancerous tissues (P>0.05). No correlation was found between SNC73 expression level and various clinicopathological factors, including sex, age, site,grade of differentiation, depth of invasion and metastases of CRC patients.CONCLUSION: Down-regulation of SNC73 expression may be a relatively specific phenomenon in colorectal cancer.SNC73 is a potential genetic marker for the carcinongenesis of colorectal cancer. The relationship of SNC73 expression and carcinogenesis of colorectal cancer merits further study.

  19. The epithelial-mesenchymal interactions: insights into physiological and pathological aspects of oral tissues.

    Science.gov (United States)

    Santosh, Arvind Babu Rajendra; Jones, Thaon Jon

    2014-03-17

    In the human biological system, the individual cells divide and form tissues and organs. These tissues are hetero-cellular. Basically any tissue consists of an epithelium and the connective tissue. The latter contains mainly mesenchymally-derived tissues with a diversified cell population. The cell continues to grow and differentiate in a pre-programmed manner using a messenger system. The epithelium and the mesenchymal portion of each tissue have two different origins and perform specific functions, but there is a well-defined interaction mechanism, which mediates between them. Epithelial mesenchymal interactions (EMIs) are part of this mechanism, which can be regarded as a biological conversation between epithelial and mesenchymal cell populations involved in the cellular differentiation of one or both cell populations. EMIs represent a process that is essential for cell growth, cell differentiation and cell multiplication. EMIs are associated with normal physiological processes in the oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary gland development, palatogenesis, and also pathological processes, such as oral cancer. This paper focuses the role EMIs in odontogenesis, salivary gland development, palatogenesis and oral cancer.

  20. The epithelial-mesenchymal interactions: insights into physiological and pathological aspects of oral tissues

    Directory of Open Access Journals (Sweden)

    Arvind Babu Rajendra Santosh

    2014-03-01

    Full Text Available In the human biological system, the individual cells divide and form tissues and organs. These tissues are hetero-cellular. Basically any tissue consists of an epithelium and the connective tissue. The latter contains mainly mesenchymally-derived tissues with a diversified cell population. The cell continues to grow and differentiate in a pre-programmed manner using a messenger system. The epithelium and the mesenchymal portion of each tissue have two different origins and perform specific functions, but there is a well-defined interaction mechanism, which mediates between them. Epithelial mesenchymal interactions (EMIs are part of this mechanism, which can be regarded as a biological conversation between epithelial and mesenchymal cell populations involved in the cellular differentiation of one or both cell populations. EMIs represent a process that is essential for cell growth, cell differentiation and cell multiplication. EMIs are associated with normal physiological processes in the oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary gland development, palatogenesis, and also pathological processes, such as oral cancer. This paper focuses the role EMIs in odontogenesis, salivary gland development, palatogenesis and oral cancer.

  1. Limitations of tissue micro array in Duke's B colon cancer

    DEFF Research Database (Denmark)

    Kjær-Frifeldt, Sanne; Lindebjerg, Jan; Brunner, Nils;

    2012-01-01

    Tissue micro array (TMA) is widely used in cancer research in search of new predictive and prognostic markers. Colon cancer is known to be heterogeneous and the present study addresses some methodological aspects using cores of different size and analysing markers with different cellular...... distribution. We selected 61 paraffin-embedded tissue blocks representing patients diagnosed with Dukes B colon cancer. Two 1 mm and two 2 mm cores were taken from both the centre and the invasive front of the tumour respectively. The immunostaining included MLH1, MSH2, PMS2, p53, COX-2, TIMP and Betacatenin...... moderate to high agreement (kappa = 0.54-0.9) whereas TIMP-1 had the lowest score (kappa 0.19-0.25). The application of TMA in Dukes B colon cancer has several pitfalls and depends substantially on the immunohistochemical marker in question. Therefore a validation study seems justified before applying...

  2. Regulation of Breast Cancer Stem Cell by Tissue Rigidity

    Science.gov (United States)

    2015-06-01

    Gilman Drive, La Jolla, California 92093-0819, USA. 7Present address: Department of Immunology , The University of Texas MD Anderson Cancer Center, 7455...AD_________________ Award Number: W81XWH-13-1-0132 TITLE: Regulation of Breast Cancer Stem Cell by Tissue Rigidity PRINCIPAL INVESTIGATOR: Jing...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of

  3. Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis

    Science.gov (United States)

    Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2011-07-01

    Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

  4. GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues.

    Directory of Open Access Journals (Sweden)

    Gayatri Gowrishankar

    Full Text Available F18 2-Fluoro 2-deoxyglucose (FDG has been the gold standard in positron emission tomography (PET oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues.

  5. Tissue Microarray A New Tool for Cancer Research

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Shanghai Outdo Biotech Co.Ltd. (Outdo Biotech) is a leading company in human/animal Tissue Microarrays (TMA) and "Clinical-Type" Gene Chip (CTGC) in China. Our shareholders are Shanghai Biochip Co., Ltd. & National Engineering Center for Biochip at Shanghai, Shanghai Cancer institute and Eastern Liver and Bladder Hospital of Second Military Medical University. TMA is a mean of combining tens to hundreds of specimens of tissue, paraffin embedded or frozen, onto a single slide for analysis at once. Our constr...

  6. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Federica Marchesi

    2011-12-01

    Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  7. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

    2011-12-28

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  8. The role of adipose tissue in cancer-associated cachexia.

    Science.gov (United States)

    Vaitkus, Janina A; Celi, Francesco S

    2017-03-01

    Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

  9. Accessory breast tissue in axilla masquerading as breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Goyal Shikha

    2008-01-01

    Full Text Available Ectopic or accessory breast tissue is most commonly located in the axilla, though it may be present anywhere along the milk line. Development is hormone dependent, similar to normal breast tissue. These lesions do not warrant any intervention unless they produce discomfort, thus their identification and distinction from other breast pathologies, both benign and malignant, is essential. We report a case with locally advanced breast cancer who presented with an ipsilateral axillary mass following surgery, radiotherapy, and chemotherapy. Subsequent evaluation with excision biopsy showed duct ectasia in axillary breast tissue and the patient was continued on hormone therapy with tamoxifen.

  10. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

    Science.gov (United States)

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J; Sirota, Marina

    2016-05-04

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.

  11. Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification.

    Science.gov (United States)

    Bertazzo, Sergio; Gentleman, Eileen; Cloyd, Kristy L; Chester, Adrian H; Yacoub, Magdi H; Stevens, Molly M

    2013-06-01

    The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.

  12. The Function of Steroid Receptor Coactivator-1 in Normal Tissues and Cancer

    Directory of Open Access Journals (Sweden)

    Claire A. Walsh, Li Qin, Jean Ching-Yi Tien, Leonie S. Young, Jianming Xu

    2012-01-01

    Full Text Available In 1995, the steroid receptor coactivator-1 (SRC-1 was identified as the first authentic steroid receptor coactivator. Since then, the SRC proteins have remained at the epicenter of coregulator biology, molecular endocrinology and endocrine-related cancer. Cumulative works on SRC-1 have shown that it is primarily a nuclear receptor coregulator and functions to construct highly specific enzymatic protein complexes which can execute efficient and successful transcriptional activation of designated target genes. The versatile nature of SRC-1 enables it to respond to steroid dependent and steroid independent stimulation, allowing it to bind across many families of transcription factors to orchestrate and regulate complex physiological reactions. This review highlights the multiple functions of SRC-1 in the development and maintenance of normal tissue functions as well as its major role in mediating hormone receptor responsiveness. Insights from genetically manipulated mouse models and clinical data suggest SRC-1 is significantly overexpressed in many cancers, in particular, cancers of the reproductive tissues. SRC-1 has been associated with cellular proliferation and tumor growth but its major tumorigenic contributions are promotion and execution of breast cancer metastasis and mediation of resistance to endocrine therapies. The ability of SRC-1 to coordinate multiple signaling pathways makes it an important player in tumor cells' escape of targeted therapy.

  13. Tissue-engineered models of human tumors for cancer research

    Science.gov (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

    Introduction Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research. Areas covered In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing. Expert opinion While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function. PMID:25662589

  14. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    Science.gov (United States)

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  15. Insights into cancer severity from biomolecular interaction mechanisms

    Science.gov (United States)

    Raimondi, Francesco; Singh, Gurdeep; Betts, Matthew J.; Apic, Gordana; Vukotic, Ranka; Andreone, Pietro; Stein, Lincoln; Russell, Robert B.

    2016-01-01

    To attain a deeper understanding of diseases like cancer, it is critical to couple genetics with biomolecular mechanisms. High-throughput sequencing has identified thousands of somatic mutations across dozens of cancers, and there is a pressing need to identify the few that are pathologically relevant. Here we use protein structure and interaction data to interrogate nonsynonymous somatic cancer mutations, identifying a set of 213 molecular interfaces (protein-protein, -small molecule or –nucleic acid) most often perturbed in cancer, highlighting several potentially novel cancer genes. Over half of these interfaces involve protein-small-molecule interactions highlighting their overall importance in cancer. We found distinct differences in the predominance of perturbed interfaces between cancers and histological subtypes and presence or absence of certain interfaces appears to correlate with cancer severity. PMID:27698488

  16. Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury, and allograft tolerance.

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A; Thomson, Angus W

    2016-04-01

    The surgically demanding mouse orthotopic liver transplant model was first described in 1991. It has proved to be a powerful research tool for the investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction, and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, because the mouse genome is well characterized and there is much greater availability of both genetically modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice have provided valuable mechanistic insights into the immunobiology and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in the regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/immune-mediated events in the hepatic environment and systemically. In conclusion, orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology, and allograft tolerance that may result in therapeutic innovation in the liver and in the treatment of other diseases.

  17. An informatics model for tissue banks – Lessons learned from the Cooperative Prostate Cancer Tissue Resource

    Directory of Open Access Journals (Sweden)

    Melamed Jonathan

    2006-05-01

    Full Text Available Abstract Background Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE development, query interfaces, data curation, and quality control. Methods Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Results Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA. The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a

  18. A role of active brown adipose tissue in cancer cachexia?

    Directory of Open Access Journals (Sweden)

    Emiel Beijer

    2012-06-01

    Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  19. Insights from Epidemiology into Dichloromethane and Cancer Risk

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    Cheryl Siegel Scott

    2011-08-01

    Full Text Available Dichloromethane (methylene chloride is a widely used chlorinated solvent. We review the available epidemiology studies (five cohort studies, 13 case-control studies, including seven of hematopoietic cancers, focusing on specific cancer sites. There was little indication of an increased risk of lung cancer in the cohort studies (standardized mortality ratios ranging from 0.46 to 1.21. These cohorts are relatively small, and variable effects (e.g., point estimates ranging from 0.5 to 2.0 were seen for the rarer forms of cancers such as brain cancer and specific hematopoietic cancers. Three large population-based case-control studies of incident non-Hodgkin lymphoma in Europe and the United States observed odds ratios between 1.5 and 2.2 with dichloromethane exposure (ever exposed or highest category of exposure, with higher risk seen in specific subsets of disease. More limited indications of associations with brain cancer, breast cancer, and liver and biliary cancer were also seen in this collection of studies. Existing cohort studies, given their size and uneven exposure information, are unlikely to resolve questions of cancer risks and dichloromethane exposure. More promising approaches are population-based case-control studies of incident disease, and the combination of data from such studies, with robust exposure assessments that include detailed occupational information and exposure assignment based on industry-wide surveys or direct exposure measurements.

  20. Prostate cancer outcome and tissue levels of metal ions

    Science.gov (United States)

    Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Michael A.; Kajdacsy-Balla, A.

    2011-01-01

    BACKGROUND There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome. METHODS We obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case-control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se. RESULTS Patients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 ??g/g vs. 111 ??g/g; P = 0.04) and 21% lower zinc (279 ??g/g vs. 346 ??g/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 ??g/g vs. 0.439 ??g/g; 4% higher) and selenium (1.68 ??g/g vs. 1.58 ??g/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively). CONCLUSIONS There is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. Copyright ?? 2011 Wiley-Liss, Inc.

  1. Insights from Epidemiology into Dichloromethane and Cancer Risk

    OpenAIRE

    Cheryl Siegel Scott; Cooper, Glinda S.; Bale, Ambuja S.

    2011-01-01

    Dichloromethane (methylene chloride) is a widely used chlorinated solvent. We review the available epidemiology studies (five cohort studies, 13 case-control studies, including seven of hematopoietic cancers), focusing on specific cancer sites. There was little indication of an increased risk of lung cancer in the cohort studies (standardized mortality ratios ranging from 0.46 to 1.21). These cohorts are relatively small, and variable effects (e.g., point estimates ranging from 0.5 to 2.0) we...

  2. Tissue inhibitor of metalloproteinases-1 in breast cancer

    DEFF Research Database (Denmark)

    Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Sørensen, Nanna Møller

    2005-01-01

    biological functions of TIMP-1 such as growth-stimulating functions, as well as anti-apoptotic and pro-angiogenetic effects, may in part explain this paradox. The purpose of this review is to give an update on the current status of TIMP-1 in breast cancer, emphasizing the prognostic utility of the inhibitor......Whether patients diagnosed with primary breast cancer are offered adjuvant systemic therapy following surgical removal of the tumor is based on prognosis. Prognosis is estimated in every patient using established prognostic variables. Unfortunately, when using the currently available prognostic...... parameters a significant proportion of patients are over-treated. Thus, in order to improve stratification of breast cancer patients, additional prognostic factors need to be identified. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the promising candidates for new prognostic markers in breast...

  3. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.

    Directory of Open Access Journals (Sweden)

    Yuki Togashi

    Full Text Available The promising results of anaplastic lymphoma kinase (ALK inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE, and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.

  4. Automated prostate cancer diagnosis and Gleason grading of tissue microarrays

    Science.gov (United States)

    Tabesh, Ali; Kumar, Vinay P.; Pang, Ho-Yuen; Verbel, David; Kotsianti, Angeliki; Teverovskiy, Mikhail; Saidi, Olivier

    2005-04-01

    We present the results on the development of an automated system for prostate cancer diagnosis and Gleason grading. Images of representative areas of the original Hematoxylin-and-Eosin (H&E)-stained tissue retrieved from each patient, either from a tissue microarray (TMA) core or whole section, were captured and analyzed. The image sets consisted of 367 and 268 color images for the diagnosis and Gleason grading problems, respectively. In diagnosis, the goal is to classify a tissue image into tumor versus non-tumor classes. In Gleason grading, which characterizes tumor aggressiveness, the objective is to classify a tissue image as being from either a low- or high-grade tumor. Several feature sets were computed from the image. The feature sets considered were: (i) color channel histograms, (ii) fractal dimension features, (iii) fractal code features, (iv) wavelet features, and (v) color, shape and texture features computed using Aureon Biosciences' MAGIC system. The linear and quadratic Gaussian classifiers together with a greedy search feature selection algorithm were used. For cancer diagnosis, a classification accuracy of 94.5% was obtained on an independent test set. For Gleason grading, the achieved accuracy of classification into low- and high-grade classes of an independent test set was 77.6%.

  5. Electrical impedance characterization of normal and cancerous human hepatic tissue.

    Science.gov (United States)

    Laufer, Shlomi; Ivorra, Antoni; Reuter, Victor E; Rubinsky, Boris; Solomon, Stephen B

    2010-07-01

    The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1-400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 +/- 0.06 S m(-1) versus 0.03 +/- 0.01 S m(-1) at 1 kHz to 0.25 +/- 0.06 S m(-1) versus 0.15 +/- 0.03 S m(-1) at 400 kHz). The Cole-Cole models were estimated from the experimental data and the four parameters (rho(0), rho(infinity), alpha, f(c)) were obtained using a least-squares fit algorithm. The Cole-Cole parameters for the cancerous and normal liver are 9 +/- 4 Omega m(-1), 2.2 +/- 0.7 Omega m(-1), 0.5 +/- 0.2, 140 +/- 103 kHz and 50 +/- 28 Omega m(-1), 3.2 +/- 0.6 Omega m(-1), 0.64 +/- 0.04, 10 +/- 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation.

  6. Heterogeneous response of adipose tissue to cancer cachexia

    Directory of Open Access Journals (Sweden)

    P.S. Bertevello

    2001-09-01

    Full Text Available Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES, retroperitoneal (RPAT, and epididymal (EAT adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections and EAT (nuclear bodies.

  7. Robust multi-tissue gene panel for cancer detection

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    Talantov Dmitri

    2010-06-01

    Full Text Available Abstract Background We have identified a set of genes whose relative mRNA expression levels in various solid tumors can be used to robustly distinguish cancer from matching normal tissue. Our current feature set consists of 113 gene probes for 104 unique genes, originally identified as differentially expressed in solid primary tumors in microarray data on Affymetrix HG-U133A platform in five tissue types: breast, colon, lung, prostate and ovary. For each dataset, we first identified a set of genes significantly differentially expressed in tumor vs. normal tissue at p-value = 0.05 using an experimentally derived error model. Our common cancer gene panel is the intersection of these sets of significantly dysregulated genes and can distinguish tumors from normal tissue on all these five tissue types. Methods Frozen tumor specimens were obtained from two commercial vendors Clinomics (Pittsfield, MA and Asterand (Detroit, MI. Biotinylated targets were prepared using published methods (Affymetrix, CA and hybridized to Affymetrix U133A GeneChips (Affymetrix, CA. Expression values for each gene were calculated using Affymetrix GeneChip analysis software MAS 5.0. We then used a software package called Genes@Work for differential expression discovery, and SVM light linear kernel for building classification models. Results We validate the predictability of this gene list on several publicly available data sets generated on the same platform. Of note, when analysing the lung cancer data set of Spira et al, using an SVM linear kernel classifier, our gene panel had 94.7% leave-one-out accuracy compared to 87.8% using the gene panel in the original paper. In addition, we performed high-throughput validation on the Dana Farber Cancer Institute GCOD database and several GEO datasets. Conclusions Our result showed the potential for this panel as a robust classification tool for multiple tumor types on the Affymetrix platform, as well as other whole genome arrays

  8. MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

    Directory of Open Access Journals (Sweden)

    Jessica Anne Crawford

    2013-04-01

    Full Text Available Ovarian cancer is the most common pediatric gynecologic malignancy. When diag-nosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have re-cently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers and developing targeted therapies are discussed.

  9. Transcriptome profiling of the cancer, adjacent non-tumor and distant normal tissues from a colorectal cancer patient by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Yan'an Wu

    Full Text Available Colorectal cancer (CRC is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.

  10. Stem cell biology in thyroid cancer: Insights for novel therapies

    Institute of Scientific and Technical Information of China (English)

    Parisha; Bhatia; Koji; Tsumagari; Zakaria; Y; Abd; Elmageed; Paul; Friedlander; Joseph; F; Buell; Emad; Kandil

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

  11. Stem cell biology in thyroid cancer: Insights for novel therapies

    Science.gov (United States)

    Bhatia, Parisha; Tsumagari, Koji; Abd Elmageed, Zakaria Y; Friedlander, Paul; Buell, Joseph F; Kandil, Emad

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review. PMID:25426258

  12. Nanomaterials and Autophagy: New Insights in Cancer Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Panzarini, Elisa; Inguscio, Valentina; Tenuzzo, Bernardetta Anna; Carata, Elisabetta; Dini, Luciana, E-mail: luciana.dini@unisalento.it [Department of Biological and Environmental Science and Technology (Di.S.Te.B.A.), University of Salento, Lecce 73100 (Italy)

    2013-03-21

    Autophagy represents a cell’s response to stress. It is an evolutionarily conserved process with diversified roles. Indeed, it controls intracellular homeostasis by degradation and/or recycling intracellular metabolic material, supplies energy, provides nutrients, eliminates cytotoxic materials and damaged proteins and organelles. Moreover, autophagy is involved in several diseases. Recent evidences support a relationship between several classes of nanomaterials and autophagy perturbation, both induction and blockade, in many biological models. In fact, the autophagic mechanism represents a common cellular response to nanomaterials. On the other hand, the dynamic nature of autophagy in cancer biology is an intriguing approach for cancer therapeutics, since during tumour development and therapy, autophagy has been reported to trigger both an early cell survival and a late cell death. The use of nanomaterials in cancer treatment to deliver chemotherapeutic drugs and target tumours is well known. Recently, autophagy modulation mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as adjuvant in chemotherapy or in the development of cancer vaccines or as a potential anti-cancer agent. Herein, we summarize the effects of nanomaterials on autophagic processes in cancer, also considering the therapeutic outcome of synergism between nanomaterials and autophagy to improve existing cancer therapies.

  13. NIH scientists provide new insight into rare kidney cancer

    Science.gov (United States)

    NIH scientists have discovered a unique feature of a rare, hereditary form of kidney cancer that may provide a better understanding of its progression and metastasis, possibly laying the foundation for the development of new targeted therapies.

  14. Proteomic analysis of formalin-fixed prostate cancer tissue.

    Science.gov (United States)

    Hood, Brian L; Darfler, Marlene M; Guiel, Thomas G; Furusato, Bungo; Lucas, David A; Ringeisen, Bradley R; Sesterhenn, Isabell A; Conrads, Thomas P; Veenstra, Timothy D; Krizman, David B

    2005-11-01

    Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.

  15. Organoid culture systems for prostate epithelial and cancer tissue.

    Science.gov (United States)

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-02-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumor. We explain how to establish these cultures in the fully defined serum-free conditioned medium that is required to sustain organoid growth. Starting with the plating of digested tissue material, full-grown organoids can usually be obtained in ∼2 weeks. The culture protocol we describe here is currently the only one that allows the growth of both the luminal and basal prostatic epithelial lineages, as well as the growth of advanced prostate cancers. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery.

  16. Clinical and molecular insights into primary pediatric liver cancer

    NARCIS (Netherlands)

    V.B. Weeda

    2016-01-01

    This thesis aims to give insight into the clinical status quo of primary pediatric liver tumors and investigate signaling pathways that may be of importance for liver tumorigenesis. The most recent series of the International Childhood Liver Tumors Strategy Group (SIOPEL) of hepatocellular carcinoma

  17. Dynamics of tissue topology during cancer invasion and metastasis

    Science.gov (United States)

    Munn, Lance L.

    2013-12-01

    During tumor progression, cancer cells mix with other cell populations including epithelial and endothelial cells. Although potentially important clinically as well as for our understanding of basic tumor biology, the process of mixing is largely a mystery. Furthermore, there is no rigorous, analytical measure available for quantifying the mixing of compartments within a tumor. I present here a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of observed tumor behaviors with correct tissue compartmentalization and connectivity. The resulting dynamics are analyzed in light of the Euler characteristic number (χ), which describes key topological features such as fragmentation, looping and cavities. The analysis predicts a number of regimes in which the cancer cells can encapsulate normal tissue, form a co-interdigitating mass, or become fragmented and encapsulated by endothelial or epithelial structures. Key processes that affect the topological changes are the production of provisional matrix in the tumor, and the migration of endothelial or epithelial cells on this matrix. Furthermore, the simulations predict that topological changes during tumor invasion into blood vessels may contribute to metastasis. The topological analysis outlined here could be useful for tumor diagnosis or monitoring response to therapy and would only require high resolution, 3D image data to resolve and track the various cell compartments.

  18. New insights into calcium, dairy and colon cancer

    Institute of Scientific and Technical Information of China (English)

    Peter R Holt

    2008-01-01

    This paper is to review recent information about the relationship of calcium and dairy foods to colon cancer.The review focuses on primary prevention, discusses the potential components in dairy foods that might be anti-neoplastic, reviews the epidemiologic information and describes intervention studies demonstrating efficacy of calcium and vitamin D in reducing colorectal polyp recurrence. Since vitamin D is important in cancer prevention, pertinent data is discussed and potential mechanisms of actions presented. Calcium and vitamin D are important agents for the primary prevention of colorectal neoplasia.

  19. Nonsmall Cell Lung Cancer Therapy: Insight into Multitargeted Small-Molecule Growth Factor Receptor Inhibitors

    Directory of Open Access Journals (Sweden)

    Mridul Roy

    2013-01-01

    Full Text Available To date, lung cancer is the leading cause of cancer-related death worldwide, among which nonsmall cell lung cancer (NSCLC comprises about 85%. Taking into account the side effects of surgery, radiation, platinum-based doublet chemotherapy, and the growth self-sufficiency characteristic of cancer cells, drugs have been discovered toward growth factor receptor (GFR to treat NSCLC. As expected, these drugs provide a greater benefit. To increase the efficacy of such growth factor receptor tyrosine kinase inhibitors (RTKIs, coinhibition of GFR signaling pathways and combination of inhibitors along with radiation or chemotherapy have drew intense insight. Although clinical trials about single-agent RTKIs or their combination strategies suggest their increase potency against cancer, they are not beyond adverse effects, and sometimes the effects are more deadly than chemotherapy. Nevertheless the hope for RTKIs may be proved true by further researches and digging deep into cancer therapeutics.

  20. ADVANTAGES AND APPLICATIONS OF TISSUE MICROARRAY TECHNOLOGY ON CANCER RESEARCH

    Institute of Scientific and Technical Information of China (English)

    张喜平; 苏丹; 程琪辉

    2003-01-01

    S To provide evidences for exploiting tissue microarray (TMA) technology, we reviewed advantages and applications of TMA on tumor research. TMA has many advantages, including (1) section from TMA blocks can be utilized for the simultaneous analysis of up to 1,000 different tumors at DNA, RNA or protein level; (2) TMA is highly representative of their donor tissues; (3) TMA can improve conservation of tissue resources and experimental reagents, improve internal experimental control, and increase sample numbers per experiment, and can be used for large-scale, massively parallel in situ analysis; (4) TMA facilitates rapid translation of molecular discoveries to clinical applications. TMA has been applied to tumor research, such as glioma, breast tumor, lung cancer and so on. The development of novel biochip technologies has opened up new possibilities for the high-throughput molecular profiling of human tumors. Novel molecular markers emerging from high-throughput expression surveys could be analyzed on tumor TMA. It is anticipated that TMA, a new member of biochip, will soon become a widely used tool for all types of tissue-based research. TMA will lead to a significant acceleration of the transition of basic research findings into clinical applications.

  1. Monitoring cancer stem cells: insights into clinical oncology

    Directory of Open Access Journals (Sweden)

    Lin SC

    2016-02-01

    Full Text Available ShuChen Lin,1,* YingChun Xu,2,* ZhiHua Gan,1 Kun Han,1 HaiYan Hu,3 Yang Yao,3 MingZhu Huang,4 DaLiu Min1 1Department of Oncology, Shanghai Sixth People’s Hospital East Campus, Shanghai Jiao Tong University, 2Department of Oncology, Renji Hospital, Shanghai Jiao Tong University, 3Department of Oncology, The Sixth People’s Hospital, Shanghai Jiao Tong University, 4Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer stem cells (CSCs are a small, characteristically distinctive subset of tumor cells responsible for tumor initiation and progression. Several treatment modalities, such as surgery, glycolytic inhibition, driving CSC proliferation, immunotherapy, and hypofractionated radiotherapy, may have the potential to eradicate CSCs. We propose that monitoring CSCs is important in clinical oncology as CSC populations may reflect true treatment response and assist with managing treatment strategies, such as defining optimal chemotherapy cycles, permitting pretreatment cancer surveillance, conducting a comprehensive treatment plan, modifying radiation treatment, and deploying rechallenge chemotherapy. Then, we describe methods for monitoring CSCs. Keywords: cancer stem cells, glycolytic inhibition, watchful waiting, rechallenge, immunotherapy

  2. Hierarchical mechanics of connective tissues: integrating insights from nano to macroscopic studies.

    Science.gov (United States)

    Gohl, Kheng Lim; Listrat, Anne; Béchet, Daniel

    2014-10-01

    As the key component of the musculoskeletal system, the extracellular matrix of soft connective tissues such as ligaments and tendons is a biological example of fibre-reinforced composite but with a complex hierarchical architecture. To establish a comprehensive structure-function relationship at the respective levels (i.e., from molecule to tissue) of the hierarchical architecture is challenging and requires a multidisciplinary approach, involving the integration of findings from the fields of molecular biology, biochemistry, structural biology, materials science and biophysics. Accordingly, in recent years, some of these fields, namely structural biology, materials science and biophysics, have made significant progress in the microscale and nanoscale studies of extracellular matrix using new tools, such as microelectromechanical systems, optical tweezers and atomic force microscopy, complemented by new techniques in simultaneous imaging and mechanical testing and computer modelling. The intent of this paper is to review the key findings on the mechanical response of extracellular matrix at the respective levels of the hierarchical architecture. The main focus is on the structure and function--the findings are compared across the different levels to provide insights that support the goal of establishing a comprehensive structure-function relationship of extracellular matrix. For this purpose, the review is divided into two parts. The first part explores the features of key structural units of extracellular matrix, namely tropocollagen molecule (the lowest level), microfibril, collagen fibril, collagen fibre and fascicle. The second part examines the mechanics of the structural units at the respective levels. Finally a framework for extracellular matrix mechanics is proposed to support the goal to establish a comprehensive structure-function relationship. The framework describes the integration of the mechanisms of reinforcement by the structural units at the

  3. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Maria Grazia Daidone

    2011-03-01

    Full Text Available There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC. BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24−/low and/or CD133+ expression or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+, have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  4. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia, E-mail: mariagrazia.daidone@istitutotumori.mi.it [Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Via Amadeo 42, Milan 20133 (Italy)

    2011-03-16

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44{sup +}/CD24{sup −/low} and/or CD133{sup +} expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1{sup +}), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  5. Cancer tissue engineering - new perspectives in understanding the biology of solid tumours - a critical review

    NARCIS (Netherlands)

    Ricci, C.; Moroni, L.; Danti, S.

    2013-01-01

    Understanding cancer biology is a major challenge of this century. The recent insight about carcinogenesis mechanisms, including the role exerted by the tumour microenvironment and cancer stem cells in chemoresistance, relapse and metastases, has made it self-evident that only new cancer models, wit

  6. Implementation of tissue microarrays technique for cancer research in Cuba

    Directory of Open Access Journals (Sweden)

    Tania Lahera-Sánchez

    2015-08-01

    Full Text Available The tissue microarray (TMA technique is based on making cylindrical cores from paraffin donor blocks and transfer to a single recipient block. The TMA has revolutionized the field of pathology for the possibility to evaluate multiple samples in one slide. There is no precedent of this subject in Cuba, so the objective of this research was to implement the TMA technique. The concordance of the results obtained by complete section and the TMA were evaluated for this purpose, in the evaluation of the estrogen receptors (ER, progesterone (PR and epidermal growth factor type 2 (HER2 in samples of breast cancer. Forty-five paraffin-embedded samples from women diagnosed with breast cancer at the Institute of Oncology in 2012 were studied. Two TMA blocks were constructed, and subsequently the expression of markers ER, PR and HER2 was determined by immunohistochemistry, in the complete section of tissue and in the TMA. Kappa index was used for concordance analysis. A good concordance was obtained for all three markers (ER k=0.8272; PR k=0.793 and HER2 k=0.716. This study constitutes the first report on the TMA technique in Cuba and shows that it is a valuable tool, suggesting its potential use in translational research and clinical trials on vaccines.

  7. Adipose tissue-secreted miR-27a promotes liver cancer by targeting FOXO1 in obese individuals

    Directory of Open Access Journals (Sweden)

    Sun B

    2015-04-01

    Full Text Available Baozhen Sun,1,* Jing Li,2,* Dan Shao,2 Yue Pan,2 Yujing Chen,2 Suo Li,1 Xiaoxiao Yao,1 Hang Li,1 Weiwei Liu,3 Ming Zhang,2 Xuewen Zhang,1 Li Chen2 1Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of China; 3School of Stomatology, Jilin University, Changchun, People’s Republic of China *These authors contributed equally to this work Abstract: The current notion that obesity is a major risk factor for the development of and the mortality associated with a subset of liver cancer is well appreciated. However, detailed mechanistic insights underlying this relationship are lacking. Better understanding of the adipose tissue-secreted miRNAs that play a potential role in defining primary liver cancer development and mediating the obesity-cancer communication offers the potential for new insights into tumor growth and interventions to modulate tumor formation and progression. In this study, we clearly demonstrated that miR-27a is more highly upregulated in cancer, plasma, and adipose samples from obese liver cancer cases, and therefore reasoned that miR-27a excreted from adipose tissue leads to liver cancer development. To address this idea, we prepared miR-27a-overexpressing 3T3-L1 adipocytes and cocultured them with HepG2 liver cancer cells. Our results demonstrated that secretory miR-27a promoted liver cancer cell proliferation through the downregulation of the transcription factor FOXO1 and promoted the G1/S cell cycle transition by decreasing the cell cycle inhibitors p21 and p27 and increasing the cell cycle regulator cyclin D1. These findings improve our understanding of the involvement of miR-27a in obesity-liver cancer communication and might provide a novel putative target for obesity

  8. Expression of Uncoupling Protein 2 in Breast Cancer Tissue and Drug-resistant Cells

    Institute of Scientific and Technical Information of China (English)

    Sun Yan; Yuan Yuan; Zhang Lili; Zhu Hong; Hu Sainan

    2013-01-01

    Objective:To explore the expression of uncoupling protein-2 (UCP2) in clinical breast cancer tissue and drug-resistant cells. Methods:The expression of UCP2 in breast cancer tissue and normal tissue adjacent to carcinoma as well as breast cancer cell MCF-7 and paclitaxel-resistant cell MX-1/T were respectively detected by immunohistochemistry and Western blot. Results:The expression of UCP2 in breast cancer tissue was signiifcantly higher than in normal tissue adjacent to carcinoma, and that in paclitaxel-resistant cell MX-1/T obviously higher than in breast cancer cell MCF-7. Conclusion:UCP2 is highly expressed in breast cancer tissue and drug-resistant cells.

  9. Insight view on possible role of fluoroquinolones in cancer therapy.

    Science.gov (United States)

    Sharma, Prabodh C; Chaudhary, Monika; Sharma, Archana; Piplani, Mona; Rajak, Harish; Prakash, Om

    2013-08-01

    Cancer is a disease without limits turning out to be prime cause for raising death toll around the world. Several treatment strategies including chemotherapy, surgery and radiotherapy are being employed worldwide to combat this disease. Due to the unwanted effects of currently available therapies, scientific community is immensely interested in exploring newer alternative pathways. Fluoroquinolones have been employed as potent anti-microbial agents for last few decades and now being looked up as potential therapeutic agents in the other ailments also. Several research endeavours are carried out in different parts of the world to focus on the prospective role of fluoroquinolones in carcinogenesis and mutagenesis. This article is an earnest attempt to present recent research work carried out on fluoroquinolones in the context to cancer treatment therapies.

  10. Nutrition support and dietary interventions for patients with lung cancer: current insights

    Directory of Open Access Journals (Sweden)

    Kiss N

    2016-01-01

    Full Text Available Nicole Kiss1,2 1Nutrition and Speech Pathology Department, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; 2Department of Cancer Experiences Research, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia Abstract: Malnutrition and weight loss are prevalent in patients with lung cancer. The impact of malnutrition on patients with cancer, and specifically in patients with lung cancer, has been demonstrated in a large number of studies. Malnutrition has been shown to negatively affect treatment completion, survival, quality of life, physical function, and health care costs. Emerging evidence is providing some insight into which lung cancer patients are at higher nutritional risk. In lung cancer patients treated with radiotherapy, stage III or more disease, treatment with concurrent chemotherapy and the extent of radiotherapy delivered to the esophagus appear to confer a higher risk of weight loss during and post-treatment. Studies investigating nutrition interventions for lung cancer patients have examined intensive dietary counseling, supplementation with fish oils, and interdisciplinary models of nutrition and exercise interventions and show promise for improved outcomes from these interventions. However, further research utilizing these interventions in large clinical trials is required to definitively establish effective interventions in this patient group. Keywords: lung cancer, nutrition, malnutrition

  11. Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta-analysis of observational studies

    DEFF Research Database (Denmark)

    Svahn, Malene F; Faber, Mette Tuxen; Christensen, Jane

    2014-01-01

    The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue.......The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue....

  12. Folate receptor and Ki-67 nucleoprotein expressions in cervical cancer tissue and their correlation

    Institute of Scientific and Technical Information of China (English)

    Ran Yan; Feng Li

    2016-01-01

    Objective:To detect the expression of both FR-α protein and ki-67 in cervical cancer tissues, and discuss the relationship between them and clinical significance.Methods:Using immunohistochemical method test normal cervical tissue and cervical cancer tissue before FR-α protein expression and the expression of Ki-67.Results:FR- protein expression in normal cervical tissues was positive for 7.0% while in cervical cancer tissue the positive rate was 82.1%. The difference was statistically significant. Ki-67 protein expression in normal cervical tissues was 0% while in cervical cancer tissue the positive rate was 80.2%. The difference was statistically significant. The two protein expression in cervical cancer stageⅠ,Ⅱ and stageⅢ were different, but the difference was not statistically significant. In cervical cancer tissues, both the two protein were positively correlated. There are correlations between them. Difference was statistically significant.Conclusion:FR-α elevated protein expression is involved in the pathogenesis of cervical cancer. FR-α protein expression in cervical cancer and precancerous tissue has correlation with Ki-67, FR-α protein maybe participate in the occurrence and development of the cell proliferation in cervical cancer.

  13. Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.

    Science.gov (United States)

    Ali Hassan, Nur Zarina; Mokhtar, Norfilza Mohd; Kok Sin, Teow; Mohamed Rose, Isa; Sagap, Ismail; Harun, Roslan; Jamal, Rahman

    2014-01-01

    Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV) and gene expression in colorectal cancer (CRC) samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

  14. Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.

    Directory of Open Access Journals (Sweden)

    Nur Zarina Ali Hassan

    Full Text Available Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV and gene expression in colorectal cancer (CRC samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

  15. Two New Complete Genome Sequences Offer Insight into Host and Tissue Specificity of Plant Pathogenic Xanthomonas spp.▿†

    Science.gov (United States)

    Bogdanove, Adam J.; Koebnik, Ralf; Lu, Hong; Furutani, Ayako; Angiuoli, Samuel V.; Patil, Prabhu B.; Van Sluys, Marie-Anne; Ryan, Robert P.; Meyer, Damien F.; Han, Sang-Wook; Aparna, Gudlur; Rajaram, Misha; Delcher, Arthur L.; Phillippy, Adam M.; Puiu, Daniela; Schatz, Michael C.; Shumway, Martin; Sommer, Daniel D.; Trapnell, Cole; Benahmed, Faiza; Dimitrov, George; Madupu, Ramana; Radune, Diana; Sullivan, Steven; Jha, Gopaljee; Ishihara, Hiromichi; Lee, Sang-Won; Pandey, Alok; Sharma, Vikas; Sriariyanun, Malinee; Szurek, Boris; Vera-Cruz, Casiana M.; Dorman, Karin S.; Ronald, Pamela C.; Verdier, Valérie; Dow, J. Maxwell; Sonti, Ramesh V.; Tsuge, Seiji; Brendel, Volker P.; Rabinowicz, Pablo D.; Leach, Jan E.; White, Frank F.; Salzberg, Steven L.

    2011-01-01

    Xanthomonas is a large genus of bacteria that collectively cause disease on more than 300 plant species. The broad host range of the genus contrasts with stringent host and tissue specificity for individual species and pathovars. Whole-genome sequences of Xanthomonas campestris pv. raphani strain 756C and X. oryzae pv. oryzicola strain BLS256, pathogens that infect the mesophyll tissue of the leading models for plant biology, Arabidopsis thaliana and rice, respectively, were determined and provided insight into the genetic determinants of host and tissue specificity. Comparisons were made with genomes of closely related strains that infect the vascular tissue of the same hosts and across a larger collection of complete Xanthomonas genomes. The results suggest a model in which complex sets of adaptations at the level of gene content account for host specificity and subtler adaptations at the level of amino acid or noncoding regulatory nucleotide sequence determine tissue specificity. PMID:21784931

  16. Two new complete genome sequences offer insight into host and tissue specificity of plant pathogenic Xanthomonas spp.

    Science.gov (United States)

    Bogdanove, Adam J; Koebnik, Ralf; Lu, Hong; Furutani, Ayako; Angiuoli, Samuel V; Patil, Prabhu B; Van Sluys, Marie-Anne; Ryan, Robert P; Meyer, Damien F; Han, Sang-Wook; Aparna, Gudlur; Rajaram, Misha; Delcher, Arthur L; Phillippy, Adam M; Puiu, Daniela; Schatz, Michael C; Shumway, Martin; Sommer, Daniel D; Trapnell, Cole; Benahmed, Faiza; Dimitrov, George; Madupu, Ramana; Radune, Diana; Sullivan, Steven; Jha, Gopaljee; Ishihara, Hiromichi; Lee, Sang-Won; Pandey, Alok; Sharma, Vikas; Sriariyanun, Malinee; Szurek, Boris; Vera-Cruz, Casiana M; Dorman, Karin S; Ronald, Pamela C; Verdier, Valérie; Dow, J Maxwell; Sonti, Ramesh V; Tsuge, Seiji; Brendel, Volker P; Rabinowicz, Pablo D; Leach, Jan E; White, Frank F; Salzberg, Steven L

    2011-10-01

    Xanthomonas is a large genus of bacteria that collectively cause disease on more than 300 plant species. The broad host range of the genus contrasts with stringent host and tissue specificity for individual species and pathovars. Whole-genome sequences of Xanthomonas campestris pv. raphani strain 756C and X. oryzae pv. oryzicola strain BLS256, pathogens that infect the mesophyll tissue of the leading models for plant biology, Arabidopsis thaliana and rice, respectively, were determined and provided insight into the genetic determinants of host and tissue specificity. Comparisons were made with genomes of closely related strains that infect the vascular tissue of the same hosts and across a larger collection of complete Xanthomonas genomes. The results suggest a model in which complex sets of adaptations at the level of gene content account for host specificity and subtler adaptations at the level of amino acid or noncoding regulatory nucleotide sequence determine tissue specificity.

  17. Alteration of osteoblast arrangement via direct attack by cancer cells: New insights into bone metastasis

    Science.gov (United States)

    Kimura, Yumi; Matsugaki, Aira; Sekita, Aiko; Nakano, Takayoshi

    2017-01-01

    Intact bone tissue exhibits a characteristic anisotropic microstructure derived from collagen fiber alignment and the related c-axis orientation of apatite crystals, which govern the mechanical properties of bone tissue. In contrast, tumor-invaded bone exhibits a disorganized, less-aligned microstructure that results in severely disrupted mechanical function. Despite its importance both in basic principle and in therapeutic applications, the classical understanding of bone metastasis is limited to alterations in bone mass regulated by metastatic cancer cells. In this study, we demonstrate a novel mechanism underlying the disruption of bone tissue anisotropy in metastasized bone. We observed that direct attack by cancer cells on osteoblasts induces the less-organized osteoblast arrangement. Importantly, the crystallographic anisotropy of bone tissue is quantitatively determined by the level of osteoblast arrangement. Osteoblast arrangement was significantly disrupted by physical contact with cancer cells such as osteolytic melanoma B16F10, breast cancer MDA-MB-231, and osteoblastic prostate cancer MDA-PCa-2b cells. The present findings demonstrate that the abnormal arrangement of osteoblasts induced by physical contact with cancer cells facilitates the disorganized microstructure of metastasized bone. PMID:28303941

  18. New insights of epithelial-mesenchymal transition in cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yadi Wu; Binhua P.Zhou

    2008-01-01

    Epithelial-mesenchymal transition (EMT) is a key step during embryonic morphogenesis,heart development,chronic degenerative fibrosis,and cancer metastasis.Several distinct traits have been conveyed by EMT,including cell motility,invasiveness,resistance to apoptosis,and some properties of stem cells.Many signal pathways have contributed to the induction of EMT,such as transforming growth factor-β,Wnt,Hedgehog,Notch,and nuclear factor-κB.Over the last few years,increasing evidence has shown that EMT plays an essential role in tumor progression and metastasis.Understanding the molecular mechanism of EMT has a great effect in unraveling the metastatic cascade and may lead to novel interventions for metastatic disease.

  19. Clinic application of tissue engineered bronchus for lung cancer treatment

    Science.gov (United States)

    Liu, Ruijun; Chen, Xiaoke; Wu, Jingxiang; Pan, Yinggen; Lu, Shun; Weder, Walter; Luo, Qingquan

    2017-01-01

    Background Delayed revascularization process and substitute infection remain to be key challenges in tissue engineered (TE) airway reconstruction. We propose an “in-vivo bioreactor” design, defined as an implanted TE substitutes perfused with an intra-scaffold medium flow created by an extracorporeal portable pump system for in situ organ regeneration. The perfusate keeps pre-seeded cells alive before revascularization. Meanwhile the antibiotic inside the perfusate controls topical infection. Methods A stage IIIA squamous lung cancer patient received a 5-cm TE airway substitute, bridging left basal segment bronchus to carina, with the in-vivo bioreactor design to avoid left pneumonectomy. Continuous intra-scaffold Ringer’s-gentamicin perfusion lasted for 1 month, together with orthotopic peripheral total nucleated cells (TNCs) injection twice a week. Results The patient recovered uneventfully. Bronchoscopy follow-up confirmed complete revascularization and reepithelialization four months postoperatively. Perfusate waste test demonstrated various revascularization growth factors secreted by TNCs. The patient received two cycles of chemotherapy and 30 Gy radiotherapy thereafter without complications related to the TE substitute. Conclusions In-vivo bioreactor design combines the traditionally separated in vitro 3D cell-scaffold culture system and the in vivo regenerative processes associated with TE substitutes, while treating the recipients as bioreactors for their own TE prostheses. This design can be applied clinically. We also proved for the first time that TE airway substitute is able to tolerate chemo-radiotherapy and suitable to be used in cancer treatment.

  20. Understanding community beliefs of Chinese-Australians about cancer: initial insights using an ethnographic approach.

    Science.gov (United States)

    Yeo, Soo See; Meiser, Bettina; Barlow-Stewart, Kristine; Goldstein, David; Tucker, Katherine; Eisenbruch, Maurice

    2005-03-01

    Ethnography was employed to investigate the hypothesis that the cultural meaning of cancer is one of the possible barriers to access of cancer services. The objectives were to identify indigenous terminologies, taxonomies and illness explanatory models of cancer in a community-based sample of 15 Chinese-Australians and a sample of 16 informants who had been recruited through two Sydney familial cancer clinics. Many of the informants included in their narrative terms that seemed to match Western biomedical explanations for cancer. The majority of informants also maintained traditional Chinese beliefs, despite high acculturation and beliefs in biomedical explanations about cancer. Explanations of illness including cancer, referred to the following concepts: (i) karma (yeh), (ii) retribution (bao ying), (iii) fate (ming yun) or Heaven's or God's will, (iv) geomancy (feng-shui), (v) touched evil (zhong chia), (vi) misfortune or bad luck (shui wan, dong hark); (vii) offending the gods or deities requiring prayers or offerings for appeasement; and (viii) kong-tau (spells invoked through human intervention). Taking into consideration the heterogeneity of the Chinese population, the findings provide an insight into Chinese illness conceptualization that may assist health professionals to develop an understanding of how the cultural explanatory models affect access to screening services, communication of diagnosis of cancer and management of treatment regimen.

  1. HER1-4 protein concentrations in normal breast tissue from breast cancer patients are expressed by the same profile as in the malignant tissue

    DEFF Research Database (Denmark)

    Olsen, Dorte Aa; Ostergaard, Birthe; Bokmand, Susanne;

    2009-01-01

    and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8x10(-6)), while HER2 (p...-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. Methods: Tissue samples from malignant...

  2. Fat accumulation in adipose tissues as a risk factor for the development of endometrial cancer.

    Science.gov (United States)

    Nakamura, Keiichiro; Hongo, Atsushi; Kodama, Junichi; Hiramatsu, Yuji

    2011-07-01

    Fat accumulation in adipose tissues is a risk factor for the development of human cancers. However, there are no studies describing the fat accumulation in adipose tissue or its distribution in human endometrial cancer. We first examined fat accumulation in adipose tissues separately on CT images of 122 patients with endometrial cancer, and investigated the correlation of these findings with various histological types of endometrial cancers. Fat accumulation in adipose tissues [subcutaneous fat area (SFA) and/or visceral fat areas (VFA)] was strongly correlated with the group of obesity-related biological parameters (weight, body mass index (BMI), waist and body surface area (BSA)) in endometrial cancer. The incidence of type I endometrial cancer was more closely correlated with an increase in obesity-related parameters such as weight (p=0.011), BMI (p=0.006), waist circumference (p=0.038), BSA (p=0.016), SFA (p=0.005), total fat area (TFA) (p=0.006) and total cholesterol (T.Cho) (P=0.010) than type II endometrial cancer. In particular, the SFA was most strongly correlated with obesity-related biological parameters of type I endometrial cancer. The present findings indicate that type I endometrial cancer has a statistically significant increase in obesity-related biological parameters than type II endometrial cancer. We propose that the subcutaneous fat accumulation in adipose tissue is a strong risk factor for developing type I endometrial cancer.

  3. DETECTION AND CLINICAL SIGNIFICANCE OF THROMBOMODULIN IN BOTH PLASMA AND TISSUE EXTRACTS OF CANCER PATIENTS

    Institute of Scientific and Technical Information of China (English)

    许晓华; 卢兴国; 徐根波; 朱蕾; 黄连生

    2004-01-01

    Objective: To study the changes of thrombomodulin (TM) in both plasma and tissue extracts of cancer patients for evaluating its clinical significance. Methods: Plasma TM levels were measured by enzyme-linked immunosorbent assay (ELISA) in both plasma of 188 cancer patients and 24 cancer tissue extracts including their adjacent non-cancer tissues. Results: The plasma TM levels both in cancer patients and in metastasis patients were significantly higher than that in controls [(33.47±14.25)μg/L, (41.68±16.96)μg/L, vs(20.40±7.22)μg/L,P0.05). The TM levels in cancer tissue extracts were significantly lower than that in their adjacent non-cancer tissue extracts [(647.71±317.51)μg/L vs (1455.63±772.22)μg/L, P<0.01]. On the contrary, the plasma TM levels in these cancers were significantly higher than that in controls. Conclusion: The rise of plasma TM levels in cancer patients was associated with metastasis and diffusion of cancers. The TM levels can be served as an sensitive index for judging progression and metastasis of cancers.

  4. Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

    OpenAIRE

    Nicastro, Holly L.; Dunn, Barbara K.

    2013-01-01

    The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was ...

  5. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  6. Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and colon cancer tissue

    DEFF Research Database (Denmark)

    Usher, Pernille Autzen; Sieuwerts, A.M.; Bartels, Annette

    2007-01-01

    TIMP-1 is a promising new candidate as a prognostic marker in colorectal and breast cancer. We now describe the discovery of two alternatively spliced variants of TIMP-1 mRNA. The two variants lacking exon 2 (del-2) and 5 (del-5), respectively, were identified in human cancer cell lines by RT......-PCR. The del-2 variant was, furthermore, detected in extracts from 12 colorectal cancer tissue samples. By western blotting additional bands of lower molecular mass than full-length TIMP-1 were identified in tumor tissue, but not in plasma samples obtained from cancer patients. The two splice variants of TIMP...

  7. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

    Science.gov (United States)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

  8. Insights into esophagus tissue architecture using two-photon confocal microscopy

    Science.gov (United States)

    Liu, Nenrong; Wang, Yue; Feng, Shangyuan; Chen, Rong

    2013-08-01

    In this paper, microstructures of human esophageal mucosa were evaluated using the two-photon laser scanning confocal microscopy (TPLSCM), based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). The distribution of epithelial cells, muscle fibers of muscularis mucosae has been distinctly obtained. Furthermore, esophageal submucosa characteristics with cancer cells invading into were detected. The variation of collagen, elastin and cancer cells is very relevant to the pathology in esophagus, especially early esophageal cancer. Our experimental results indicate that the MPM technique has the much more advantages for label-free imaging, and has the potential application in vivo in the clinical diagnosis and monitoring of early esophageal cancer.

  9. Correlation of microRNA-124 expression in cervical cancer tissue with cancer cell growth and invasion

    Institute of Scientific and Technical Information of China (English)

    Yi Zhu

    2016-01-01

    Objective:To study the correlation of microRNA-124 expression in cervical cancer tissue with cancer cell growth and invasion.Methods: A total of 56 cases of cervical cancer tissue samples and 60 cases of normal cervical tissue samples were selected for study, and microRNA-124 expression levels as well as protein content of proliferation, apoptosis and invasion genes in cervical tissue samples were determined.Results: The relative expression level of miR-124 in cervical cancer tissue was significantly lower than that in normal cervical tissue and the higher the FIGO staging, the lower the relative expression level of miR-124; cervical cancer tissue with different miR-124 expression was divided into group A-D according to quartile, there were differences in the protein content of cyclinD1, CDK4, CDK6, Prdx4, TNFAIP8, Piwil2, p16, p27, Caspase-3, Ezrin, CD44v6, E-cadherin andβ-catenin in cervical cancer tissue of group A, B, C and D, and the lower the relative expression level of miR-124, the higher the protein content of cyclinD1, CDK4, CDK6, Prdx4, TNFAIP8, Piwil2 as well as Ezrin and CD44v6, and the lower the protein content of p16, p27, Caspase-3 as well as E-cadherin andβ-catenin.Conclusions: microRNA-124 shows a trend of lower expression in cervical cancer tissue and is closely related to the excessive proliferation, insufficient apoptosis and invasive growth of cancer cells.

  10. Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer.

    NARCIS (Netherlands)

    Waas, E.T.; Lomme, R.M.L.M.; Groot, J. de; Wobbes, Th.; Hendriks, T.

    2002-01-01

    The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a li

  11. Warburg effect's manifestation in aggressive pheochromocytomas and paragangliomas: insights from a mouse cell model applied to human tumor tissue.

    Directory of Open Access Journals (Sweden)

    Stephanie M J Fliedner

    Full Text Available A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs with distinct underlying gene defects, including von Hippel-Lindau (VHL and succinate dehydrogenase B (SDHB mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT cells has been developed from mouse PHEO cells (MPC. We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS, SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in

  12. NMR Spectroscopy of Human Eye Tissues: A New Insight into Ocular Biochemistry

    Directory of Open Access Journals (Sweden)

    Tomasz Kryczka

    2014-01-01

    Full Text Available Background. The human eye is a complex organ whose anatomy and functions has been described very well to date. Unfortunately, the knowledge of the biochemistry and metabolic properties of eye tissues varies. Our objective was to reveal the biochemical differences between main tissue components of human eyes. Methods. Corneas, irises, ciliary bodies, lenses, and retinas were obtained from cadaver globes 0-1/2 hours postmortem of 6 male donors (age: 44–61 years. The metabolic profile of tissues was investigated with HR MAS 1H NMR spectroscopy. Results. A total of 29 metabolites were assigned in the NMR spectra of the eye tissues. Significant differences between tissues were revealed in contents of the most distant eye-tissues, while irises and ciliary bodies showed minimal biochemical differences. ATP, acetate, choline, glutamate, lactate, myoinositol, and taurine were identified as the primary biochemical compounds responsible for differentiation of the eye tissues. Conclusions. In this study we showed for the first time the results of the analysis of the main human eye tissues with NMR spectroscopy. The biochemical contents of the selected tissues seemed to correspond to their primary anatomical and functional attributes, the way of the delivery of the nutrients, and the location of the tissues in the eye.

  13. Nutrition support and dietary interventions for patients with lung cancer: current insights.

    Science.gov (United States)

    Kiss, Nicole

    2016-01-01

    Malnutrition and weight loss are prevalent in patients with lung cancer. The impact of malnutrition on patients with cancer, and specifically in patients with lung cancer, has been demonstrated in a large number of studies. Malnutrition has been shown to negatively affect treatment completion, survival, quality of life, physical function, and health care costs. Emerging evidence is providing some insight into which lung cancer patients are at higher nutritional risk. In lung cancer patients treated with radiotherapy, stage III or more disease, treatment with concurrent chemotherapy and the extent of radiotherapy delivered to the esophagus appear to confer a higher risk of weight loss during and post-treatment. Studies investigating nutrition interventions for lung cancer patients have examined intensive dietary counseling, supplementation with fish oils, and interdisciplinary models of nutrition and exercise interventions and show promise for improved outcomes from these interventions. However, further research utilizing these interventions in large clinical trials is required to definitively establish effective interventions in this patient group.

  14. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

    DEFF Research Database (Denmark)

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M

    2014-01-01

    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform...... on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset...... of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides...

  15. Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers

    Science.gov (United States)

    Brozek-Pluska, B.; Kopec, M.

    2016-12-01

    Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed.

  16. Expression and Clinical Significance of REGy in Gastric Cancer Tissue and Variously Differentiated Gastric Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Jia Li; Tian Tian; Xiaoyi Wang; Fan Li; Guosheng Ren

    2009-01-01

    OBJECTIVE To evaluate the REGy expression in gastric cancer tissue and gastric cancer cell lines of various differentiation levels and its clinical significance.METHODS Immunohistochemistry was used to detect the expression of REGy protein in 70 specimens of gastric cancer and 30 specimens of normal gastric mucosa. The relationship between the expression of REGy protein and the biological behaviors of gastric cancer was analyzed. RT-PCR and Western blot were used to detect the mRNA level and the protein expression of REGγ in normal gastric cell line GES-1, well differentiated gastric cancer cell line MKN-28, moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823.RESULTS The expression rate of REGγprotein in gastric cancer tissue (52/70, 74.29%) was significantly higher than that in normal gastric tissue (12/30, 40%) (P<0.01). The expression rate of REGywas correlated with tumor size (P<0.01), lymph node metastasis (P<0.05), differentiation degree (P<0.01), infiltration depth (P<0.01)and distant metastasis (P<0.05). RT-PCR analysis showed that theexpression of REGγ mRNA was 0.459±0.079 in the normal gastric mucosa cell line, 0.588±0.118 in the well differentiated gastric cancer cell line, 0.715±0.066 in the moderately differentiated gastric cancer cell line, and 0.873±0.099 in the poorly differentiated gastric cancer cell line, showing a negative correla- tion between REGγmRNA expression and differentiation level (P <0.05). Western blot analysis showed that the expression of REGy protein was 0.712±0.065 in the normal gastric mucosa cell line, 1.176±0.185 in the well differentiated gastric cancer cell line, 1.533 ±0.127 in the moderately differentiated gastric cancer cell line, and 2.061±0.398 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγprotein expression and differentiation level (P<0.05).CONCLUSION REGγ is expressed in gastric cancer

  17. Trace elemental analysis in cancer-afflicted tissues of penis and testis by PIXE technique

    Energy Technology Data Exchange (ETDEWEB)

    Naga Raju, G.J. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); John Charles, M. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Bhuloka Reddy, S. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India)]. E-mail: sbr_r@yahoo.com; Sarita, P. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Seetharami Reddy, B. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Rama Lakshmi, P.V.B. [Pathology Department, Andhra Medical College, Visakhapatnam 530 002 (India); Vijayan, V. [Institute of Physics, Sachivalaya Marg, Bhubaneswar 751 001 (India)

    2005-04-01

    PIXE technique was employed to estimate the trace elemental concentrations in the biological samples of cancerous penis and testis. A 3 MeV proton beam was employed to excite the samples. From the present results it can be seen that the concentrations of Cl, Fe and Co are lower in the cancerous tissue of the penis when compared with those in normal tissue while the concentrations of Cu, Zn and As are relatively higher. The concentrations of K, Ca, Ti, Cr, Mn, Br, Sr and Pb are in agreement within standard deviations in both cancerous and normal tissues. In the cancerous tissue of testis, the concentrations of K, Cr and Cu are higher while the concentrations of Fe, Co and Zn are lower when compared to those in normal tissue of testis. The concentrations of Cl, Ca, Ti and Mn are in agreement in both cancerous and normal tissues of testis. The higher levels of Cu lead to the development of tumor. Our results also support the underlying hypothesis of an anticopper, antiangiogenic approach to cancer therapy. The Cu/Zn ratios of both penis and testis were higher in cancer tissues compared to that of normal.

  18. Cell type-specific properties and environment shape tissue specificity of cancer genes.

    Science.gov (United States)

    Schaefer, Martin H; Serrano, Luis

    2016-02-09

    One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer.

  19. Classification of normal and cancerous lung tissues by electrical impendence tomography.

    Science.gov (United States)

    Gao, Jianling; Yue, Shihong; Chen, Jun; Wang, Huaxiang

    2014-01-01

    Biological tissue impedance spectroscopy can provide rich physiological and pathological information by measuring the variation of the complex impedance of biological tissues under various frequencies of driven current. Electrical Impedance Tomography (EIT) technique can measure the impedance spectroscopy of biological tissue in medical field. Before application, a key problem must be solved on how to generally distinguish normal tissues from the cancerous in terms of measurable EIT data. In this paper, the impedance spectroscopy characteristics of human lung tissue are studied. On the basis of the measured data of 109 lung cancer patients, Cole-Cole Circle radius (CCCR) and the complex modulus are extracted. In terms of the two characteristics, 71.6% and 66.4% samples of cancerous and normal tissues can be correctly classified, respectively. Furthermore, two characteristics of the measured EIT data of each patient consist of a two-dimensional vector and all such vectors comprise a set of vectors. When classifying the vector set, the rate of correctly partitioning normal and cancerous tissues can be raised to 78.2%. The main factors to affect the classification results on normal and cancerous tissues are generally analyzed. The proposed method will play an important role in further working out an efficient and feasible diagnostic method for potential lung cancer patients, and provide theoretical basis and reference data for electrical impedance tomography technology in monitoring pulmonary function.

  20. Expression of BCRP Gene in the Normal Lung Tissue and Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of novel multidrugresistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients' RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients' RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it's overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

  1. Raman spectra of normal and cancerous mouse mammary gland tissue using near infrared excitation energy

    Science.gov (United States)

    Naik, Vaman; Serhatkulu, G. K.; Dai, H.; Shukla, N.; Weber, R.; Thakur, J. S.; Freeman, D. C.; Pandya, A. K.; Auner, G. W.; Naik, R.; Miller, R. F.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra of normal mammary gland tissues, malignant mammary gland tumors, and lymph nodes have been recorded using fresh tissue from mice. Tumors were induced in mice by subcutaneously injecting 4T1 BALB/c mammary tumor (a highly malignant) cell line. The Raman spectra were collected using the same tissues that were examined by histopathology for determining the cancerous/normal state of the tissue. Differences in various peak intensities, peak shifts and peak ratios were analyzed to determine the Raman spectral features that differentiate mammary gland tumors from non-tumorous tissue. Tissues that were confirmed by pathology as cancerous (tumors) show several distinctive features in the Raman spectra compared to the spectra of the normal tissues. For example, the cancerous tissues show Raman peaks at 621, 642, 1004, 1032, 1175 and 1208 cm-1 that are assignable to amino acids containing aromatic side-chains such as phenylalanine, tryptophan and tyrosine. Further, the cancerous tissues show a greatly reduced level of phospholipids compared to the normal tissues. The Raman spectral regions that are sensitive to pathologic alteration in the tissue will be discussed.

  2. Selenium and prostate cancer prevention: insights from the selenium and vitamin E cancer prevention trial (SELECT).

    Science.gov (United States)

    Nicastro, Holly L; Dunn, Barbara K

    2013-04-03

    The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.

  3. Overexpression of Gli1 in cancer interstitial tissues predicts early relapse after radical operation of breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ying-Hua Li; Hai-Feng Gao; Yan Wang; Fang Liu; Xiao-Feng Tian; Yang Zhang

    2012-01-01

    Objective:To investigate whether Gli1 expression is important in relapse after radical operation of breast cancer.Methods:Using immunohistochemistry,Glil expression was analyzed in human primary breast cancer (n=284) and paracancerous tissues (n=20),and also in local lymph nodes (n=28) and metastatic lymph nodes (n=28).Results:Initial analysis of Gli1 expression in a small cohort of 20 breast tumors and their paracancerous tissues showed a tendency towards Gli1 overexpression in breast cancer tissues (P<0.001).Further,Gli1 expression in 284 breast cancer tissue samples was analyzed and a significant correlation was found between increased expression of nuclear Gli1 and unfavorable recurrence-free survival (RFS) (P<0.05).The nuclear expression of Gli1 in metastatic lymph nodes following relapse after radical operation was much higher than that in the local lymph nodes of primary carcinoma (P<0.05).Most interestingly,the expression of Gli1 was much higher in the interstitial tissues of the relapsed group than of the non-relapsed group (P<0.001).Conclusions:Breast cancer shows a high prevalence of Gli1 expression,which is significantly correlated with aggressive features and unfavorable RFS.Nuclear Gli1 overexpression,especially in the interstitial tissues,signified early relapse after radical operation of breast cancer.

  4. KLF5 expression in prostate cancer tissue and effect of KLF5 knockdown on prostate cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Chong-Jun Shi; Wei-Zhong Yang; Yuan-Rong Kong; Wen-Guang Zhou

    2016-01-01

    Objective:To study the KLF5 expression in prostate cancer tissue and the effect of KLF5 knockdown on prostate cancer cell growth.Methods:Prostate cancer and benign prostatic hyperplasia tissue were collected to extract RNA and determine the mRNA levels ofKLF5as well as proliferation and epithelial-mesenchymal transition-related genes; DU145 cells were cultured and transfected with KLF5 siRNA and negative control siRNA, and then RNA was extracted to determine the mRNA levels of proliferation and epithelial-mesenchymal transition-related genes.Results:KLF5, SRSF1, Survivin, MACC1, c-Met, N-cadherinand Vimentin mRNA levels in prostate cancer tissue were significantly higher than those in benign prostatic hyperplasia tissue whileTGF-β,E-cadherinandβ-catenin mRNA levels were significantly lower than those in benign prostatic hyperplasia tissue;SRSF1, Survivin, MACC1, c-Met, TGF-β,N-cadherin andVimentinmRNA levels in si-KLF5 group were significantly lower than those in si-NC group while E-cadherin andβ-cateninmRNA levels were significantly higher than those in si-NC group.Conclusions: KLF5 expression levels are unusually high in prostate cancer tissue, and targeted knockdown of KLF5 expression can inhibit the prostate cancer cell proliferation and epithelial-mesenchymal transition.

  5. Study on the correlation of helicobacter pylori infection with proliferation, invasion and angiogenesis molecules in gastric cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Sa-Mei Lv; Jian Zhang; You-Wei Wu; Jian Zhou; Li-Ping Shi

    2016-01-01

    Objective:To study the correlation of helicobacter pylori infection with proliferation, invasion and angiogenesis molecules in gastric cancer tissue.Methods: A total of 60 cases of cancer tissue samples and 60 cases of normal tissue samples more than 5 cm away from cancer tissue edge were collected for study from gastric cancer patients treated in our hospital, and according to the testing results of helicobacter pylori (Hp), gastric cancer tissue was divided into Hp-L(+) and Hp-L(-), and the levels of proliferation, invasion and angiogenesis molecules were determined.Results:Bcl-2, Survivin, KLK8, N-cadherin, Vimentin, Snail, Twist, VEGFR, COX-2 and HIF-1α protein levels in gastric cancer tissue were significantly higher than those in normal tissue, and E-cadherin protein level was significantly lower than that in normal tissue; Bcl-2, Survivin, KLK8, N-cadherin, Vimentin, Snail, Twist, VEGF, VEGFR, COX-2 and HIF-1α protein levels in Hp-L(+) gastric cancer tissue were significantly higher than those in Hp-L(-) gastric cancer tissue, and E-cadherin protein level was significantly lower than that in Hp-L(-) gastric cancer tissue.Conclusion:Helicobacter pylori infection in gastric cancer tissue can promote cancer cell proliferation, epithelial-mesenchymal transition and angiogenesis.

  6. Detergent-enzymatic decellularization of swine blood vessels: insight on mechanical properties for vascular tissue engineering.

    Science.gov (United States)

    Pellegata, Alessandro F; Asnaghi, M Adelaide; Stefani, Ilaria; Maestroni, Anna; Maestroni, Silvia; Dominioni, Tommaso; Zonta, Sandro; Zerbini, Gianpaolo; Mantero, Sara

    2013-01-01

    Small caliber vessels substitutes still remain an unmet clinical need; few autologous substitutes are available, while synthetic grafts show insufficient patency in the long term. Decellularization is the complete removal of all cellular and nuclear matters from a tissue while leaving a preserved extracellular matrix representing a promising tool for the generation of acellular scaffolds for tissue engineering, already used for various tissues with positive outcomes. The aim of this work is to investigate the effect of a detergent-enzymatic decellularization protocol on swine arteries in terms of cell removal, extracellular matrix preservation, and mechanical properties. Furthermore, the effect of storage at -80°C on the mechanical properties of the tissue is evaluated. Swine arteries were harvested, frozen, and decellularized; histological analysis revealed complete cell removal and preserved extracellular matrix. Furthermore, the residual DNA content in decellularized tissues was far low compared to native one. Mechanical testings were performed on native, defrozen, and decellularized tissues; no statistically significant differences were reported for Young's modulus, ultimate stress, compliance, burst pressure, and suture retention strength, while ultimate strain and stress relaxation of decellularized vessels were significantly different from the native ones. Considering the overall results, the process was confirmed to be suitable for the generation of acellular scaffolds for vascular tissue engineering.

  7. Detergent-Enzymatic Decellularization of Swine Blood Vessels: Insight on Mechanical Properties for Vascular Tissue Engineering

    Science.gov (United States)

    Pellegata, Alessandro F.; Asnaghi, M. Adelaide; Stefani, Ilaria; Maestroni, Anna; Maestroni, Silvia; Dominioni, Tommaso; Zonta, Sandro; Zerbini, Gianpaolo; Mantero, Sara

    2013-01-01

    Small caliber vessels substitutes still remain an unmet clinical need; few autologous substitutes are available, while synthetic grafts show insufficient patency in the long term. Decellularization is the complete removal of all cellular and nuclear matters from a tissue while leaving a preserved extracellular matrix representing a promising tool for the generation of acellular scaffolds for tissue engineering, already used for various tissues with positive outcomes. The aim of this work is to investigate the effect of a detergent-enzymatic decellularization protocol on swine arteries in terms of cell removal, extracellular matrix preservation, and mechanical properties. Furthermore, the effect of storage at −80°C on the mechanical properties of the tissue is evaluated. Swine arteries were harvested, frozen, and decellularized; histological analysis revealed complete cell removal and preserved extracellular matrix. Furthermore, the residual DNA content in decellularized tissues was far low compared to native one. Mechanical testings were performed on native, defrozen, and decellularized tissues; no statistically significant differences were reported for Young's modulus, ultimate stress, compliance, burst pressure, and suture retention strength, while ultimate strain and stress relaxation of decellularized vessels were significantly different from the native ones. Considering the overall results, the process was confirmed to be suitable for the generation of acellular scaffolds for vascular tissue engineering. PMID:23865072

  8. Detergent-Enzymatic Decellularization of Swine Blood Vessels: Insight on Mechanical Properties for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Alessandro F. Pellegata

    2013-01-01

    Full Text Available Small caliber vessels substitutes still remain an unmet clinical need; few autologous substitutes are available, while synthetic grafts show insufficient patency in the long term. Decellularization is the complete removal of all cellular and nuclear matters from a tissue while leaving a preserved extracellular matrix representing a promising tool for the generation of acellular scaffolds for tissue engineering, already used for various tissues with positive outcomes. The aim of this work is to investigate the effect of a detergent-enzymatic decellularization protocol on swine arteries in terms of cell removal, extracellular matrix preservation, and mechanical properties. Furthermore, the effect of storage at −80°C on the mechanical properties of the tissue is evaluated. Swine arteries were harvested, frozen, and decellularized; histological analysis revealed complete cell removal and preserved extracellular matrix. Furthermore, the residual DNA content in decellularized tissues was far low compared to native one. Mechanical testings were performed on native, defrozen, and decellularized tissues; no statistically significant differences were reported for Young’s modulus, ultimate stress, compliance, burst pressure, and suture retention strength, while ultimate strain and stress relaxation of decellularized vessels were significantly different from the native ones. Considering the overall results, the process was confirmed to be suitable for the generation of acellular scaffolds for vascular tissue engineering.

  9. Expression of CD44v6 and Livin in gastric cancer tissue

    Institute of Scientific and Technical Information of China (English)

    LIANG Yi-zhi; FANG Tai-yong; XU Hai-gang; ZHUO Zhi-qiang

    2012-01-01

    Background CD44v6 plays an important role in invasion and metastasis of tumor,Livin has anti-apoptotic effects.The present study aimed to explore the expression and clinical significance of CD44v6 and Livin in gastric cancer tissue.Methods Streptavidin-peroxidase linked immunohistochemical method was used to determine the expression of CD44v6 and Livin in gastric cancer tissue and adjacent normal gastric tissues from 59 patients with histopathologically confirmed gastric cancer,and in gastric tissue specimens of 15 patients with gastric polyps,and 15 patients with chronic non-atrophic gastritis.The chi-square test was used for comparison of the relevant factors,Spearman's rank correlation test was applied for relationship among positive expression of the proteins.Results The expresion of CD44v6 was positive in 64.4% of the gastric cancer patients; 5.1%,0 and 13.3% in specimens of normal tissues adjacent to the cancer tissues,in gastric tissue specimens of patients with gastric polyps,and patients with chronic non-atrophic gastritis,respectively.The expression of Livin was positive in 52.5% of the gastric cancer tissues,6.8%,0 and 6.7% in the adjacent normal gastric tissue,specimens of patients with gastric polyps and chronic non-atrophic gastritis,respectively.The expression of CD44v6 was significantly correlated with the depth of invasion,the degree of differentiation,and lymphnode metastasis of gastric cancer (P <0.05).The positive expression rate of Livin protein was also significantly correlated with degree of differentiation of gastric cancer cells and metastasis to lymphnodes (P <0.05),but not correlated with the depth of invasion and pathological types (P >0.05).The expression of CD44v6 and Livin in the gastric cancer tissue was positively correlated (rs=0.286,P=-0.028).Conclusions The increased expression of CD44v6 and Livin in gastric cancer tissue may be closely related with development and progression of gastric cancer.CD44v6 and Livin

  10. Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

    Science.gov (United States)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

  11. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    Science.gov (United States)

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  12. Progesterone and adiponectin receptor family member 3 expression and clinical significance in breast cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qiang Dai; Hai-Liang Zhang; Hong-Mei Li

    2016-01-01

    Objective:To discuss progesterone and adiponectin receptor family member 3 expression and clinical significance in breast cancer tissues. Method:A total of 90 cases with breast cancer who were admitted in our hospital from Jan 2000 to Jan 2010 were selected. Meanwhile, normal tumor-adjacent breast tissues were selected as comparison. Diagnosis of all patients was confirmed by postoperative pathological examinations. Immunohistochemistry method was adopted to detect PAQR3 protein expression in breast cancer tissues and normal tumor-adjacent breast tissues and its clinical significance was discussed. Results:PAQR3 protein positive expression rate in breast cancer tissues was 25.6%, which was significantly lower than that (78.9%) in normal tumor-adjacent breast tissues;PAQR3 protein positive expression rate had nothing to do with age, tumor size, pathological types and differentiated degree of patients, but had significant correlation with TNM staging and lymphatic metastasis existence of patients. Kaplan–Meier survival analysis results showed that five years survival rate of patients with PAQR3 protein positive expression was significantly higher than whom with negative expression. Conclusion:PAQR3 protein expression in breast cancer tissues was significantly reduced, which indicated that PAQR3 protein possibly played an important role in pathogenesis of breast cancer.

  13. The nanomechanical signature of liver cancer tissues and its molecular origin

    Science.gov (United States)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-07-01

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus

  14. Insights into the key roles of proteoglycans in breast cancer biology and translational medicine.

    Science.gov (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Neill, Thomas; Multhaupt, Hinke A B; Hubo, Mario; Frey, Helena; Gopal, Sandeep; Gomes, Angélica; Afratis, Nikos; Lim, Hooi Ching; Couchman, John R; Filmus, Jorge; Sanderson, Ralph D; Schaefer, Liliana; Iozzo, Renato V; Karamanos, Nikos K

    2015-04-01

    Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer.

  15. NIH scientists map gene changes driving tumors in common pediatric soft-tissue cancer

    Science.gov (United States)

    Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric soft-tissue cancer, and found that the disease is characterized by two distinct genotypes. The genetic alterations identified in this malignancy could be useful

  16. RELATED GENES IN LUNG CANCER TISSUES ASSOCIATED WITH RESIDENTIAL HIGH RADON EXPOSURE

    Institute of Scientific and Technical Information of China (English)

    夏英; 杨梅英; 张守志; 叶常青

    2002-01-01

    Objective: To investigate the related genes in lung cancer tissues associated with residential high radon exposure. Methods: Differentially expressed gene fragments in lung cancer and normal lung tissues were discovered by differential display and reverse Northern blot hybridization method. The fragments positive in lung cancer and negative in normal lung tissue were determined. Results: Seven differential displayed fragments were sequenced. One of them named NA7 is 95% homologous with AI208667 in EAT of Genbank. Another fragment named NG2 is up to 98% homologous with five fragments. The remained one CA1 may be a new gene fragment. Conclusion: 3 gene fragments were discovered from lung cancer and normal lung tissues of high radon exposure resident.

  17. Host tissues as microhabitats for Wolbachia and quantitative insights into the bacterial community in terrestrial isopods.

    Science.gov (United States)

    Dittmer, J; Beltran-Bech, S; Lesobre, J; Raimond, M; Johnson, M; Bouchon, D

    2014-05-01

    Animal-bacterial symbioses are highly dynamic in terms of multipartite interactions, both between the host and its symbionts as well as between the different bacteria constituting the symbiotic community. These interactions will be reflected by the titres of the individual bacterial taxa, for example via host regulation of bacterial loads or competition for resources between symbionts. Moreover, different host tissues represent heterogeneous microhabitats for bacteria, meaning that host-associated bacteria might establish tissue-specific bacterial communities. Wolbachia are widespread endosymbiotic bacteria, infecting a large number of arthropods and filarial nematodes. However, relatively little is known regarding direct interactions between Wolbachia and other bacteria. This study represents the first quantitative investigation of tissue-specific Wolbachia-microbiota interactions in the terrestrial isopod Armadillidium vulgare. To this end, we obtained a more complete picture of the Wolbachia distribution patterns across all major host tissues, integrating all three feminizing Wolbachia strains (wVulM, wVulC, wVulP) identified to date in this host. Interestingly, the different Wolbachia strains exhibited strain-specific tissue distribution patterns, with wVulM reaching lower titres in most tissues. These patterns were consistent across different host genetic backgrounds and might reflect different co-evolutionary histories between the Wolbachia strains and A. vulgare. Moreover, Wolbachia-infected females carried higher total bacterial loads in several, but not all, tissues, irrespective of the Wolbachia strain. Taken together, this quantitative approach indicates that Wolbachia is part of a potentially more diverse bacterial community, as exemplified by the presence of highly abundant bacterial taxa in the midgut caeca of several A. vulgare populations.

  18. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence

    DEFF Research Database (Denmark)

    Ernst, EH; Offersen, Birgitte Vrou; Andersen, Claus Yding;

    2013-01-01

    To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer.......To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer....

  19. Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays

    OpenAIRE

    2016-01-01

    In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much ...

  20. Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT

    Directory of Open Access Journals (Sweden)

    Holly L. Nicastro

    2013-04-01

    Full Text Available The Selenium and Vitamin E Cancer Prevention Trial (SELECT was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.

  1. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

    Directory of Open Access Journals (Sweden)

    Ribeiro Ricardo

    2012-09-01

    Full Text Available Abstract Background Periprostatic (PP adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW and prostate cancer patients. Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia. Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA was used to investigate gene ontology, canonical pathways and functional networks. Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated. Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis, whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH. Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable

  2. The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

    Directory of Open Access Journals (Sweden)

    Brábek Jan

    2010-09-01

    Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

  3. Comparison of nuclear matrix proteins between gastric cancer and normal gastric tissue

    Institute of Scientific and Technical Information of China (English)

    Qin-Xian Zhang; Yi Ding; Zhuo Li; Xiao-Ping Le; Wei Zhang; Ling Sun; Hui-Rong Shi

    2004-01-01

    AIM: To study the alteration of nuclear matrix proteins (NMPs) in gastric cancer.METHODS: The NMPs extracted from 22 cases of gastric cancer and normal gastric tissues were investigated by SDS-PAGE technique and the data were analyzed using Genetools analysis software.RESULTS: Compared with normal gastric tissue, the expression of 30 ku and 28 ku NMPs in gastric cancer decreased significantly (P=0.002, P=0.001, P<0.05). No significant difference was found in the expression of the two NMPs between the various differentiated grades (P=0.947, P=0.356) and clinical stages of gastric cancer (P=0.920, P=0.243, P>0.05).CONCLUSION: The results suggested that the alteration of NMPs in gastric cancer occurred at the early stage of gastric cancer development.

  4. Mechanistic insight into the ability of American ginseng to suppress colon cancer associated with colitis.

    Science.gov (United States)

    Cui, Xiangli; Jin, Yu; Poudyal, Deepak; Chumanevich, Alexander A; Davis, Tia; Windust, Anthony; Hofseth, Anne; Wu, Wensong; Habiger, Joshua; Pena, Edsel; Wood, Patricia; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Hofseth, Lorne

    2010-10-01

    We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis. To explore the molecular mechanisms of the anticancer effects of AG, we also carried out antibody array experiments on colon cells isolated at a precancerous stage. We found there were 82 protein end points that were either significantly higher (41 proteins) or significantly lower (41 proteins) in the AOM + DSS group compared with the AOM-alone (control) group. In contrast, there were only 19 protein end points that were either significantly higher (10 proteins) or significantly lower (9 proteins) in the AOM + DSS + AG group compared with the AOM-alone (control) group. Overall, these results suggest that AG keeps the colon environment in metabolic equilibrium when mice are treated with AOM + DSS and gives insight into the mechanisms by which AG protects from colon cancer associated with colitis.

  5. Recent insights in the therapeutic management of patients with gastric cancer.

    Science.gov (United States)

    de Mestier, Louis; Lardière-Deguelte, Sophie; Volet, Julien; Kianmanesh, Reza; Bouché, Olivier

    2016-09-01

    Gastric cancer remains frequent and one of the most lethal malignancies worldwide. In this article, we aimed to comprehensively review recent insights in the therapeutic management of gastric cancer, with focus on the surgical and perioperative management of resectable forms, and the latest advances regarding advanced diseases. Surgical improvements comprise the use of laparoscopic surgery including staging laparoscopy, a better definition of nodal dissection, and the development of hyperthermic intraperitoneal chemotherapy. The best individualized perioperative management should be assessed before curative-intent surgery for all patients and can consists in perioperative chemotherapy, adjuvant chemo-radiation therapy or adjuvant chemotherapy alone. The optimal timing and sequence of chemotherapy and radiation therapy with respect to surgery should be further explored. Patients with advanced gastric cancer have a poor prognosis. Nevertheless, they can benefit from doublet or triplet chemotherapy combination, including trastuzumab in HER2-positive patients. Upon progression, second-line therapy can be considered in patients with good performance status. Although anti-HER2 (trastuzumab) and anti-VEGFR (ramucirumab) may yield survival benefit, anti-EGFR and anti-HGFR therapies have failed to improve outcomes. Nevertheless, combination regimens containing cytotoxic drugs and targeted therapies should be further evaluated; keeping in mind that gastric cancer biology is different between Asia and the Western countries.

  6. 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

  7. The AKT-mTOR signalling pathway in kidney cancer tissues

    Science.gov (United States)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Kolegova, E. S.

    2015-11-01

    An increased expression of phospho-AKT, m-TOR, glycogen regulator GSK-3-beta and transcription inhibitor 4E-BP1 was observed in kidney cancer tissues. Tumor size growth was associated with a high level of c-Raf and low content of phospho-m-TOR. Cancer metastasis development led to a decreased PTEN and phospho-AKT expression.

  8. Iodine-125 radioactive seed tissue implantation as a remedy treatment for recurrent cervical cancer

    Directory of Open Access Journals (Sweden)

    Lei Han

    2016-01-01

    Conclusion: Iodine-125 radioactive seed tissue implantation is a feasible, effective, and safe treatment method for remedying or palliative treatment of recurrent cervical cancer. Patients who have recurrent cervical cancer and responded effectively to radioactive seed implantation will have a longer survival period.

  9. Extensive adipose tissue necrosis following pfannenstiel incision for endometrial cancer.

    Science.gov (United States)

    Lavoie, Maryse Céline; Plante, Marie; Lemieux, Marie-Carine; Roberge, Céline; Renaud, Marie-Claude; Grégoire, Jean; Roy, Michel; Sebastianelli, Alexandra

    2014-03-01

    Contexte : Les hématomes sont des complications postopératoires qui peuvent en venir à se manifester à la suite du recours à des incisions de Pfannenstiel. Habituellement, ils se résorbent de façon spontanée ou font l’objet d’un drainage (en fonction de leur ampleur). Des facteurs de risque importants (comme l’obésité et le diabète) pourraient mener à des complications surajoutées et aggraver davantage l’issue. Cas : Dix jours après avoir subi une hystérectomie abdominale totale par incision de Pfannenstiel en raison d’un cancer de l’endomètre, une femme de 73 ans a présenté un gros hématome sous-cutané. L’hématome en question a évolué et a mené à une nécrose étendue du tissu adipeux sous-cutané. La mise en œuvre d’un débridement de grande envergure s’est avérée nécessaire et la plaie a été traitée par pression négative au moyen de gaze afin de permettre une cicatrisation par deuxième intention. Une guérison satisfaisante a été constatée après 82 jours de traitement, sans greffe cutanée. Conclusion : Ce cas souligne l’utilité du traitement de plaie par pression négative au moyen de gaze, ainsi que la nécessité d’avoir recours à une approche multidisciplinaire au moment d’assurer la prise en charge de complications de plaie d’une telle complexité.

  10. 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.

  11. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Directory of Open Access Journals (Sweden)

    Esther Reina-Romo

    2011-11-01

    Full Text Available Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

  12. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Science.gov (United States)

    Sanz-Herrera, Jose A.; Reina-Romo, Esther

    2011-01-01

    Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

  13. Tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker in gastric cancer

    DEFF Research Database (Denmark)

    Grunnet, Mie; Mau-Sørensen, Morten; Brünner, Nils

    2013-01-01

    The value of Tissue Inhibitor of MetalloProteinase-1 (TIMP-1) as a biomarker in patients with gastric cancer (GC) is widely debated. The aim of this review is to evaluate available literature describing the association between levels of TIMP-1 in tumor tissue and/or blood and the prognosis...

  14. The nanomechanical signature of liver cancer tissues and its molecular origin.

    Science.gov (United States)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-08-14

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the "gold standard" in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.

  15. Magnetically actuated tissue engineered scaffold: insights into mechanism of physical stimulation

    Science.gov (United States)

    Sapir-Lekhovitser, Yulia; Rotenberg, Menahem Y.; Jopp, Juergen; Friedman, Gary; Polyak, Boris; Cohen, Smadar

    2016-02-01

    Providing the right stimulatory conditions resulting in efficient tissue promoting microenvironment in vitro and in vivo is one of the ultimate goals in tissue development for regenerative medicine. It has been shown that in addition to molecular signals (e.g. growth factors) physical cues are also required for generation of functional cell constructs. These cues are particularly relevant to engineering of biological tissues, within which mechanical stress activates mechano-sensitive receptors, initiating biochemical pathways which lead to the production of functionally mature tissue. Uniform magnetic fields coupled with magnetizable nanoparticles embedded within three dimensional (3D) scaffold structures remotely create transient physical forces that can be transferrable to cells present in close proximity to the nanoparticles. This study investigated the hypothesis that magnetically responsive alginate scaffold can undergo reversible shape deformation due to alignment of scaffold's walls in a uniform magnetic field. Using custom made Helmholtz coil setup adapted to an Atomic Force Microscope we monitored changes in matrix dimensions in situ as a function of applied magnetic field, concentration of magnetic particles within the scaffold wall structure and rigidity of the matrix. Our results show that magnetically responsive scaffolds exposed to an externally applied time-varying uniform magnetic field undergo a reversible shape deformation. This indicates on possibility of generating bending/stretching forces that may exert a mechanical effect on cells due to alternating pattern of scaffold wall alignment and relaxation. We suggest that the matrix structure deformation is produced by immobilized magnetic nanoparticles within the matrix walls resulting in a collective alignment of scaffold walls upon magnetization. The estimated mechanical force that can be imparted on cells grown on the scaffold wall at experimental conditions is in the order of 1 pN, which

  16. Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khlifi, Rim, E-mail: rimkhlifi@yahoo.fr [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia); Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Olmedo, Pablo; Gil, Fernando [Department of Legal Medicine and Toxicology, University of Granada (Spain); Hammami, Bouthaina; Chakroun, Amine [Department of Otorhinolaryngology, HUC Habib Borguiba Hospital, Sfax (Tunisia); Rebai, Ahmed [Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Hamza-Chaffai, Amel [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia)

    2013-05-01

    Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p < 0.05), respectively. Tumor tissue metal levels were higher in men than in women. As and Cd levels in tumor and healthy tissue samples of patients smokers are significantly higher than those of non-smokers (p < 0.05). A strong effect of cumulative smoking as expressed in the number of pack per year, and tumor tissue Cd levels were positively associated with three groups of age (< 40, 51–60 and > 60 years) in both never-smokers and ever-smokers (< 20 and ≥ 20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population. - Highlights: ► Heavy metal levels in tumor tissues were higher than those in healthy tissues. ► Tumor tissue Cd levels were positively associated with age in smokers. ► Tumor tissue metal levels were higher in men than in women. ► The highest Cd and Cr concentrations among workers were observed in tumor tissues

  17. Biomimetic tissue-engineered systems for advancing cancer research: NCI Strategic Workshop report.

    Science.gov (United States)

    Schuessler, Teresa K; Chan, Xin Yi; Chen, Huanhuan Joyce; Ji, Kyungmin; Park, Kyung Min; Roshan-Ghias, Alireza; Sethi, Pallavi; Thakur, Archana; Tian, Xi; Villasante, Aranzazu; Zervantonakis, Ioannis K; Moore, Nicole M; Nagahara, Larry A; Kuhn, Nastaran Z

    2014-10-01

    Advanced technologies and biomaterials developed for tissue engineering and regenerative medicine present tractable biomimetic systems with potential applications for cancer research. Recently, the National Cancer Institute convened a Strategic Workshop to explore the use of tissue biomanufacturing for development of dynamic, physiologically relevant in vitro and ex vivo biomimetic systems to study cancer biology and drug efficacy. The workshop provided a forum to identify current progress, research gaps, and necessary steps to advance the field. Opportunities discussed included development of tumor biomimetic systems with an emphasis on reproducibility and validation of new biomimetic tumor models, as described in this report.

  18. Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation.

    Directory of Open Access Journals (Sweden)

    David Holt

    Full Text Available Defining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR imaging can be used during surgery to differentiate tumors from normal tissue.We enrolled 8 canines and 5 humans undergoing cancer surgery for NIR imaging. The patients were injected with indocyanine green (ICG, an FDA approved non-receptor specific NIR dye that accumulates in hyperpermeable tissues, 16-24 hours prior to surgery. During surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue.NIR imaging identified all tumors with a mean signal-to-background ratio of 6.7. Optical images were useful during surgery in discriminating normal tissue from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor was inflamed due to obstruction of the vascular supply due to mass effect. In these instances, NIR imaging could not distinguish tumor tissue from tissue that was congested, edematous and did not contain cancer.This study shows that NIR imaging can identify tumors from normal tissues, provides excellent tissue contrast, and it facilitates the resection of tumors. However, in situations where there is significant peritumoral inflammation, NIR imaging with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate in hyperpermeable tissues will have significant limitations in the future, and receptor-specific NIR dyes may be necessary to overcome this problem.

  19. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    Science.gov (United States)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  20. The distribution of tissue fibronectin and sialic acid in human breast cancer.

    Science.gov (United States)

    Süer, S; Baloğlu, H; Güngör, Z; Sönmez, H; Kökoğlu, E

    1998-06-01

    Our findings indicate that sialic acid and fibronectin levels in breast tumors are higher than those in normal tissues. The mean tissue fibronectin and sialic acid concentrations for patients with breast cancer were 30.90 +/- 9.68 microg/mg protein and 21.60 +/- 9.35 microg/mg protein, respectively, and for normal controls were 12.47 +/- 5.69 microg/mg protein, respectively. Tissue fibronectin and sialic acid can be important markers for human breast cancer.

  1. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

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    Nasar Yousuf ALWAHAIBI

    2011-01-01

    Full Text Available Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca, copper (Cu, iron (Fe and carcinoembryonic antigen (CEA in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer. Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively. Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  2. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

    Institute of Scientific and Technical Information of China (English)

    Nasar Yousuf ALWAHAIBI; Jokha Sultan ALGHARIBI; Amna Salim ALSHUKAILI; Ahmed Khalifa ALSHUKAILI

    2011-01-01

    Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca), copper (Cu), iron (Fe) and carcinoembryonic antigen (CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer.Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively.Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  3. Electric fish: new insights into conserved processes of adult tissue regeneration.

    Science.gov (United States)

    Unguez, Graciela A

    2013-07-01

    Biology is replete with examples of regeneration, the process that allows animals to replace or repair cells, tissues and organs. As on land, vertebrates in aquatic environments experience the occurrence of injury with varying frequency and to different degrees. Studies demonstrate that ray-finned fishes possess a very high capacity to regenerate different tissues and organs when they are adults. Among fishes that exhibit robust regenerative capacities are the neotropical electric fishes of South America (Teleostei: Gymnotiformes). Specifically, adult gymnotiform electric fishes can regenerate injured brain and spinal cord tissues and restore amputated body parts repeatedly. We have begun to identify some aspects of the cellular and molecular mechanisms of tail regeneration in the weakly electric fish Sternopygus macrurus (long-tailed knifefish) with a focus on regeneration of skeletal muscle and the muscle-derived electric organ. Application of in vivo microinjection techniques and generation of myogenic stem cell markers are beginning to overcome some of the challenges owing to the limitations of working with non-genetic animal models with extensive regenerative capacity. This review highlights some aspects of tail regeneration in S. macrurus and discusses the advantages of using gymnotiform electric fishes to investigate the cellular and molecular mechanisms that produce new cells during regeneration in adult vertebrates.

  4. Analysis of human cancer prostate tissues using FTIR microspectroscopy and SRIXE techniques

    Science.gov (United States)

    Paluszkiewicz, Czesława; Kwiatek, Wojciech M.

    2001-05-01

    It is known that Fourier transform infrared (FTIR) spectra of human tissues are specific and can be used to discriminate between various disease states. In this study, cancer and healthy parts of prostate tissues were examined. The human prostate tissues were obtained during surgical operation. Sections of samples were mounted onto Mylar foils and measured by both FTIR microspectroscopy and synchrotron radiation induced X-ray emission (SRIXE) methods. Neighboring sections of tissues analyzed by FTIR and SRIXE were also examined by a histopathologist. Since the SRIXE technique is suitable for trace element analysis the two-dimensional scans on both cancerous and non-cancerous parts of the prostate tissues were done in order to find elemental distribution of trace elements. The single point analysis on selected areas were also performed. Then the same samples were studied in the mid infrared region on Excalibur spectrometer with infrared microscope UMA-500 equipped with an automatic xy-stage and video camera. Both FTIR spectra and elemental distribution show differences between cancerous and non-cancerous parts of the analyzed tissues.

  5. Gender-Associated Genomic Differences in Colorectal Cancer: Clinical Insight from Feminization of Male Cancer Cells

    Directory of Open Access Journals (Sweden)

    Rola H. Ali

    2014-09-01

    Full Text Available Gender-related differences in colorectal cancer (CRC are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high. Using array comparative genomic hybridization, we analyzed a cohort of 116 CRCs (57 males, 59 females for chromosomal copy number aberrations (CNA and found that CRC in females had significantly higher numbers of gains involving chromosome arms 1q21.2–q21.3, 4q13.2, 6p21.1 and 16p11.2 and copy number losses of chromosome arm 11q25 compared to males. Interestingly, a subset of male CRCs (46% exhibited a "feminization" phenomenon in the form of gains of X chromosomes (or an arm of X and/or losses of the Y chromosome. Feminization of cancer cells was significantly associated with microsatellite-stable CRCs (p-value 0.003 and wild-type BRAF gene status (p-value 0.009. No significant association with other clinicopathological parameters was identified including disease-free survival. In summary, our data show that some CNAs in CRC may be gender specific and that male cancers characterized by feminization may constitute a specific subset of CRCs that warrants further investigation.

  6. Gender-associated genomic differences in colorectal cancer: clinical insight from feminization of male cancer cells.

    Science.gov (United States)

    Ali, Rola H; Marafie, Makia J; Bitar, Milad S; Al-Dousari, Fahad; Ismael, Samar; Bin Haider, Hussain; Al-Ali, Waleed; Jacob, Sindhu P; Al-Mulla, Fahd

    2014-09-29

    Gender-related differences in colorectal cancer (CRC) are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high). Using array comparative genomic hybridization, we analyzed a cohort of 116 CRCs (57 males, 59 females) for chromosomal copy number aberrations (CNA) and found that CRC in females had significantly higher numbers of gains involving chromosome arms 1q21.2-q21.3, 4q13.2, 6p21.1 and 16p11.2 and copy number losses of chromosome arm 11q25 compared to males. Interestingly, a subset of male CRCs (46%) exhibited a "feminization" phenomenon in the form of gains of X chromosomes (or an arm of X) and/or losses of the Y chromosome. Feminization of cancer cells was significantly associated with microsatellite-stable CRCs (p-value 0.003) and wild-type BRAF gene status (p-value 0.009). No significant association with other clinicopathological parameters was identified including disease-free survival. In summary, our data show that some CNAs in CRC may be gender specific and that male cancers characterized by feminization may constitute a specific subset of CRCs that warrants further investigation.

  7. Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

    Science.gov (United States)

    Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

    2015-07-01

    Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

  8. Study on nasopharyngeal cancer tissue using surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Ge, Xiaosong; Lin, Xueliang; Xu, Zhihong; Wei, Guoqiang; Huang, Wei; Lin, Duo

    2016-10-01

    Surface-enhanced Raman spectroscopy (SERS) can provide detailed molecular structure and composition information, and has demonstrated great potential in biomedical filed. This spectroscopy technology has become one of the most important optical techniques in the early diagnosis of cancer. Nasopharyngeal cancer (NPC) is a malignant neoplasm arising in the nasopharyngeal epithelial lining, which has relatively high incidence and death rate in Southeast Asia and southern China. This paper reviews the current progress of SERS in the field of cancer diagnostics, including gastric cancer, colorectal cancer, cervical cancer and nasopharyngeal cancer. In addition to above researches, we recently develop a novel NPC detection method based on tissue section using SERS, and obtain primary results. The proposed method has promising potential for the detection of nasopharyngeal carcinoma.

  9. Insights on Metal Based Dental Implants and their Interaction with the Surrounding Tissues.

    Science.gov (United States)

    Popa, Marcela; Hussien, Mohamed D; Cirstea, Alexandra; Grigore, Raluca; Lazar, Veronica; Bezirtzoglou, Eugenia; Chifiriuc, Mariana Carmen; Sakizlian, Monica; Stavropoulou, Elisavet; Bertesteanu, Serban

    2015-01-01

    At present, the use of dental implants is a very common practice as tooth loss is a frequent problem and can occur as a result of disease or trauma. An implant is usually made of biocompatible materials that do not cause rejection reactions and allow the implant union with the respective bone. To achieve this goal, the implant surface may have different structures and coatings, generally used to increase the adherence of the implant to the bone and to decrease the risk of the periimplantar inflammatory reactions. This review gives some insights of the metal based materials used for dental implants, their limits, improvement strategies as well as the pathophysiology, diagnosis, treatment and prevention of periimplantary diseases.

  10. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  11. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

    Energy Technology Data Exchange (ETDEWEB)

    Arrebola, J.P., E-mail: jparrebola@ugr.es [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); CIBER en Epidemiología y Salud Pública (CIBERESP) (Spain); Fernández-Rodríguez, M.; Artacho-Cordón, F. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); University of Granada, Radiology and Physical Medicine Department (Spain); Garde, C. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Perez-Carrascosa, F.; Linares, I.; Tovar, I. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); González-Alzaga, B. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Escuela Andaluza de Salud Pública, Granada (Spain); Expósito, J. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); Torne, P. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); and others

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends = 0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends = 0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend = 0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends = 0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend = 0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. - Highlights: • The role of POP exposure on the pathogenesis breast cancer is still controversial. • POPs were analyzed in serum and adipose tissue from breast cancer patients. • POP concentrations were associated with breast cancer prognostic markers. • POPs in serum and adipose tissue of breast cancer patients may provide different clues.

  12. Analysis of different components in the peritumoral tissue microenvironment of colorectal cancer: A potential prospect in tumorigenesis.

    Science.gov (United States)

    Huang, Chao; Liu, Hong; Gong, Xiuli; Wen, Bin; Chen, Dan; Liu, Jinyuan; Hu, Fengliang

    2016-09-01

    The present study aimed to observe the varying expression of biomarkers in the microenvironment adjacent to colorectal cancer lesions to provide additional insight into the functions of microenvironment components in carcinogenesis and present a novel or improved indicator for early diagnosis of cancer. A total of 144 human samples from three different locations in 48 patients were collected, these locations were 10, 5 and 2 cm from the colorectal cancer lesion, respectively. The biomarkers analyzed included E‑cadherin, cytokeratin 18 (CK18), hyaluronidase‑1 (Hyal‑1), collagen type I (Col‑I), Crumbs3 (CRB3), vimentin, proteinase activated receptor 3 (PAR‑3), α‑smooth muscle actin (α‑SMA), cyclin D1 (CD1) and cluster of differentiation (CD)133. In addition, crypt architecture was observed. Related functional analysis of proteins was performed using hierarchical index cluster analysis. More severe destroyed crypt architecture closer to the cancer lesions was observed compared with the 10 cm sites, with certain crypts degraded entirely. Expression levels of E‑cadherin, CK18, CRB3 and PAR‑3 were lower in 2 cm sites compared with the 10 cm sites (all P0.05 and P=0.0001, respectively), while the expression of vimentin, α‑SMA, CD1 and CD133 were not. Hyal‑1 and Col‑I may be independently important in cancer initiation in the tumor microenvironment. The results of the present study suggest that the biomarkers in the tissue microenvironment are associated with early tumorigenesis and may contribute to the development of carcinomas. These observations may be useful for early diagnosis of colorectal cancer.

  13. Upregulation of RHOXF2 and ODF4 Expression in Breast Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Golnesa Kazemi-Oula

    2015-10-01

    Full Text Available Objective: During the past decade, the importance of biomarker discovery has been highlighted in many aspects of cancer research. Biomarkers may have a role in early detection of cancer, prognosis and survival evaluation as well as drug response. Cancer-testis antigens (CTAs have gained attention as cancer biomarkers because of their expression in a wide variety of tumors and restricted expression in testis. The aim of this study was to find putative biomarkers for breast cancer. Materials and Methods: In this applied-descriptive study, the expression of 4 CTAs, namely acrosin binding protein (ACRBP, outer dense fiber 4 (ODF4, Rhox homeobox family member 2 (RHOXF2 and spermatogenesis associated 19 (SPATA19 were analyzed at the transcript level in two breast cancer lines (MCF-7 and MDA-MB-231, 40 invasive ductal carcinoma samples and their adjacent normal tissues as well as 10 fibroadenoma samples by means of quantitative real-time reverse transcription polymerase chain reaction (RT-PCR. Results: All four genes were expressed in both cell lines. Expression of ODF4 and RHOXF2 was detected in 62.5% and 60% of breast cancer tissues but in 22.5 and 17.5% of normal tissues examined respectively. The expression of both RHOXF2 and ODF4 was upregulated in cancerous tissues compared with their normal adjacent tissues by 3.31- and 2.96-fold respectively. The expression of both genes was correlated with HER2/neu overexpression. RHOXF2 expression but not ODF4 was correlated with higher stages of tumors. However, no significant association was seen between expression patterns and estrogen and progesterone receptors status. Conclusion: ODF4 and RHOXF2 are proposed as putative breast cancer biomarkers at the transcript level. However, their expression at protein level should be evaluated in future studies.

  14. 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.

  15. Cancer Detection in Human Tissue Samples Using a Fiber-Tip pH Probe.

    Science.gov (United States)

    Schartner, Erik P; Henderson, Matthew R; Purdey, Malcolm; Dhatrak, Deepak; Monro, Tanya M; Gill, P Grantley; Callen, David F

    2016-12-01

    Intraoperative detection of tumorous tissue is an important unresolved issue for cancer surgery. Difficulty in differentiating between tissue types commonly results in the requirement for additional surgeries to excise unremoved cancer tissue or alternatively in the removal of excess amounts of healthy tissue. Although pathologic methods exist to determine tissue type during surgery, these methods can compromise postoperative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis, and are restricted to excised tissue. In this work, we report the development of an optical fiber probe that could potentially find use as an aid for margin detection during surgery. A fluorophore-doped polymer coating is deposited on the tip of an optical fiber, which can then be used to record the pH by monitoring the emission spectra from this dye. By measuring the tissue pH and comparing with the values from regular tissue, the tissue type can be determined quickly and accurately. The use of a novel lift-and-measure technique allows for these measurements to be performed without influence from the inherent autofluorescence that commonly affects fluorescence-based measurements on biological samples. The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration, which could find use in the operating theater. Use of this probe in surgery either on excised or in vivo tissue has the potential to improve success rates for complete removal of cancers. Cancer Res; 76(23); 6795-801. ©2016 AACR.

  16. PREFACE: 1st Nano-IBCT Conference 2011 - Radiation Damage of Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy

    Science.gov (United States)

    Huber, Bernd A.; Malot, Christiane; Domaracka, Alicja; Solov'yov, Andrey V.

    2012-07-01

    The 1st Nano-IBCT Conference entitled 'Radiation Damage in Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy' was held in Caen, France, in October 2011. The Meeting was organised in the framework of the COST Action MP1002 (Nano-IBCT) which was launched in December 2010 (http://fias.uni-frankfurt.de/nano-ibct). This action aims to promote the understanding of mechanisms and processes underlying the radiation damage of biomolecular systems at the molecular and nanoscopic level and to use the findings to improve the strategy of Ion Beam Cancer Therapy. In the hope of achieving this, participants from different disciplines were invited to represent the fields of physics, biology, medicine and chemistry, and also included those from industry and the operators of hadron therapy centres. Ion beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal healthy tissue, while maximizing cell killing within the tumour. Several ion beam cancer therapy clinical centres are now operating in Europe and elsewhere. However, the full potential of such therapy can only be exploited by better understanding the physical, chemical and biological mechanisms that lead to cell death under ion irradiation. Considering a range of spatio-temporal scales, the proposed action therefore aims to combine the unique experimental and theoretical expertise available within Europe to acquire greater insight at the nanoscopic and molecular level into radiation damage induced by ion impact. Success in this endeavour will be both an important scientific breakthrough and give great impetus to the practical improvement of this innovative therapeutic technique. Ion therapy potentially provides an important advance in cancer therapy and the COST action MP1002 will be very significant in ensuring Europe's leadership in this field, providing the scientific background, required data and mechanistic insight which

  17. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    Science.gov (United States)

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  18. Adipose tissue development during early life: novel insights into energy balance from small and large mammals.

    Science.gov (United States)

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2012-08-01

    Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.

  19. 3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration.

    Science.gov (United States)

    Hsieh, Fu-Yu; Hsu, Shan-hui

    2015-01-01

    Acute traumatic injuries and chronic degenerative diseases represent the world's largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37 °C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration.

  20. Effect of Static Magnetic Field on Oxidant/Antioxidant Parameters in Cancerous and Noncancerous Human Gastric Tissues

    Directory of Open Access Journals (Sweden)

    Bahadır Öztürk

    2016-01-01

    Full Text Available Aim. To investigate the effects of static magnetic field (SMF on oxidant and antioxidant parameters of the cancerous and noncancerous human gastric tissues. Materials and Methods. Gastric tissues obtained from patients with gastric cancer were used in the study. SMF was created by using two static magnets. Before and after treatment with SMF, oxidant and antioxidant parameters were measured in the tissue samples. Results. In the cancerous tissue, superoxide dismutase (SOD activity was found higher and malondialdehyde (MDA level was found lower as compared with noncancerous tissue. SMF affects oxidant/antioxidant parameters differently in the cancerous and noncancerous tissues. In this regard, SMF causes increase in SOD activity and decrease in MDA level in the noncancerous tissue. However, it decreases SOD and glutathione peroxidase (GSH-Px activities and increases MDA level and catalase (CAT activity in the cancerous tissue. There were no differences between nitric oxide (NO and nitric oxide synthase (NOS parameters in or among the cancerous and noncancerous tissues. Conclusions. SMF accelerates peroxidation reactions possibly by suppressing SOD and GSH-Px enzymes in the cancerous gastric tissue. This event caused by SMF might play part in the death of cancer cells, which may be a good supportive vehicle for the cancer therapy.

  1. Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.

    Science.gov (United States)

    Crowell, Ed; Wang, Gufeng; Cox, Jason; Platz, Charles P; Geng, Lei

    2005-03-01

    Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer

  2. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE) Prostate Cancer Tissue

    Science.gov (United States)

    Menon, Roopika; Deng, Mario; Boehm, Diana; Braun, Martin; Fend, Falko; Boehm, Detlef; Biskup, Saskia; Perner, Sven

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE) tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing. PMID:22942743

  3. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE Prostate Cancer Tissue

    Directory of Open Access Journals (Sweden)

    Saskia Biskup

    2012-07-01

    Full Text Available Next generation sequencing (NGS technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing.

  4. [Determination of thirty three elements in lung cancer tissues of patients with lung cancer by microwave digestion-ICP-MS].

    Science.gov (United States)

    Zhang, Lin-Lin; Ma, Qian-Li; Huang, Yun-Chao; Wu, Guo-Ping; Wei, Fu-Sheng

    2009-12-01

    A method for determining 33 elements in lung tissues of patients with lung cancer was developed by using vacuum freeze-drying microwave digestion-ICP-MS. The lung tissue samples were treated by vacuum freeze-drying equipment. After microwave digestion in HNO3-H2O2 solution system, the samples were diluted with the method of constant volume. Under the optimized conditions the samples were analyzed by ICP-MS. The double internal standard elements Rh and Re were used to compensate for matrix suppression effect and sensitivity drift. The analytical results showed that the detection limits of the 33 elements were 0.01-0.45 ng x mL(-1). The national standard reference material GBW(E)080193 bovine liver was analyzed by the described method and the measured element values accorded with the standard values or the reference values. The relative standard deviation (RSD) of the method was 2.1%-14.3%. The recovery rates of the studied elements were 90.1%-117.5%. The contents of 33 elements in lung cancer tissues, paracancerous lung tissues and benign lung tissues of 6 patients with lung cancer were determined by the method. It was indicated that the method is rapid, simple and accurate for determining multi-elements in human lung tissue and other biological samples.

  5. Distinction of gastric cancer tissue based on surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Ma, Jun; Zhou, Hanjing; Gong, Longjing; Liu, Shu; Zhou, Zhenghua; Mao, Weizheng; Zheng, Rong-er

    2012-12-01

    Gastric cancer is one of the most common malignant tumors with high recurrence rate and mortality rate in China. This study aimed to evaluate the diagnostic capability of Surface-enhanced Raman spectroscopy (SERS) based on gold colloids for distinguishing gastric tissues. Gold colloids were directly mixed with the supernatant of homogenized tissues to heighten the Raman signal of various biomolecule. A total of 56 samples were collected from normal (30) and cancer (26). Raman spectra were obtained with a 785nm excitation in the range of 600-1800 cm-1. Significant spectral differences in SERS mainly belong to nucleic acid, proteins and lipids, particularly in the range of 653, 726, 828, 963, 1004, 1032, 1088, 1130, 1243, 1369, 1474, 1596, 1723 cm-1. PCA-LDA algorithms with leave-one-patient-out cross validation yielded diagnostic sensitivities of 90% (27/30), specificities of 88.5% (23/26), and accuracy of 89.3% (50/56), for classification of normal and cancer tissues. The receiver operating characteristic (ROC) surface is 0.917, illustrating the diagnostic utility of SERS together with PCA-LDA to identify gastric cancer from normal tissue. This work demonstrated the SERS techniques can be useful for gastric cancer detection, and it is also a potential technique for accurately identifying cancerous tumor, which is of considerable clinical importance to real-time diagnosis.

  6. Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.

    Science.gov (United States)

    Olszewski, Waldemar L; Stanczyk, Marek; Gewartowska, Magdalena; Domaszewska-Szostek, Anna; Durlik, Marek

    2012-09-01

    There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.

  7. Tissue/planar cell polarity in vertebrates: new insights and new questions.

    Science.gov (United States)

    Wang, Yanshu; Nathans, Jeremy

    2007-02-01

    This review focuses on the tissue/planar cell polarity (PCP) pathway and its role in generating spatial patterns in vertebrates. Current evidence suggests that PCP integrates both global and local signals to orient diverse structures with respect to the body axes. Interestingly, the system acts on both subcellular structures, such as hair bundles in auditory and vestibular sensory neurons, and multicellular structures, such as hair follicles. Recent work has shown that intriguing connections exist between the PCP-based orienting system and left-right asymmetry, as well as between the oriented cell movements required for neural tube closure and tubulogenesis. Studies in mice, frogs and zebrafish have revealed that similarities, as well as differences, exist between PCP in Drosophila and vertebrates.

  8. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

  9. Expression of CD40 and CD40L in Gastric Cancer Tissue and Its Clinical Significance

    Directory of Open Access Journals (Sweden)

    Rui Li

    2009-09-01

    Full Text Available To study expression of CD40 and CD40L in gastric cancer tissue we assessed gastric cancer patients admitted to the Department of Gastroenterology of The First Affiliated Hospital of Soochow University and control subjects. Gastric cancer and normal (from around tumours tissue samples were obtained from patients. Venous blood samples (gastric cancer and ulcer groups were drawn on the morning of the day before surgery for the measurement of peripheral sCD40L. The expression of CD40 in gastric carcinoma specimens was examined immuno-histochemically. The clinicopathological factors, including age, sex, tumor size, gross appearance, degree of cellular differentiation, histological classification, depth of tumor invasion, lymph node metastasis, peritoneal dissemination, and TNM stage were analyzed according to the different expression of CD40. The results indicated a high CD40 expression in gastric cancer tissues. This positive expression of CD40 revealed a significant (P < 0.05 correlation with lymphatic metastasis and tumor TNM stage in gastric cancer patients. It is concluded that higher CD40 expression existed in expanding type tumors and could play an important role in clinical diagnosis of gastric cancer patients.

  10. Prognostic microRNAs in cancer tissue from patients operated for pancreatic cancer--five microRNAs in a prognostic index

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Andersen, Klaus; Roslind, Anne;

    2012-01-01

    The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC).......The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC)....

  11. Raising an Antibody Specific to Breast Cancer Subpopulations Using Phage Display on Tissue Sections

    DEFF Research Database (Denmark)

    Larsen, Simon Asbjørn; Meldgaard, Theresa; Fridriksdottir, Agla Jael Rubner

    2016-01-01

    BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody...... fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers. MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against...... small subpopulations of breast cancer cells. Selections were performed against a subpopulation of breast cancer cells expressing CD271(+), as these previously have been indicated to be potential breast cancer stem cells. The selected antibody fragments were screened by phage ELISA on both breast cancer...

  12. System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis.

    Science.gov (United States)

    Pozniak, Yair; Balint-Lahat, Nora; Rudolph, Jan Daniel; Lindskog, Cecilia; Katzir, Rotem; Avivi, Camilla; Pontén, Fredrik; Ruppin, Eytan; Barshack, Iris; Geiger, Tamar

    2016-03-23

    The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.

  13. BRMS1 and Cx43 expression in fine needle aspiration thyroid cancer tissue and their correlation with tumor malignancy

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo Sheng; Bin Wang; Zong-Ping Diao; Kun-Kun Cao; Sai Zhang; Zheng-Guo Pu

    2016-01-01

    Objective:To study the BRMS1 and Cx43 expression in fine needle aspiration thyroid cancer tissue and their correlation with tumor malignancy.Methods:Patients undergoing thyroid fine needle aspiration biopsy in our hospital from April 2012 to October 2015 were selected for study, 60 patients with thyroid cancer and 60 patients with benign thyroid tumor were screened after pathological diagnosis, biopsy tissue was collected to determine the expression of BRMS1 and Cx43, and serum specimens were collected to determin Gal-3, CEACAM1, MMP2 and MMP9 content.Results: mRNA levels and positive expression rate of BRMS1 andCx43in thyroid cancer tissue were significantly lower than those in benign thyroid tumor tissue; mRNA levels ofBRMS1andCx43in thyroid cancer tissue with different pathological types and tumor diameters were not different, mRNA level ofCx43in thyroid cancer tissue with TNM III-IV stage was significantly lower than that in thyroid cancer tissue with TNM I-II stage, mRNA levels ofBRMS1 in thyroid cancer tissue with different TNM stages were not different, and mRNA levels ofBRMS1andCx43in thyroid carcinoma tissue with lymph node metastasis were significantly lower than those in thyroid carcinoma tissue without lymph node metastasis; serum Gal-3, CEACAM1, MMP2 and MMP9 levels in patients with positive BRMS1 and Cx43 expression in thyroid cancer tissue were significantly lower than those in patients with negative BRMS1 and Cx43 expression in thyroid cancer tissue.Conclusions:Lower expression of BRMS1 and Cx43 in fine needle aspiration thyroid cancer tissue is associated with the distant metastasis and malignant degree of tumor, and lower expression of Cx43 is also associated with the growth of tumor and cancer cell proliferation.

  14. Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments.

    Science.gov (United States)

    Muralidharan, Arjun; Smith, Maree T

    2013-10-01

    Prostate cancer (PCa) has a high propensity for metastasis to bone. Despite the availability of multiple treatment options for relief of PCa-induced bone pain (PCIBP), satisfactory relief of intractable pain in patients with advanced bony metastases is challenging for the clinicians because currently available analgesic drugs are often limited by poor efficacy and/or dose-limiting side effects. Rodent models developed in the past decade show that the pathobiology of PCIBP comprises elements of inflammatory, neuropathic and ischemic pain arising from ectopic sprouting and sensitization of sensory nerve fibres within PCa-invaded bones. In addition, at the cellular level, PCIBP is underpinned by dynamic cross talk between metastatic PCa cells, cellular components of the bone matrix, factors associated with the bone microenvironment as well as peripheral components of the somatosensory system. These insights are aligned with the clinical management of PCIBP involving use of a multimodal treatment approach comprising analgesic agents (opioids, NSAIDs), radiotherapy, radioisotopes, cancer chemotherapy agents and bisphosphonates. However, a major drawback of most rodent models of PCIBP is their short-term applicability due to ethical concerns. Thus, it has been difficult to gain insight into the mal(adaptive) neuroplastic changes occurring at multiple levels of the somatosensory system that likely contribute to intractable pain at the advanced stages of metastatic disease. Specifically, the functional responsiveness of noxious circuitry as well as the neurochemical signature of a broad array of pro-hyperalgesic mediators in the dorsal root ganglia and spinal cord of rodent models of PCIBP is relatively poorly characterized. Hence, recent work from our laboratory to develop a protocol for an optimized rat model of PCIBP will enable these knowledge gaps to be addressed as well as identification of novel targets for drug discovery programs aimed at producing new analgesics

  15. Organoid culture systems for prostate epithelial and cancer tissue

    NARCIS (Netherlands)

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-01-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material cont

  16. A targeting ligand enhances infectivity and cytotoxicity of an oncolytic adenovirus in human pancreatic cancer tissues.

    Science.gov (United States)

    Yamamoto, Yuki; Hiraoka, Nobuyoshi; Goto, Naoko; Rin, Yosei; Miura, Kazuki; Narumi, Kenta; Uchida, Hiroaki; Tagawa, Masatoshi; Aoki, Kazunori

    2014-10-28

    The addition of a targeting strategy is necessary to enhance oncolysis and secure safety of a conditionally replicative adenovirus (CRAd). We have constructed an adenovirus library displaying random peptides on the fiber, and have successfully identified a pancreatic cancer-targeting ligand (SYENFSA). Here, the usefulness of cancer-targeted CRAd for pancreatic cancer was examined as a preclinical study. First, we constructed a survivin promoter-regulated CRAd expressing enhanced green fluorescent protein gene (EGFP), which displayed the identified targeting ligand (AdSur-SYE). The AdSur-SYE resulted in higher gene transduction efficiency and oncolytic potency than the untargeted CRAd (AdSur) in several pancreatic cancer cell lines. An intratumoral injection of AdSur-SYE significantly suppressed the growth of subcutaneous tumors, in which AdSur-SYE effectively proliferated and spread. An ectopic infection in adjacent tissues and organs of intratumorally injected AdSur-SYE was decreased compared with AdSur. Then, to examine whether the targeting ligand actually enhanced the infectivity of CRAd in human pancreatic cancer tissues, tumor cells prepared from surgical specimens were infected with viruses. The AdSur-SYE increased gene transduction efficiency 6.4-fold higher than did AdSur in single cells derived from human pancreatic cancer, whereas the infectivity of both vectors was almost the same in the pancreas and other cancers. Immunostaining showed that most EGFP(+) cells were cytokeratin-positive in the sliced tissues, indicating that pancreatic cancer cells but not stromal cells were injected with AdSur-SYE. AdSur-SYE resulted in a stronger oncolysis in the primary pancreatic cancer cells co-cultured with mouse embryonic fibroblasts than AdSur did. CRAd in combination with a tumor-targeting ligand is promising as a next-generation of oncolytic virotherapy for pancreatic cancer.

  17. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, R K; Bissell, M J

    2000-06-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

  18. [Concentration of cadmium in breast cancer tissue of women living in the Wielkopoiska region].

    Science.gov (United States)

    Rydzewska, Anna; Król, Iwona; Lipiński, Leszek

    2004-01-01

    The research was carried out concerning the contents of cadmium in breast cancer tissues in 52 women aged 35-81 years (x = 67.62 +/- 12.43) living in the Wielkopolska region. Particular concentrations of this metal in the range of 0.01-1.08 mg/g wet wt. (x = 0.13 +/- 0.18) were found in all the studied specimens. The obtained results were assessed regarding the women's place of residence--Kalisz, Leszno, Pila or Poznan voivodships--and a particular living area: an industrialised town, other towns or villages of the Wielkopolska region. A statistically significant difference in the content of cadmium in breast cancer tissues was found in women inhabiting the Poznan and Pila voivodships. Moreover, marked differences were observed between the average cadmium concentrations in the breast cancer tissue samples in women living in the remaining voivodships and the types of living areas.

  19. Blood and tissue biomarkers in prostate cancer: state of the art.

    Science.gov (United States)

    Fiorentino, Michelangelo; Capizzi, Elisa; Loda, Massimo

    2010-02-01

    The prevalence of prostate cancer (PCa) is high and increases with age. PCa is the most common cutaneous cancer in American men. Prostate-specific antigen (PSA) screening has impacted the detection of PCa and is directly responsible for a dramatic decrease in stage at diagnosis. Gleason score and stage at the time of diagnosis remain the mainstay to predict prognosis, in the absence of more accurate and reliable tissue or blood biomarkers. Despite extensive research efforts, very few biomarkers of PCa have been introduced to date in clinical practice. Even screening with PSA has recently been questioned. A thorough analysis of all tissue and serum biomarkers in prostate cancer research cannot be easily synthesized, and goes beyond the scope of the present article. Therefore the authors focus here on the most recently reported tissue and circulating biomarkers for PCa whose application in clinical practice is either current or expected in the near future.

  20. Preventing premature deaths from breast and cervical cancer among underserved women in the United States: insights gained from a national cancer screening program.

    Science.gov (United States)

    White, Mary C; Wong, Faye L

    2015-05-01

    This commentary highlights some of the valuable insights gained from a special collection of papers that utilized data from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and appear in this special issue. The data and experiences of the NBCCEDP can inform the identification of new opportunities and directions for meeting the cancer screening needs of underserved women in a complex and changing health care environment.

  1. Insight into the exoproteome of the tissue-derived trypomastigote form of Trypanosoma cruzi

    Science.gov (United States)

    Queiroz, Rayner; Ricart, Carlos; Machado, Mara; Bastos, Izabela; Santana, Jaime; Sousa, Marcelo; Roepstorff, Peter; Charneau, Sébastien

    2016-11-01

    The protozoan parasite Trypanosoma cruzi causes Chagas disease, one of the major neglected infectious diseases. It has the potential to infect any nucleated mammalian cell. The secreted/excreted protein repertoire released by T. cruzi trypomastigotes is crucial in host-pathogen interactions. In this study, mammalian tissue culture-derived trypomastigotes (Y strain) were used to characterize the exoproteome of the infective bloodstream life form. Proteins released into the serum-free culture medium after 3h of incubation were harvested and digested with trypsin. NanoLC-MS/MS analysis resulted in the identification of 540 proteins, the largest set of released proteins identified to date in Trypanosome spp. Bioinformatic analysis predicted most identified proteins as secreted, predominantly by non-classical pathways, and involved in host-cell infection. Some proteins possess predicted GPI-anchor signals, these being mostly trans-sialidases, mucin associated surface proteins and surface glycoproteins. Moreover, we enriched phosphopeptides and glycopeptides from tryptic digests. The majority of identified glycoproteins are trans-sialidases and surface glycoproteins involved in host-parasite interaction. Conversely, most identified phosphoproteins have no Gene Ontology classification. The existence of various proteins related to similar functions in the exoproteome likely reflects this parasite’s enhanced mechanisms for adhesion, invasion and internalization of different host-cell types, and escape from immune defences.

  2. N-glycoprotein analysis discovers new up-regulated glycoproteins in colorectal cancer tissue.

    Science.gov (United States)

    Nicastri, Annalisa; Gaspari, Marco; Sacco, Rosario; Elia, Laura; Gabriele, Caterina; Romano, Roberto; Rizzuto, Antonia; Cuda, Giovanni

    2014-11-07

    Colorectal cancer is one of the leading causes of death due to cancer worldwide. Therefore, the identification of high-specificity and -sensitivity biomarkers for the early detection of colorectal cancer is urgently needed. Post-translational modifications, such as glycosylation, are known to play an important role in cancer progression. In the present work, we used a quantitative proteomic technique based on (18)O stable isotope labeling to identify differentially expressed N-linked glycoproteins in colorectal cancer tissue samples compared with healthy colorectal tissue from 19 patients undergoing colorectal cancer surgery. We identified 54 up-regulated glycoproteins in colorectal cancer samples, therefore potentially involved in the biological processes of tumorigenesis. In particular, nine of these (PLOD2, DPEP1, SE1L1, CD82, PAR1, PLOD3, S12A2, LAMP3, OLFM4) were found to be up-regulated in the great majority of the cohort, and, interestingly, the association with colorectal cancer of four (PLOD2, S12A2, PLOD3, CD82) has not been hitherto described.

  3. Tissue microarrays for testing basal biomarkers in familial breast cancer cases

    Directory of Open Access Journals (Sweden)

    Rozany Mucha Dufloth

    Full Text Available CONTEXT AND OBJECTIVE: The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunopro-file of a breast cancer case series using tissue microarray technology. DESIGN AND SETTING: This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Mo-lecular Immunology, Porto, Portugal. METHODS: Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER and Human Epidermal Receptor Growth Factor 2 (HER2, was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. RESULTS: Familial tumors were more frequently positive for the p-cadherin (p = 0.0004, p63 (p < 0.0001 and CK5 (p < 0.0001 than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34, while absence of coexpression (OR = 0.13 was associ-ated with the sporadic cancer phenotype. CONCLUSION: Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.

  4. Mathematical modelling of the influence of heat shock proteins on cancer invasion of tissue.

    Science.gov (United States)

    Szymańska, Zuzanna; Urbański, Jakub; Marciniak-Czochra, Anna

    2009-04-01

    Tumour cell invasion is crucial for cancer metastasis, which is the main cause of cancer mortality. An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while they are invading tissue, but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9), which are very important for cancer metastasis, acting as extracellular matrix (ECM) degrading enzymes. To test different biological hypotheses regarding how precisely Hsp90 influences tumour invasion, in this paper we use a model of solid tumour growth which accounts for the interactions between Hsp90 dynamics and the migration of cancer cells and, alternatively, between Hsp90 dynamics and the synthesis of matrix degrading enzymes (MDEs). The model consists of a system of reaction-diffusion-taxis partial differential equations describing interactions between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations we investigate the effects of the administration of Hsp90 inhibitors on the dynamics of tumour invasion. Alternative mechanisms of reduction of cancer invasiveness result in different simulated patterns of the invading tumour cells. Therefore, predictions of the model suggest experiments which might be performed to develop a deeper understanding of the tumour invasion process.

  5. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    Science.gov (United States)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  6. Identification of vitamin D3 target genes in human breast cancer tissue.

    Science.gov (United States)

    Sheng, Lei; Anderson, Paul H; Turner, Andrew G; Pishas, Kathleen I; Dhatrak, Deepak J; Gill, Peter G; Morris, Howard A; Callen, David F

    2016-11-01

    Multiple epidemiological studies have shown that high vitamin D3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN, SERPINB1, EFTUD1, and KLK6were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN, SERPINB1, and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1, and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D3 levels may improve breast cancer outcome.

  7. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

    Directory of Open Access Journals (Sweden)

    Wenyan Hu

    Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

  8. Nitrate dynamics in natural plants: Insights based on the concentration and natural isotope abundances of tissue nitrate

    Directory of Open Access Journals (Sweden)

    Xue Yan Liu

    2014-07-01

    Full Text Available The dynamics of nitrate (NO3-, a major nitrogen (N source for natural plants, has been studied mostly through experimental N addition, enzymatic assay, isotope labeling, and genetic expression. However, artificial N supply may not reasonably reflect the N strategies in natural plants because NO3- uptake and reduction may vary with external N availability. Abrupt application and short operation times, field N addition, and isotopic labeling hinder the elucidation of in situ NO3--use mechanisms. The concentration and natural isotopes of tissue NO3- can offer insights into the plant NO3- sources and dynamics in a natural context. Furthermore, they facilitate the exploration of plant NO3- utilization and its interaction with N pollution and ecosystem N cycles without disturbing the N pools. The present study was conducted to review the application of the denitrifier method for concentration and isotope analyses of NO3- in plants. Moreover, this study highlights the utility and benefits of these parameters in interpreting NO3- sources and dynamics in natural plants. We summarize the major sources and reduction processes of NO3- in plants, and discuss the implications of NO3- concentration in plant tissues based on existing data. Particular emphasis was laid on the regulation of soil NO3 - and plant ecophysiological functions in interspecific and intra-plant NO3- variations. We introduce N and O isotope systematics of NO3- in plants and discusse the principles and feasibilities of using isotopic enrichment and fractionation factors; the correlation between concentration and isotopes (N and O isotopes: δ18O and ∆17O; and isotope mass-balance calculations to constrain sources and reduction of NO3- in possible scenarios for natural plants are deliberated. Finally, we construct a preliminary framework of intraplant δ18O-NO3- variation, and summarize the uncertainties in using tissue NO3- parameters to interpret plant NO3- utilization.

  9. Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments

    OpenAIRE

    2015-01-01

    IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray a...

  10. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself.

    Science.gov (United States)

    Laviano, Alessandro; Meguid, Michael M; Inui, Akio; Muscaritoli, Maurizio; Rossi-Fanelli, Filippo

    2005-03-01

    Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia-cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass--and to a lesser extent adipose tissue--occurring even before weight loss becomes apparent. Cancer anorexia-cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic-cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

  11. Increased expression of cysteine cathepsins in ovarian tissue from chickens with ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ahn Suzie E

    2010-08-01

    Full Text Available Abstract Background Cysteine cathepsins (CTSs are involved in the degradation and remodeling of the extracellular matrix and are associated with cell transformation, differentiation, motility, and adhesion. These functions are also related to cancer cell invasion and metastasis. Chickens spontaneously develop epithelial ovarian cancer and are therefore a good animal model for human ovarian cancer. However, no studies have investigated the expression of CTSs in chickens with ovarian cancer. Methods Cancerous (n = 5 and normal (n = 3 ovaries were collected from 2-to 3-year-old hens, and ovarian tissue samples were collected for study. Ovarian cancers were evaluated with hematoxylin and eosin staining. Reverse transcriptase and quantitative PCR analyses, in situ hybridization analysis were performed to examine the mRNA expression pattern of three CTSs in detail, and protein expression of CTSB was evaluated. Results The CTSB, CTSC, and CTSS genes were highly expressed in cancerous chicken ovaries. Messenger RNAs for the three CTSs were localized to a nodule area, a major characteristic of cancerous ovaries, but the three CTSs showed no specific localization in normal ovaries. Immunoreactive CTSB protein was present in the nodule area of cancerous ovaries. Conclusion Our results suggest that CTSB, CTSC, and CTSS have important functions in the development of epithelial ovarian cancer.

  12. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.

    Science.gov (United States)

    Kir, Serkan; White, James P; Kleiner, Sandra; Kazak, Lawrence; Cohen, Paul; Baracos, Vickie E; Spiegelman, Bruce M

    2014-09-04

    Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat. How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival.

  13. Elevated levels of G-quadruplex formation in human stomach and liver cancer tissues.

    Science.gov (United States)

    Biffi, Giulia; Tannahill, David; Miller, Jodi; Howat, William J; Balasubramanian, Shankar

    2014-01-01

    Four-stranded G-quadruplex DNA secondary structures have recently been visualized in the nuclei of human cultured cells. Here, we show that BG4, a G-quadruplex-specific antibody, can be used to stain DNA G-quadruplex structures in patient-derived tissues using immunohistochemistry. We observe a significantly elevated number of G-quadruplex-positive nuclei in human cancers of the liver and stomach as compared to background non-neoplastic tissue. Our results suggest that G-quadruplex formation can be detected and measured in patient-derived material and that elevated G-quadruplex formation may be a characteristic of some cancers.

  14. Regulation of Breast Cancer Stem Cells by Tissue Rigidity

    Science.gov (United States)

    2015-06-01

    of G3BP2 together predict poor survival. Our findings reveal a TWIST1–G3BP2 mechanotransduction pathway that responds to biomechanical signals from the...and fibroblasts can also contribute to EMT. IL6 promotes EMT in head and neck cancer cells and correlates with increased TWIST1 and SNAIL1 expres...activation, was tested in phase II clinical studies with metastatic gastric adenocarcinoma, and recurrent and metastatic head and neck squamous cell car

  15. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    Directory of Open Access Journals (Sweden)

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH, ductal carcinoma in situ (DCIS and invasive breast cancer (IBC. Methods Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.

  16. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  17. Proteomic Analysis of Stage-II Breast Cancer from Formalin-Fixed Paraffin-Embedded Tissues

    Directory of Open Access Journals (Sweden)

    Naif Abdullah Al-Dhabi

    2016-01-01

    Full Text Available Breast cancer is the most frequently occurring disease among women worldwide. The early stage of breast cancer identification is the key challenge in cancer control and prevention procedures. Although gene expression profiling helps to understand the molecular mechanism of diseases or disorder in the living system, gene expression pattern alone is not sufficient to predict the exact mechanisms. Current proteomics tools hold great application for analysis of cancerous conditions. Hence, the generation of differential protein expression profiles has been optimized for breast cancer and normal tissue samples in our organization. Normal and tumor tissues were collected from 20 people from a local hospital. Proteins from the diseased and normal tissues have been investigated by 2D gel electrophoresis and MALDI-TOF-MS. The peptide mass fingerprint data were fed into various public domains like Mascot, MS-Fit, and Pept-ident against Swiss-Prot protein database and the proteins of interest were identified. Some of the differentially expressed proteins identified were human annexin, glutathione S-transferase, vimentin, enolase-1, dihydrolipoamide dehydrogenase, glutamate dehydrogenase, Cyclin A1, hormone sensitive lipase, beta catenin, and so forth. Many types of proteins were identified as fundamental steps for developing molecular markers for diagnosis of human breast cancer as well as making a new proteomic database for future research.

  18. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  19. TGF β1 expression and angiogenesis in colorectal cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Bin Xiong; Ling-Ling Gong; Feng Zhang; Ming-Bo Hu; Hong-Yin Yuan

    2002-01-01

    AIM: Transforming growth factor(TGF)β1 is involved in avariety of important cellular functions, including cell growthand differentiation, angiogenesis, immune function andextracellular matrix formation. However, the role of TGF β1as an angiogenic factor in colorectal cancer is still unclear.We investigate the relationship between transforming growthfactor β1 and angiogenesis by analyzing the expression oftransforming growth factor(TGF) β1 in colorectal cancer, aswell as its association with VEGF and MVDMETHODS: The expression of TGF β1 、VEGF, as well as MVDwere detected in 98 colorectal cancer by immunohistochemicalstaining. The relationship between the TGF β1 expression andVEGF expression、MVD was evaluated. To evaluate the effect ofTGF β1 on the angiogenesis of colorectal cancers.RESULTS: Among 98 cases of colorectal cancer, 37 werepositive for TGF β1 (37. 8 %),36 for VEGF(36. 7 %),respectively. The microvessel counts ranged from 19 to 139.8, with a mean of 48.7 (standard deviation, 21. 8). Theexpression of TGF β1 was correlated significantly with thedepth of invasion, stage of disease, lymph nodemetastasis, VEGF expression and MVD. Patients in T3-T4,stage Ⅲ-Ⅳ and with lymph node metastasis had muchhigher expression of TGF β1 than patients in T1-T2, stage Ⅰ -Ⅱ and without lymph node metastasis ( P < 0.05).Thepositive expression rate of VEGF (58.3 %) in the TGF-β1positive group is higher than that in the TGF-β1 negativegroup(41.7 %, P< 0.05). Also, the microvessel count (54+ 18) in TGF-β1 positive group is significantly highar thanthat in TGF-β1 negative group (46 + 15, P < 0.05 ). Themicrovessel count in tumors with both TGF-β1 and VEGFpositive were the highest (58 + 20, 36-140, P < 0. 05 ).Whereas that in tumors with both TGF-β1 and VEGF negativewere the lowest (38+ 16, 19-60, P<0.05).CONCLUSION: TGF β1 might be associated with tumorprogression by madulating the angiogenesis in colorectalcancer and TGF β1 may be used as a

  20. Delivery of Encapsulated Drugs to Cancer Cells and Tissue: The Impact of Ultrasound

    OpenAIRE

    Afadzi, Mercy

    2013-01-01

    Encapsulated drugs have improved tumor to normal tissue uptake compared to free drugs, however, the concentration of drugs at the tumor site is still low and heterogeneous due to the tumor microenvironment which serves as barriers for the delivery to the target site. Combining ultrasound (US) with encapsulated drugs might enhance the transport of the encapsulated drug across the vasculature and into tumor tissues. US can also increase local drug release and the uptake of the drug into cancer ...

  1. Contribution of epigenetic mechanisms to variation in cancer risk among tissues

    Science.gov (United States)

    Klutstein, Michael; Moss, Joshua; Kaplan, Tommy; Cedar, Howard

    2017-01-01

    Recently, it was suggested that tissue variation in cancer risk originates from differences in the number of stem-cell divisions underlying each tissue, leading to different mutation loads. We show that this variation is also correlated with the degree of aberrant CpG island DNA methylation in normal cells. Methylation accumulates during aging in a subset of molecules, suggesting that the epigenetic landscape within a founder-cell population may contribute to tumor formation. PMID:28193856

  2. EXPRESSION AND SIGNIFICANCE OF SURVIVIN mRNA IN LUNG CANCER TISSUE MICROARRAY DETECTED BY FISH

    Institute of Scientific and Technical Information of China (English)

    Xin-yun Wang; Xing-ye Wu; Zhi Yao; Yan Li; Ting Liu; Hai-yan Zheng; Cong-zhong Zhu; Cui-yun Sun; Ai-xiang Wang; Min Zhao

    2005-01-01

    Objective To investigate the expression of Survivin mRNA in lung cancer tissue microarray (TMA) by fluorescence in situ hybridization (FISH) method, and determine the role and significance of it in lung cancer genesis and progress. Methods The expression of Survivin mRNA was detected by FISH method and TMA technology. Fifty-four cases of lung cancer and 10 cases of normal lung tissue were examined. Results Survivin mRNA was expressed in 66.7% (36/54) of lung cancer; the positive ratio of lung cancer was significantly higher than that of normal lung tissue (0/10; x2= 15.238, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in poor differentiated cancer (20/24, 83.3%) than moderate and well differentiated cancer (16/30, 53.3%; x2= 5.40, P <0.05). The positive ratio of Survivin mRNA was significantly higher in group with lymph node metastasis (27/32, 84.4%) than without lymph node metastasis (9/22, 40.9%; x2= 11.084, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in stage Ⅲ-Ⅳ(12/13, 92.3%) than stage Ⅰ - Ⅱ (24/41, 58.5%; x2= 5.066, P < 0.05). Conclusion Survivin mRNA highly expresses in lung cancer, which is related to the progress and malignant behavior. Survivin may play a promoting role in lung cancer genesis and progress and provide a basis for estimating prognosis and treatment.

  3. Optimum 3D Matrix Stiffness for Maintenance of Cancer Stem Cells Is Dependent on Tissue Origin of Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Esmaiel Jabbari

    Full Text Available The growth and expression of cancer stem cells (CSCs depend on many factors in the tumor microenvironment. The objective of this work was to investigate the effect of cancer cells' tissue origin on the optimum matrix stiffness for CSC growth and marker expression in a model polyethylene glycol diacrylate (PEGDA hydrogel without the interference of other factors in the microenvironment.Human MCF7 and MDA-MB-231 breast carcinoma, HCT116 colorectal and AGS gastric carcinoma, and U2OS osteosarcoma cells were used. The cells were encapsulated in PEGDA gels with compressive moduli in the 2-70 kPa range and optimized cell seeding density of 0.6x106 cells/mL. Micropatterning was used to optimize the growth of encapsulated cells with respect to average tumorsphere size. The CSC sub-population of the encapsulated cells was characterized by cell number, tumorsphere size and number density, and mRNA expression of CSC markers.The optimum matrix stiffness for growth and marker expression of CSC sub-population of cancer cells was 5 kPa for breast MCF7 and MDA231, 25 kPa for colorectal HCT116 and gastric AGS, and 50 kPa for bone U2OS cells. Conjugation of a CD44 binding peptide to the gel stopped tumorsphere formation by cancer cells from different tissue origin. The expression of YAP/TAZ transcription factors by the encapsulated cancer cells was highest at the optimum stiffness indicating a link between the Hippo transducers and CSC growth. The optimum average tumorsphere size for CSC growth and marker expression was 50 μm.The marker expression results suggest that the CSC sub-population of cancer cells resides within a niche with optimum stiffness which depends on the cancer cells' tissue origin.

  4. Bioluminescence-activated deep-tissue photodynamic therapy of cancer.

    Science.gov (United States)

    Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

    2015-01-01

    Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.

  5. Breast Cancer and Estrogen Biosynthesis in Adipose Tissue

    Science.gov (United States)

    1998-10-01

    displaced inconspicuous nuclei (Fig. 1). Fibroblasts, on the other hand, are spindly cells with eosinophilic cytoplasms and dark and elongated nuclei...pre-ovulatory stage. During this stage, increasing stimulation of cAMP by FSH elevates expression of CYP19, CYP11A (P450scc) and LH receptor in granu ...aromatase expression occurs in a number of human tissues and cell types, including the syncytiotrophoblast of the placenta (13), ovarian granu - losa

  6. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    ALG-2 was isolated in a screen for proteins involved in programmed cell death and is the first Ca(2+)-binding protein found to be directly involved in apoptosis. We have generated polyclonal antibodies that are suitable for detecting ALG-2 using different immunological methods. Three commercial......, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...

  7. The importance of tissue environment surrounding the tumor on the development of cancer cachexia.

    Science.gov (United States)

    Chiba, Fumihiro; Soda, Kuniyasu; Yamada, Shigeki; Tokutake, Yuka; Chohnan, Shigeru; Konishi, Fumio; Rikiyama, Toshiki

    2014-01-01

    The relationship between host factors and cancer cachexia was investigated. A single cell clone (clone 5 tumor) established from colon 26 adenocarcinoma by limiting dilution cell cloning methods was employed to eliminate the inoculation site-dependent differences in the composition of cell clones. Clone 5 tumor did not provoke manifestations of cancer cachexia when inoculated in subcutaneous tissue. However, when inoculated in the gastrocnemius muscle, the peritoneal cavity or the thoracic cavity of CD2F1 male mice, typical manifestations of cancer cachexia were observed in all groups of mice with intergroup variations. The blood levels of various cytokines, chemokines and hormones were increased but with wide intergroup variations. Analyses by stepwise multiple regression models revealed that serum interleukin-10 was the most significant factor associated with manifestations of cancer cachexia, suggesting the possible involvement of mechanisms similar to cancer patients suffering cancer cachexia. White blood cells, especially neutrophils, seemed to have some roles on the induction of cancer cachexia, because massive infiltrations and an increase in peripheral blood were observed in cachectic mice bearing clone 5 tumors. The amount of malonyl-CoA in liver correlated with manifestations of cancer cachexia, however the mRNA levels of spermidine/spermine N-1 acetyl transferase (SSAT) (of which overexpression has been shown to provoke manifestations similar to cancer cachexia) were not necessarily associated with cancer cachexia. These data suggest that the induction of cancer cachexia depends on the environment in which the tumor grows and that the infiltration of host immune cells into the tumor and the resultant increase in inflammation result in the production of cachectic factors, such as cytokines, leading to SSAT activation. Further, multiple factors likely mediate the mechanisms of cancer cachexia. Finally, this animal model was suitable for the investigation

  8. The aluminium content of breast tissue taken from women with breast cancer.

    Science.gov (United States)

    House, Emily; Polwart, Anthony; Darbre, Philippa; Barr, Lester; Metaxas, George; Exley, Christopher

    2013-10-01

    The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content

  9. Concentration of Cd, Pb, Hg, and Se in Different Parts of Human Breast Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Mohammadi

    2014-01-01

    Full Text Available Breast cancer is the major cause of cancer morbidity and mortality between women in the world. Metals involved in environmental toxicology are closely related to tumor growth and cancer. On the other hand, some metals such as selenium have anticarcinogenic properties. The aim of this study is to determine the concentration of cadmium, lead, mercury, and selenium in separated parts of tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues which have been analyzed by graphite furnace atomic absorption (AA-670 and ICP-OES (ULTIMA 2CE. Our results show that Se and Hg have maximum and minimum concentration, respectively. Statistical analysis reveals no significant differences between metal accumulations in different parts of cancer tissues (P>0.05 and this observation might be due to the close relation of separated parts of fatty breast organ. Thus, we could conclude that a high level of these heavy metals is accumulated in Iranian cancerous breasts and their presence can be one of the reasons of cancer appearance.

  10. PUTATIVE ROLE OF ADIPOSE TISSUE IN GROWTH AND METABOLISM OF COLON CANCER CELLS

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    Betty eSchwartz

    2014-06-01

    Full Text Available Newly emerging data highlight obesity as an important risk factor for developing certain types of cancer, including colorectal cancer. Although evidence supports a link between the two, the mechanisms responsible for this relationship have not yet been fully elucidated. Hypertrophied and dysfunctional adipose tissue of the obese state is characterized by low-grade inflammation. Adipokines and cytokines secreted from adipocytes, together with the abundant availability of lipids from adipocytes in the tumor microenvironment, promote adhesion, migration, and invasion of tumor cells and support tumor progression and uncontrolled growth. One of the predisposed targets of the deleterious effects exerted by secretions from adipose tissue in obesity are the activities associated with the cellular mitochondria. Mitochondrial oxidative metabolism plays a key role in meeting cells' energetic demands by oxidative phosphorylation (OxPhos. Here we discuss: (a the dynamic relationship between glycolysis, the tricarboxylic acid (TCA cycle, and OxPhos; (b the evidence for impaired OxPhos (i.e. mitochondrial dysfunction in colon cancer; (c the mechanisms by which mitochondrial dysfunction can predispose to cancer. We propose that impaired OxPhos increases susceptibility to colon cancer since OxPhos is sensitive to a large number of factors that are intrinsic to the host (e.g. inflammation.Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities.

  11. EXPRESSION AND SIGNIFICANCE OF C-erbB-2 IN THE TISSUES OF LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To elucidate the expression and clinical significance of C-erbB-2 in the tissue of lung cancer. Methods Immunohistochemistry method was used to detect the protein expression of C-erbB-2 in lung cancer tissue. Results The positive expression rate of C-erbB-2 protein in 38 cases of lung cancer was 53.3% (21/38),which was higher than those in lung benign control group (P<0. 001). The significant correlation were found between the protein level and tumor stage(r= +0. 64,P<0.02). The order was stage Ⅳ>stage Ⅲ >stage Ⅱ >stage Ⅰ . There was no correlation among protein expression of C-erbB-2 in various histological types of lung cancer (P>0.05 for all). Conclusion The positive expression rates of C-erbB-2 were significantly higher in lung cancer group than those in benign control group. There is significant correlation between C-erbB-2 expression and lung cancer stage. There is no correlation among protein expression of C-erbB-2 and histological types of lung cancer.

  12. Expression and significance of multidrug resistance gene in the colorectal cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Lu; Min-Hong Pang

    2015-01-01

    Objective:To explore the correlation of expressions of MDR1/P-gp and CerbB-2 in the colorectal cancer tissues and their clinical significance.Methods:A total of 86 colorectal cancer tissues specimens were included in the study. The immunohistochemical S-P method was used to detect the expressions of P-gp and CerbB-2, and their correlations were analyzed.Results:The positive rates of the expressions of MDR1/P-gp and CerbB-2 were 36% (31/86) and 28% (24/86), respectively. The positive expression rate of CerbB-2 in the colorectal cancer tissues at a clinical stage of III was significantly higher than that at stage I and II. The positive expression rates of MDR1/P-gp and CerbB-2 in the colorectal cancer tissues with axillary lymph node metastasis were significantly higher than those in the tissues without axillary lymph node metastasis. In the P-gp positive expression group, the positive rate of CerbB-2 was 75.5% (37/49), while the negative rate of CerbB-2 was 24.48% (12/49), and the difference was statistically significant (P<0.01). P-gp had a certain positive correlation with the positive expression rate of CerbB-2. Conclusions:P-gp and CerbB-2 play a certain role in the occurrence of multidrug resistance of colorectal cancer, and their expressions are correlated; therefore, the combination detection can provide an evidence for the chemotherapy choice of colorectal cancer.

  13. Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood, gallbladder cancer and surrounding tissue

    Institute of Scientific and Technical Information of China (English)

    Gang Liu; Hong Ren; Xue-Jun Sun; Jing-Sen Shi

    2007-01-01

    BACKGROUND:The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to deifne the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS:The numbers of CD4+and CD8+T-lymphocytes and NK cells were measured by lfow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS:The numbers of CD4+and CD8+T-cells and NK cells in gallbladder cancer tissues were signiifcantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4+/CD8+was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4+ and CD8+ T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were signiifcantly different. CONCLUSIONS:Disproportionate and imbalanced distri-bution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4+, CD8+and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.

  14. Expression and Clinical Significance of SHP2 in the Tumor Tissues of Smokers with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xuemei ZHAN

    2010-09-01

    Full Text Available Background and objective It has been proved that protein phosphorylation and dephosphorylation were important mechanisms in lung cancer development, and tobacco smoking is an important risk factor of lung cancer. The aim of this study is to investigate the expression and clinical significance of protein tyrosine phosphatase SHP2 in non-small cell lung cancer (NSCLC and small cell lung cancer (SCLC; the relationship between tobacco smoking and the expression of SHP2 is also studied. Methods Immunohistochemistry (Invision and fluorescence in situ hybridization (FISH were used to detect the expression of SHP2 and the augment of SHP2 mRNA in the 53 lung cancer specimens. Results The weak positive rate of SHP2 was 80% (which was also the total positive rate in normal bronchial epithelium. The weak, moderate and strong positive rates were 35.4%, 43.8% and 6.2% (total positive rate was 85.4% in 48 NSCLC patients, 0%, 80% and 20% (total positve rate was 100% in 5 SCLC patients, 40.7%, 37.4% and 3.7% (total positive rate was 81.5% in the tumor tissues of 27 NSCLC patients who didn’t smoke and 23.8%, 71.4% and 4.7% (total positive rate was 100% in the tumor tissues of 21 NSCLC patients whose smoking indexes were ≥400. Significant differences of SHP2 expression were observed between tumor tissues and normal bronchial epithelium, NSCLC and SCLC, and between different smoking indexes (P < 0.05. Conclusion The enhancement of SHP2 expression in the tumor tissues of NSCLC patients who smoke may be correlated with tobacco smoking; SHP2 may play certain role in the development of lung cancer; SHP2 prospectively provides new ideas for the drug research and development of lung cancer treatment.

  15. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  16. Proteomic analysis of tissue samples in translational breast cancer research

    DEFF Research Database (Denmark)

    Gromov, Pavel; Moreira, José; Gromova, Irina

    2014-01-01

    , and both prognosis and prediction of outcome of chemotherapy. The purpose of this review is to critically appraise what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate......In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis...

  17. Tissue temperature distribution measurement by MRI and laser immunology for cancer treatment

    Science.gov (United States)

    Chen, Yichao; Gnyawali, Surya C.; Wu, Feng; Liu, Hong; Tesiram, Yasvir A.; Abbott, Andrew; Towner, Rheal A.; Chen, Wei R.

    2007-02-01

    In cancer treatment and immune response enhancement research, Magnetic Resonance Imaging (MRI) is an ideal method for non-invasive, three-dimensional temperature measurement. We used a 7.1-Tesla magnetic resonance imager for ex vivo tissues and small animal to determine temperature distribution of target tissue during laser irradiation. The feasibility of imaging is approved with high spatial resolution and high signal-noise- ratio. Tissue-simulating gel phantom gel, biological tissues, and tumor-bearing animals were used in the experiments for laser treatment and MR imaging. Thermal couple measurement of temperature in target samples was used for system calibration. An 805-nm laser was used to irradiate the samples with a laser power in the range of 1 to 2.5 watts. Using the MRI system and a specially developed processing algorithm, a clear temperature distribution matrix in the target tissue and surrounding tissue was obtained. The temperature profiles show that the selective laser photothermal effect could result in tissue temperature elevation in a range of 10 to 45 °C. The temperature resolution of the measurement was about 0.37°C including the total system error. The spatial resolution was 0.4 mm (128x128 pixels with field of view of 5.5x5.5 cm). The temperature distribution provided in vivo thermal information and future reference for optimizing dye concentration and irradiation parameters to achieve optimal thermal effects in cancer treatment.

  18. Evaluation of tissue and urinary survivin expression in non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    S. Sharaf

    2012-12-01

    Conclusion: Urinary survivin is a useful marker for non-invasive detection of non-muscle-invasive bladder cancer recurrence. Its detection is better using ELISA technique than WB and there is no correlation between its expression in tissue and urine.

  19. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

    DEFF Research Database (Denmark)

    Holten Andersen, MN; Brunner, N; Nielsen, HJ;

    2006-01-01

    Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  20. Tissue inhibitor of metalloproteinases-1 as a biological marker ?in colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Louise; Ladelund, Steen; Brünner, Nils Aage;

    2013-01-01

    At present plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) is undergoing validation as a biological marker in colorectal cancer (CRC). The clinical implementation of plasma TIMP-1 in prognosis, prediction, screening and monitoring CRC requires robust information as to the influence...

  1. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Mads Nikolaj; Brünner, Nils; Nielsen, Hans Jørgen;

    2006-01-01

    AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  2. Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Berckmans, R.J.; Böing, A.N.; Sturk, A.; Büller, H.R.; Kamphuisen, P.W.; Nieuwland, R.

    2012-01-01

    Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-e

  3. TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

    NARCIS (Netherlands)

    MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

    1993-01-01

    The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

  4. Identification of potential prognostic markers for vulvar cancer using immunohistochemical staining of tissue microarrays.

    NARCIS (Netherlands)

    Fons, G.; Burger, M.P.; Kate, F.J. ten; Velden, J. van der

    2007-01-01

    The aim of this study is to determine immunohistochemical markers with prognostic significance for disease-specific survival in patients with squamous cell cancer of the vulva. The study material consisted of slides and paraffin blocks of 50 vulvectomy specimens. A tissue microarray was constructed

  5. Significance of differential metal loads in normal versus cancerous cadaver tissues - biomed 2010.

    Science.gov (United States)

    Farah, Ibrahim O; Trimble, Quannesha; Ndebele, Kenneth; Mawson, Anthony

    2010-01-01

    The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life. To this end the etiology of diseases including cancer has been linked with the accumulation of potentially toxic or nonessential trace metals. However, scarce literature / experimental evidence exist as a scientific proof that metal concentrations play important role in the etiology and development of cancer phenotypes. The aim of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans. The originated hypothesis was that elemental / metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans. This study also establishes critical elemental /metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast and liver tissues used in this study were obtained from US Biomax Company. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). This equipment was utilized to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Twelve major elements of Al, Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Se, Sr, and Zn were found to be significantly different in term of their

  6. Breast tissue and breast cancer risk in abnormal secernation

    Directory of Open Access Journals (Sweden)

    G. Kh. Khanafiev

    2014-01-01

    Full Text Available From 122 of women with aseptic discharge from breast milk glands in 42.6 % of the cases in history was celebrated mastitis or postpartum lactostasis (25.4 %. Study the contents of the bile ducts, the state of periductale tissue of mammary glands of these women showed that a high titer of bacterial invasion was typical for women in the age of 35–55 years as among parous (10.7 %, and in nulliparous (8.2 %. The proliferating epithelium in the ducts is more marked in women who have had an abortion (4.9 % and parous women of reproductive age (4.1 %. For сецернирующих of mammary glands is more characteristic of differentiation on the grounds of proliferation and autoimmunisacion. Cistic-advanced ducts, as a source of excessive hormone concentrations, leading to displastic processes of the walls of the cystic formations and periductale tissue, is an indication for the beginning of the immediate treatment of the patient.

  7. Androgen receptor isoforms in human prostatic cancer tissue and LNCaP cell line

    Institute of Scientific and Technical Information of China (English)

    Shu-Jie XIA; Xiao-Da TANG; Qing-Zheng MA

    2001-01-01

    Aim: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaP cell line. Methods: With high resolution isoelectric focusing (IEF) method we demonstrated the different expressions of AR isoforms in human prostatic cancer tissues and LNCaP cell line. Results: Data were obtained from three prostatic cancer specimens and the LNCaP cell line. Three types of AR isoforms were detected with pI values at 6.5,6.0, and 5.3. For the 3 prostatic cancer specimens, 1 sample showed all the three types of AR isoforms, the second specimen expressed at 6.5 and 6.0, and the third failed to show any type of isoforms. The LNCaP cell line expressed all the three AR isoforms. Binding of 3H-dihydrotestosterone (3H-DHT) to these three isoforms was inhibited by the addition ofl00-fold excess of DHT or testosterone, while not by progesterone, oestradiol and diethylstilboestrol. Conclusion: The expression of AR isofonns is different in different prostate cancer tissues, which may be related to the difference in the effect of anti-androgen therapy in different patients.

  8. Analysis of differentially expressed proteins in cancerous and normal colonic tissues

    Institute of Scientific and Technical Information of China (English)

    Lay-Harn Gam; Chiuan-Herng Leow; Che Nin Man; Boon-Hui Gooi; Manjit Singh

    2006-01-01

    AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.METHODS: Colon tissues (normal and cancerous)were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

  9. Effect of implant vs. tissue reconstruction on cancer specific survival varies by axillary lymph node status in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Qian Ouyang

    Full Text Available To compare the breast cancer-specific survival (BCSS between patients who underwent tissue or implant reconstruction after mastectomy.We used the database from Surveillance, Epidemiology, and End Results (SEER registries and compared the BCSS between patients who underwent tissue and implant reconstruction after mastectomy. Cox-regression models were fitted, adjusting for known clinicopathological features. The interaction between the reconstruction types (tissue/implant and nodal status (N-stage was investigated.A total of 6,426 patients with a median age of 50 years were included. With a median follow up of 100 months, the 10-year cumulative BCSS and non-BCSS were 85.1% and 95.4%, respectively. Patients who underwent tissue reconstruction had tumors with a higher T-stage, N-stage, and tumor grade and tended to be ER/PR-negative compared to those who received implant reconstruction. In univariate analysis, implant-reconstruction was associated with a 2.4% increase (P = 0.003 in the BCSS compared with tissue-reconstruction. After adjusting for significant risk factors of the BCSS (suggested by univariate analysis and stratifying based on the N-stage, there was only an association between the reconstruction type and the BCSS for the N2-3 patients (10-year BCSS of implant vs. tissue-reconstruction: 68.7% and 59.0%, P = 0.004. The 10-year BCSS rates of implant vs. tissue-reconstruction were 91.7% and 91.8% in N0 patients (P>0.05 and 84.5% and 84.4% in N1 patients (P>0.05, respectively.The implant (vs. tissue reconstruction after mastectomy was associated with an improved BCSS in N2-3 breast cancer patients but not in N0-1 patients. A well-designed, prospective study is needed to further confirm these findings.

  10. Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients

    DEFF Research Database (Denmark)

    Heeran, Mel C; Høgdall, Claus K; Kjaer, Susanne K

    2012-01-01

    The primary objective of this study was to assess the expression of cyclin E in tumour tissues from 661 patients with epithelial ovarian tumours. The second was to evaluate whether cyclin E tissue expression levels correlate with clinico-pathological parameters and prognosis of the disease. Using...... tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut-off level for cyclin E......-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients....

  11. YKL-40 tissue expression and plasma levels in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Estrid V S; Ringsholt, Merete; Høgdall, Claus K;

    2009-01-01

    BACKGROUND: YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall...... survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. METHODS: YKL-40 protein expression was determined by immunohistochemistry...... in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. RESULTS: YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor...

  12. Protein profile study of breast cancer tissues using HPLC-LIF: a pilot study

    Science.gov (United States)

    Menon, Suraj; Sujatha; Kumar, K. Kalyan; Kurien, Jacob; Krishnanand, B. R.; Mahato, K. K.; George, Sajan D.; Kartha, V. B.; C, Santhosh

    2007-02-01

    Proteomics based techniques are rapidly emerging as alternative techniques to conventional histo-pathological methods for detection and diagnosis of cancers. Tumor markers are of considerable importance in the study of various cancers. A study of various changes in the protein profile associated with breast cancer will facilitate a better understanding of the various dynamic changes associated with the disease. In our study we have used High Performance Liquid Chromatography coupled with highly sensitive Laser Induced Fluorescence for recording the protein profiles of breast tissue homogenates. The protein profiles were recorded from pathologically certified normal as well as malignant breast tissue samples. The recorded protein profiles were studied by using Principal Component Analysis. Good discrimination of normal, benign and malignant samples was achieved in this pilot study.

  13. The tissue organization field theory of cancer: A testable replacement for the somatic mutation theory

    Science.gov (United States)

    Soto, Ana M.; Sonnenschein, Carlos

    2014-01-01

    The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell-based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue-based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context. PMID:21503935

  14. Detection of Slit2 promoter hypermethylation in tissue and serum samples from breast cancer patients.

    Science.gov (United States)

    Kim, Ga-Eon; Lee, Kyung Hwa; Choi, Yoo Duk; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan; Park, Min Ho; Yoon, Jung Han

    2011-10-01

    Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was investigated in 210 tissue samples (15 breast with no pathological findings, 26 DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific polymerase chain reaction. Immunohistochemical staining for Slit2 was also performed using tissue microarray blocks to determine whether Slit2 promoter hypermethylation correlated with loss of Slit2 expression. Slit2 promoter hypermethylation was not detected in breast tissue and serum samples from patients with no pathological findings. DCIS or IBC showed a statistically higher frequency of Slit2 promoter hypermethylation compared to breast with no pathological findings in both the tissue and serum samples; however, there were no statistically significant differences between DCIS and IBC samples. Similar Slit2 promoter hypermethylation patterns were seen in the tissue samples and corresponding serum specimens (p Slit2 promoter hypermethylation was associated with loss of Slit2 expression. These results suggest that Slit2 promoter hypermethylation appears to be responsible for functionally silencing Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible serum marker for early detection of breast cancer.

  15. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

  16. CALCIUM AND MAGNESIUM CONTENT IN CANCEROUS AND HEALTHY TISSUES OF GASTROINTESTINAL TRACT

    Directory of Open Access Journals (Sweden)

    Marta Głogowska

    2012-10-01

    Full Text Available Studies concerning concentration of biogenic metals in tissues of digestive system are sparse and diversified. The objectives of this study were to determine the mean concentration of biogenic metals: Mg and Ca, in cancerous and normal tissues of digestive system. Research was conducted on samples taken from different segments of human digestive tract. Tissues were taken during biopsy, surgery, and post-mortem from Military Hospital and PROSMED Health Center Patients’ located in Cracow. Samples were mineralized by wet digestion. First, they were dried and after dry mass were obtained the samples were put into digestion flasks and 1cm3 of nitric acid 65% was added to each of them. The samples were heated for about 2 hours, at 105°C. Mineralized material was moved to tubes with a capacity of 10 cm3 and filled with distilled water up to this volume. The resulting solutions were used to analyze the content of selected elements by FAAS method. The results are expressed in micrograms per gram of dry weight of tissue (µg•g-1d.m.. Average calcium content is higher in the tissues of the gastrointestinal tract of both healthy women (15890,28 µg•g-1d.m. and men (13040,24 µg•g-1d.m. in comparison with tumor tissues of the gastrointestinal tract of women (5365,19 µg•g-1 d.m. and men (2459,42 µg•g-1d.m.. Average magnesium content is higher in the tissues of the gastrointestinal tract of both healthy women (2887,19 µg•g-1 d.m. and men (1112,69 µg•g-1 d.m., in comparison with gastrointestinal cancerous tissues of women (1146,77 µg•g-1 d.m. and men (621,42 µg•g-1 d.m.. It was shown that differences between calcium and magnesium contents in the digestive tract tissues depend on the state of health - significantly higher contents of Ca and Mg were present in the tissues of healthy men and women in comparison to the tissues of men and women with digestive tract cancer. Magnesium and calcium have protective properties (they prevent the

  17. Soft tissue metastases from differentiated thyroid cancer diagnosed by {sup 18}F FDG PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Califano, Ines; Quildrian, Sergio; Otero, Jose; Coduti, Martin; Califano, Leonardo; Rojas Bilbao, Erica, E-mail: ines.m.califano@gmail.com [Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires (Argentina)

    2013-06-15

    Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases (STM) are extremely rare. We describe two cases of patients with differentiated thyroid cancer metastasizing to soft tissues. Both patients had widespread metastatic disease; clinically asymptomatic soft tissue metastases were found by 18-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET-CT), and confirmed by cytological and/or histopathological studies. These findings underscore the ability of {sup 18}F FDG PET-CT in accurately assessing the extent of the disease, as well as the utility of the method to evaluate regions of the body that are not routinely explored. (author)

  18. Statistical Analysis of Tissue Images for Detection and Classification of Cervical Cancer

    CERN Document Server

    Jagtap, Jaidip; Pandey, Kiran; Agarwa, Asha; Panigrahi, Prasanta K; Pradhan, Asima

    2011-01-01

    Cervical cancer is one of the major health threats in women worldwide. The current "gold standard" for detecting cancer of the epithelial tissue is the histopathology analysis of biopsy samples. However it relies on the pathologist's judgment of the disease. We investigate the utility of statistical parameters as a potential tool for detection and discrimination of the stages of dysplasia. Digital images of the tissue slides are captured with the help of a digital camera plugged to a microscope. Statistical data analysis is performed with the help of software to evaluate parameters such as mean, maxima, full width half maxima, skewness, kurtosis etc. for the images. We believe that these parameters can help effectively to improve the diagnosis and further classify normal and abnormal tissue sections. These parameters can be used independently as well as in tandem with other parameters as features in classification algorithms that involve the use of Neural networks or Principal component analysis.

  19. Hsp90 as a "Chaperone" of the Epigenome: Insights and Opportunities for Cancer Therapy.

    Science.gov (United States)

    Isaacs, Jennifer S

    2016-01-01

    The cellular functions of Hsp90 have historically been attributed to its ability to chaperone client proteins involved in signal transduction. Although numerous stimuli and the signaling cascades they activate contribute to cancer progression, many of these pathways ultimately require transcriptional effectors to elicit tumor-promoting effects. Despite this obvious connection, the majority of studies evaluating Hsp90 function in malignancy have focused upon its regulation of cytosolic client proteins, and particularly members of receptor and/or kinase families. However, in recent years, Hsp90 has emerged as a pivotal orchestrator of nuclear events. Discovery of an expanding repertoire of Hsp90 clients has illuminated a vital role for Hsp90 in overseeing nuclear events and influencing gene transcription. Hence, this chapter will cast a spotlight upon several regulatory themes involving Hsp90-dependent nuclear functions. Highlighted topics include a summary of chaperone-dependent regulation of key transcription factors (TFs) and epigenetic effectors in malignancy, as well as a discussion of how the complex interplay among a subset of these TFs and epigenetic regulators may generate feed-forward loops that further support cancer progression. This chapter will also highlight less recognized indirect mechanisms whereby Hsp90-supported signaling may impinge upon epigenetic regulation. Finally, the relevance of these nuclear events is discussed within the framework of Hsp90's capacity to enable phenotypic variation and drug resistance. These newly acquired insights expanding our understanding of Hsp90 function support the collective notion that nuclear clients are major beneficiaries of Hsp90 action, and their impairment is likely responsible for many of the anticancer effects elicited by Hsp90-targeted approaches.

  20. Computerized prediction of breast cancer risk: comparison between the global and local bilateral mammographic tissue asymmetry

    Science.gov (United States)

    Wang, Xingwei; Lederman, Dror; Tan, Jun; Wang, Xiao Hui; Zheng, Bin

    2011-03-01

    We have developed and preliminarily tested a new breast cancer risk prediction model based on computerized bilateral mammographic tissue asymmetry. In this study, we investigated and compared the performance difference of our risk prediction model when the bilateral mammographic tissue asymmetrical features were extracted in two different methods namely (1) the entire breast area and (2) the mirror-matched local strips between the left and right breast. A testing dataset including bilateral craniocaudal (CC) view images of 100 negative and 100 positive cases for developing breast abnormalities or cancer was selected from a large and diverse full-field digital mammography (FFDM) image database. To detect bilateral mammographic tissue asymmetry, a set of 20 initial "global" features were extracted from the entire breast areas of two bilateral mammograms in CC view and their differences were computed. Meanwhile, a pool of 16 local histogram-based statistic features was computed from eight mirror-matched strips between the left and right breast. Using a genetic algorithm (GA) to select optimal features, two artificial neural networks (ANN) were built to predict the risk of a test case developing cancer. Using the leave-one-case-out training and testing method, two GAoptimized ANNs yielded the areas under receiver operating characteristic (ROC) curves of 0.754+/-0.024 (using feature differences extracted from the entire breast area) and 0.726+/-0.026 (using the feature differences extracted from 8 pairs of local strips), respectively. The risk prediction model using either ANN is able to detect 58.3% (35/60) of cancer cases 6 to 18 months earlier at 80% specificity level. This study compared two methods to compute bilateral mammographic tissue asymmetry and demonstrated that bilateral mammographic tissue asymmetry was a useful breast cancer risk indicator with high discriminatory power.

  1. Differential expression of the UGT1A family of genes in stomach cancer tissues.

    Science.gov (United States)

    Cengiz, Beyhan; Yumrutas, Onder; Bozgeyik, Esra; Borazan, Ersin; Igci, Yusuf Ziya; Bozgeyik, Ibrahim; Oztuzcu, Serdar

    2015-08-01

    Uridine 5'-diphospho-glucuronosyltransferases (UGT) are the key players in the biotransformation of drugs, xenobiotics, and endogenous compounds. Particularly, UDP-glucuronosyltransferase 1A (UGT1A) participates in a wide range of biological and pharmacological processes and plays a critical role in the conjugation of endogenous and exogenous components. Thirteen alternative splicing products were produced from UGT1A gene locus designated as UGT1A1 and UGT1A3-10. A growing amount of evidence suggests that they have important roles in the carcinogenesis which is well documented by colon, liver, pancreas, and kidney cancer studies. Here, we report differential expressions of UGT1A genes in normal and tumor tissues of stomach cancer patients. Total numbers of 49 patients were enrolled for this study, and expression analysis of UGT1A genes was evaluated by the real-time PCR method. Accordingly, UGT1A1, UGT1A8, and UGT1A10 were found to be upregulated, and UGT1A3, UGT1A5, UGT1A7, and UGT1A9 were downregulated in stomach tumors. No expression changes were observed in UGT1A4. Also, UGT1A6 transcription variants were significantly upregulated in stomach cancer tissues compared to normal stomach tissue. Additionally, UGT1A7 gene showed highest expression in both normal and tumoral tissues, and interestingly, UGT1A7 gene expression was significantly reduced in stage II patients as compared to other patients. In conclusion, UGT1A genes are differentially expressed in normal and tumoral stomach tissues and expression changes of these genes may affect the development and progression of various types of cancer including the cancer of the stomach.

  2. Ex-vivo evaluation of gene therapy vectors in human pancreatic (cancer) tissue slices

    Institute of Scientific and Technical Information of China (English)

    Michael A van Geer; Koert FD Kuhlmann; Conny T Bakker; Fibo JW ten Kate; Ronald PJ Oude Elferink; Piter J Bosma

    2009-01-01

    AIM: To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions.METHODS: Human pancreatic tissue samples (malignant and normal) were obtained from surgical specimens and processed immediately to tissue slices.Tissue slices were cultured ex vivo for 1-6 d in an incubator using 95% O2. Slices were subsequently analyzed for viability and morphology. In addition the slices were incubated with different viral vectors expressing the repor ter genes GFP or DsRed.Expression of these reporter genes was measured at 72 h after infection.RESULTS: With the Krumdieck tissue slicer, uniform slices could be generated from pancreatic tissue but only upon embedding the tissue in 3% low melting agarose. Immunohistological examination showed the presence of all pancreatic cell types. Pancreatic normal and cancer tissue slices could be cultured for up to 6 d, while retaining viability and a moderate to good morphology. Reporter gene expression indicated that the slices could be infected and transduced efficiently by adenoviral vectors and by adeno associated viral vectors, whereas transduction with lentiviral vectors was limited. For the adenoviral vector, the transduction seemed limited to the peripheral layers of the explants.CONCLUSION: The presented sys tem al lows reproducible processing of minimal amounts of pancreatic tissue into slices uniform in size, suitable for pre-clinical evaluation of gene therapy vectors.

  3. Using endografts from superelastic titanium-nickelid-based alloy singular tissue plural tissues in organ-preserving surgery of laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kulbakin, D. E., E-mail: kulbakin-d@mail.ru [Tomsk Cancer Research Institute, 5 Kooperativny Street, Tomsk, 634050 (Russian Federation); Tomsk State University, 36, Lenin Avenue, Tomsk, 634050 (Russian Federation); Mukhamedov, M. R., E-mail: muhamedov@oncology.tomsk.ru [Tomsk Cancer Research Institute, 5 Kooperativny Street, Tomsk, 634050 (Russian Federation); Siberian State Medical University, 2, Moscow Highway, Tomsk, 634050 (Russian Federation); Choynzonov, E. L., E-mail: choynzonov@gmail.com [Tomsk Cancer Research Institute, 5 Kooperativny Street, Tomsk, 634050 (Russian Federation); Siberian State Medical University, 2, Moscow Highway, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, 30, Lenin Avenue, Tomsk, 634050 (Russian Federation); Gynter, V. E., E-mail: tc77@rec.tsu.ru [Tomsk State University, 36, Lenin Avenue, Tomsk, 634050 (Russian Federation); Research Institute of Medical Materials, 17, 19 Gv. Divizii, Tomsk, 634034 (Russian Federation)

    2015-11-17

    Our study has demonstrated feasibility of performing larynx preservation surgeries in patients with recurrent laryngeal cancer after failure of radiotherapy. The technique of combined laryngeal reconstruction with endografts from superelastic titanium-nickelid-based alloy Singular tissue Plural tissues results in improvement of life quality by preserving laryngeal functions.

  4. SU-E-J-31: Biodynamic Imaging of Cancer Tissue and Response to Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nolte, D; Turek, J; Childress, M; An, R; Merrill, D [Purdue University, West Lafayette, IN (United States); Matei, D [Indiana University School of Medicine, Indianapolis, IN (United States)

    2014-06-01

    Purpose: To measure intracellular motions inside three-dimensional living cancer tissue samples to establish a novel set of biodynamic biomarkers that assess tissue proliferative activity and sensitivity or resistance to chemotherapy. Methods: Biodynamic imaging (BDI) uses digital holography with low-coherence low-intensity light illumination to construct 3D holograms from depths up to a millimeter deep inside cancer tissue models that include multicellular tumor spheroids and ex vivo cancer biopsies from canine non-Hodgkins lymphoma and epithelial ovarian cancer (EOC) mouse explants. Intracellular motions modulate the holographic intensity with frequencies related to the Doppler effect caused by the motions of a wide variety of intracellular components. These motions are affected by applied therapeutic agents, and BDI produces unique fingerprints of the action of specific drugs on the motions in specific cell types. In this study, chemotherapeutic agents (doxorubicin for canine lymphoma and oxoplatin for ovarian) are applied to the living tissue models and monitored over 10 hours by BDI. Results: Multicellular spheroids and patient biopsies are categorized as either sensitive or insensitive to applied therapeutics depending on the intracellular Doppler signatures of chemotherapy response. For both lymphoma and EOC there is strong specificity to the two types of sensitivities, with sensitive cell lines and biopsies exhibiting a global cessation of proliferation and strong suppression of metabolic activity, while insensitive cell lines and biopsies show moderate activation of Doppler frequencies associated with membrane processes and possible membrane trafficking. Conclusion: This work supports the hypothesis that biodynamic biomarkers from three-dimensional living tumor tissue, that includes tissue heterogeneity and measured within 24 hours of surgery, is predictive of near-term patient response to therapy. Future work will correlate biodynamic biomarkers with

  5. Evaluating the Potential of Adipose Tissue-Derived MSCs as Anticancer Gene Delivery Vehicles to Bone-Metastasized Prostate Cancer

    Science.gov (United States)

    2012-10-01

    potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 2009;11(3):289-98. PMID:19308770. 5: Zhao M, Sachs PC, Wang...Park H, Lim EH, Lee KW. Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int J...JH, Shin JW, Lee KW. Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional

  6. Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the euramic study

    NARCIS (Netherlands)

    Simonsen, N.; Veer, P. van 't; Strain, J.J.; Martin-Moreno, J.M.; Huttunen, J.K.; Navajas, J.F.-C.; Martin, B.C.; Thamm, M.; Kardinaal, A.F.M.; Kok, F.J.; Kohlmeier, L.

    1998-01-01

    The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fa

  7. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Alan eDal Pra

    2016-02-01

    Full Text Available Radiation therapy (RT is one of the mainstay treatments for prostate cancer (PCa. The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: I. androgen signaling pathway; II. hypoxic tumor cells and regions; III. DNA damage response (DDR pathway; and IV. abnormal extra/intra-cell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa.

  8. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice.

    Science.gov (United States)

    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

  9. Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.

    Science.gov (United States)

    Schummer, Michèl; Green, Ann; Beatty, J David; Karlan, Beth Y; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-02-09

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.

  10. Mining the epigenetic landscape of tissue polarity in search of new targets for cancer therapy.

    Science.gov (United States)

    Atrian, Farzaneh; Lelièvre, Sophie A

    2015-01-01

    The epigenetic nature of cancer encourages the development of inhibitors of epigenetic pathways. Yet, the clinical use for solid tumors of approved epigenetic drugs is meager. We argue that this situation might improve upon understanding the coinfluence between epigenetic pathways and tissue architecture. We present emerging information on the epigenetic control of the polarity axis, a central feature of epithelial architecture created by the orderly distribution of multiprotein complexes at cell-cell and cell-extracellular matrix contacts and altered upon cancer onset (with apical polarity loss), invasive progression (with basolateral polarity loss) and metastatic development (with basoapical polarity imbalance). This information combined with the impact of polarity-related proteins on epigenetic mechanisms of cancer enables us to envision how to guide the choice of drugs specific for distinct epigenetic modifiers, in order to halt cancer development and counter the consequences of polarity alterations.

  11. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  12. Human breast biomonitoring and environmental chemicals: use of breast tissues and fluids in breast cancer etiologic research.

    Science.gov (United States)

    LaKind, Judy S; Wilkins, Amy A; Bates, Michael N

    2007-09-01

    Extensive research indicates that the etiology of breast cancer is complex and multifactorial and may include environmental risk factors. Breast cancer etiology and exposure to xenobiotic compounds, diet, electromagnetic fields, and lifestyle have been the subject of numerous scientific inquiries, but research has yielded inconsistent results. Biomonitoring has been used to explore associations between breast cancer and levels of environmental chemicals in the breast. Research using breast tissues and fluids to cast light on the etiology of breast cancer is, for the most part, predicated on the assumption that the tissue or fluid samples either contain measurable traces of the environmental agent(s) associated with the cancer or that they retain biological changes that are biomarkers of such exposure or precursors of carcinogenic effect. In this paper, we review breast cancer etiology research utilizing breast biomonitoring. We first provide a brief synopsis of the current state of understanding of associations between exposure to environmental chemicals and breast cancer etiology. We then describe the published breast cancer research on tissues and fluids, which have been used for biomonitoring, specifically human milk and its components, malignant and benign breast tissue, nipple aspirate fluid (NAF) and breast cyst fluid. We conclude with a discussion on recommendations for biomonitoring of breast tissues and fluids in future breast cancer etiology research. Both human milk and NAF fluids, and the cells contained therein, hold promise for future biomonitoring research into breast cancer etiology, but must be conducted with carefully delineated hypotheses and a scientifically supportable epidemiological approach.

  13. The expression of HER-2/neu gene in colon cancer tissues and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Jing Jin; Yuxuan Che; Qimin Wang; Fang Liu; Man Li; Lifen Wang; Xiuhua Sun; Yang Zhang

    2013-01-01

    Objective:The article aims to detect the expression of HER-2/neu gene in colon cancer tissues and adjacent tissues, to analyze the relationship between dif erent pathologic types and clinical features, also to invest the distribution of patients with positive expression of HER-2 gene. Methods:The expression of HER-2 gene in the 223 samples with colon can-cer was detected by immunochemical approach. The expression of HER-2 gene in colon cancer tissues and adjacent tissues and dif erent pathologic types was analyzed byχ2 test. The correlation between the expression of HER-2 gene and clinical features was analyzed by Spearman. Results:The number of positive expression of HER-2 gene in colon cancer tissues and adjacent tissues were 74 and 0 respectively, the dif erence has statistical significance. The number of papil ary or tubular adenocarcinoma was 182, among them, 60 cases were positive expression. The number of mucinous adenocarcinoma was 41, among them, 14 cases were positive expression. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, which has no statistical significance. However, the expression of HER-2/neu gene has correlation with metastasis of lymph node and Dukes stage, which has statistical significance. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The correlated coef icient index was 0.320 and 0.320 respectively. In the 74 patients with positive expression of HER-2 gene, 59.4%of them were 60-74 years old. And there was 97.3%of the patients without family history of adenocarcinoma. Conclusion:The expression of HER-2/neu gene in colon cancer tissues was higher than in adjacent tissues. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, but has correlation with metastasis of

  14. Fluorescence In Situ Hybridization for MicroRNA Detection in Archived Oral Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Zonggao Shi

    2012-01-01

    Full Text Available The noncoding RNA designated as microRNA (miRNA is a large group of small single-stranded regulatory RNA and has generated wide-spread interest in human disease studies. To facilitate delineating the role of microRNAs in cancer pathology, we sought to explore the feasibility of detecting microRNA expression in formalin-fixed paraffin-embedded (FFPE tissues. Using FFPE materials, we have compared fluorescent in situ hybridization (FISH procedures to detect miR-146a with (a different synthetic probes: regular custom DNA oligonucleotides versus locked nucleic acid (LNA incorporated DNA oligonucleotides; (b different reporters for the probes: biotin versus digoxigenin (DIG; (c different visualization: traditional versus tyramide signal amplification (TSA system; (d different blocking reagents for endogenous peroxidase. Finally, we performed miR-146a FISH on a commercially available oral cancer tissue microarray, which contains 40 cases of oral squamous cell carcinoma (OSCC and 10 cases of normal epithelia from the human oral cavity. A sample FISH protocol for detecting miR-146a is provided. In summary, we have established reliable in situ hybridization procedures for detecting the expression of microRNA in FFPE oral cancer tissues. This method is an important tool for studies on the involvement of microRNA in oral cancer pathology and may have potential prognostic or diagnostic value.

  15. Characterization of breast tissue composition and breast cancer risk assessment using non-invasive transillumination breast spectroscopy (TIBS)

    Science.gov (United States)

    Blackmore, Kristina M.; Weersink, Robert; Lilge, Lothar

    2005-09-01

    Tissue undergoing transformation into a state that is more favourable for tumor growth may present itself with different tissue optical properties and contain different amounts of the major tissue chromophores. Here, we decomposed transillumination spectra obtain in women from various risk levels of developing breast cancer.

  16. Early Growth Response1and Fatty Acid Synthase Expression is Altered in Tumor Adjacent Prostate Tissue and Indicates Field Cancerization

    Science.gov (United States)

    Jones, Anna C.; Trujillo, Kristina A.; Phillips, Genevieve K.; Fleet, Trisha M.; Murton, Jaclyn K.; Severns, Virginia; Shah, Satyan K.; Davis, Michael S.; Smith, Anthony Y.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco

    2011-01-01

    BACKGROUND Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention. PMID:22127986

  17. The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk.

    Science.gov (United States)

    Chang, Wen-Shin; Liu, Liang-Chih; Hsiao, Chieh-Lun; Su, Chen-Hsien; Wang, Hwei-Chung; Ji, Hong-Xue; Tsai, Chia-Wen; Maa, Ming-Chei; Bau, Da-Tian

    2016-03-01

    The tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins which have been shown to be upregulated in various types of cancers. However, the contribution of TIMPs in breast cancer is not fully understood, not to mention triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of breast cancer, especially the subtype of TNBC. The contributions of these TIMP-1 genotypes to cancer risk were examined among 1232 breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP-1s, and the results showed that the C allele of TIMP-1 rs4898 contributes to an increase in breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker.

  18. Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early-stage cancer detection

    Science.gov (United States)

    Tate, Tyler H.; Baggett, Brenda; Rice, Photini F. S.; Koevary, Jennifer Watson; Orsinger, Gabriel V.; Nymeyer, Ariel C.; Welge, Weston A.; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth D.; Chambers, Setsuko K.; Utzinger, Urs; Barton, Jennifer Kehlet

    2016-05-01

    With early detection, 5-year survival rates for ovarian cancer exceed 90%, yet no effective early screening method exists. Emerging consensus suggests over 50% of the most lethal form of the disease originates in the fallopian tube. Twenty-eight women undergoing oophorectomy or debulking surgery provided informed consent for the use of surgical discard tissue samples for multispectral fluorescence imaging. Using multiple ultraviolet and visible excitation wavelengths and emissions bands, 12 fluorescence and 6 reflectance images of 47 ovarian and 31 fallopian tube tissue samples were recorded. After imaging, each sample was fixed, sectioned, and stained for pathological evaluation. Univariate logistic regression showed cancerous tissue samples had significantly lower intensity than noncancerous tissue for 17 image types. The predictive power of multiple image types was evaluated using multivariate logistic regression (MLR) and quadratic discriminant analysis (QDA). Two MLR models each using two image types had receiver operating characteristic curves with area under the curve exceeding 0.9. QDA determined 56 image type combinations with perfect resubstituting using as few as five image types. Adaption of the system for future in vivo fallopian tube and ovary endoscopic imaging is possible, which may enable sensitive detection of ovarian cancer with no exogenous contrast agents.

  19. Predominant expression of Th1-type cytokines in primary hepatic cancer and adjacent liver tissues

    Institute of Scientific and Technical Information of China (English)

    Fa-Bo Qiu; Li-Qun Wu; Yun Lu; Shun Zhang; Bing-Yuan Zhang

    2007-01-01

    BACKGROUND: Research has revealed a shift towards Th2 in many types of malignant tumor, but the state of Th1/Th2 is not clear in patients with primary hepatic cancer (PHC). This study was designed to determine the expression of Th1-versus Th2-type cytokines in primary hepatic cancer and the adjacent liver tissue in order to provide evidence for treatment of the Th1/Th2 shift. METHODS:Samples were collected from 11 patients with PHC. The gene expression of Th1/Th2 cytokines was detected by reverse transcriptase polymerase chain reaction (RT-PCR) using IFN-γ and IL-2 as Th1-type cytokine genes, and IL-4 and IL-10 as Th2-type cytokine genes. RESULTS: Th1-type cytokines were expressed in 7/11 PHCs and 9/11 adjacent liver tissues, while Th0 type cytokines occurred in 4/11 PHCs and 2/11 adjacent liver tissues. CONCLUSION: Th1-type cytokines are expressed predominantly in primary hepatic cancer and the adjacent liver tissue.

  20. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    Science.gov (United States)

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  1. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  2. Tissue pattern recognition error rates and tumor heterogeneity in gastric cancer.

    Science.gov (United States)

    Potts, Steven J; Huff, Sarah E; Lange, Holger; Zakharov, Vladislav; Eberhard, David A; Krueger, Joseph S; Hicks, David G; Young, George David; Johnson, Trevor; Whitney-Miller, Christa L

    2013-01-01

    The anatomic pathology discipline is slowly moving toward a digital workflow, where pathologists will evaluate whole-slide images on a computer monitor rather than glass slides through a microscope. One of the driving factors in this workflow is computer-assisted scoring, which depends on appropriate selection of regions of interest. With advances in tissue pattern recognition techniques, a more precise region of the tissue can be evaluated, no longer bound by the pathologist's patience in manually outlining target tissue areas. Pathologists use entire tissues from which to determine a score in a region of interest when making manual immunohistochemistry assessments. Tissue pattern recognition theoretically offers this same advantage; however, error rates exist in any tissue pattern recognition program, and these error rates contribute to errors in the overall score. To provide a real-world example of tissue pattern recognition, 11 HER2-stained upper gastrointestinal malignancies with high heterogeneity were evaluated. HER2 scoring of gastric cancer was chosen due to its increasing importance in gastrointestinal disease. A method is introduced for quantifying the error rates of tissue pattern recognition. The trade-off between fully sampling tumor with a given tissue pattern recognition error rate versus randomly sampling a limited number of fields of view with higher target accuracy was modeled with a Monte-Carlo simulation. Under most scenarios, stereological methods of sampling-limited fields of view outperformed whole-slide tissue pattern recognition approaches for accurate immunohistochemistry analysis. The importance of educating pathologists in the use of statistical sampling is discussed, along with the emerging role of hybrid whole-tissue imaging and stereological approaches.

  3. A low dimensional entropy-based descriptor of several tissues in skin cancer histopathology samples

    Science.gov (United States)

    Álvarez, Pablo; Corredor, Germán.; García-Arteaga, Juan D.; Romero, Eduardo

    2015-12-01

    The use of low-level visual features to assign high level labels in datasets of histopathology images is a possible solution to the problems derived from manual labeling by experts. However, in many cases, the visual cues are not enough. In this article we propose the use of features derived exclusively from the spatial distribution of the cell nuclei. These features are calculated using the weight of k-nn graphs constructed from the distances between cells. Results show that there are k values with enhanced discriminatory power, especially when comparing cancerous and non-cancerous tissue.

  4. Extracellular vesicles, tissue factor, cancer and thrombosis – discussion themes of the ISEV 2014 Educational Day

    Directory of Open Access Journals (Sweden)

    Chris Gardiner

    2015-03-01

    Full Text Available Although the association between cancer and venous thromboembolism (VTE has long been known, the mechanisms are poorly understood. Circulating tissue factor–bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV and International Society on Thrombosis and Haemostasis (ISTH held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed.

  5. Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

    DEFF Research Database (Denmark)

    Bjerre, Christina Annette; Knoop, Ann; Bjerre, Karsten;

    2013-01-01

    Background. The role of tissue inhibitor of metalloproteinases-1 (TIMP-1) in estrogen receptor (ER) positive breast cancer remains to be fully elucidated. We evaluated TIMP-1 as a prognostic marker in patients treated with adjuvant tamoxifen and investigated TIMP-1s association with Ki67 and ER...... = 0.48; OR 0.68; 95% CI 0.23-1.99). Conclusion. TIMP-1 does not appear to be prognostic in breast cancer patients receiving adjuvant tamoxifen. We identified a negative association between TIMP-1 and Ki67. We did not confirm our previous in vitro findings of a negative association between TIMP-1...

  6. Large-scale proteomic identification of S100 proteins in breast cancer tissues

    Directory of Open Access Journals (Sweden)

    Cancemi Patrizia

    2010-09-01

    Full Text Available Abstract Background Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. Methods Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing. Results The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. Conclusions This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis

  7. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yan

    2011-09-01

    Full Text Available Abstract Background Connective tissue growth factor (CTGF has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  8. Expressions of SEL 1L and C-erbB-2 in Gastric Cancer Tissues and Its Clinical Signiifcance

    Institute of Scientific and Technical Information of China (English)

    Xu Guanghui; Li Yu; Li Yan

    2014-01-01

    Objective: To investigate the expressions and clinical signiifcance of human sel-1-like (SEL 1L) gene and oncogene c-erbB-2 in gastric cancer tissue. Methods:SEL 1L and c-erbB-2 expressions in gastric cancer tissues of 96 patients with gastric cancer were detected by immunohistochemical method. Results: The positive expression rate of SEL 1L gene in gastric cancer tissue was 84.4% (81/96), and its expression was significantly associated with the differentiated degree of gastric cancer tissue (P=0.001), but had no association with the age, gender, tumor size, infiltration depth, lymphatic metastasis and TNM staging (P>0.05). The positive expression rate of c-erbB-2 was 70.8% (68/96), and its expression was related to the differentiated degree of gastric cancer tissue, inifltration depth, lymphatic metastasis and TNM staging (P=0.002,P0.05). SEL 1L and c-erbB-2 expressions had a signiifcantly positive correlation (r=0.568,P<0.01). Conclusion: Both SEL 1L and c-erbB-2 are highly expressed in gastric cancer tissues and their joint detection can be considered as a biomarker for identifying the high-risk patients with gastric cancer.

  9. Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis

    Directory of Open Access Journals (Sweden)

    Gabet Yankel

    2010-09-01

    Full Text Available Abstract Background Prostate cancer (PCa cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2. Results We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which Doxycycline (Dox treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1, proteolytic enzymes (MMP9, CST7, cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A, intracellular signaling molecules (DUSP1, SPHK1, RASD1 and transcription factors (Sox9, SNAI2, SMAD3 functioning in epithelium to mesenchyme transition (EMT, tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is

  10. A curated collection of tissue microarray images and clinical outcome data of prostate cancer patients

    Science.gov (United States)

    Zhong, Qing; Guo, Tiannan; Rechsteiner, Markus; Rüschoff, Jan H.; Rupp, Niels; Fankhauser, Christian; Saba, Karim; Mortezavi, Ashkan; Poyet, Cédric; Hermanns, Thomas; Zhu, Yi; Moch, Holger; Aebersold, Ruedi; Wild, Peter J.

    2017-01-01

    Microscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies. PMID:28291248

  11. Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression

    Science.gov (United States)

    Hendrickson, Whitney K.; Flavin, Richard; Kasperzyk, Julie L.; Fiorentino, Michelangelo; Fang, Fang; Lis, Rosina; Fiore, Christopher; Penney, Kathryn L.; Ma, Jing; Kantoff, Philip W.; Stampfer, Meir J.; Loda, Massimo; Mucci, Lorelei A.; Giovannucci, Edward

    2011-01-01

    Purpose Data suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies. Patients and Methods We examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI. Results Men whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression. Conclusion High VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression. PMID:21537045

  12. A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection

    Directory of Open Access Journals (Sweden)

    Van Neste Leander

    2012-06-01

    Full Text Available Abstract Background PSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence. Results An initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP. The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 μm can be used to detect methylation in a reliable manner. The age of FFPE-samples does have a negative impact on DNA quality and quantity. Conclusions The developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples.

  13. Regional spectroscopy of paraffin-embedded breast cancer tissue using pulsed terahertz transmission imaging

    Science.gov (United States)

    Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas

    2016-03-01

    This work seeks to obtain the properties of paraffin-embedded breast cancer tumor tissues using transmission imaging and spectroscopy. Formalin-fixed and paraffin-embedded breast tumors are first sectioned into slices of 20 μm and 30 μm and placed between two tsurupica slides. The slides are then scanned in a pulsed terahertz system using transmission imaging. The tissue regions in adjacent pathology section are compared to the transmission imaging scan in order to define a region of points over which to average the electrical properties results from the scan.

  14. Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy

    Science.gov (United States)

    Terentyuk, Georgy S.; Maslyakova, Galina N.; Suleymanova, Leyla V.; Khlebtsov, Nikolai G.; Khlebtsov, Boris N.; Akchurin, Garif G.; Maksimova, Irina L.; Tuchin, Valery V.

    2009-03-01

    We describe an application of plasmonic silica/gold nanoshells to produce a controllable laser hyperthermia in tissues with the aim of the enhancement of cancer photothermal therapy. Laser irradiation parameters are optimized on the basis of preliminary experimental studies using a test-tube phantom and laboratory rats. Temperature distributions on the animal skin surface at hypodermic and intramuscular injection of gold nanoparticle suspensions and affectations by the laser radiation are measured in vivo with a thermal imaging system. The results of temperature measurements are compared with tissue histology.

  15. CRISPRi and CRISPRa: New Functional Genomics Tools Provide Complementary Insights into Cancer Biology and Therapeutic Strategies | Office of Cancer Genomics

    Science.gov (United States)

    A central goal of research for targeted cancer therapy, or precision oncology, is to reveal the intrinsic vulnerabilities of cancer cells and exploit them as therapeutic targets. Examples of cancer cell vulnerabilities include driver oncogenes that are essential for the initiation and progression of cancer, or non-oncogene addictions resulting from the cancerous state of the cell. To identify vulnerabilities, scientists perform genetic “loss-of-function” and “gain-of-function” studies to better understand the roles of specific genes in cancer cells.

  16. Atomic Insight into the Altered O6-Methylguanine-DNA Methyltransferase Protein Architecture in Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Naveed Anjum Chikan

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT is one of the major DNA repair protein that counteracts the alkalyting agent-induced DNA damage by replacing O6-methylguanine (mutagenic lesion back to guanine, eventually suppressing the mismatch errors and double strand crosslinks. Exonic alterations in the form of nucleotide polymorphism may result in altered protein structure that in turn can lead to the loss of function. In the present study, we focused on the population feared for high exposure to alkylating agents owing to their typical and specialized dietary habits. To this end, gastric cancer patients pooled out from the population were selected for the mutational screening of a specific error prone region of MGMT gene. We found that nearly 40% of the studied neoplastic samples harbored missense mutation at codon151 resulting into Serine to Isoleucine variation. This variation resulted in bringing about the structural disorder, subsequently ensuing into a major stoichiometric variance in recognition domain, substrate binding and selectivity loop of the active site of the MGMT protein, as observed under virtual microscope of molecular dynamics simulation (MDS. The atomic insight into MGMT protein by computational approach showed a significant change in the intra molecular hydrogen bond pattern, thus leading to the observed structural anomalies. To further examine the mutational implications on regulatory plugs of MGMT that holds the protein in a DNA-Binding position, a MDS based analysis was carried out on, all known physically interacting amino acids essentially clustered into groups based on their position and function. The results generated by physical-functional clustering of protein indicated that the identified mutation in the vicinity of the active site of MGMT protein causes the local and global destabilization of a protein by either eliminating the stabilizing salt bridges in cluster C3, C4, and C5 or by locally destabilizing the

  17. Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Satoshi [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and σΛ, as well as the standard hole burning parameters (namely, γ and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (fΔμ) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between fΔμs in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the complete absence of

  18. Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Satoshi Matsuzaki

    2004-12-19

    Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and {sigma}{sub {lambda}}, as well as the standard hole burning parameters (namely, {gamma} and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (f{Delta}{mu}) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between f{Delta}{mu}s in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the

  19. Reduced expression of tissue factor pathway inhibitor-2 contributes to apoptosis and angiogenesis in cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhang Qiao

    2012-01-01

    Full Text Available Abstract Background Tissue factor pathway inhibitor-2 (TFPI-2 is an extracellular matrix associated broad-spectrum Kunitz-type serine proteinase inhibitor. Recently, down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers. Methods This study involved 12 normal cervical squamous epithelia, 48 cervical intraepithelial neoplasia (CIN, and 68 cervical cancer. The expression of TFPI-2, Ki-67 and vascular endothelial growth factor (VEGF were investigated by immunohistochemistry staining. The apoptolic index(AI was determined with an in situ end-labeling assay(TUNEL. And the marker of CD34 staining was used as an indicator of microvessel density (MVD. Results TFPI-2 expression has a decreasing trend with the progression of cervical cancer and was significantly correlated with FIGO stage, lymph node metastasis and HPV infection. In addition, there were significant positive correlations between the grading of TFPI-2 expression and AI(P = 0.004. In contrast, the expression of TFPI-2 and VEGF or MVD was negatively correlated (both p Conclusions The results suggested that the expression of TFPI-2 had a decreasing trend with tumor progression of cervical cancer. There was a close association between the expression of TFPI-2 and tumor cell apoptosis and angiogenesis in patients with cervical cancer. TFPI-2 may play an inhibitive role during the development of cervical cancer.

  20. Integrative Tissue-Specific Functional Annotations in the Human Genome Provide Novel Insights on Many Complex Traits and Improve Signal Prioritization in Genome Wide Association Studies

    Science.gov (United States)

    Wang, Qian; He, Beixin Julie; Zhao, Hongyu

    2016-01-01

    Extensive efforts have been made to understand genomic function through both experimental and computational approaches, yet proper annotation still remains challenging, especially in non-coding regions. In this manuscript, we introduce GenoSkyline, an unsupervised learning framework to predict tissue-specific functional regions through integrating high-throughput epigenetic annotations. GenoSkyline successfully identified a variety of non-coding regulatory machinery including enhancers, regulatory miRNA, and hypomethylated transposable elements in extensive case studies. Integrative analysis of GenoSkyline annotations and results from genome-wide association studies (GWAS) led to novel biological insights on the etiologies of a number of human complex traits. We also explored using tissue-specific functional annotations to prioritize GWAS signals and predict relevant tissue types for each risk locus. Brain and blood-specific annotations led to better prioritization performance for schizophrenia than standard GWAS p-values and non-tissue-specific annotations. As for coronary artery disease, heart-specific functional regions was highly enriched of GWAS signals, but previously identified risk loci were found to be most functional in other tissues, suggesting a substantial proportion of still undetected heart-related loci. In summary, GenoSkyline annotations can guide genetic studies at multiple resolutions and provide valuable insights in understanding complex diseases. GenoSkyline is available at http://genocanyon.med.yale.edu/GenoSkyline. PMID:27058395

  1. Integrative Tissue-Specific Functional Annotations in the Human Genome Provide Novel Insights on Many Complex Traits and Improve Signal Prioritization in Genome Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Qiongshi Lu

    2016-04-01

    Full Text Available Extensive efforts have been made to understand genomic function through both experimental and computational approaches, yet proper annotation still remains challenging, especially in non-coding regions. In this manuscript, we introduce GenoSkyline, an unsupervised learning framework to predict tissue-specific functional regions through integrating high-throughput epigenetic annotations. GenoSkyline successfully identified a variety of non-coding regulatory machinery including enhancers, regulatory miRNA, and hypomethylated transposable elements in extensive case studies. Integrative analysis of GenoSkyline annotations and results from genome-wide association studies (GWAS led to novel biological insights on the etiologies of a number of human complex traits. We also explored using tissue-specific functional annotations to prioritize GWAS signals and predict relevant tissue types for each risk locus. Brain and blood-specific annotations led to better prioritization performance for schizophrenia than standard GWAS p-values and non-tissue-specific annotations. As for coronary artery disease, heart-specific functional regions was highly enriched of GWAS signals, but previously identified risk loci were found to be most functional in other tissues, suggesting a substantial proportion of still undetected heart-related loci. In summary, GenoSkyline annotations can guide genetic studies at multiple resolutions and provide valuable insights in understanding complex diseases. GenoSkyline is available at http://genocanyon.med.yale.edu/GenoSkyline.

  2. Evaluation of algorithm methods for fluorescence spectra of cancerous and normal human tissues

    Science.gov (United States)

    Pu, Yang; Wang, Wubao; Alfano, Robert R.

    2016-03-01

    The paper focus on the various algorithms on to unravel the fluorescence spectra by unmixing methods to identify cancerous and normal human tissues from the measured fluorescence spectroscopy. The biochemical or morphologic changes that cause fluorescence spectra variations would appear earlier than the histological approach; therefore, fluorescence spectroscopy holds a great promise as clinical tool for diagnosing early stage of carcinomas and other deceases for in vivo use. The method can further identify tissue biomarkers by decomposing the spectral contributions of different fluorescent molecules of interest. In this work, we investigate the performance of blind source un-mixing methods (backward model) and spectral fitting approaches (forward model) in decomposing the contributions of key fluorescent molecules from the tissue mixture background when certain selected excitation wavelength is applied. Pairs of adenocarcinoma as well as normal tissues confirmed by pathologist were excited by selective wavelength of 340 nm. The emission spectra of resected fresh tissue were used to evaluate the relative changes of collagen, reduced nicotinamide adenine dinucleotide (NADH), and Flavin by various spectral un-mixing methods. Two categories of algorithms: forward methods and Blind Source Separation [such as Principal Component Analysis (PCA) and Independent Component Analysis (ICA), and Nonnegative Matrix Factorization (NMF)] will be introduced and evaluated. The purpose of the spectral analysis is to discard the redundant information which conceals the difference between these two types of tissues, but keep their diagnostically significance. The facts predicted by different methods were compared to the gold standard of histopathology. The results indicate that these key fluorophores within tissue, e.g. tryptophan, collagen, and NADH, and flavin, show differences of relative contents of fluorophores among different types of human cancer and normal tissues. The

  3. Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

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    Srivastava Mousami

    2012-11-01

    Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

  4. 3-Dimensional quantitative detection of nanoparticle content in biological tissue samples after local cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Rahn, Helene, E-mail: helene.rahn@gmail.com [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany); Alexiou, Christoph [ENT-Department, Section for Experimental Oncology and Nanomedicine (Else Kröner-Fresenius-Stiftungsprofessur), University Hospital Erlangen, Waldstraße 1, Erlangen 91054 (Germany); Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, Berlin 10587 (Germany); Odenbach, Stefan [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany)

    2014-06-01

    X-ray computed tomography is nowadays used for a wide range of applications in medicine, science and technology. X-ray microcomputed tomography (XµCT) follows the same principles used for conventional medical CT scanners, but improves the spatial resolution to a few micrometers. We present an example of an application of X-ray microtomography, a study of 3-dimensional biodistribution, as along with the quantification of nanoparticle content in tumoral tissue after minimally invasive cancer therapy. One of these minimal invasive cancer treatments is magnetic drug targeting, where the magnetic nanoparticles are used as controllable drug carriers. The quantification is based on a calibration of the XµCT-equipment. The developed calibration procedure of the X-ray-µCT-equipment is based on a phantom system which allows the discrimination between the various gray values of the data set. These phantoms consist of a biological tissue substitute and magnetic nanoparticles. The phantoms have been studied with XµCT and have been examined magnetically. The obtained gray values and nanoparticle concentration lead to a calibration curve. This curve can be applied to tomographic data sets. Accordingly, this calibration enables a voxel-wise assignment of gray values in the digital tomographic data set to nanoparticle content. Thus, the calibration procedure enables a 3-dimensional study of nanoparticle distribution as well as concentration. - Highlights: • Local cancer treatments are promising in reducing negative side effects occurring during conventional chemotherapy. • The nanoparticles play an important role in delivering drugs to the designated area during local cancer treatments as magnetic drug targeting. • We study the nanoparticles distribution in tumor tissue after magnetic drug targeting with X-ray computed tomography. • We achieved a 3-dimensional quantification of the nanoparticles content in tumor tissue out of digital tomographic data.

  5. Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores

    Directory of Open Access Journals (Sweden)

    Gugger Mathias

    2008-11-01

    Full Text Available Abstract Background Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection. Methods In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR. Results Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan® Low Density Arrays (16 invasive ductal carcinoma (IDC, 8 ductal carcinoma in situ (DCIS and 6 normal tissue, and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO, the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores

  6. Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology.

    Science.gov (United States)

    Lin, Mao Song; Huang, Jun Xing; Chen, Wei Chang; Zhang, Bao Feng; Fang, Jing; Zhou, Qiong; Hu, Ying; Gao, Heng Jun

    2011-11-01

    Although aberrations of peroxisome proliferator-activated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin-embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

  7. Label-free discrimination of normal and pulmonary cancer tissues using multiphoton fluorescence ratiometric microscopy

    Science.gov (United States)

    Wang, Chun-Chin; Wu, Ruei-Jr; Lin, Sung-Jan; Chen, Yang-Fang; Dong, Chen-Yuan

    2010-07-01

    We performed multiphoton excited autofluorescence and second harmonic generation microscopy for the distinction of normal, lung adenocarcinoma (LAC), and squamous cell carcinoma (SCC) specimens. In addition to morphological distinction, we derived quantitative metrics of cellular redox ratios for cancer discrimination. Specifically, the redox ratios of paired normal/SCC and normal/LAC specimens were found to be 0.53±0.05/0.41±0.06 and 0.56±0.02/0.35±0.06, respectively. The lower redox ratios in cancer specimens, indicating an increase in metabolic activity. These results show that the combination of morphological multiphoton imaging along with redox ratio indices can be used for the discrimination of normal and pulmonary cancer tissues.

  8. Deep learning for tissue microarray image-based outcome prediction in patients with colorectal cancer

    Science.gov (United States)

    Bychkov, Dmitrii; Turkki, Riku; Haglund, Caj; Linder, Nina; Lundin, Johan

    2016-03-01

    Recent advances in computer vision enable increasingly accurate automated pattern classification. In the current study we evaluate whether a convolutional neural network (CNN) can be trained to predict disease outcome in patients with colorectal cancer based on images of tumor tissue microarray samples. We compare the prognostic accuracy of CNN features extracted from the whole, unsegmented tissue microarray spot image, with that of CNN features extracted from the epithelial and non-epithelial compartments, respectively. The prognostic accuracy of visually assessed histologic grade is used as a reference. The image data set consists of digitized hematoxylin-eosin (H and E) stained tissue microarray samples obtained from 180 patients with colorectal cancer. The patient samples represent a variety of histological grades, have data available on a series of clinicopathological variables including long-term outcome and ground truth annotations performed by experts. The CNN features extracted from images of the epithelial tissue compartment significantly predicted outcome (hazard ratio (HR) 2.08; CI95% 1.04-4.16; area under the curve (AUC) 0.66) in a test set of 60 patients, as compared to the CNN features extracted from unsegmented images (HR 1.67; CI95% 0.84-3.31, AUC 0.57) and visually assessed histologic grade (HR 1.96; CI95% 0.99-3.88, AUC 0.61). As a conclusion, a deep-learning classifier can be trained to predict outcome of colorectal cancer based on images of H and E stained tissue microarray samples and the CNN features extracted from the epithelial compartment only resulted in a prognostic discrimination comparable to that of visually determined histologic grade.

  9. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-05-08

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

  10. Human BLCAP transcript: new editing events in normal and cancerous tissues.

    Science.gov (United States)

    Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

    2010-07-01

    Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

  11. Detection of miRNA-21 content in cervical cancer tissue and preliminary analysis of its downstream target molecules

    Institute of Scientific and Technical Information of China (English)

    Rong Shen; Jian-Wu Gao; Yan-Yu Li; Peng Teng

    2015-01-01

    Objective:To study the miRNA-21 content in cervical cancer tissue and analyze its downstream target molecules.Methods:Patients with different FIGO stages of cervical cancer and healthy subjects were selected, cervical cancer tissue and normal cervical tissue were collected, and contents of miRNA-21 and apoptotic genes were detected; cervical cancer SiHa cells were cultured, miRNA-21 mimics and inhibitors were transfected, and then apoptotic gene contents were detected.Results:miRNA-21 contents in different stages of cervical cancer tissue were all higher than those in normal cervical tissue, mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 were lower than those in normal tissue, and mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 were negatively correlated with miRNA-21 contents; after miRNA-21 mimics were transfected, mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 significantly decreased, and after miRNA-21 inhibitors were transfected, mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 significantly increased.Conclusion:miRNA-21 contents in cervical cancer tissue significantly increase; downstream target genes of this miRNA may be apoptotic genes p16ink4a, ASPP1, Fas and GRIM-19.

  12. Targeted proteomic approach in prostatic tissue: a panel of potential biomarkers for cancer detection

    Science.gov (United States)

    Terracciano, Rosa; Damiano, Rocco; Savino, Rocco; Sindona, Giovanni; Napoli, Anna

    2016-01-01

    Prostate cancer (PCa) is the sixth highest causes of cancer-related deaths in men. The molecular events underlying its behavior and evolution are not completely understood. Prostate-specific antigen (PSA) is the only approved Food and Drug Administration biomarker. A panel of ten stage-specific tumoral and adjacent non tumoral tissues from patients affected by PCa (Gleason score 6, 3+3; PSA 10 ÷19 ng/ml) was investigated by MS-based proteomics approach. The proposed method was based on identifying the base-soluble proteins from tissue, established an efficient study, which lead to a deeper molecular perspective understanding of the PCa. A total of 164 proteins were found and 132 of these were evaluated differentially expressed in tumoral tissues. The Ingenuity Pathway Analysis (IPA) showed that among all dataset obtained, 105 molecules were involved in epithelial neoplasia with a p-value of 3.62E-05, whereas, only 11 molecules detected were ascribed to sentinel tissue and bodily fluids. PMID:27713912

  13. STED super-resolution microscopy of clinical paraffin-embedded human rectal cancer tissue.

    Directory of Open Access Journals (Sweden)

    Peter Ilgen

    Full Text Available Formalin fixed and paraffin-embedded human tissue resected during cancer surgery is indispensable for diagnostic and therapeutic purposes and represents a vast and largely unexploited resource for research. Optical microscopy of such specimen is curtailed by the diffraction-limited resolution of conventional optical microscopy. To overcome this limitation, we used STED super-resolution microscopy enabling optical resolution well below the diffraction barrier. We visualized nanoscale protein distributions in sections of well-annotated paraffin-embedded human rectal cancer tissue stored in a clinical repository. Using antisera against several mitochondrial proteins, STED microscopy revealed distinct sub-mitochondrial protein distributions, suggesting a high level of structural preservation. Analysis of human tissues stored for up to 17 years demonstrated that these samples were still amenable for super-resolution microscopy. STED microscopy of sections of HER2 positive rectal adenocarcinoma revealed details in the surface and intracellular HER2 distribution that were blurred in the corresponding conventional images, demonstrating the potential of super-resolution microscopy to explore the thus far largely untapped nanoscale regime in tissues stored in biorepositories.

  14. STED super-resolution microscopy of clinical paraffin-embedded human rectal cancer tissue.

    Science.gov (United States)

    Ilgen, Peter; Stoldt, Stefan; Conradi, Lena-Christin; Wurm, Christian Andreas; Rüschoff, Josef; Ghadimi, B Michael; Liersch, Torsten; Jakobs, Stefan

    2014-01-01

    Formalin fixed and paraffin-embedded human tissue resected during cancer surgery is indispensable for diagnostic and therapeutic purposes and represents a vast and largely unexploited resource for research. Optical microscopy of such specimen is curtailed by the diffraction-limited resolution of conventional optical microscopy. To overcome this limitation, we used STED super-resolution microscopy enabling optical resolution well below the diffraction barrier. We visualized nanoscale protein distributions in sections of well-annotated paraffin-embedded human rectal cancer tissue stored in a clinical repository. Using antisera against several mitochondrial proteins, STED microscopy revealed distinct sub-mitochondrial protein distributions, suggesting a high level of structural preservation. Analysis of human tissues stored for up to 17 years demonstrated that these samples were still amenable for super-resolution microscopy. STED microscopy of sections of HER2 positive rectal adenocarcinoma revealed details in the surface and intracellular HER2 distribution that were blurred in the corresponding conventional images, demonstrating the potential of super-resolution microscopy to explore the thus far largely untapped nanoscale regime in tissues stored in biorepositories.

  15. Polymer-based platforms by electric field-assisted techniques for tissue engineering and cancer therapy.

    Science.gov (United States)

    Guarino, Vincenzo; Cirillo, Valentina; Altobelli, Rosaria; Ambrosio, Luigi

    2015-01-01

    A large variety of processes and tools has been investigated to acquire better knowledge on the natural evolution of healthy or pathological tissues in 3D scaffolds to discover new solutions for tissue engineering and cancer therapy. Among them, electrodynamic techniques allow revisiting old scaffold manufacturing approach by utilizing electrostatic forces as the driving force to assemble fibers and/or particles from an electrically charged solution. By carefully selecting materials and processing conditions, they allow to fine control of characteristic shapes and sizes from micro to sub-micrometric scale and incorporate biopolymers/molecules (e.g., proteins, growth factors) for time- and space-controlled release for use in drug delivery and passive/active targeting. This review focuses on current advances to design micro or nanostructured polymer platforms by electrodynamic techniques, to be used as innovative scaffolds for tissue engineering or as 3D models for preclinical in vitro studies of in vivo tumor growth.

  16. Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression.

    Science.gov (United States)

    Gucalp, Ayca; Iyengar, Neil M; Hudis, Clifford A; Dannenberg, Andrew J

    2016-02-01

    The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies.

  17. Novel Insights into Gastric Cancer: Methylation of R-spondins and Regulation of LGR5 by SP1.

    Science.gov (United States)

    Wilhelm, Franziska; Simon, Eva; Boger, Christine; Behrens, Hans-Michael; Kruger, Sandra; Rocken, Christoph

    2017-02-20

    Recently it was shown that leucine-rich repeat-containing receptor 5 (LGR5) expressing stem cells are the cellular origin of intestinal-type gastric cancer. The aim of our study was to uncover regulatory mechanisms of LGR5 expression in gastric mucosa and their implications for cancer development. Reporter assays identified a LGR5 promoter fragment, which is highly relevant for active LGR5 expression. Chromatin immunoprecipitation (ChIP) verified that SP1 is bound within this region and reporter activity increased in SP1 transfected cells. Subsequently, the expression of R-spondins (RSPO1 and RSPO2), ligands of LGR5, were explored in neoplastic and non-neoplastic gastric tissue and gastric cancer cell lines. Using immunohistochemistry (IHC), distinct spatial expression patterns of LGR5, RSPO1 and RSPO2 were found in non-neoplastic stomach mucosa and gastric cancer. RSPO expression was lower in gastric cancer compared with non-neoplastic mucosa on both the transcriptional (p=0.003 for RSPO1 and p=0.000 for RSPO2; n=50) and the translational level. Methylation-specific PCR showed higher methylation levels of RSPO1/2 and re-expression of RSPOs in the gastric cancer cell lines MKN45 and MKN74 was induced by demethylating 5-azaC treatment. Finally, expression patterns of LGR5 and RSPO were similar in gastric cancer.

  18. Organoid Culture of Isolated Cells from Patient-derived Tissues with Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Bing-Ying Xie; Ai-Wen Wu

    2016-01-01

    Background:Colorectal cancer (CRC) is a heterogeneous disease;current research relies on cancer cell lines and animal cancer models,which may not precisely imitate inner human tumors and guide clinical medicine.The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy.Methods:We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs).Isolated cells from PDXs at appropriate tumor size were mingled with Matrigel,and then seeded in ultra-low attachment 96-well plates at four cell densities (500,1000,2000,and 4000 single cells/well).Cells were cultured with advanced Dulbecco's Modified Eagle Mediurn/F 12 medium additional with various factors added to maintain tumor's biological traits and growth activity.The growth curves of the four cell densities were measured after 24 h of culture until 25 days.We evaluated the effects of four chemotherapeutic agents on organoid model by the CellTiter-Glo(R) Luminescent Cell Viability Assay.Hematoxylin and eosin (H and E) staining of 3D organoids was performed and compared with patient and CRC PDX tissues.Furthermore,immunohistochemistry was performed,in which the organoids were stained with the proliferation marker,Ki-67.During the experimental process,a phase-contrast microscope was used.Results:Phenotype experimental results showed that 3D organoids were tightly packed together and grew robustly over time.All four densities of cells formed organoids while that composed of 2000 cells/well provided an adequate cultivation system and grew approximately 8-fold at the 25th day.The chemosensitivity of the four conventional drugs was [s]-l 0-hydroxycamptothecin > mitomycin C > adriamycin > paclitaxel,which can guide clinical treatment.Histological features of CRC patient's tumor tissues and mice tumor xenograft tissues were highly similar

  19. Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients.

    Science.gov (United States)

    Groblewska, Magdalena; Mroczko, Barbara; Gryko, Mariusz; Pryczynicz, Anna; Guzińska-Ustymowicz, Katarzyna; Kędra, Bogusław; Kemona, Andrzej; Szmitkowski, Maciej

    2014-04-01

    The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients' survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.

  20. Comparative genetics of longevity and cancer: insights from long-lived rodents

    Science.gov (United States)

    Gorbunova, Vera; Seluanov, Andrei; Zhang, Zhengdong; Gladyshev, Vadim N.; Vijg, Jan

    2015-01-01

    Mammals have evolved a dramatic diversity of aging rates. Within the single order of Rodentia maximum lifespans differ from four years in mice to 32 years in naked mole rats. Cancer rates also differ significantly, from cancer-prone mice to virtually cancer-proof naked and blind mole rats. Recent progress in rodent comparative biology, in combination with the emergence of whole genome sequence information, has opened opportunities for the discovery of genetic factors controlling longevity and cancer susceptibility. PMID:24981598

  1. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

    Directory of Open Access Journals (Sweden)

    Yuan Shinsheng

    2011-09-01

    Full Text Available Abstract Background To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. Results By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis. Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. Conclusions These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  2. Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens.

    Science.gov (United States)

    Chang, Xiaojing; Zhang, Shuanglong; Ma, Jinguo; Li, Zhenhua; Zhi, Yu; Chen, Jing; Lu, Yao; Dai, Dongqiu

    2013-05-01

    NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer.

  3. Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1.

    Science.gov (United States)

    Ramer, Robert; Merkord, Jutta; Rohde, Helga; Hinz, Burkhard

    2010-04-01

    Although cannabinoids exhibit a broad variety of anticarcinogenic effects, their potential use in cancer therapy is limited by their psychoactive effects. Here we evaluated the impact of cannabidiol, a plant-derived non-psychoactive cannabinoid, on cancer cell invasion. Using Matrigel invasion assays we found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa, C33A) and human lung cancer cells (A549) that was reversed by antagonists to both CB(1) and CB(2) receptors as well as to transient receptor potential vanilloid 1 (TRPV1). The decrease of invasion by cannabidiol appeared concomitantly with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Knockdown of cannabidiol-induced TIMP-1 expression by siRNA led to a reversal of the cannabidiol-elicited decrease in tumor cell invasiveness, implying a causal link between the TIMP-1-upregulating and anti-invasive action of cannabidiol. P38 and p42/44 mitogen-activated protein kinases were identified as upstream targets conferring TIMP-1 induction and subsequent decreased invasiveness. Additionally, in vivo studies in thymic-aplastic nude mice revealed a significant inhibition of A549 lung metastasis in cannabidiol-treated animals as compared to vehicle-treated controls. Altogether, these findings provide a novel mechanism underlying the anti-invasive action of cannabidiol and imply its use as a therapeutic option for the treatment of highly invasive cancers.

  4. Comparative Proteome Analysis of Breast Cancer and Adjacent Normal Breast Tissues in Human

    Institute of Scientific and Technical Information of China (English)

    Shi-Shan Deng; Tian-Yong Xing; Hong-Ying Zhou; Ruo-Hong Xiong; You-Guang Lu; Bin Wen; Shang-Qing Liu; Hui-Jun Yang

    2006-01-01

    Two-dimensional polyacryiamide gel electrophoresis (2D-PAGE) and matrixassisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), incorporated with online database searching, were performed to investigate differential proteins of breast cancer and adjacent normal breast tissues. Considering that serum albumin is abundantly presented in normal control samples, 15 differential spots detected in 11 out of 12 (91.7%) breast cancer samples were identified by online SIENA-2DPAGE database searching and MALDI-TOF/TOF-MS analysis. The results indicate that pathological changes of breast cancer are concerned with augmentation of substance metabolism, promotion of proteolytic activity, decline of activity of some inhibitors of enzymes, and so on. Some important proteins involved in the pathological process of breast cancer with changed expression may be useful biomarkers, such as alpha-1-antitrypsin, EF1-beta, cathepsin D, TCTP, SMT3A, RPS12, and PSMA1, among which SMT3A,RPS12, and PSMA1 were first reported for breast cancer in this study.

  5. Amino acid uptake in arterio-venous serum of normal and cancerous colon tissues

    Institute of Scientific and Technical Information of China (English)

    Lin-Bo Wang; Jian-Guo Shen; Su-Zhan Zhang; Ke-Feng Ding; Shu Zheng

    2004-01-01

    AIM: To investigate the difference of amino acid uptake between normal and cancerous colon tissues.METHODS: Sixteen patients with colon cancer were enrolled in our study. Blood samples were taken during operations, serum amino acid concentrations of blood from cancerous or normal colon were analyzed. Amino acid uptake rate was calculated by the A-V difference and evaluated statistically.RESULTS: Except for methionine, the uptake rate of amino acids in cancer was higher than that in normal colon (25.01% vs-2.29%, P<0.01). The amino acid uptake rate did not correlate to the size of tumor mass (P>0.05). There was no statistical significance in the amino acid uptake rate according to the Dukes stage, though it was higher in patients with Dukes stage C or D than that with Dukes stage B (P>0.05).CONCLUSION: Abnormal synthetic metabolism of colon cancer may contribute to its higher amino acid uptake rate than that of normal colon.

  6. Expression of γ-synuclein in colorectal cancer tissues and its role on colorectal cancer cell line HCT116

    Institute of Scientific and Technical Information of China (English)

    Qing Ye; Bo Feng; Yuan-Fei Peng; Xue-Hua Chen; Qu Cai; Bei-Qin Yu; Liang-Hui Li; Ming-Yuan Qiu; Bing-Ya Liu; Min-Hua Zheng

    2009-01-01

    AIM: To investigate the expression pattern of γ-synuclein in colorectal cancer (CRC) tissues, and to study the effects of γ-synuclein on CRC cell line HCT116 biological features in vitro.METHODS: The expression pattern of γ-synuclein was determined in 54 CRC tissues and 30 tumormatched nonneoplastic adjacent tissues (NNAT) 5 cm away from the tumor via real-time quantitative reverse transcription PCR (RT-PCR) and immunohistochemistry.The relationship between γ-synuclein protein expression and clinicopathological factors of CRC tissues was analyzed. Three small interfering RNA (siRNA) targeting γ-synuclein mRNA plasmids were constructed and transfected into the CRC cell line HCT116. The stable cell lines were selected with G-418 for 28 d, and the biological features of these cells were examined by cell growth curve, soft agar assay, and cell migration and invasion assays in vitro.RESULTS: The expression of γ-synuclein mRNA and protein was much higher in CRC tissue samples than in NNAT samples ( P = 0.02, P = 0.036). There was a significant correlation between the γ-synuclein protein expression and clinical stage and lymph node involvement of CRC ( P = 0.02, P = 0.033). In functional analysis we found that down-regulation of γ-synuclein expression in HCT116 cells could inhibit the growth, colony formation rate, and migration and invasion ability of HCT116 cells.CONCLUSION: Increased expression of γ-synuclein in CRC tissues and the biological effects of reduced γ-synuclein expression on HCT116 cells suggest that γ-synuclein may play a positive role in the progression of CRC.

  7. Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue

    Science.gov (United States)

    González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.

    2013-04-01

    Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

  8. A targeted quantitative proteomics strategy for global kinome profiling of cancer cells and tissues.

    Science.gov (United States)

    Xiao, Yongsheng; Guo, Lei; Wang, Yinsheng

    2014-04-01

    Kinases are among the most intensively pursued enzyme superfamilies as targets for anti-cancer drugs. Large data sets on inhibitor potency and selectivity for more than 400 human kinases became available recently, offering the opportunity to design rationally novel kinase-based anti-cancer therapies. However, the expression levels and activities of kinases are highly heterogeneous among different types of cancer and even among different stages of the same cancer. The lack of effective strategy for profiling the global kinome hampers the development of kinase-targeted cancer chemotherapy. Here, we introduced a novel global kinome profiling method, based on our recently developed isotope-coded ATP-affinity probe and a targeted proteomic method using multiple-reaction monitoring (MRM), for assessing simultaneously the expression of more than 300 kinases in human cells and tissues. This MRM-based assay displayed much better sensitivity, reproducibility, and accuracy than the discovery-based shotgun proteomic method. Approximately 250 kinases could be routinely detected in the lysate of a single cell line. Additionally, the incorporation of iRT into MRM kinome library rendered our MRM kinome assay easily transferrable across different instrument platforms and laboratories. We further employed this approach for profiling kinase expression in two melanoma cell lines, which revealed substantial kinome reprogramming during cancer progression and demonstrated an excellent correlation between the anti-proliferative effects of kinase inhibitors and the expression levels of their target kinases. Therefore, this facile and accurate kinome profiling assay, together with the kinome-inhibitor interaction map, could provide invaluable knowledge to predict the effectiveness of kinase inhibitor drugs and offer the opportunity for individualized cancer chemotherapy.

  9. Insights into erlotinib action in pancreatic cancer cells using a combined experimental and mathematical approach

    Institute of Scientific and Technical Information of China (English)

    Falko Lange; Katja Rateitschak; Christina Kossow; Olaf Wolkenhauer; Robert Jaster

    2012-01-01

    AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells.METHODS:Two PC cell lines,BxPC-3 and Capan-1,were treated with various concentrations of erlotinib,the specific mitogen-activated protein kinase kinase (MEK) inhibitor U0126,and protein kinase B (AKT) inhibitor XIV.DNA synthesis was measured by 5-bromo2'-deoxyuridine (BrdU) assays.Expression and phosphorylation of the epidermal growth factor receptor (EGFR) and downstream signaling molecules were quantified by Western blot analysis.The data were processed to calibrate a mathematical model,based on ordinary differential equations,describing the EGFRmediated signal transduction.RESULTS:Erlotinib significantly inhibited BrdU incorporation in BxPC-3 cells at a concentration of 1 μmol/L,whereas Capan-1 cells were much more resistant.In both cell lines,MEK inhibitor U0126 and erlotinib attenuated DNA synthesis in a cumulative manner,whereas the AKT pathway-specific inhibitor did not enhance the effects of erlotinib.While basal phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) did not differ much between the two cell lines,BxPC-3 cells displayed a more than five-times higher basal phospho-AKT level than Capan-1 cells.Epidermal growth factor (EGF) at 10 ng/mL induced the phosphorylation of EGFR,AKT and ERK in both cell lines with similar kinetics.In BxPC-3 cells,higher levels of phospho-AKT and phospho-ERK (normalized to the total protein levels) were observed.Independent of the cell line,erlotinib efficiently inhibited phosphorylation of EGFR,AKT and ERK.The mathematical model successfully simulated the experimental findings and provided predictions regarding phosphoprotein levels that could be verified experimentally.CONCLUSION:Our data suggest basal AKT phosphorylation and the degree of EGF-induced activation of AKT and ERK as molecular determinants of erlotinib efficiency in PC cells.

  10. Tumor-induced inflammation in mammary adipose tissue stimulates a vicious cycle of autotaxin expression and breast cancer progression.

    Science.gov (United States)

    Benesch, Matthew G K; Tang, Xiaoyun; Dewald, Jay; Dong, Wei-Feng; Mackey, John R; Hemmings, Denise G; McMullen, Todd P W; Brindley, David N

    2015-09-01

    Compared to normal tissues, many cancer cells overexpress autotaxin (ATX). This secreted enzyme produces extracellular lysophosphatidate, which signals through 6 GPCRs to drive cancer progression. Our previous work showed that ATX inhibition decreases 4T1 breast tumor growth in BALB/c mice by 60% for about 11 d. However, 4T1 cells do not produce significant ATX. Instead, the ATX is produced by adjacent mammary adipose tissue. We investigated the molecular basis of this interaction in human and mouse breast tumors. Inflammatory mediators secreted by breast cancer cells increased ATX production in adipose tissue. The increased lysophosphatidate signaling further increased inflammatory mediator production in adipose tissue and tumors. Blocking ATX activity in mice bearing 4T1 tumors with 10 mg/kg/d ONO-8430506 (a competitive ATX inhibitor, IC90 = 100 nM; Ono Pharma Co., Ltd., Osaka, Japan) broke this vicious inflammatory cycle by decreasing 20 inflammatory mediators by 1.5-8-fold in cancer-inflamed adipose tissue. There was no significant decrease in inflammatory mediator levels in fat pads that did not bear tumors. ONO-8430506 also decreased plasma TNF-α and G-CSF cytokine levels by >70% and leukocyte infiltration in breast tumors and adjacent adipose tissue by >50%. Hence, blocking tumor-driven inflammation by ATX inhibition is effective in decreasing tumor growth in breast cancers where the cancer cells express negligible ATX.

  11. Clinical research on the expression of Lgr5 in the colon cancer tissues and its transfer promoting role

    Institute of Scientific and Technical Information of China (English)

    Xin-Jun Shu

    2016-01-01

    Objective:To detect the expression of Lgr5 in the colon cancer tissue, and to explore its correlation with the clinical and pathological characteristics and its role in promoting the tumor invasion and metastasis.Methods:A total of 102 specimens from the patients with colon cancer who were admitted in the General Surgery Department of our hospital for resection from April, 2013 to October, 2015 were included in the study; meanwhile, 35 colorectal adenoma specimens, and 137 normal colon tissue specimens were collected. The immunohistochemical method was used to detect the expression of Lgr5.Results:The positive rate of Lgr5 in the colon cancer tissues (62.75%) was significantly higher than that in the adenoma tissues (28.57%) and normal tissues (16.06%). The positive expression of Lgr5 in the colon cancer tissues was associated with the adenocarcinoma differentiation degree, Dukes staging, lymphatic metastasis, and distant metastasis. Meanwhile, it was found by the Logistic regression that the adenocarcinoma differentiation degree, lymphatic metastasis, and distant metastasis were the independent predictive factors for the positive expression of Lgr5. Conclusions:The increasement of Lgr5 expression is probably involved in the formation, differentiation, invasion, and metastasis of colon cancer; therefore, Lgr5 is expected to be a new therapeutic target aiming at colon cancer stem cells.

  12. Polymorphisms in miRNA binding site: new insight into small cell lung cancer susceptibility

    Institute of Scientific and Technical Information of China (English)

    Hong-yu LIU; Jun CHEN

    2011-01-01

    Lung cancer is a leading cause in cancer-related deaths with less than 15% five-year survival worldwide.Small cell lung cancer (SCLC),which accounts for about 15%-18% of lung cancer,carries the worst prognosis within the lung cancer patients.SCLC differs from other lung cancers,so called non-small cell lung cancers (NSCLCs),in the specifically clinical and biologic characteristics.It exhibits aggressive behavior,with rapid growth,early spread to distant sites.Although exquisite sensitive to chemotherapy and radiation,SCLC recurs rapidly with only 5% of patients surviving five years and frequent association with distinct paraneoplastic syndromes[1].

  13. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  14. New Insights into the Role of Macrophages in Adipose Tissue Inflammation and Fatty Liver Disease: Modulation by Endogenous Omega-3 Fatty Acid-derived Lipid Mediators

    Directory of Open Access Journals (Sweden)

    Joan eClària

    2011-10-01

    Full Text Available Obesity is causally linked to a chronic state of low-grade inflammation in adipose tissue. Prolonged, unremitting inflammation in this tissue has a direct impact on insulin-sensitive tissues (i.e. liver and its timely resolution is a critical step toward reducing the prevalence of related co-morbidities such as insulin resistance and non-alcoholic fatty liver disease. This article describes the current state-of-the-art knowledge and novel insights into the role of macrophages in adipose tissue inflammation, with special emphasis on the progressive changes in macrophage polarization observed over the course of obesity. In addition, this article extends the discussion to the contribution of Kupffer cells, the liver resident macrophages, to metabolic liver disease. Special attention is given to the modulation of macrophage responses by omega-3-PUFAs, and more importantly by resolvins, which are potent anti-inflammatory and pro-resolving autacoids generated from docosahexaenoic and eicosapentaenoic acids. In fact, resolvins have been shown to work as endogenous stop signals in inflamed adipose tissue and to return this tissue to homeostasis by inducing a phenotypic switch in macrophage polarization toward a pro-resolving phenotype. Collectively, this article offers new views on the role of macrophages in metabolic disease and their modulation by endogenously-generated omega-3-PUFA-derived lipid mediators.

  15. Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yoshifumi; Shioya, Sumie; Kurita, Daisaku; Ohta, Takashi; Haida, Munetaka; Ohta, Yasuyo [Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine; Suda, Syuichi; Fukuzaki, Minoru

    1994-12-01

    We investigated the nuclear magnetic resonance (NMR) relaxation times, T{sub 1} and T{sub 2}, for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinomas, five necrotic squamous cell carcinomas, 15 adenocarcinomas, two benign mesotheliomas, and 13 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were correlated with histological changes. The values of T{sub 1} and T{sub 2} for squamous cell carcinoma and mesothelioma were significantly longer than those of adenocarcinoma and fibrotic lung tissue. There were no significant differences in values of T{sub 1} and T{sub 2} between adenocarcinoma and lung tissue. The values of T{sub 1} and T{sub 2} for benign mesothelioma were similar to those of squamous cell carcinoma, which suggested that increases in T{sub 1} and T{sub 2} are not specific to malignant tissues. (author).

  16. FIRST LINE 5-FU-BASED CHEMOTHERAPY WITH/WITHOUT BEVACIZUMAB FOR METASTATIC COLORECTAL CANCER: TISSUE BIOMARKER CANDIDATES

    OpenAIRE

    Assia Konsoulova; Ivan Donev; Nikolay Conev; Sonya Draganova; Nadezhda Petrova; Eleonora Dimitrova; Hristo Popov; Kameliya Bratoeva; Petar Ghenev

    2016-01-01

    Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS) but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with resp...

  17. Expression of Bmi-1 and EZH2 in tissues adjacent to human epithelial ovarian cancer cells of orthotopic implantation in nude mice

    Institute of Scientific and Technical Information of China (English)

    Genhai Zhu; Lan Hong; Shengtan Wang; Zhaoxin Yang; Chunying Chen; Shixuan Wang

    2015-01-01

    Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The human epithelial ovarian cancer cel line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopical y implanted. The expression levels of Bmi-1 and EZH2 were detected by immunohistochemical staining and RT-PCR in cancer tissues, proximal and remote tissues with respect to the cancer tissues, and normal ovarian tissues of nude mice. Results Thirty-five ovarian tissue samples with normal biopsy results were obtained from 40 cases of human epithelial ovarian cancer in the nude mice in which the tumor tissues were orthotopical y implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples (P Conclusion The expression levels of Bmi-1 and EZH2 were reduced with increasing distance from the cancer tissues. Negative expression of these tumor-associated genes can be used as a standard for the screening of normal ovarian tissues adjacent to tumor tissues. Normal ovarian tissues can be obtained from the tissues adjacent to tumors.

  18. MicroRNA-181b expression in prostate cancer tissues and its influence on the biological behavior of the prostate cancer cell line PC-3.

    Science.gov (United States)

    He, L; Yao, H; Fan, L H; Liu, L; Qiu, S; Li, X; Gao, J P; Hao, C Q

    2013-04-02

    We examined microRNA-181b (miRNA) expression in prostate cancer tissues and its effect on the prostate cancer cell line PC-3. Tissues from 27 cases of prostate cancer and 30 samples of normal human prostate were collected by surgical removal. Total miRNA was extracted, and the relative expression of miR-181b was quantified using RT-PCR. miR-181b ASO was transfected into prostate cancer PC-3 cells. miR-181b expression in transfected and non-transfected cells was measured using RT-PCR. Changes in cell apoptosis were measured using flow cytometry. MTT and cell growth curve methods were used to assess the influence of miR-181b expression on cell proliferation. The changes in cell invasive ability in vitro were detected using the Transwell chamber method. miR-181b was up-regulated in the prostate cancer tissues compared with the normal prostate samples. It was down-regulated after miR-181b ASO transfection into the prostate cancer PC-3 cells. Down-regulation of miR-181b in the PC-3 cell induced apoptosis, inhibited proliferation, and depressed invasion of PC-3 cells in vitro. As miR-181b is over-expressed in prostate cancer, its down-regulation could have potential as gene therapy for prostate cancer by inducing apoptosis, inhibiting proliferation and depressing invasion by cancer cells.

  19. Quantitative analysis of collagen change between normal and cancerous thyroid tissues based on SHG method

    Science.gov (United States)

    Chen, Xiwen; Huang, Zufang; Xi, Gangqin; Chen, Yongjian; Lin, Duo; Wang, Jing; Li, Zuanfang; Sun, Liqing; Chen, Jianxin; Chen, Rong

    2012-03-01

    Second-harmonic generation (SHG) is proved to be a high spatial resolution, large penetration depth and non-photobleaching method. In our study, SHG method was used to investigate the normal and cancerous thyroid tissue. For SHG imaging performance, system parameters were adjusted for high-contrast images acquisition. Each x-y image was recorded in pseudo-color, which matches the wavelength range in the visible spectrum. The acquisition time for a 512×512-pixels image was 1.57 sec; each acquired image was averaged four frames to improve the signal-to-noise ratio. Our results indicated that collagen presence as determined by counting the ratio of the SHG pixels over the whole pixels for normal and cancerous thyroid tissues were 0.48+/-0.05, 0.33+/-0.06 respectively. In addition, to quantitatively assess collagen-related changes, we employed GLCM texture analysis to the SHG images. Corresponding results showed that the correlation both fell off with distance in normal and cancerous group. Calculated value of Corr50 (the distance where the correlation crossed 50% of the initial correlation) indicated significant difference. This study demonstrates that SHG method can be used as a complementary tool in thyroid histopathology.

  20. Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

    Science.gov (United States)

    CRUZ*, ISA N.; COLEY*, HELEN M.; KRAMER, HOLGER B.; MADHURI, THUMULURU KAVITAH; SAFUWAN, NUR A.M.; ANGELINO, ANA RITA; YANG, MIN

    2016-01-01

    Background: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. Materials and Methods: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes. Results: A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease. Conclusion: Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer. *These Authors contributed equally to this study. PMID:28031236

  1. Preservation of biomolecules in breast cancer tissue by a formalin-free histology system

    Directory of Open Access Journals (Sweden)

    Morales Azorides R

    2008-01-01

    Full Text Available Abstract Background The potential problems associated with the use of formalin in histology, such as health hazards, degradation of RNA and cross-linking of proteins are well recognized. We describe the utilization of a formalin-free fixation and processing system for tissue detection of two important biopredictors in breast cancer – estrogen receptor and HER2 – at the RNA and protein levels. Methods Parallel sections of 62 cases of breast cancer were fixed in an alcohol-based molecular fixative and in formalin. Molecular fixative samples were processed by a novel formalin-free microwave-assisted processing system that preserves DNA, RNA and proteins. Formalin-fixed samples were processed using the conventional method. Estrogen receptor was assessed by immunohistochemistry and real-time PCR. HER2 was assessed by immunohistochemistry, FISH, CISH and real-time PCR. Results The immunohistochemical reaction for estrogen receptor was similar in molecular- and formalin-fixed samples (Spearman Rank R = 0.83, p Conclusion The formalin-free tissue fixation and processing system is a practical platform for evaluation of biomolecular markers in breast cancer and it allows reliable DNA and RNA and protein studies.

  2. IMMUNOHISTOCHEMICAL OBSERVATION OF MACROPHAGE COLONY STIMULATING FACTOR AND ITS RECEPTOR IN BREAST CANCER AND HEPATOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To study the potential role of cellular macrophageolony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor's process.

  3. Role of deregulated microRNAs in breast cancer progression using FFPE tissue.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available MicroRNAs (miRNAs contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH, ductal carcinoma in situ (DCIS and invasive ductal carcinoma (IDC. To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.

  4. Risk assessment of mouse gastric tissue cancer induced by dichlorvos and dimethoate.

    Science.gov (United States)

    Wang, Qing-Lu; Zhang, Yu-Jun; Zhou, Cai-Xia; Zhang, Jie; Dou, Ye; Li, Qiao-Qiao

    2013-04-01

    Cancer hazards from pesticide residues in food have been much discussed in the past decade. In this study, we showed that dichlorvos and dimethoate affect hemoglobin content and hematocrit value, but had no effect on red blood cell counts and total plasma protein in mice. A 40-mg/kg/day dose of dichlorvos upregulated the expression of p16, Bcl-2 and c-myc genes in mouse gastric tissue. By contrast, expression of the p16, Bcl-2 and c-myc genes induced by low doses (5, 10 and 20 mg/kg/day) of dichlorvos demonstrated no change in the control check group (CK; 200 μl sterile saline perfused group; 0 mg/kg/day). Different doses of dimethoate all upregulated the expression of p16, Bcl-2 and c-myc genes in mouse gastric tissue. The results further demonstrated that mouse gastric tissue, exposed in the long-term to low doses of dichlorvos and dimethoate, has the potential to become cancerous.

  5. Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro.

    Science.gov (United States)

    Xiao, Songshu; Zhou, Yanhong; Yi, Wei; Luo, Guijuan; Jiang, Bin; Tian, Qi; Li, Yueran; Xue, Min

    2015-04-01

    Cervical cancer is a potentially preventable disease; however, it is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. Cervical cancer is thought to develop through a multistep process involving virus, tumor suppressor genes, proto-oncogenes and immunological factors. It is known that human papillomavirus (HPV) infection is necessary but insufficient to cause malignancy. At present, the etiology of cervical carcinoma remains poorly understood. In this study, we found that the expression of FOS-like antigen-1 (Fra-1) gene was downregulated in cervical cancer compared with the adjacent non-cancerous tissues by RT-qPCR, immunohistochemistry (IHC) and western blotting techniques. To uncover the effect of Fra-1 on cervical cancer, we tested and confirmed that Fra-1 significantly inhibited the proliferation of HeLa cells by MMT assays in vitro. At the same time, overexpression of Fra-1 promoted apoptosis of HeLa cells. To explore the possible mechanism of Fra-1 in cervical cancer, we tested the expression levels of key molecules in p53 signaling pathway by western blotting technology. The results showed that p53 was downregulated in cervical cancer compared with the adjacent non-cancerous tissues, but MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) was upregulated in cervical cancer. In vitro, the p53 was upregulated and MDM2 was downregulated in HeLa cells with Fra-1 overexpression. In summary, our results suggested that Fra-1 expression is low in cervical cancer tissues and promotes apoptosis of cervical cancer cells by p53 signaling pathway.

  6. Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

    OpenAIRE

    Patel, Shyam A.; Helmy, Karim Y; Dave, Meneka A.; Murthy, Raghav G.; Pranela Rameshwar

    2011-01-01

    Among all cancers, malignancies of the breast are the second leading cause of cancer death in the United States after carcinoma of the lung. One of the major factors considered when assessing the prognosis of breast cancer patients is whether the tumor has metastasized to distant organs. Although the exact phenotype of the malignant cells responsible for metastasis and dormancy is still unknown, growing evidence has revealed that they may have stem cell-like properties that may account for re...

  7. Contribution of endothelial precursors of adipose tissue to breast cancer: progression-link with fat graft for reconstructive surgery.

    Science.gov (United States)

    Bertolini, Francesco

    2013-05-01

    Obesity, an excess accumulation of adipose tissue occurring in mammalians when caloric intake exceeds energy expenditure, is associated with an increased frequency and progression of several types of neoplastic diseases including postmenopausal breast cancer. Recent studies have suggested that obesity-related disruption of the energy homeostasis results in inflammation and alterations of adipokine signalling that may foster cancer initiation and progression. Moreover, two populations of human white adipose tissue (WAT) progenitors cooperate in breast cancer angiogenesis, growth and metastatic progression. This raises the issue of lipotransfer in patients undergoing plastic or reconstructive surgery.

  8. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

  9. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Adrian Thomas E

    2003-01-01

    Full Text Available Abstract The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1 our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2 the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention.

  10. Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shao-fei; HU San-yuan; MA Lei; MIAO Lei; MAO Wei-zheng

    2013-01-01

    Background The relationship between the presence of metalloproteinases and thyroid cancer remains unknown,and many controversies still exist in this field.The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2.Methods The correlations were studied by detecting the levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma,27 patients with benign thyroid disease,and 25 healthy volunteers.Results The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers (P <0.05).However,there were no significant differences between patients with benign thyroid disease and healthy volunteers (P >0.05).The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%.Conclusions The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

  11. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Kapil, E-mail: kmehta@mdanderson.org; Han, Amy [Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030 (United States)

    2011-02-25

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

  12. Intravenous Tissue Plasminogen Activator for an Ischemic Stroke with Occult Double Primary Cancer

    Directory of Open Access Journals (Sweden)

    Yukihiro Yoneda

    2014-10-01

    Full Text Available Background: In patients with advanced-stage cancer, systemic thrombolysis with tissue plasminogen activator (tPA for hyperacute ischemic stroke is not strictly off-label, but it is at higher risk of complications (including bleeding. Case Report: A 71-year-old male with unrecognizable malignancy developed a hemispheric ischemic stroke and received intravenous tPA within 4.5 h of onset, followed by anticoagulation treatment after 24 h of thrombolysis. Two days later, the patient had tarry stool and progressive anemia, receiving a blood transfusion. The systemic workup documented the presence of double primary cancers with advanced stage gastric and rectal cancers, and the patient subsequently received palliative care. The outcome at 3 months was a modified Rankin Scale of 5, and the patient died 6 months after the stroke. Discussion: Although systemic thrombolysis with tPA for ischemic stroke in patients with advanced-stage cancer may be performed relatively safely, optimal post-thrombolysis management is important to prevent the complications.

  13. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer.

    Science.gov (United States)

    Obaidat, Amanda; Roth, Megan; Hagenbuch, Bruno

    2012-01-01

    Organic anion transporting polypeptides (OATPs) are members of the SLCO gene superfamily of proteins. The 11 human OATPs are classified into 6 families and subfamilies on the basis of their amino acid sequence similarities. OATPs are expressed in several epithelial tissues throughout the body and transport mainly amphipathic molecules with molecular weights of more than 300 kDa. Members of the OATP1 and OATP2 families are functionally the best-characterized OATPs. Among these are the multispecific OATP1A2, OATP1B1, OATP1B3, and OATP2B1. They transport various endo- and xenobiotics, including hormones and their conjugates as well as numerous drugs such as several anticancer agents. Recent reports demonstrate that some OATPs are up- or downregulated in several cancers and that OATP expression might affect cancer development. On the basis of the findings summarized in this review, we propose that OATPs could be valuable targets for anticancer therapy.

  14. Model-integrated estimation of normal tissue contamination for cancer SNP allelic copy number data.

    Science.gov (United States)

    Stjernqvist, Susann; Rydén, Tobias; Greenman, Chris D

    2011-01-01

    SNP allelic copy number data provides intensity measurements for the two different alleles separately. We present a method that estimates the number of copies of each allele at each SNP position, using a continuous-index hidden Markov model. The method is especially suited for cancer data, since it includes the fraction of normal tissue contamination, often present when studying data from cancer tumors, into the model. The continuous-index structure takes into account the distances between the SNPs, and is thereby appropriate also when SNPs are unequally spaced. In a simulation study we show that the method performs favorably compared to previous methods even with as much as 70% normal contamination. We also provide results from applications to clinical data produced using the Affymetrix genome-wide SNP 6.0 platform.

  15. Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression.

    Science.gov (United States)

    Heissig, Beate; Dhahri, Douaa; Eiamboonsert, Salita; Salama, Yousef; Shimazu, Hiroshi; Munakata, Shinya; Hattori, Koichi

    2015-12-01

    Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules. MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed.

  16. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Peng-hui Zhuang; Zhao-hui Liu; Xiao-gang Jiang; Cheng-en Pan

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKC伪 double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

  17. Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

    Science.gov (United States)

    Deja, Stanislaw; Porebska, Irena; Kowal, Aneta; Zabek, Adam; Barg, Wojciech; Pawelczyk, Konrad; Stanimirova, Ivana; Daszykowski, Michal; Korzeniewska, Anna; Jankowska, Renata; Mlynarz, Piotr

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.

  18. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

    Science.gov (United States)

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

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  19. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    Science.gov (United States)

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

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  20. Tissue-scale, personalized modeling and simulation of prostate cancer growth

    Science.gov (United States)

    Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-11-01

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

  1. A Comprehensive MicroRNA Expression Profile of Liver and Lung Metastases of Colorectal Cancer with Their Corresponding Host Tissue and Its Prognostic Impact on Survival

    Science.gov (United States)

    Pecqueux, Mathieu; Liebetrau, Isabell; Werft, Wiebke; Dienemann, Hendrik; Muley, Thomas; Pfannschmidt, Joachim; Müssle, Benjamin; Rahbari, Nuh; Schölch, Sebastian; Büchler, Markus W.; Weitz, Jürgen; Reissfelder, Christoph; Kahlert, Christoph

    2016-01-01

    MicroRNAs are small non-coding RNAs with a length of 18–25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations—tumor, associated stroma, and host tissue—can provide new insights into the complex tumor biology of colorectal cancer. Frozen tissue samples of colorectal liver (n = 25) and lung metastases (n = 24) were laser microdissected to separate tumor cells and the adjacent tumor-associated stroma cells. Additionally, normal lung and liver tissue was collected from the same patients. We performed a microarray analysis in four randomly selected liver metastases and four randomly selected lung metastases, analyzing a total of 939 human miRNAs. miRNAs with a significant change >2-fold between the tumor, tumor stroma, and host tissue were analyzed in all samples using RT-qPCR (11 miRNAs) and correlated with the clinical data. We found a differential expression of several miRNAs between the tumor, the tumor-associated stroma, and the host tissue compartment. When comparing liver and lung metastases, miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and, finally, miR-199-5 a 12.5-fold downregulation in liver metastases compared to lung metastases. Furthermore miR-19, miR-125, miR-127, miR-192, miR-194, miR-199-5, and miR-215 showed a significant upregulation in the normal liver tissue compared to the normal lung tissue. Univariate analysis identified an association of poor survival with the expression of miR-125 (p = 0

  2. ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis.

    Science.gov (United States)

    Gefen, Smadar; Tretiak, Oleh J; Piccoli, Catherine W; Donohue, Kevin D; Petropulu, Athina P; Shankar, P Mohana; Dumane, Vishruta A; Huang, Lexun; Kutay, M Alper; Genis, Vladimir; Forsberg, Flemming; Reid, John M; Goldberg, Barry B

    2003-02-01

    Breast cancer diagnosis through ultrasound tissue characterization was studied using receiver operating characteristic (ROC) analysis of combinations of acoustic features, patient age, and radiological findings. A feature fusion method was devised that operates even if only partial diagnostic data are available. The ROC methodology uses ordinal dominance theory and bootstrap resampling to evaluate A(z) and confidence intervals in simple as well as paired data analyses. The combined diagnostic feature had an A(z) of 0.96 with a confidence interval of at a significance level of 0.05. The combined features show statistically significant improvement over prebiopsy radiological findings. These results indicate that ultrasound tissue characterization, in combination with patient record and clinical findings, may greatly reduce the need to perform biopsies of benign breast lesions.

  3. Insights from Breast Cancer Survivors: The Interplay between Context, Epistemology, and Change

    Science.gov (United States)

    Hoggan, Chad

    2014-01-01

    This study explored the processes by which a group of breast cancer survivors experienced positive learning and growth from their cancer experiences. The author argues that such learning and growth can be considered transformative learning, especially from ontological perspectives of the theory. The participants' change process consisted of…

  4. The correlation analysis of the expression of VEGF and the DCs’ infiltration density of gastric cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Feng Yang; Ai-Mei Li; De-Huai Jing

    2016-01-01

    Objective:To investigate the correlation of the expression of vascular endothecial growth factor (VEGF) and the dendritic cells (DCs) infiltration density of tumor tissues in patients with gastric cancer and the correlation of the frequency of DCs of VEGF in gastric cancer tissues and the clinic stages; and to analyze the expressions of HLA-DR and CD86 on peripheral blood monocyte-derived DCs.Methods:Immuno fluorescence method was applied to test the expressions of CD11c and VEGF in gastric cancer tissues and para-carcinoma tissues and enzyme-linked immune sorbent assay was used to detect the concentration of serum VEGF. Peripheral blood mononuclear cells of the gastric cancer patients and healthy people were separated and induced DCs by GM-CSF and IL-4in vitro. Then, the expressions of HLA-DR and CD86 on DCs were tested by flow cytometry. Finally, the recombinant VEGF protein was added into DCs cultures to explore how VEGF affected the expression of CD86. Results: There was a negative correlation between the expression intensity of VEGF on gastric cancer cells and the tumor-infiltrating density of DCs; while there was a certain positive correlation between the frequency of DCs of VEGF and the development of the disease. The concentration of serum VEGF had no association with the density of tumor-infiltrating DCs. As for peripheral blood mononuclear cell, it had a certain induced effect on the decrease of DCs, the expressions of HLA-DR and CD86 and the expression of CD86 on DCs’ cell surface by VEGF.Conclusions:The activities of DCs were inhibited by VEGF secretion of gastric cancer tissues so as to mediate immune escape of the cancer cells. In addition, DCs infiltrated in gastric cancer tissues may secrete VEGF to participate the development of the disease.

  5. Relationship between promoter methylation & tissue expression of MGMT gene in ovarian cancer

    Directory of Open Access Journals (Sweden)

    V Shilpa

    2014-01-01

    Full Text Available Background & objectives: Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumour suppressor genes. O 6 -methyguanine-DNA methyltransferase (MGMT is a DNA repair gene that removes mutagenic and cytotoxic adducts from the O 6 -position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression has been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human epithelial ovarian carcinoma. Methods: A total of 88 epithelial ovarian cancer (EOC tissue samples, 14 low malignant potential (LMP tumours and 20 benign ovarian tissue samples were analysed for MGMT promoter methylation by nested methylation-specific polymerase chain reaction (MSP after bisulphite modification of DNA. A subset of 64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples were analysed for protein expression by immunohistochemistry. Results: The methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and 20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP, benign tumours and normal ovarian tissue samples. Promoter hypermethylation with loss of protein expression was seen only in one case of EOC. Interpretation & conclusions: Our results suggest that MGMT promoter hypermethylation does not always reflect gene expression.

  6. New Insights into the Androgen-Targeted Therapies and Epigenetic Therapies in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Abhijit M. Godbole

    2011-01-01

    Full Text Available Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR, a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC. Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes, posttranslational modifications of AR such as sumoylation. Herein, we provide an overview of the structure of human AR and its key structural domains that can be used as targets to develop novel antiandrogens. We also summarize recent findings about the antiandrogens and the epigenetic factors that modulate the action of AR.

  7. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

    Directory of Open Access Journals (Sweden)

    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  8. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention.

    Science.gov (United States)

    Nezhat, Farr R; Apostol, Radu; Nezhat, Camran; Pejovic, Tanja

    2015-09-01

    Despite advances in medicine, ovarian cancer remains the deadliest of the gynecological malignancies. Herein we present the latest information on the pathophysiology of ovarian cancer and its significance for ovarian cancer screening and prevention. A new paradigm for ovarian cancer pathogenesis presupposes 2 distinct types of ovarian epithelial carcinoma with distinct molecular profiles: type I and type II carcinomas. Type I tumors include endometrioid, clear-cell carcinoma, and low-grade serous carcinoma and mostly arise via defined sequence either from endometriosis or from borderline serous tumors, mostly presenting in an early stage. More frequent type II carcinomas are usually high-grade serous tumors, and recent evidence suggests that the majority arise from the fimbriated end of the fallopian tube. Subsequently, high-grade serous carcinomas usually present at advanced stages, likely as a consequence of the rapid peritoneal seeding from the open ends of the fallopian tubes. On the other hand, careful clinical evaluation should be performed along with risk stratification and targeted treatment of women with premalignant conditions leading to type I cancers, most notably endometriosis and endometriomas. Although the chance of malignant transformation is low, an understanding of this link offers a possibility of prevention and early intervention. This new evidence explains difficulties in ovarian cancer screening and helps in forming new recommendations for ovarian cancer risk evaluation and prophylactic treatments.

  9. Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue.

    Science.gov (United States)

    Ding, Lei; Wang, Liyong; Sui, Leiming; Zhao, Huanying; Xu, Xiaoxue; Li, Tengyan; Wang, Xiaonan; Li, Wenjing; Zhou, Ping; Kong, Lu

    2016-08-01

    The claudin family of proteins is integral to the structure and function of tight junctions. The role of claudin-7 (Cldn-7, CLDN7) in regulating the integrin/focal adhesion kinase (FAK)/ERK signaling pathway remains poorly understood. Therefore, we investigated differences in gene expression, primarily focusing on CLDN7 and integrin/FAK/ERK signaling pathway genes, between colon cancer and adjacent normal tissues. Quantitative real-time reverse transcription-PCR and immunohistochemistry were utilized to verify the results of mRNA and protein expression, respectively. In silico analysis was used to predict co-regulation between Cldn-7 and integrin/FAK/ERK signaling pathway components, and the STRING database was used to analyze protein-protein interaction pairs among these proteins. Meta-analysis of expression microarrays in The Cancer Genome Atlas (TCGA) database was used to identify significant correlations between Cldn-7 and components of predicted genes in the integrin/FAK/ERK signaling pathway. Our results showed marked cancer stage-specific decreases in the protein expression of Cldn-7, Gelsolin, MAPK1 and MAPK3 in colon cancer samples, and the observed changes for all proteins except Cldn-7 were in agreement with changes in the corresponding mRNA levels. Cldn-7 might indirectly regulate MAPK3 via KRT8 due to KRT8 co-expression with MAPK3 or CLDN7. Our bioinformatics methods supported the hypothesis that Cldn-7 does not directly regulate any genes in the integrin/FAK/ERK signaling pathway. These factors may participate in a common network that regulates cancer progression in which the MAPK pathway serves as the central node.

  10. Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

    DEFF Research Database (Denmark)

    Theocharis, Achilleas D.; Skandalis, Spyros S.; Neill, Thomas

    2015-01-01

    of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor...... in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel...

  11. Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in colorectal cancer cell lines and cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Kyung-Hee Kim; Jin-Sung Choi; Il-Jin Kim; Ja-Lok Ku; Jae-Gahb Park

    2006-01-01

    AIM: To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines.METHODS: We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues.RESULTS: Of the 32 cell lines,MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MSPCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each.Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%,respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively.CONCLUSION: The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.

  12. LRG-1 expression in tongue cancer tissue and effect of targeted inhibition of LRG-1 by siRNA on tongue cancer viability

    Institute of Scientific and Technical Information of China (English)

    Ya-Jun Li; Zhi-Zhong Zhang; Ke-Qian Zhi; Liang-Zhi Du

    2016-01-01

    Objective:To study LRG-1 expression in tongue cancer tissue and the effect of targeted inhibition of LRG-1 by siRNA on tongue cancer viability.Methods:Tongue cancer tissue and para-carcinoma tissue were collected to determine LRG-1 expression; tongue cancer cell lines Tca8113 were cultured and transfected with negative control siRNA (NC-siRNA group) and LRG1-targeted siRNA (LRG1-siRNA group) respectively, and the cell viability as well as the expression levels of angiogenesis molecules, apoptosis molecules and autophagy molecules were determined.Results:LRG-1 expression level in tongue cancer tissue was significantly higher than that in para-carcinoma tissue; after siRNA transfection, cell OD value of NC-siRNA group showed increasing trend, cell OD value of LRG1-siRNA group showed decreasing trend, cell OD values of LRG1-siRNA group at all points in time after transfection were significantly lower than those of NC-siRNA group; 24h after transfection, angiogenesis-related molecules HIF-1α, PI3K, Akt and VEGF as well as anti-apoptotic molecules Bcl-2, Bmi-1 and Survivin expression levels in cells of LRG1-siRNA group were significantly lower than those of NC-siRNA group, pro-apoptotic molecules p53 and Caspase-3 as well as autophagy molecules Beclin-1 and LC3II expression levels were significantly higher than those of NC-siRNA group, and LC3I expression level was not significantly different from that of NC-siRNA group.Conclusions:LRG-1 shows a trend of high expression in tongue cancer tissue, and targeted inhibition of LRG-1 expression can reduce tongue cancer cell viability, inhibit angiogenesis and promote cell apoptosis and autophagy process.

  13. Expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Xuan-Hong Yi; Jing Wang

    2016-01-01

    Objective:To study the expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines.Methods:Cancer tissue and adjacent normal lung tissue were collected and mRNA contents of Klf8 were detected; lung cancer A549 cell lines were cultured, and after transfection of Klf8 siRNA, cell cycle, cell invasion and epithelial-mesenchymal transition were detected.Results:mRNA contents of Klf8 in lung cancer tissue were higher than those in adjacent normal lung tissue; after transfection of Klf8 siRNA, Klf8 mRNA inhibition rate was 74.31%; G0/G1 phase ratio of Klf8 siRNA group was higher than that of negative control siRNA group; ratios of S-phase and G2/M phase cells, mRNA contents of Cyclin D1 and number of cells invading to the outer side of the transwell microporous membrane were lower than those of negative control siRNA group; mRNA contents of CDH1 and CK18 as well as Snail and Slug of Klf8 siRNA group were higher than those of negative control siRNA group; mRNA contents of VIM and N-cadherin were lower than those of negative control siRNA group.Conclusion:The expression of Klf8 in lung cancer tissue abnormally elevates; downregulation of Klf8 expression in lung cancer cell lines can inhibit malignant biological effect of cells, manifested as cell cycle arrest as well as the inhibition of cell invasion and epithelial-mesenchymal transition processes.

  14. Expression Levels of RFP in Normal and Cancer Human Tissues via Real-time RT-PCR Detection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Ret finger protein(RFP) is a member of the tripartite motif family, which is characterized by a conserved RING finger of motif, a B-box, and a coiled-coil domain(they are called RBCC generally). Although RFP was known to be an oncogene when its RBCC moiety was connected with a tyrosine kinase domain by DNA rearrangement, its biological function was not well defined. In this study, by using real-time RT-PCR, the RFP expressions in human and mouse normal tissues, and in the cervical squamous cell carcinoma, endometrial adenocarcinoma, gastric adenocarcinoma, esophageal squamous cell carcinoma, and brain cancer tissues were analyzed. The result of the study proved that the highest level of mRNA reverse transcription appeared in the normal testical tissue, whereas that in other normal tissues of human and mice were low. The mRNA reverse transcription level of RFP was higher in the endometrial adenocarcinoma tissue than in the cervical squamous cell carcinoma tissue; the mRNA reverse transcription level of RFP in the gastric adenocarcinoma tissue was significantly higher than that in the esophageal squamous cell carcinoma tissue. It was also found that the mRNA reverse transcription level of RFP in the brain cancer tissue was higher than that in the normal brain tissue. These results suggested that RFP could possibly be a useful molecular target for the development of new therapeutics for malignant tumors.

  15. Molecular profiling of signalling pathways in formalin-fixed and paraffin-embedded cancer tissues.

    Science.gov (United States)

    Berg, Daniela; Hipp, Susanne; Malinowsky, Katharina; Böllner, Claudia; Becker, Karl-Friedrich

    2010-01-01

    In most hospitals word-wide, histopathological cancer diagnosis is currently based on formalin-fixed and paraffin-embedded (FFPE) tissues. In the last few years new approaches and developments in patient-tailored cancer therapy have raised the need to select more precisely those patients, who will respond to personalised treatments. The most efficient way for optimal therapy and patient selection is probably to provide a tumour-specific protein network portrait prior to treatment. The discovery and characterisation of deregulated signalling molecules (e.g. human epidermal growth factor receptor 2, mitogen-activated protein kinases) are very promising candidates for the identification of new suitable therapy targets and for the selection of those patients who will receive the greatest benefit from individualised treatments. The reverse phase protein array (RPPA) is a promising new technology that allows quick, precise and simultaneous analysis of many components of a network. Importantly it requires only limited amounts of routine clinical material (e.g. FFPE biopsies) and can be used for absolute protein measurements. We and other research groups have described successful protein extraction from routine FFPE tissues. In this manuscript we show how these recent developments might facilitate the implementation of RPPA in clinical trials and routine settings.

  16. Lung cancer in uranium miners: A tissue resource and pilot study. Final performance report

    Energy Technology Data Exchange (ETDEWEB)

    Samet, J.; Gilliland, F.D.

    1998-08-13

    This project incorporates two related research projects directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first project involved a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second project was a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives including facilitating the investigation of molecular changes in radon exposed lung cancer cases, developing methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and assessing the feasibility of recruiting former uranium miners into a longitudinal study that collected multiple biological specimens. A pilot study was conducted to determine whether blood collection, induced sputum, bronchial brushing, washings, and mucosal biopsies from participants at two of the hospitals could be included efficiently. A questionnaire was developed for the extended study and all protocols for specimen collection and tissue handling were completed. Resource utilization is in progress at ITRI and the methods have been developed to study molecular and cellular changes in exfoliated cells contained in sputum as well as susceptibility factors.

  17. Twist and YB-1 gene expression in cervical cancer and cervical intraepithelial neoplasia tissue as well as its correlation with epithelial-mesenchymal transition

    Institute of Scientific and Technical Information of China (English)

    Qin Liu; Hong Li; Yu Zhang

    2016-01-01

    Objective:To study the Twist and YB-1 gene expression in cervical cancer and cervical intraepithelial neoplasia tissue as well as its correlation with epithelial-mesenchymal transition. Methods:Normal cervical tissue, cervical intraepithelial neoplasia tissue and cervical cancer tissue were collected for study. ELISA kits were used to detect Twist, YB-1, E-cadherin,β-catenin, N-cadherin and Vimentin contents in cervical tissue, and immunohistochemistry was used to detect Twist and YB-1 expression levels in cervical tissue.Results:Twist and YB-1 contents, cell positive rate and immunohistochemical scores as well as N-cadherin and Vimentin contents in cervical cancer tissue and cervical intraepithelial neoplasia tissue were significantly higher than those in normal cervical tissue while E-cadherin andβ-catenin contents were lower than those in normal cervical tissue; Twist and YB-1 contents, cell positive rate and immunohistochemical scores as well as N-cadherin and Vimentin contents in cervical cancer tissue were significantly higher than those in cervical intraepithelial neoplasia tissue while E-cadherin andβ-catenin contents were lower than those in cervical intraepithelial neoplasia tissue; the higher the Twist and YB-1 expression levels in cervical cancer tissue, the lower the E-cadherin andβ-catenin contents, and the higher the N-cadherin and Vimentin contents.Conclusions: Twist and YB-1 gene overexpression can promote epithelial-mesenchymal transition to be involved in the occurrence of cervical cancer and cervical intraepithelial neoplasia.

  18. Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

    Science.gov (United States)

    Pu, Yang; Chen, Jun; Wang, Wubao

    2014-02-01

    The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

  19. Circulating tumor cells in early bladder cancer: insight into micrometastatic disease.

    Science.gov (United States)

    Raimondi, Cristina; Gradilone, Angela; Gazzaniga, Paola

    2014-05-01

    Although several studies have demonstrated the prognostic and predictive potential of circulating tumor cells (CTCs), to date their evaluation still has not impacted the treatment strategy. There is wide consensus that CTC assessment would be more beneficial in early stage cancer, especially in those tumor types characterized by early progression and a lack of prognostic markers. Non-muscle-invasive bladder cancer represents an optimal model to this purpose. In fact, the rate of metastatic spread ranges between 20 and 40%, which is unacceptable for a 'superficial' tumor and unexpected in an early stage cancer. This may be due to the presence of non-clinically detectable micrometastases. CTCs may be used as a noninvasive, real-time tool for the stratification of early stage bladder cancer patients according to individual risk of progression.

  20. New Insights into p53 Signaling and Cancer Cell Response to DNA Damage: Implications for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Razmik Mirzayans

    2012-01-01

    Full Text Available Activation of the p53 signaling pathway by DNA-damaging agents was originally proposed to result either in cell cycle checkpoint activation to promote survival or in apoptotic cell death. This model provided the impetus for numerous studies focusing on the development of p53-based cancer therapies. According to recent evidence, however, most p53 wild-type human cell types respond to ionizing radiation by undergoing stress-induced premature senescence (SIPS and not apoptosis. SIPS is a sustained growth-arrested state in which cells remain viable and secrete factors that may promote cancer growth and progression. The p21WAF1 (hereafter p21 protein has emerged as a key player in the p53 pathway. In addition to its well-studied role in cell cycle checkpoints, p21 regulates p53 and its upstream kinase (ATM, controls gene expression, suppresses apoptosis, and induces SIPS. Herein, we review these and related findings with human solid tumor-derived cell lines, report new data demonstrating dynamic behaviors of p53 and p21 in the DNA damage response, and examine the gain-of-function properties of cancer-associated p53 mutations. We point out obstacles in cancer-therapeutic strategies that are aimed at reactivating the wild-type p53 function and highlight some alternative approaches that target the apoptotic threshold in cancer cells with differing p53 status.

  1. Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue.

    Science.gov (United States)

    Wen, Yanghui; Da, Mingxu; Zhang, Yongbin; Peng, Lingzhi; Yao, Jibin; Duan, Yaoxing

    2015-01-01

    Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ(2) test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer.

  2. Insights into pancreatic cancer etiology from pathway analysis of genome-wide association study data.

    Directory of Open Access Journals (Sweden)

    Peng Wei

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in the U.S. and the etiology of this highly lethal disease has not been well defined. To identify genetic susceptibility factors for pancreatic cancer, we conducted pathway analysis of genome-wide association study (GWAS data in 3,141 pancreatic cancer patients and 3,367 controls with European ancestry.Using the gene set ridge regression in association studies (GRASS method, we analyzed 197 pathways identified from the Kyoto Encyclopedia of Genes and Genomes database. We used the logistic kernel machine (LKM test to identify major contributing genes to each pathway. We conducted functional enrichment analysis of the most significant genes (P<0.01 using the Database for Annotation, Visualization, and Integrated Discovery (DAVID.Two pathways were significantly associated with risk of pancreatic cancer after adjusting for multiple comparisons (P<0.00025 and in replication testing: neuroactive ligand-receptor interaction, (Ps<0.00002, and the olfactory transduction pathway (P = 0.0001. LKM test identified four genes that were significantly associated with risk of pancreatic cancer after Bonferroni correction (P<1×10(-5: ABO, HNF1A, OR13C4, and SHH. Functional enrichment analysis using DAVID consistently found the G protein-coupled receptor signaling pathway (including both neuroactive ligand-receptor interaction and olfactory transduction pathways to be the most significant pathway for pancreatic cancer risk in this study population.These novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer.

  3. CT-based compartmental quantification of adipose tissue versus body metrics in colorectal cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Nattenmueller, Johanna; Hoegenauer, Hanna; Grenacher, Lars; Kauczor, Hans-Ulrich [University Hospital, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Boehm, Juergen; Ulrich, Cornelia [Huntsman Cancer Institute, Department of Population Health Sciences, Salt Lake City, UT (United States); Scherer, Dominique; Paskow, Michael; Gigic, Biljana; Schrotz-King, Petra [National Center for Tumor Diseases and German Cancer Research Center, Division of Preventive Oncology, Heidelberg (Germany)

    2016-11-15

    While obesity is considered a prognostic factor in colorectal cancer (CRC), there is increasing evidence that not simply body mass index (BMI) alone but specifically abdominal fat distribution is what matters. As part of the ColoCare study, this study measured the distribution of adipose tissue compartments in CRC patients and aimed to identify the body metric that best correlates with these measurements as a useful proxy for adipose tissue distribution. In 120 newly-diagnosed CRC patients who underwent multidetector computed tomography (CT), densitometric quantification of total (TFA), visceral (VFA), intraperitoneal (IFA), retroperitoneal (RFA), and subcutaneous fat area (SFA), as well as the M. erector spinae and psoas was performed to test the association with gender, age, tumor stage, metabolic equivalents, BMI, waist-to-height (WHtR) and waist-to-hip ratio (WHR). VFA was 28.8 % higher in men (p{sub VFA}<0.0001) and 30.5 % higher in patients older than 61 years (p{sub VFA}<0.0001). WHtR correlated best with all adipose tissue compartments (r{sub VFA}=0.69, r{sub TFA}=0.84, p<0.0001) and visceral-to-subcutaneous-fat-ratio (VFR, r{sub VFR}=0.22, p=<0.05). Patients with tumor stages III/IV showed significantly lower overall adipose tissue than I/II. Increased M. erector spinae mass was inversely correlated with all compartments. Densitometric quantification on CT is a highly reproducible and reliable method to show fat distribution across adipose tissue compartments. This distribution might be best reflected by WHtR, rather than by BMI or WHR. (orig.)

  4. Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment.

    Science.gov (United States)

    Vlaisavljevich, Eli; Maxwell, Adam; Mancia, Lauren; Johnsen, Eric; Cain, Charles; Xu, Zhen

    2016-10-01

    Histotripsy is a non-invasive ultrasonic ablation method that uses cavitation to mechanically fractionate tissue into acellular debris. With a sufficient number of pulses, histotripsy can completely fractionate tissue into a liquid-appearing homogenate with no cellular structures. The location, shape and size of lesion formation closely match those of the cavitation cloud. Previous work has led to the hypothesis that the rapid expansion and collapse of histotripsy bubbles fractionate tissue by inducing large stress and strain on the tissue structures immediately adjacent to the bubbles. In the work described here, the histotripsy bulk tissue fractionation process is visualized at the cellular level for the first time using a custom-built 2-MHz transducer incorporated into a microscope stage. A layer of breast cancer cells were cultured within an optically transparent fibrin-based gel phantom to mimic cells inside a 3-D extracellular matrix. To test the hypothesis, the cellular response to single and multiple histotripsy pulses was investigated using high-speed optical imaging. Bubbles were always generated in the extracellular space, and significant cell displacement/deformation was observed for cells directly adjacent to the bubble during both bubble expansion and collapse. The largest displacements were observed during collapse for cells immediately adjacent to the bubble, with cells moving more than 150-300 μm in less than 100 μs. Cells often underwent multiple large deformations (>150% strain) over multiple pulses, resulting in the bisection of cells multiple times before complete removal. To provide theoretical support to the experimental observations, a numerical simulation was conducted using a single-bubble model, which indicated that histotripsy exerts the largest strains and cell displacements in the regions immediately adjacent to the bubble. The experimental and simulation results support our hypothesis, which helps to explain the formation of the

  5. Naturally occurring cancers in dogs: insights for translational genetics and medicine.

    Science.gov (United States)

    Alvarez, Carlos E

    2014-01-01

    Here, we briefly review the state of knowledge of human cancer genetics to elaborate on the need for different types of mammalian models, highlighting the strengths of the dog. Mouse models are unparalleled for their experimental tractability and rapid genetic manipulation but have some key limitations in the area of human relevance. Companion dog models are attractive, because they are genetically more similar to humans, share environmental exposures with their owners, suffer from the same diseases as humans, and receive a high level of health care. They are ideal for the study of chronic diseases, because they age five to eight times faster than humans and generally live to old age. In addition, each dog breed is on the order of 100-fold genetically simpler than the whole human or dog population. These traits make the dog ideal for the study of complex genetics of naturally occurring cancers. Here, we contrast the relative strengths of cancer genetics in humans and dogs. We propose that humans are most ideal for the study of somatic cancer genetics, whereas dogs are most ideal for germline genetics. That proposition is supported by comparison of genome-wide association studies (GWASs) in human and canine cancer. One of the advantages of dog cancer GWASs is the ability to rapidly map complex traits, conduct fine mapping and identification of causative variation, and thus be in a position to move on to functional studies. We mention how these strengths of dog models will lead to rapid advances in translational medicine.

  6. Ovarian Cancer: Can Proteomics Give New Insights for Therapy and Diagnosis?

    Directory of Open Access Journals (Sweden)

    Massimo Federico

    2013-04-01

    Full Text Available The study of the ovarian proteomic profile represents a new frontier in ovarian cancer research, since this approach is able to enlighten the wide variety of post-translational events (such as glycosylation and phosphorylation. Due to the possibility of analyzing thousands of proteins, which could be simultaneously altered, comparative proteomics represent a promising model of possible biomarker discovery for ovarian cancer detection and monitoring. Moreover, defining signaling pathways in ovarian cancer cells through proteomic analysis offers the opportunity to design novel drugs and to optimize the use of molecularly targeted agents against crucial and biologically active pathways. Proteomic techniques provide more information about different histological types of ovarian cancer, cell growth and progression, genes related to tumor microenvironment and specific molecular targets predictive of response to chemotherapy than sequencing or microarrays. Estimates of specificity with proteomics are less consistent, but suggest a new role for combinations of biomarkers in early ovarian cancer diagnosis, such as the OVA1 test. Finally, the definition of the proteomic profiles in ovarian cancer would be accurate and effective in identifying which pathways are differentially altered, defining the most effective therapeutic regimen and eventually improving health outcomes.

  7. Selenium and cancer: a story that should not be forgotten-insights from genomics.

    Science.gov (United States)

    Méplan, Catherine; Hesketh, John

    2014-01-01

    Selenium (Se) is an essential micronutrient that is incorporated into selenoproteins. Although epidemiological studies suggest that low Se intake is associated with increased risk of various cancers, the results of supplementation trials have been confusing. These conflicting results may be due to different baseline Se status and/or genetic factors. In addition, mechanistic links between Se intake, selenoproteins and carcinogenesis are not clear. In this article, we discuss the functional significance of single-nucleotide polymorphisms (SNP) in selenoprotein genes and the evidence as to whether or not they influence risk of colorectal, prostate, lung or breast cancers. Both in vitro and in vivo studies have shown that a small number of SNPs in genes encoding glutathione peroxidases 1 and 4, selenoprotein P, selenoprotein S and 15-kDa selenoprotein have functional consequences. Data from case-control studies suggest that a variant at codon 198 in glutathione peroxidase 1 influences the effect of Se status on prostate cancer and risk, and it has also been associated with breast cancer and lung cancer risk, whereas variants in glutathione peroxidase 4, selenoprotein P and selenoprotein S may influence the risk of colorectal cancer. In addition, the results of gene microarray (transcriptomic) studies have identified novel selenoprotein biomarkers of Se status and novel downstream Se-targeted pathways. The work highlights the need to take baseline Se status and genetic factors into account in the design of future intervention trials.

  8. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

    Science.gov (United States)

    Hugo, Honor J; Saunders, C; Ramsay, R G; Thompson, E W

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

  9. Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice

    Science.gov (United States)

    Tondera, Christoph; Hauser, Sandra; Krüger-Genge, Anne; Jung, Friedrich; Neffe, Axel T.; Lendlein, Andreas; Klopfleisch, Robert; Steinbach, Jörg; Neuber, Christin; Pietzsch, Jens

    2016-01-01

    Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue. PMID:27698944

  10. Effects of aqueous extract from Silybum marianum on adenosine deaminase activity in cancerous and noncancerous human gastric and colon tissues

    Directory of Open Access Journals (Sweden)

    Bahadır Öztürk

    2015-01-01

    Full Text Available Objective: Investigation of possible effects of Silybum marianum extract (SME on adenosine deaminase (ADA activity in cancerous and noncancerous human gastric and colon tissues to obtain information about possible mechanism of anticancer action of S. marianum. Materials and Methods: Cancerous and noncancerous human gastric and colon tissues removed from patients by surgical operations were used in the studies. The extract was prepared in distilled water. Before and after treatment with the extract, ADA activities in the samples were measured. Results: ADA activity was found to be lowered significantly in cancerous gastric tissues but not in noncancerous gastric tissues after treatment with the SME. In the colon tissues, ADA activities were however found to increase after the treatment of SME. Conclusion: Our results suggest that the aqueous extract from S. marianum inhibits ADA activity in cancerous gastric tissues significantly. It is suggested that in addition to other proposed mechanisms, accumulated adenosine due to the inhibition of ADA might also play a part in the anticancer properties of the S. marianum.

  11. Head and neck cancer in elderly patients: is microsurgical free-tissue transfer a safe procedure?

    Science.gov (United States)

    Tarsitano, A; Pizzigallo, A; Sgarzani, R; Oranges, C M; Cipriani, R; Marchetti, C

    2012-12-01

    The safety and success of microvascular transfer have been well documented in the general population, but the good results achieved with the use of free flaps in elderly patients have received little attention. This study sought to identify differences in complications, morbidity and functional outcomes between elderly (≥ 75 years) and younger (patients treated surgically for advanced head and neck cancer using the Head and Neck 35 module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire. Patient treatment consisted of composite resection, including excision of the primary tumour with ipsilateral or bilateral neck dissection and microvascular reconstruction. Eighty-five microvascular tissue transfers were performed to reconstruct major surgical defects. Postoperative radiation therapy was performed when indicated. Total flap loss occurred in three cases in elderly patients and two cases in younger patients. The rates of major surgical complication were 9% in young patients and 11% in elderly patients. No significant difference was observed between the two groups in the rates of major and minor flap complications, morbidity or long-term functional outcome. The results of the present analysis indicate that free-flap microvascular reconstruction can be considered a safe procedure in elderly patients with head and neck cancer.

  12. Serum matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in esophageal cancer patients.

    Science.gov (United States)

    Groblewska, Magdalena; Mroczko, Barbara; Kozlowski, Miroslaw; Niklinski, Jacek; Laudanski, Jerzy; Szmitkowski, Maciej

    2012-01-01

    The positive expression of MMP-2 and TIMP-2 were found in esophageal cancer (EC) tissue and correlated with cancer stage and clinico-pathological features of tumor and patients' survival. However, little is known about serum levels of those proteins in EC patients. The aim of the present study was to investigate the diagnostic significance of MMP-2 and TIMP-2 serum levels in EC patients in relation to clinico-pathological features of cancer. The study included 53 EC patients and 92 healthy controls. The serum levels of MMP-2, TIMP-2 and classical tumor markers CEA (carcinoembryonic antigen) and SCC (squamous cell carcinoma antigen) were assayed. The prognostic values and diagnostic criteria for the biomarkers tested were defined. Serum levels of MMP-2, TIMP-2 in EC patients were significantly lower, whereas CEA and SCC significantly higher than in control group. The diagnostic sensitivity of TIMP-2 (57%) was higher than those for other biomarkers tested and increased in combination with SCC (70%). Area under ROC curve for TIMP-2 (0.8698) was larger than for other proteins. In Cox's univariate analysis only SCC serum levels were significant prognostic factors for EC patients' survival. The results suggest the limited value of serum analyses of MMP-2 for tumor staging and prognosis in EC and the better usefulness of TIMP-2 than MMP-2 as a tumor marker in the diagnosis of EC, especially in combined use with SCC.

  13. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Science.gov (United States)

    Ihnatovych, Ivanna; Sielski, Neil L; Hofmann, Wilma A

    2014-01-01

    Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C). Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP) model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate-) cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN) lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  14. Transforming Big Data into Cancer-Relevant Insight: An Initial, Multi-Tier Approach to Assess Reproducibility and Relevance.

    Science.gov (United States)

    2016-08-01

    The Cancer Target Discovery and Development (CTD(2)) Network was established to accelerate the transformation of "Big Data" into novel pharmacologic targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding. This article represents a first attempt to delineate the challenges of supporting and confirming discoveries arising from the systematic analysis of large-scale data resources in a collaborative work environment and to provide a framework that would begin a community discussion to resolve these challenges. The Network implemented a multi-tier framework designed to substantiate the biological and biomedical relevance as well as the reproducibility of data and insights resulting from its collaborative activities. The same approach can be used by the broad scientific community to drive development of novel therapeutic and biomarker strategies for cancer. Mol Cancer Res; 14(8); 675-82. ©2016 AACR.

  15. Eliminating tissue-fold artifacts in histopathological whole-slide images for improved image-based prediction of cancer grade

    Directory of Open Access Journals (Sweden)

    Sonal Kothari

    2013-01-01

    Full Text Available Background: Analysis of tissue biopsy whole-slide images (WSIs depends on effective detection and elimination of image artifacts. We present a novel method to detect tissue-fold artifacts in histopathological WSIs. We also study the effect of tissue folds on image features and prediction models. Materials and Methods: We use WSIs of samples from two cancer endpoints - kidney clear cell carcinoma (KiCa and ovarian serous adenocarcinoma (OvCa - publicly available from The Cancer Genome Atlas. We detect tissue folds in low-resolution WSIs using color properties and two adaptive connectivity-based thresholds. We optimize and validate our tissue-fold detection method using 105 manually annotated WSIs from both cancer endpoints. In addition to detecting tissue folds, we extract 461 image features from the high-resolution WSIs for all samples. We use the rank-sum test to find image features that are statistically different among features extracted from the same set of WSIs with and without folds. We then use features that are affected by tissue folds to develop models for predicting cancer grades. Results: When compared to the ground truth, our method detects tissue folds in KiCa with 0.50 adjusted Rand index (ARI, 0.77 average true rate (ATR, 0.55 true positive rate (TPR, and 0.98 true negative rate (TNR; and in OvCa with 0.40 ARI, 0.73 ATR, 0.47 TPR, and 0.98 TNR. Compared to two other methods, our method is more accurate in terms of ARI and ATR. We found that 53 and 30 image features were significantly affected by the presence of tissue-fold artifacts (detected using our method in OvCa and KiCa, respectively. After eliminating tissue folds, the performance of cancer-grade prediction models improved by 5% and 1% in OvCa and KiCa, respectively. Conclusion: The proposed connectivity-based method is more effective in detecting tissue folds compared to other methods. Reducing tissue-fold artifacts will increase the performance of cancer-grade prediction

  16. Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue

    OpenAIRE

    Cooper, Colin S.; Eeles, Rosalind; Wedge, David C.; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G.; Camacho, Niedzica; Massie, Charlie E.; Kay, Jonathan; Luxton, Hayley J.; Edwards, Sandra; Kote-Jarai, Zsofia

    2015-01-01

    Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of on-going abnormal mutational pr...

  17. Insight into the impact of dietary saturated fat on tissue-specific cellular processes underlying obesity-related diseases.

    Science.gov (United States)

    Enos, Reilly T; Velázquez, Kandy T; Murphy, E Angela

    2014-06-01

    This study investigated the influence of three high-fat diets (HFDs), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, 24%) but identical in total fat (40%), for a 16-week period in mice on a variety of tissue-specific cellular processes believed to be at the root of obesity-related diseases. Specifically, we examined ectopic lipid accumulation, oxidative capacity [peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA and protein; mtDNA; Cox IV and cytochrome C protein; citrate synthase activity; and gene expression of fission 1, mitofusin (Mfn) 1 and Mfn2], oxidative stress (4-hydroxy-2-nonenal), endoplasmic reticulum (ER) stress (binding immunoglobulin protein, activating transcription factor 6-p50, p-eukaryotic initiation factor 2 alpha and x-box binding protein 1 spliced protein), inflammatory [p-c-Jun N-terminal kinase (JNK), p-nuclear factor kappa-B, p-p38 mitogen-activated protein kinase) and insulin signaling (p-Akt), and inflammation [tumor necrosis factor-alpha, monocyte chemotactic protein-1, interleukin-6, F4/80, toll-like receptor (TLR)2 and TLR4 gene expression] in various tissues, including the adipose tissue, liver, skeletal muscle and heart. In general, adipose and hepatic tissues were the only tissues which displayed evidence of dysfunction. All HFDs down-regulated adipose, cardiac and hepatic PGC-1α mRNA and hepatic citrate synthase activity, and induced adipose tissue oxidative stress, whereas only the 6%-SF and 12%-SF diet produced hepatic steatosis. However, compared to the 6%-SF and 24%-SF diets, consumption of the 12%-SF diet resulted in the greatest degree of dysregulation (hepatic ER and oxidative stress, JNK activation, increased F4/80 gene expression and down-regulation of adipose tissue Akt signaling). These findings suggest that the saturated fatty acid composition of an HFD can greatly influence the processes responsible for obesity-related diseases - nonalcoholic fatty

  18. Novel Insights into the Role of Caveolin-2 in Cell- and Tissue-Specific Signaling and Function

    Directory of Open Access Journals (Sweden)

    Grzegorz Sowa

    2011-01-01

    Full Text Available Caveolin-2 is one of the major protein components of cholesterol- and glycosphingolipid-rich flask-shaped invaginations of plasma membrane caveolae. A new body of evidence suggests that caveolin-2 plays an important, and often more direct, role than caveolin-1 in regulating signaling and function in a cell- and tissue type-specific manner. The purpose of this paper is to primarily focus on discussing how these recent discoveries may help better understand the specific contribution of caveolin-2 to lipid raft- and caveolae-regulated cell/tissue-specific signaling and functions.

  19. Biomimetic tissue platform for photothermal cancer therapy using gold nanorods (GNRs)

    Science.gov (United States)

    Nam, Ki-Hwan; Bae, Ji Yong; Jeong, Chan Bae; Kim, Gunhee; Lee, Kye-Sung; Chang, Ki-Soo

    2016-09-01

    Photothermal therapy (PT) provides a strong potential in treatment of tumors, selective cell death, through the ability of gold nanoparticles to target destructive heat preferentially to tumor regions. And yet, clinical application of the thermal therapies has not accomplished due to insufficient processes of the heating methods and temperature measuring techniques leading to low reproducibility of such treatment. In this study, we created a 3 dimensional tissue platform to characterize the heating method and to control the generated heat in the tissue used for a superficial cancer model using gold nanorods (GNRs) and near-infrared (NIR, 808 nm) laser. The 3D tissue platform involved a 2 mm wide hemisphere to confine the GNRs covered with20 μm thick polymer film designed to mimic localized nanoparticles in tumor. Moreover, this platform provides an easy way to measure heat distribution and temperature created in tumor cross section. To investigate the photothermal effect of GNRs on heat generation, the amount of GNRs and laser power density were controlled. The GNRs were shown to be the large absorption cross sections generating localized photothermal effects and hyperthermic effects on destructive consequences in the cell dynamics causing a partial tumor regression.

  20. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues

    Directory of Open Access Journals (Sweden)

    MunJu eKim

    2013-11-01

    Full Text Available Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  1. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  2. Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength

    Science.gov (United States)

    Pu, Yang; Wang, Wubao; Tang, Guichen; Alfano, Robert R.

    2010-07-01

    The fluorescence spectra of human cancerous and normal prostate tissues obtained by the selective excitation wavelength of 340 nm were measured. The contributions of principle biochemical components to tissue fluorescence spectra were investigated using the method of multivariate curve resolution with alternating least squares. The results show that there is a reduced contribution from the emission of collagen and increased contribution from nicotinamide adenine dinucleotide (NADH) in cancerous tissues as compared with normal tissue. This difference is attributed to the changes of relative contents of NADH and collagen during cancer development. This research may present a potential native biomarker for prostate cancer detection.

  3. Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer

    Science.gov (United States)

    Smolle, Maria A.; Bauernhofer, Thomas; Pummer, Karl; Calin, George A.; Pichler, Martin

    2017-01-01

    The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread. PMID:28241429

  4. A tissue biomarker panel predicting systemic progression after PSA recurrence post-definitive prostate cancer therapy.

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    Tohru Nakagawa

    Full Text Available BACKGROUND: Many men develop a rising PSA after initial therapy for prostate cancer. While some of these men will develop a local or metastatic recurrence that warrants further therapy, others will have no evidence of disease progression. We hypothesized that an expression biomarker panel can predict which men with a rising PSA would benefit from further therapy. METHODOLOGY/PRINCIPAL FINDINGS: A case-control design was used to test the association of gene expression with outcome. Systemic (SYS progression cases were men post-prostatectomy who developed systemic progression within 5 years after PSA recurrence. PSA progression controls were matched men post-prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years. Using expression arrays optimized for paraffin-embedded tissue RNA, 1021 cancer-related genes were evaluated-including 570 genes implicated in prostate cancer progression. Genes from 8 previously reported marker panels were included. A systemic progression model containing 17 genes was developed. This model generated an AUC of 0.88 (95% CI: 0.84-0.92. Similar AUCs were generated using 3 previously reported panels. In secondary analyses, the model predicted the endpoints of prostate cancer death (in SYS cases and systemic progression beyond 5 years (in PSA controls with hazard ratios 2.5 and 4.7, respectively (log-rank p-values of 0.0007 and 0.0005. Genes mapped to 8q24 were significantly enriched in the model. CONCLUSIONS/SIGNIFICANCE: Specific gene expression patterns are significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence.

  5. Quantum-dot-based immunofluorescent imaging of HER2 and ER provides new insights into breast cancer heterogeneity

    Science.gov (United States)

    Chen, Chuang; Peng, Jun; Xia, Heshun; Wu, Qiongshui; Zeng, Libo; Xu, Hao; Tang, Hongwu; Zhang, Zhiling; Zhu, Xiaobo; Pang, Daiwen; Li, Yan

    2010-03-01

    Breast cancer (BC) is a heterogeneous tumor, and better understanding of its heterogeneity is essential to improving treatment effect. Quantum dot (QD)-based immunofluorescent nanotechnology (QD-IHC) for molecular pathology has potential advantages in delineating tumor heterogeneity. This potential is explored in this paper by QD-IHC imaging of HER2 and ER. BC heterogeneity can be displayed more clearly and sensitively by QD-IHC than conventional IHC in BC tissue microarrays. Furthermore, the simultaneous imaging of ER and HER2 might help understand their interactions during the process of evolution of heterogeneous BC.

  6. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  7. New insights into the autotaxin/LPA axis in cancer development and metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Leblanc, Raphaël; Peyruchaud, Olivier, E-mail: olivier.peyruchaud@inserm.fr

    2015-05-01

    Lysophosphatidic acid (LPA) is a simple lipid with a single fatty acyl chain linked to a glycerophosphate backbone. Despite the simplicity of its structure but owing to its interactions with a series of at least six G protein-coupled receptors (LPA{sub 1–6}), LPA exerts pleiotropic bioactivities including stimulation of proliferation, migration and survival of many cell types. Autotaxin (ATX) is a unique enzyme with a lysophospholipase D (lysoPLD) activity that is responsible for the levels of LPA in the blood circulation. Both LPA receptor family members and ATX/LysoPLD are aberrantly expressed in many human cancers. This review will present the more striking as well as novel experimental evidences using cell lines, cancer mouse models and transgenic animals identifying the roles for ATX and LPA receptors in cancer progression, tumor cell invasion and metastasis.

  8. Expression and significance of S100P, CD147, and OCT4 in different prostate cancer tissue TNM stages.

    Science.gov (United States)

    Wang, Q; Zhang, J G; Wang, W

    2015-06-18

    The aim of this project was to investigate the expression and significance of S100P, CD147, and OCT4 in prostate cancer tissue at different TNM stages. We enrolled 54 patients with prostate cancer, 40 with benign prostatic hyperplasia, and 20 subjects with normal prostates. S100P, CD147, and OCT4 were detected by immunohistochemistry. The positive rate of S100P detection was 18.52% in prostate cancer tissues, significantly lower than in normal and benign prostate hyperplasia tissues (P ˂ 0.05). The positive expression rate of CD147 and OCT4 were 100 and 77.38% in prostate cancer tissue, respectively, both markedly higher than in normal and benign prostate hyperplasia tissue (P ˂ 0.05). The positive rate of S100P in stage V was 0, which was significantly lower than in stages I (37.50%) and II (35.71%) (P ˂ 0.05). OCT4 expression in stages III (86.67%) and V (94.12%) was higher than in stage I (37.50%). The positive rate of S100P in patients with distant metastasis was 4%, which was significantly lower than that in patients without metastases (P ˂ 0.05). In contrast, the positive rate of OCT4 in patients with distant metastasis was 92%. S100P, CD147, and OCT4 expression in prostate cancer patients with different degrees of differentiation had no significant difference (P > 0.05). Overall, our results demonstrated that S100P expression in prostate cancer tissue was significantly decreased, whereas CD147 and OCT4 expression was increased. Their expression levels were closely associated with TNM stage and distant metastasis, but were not related to the degree of differentiation.

  9. Mathematical models of tissue stem and transit target cell divisions and the risk of radiation- or smoking-associated cancer.

    Science.gov (United States)

    Little, Mark P; Hendry, Jolyon H

    2017-02-01

    There is compelling biological data to suggest that cancer arises from a series of mutations in single target cells, resulting in defects in cell renewal and differentiation processes which lead to malignancy. Because much mutagenic damage is expressed following cell division, more-rapidly renewing tissues could be at higher risk because of the larger number of cell replications. Cairns suggested that renewing tissues may reduce cancer risk by partitioning the dividing cell populations into lineages comprising infrequently-dividing long-lived stem cells and frequently-dividing short-lived daughter transit cells. We develop generalizations of three recent cancer-induction models that account for the joint maintenance and renewal of stem and transit cells, also competing processes of partially transformed cell proliferation and differentiation/apoptosis. We are particularly interested in using these models to separately assess the probabilities of mutation and development of cancer associated with "spontaneous" processes and with those linked to a specific environmental mutagen, specifically ionizing radiation or cigarette smoking. All three models demonstrate substantial variation in cancer risks, by at least 20 orders of magnitude, depending on the assumed number of critical mutations required for cancer, and the stem-cell and transition-cell mutation rates. However, in most cases the conditional probabilities of cancer being mutagen-induced range between 7-96%. The relative risks associated with mutagen exposure compared to background rates are also stable, ranging from 1.0-16.0. Very few cancers, generally Little difference is made to relative risks if competing processes of proliferation and differentiation in the partially transformed stem and transit cell population are allowed for, nor is any difference made if one assumes that transit cells require an extra mutation to confer malignancy from the number required by stem cells. The probability of a cancer

  10. NOTCH1, HIF1A and other cancer-related proteins in lung tissue from uranium miners--variation by occupational exposure and subtype of lung cancer.

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    Beate Pesch

    Full Text Available BACKGROUND: Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative exposure to these carcinogens with NOTCH1, HIF1A and other cancer-specific proteins in lung tissue from uranium miners. METHODOLOGY/PRINCIPAL FINDINGS: Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy repository by type of lung tissue, comprising adenocarcinoma (AdCa, squamous cell carcinoma (SqCC, small cell lung cancer (SCLC, and cancer-free tissue. Within each stratum, we additionally stratified by low or high level of exposure to radon or arsenic. Lifetime exposure to radon and arsenic was estimated using a quantitative job-exposure matrix developed for uranium mining. For 22 cancer-related proteins, immunohistochemical scores were calculated from the intensity and percentage of stained cells. We explored the associations of these scores with cumulative exposure to radon and arsenic with Spearman rank correlation coefficients (r(s. Occupational exposure was associated with an up-regulation of NOTCH1 (radon r(s = 0.18, 95% CI 0.02-0.33; arsenic: r(s = 0.23, 95% CI 0.07-0.38. Moreover, we investigated whether these cancer-related proteins can classify lung cancer using supervised and unsupervised classification. MUC1 classified lung cancer from cancer-free tissue with a failure rate of 2.1%. A two-protein signature discriminated SCLC (HIF1A low, AdCa (NKX2-1 high, and SqCC (NKX2-1 low with a failure rate of 8.4%. CONCLUSIONS/SIGNIFICANCE: These results suggest that the radiation-sensitive protein NOTCH1 can be up-regulated in lung tissue from uranium miners by level of exposure to pulmonary carcinogens. We evaluated a three-protein signature consisting of a physiological protein (MUC1, a cancer-specific protein (HIF1A, and a lineage-specific protein (NKX2-1 that could discriminate lung cancer and its major subtypes with a low failure rate.

  11. Application of HPLC Combined with Laser Induced Fluorescence for Protein Profile Analysis of Tissue Homogenates in Cervical Cancer

    OpenAIRE

    Sujatha Bhat; Ajeetkumar Patil; Lavanya Rai; Kartha, V. B.; Santhosh Chidangil

    2012-01-01

    A highly objective method, High Performance Liquid Chromatography with Laser Induced Fluorescence (HPLC-LIF) technique was used to study the protein profiles of normal and cervical cancer tissue homogenates. A total of 44 samples including normal cervical biopsy samples from the hysterectomy patients and the patients suffering from different stages of the cervical cancer were recorded by HPLC-LIF and analysed by Principle Component Analysis (PCA) to get statistical information on different t...

  12. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women.

    Science.gov (United States)

    Huh, Sung Jin; Oh, Hannah; Peterson, Michael A; Almendro, Vanessa; Hu, Rong; Bowden, Michaela; Lis, Rosina L; Cotter, Maura B; Loda, Massimo; Barry, William T; Polyak, Kornelia; Tamimi, Rulla M

    2016-04-01

    The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.

  13. Expression of a plant-associated human cancer antigen in normal,premalignant and malignant esophageal tissues

    Institute of Scientific and Technical Information of China (English)

    Jun Fu; Ping Qu; Mo Li; Hai-Mei Tian; Zhen-Hai Zheng; Xin-Wen Zheng; Wei Zhang

    2003-01-01

    AIM: To study the relationship between the expression profiles of a plant-associated human cancer antigen and carcinogenesis of esophagus and its significance. METHODS: We analyzed expression of a plant-associated human cancer antigen in biopsy specimens of normal (n=29),mildly hyperplastic (n=29), mildly (n=30), moderately (n=27)and severely dysplastic (n=29) and malignant esophageal (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human cancer antigen was mainly confined to the cytoplasm and showed diffuse type of staining. Positive staining was absent or weak in normal (0/30) and mildly hyperplastic tissue samples (2/29), while strong staining was observed in severe dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference of its expression between normal mucosa and severely dysplastic tissues (P<0.001) or carcinoma in situ (P<0.001). Significant difference was also observed between mild dysplasia and severe dysplasia (P<0.001) or carcinomain situ (P<0.001). An overall trend toward increased staining intensity with increasing grade of dysplasia was found. There was a linear correlation between grade of lesions and staining intensity (r=0.794,P<0.001). Samples from esophageal cancer showed no higher levels of expression than those in severely dysplastic lesions (P>0.05). CONCLUSION: The abnormal expression of this plantassociated human cancer antigen in esophageal lesions is a frequent and early finding in the normal-dysplasiacarcinoma sequence in esophageal carcinogenesis. It might contribute to the carcinogenesis of esophageal cancer. The abnormal expression of this plant-associated human cancer antigen in esophageal lesion tissues may serve as a potential new biomarker for early identification of esophageal cancer.

  14. Post-radiation changes in oral tissues - An analysis of cancer irradiation cases

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    Jay Ashokkumar Pandya

    2014-01-01

    Full Text Available Introduction: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. Aim: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC using special stains. Materials and Methods: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months, and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining, fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Statistical Analysis: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Results: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and  cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution.

  15. Analysis of laser surgery in non-melanoma skin cancer for optimal tissue removal

    Science.gov (United States)

    Fanjul-Vélez, Félix; Salas-García, Irene; Arce-Diego, José Luis

    2015-02-01

    Laser surgery is a commonly used technique for tissue ablation or the resection of malignant tumors. It presents advantages over conventional non-optical ablation techniques, like a scalpel or electrosurgery, such as the increased precision of the resected volume, minimization of scars and shorter recovery periods. Laser surgery is employed in medical branches such as ophthalmology or dermatology. The application of laser surgery requires the optimal adjustment of laser beam parameters, taking into account the particular patient and lesion. In this work we present a predictive tool for tissue resection in biological tissue after laser surgery, which allows an a priori knowledge of the tissue ablation volume, area and depth. The model employs a Monte Carlo 3D approach for optical propagation and a rate equation for plasma-induced ablation. The tool takes into account characteristics of the specific lesion to be ablated, mainly the geometric, optical and ablation properties. It also considers the parameters of the laser beam, such as the radius, spatial profile, pulse width, total delivered energy or wavelength. The predictive tool is applied to dermatology tumor resection, particularly to different types of non-melanoma skin cancer tumors: basocellular carcinoma, squamous cell carcinoma and infiltrative carcinoma. The ablation volume, area and depth are calculated for healthy skin and for each type of tumor as a function of the laser beam parameters. The tool could be used for laser surgery planning before the clinical application. The laser parameters could be adjusted for optimal resection volume, by personalizing the process to the particular patient and lesion.

  16. Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and their derived cancer stem cells.

    Science.gov (United States)

    D'Alessio, Alessio; Proietti, Gabriella; Lama, Gina; Biamonte, Filippo; Lauriola, Libero; Moscato, Umberto; Vescovi, Angelo; Mangiola, Annunziato; Angelucci, Cristiana; Sica, Gigliola

    2016-11-29

    The formation of new blood vessels represents a crucial event under both physiological and pathological circumstances. In this study, we evaluated by immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR the expression of HIF1α, HIF2α, VEGF, VEGFR1 and VEGFR2 in surgical glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50 patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro. Immunohistochemistry demonstrated the expression of angiogenesis markers in both GBM and peritumoral tissue. In addition, in vitro tube formation assay indicated that both GCSCs and PCSCs stimulate EC proliferation as well as tube-like vessel formation. An increased migration aptitude was mainly observed when ECs were cultured in the presence of GCSCs rather than in the presence of PCSCs. These findings suggest that relevant neoangiogenetic events may occur in GBM. In particular, VEGF/VEGFR co-expression in PCSCs leads to hypothesize the involvement of an autocrine signaling. Moreover, our results suggest that both GCSCs and PCSCs own the skill of activating the "angiogenic switch" and the capability of modulating EC behavior, indicating that both cell types are either responsive to angiogenic stimuli or able to trigger angiogenic response. Together with our previous findings, this study adds a further piece to the challenging puzzle of the characterization of peritumoral tissue and of the definition of its real role in GBM pathophysiology.

  17. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of...

  18. Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: The case of thyroid cancer

    Directory of Open Access Journals (Sweden)

    Gregoire B Morand

    2014-11-01

    Full Text Available Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer, we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signalling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the re-valuation of the potential preventive and anticancer properties of vitamin D in thyroid cancer.

  19. Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists

    OpenAIRE

    Garcia, Jorge A.

    2011-01-01

    Sipuleucel-T represents a novel immunotherapeutic compound designed to stimulate an immune response against castration-resistant prostate cancer (CRPC). Sipuleucel-T is an autologous active cellular immunotherapy product, which includes autologous dendritic cells pulsed ex vivo with PAP2024, a recombinant fusion protein made of prostatic acid phosphatase and granulocyte-macrophag...

  20. Molecular insights into mitochondrial dysfunction in cancer-related muscle wasting.

    Science.gov (United States)

    Antunes, Diana; Padrão, Ana Isabel; Maciel, Elisabete; Santinha, Deolinda; Oliveira, Paula; Vitorino, Rui; Moreira-Gonçalves, Daniel; Colaço, Bruno; Pires, Maria João; Nunes, Cláudia; Santos, Lúcio L; Amado, Francisco; Duarte, José Alberto; Domingues, Maria Rosário; Ferreira, Rita

    2014-06-01

    Alterations in muscle mitochondrial bioenergetics during cancer cachexia were previously suggested; however, the underlying mechanisms are not known. So, the goal of this study was to evaluate mitochondrial phospholipid remodeling in cancer-related muscle wasting and its repercussions to respiratory chain activity and fiber susceptibility to apoptosis. An animal model of urothelial carcinoma induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and characterized by significant body weight loss due to skeletal muscle mass decrease was used. Morphological evidences of muscle atrophy were associated to decreased respiratory chain activity and increased expression of mitochondrial UCP3, which altogether highlight the lower ability of wasted muscle to produce ATP. Lipidomic analysis of isolated mitochondria revealed a significant decrease of phosphatidic acid, phosphatidylglycerol and cardiolipin in BBN mitochondria, counteracted by increased phosphatidylcholine levels. Besides the impact on membrane fluidity, this phospholipid remodeling seems to justify, at least in part, the lower oxidative phosphorylation activity observed in mitochondria from wasted muscle and their increased susceptibility to apoptosis. Curiously, no evidences of lipid peroxidation were observed but proteins from BBN mitochondria, particularly the metabolic ones, seem more prone to carbonylation with the consequent implications in mitochondria functionality. Overall, data suggest that bladder cancer negatively impacts skeletal muscle activity specifically by affecting mitochondrial phospholipid dynamics and its interaction with proteins, ultimately leading to the dysfunction of this organelle. The regulation of phospholipid biosynthetic pathways might be seen as potential therapeutic targets for the management of cancer-related muscle wasting.

  1. Recent insights into cigarette smoking as a lifestyle risk factor for breast cancer

    Directory of Open Access Journals (Sweden)

    Kispert S

    2017-03-01

    Full Text Available Shannon Kispert, Jane McHowat Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO, USA Abstract: There have been many cohort studies published reviewing the epidemiological evidence that links breast cancer to cigarette smoking, yet the underlying mechanisms are largely unknown and research studies are few and incomplete. Although cohort studies are important in establishing a connection between breast cancer and cigarette smoking, basic science research is necessary to prove the relationship and to highlight potential interventions and drug targets that can be used to manage the disease. This subject has been controversial for many decades; however, there has been a recent resurgence in interest because of the widespread acknowledgment of the role lifestyle choices play in cancer development and progression. This review will detail the current statistics associated with cigarette smoking and discuss recent cohort and basic research studies that highlight the association of cigarette smoking and breast cancer initiation and progression. Keywords: metastasis, tobacco, tumor growth

  2. Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

    Directory of Open Access Journals (Sweden)

    Shyam A. Patel

    2011-06-01

    Full Text Available Among all cancers, malignancies of the breast are the second leading cause of cancer death in the United States after carcinoma of the lung. One of the major factors considered when assessing the prognosis of breast cancer patients is whether the tumor has metastasized to distant organs. Although the exact phenotype of the malignant cells responsible for metastasis and dormancy is still unknown, growing evidence has revealed that they may have stem cell-like properties that may account for resistance to chemotherapy and radiation. One process that has been attributed to primary tumor metastasis is the epithelial- to-mesenchymal transition. In this review, we specifically discuss breast cancer dissemination to the bone marrow and factors that ultimately serve to shelter and promote tumor growth, including the complex relationship between mesenchymal stem cells (MSCs and various aspects of the immune system, carcinoma-associated fibroblasts, and the diverse components of the tumor microenvironment. A better understanding of the journey from the primary tumor site to the bone marrow and subsequently the oncoprotective role of MSCs and other factors within that microenvironment can potentially lead to development of novel therapeutic targets.

  3. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    -assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

  4. Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer Cells.

    Science.gov (United States)

    Lizarraga, Floria; Ceballos-Cancino, Gisela; Espinosa, Magali; Vazquez-Santillan, Karla; Maldonado, Vilma; Melendez-Zajgla, Jorge

    2015-01-01

    Tissue inhibitor of metalloproteinase-4 (TIMP-4) is a member of extracellular matrix (ECM) metalloproteinases inhibitors that has pleiotropic functions. However, TIMP-4 roles in carcinogenesis are not well understood. Cell viability and flow cytometer assays were employed to evaluate cell death differences between H-Vector and H-TIMP-4 cell lines. Immunobloting and semi-quantitative RT-PCR were used to evaluate the expression of apoptosis regulators. We showed that TIMP-4 has apoptosis-sensitizing effects towards several death stimuli. Consistent with these findings, regulators of apoptosis from Inhibitors of Apoptosis Proteins (IAP), FLICE-like inhibitor proteins (FLIP) and Bcl-2 family members were modulated by TIMP-4. In addition, TIMP-4 knockdown resulted in cell survival increase after serum deprivation, as assessed by clonogenic cell analyses. This report shows that TIMP-4 regulates carcinogenesis through apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in tumorigenesis may provide clues for future therapies.

  5. Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Floria Lizarraga

    Full Text Available Tissue inhibitor of metalloproteinase-4 (TIMP-4 is a member of extracellular matrix (ECM metalloproteinases inhibitors that has pleiotropic functions. However, TIMP-4 roles in carcinogenesis are not well understood. Cell viability and flow cytometer assays were employed to evaluate cell death differences between H-Vector and H-TIMP-4 cell lines. Immunobloting and semi-quantitative RT-PCR were used to evaluate the expression of apoptosis regulators. We showed that TIMP-4 has apoptosis-sensitizing effects towards several death stimuli. Consistent with these findings, regulators of apoptosis from Inhibitors of Apoptosis Proteins (IAP, FLICE-like inhibitor proteins (FLIP and Bcl-2 family members were modulated by TIMP-4. In addition, TIMP-4 knockdown resulted in cell survival increase after serum deprivation, as assessed by clonogenic cell analyses. This report shows that TIMP-4 regulates carcinogenesis through apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in tumorigenesis may provide clues for future therapies.

  6. ENO1 Protein Levels in the Tumor Tissues and Circulating Plasma Samples of Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ying ZHANG

    2010-12-01

    Full Text Available Background and objective Proper tumor markers are useful to diagnosis, prognosis and treatment for lung cancer. The aim of this study is to examine the levels of alpha-enolase (ENO1 protein in the tumor tissues and peripheral plasma samples obtained from non-small cell lung cancer (NSCLC patients, and evaluate its potential clinical significance. Methods The ENO1 protein levels in the tumor tissues and corresponding normal tissues from 16 cases of lung squamous cell carcinoma were analyzed by Western blot. The ENO1 protein levels in the plasma samples from 42 healthy individuals, 34 patients with lung benign disease and 84 patients with NSCLC were measured by double antibody sandwich enzyme-linked immunosorbent assay. Results For 87.5% (14/16 of the patients with lung squamous cell carcinoma, the ENO1 protein level in the tumor tissues was higher than that in the corresponding normal lung tissues. The ENO1 protein level in the plasma of NSCLC patients was significantly higher than that in the plasma of healthy individuals (P=0.031 and patients with lung benign disease (P=0.019. Furthermore, the ENO1 protein level was significantly higher in the plasma of patients with lung adenocarcinoma than that of patients with lung squamous cell carcinoma. Conclusion The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer.

  7. Tumor tissue levels of tissue inhibitor of metalloproteinases-I (TIMP-I) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients

    DEFF Research Database (Denmark)

    Schrohl, Anne-Sofie; Look, Maxime P.; Gelder, Marion E. Meijer-van

    2009-01-01

    an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our......BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome...... after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. METHODS: From our original retrospectively collected tumor samples we...

  8. Nationwide survey of glandular tissue doses for the establishment of a breast cancer screening system using mammography. Analysis of technical parameters affecting the glandular tissue dose

    Energy Technology Data Exchange (ETDEWEB)

    Higashida, Yoshiharu [Kyushu Univ., Fukuoka (Japan). School of Health Sciences; Hagiwara, Akira; Asahara, Masaki [and others

    2000-09-01

    The effects of technical parameters, such as screen-film combinations, antiscatter grids, processing conditions and X-ray beam qualities, on the average glandular tissue dose of radiation were analyzed under two exposure conditions: The standard radiographic condition for an RMI 156 phantom at each facility (Standard Radiographic Condition). The radiographic condition needed to obtain a radiographic density of 1.20 to 1.40 with an RMI 156 phantom (Canonical Radiographic Condition). The analysis included 208 dose measurements at 104 facilities. The results showed that the average glandular tissue dose depends strongly on the grid types and screen-film combinations used. There were also significant differences in radiographic density between the Standard Radiographic Condition and the Canonical Radiographic Condition. This analysis of the technical parameters affecting the glandular tissue dose will be useful in establishing a standardized mammographic breast cancer screening system. (author)

  9. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  10. Autofluorescence spectroscopy for multimodal tissues characterization in colitis-associated cancer murine model

    Science.gov (United States)

    Dorez, Hugo; Sablong, Raphaël.; Canaple, Laurence; Saint-Jalmes, Hervé; Gaillard, Sophie; Moussata, Driffa; Beuf, Olivier

    2015-07-01

    The purpose of this research project is to assess mice colon wall, using three optical modalities (conventional endoscopy, confocal endomicroscopy and optical spectroscopy) and endoluminal MRI. The study is done in the context of inflammatory bowel disease and colorectal cancer that represent 13% of new cases of cancer, every year in western countries. An optical spectroscopic bench (autofluorescence and reflectance) was developed with a flexible fiber probe. This latter has been combined with a mini multi-purpose rigid endoscope and a confocal endomicroscope. The optical modalities were first used in vivo on SWISS mice. Then, a specific optical a phantom (containing two layers of distinct fluorophores) was developed in order to evaluate our two-channel spectroscopic probe as a basic depth-sensitive measurement tool. The preliminary results show the feasibility to combine such modalities in the same in vivo protocol. Conventional endoscopy is useful to depict inflammation along colon wall. Confocal endomicroscopy provides high-contrasted images of microvascularization. Measured optical spectra both depend on biochemical tissue content and layered structure of the medium. The light collected from one channel is not similar to the other, in terms of intensity and spectroscopic profile as the interaction with the medium observed volume is different. A comparative analysis of the spectra based on our in vitro model exhibits a strong correlation between simple index extracted from spectral data and two main phantom characteristics (fluorophore concentrations and superficial layer thickness). This work suggests that this technique could contribute to assess tissues alterations through autofluorescence spectroscopic measurement under endoscopy.

  11. Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Anna Kiyomi

    2015-08-01

    Full Text Available OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer–containing medium. Tissue growth and Th1/Th2/Th17 cytokine concentrations in the culture medium were analyzed and were related with hormone receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were expressed highly in culture medium of both cancer and normal tissues. However, IFN-γ, TNF-α, IL-2, and IL-17A were not detected in the supernatant of the three-dimensionally cultured normal mammary gland and are seemed to be specific to breast cancer tissues. The growth abilities of hormone receptor–negative cancer tissues were significantly higher than those of receptor-positive tissues (P = 0.0383. Cancer tissues of stage ≥IIB patients expressed significantly higher TNF-α levels as compared with those of patients with stage tissues resected from breast cancer patients can grow in the three-dimensional thermoreversible gelatin polymer culture system and produce Th1/Th2/Th17 cytokines. Hormone receptor–positive cancer tissues showed less growth ability. TNF-α is suggested to be a biomarker for the cancer stage.

  12. Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain

    DEFF Research Database (Denmark)

    Arrebola, Juan P; Fernández, Mariana F; Martín-Olmedo, Piedad;

    2014-01-01

    organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation...... of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.......01-1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort....

  13. Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.

    Science.gov (United States)

    Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M; Franklin, Ruth A; Luo, Chong T; Oh, Soyoung A; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S; Li, Ming O

    2016-01-28

    Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αβ, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a, and CD103, these cells share a gene-expression signature distinct from those of conventional NK cells, T cells, and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type-1-like innate lymphoid cells and type 1 innate-like T cells.

  14. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

    Science.gov (United States)

    Geurts, L; Neyrinck, A M; Delzenne, N M; Knauf, C; Cani, P D

    2014-03-01

    Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gut microbiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gut microbiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gut microbiota and

  15. Fluorescent marker-based and marker-free discrimination between healthy and cancerous human tissues using hyper-spectral imaging

    Science.gov (United States)

    Arnold, Thomas; De Biasio, Martin; Leitner, Raimund

    2015-06-01

    Two problems are addressed in this paper (i) the fluorescent marker-based and the (ii) marker-free discrimination between healthy and cancerous human tissues. For both applications the performance of hyper-spectral methods are quantified. Fluorescent marker-based tissue classification uses a number of fluorescent markers to dye specific parts of a human cell. The challenge is that the emission spectra of the fluorescent dyes overlap considerably. They are, furthermore disturbed by the inherent auto-fluorescence of human tissue. This results in ambiguities and decreased image contrast causing difficulties for the treatment decision. The higher spectral resolution introduced by tunable-filter-based spectral imaging in combination with spectral unmixing techniques results in an improvement of the image contrast and therefore more reliable information for the physician to choose the treatment decision. Marker-free tissue classification is based solely on the subtle spectral features of human tissue without the use of artificial markers. The challenge in this case is that the spectral differences between healthy and cancerous tissues are subtle and embedded in intra- and inter-patient variations of these features. The contributions of this paper are (i) the evaluation of hyper-spectral imaging in combination with spectral unmixing techniques for fluorescence marker-based tissue classification, (ii) the evaluation of spectral imaging for marker-free intra surgery tissue classification. Within this paper, we consider real hyper-spectral fluorescence and endoscopy data sets to emphasize the practical capability of the proposed methods. It is shown that the combination of spectral imaging with multivariate statistical methods can improve the sensitivity and specificity of the detection and the staging of cancerous tissues compared to standard procedures.

  16. Coexpression of cholecystokinin-B/gastrin receptor and gastrin gene in human gastric tissues and gastric cancer cell line

    Institute of Scientific and Technical Information of China (English)

    Jian-Jiang Zhou; Man-Ling Chen; Qun-Zhou Zhang; Jian-Kun Hu; Wen-Ling Wang

    2004-01-01

    AIM: To compare the expression patterns of cholecystokininB (CCK-B)/gastrin receptor genes in matched human gastric carcinoma and adjacent non-neoplastic mucosa of patients with gastric cancer, inflammatory gastric mucosa from patients with gastritis, normal stomachs from 2 autopsied patients and a gastric carcinoma cell line (SGC-7901), and to explore their relationship with progression to malignancy of human gastric carcinomas.METHODS: RT-PCR and sequencing were employed to detect the mRNA expression levels of CCK-B receptor and gastrin gene in specimens from 30 patients with gastric carcinoma and healthy bordering non-cancerous mucosa, 10 gastritis patients and normal stomachs from 2 autopsied patients as well as SGC-7901. The results were semi-quantified by normalizing it to the mRNA level of β-actin gene using Lab Image software. The sequences were analyzed by BLAST program. RESULTS: CCK-B receptor transcripts were detected in all of human gastric tissues in this study, including normal, inflammatory and malignant tissues and SGC-7901. However, the expression levels of CCK-B receptor in normal gastric tissues were higher than those in other groups (P<0.05),and its expressions did not correlate with the differentiation and metastasis of gastric cancer (P>0.05). On the other hand, gastrin mRNA was detected in SGC-7901 and in specimens obtained from gastric cancer patients (22/30) but not in other gastric tissues, and its expression was highly correlated with the metastases of gastric cancer (P<0.05). CONCLUSION: Human gastric carcinomas and gastric cancer cell line SGC-7901 cells coexpress CCK-B receptor and gastrin mRNA. Gastrin/CCK-B receptor autocrine or paracrine pathway may possibly play an important role in the progression of gastric cancer.

  17. Advanced endoscopic imaging for gastric cancer assessment: new insights with new optics?

    Science.gov (United States)

    Serrano, M; Kikuste, I; Dinis-Ribeiro, M

    2014-12-01

    The most immediate strategy for improving survival of gastric cancer patients is secondary prevention through diagnosis of early gastric cancer either through screening or follow-up of individuals at high risk. Endoscopy examination is therefore of paramount importance and two general steps are to be known in assessing gastric mucosa - detection and characterization. Over the past decade, the advent of advanced endoscopic imaging technology led to diverse descriptions of these modalities reporting them to be useful in this setting. In this review, we aim at summarizing the current evidence on the use of advance imaging in individuals at high-risk (i.e., advance stages of gastric atrophy/intestinal metaplasia) and in those harbouring neoplastic lesions, and address its potential usefulness providing the readers a framework to use in daily practice. Further research is also suggested.

  18. Beyond the body: insights from an Iyengar yoga program for women with disability after breast cancer.

    Science.gov (United States)

    Thomas, Roanne; Quinlan, Elizabeth; Kowalski, Kent; Spriggs, Paul; Hamoline, Rita

    2014-01-01

    Lymphedema, pain, and range of motion restrictions after breast cancer remain underexplored, and few interventions have been developed for these women. Together with a yoga instructor, our interdisciplinary research team developed a yoga program for women with lymphedema after breast cancer (n = 13). Qualitative interviews and participants' journals show that there were a number of benefits to the yoga program. Themes outlining these are (1) understanding arm morbidity; (2) becoming aware of posture; and (3) countering fatigue. More surprisingly, perhaps, the participants also described the ways in which yoga furthered their understandings of loss associated with disability, the fourth theme, and showed that yoga enhanced their experiences of embodiment, the final theme. Finally, we assert that our research demonstrates the potential for qualitative research connected to the evaluation of interventions and that it demonstrates the blurring of traditional boundaries between interventions and data collection.

  19. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients

    DEFF Research Database (Denmark)

    Ryberg, Marianne; Cortese, Giuliana; Nielsen, Gitte;

    2008-01-01

    BACKGROUND: Current recommendations that cancer patients receive a maximum cumulative dose of 900 mg/m(2) epirubicin are based on the risk of epirubicin-mediated cardiotoxicity and do not take into account the competing risk of death from cancer. Here, we identify risk factors for cardiotoxicity...... developed congestive heart failure classified as New York Heart Association class 2 or higher were recorded as having cardiotoxicity. Independent Cox multiple regression analyses for cardiotoxicity and for overall mortality were followed by competing risks analysis, with cardiotoxicity as the primary event...... and death from all other causes as the competing event. All statistical tests were two-sided. RESULTS: A total of 11.4% of patients developed cardiotoxicity. Risk factors for cardiotoxicity included increased cumulative dose of epirubicin (hazard ratio per every 100 mg/m(2) administered = 1.40, 95...

  20. Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.

    Directory of Open Access Journals (Sweden)

    Miangela M Lacle

    Full Text Available Connective tissue growth factor (CTGF/CCN2 is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC. The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109 with high expression in 31/109 cases (28.4%, but expression in tumor cells was only seen in 9.2% (10/109 of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15% assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002. Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied.

  1. Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer.

    Science.gov (United States)

    Zhao, Chunyan; Qiao, Yichun; Jonsson, Philip; Wang, Jian; Xu, Li; Rouhi, Pegah; Sinha, Indranil; Cao, Yihai; Williams, Cecilia; Dahlman-Wright, Karin

    2014-07-15

    Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties.

  2. Mechanistic insights into selective killing of OXPHOS-dependent cancer cells by arctigenin.

    Science.gov (United States)

    Brecht, Karin; Riebel, Virginie; Couttet, Philippe; Paech, Franziska; Wolf, Armin; Chibout, Salah-Dine; Pognan, Francois; Krähenbühl, Stephan; Uteng, Marianne

    2017-04-01

    Arctigenin has previously been identified as a potential anti-tumor treatment for advanced pancreatic cancer. However, the mechanism of how arctigenin kills cancer cells is not fully understood. In the present work we studied the mechanism of toxicity by arctigenin in the human pancreatic cell line, Panc-1, with special emphasis on the mitochondria. A comparison of Panc-1 cells cultured in glucose versus galactose medium was applied, allowing assessments of effects in glycolytic versus oxidative phosphorylation (OXPHOS)-dependent Panc-1 cells. For control purposes, the mitochondrial toxic response to treatment with arctigenin was compared to the anti-cancer drug, sorafenib, which is a tyrosine kinase inhibitor known for mitochondrial toxic off-target effects (Will et al., 2008). In both Panc-1 OXPHOS-dependent and glycolytic cells, arctigenin dissipated the mitochondrial membrane potential, which was demonstrated to be due to inhibition of the mitochondrial complexes II and IV. However, arctigenin selectively killed only the OXPHOS-dependent Panc-1 cells. This selective killing of OXPHOS-dependent Panc-1 cells was accompanied by generation of ER stress, mitochondrial membrane permeabilization and caspase activation leading to apoptosis and aponecrosis.

  3. Application of Small Angle X-ray Scattering (SAXS for Differentiation between Normal and Cancerous Breast Tissue

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Introduction: Small angle, between 3° and 10°, X ray scattering is predominantly coherent giving rise to diffraction effects that can be observed as constructive and destructive interferences. These interferences carry information about the molecular structure of the tissue and hence can be used to identify changes that occur due to cancer. Method: In this study an energy dispersive X-ray diffraction method was used. The optimum scattering angle, determined from a series of measurements on adipose breast tissue at several angles from 4 to 7.3 degrees, was found to be 6.5°. Once optimized the system was used to measure the diffraction profiles (corrected scattered intensity versus momentum transfer of a total of 99 breast tissue samples. The samples were both normal and tumour samples. Results: Adipose tissue showed a sharp, high intensity peak at low momentum transfer values of approximately 1.1nm-1. Adipose tissue, mixed tissue (adipose & fibroglandular and tumor have peaks at different values of momentum transfer that can be used to identify the tissue. Benign and malignant breast tissues can also be differentiated by both peak positions and peak heights. It was also observed that the results were reproducible even after the tissue had been preserved at liquid nitrogen temperatures. Conclusion: We were able to differentiate between normal, benign and malignant breast tissues by using energy dispersive small angle x-ray scattering.

  4. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  5. STUDY OF ECK GENE EXON-3 FROM HUMAN NORMAL TISSUE AND BREAST CANCER CELL LINE

    Institute of Scientific and Technical Information of China (English)

    李瑶琛; 孔令洪; 王一理; 司履生

    2003-01-01

    Objective To establish a method cloning the exon 3 of eck gene from normal tissue and ZR-75-1 cell line (a human breast cancer cell line)and study whether these genes exist mutant. Methods Designed a pair of specific primers and amplified the exon 3 of eck gene fragment from the extracted genomic DNA derived from normal epithelial cells from skin tissue and ZR-75-1 cell line respectively by PCR technique. Transformed the E.coil. JM109 with recombinant plamids constructed by inserting the amplified fragments into medium vector pUCm-T and sequenced these amplified fragments after primary screening of endonuclease restriction digestion and PCR amplification. Results ① Obtained the genomic DNA of human normal epithelial cells and ZR-75-1 cell line respectively. ② Obtained the amplified fragments of human exon 3 of eck gene through PCR technique. ③ Obtained the cloning vectors of exon 3 of eck gene of human normal epithelial cells and ZR-75-1 cell line respectively. ④ ZR-75-1 cell line exists mutation of nucleotides. Conclusion Successfully established the method of cloning the human exon 3 of eck gene and found some mutations in the detected samples. This study lays a foundation for further studying the function of eck gene in tumorgenesis.

  6. High‐throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium

    Science.gov (United States)

    Howat, William J; Daley, Frances; Zabaglo, Lila; McDuffus, Leigh‐Anne; Blows, Fiona; Coulson, Penny; Raza Ali, H; Benitez, Javier; Milne, Roger; Brenner, Herman; Stegmaier, Christa; Mannermaa, Arto; Chang‐Claude, Jenny; Rudolph, Anja; Sinn, Peter; Couch, Fergus J; Tollenaar, Rob A.E.M.; Devilee, Peter; Figueroa, Jonine; Sherman, Mark E; Lissowska, Jolanta; Hewitt, Stephen; Eccles, Diana; Hooning, Maartje J; Hollestelle, Antoinette; WM Martens, John; HM van Deurzen, Carolien; Investigators, kConFab; Bolla, Manjeet K; Wang, Qin; Jones, Michael; Schoemaker, Minouk; Broeks, Annegien; van Leeuwen, Flora E; Van't Veer, Laura; Swerdlow, Anthony J; Orr, Nick; Dowsett, Mitch; Easton, Douglas; Schmidt, Marjanka K; Pharoah, Paul D; Garcia‐Closas, Montserrat

    2016-01-01

    Abstract Automated methods are needed to facilitate high‐throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large‐scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics. TMAs were stained for Ki67 using standard immunohistochemical procedures, and scanned and digitized using the Ariol system. An automated algorithm was developed for the scoring of Ki67, and scores were compared to computer assisted visual (CAV) scores in a subset of 15 TMAs in a training set. We also assessed the correlation between automated Ki67 scores and other clinical and pathological characteristics. Overall, we observed good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64) between the automated and CAV scoring methods in the training set. The performance of the automated method varied by TMA (kappa range= 0.37–0.87) and study (kappa range = 0.39–0.69). The automated method performed better in satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p‐value for comparison = 0.005); and among cores with higher total nuclei counted by the machine (4,000–4,500 cells: kappa = 0.78) than those with lower counts (50–500 cells: kappa = 0.41; p‐value = 0.010). Among the 9,059 cases in this study, the correlations between automated Ki67 and clinical and pathological characteristics were found to be in the expected directions. Our findings indicate that automated scoring of Ki67 can be an efficient method to obtain good quality data across large numbers of TMAs from multicentre studies. However, robust algorithm development and rigorous pre‐ and post

  7. Adaptive radiotherapy for soft tissue changes during helical tomotherapy for head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Duma, M.N.; Kampfer, S.; Winkler, C.; Geinitz, H. [Universitaetsklinikum rechts der Isar, Muenchen (Germany). Dept. of Radiation Oncology; Schuster, T. [Universitaetsklinikum rechts der Isar, Muenchen (Germany). Inst. of Medical Statistics and Epidemiology

    2012-03-15

    The goal of the present study was to assess the frequency and impact of replanning triggered solely by soft tissue changes observed on the daily setup mega-voltage CT (MVCT) in head and neck cancer (H and N) helical tomotherapy (HT). A total of 11 patients underwent adaptive radiotherapy (ART) using MVCT. Preconditions were a soft tissue change > 0.5 cm and a tight mask. The dose-volume histograms (DVHs) derived from the initial planning kVCT (inPlan), the recalculated DVHs of the fraction (fx) when replanning was decided (actSit) and the DVHs of the new plan (adaptPlan) were compared. Assessed were the following: maximum dose (D{sub max}), minimum dose (D{sub min}), and mean dose (D{sub mean}) to the planning target volume (PTV) normalized to the prescribed dose; the D{sub mean}/fx to the parotid glands (PG), oral cavity (OC), and larynx (Lx); and the D{sub max}/fx to the spinal cord (SC) in Gy/fx. No patient had palpable soft tissue changes. The median weight loss at the moment of replanning was 2.3 kg. The median PTV D{sub mean} was 100% for inPlan, 103% for actSit, and 100% for adaptPlan. The PTV was always covered by the prescribed dose. A statistically significant increase was noted for all organs at risk (OAR) in the actSit. The D{sub mean} to the Lx, the D{sub mean} to the OC and the D{sub max} to the SC were statistically better in the adaptPlan. No statistically significant improvement was achieved by ART for the PGs. No significant correlations between weight and volume loss or between the volume changes of the organs to each other were observed, except a strong positive correlation of the shrinkage of the PGs ({rho} = + 0.77, p = 0.005). Soft tissue shrinkage without clinical palpable changes will not affect the coverage of the PTV, but translates into a higher delivered dose to the PTV itself and the normal tissue outside the PTV. The gain by ART in individual patients - especially in patients who receive doses close to the tolerance doses of the OAR

  8. Tissue antioxidants and postmenopausal breast cancer : the European Community Multicentre Study on Antioxidants, Myocardial Infarction and Cancer of the Breast (EURAMIC)

    NARCIS (Netherlands)

    Veer, P. van 't; Strain, J.J.; Fernandez-Crehuet, J.; Martin, B.C.; Thamm, M.; Kardinaal, A.F.M.; Kohlmeier, L.; Huttunen, J.K.; Martin-Moreno, J.M.; Kok, F.J.

    1996-01-01

    Antioxidants may protect against free radical mediated carcinogenesis. Epidemiological studies have not confirmed this hypothesis for breast cancer, possibly because of methodological limitations. Time-integrated exposure of α-tocopherol and β-carotene in adipose tissue, and selenium in toenails was

  9. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    Science.gov (United States)

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model