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Sample records for human breast colon

  1. 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.

  2. Breast and Colon Cancer Family Registries

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    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  3. Anticancer Effects of Different Seaweeds on Human Colon and Breast Cancers

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    Ghislain Moussavou

    2014-09-01

    Full Text Available Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

  4. Pink Breast Milk: Serratia marcescens Colonization.

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    Valle, Cipatli Ayuzo Del; Salinas, Emilio Treviño

    2014-11-01

    Background Breast milk can turn pink with Serratia marcescens colonization, this bacterium has been associated with several diseases and even death. It is seen most commonly in the intensive care settings. Discoloration of the breast milk can lead to premature termination of nursing. We describe two cases of pink-colored breast milk in which S. marsescens was isolated from both the expressed breast milk. Antimicrobial treatment was administered to the mothers. Return to breastfeeding was successful in both the cases. Conclusions Pink breast milk is caused by S. marsescens colonization. In such cases,early recognition and treatment before the development of infection is recommended to return to breastfeeding.

  5. Multi-target QPDR classification model for human breast and colon cancer-related proteins using star graph topological indices.

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    Munteanu, Cristian Robert; Magalhães, Alexandre L; Uriarte, Eugenio; González-Díaz, Humberto

    2009-03-21

    The cancer diagnostic is a complex process and, sometimes, the specific markers can interfere or produce negative results. Thus, new simple and fast theoretical models are required. One option is the complex network graphs theory that permits us to describe any real system, from the small molecules to the complex genetic, neural or social networks by transforming real properties in topological indices. This work converts the protein primary structure data in specific Randic's star networks topological indices using the new sequence to star networks (S2SNet) application. A set of 1054 proteins were selected from previous works and contains proteins related or not with two types of cancer, human breast cancer (HBC) and human colon cancer (HCC). The general discriminant analysis method generates an input-coded multi-target classification model with the training/predicting set accuracies of 90.0% for the forward stepwise model type. In addition, a protein subset was modified by single amino acid mutations with higher log-odds PAM250 values and tested with the new classification if can be related with HBC or HCC. In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. These results promote the use of the S2SNet in clinical proteomics.

  6. Characterization of the glycosylation profile of the human breast cancer cell line, MDA-231, and a bone colonizing variant.

    Science.gov (United States)

    Carcel-Trullols, Jaime; Stanley, Joseph S; Saha, Rinku; Shaaf, Saeid; Bendre, Manali S; Monzavi-Karbassi, Behjatolah; Suva, Larry J; Kieber-Emmons, Thomas

    2006-05-01

    The mechanisms that guide organ-specific metastases are not fully established. The aberrant expression of carbohydrates may play a fundamental role in defining the molecular mechanisms for metastases to distant organs and facilitate positive interactions within the target organ. The purpose of the present study was to determine the glycomic profile of a variant of the MDA-MB-231 breast cancer cell line that colonizes the bone and to ascribe mechanistic functions mediated by carbohydrates that might correlate with clinical bone metastases. The carbohydrate expression profiles of osteolytic MDA-MET breast cancer cells and non-osteolytic parental MDA-MB-231 cells were determined. MDA-MET cells were derived from MDA-MB-231 cells by in vivo selection of metastatic bone lesions following intracardiac inoculation. The two related breast cancer cell lines expressed distinct carbohydrate profiles; MDA-MET cells displayed an increased expression of alpha (2,6) linked sialic acid, N-beta1-6 GlcNAc, and sialylated Lewis-A antigen, and decreased expression of Galbeta1,3GalNAc as detected using a combination of lectins and anti-carbohydrate antibodies. Microarray analysis demonstrated an increased expression of glycosyltransferase genes, correlative for the distinct glycomic phenotype. The altered glycomic phenotypes of MDA-MET cells include effects on the differential binding to bone marrow endothelial cells, enhanced ECM binding and an increase in invasive potential. These data suggest that the glycomic phenotype of MDA-MET cells is associated with a select set of accumulated functions that collectively impact on the bone metastases and bone colonization capacity of breast cancer cells.

  7. Fetal microchimerism in breast and colon cancer

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, M; Biggar, R J; Stamper, Casey L

    2011-01-01

    . DNA from repository buffy coat specimens was tested for male FMc with quantitative PCR targeting the DYS14gene on the Y chromosome. For this analysis, 89 women who developed breast cancer and 67 women who developed colon cancer were evaluable for FMc. Results were compared to 272 women who remained......1574 Background: Cells acquired by a woman from her baby that durably persist in her blood and tissues is known as fetal microchimerism (FMc). In women with breast cancer, frequency and quantity of FMc in blood and breast tissue is reduced compared to healthy women. Whether the absence of fetal...... microchimerism predicts risk for developing breast cancer is unknown. FMc was evaluated in buffy coat cells from presumed healthy women who later developed breast cancer or colon cancer, a cancer in which prior pregnancy appears protective but has different associations with endocrine risk factors. METHODS...

  8. Melanocyte colonization and pigmentation of breast carcinoma

    DEFF Research Database (Denmark)

    Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine

    2012-01-01

    Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion....... The pathogenesis by which melanocyte migration takes place is not known, but a breached basement membrane is considered essential. Conclusion. Histological examination and additional staining of skin are essential to differentiate breast cancer melanosis from malignant melanoma....

  9. Modulation of toll-like receptor 7 and LL-37 expression in colon and breast epithelial cells by human beta-defensin-2.

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    Stroinigg, Nora; Srivastava, Maya D

    2005-01-01

    Breast-feeding decreases maternal breast cancer risk. Breast-fed infants have fewer infections and inflammatory-allergic diseases. We recently found inducible antimicrobial and immunomodulatory protein human beta3-defensin 2 (HBD-2) in significant amounts in human milk. We investigated if HBD-2 could contribute to benefits of breast-feeding for the mother and the child by immunomodulating effects on breast and gut epithelial cells. Human CaCo-2 colon and MCF-7 breast cell lines were cultured for 16-48 hours in RPMI 1640 5% fetal calf serum with and without HBD-2 at 0.1, 0.5, and 1.0 microg/mL. RNA was extracted and reverse-transcription polymerase chain reaction (RT-PCR) and gel electrophoresis for toll-like receptor pathway members, antimicrobial peptides, and cytokines/receptors was performed. Primers were designed with www.ncbi.nlm.nih.gov and www.broad. mit.edu/cgibin/primer/primer3 www.cgi. Based on RT-PCR results, cells were stained by immunohistochemistry using anti-toll-like receptor (TLR)-7 and anti-LL37 antibodies and DAKO EnVision Plus kits. Supernatants were analyzed for interleukin (IL)-8 and liver and activation-regulated chemokine (LARC) using enzyme-linked immunosorbent assay. In CaCo-2, messenger RNA (mRNA) for TLR-7, IL-1R-associated kinase, alpha-defensins (human neutrophil peptides 1-3), and IL-8 were down-regulated; cathelicidin/LL37 and NFkappaBp65 were up-regulated. LARC mRNA and protein were detected after 48 hours. TLR-7 protein, LARC, and IL-8 decreased with HBD-2; LL-37 protein greatly increased. In MCF-7, mRNA for LL37, inhibitor of kappaBalpha, NFkappaBp65, Tollip, MyD88, IL-1R-associated kinase, and TLR-7 were up-regulated. LARC mRNA was turned off. TLR-7 protein was induced. LARC was not detected. IL-8 was barely detectable with or without HBD-2. beta-Defensins 1 and 2; alpha-defensins 5 and 6; TLRs 1, 2, 3, 4, 5, 6, 8, 9, and 10; nucleotide binding oligomerization domain protein-2, and CCR6 mRNA were unaffected. HBD-2 profoundly

  10. Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells.

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    Croft, Amanda; Guo, Su Tang; Sherwin, Simonne; Farrelly, Margaret; Yan, Xu Guang; Zhang, Xu Dong; Jiang, Chen Chen

    2017-03-25

    The 4-phosphatase Inositol polyphosphate 4-phosphatase II (INPP4B) is a regulator of the PI3K signalling pathway and functions to suppress or promote activation of downstream kinases depending on cell type and context. Here we report the identification of a novel small transcript variant of INPP4B (INPP4B-S) that has a role in promoting proliferation of colon and breast cancer cells. INPP4B-S differed from full length INPP4B (INPP4B-FL) by the insertion of a small exon between exons 15 and 16 and the deletion of exons 20-24. Nevertheless, INPP4B-S retained all the functional domains of INPP4B-FL and was similarly located to the cytoplasm. Overexpression of INPP4B-S increased, whereas selective knockdown of INPP4B-S reduced the rate of proliferation in HCT116 and MCF-7 cells. These results warrant further investigation of the role INPP4B-S in activation of downstream kinases and in regulation of cancer pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Explant cultures of human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Barrett, L.A.; Jackson, F.E.

    1978-01-01

    Human colonic epithelium has been cultured as explants in a chemically defined medium for periods of 1 to 20 days. The viability of the explants was shown by the preservation of the ultrastructural features of the colonic epithelial cells and by active incorporation of radioactive precursors into...

  12. Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway

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    JEDINAK, ANDREJ; SLIVA, DANIEL

    2009-01-01

    In spite of the global consumption of mushrooms, only two epidemiological studies demonstrated an inverse correlation between mushroom intake and the risk of cancer. Therefore, in the present study we evaluated whether extracts from edible mushrooms Agaricus bisporus (portabella), Flammulina velutipes (enoki), Lentinula edodes (shiitake) and Pleurotus ostreatus (oyster) affect the growth of breast and colon cancer cells. Here, we identified as the most potent, P. ostreatus (oyster mushroom) which suppressed proliferation of breast cancer (MCF-7, MDA-MB-231) and colon cancer (HT-29, HCT-116) cells, without affecting proliferation of epithelial mammary MCF-10A and normal colon FHC cells. Flow cytometry revealed that the inhibition of cell proliferation by P. ostreatus was associated with the cell cycle arrest at G0/G1 phase in MCF-7 and HT-29 cells. Moreover, P. ostreatus induced the expression of the tumor suppressor p53 and cyclin-dependent kinase inhibitor p21(CIP1/WAF1), whereas inhibited the phosphorylation of retinoblastoma Rb protein in MCF-7 cells. In addition, P. ostreatus also up-regulated expression of p21 and inhibited Rb phosphorylation in HT-29 cells, suggesting that that P. ostreatus suppresses the proliferation of breast and colon cancer cells via p53-dependent as well as p53-independent pathway. In conclusion, our results indicated that the edible oyster mushroom has potential therapeutic/preventive effects on breast and colon cancer. PMID:19020765

  13. Invasive ductal breast cancer metastatic to the sigmoid colon

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    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  14. Microchimerism and survival after breast and colon cancer diagnosis

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads

    2012-01-01

    Recently, we reported microchimerism to be oppositely associated with maternal breast and colon cancer. In women with a blood test positive for male microchimerism the risk of breast cancer development was reduced to one third, whereas the risk of colon cancer was elevated 4-fold. In this article...... addendum, I report the survival of cases in the original study after being diagnosed with cancer. Despite small numbers, the analysis suggests that microchimerism may be positively associated with survival after breast and maybe colon cancer diagnosis. Despite the findings on colon cancer in our original...... report, I speculate whether microchimerism could have a general beneficial role in cancer, which in some sites may not be evident because an allogeneic maternal immune reaction hastens cancer development....

  15. Tomatine-Containing Green Tomato Extracts Inhibit Growth of Human Breast, Colon, Liver, and Stomach Cancer Cells

    Science.gov (United States)

    Tomato plants (Lycopersicon esculentum) synthesize the glycoalkaloids dehydrotomatine and a–tomatine, possibly as a defense against bacteria, fungi, viruses, and insects. We investigated six green and three red tomato extracts for their ability to induce cell death in human cancer and normal cells ...

  16. Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers.

    Science.gov (United States)

    zur Hausen, Harald; de Villiers, Ethel-Michele

    2015-08-15

    The analysis of published epidemiological data on colon and breast cancer reveals a remarkable concordance for most regions of the world. A low incidence for both cancers has been recorded in Mongolia and Bolivia. Discrepant data, however, have been reported for India, Japan and Korea. In India, the incidence of breast cancer is significantly higher than for colon cancer, in Japan and Korea colon cancer exceeds by far the rate of breast cancer. Here, studies are summarized pointing to a species-specific risk for colon cancer after consumption of beef originating from dairy cattle. Uptake of dairy products of Bos taurus-derived milk cattle, particularly consumed at early age, is suggested to represent one of the main risk factors for the development of breast cancer. A recent demonstration of reduced breast cancer rates in individuals with lactose intolerance (Ji et al., Br J Cancer 2014; 112:149-52) seems to be in line with this interpretation. Species-specific risk factors for these cancers are compatible with the transmission of different infectious factors transferred via meat or dairy products. Countries with discordant rates of colon and breast cancer reveal a similar discordance between meat and milk product consumption of dairy cattle. The recent isolation of a larger number of novel presumably viral DNAs from serum, meat and dairy products of healthy dairy cows, at least part of them infectious for human cells, deserves further investigation. Systemic infections early in life, resulting in latency and prevention of subsequent infections with the same agent by neutralizing antibodies, would require reconsideration of ongoing prospective studies conducted in the adult population. © 2015 UICC.

  17. Opposite effects of microchimerism on breast and colon cancer

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Biggar, Robert J; Tjønneland, Anne

    2012-01-01

    was to determine whether the lower concentrations predate cancer diagnosis, and whether a possible beneficial effect was specific to breast cancer. METHODS: We conducted a prospective case-cohort study of 50-64-year-old Danish women enrolled in the Diet, Cancer and Health cohort. Blood samples and questionnaire...... of male microchimerism was strongly associated with reduced risk of developing breast cancer and also the increased risk of developing colon cancer. Confirmatory findings based on an improved study design, failure to identify important confounders and the strength of the associations lead us to believe...

  18. Inhibition of human MCF-7 breast cancer cells and HT-29 colon cancer cells by rice-produced recombinant human insulin-like growth binding protein-3 (rhIGFBP-3.

    Directory of Open Access Journals (Sweden)

    Stanley C K Cheung

    Full Text Available BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3 is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I to form a complex (IGF-I/IGFBP-3 that can treat growth hormone insensitivity syndrome (GHIS and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3 in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively and HT-29 colon cancer cells (65.14 ± 3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively when compared with wild type rice. CONCLUSION/SIGNIFICANCE: These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.

  19. Aluminium and the human breast.

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    Darbre, P D

    2016-06-01

    The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Prehistoric human colonization of India.

    Science.gov (United States)

    Misra, V N

    2001-11-01

    Human colonization in India encompasses a span of at least half-a-million years and is divided into two broad periods, namely the prehistoric (before the emergence of writing) and the historic (after writing). The prehistoric period is divided into stone, bronze and iron ages. The stone age is further divided into palaeolithic, mesolithic and neolithic periods. As the name suggests, the technology in these periods was primarily based on stone. Economically, the palaeolithic and mesolithic periods represented a nomadic, hunting-gathering way of life, while the neolithic period represented a settled, food-producing way of life. Subsequently copper was introduced as a new material and this period was designated as the chalcolithic period. The invention of agriculture, which took place about 8000 years ago, brought about dramatic changes in the economy, technology and demography of human societies. Human habitat in the hunting-gathering stage was essentially on hilly, rocky and forested regions, which had ample wild plant and animal food resources. The introduction of agriculture saw it shifting to the alluvial plains which had fertile soil and perennial availability of water. Hills and forests, which had so far been areas of attraction, now turned into areas of isolation. Agriculture led to the emergence of villages and towns and brought with it the division of society into occupational groups. The first urbanization took place during the bronze age in the arid and semi-arid region of northwest India in the valleys of the Indus and the Saraswati rivers, the latter represented by the now dry Ghaggar-Hakra bed. This urbanization is known as the Indus or Harappan civilization which flourished during 3500-1500 B.C. The rest of India during this period was inhabited by neolithic and chalcolithic farmers and mesolithic hunter-gatherers. With the introduction of iron technology about 3000 years ago, the focus of development shifted eastward into the Indo-Gangetic divide and

  1. Prehistoric human colonization of India

    Indian Academy of Sciences (India)

    V N Misra

    2001-11-01

    Human colonization in India encompasses a span of at least half-a-million years and is divided into two broad periods, namely the prehistoric (before the emergence of writing) and the historic (after writing). The prehistoric period is divided into stone, bronze and iron ages. The stone age is further divided into palaeolithic, mesolithic and neolithic periods. As the name suggests, the technology in these periods was primarily based on stone. Economically, the palaeolithic and mesolithic periods represented a nomadic, hunting-gathering way of life, while the neolithic period represented a settled, food-producing way of life. Subsequently copper was introduced as a new material and this period was designated as the chalcolithic period. The invention of agriculture, which took place about 8000 years ago, brought about dramatic changes in the economy, technology and demography of human societies. Human habitat in the hunting-gathering stage was essentially on hilly, rocky and forested regions, which had ample wild plant and animal food resources. The introduction of agriculture saw it shifting to the alluvial plains which had fertile soil and perennial availability of water. Hills and forests, which had so far been areas of attraction, now turned into areas of isolation. Agriculture led to the emergence of villages and towns and brought with it the division of society into occupational groups. The first urbanization took place during the bronze age in the arid and semi-arid region of northwest India in the valleys of the Indus and the Saraswati rivers, the latter represented by the now dry Ghaggar–Hakra bed. This urbanization is known as the Indus or Harappan civilization which flourished during 3500–1500 B.C. The rest of India during this period was inhabited by neolithic and chalcolithic farmers and mesolithic hunter-gatherers. With the introduction of iron technology about 3000 years ago, the focus of development shifted eastward into the Indo-Gangetic divide

  2. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

    Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

    2017-08-02

    Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.

    Science.gov (United States)

    Boccia, Antonio; Virata, Cyrus; Lindner, Daniel; English, Nicki; Pathan, Nuzhat; Brickelmaier, Margot; Hu, Xiao; Gardner, Jennifer L; Peng, Liaomin; Wang, Xinzhong; Zhang, Xiamei; Yang, Lu; Perron, Keli; Yco, Grace; Kelly, Rebecca; Gamez, James; Scripps, Thomas; Bennett, Donald; Joseph, Ingrid B; Baker, Darren P

    2017-01-01

    Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

  4. Human milk oligosaccharides: only the breast.

    Science.gov (United States)

    McVeagh, P; Miller, J B

    1997-08-01

    Over 100 years ago it was first deduced that a major component of human milk must be an unidentified carbohydrate that was not found in cows milk. At first this was thought to be a form of lactose and was called gynolactose. We now know that this was not a single carbohydrate but a complex mixture of approximately 130 different oligosaccharides. Although small amounts of a few oligosaccharides have been found in the milk of other mammals, this rich diversity of sugars is unique to human milk. The oligosaccharide content of human milk varies with the infant's gestation, the duration of lactation, diurnally and with the genetic makeup of the mother. Milk oligosaccharides have a number of functions that may protect the health of the breast fed infant. As they are not digested in the small intestine, they form the 'soluble' fibre of breast milk and their intact structure is available to act as competitive ligands protecting the breast-fed infant from pathogens. There is a growing list of pathogens for which a specific oligosaccharide ligand has been described in human milk. They are likely to form the model for future therapeutic and prophylactic anti-microbials. They provide substrates for bacteria in the infant colon and thereby contribute to the difference in faecal pH and faecal flora between breast and formula-fed infants. They may also be important as a source of sialic acid, essential for brain development.

  5. Aluminium and human breast diseases.

    Science.gov (United States)

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.

  6. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  7. Polyamines in Human Breast Milk

    OpenAIRE

    Nihal Büyükuslu

    2015-01-01

    Human milk is the ideal food for all newborns and infants. It involves macro nutrients and functional compounds for growth and development. The composition of breast milk differs between preterm and term milk. Polyamines are essential for cell proliferation and differentiation. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as food, and intestinal microbiota. Breast milk is the first source of exogenous polyamines...

  8. Breast metastasis of primary colon cancer Metástasis en mama de carcinoma primario de colon

    Directory of Open Access Journals (Sweden)

    L. Fernández de Bobadilla

    2004-06-01

    Full Text Available Metastatic tumors to the breast from colon adenocarcinoma are very rare. They are usually indicative of disseminated disease, and the prognosis is poor. Generally, radical operation should be avoided unless needed for palliation. This case report described a patient with breast metastasis from colon adenocarcinoma treated by simple mastectomy.La metástasis en la mama de tumores de colon es una entidad muy poco frecuente. El pronóstico a largo plazo es infausto, pues esta lesión es expresión de enfermedad sistémica. El tratamiento quirúrgico debe ser lo más conservador posible, ya que es un tratamiento paliativo. Presentamos un caso de esta rara entidad, tratada mediante mastectomía.

  9. Microbial dysbiosis is associated with human breast cancer.

    Directory of Open Access Journals (Sweden)

    Caiyun Xuan

    Full Text Available Breast cancer affects one in eight women in their lifetime. Though diet, age and genetic predisposition are established risk factors, the majority of breast cancers have unknown etiology. The human microbiota refers to the collection of microbes inhabiting the human body. Imbalance in microbial communities, or microbial dysbiosis, has been implicated in various human diseases including obesity, diabetes, and colon cancer. Therefore, we investigated the potential role of microbiota in breast cancer by next-generation sequencing using breast tumor tissue and paired normal adjacent tissue from the same patient. In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae is relatively enriched in paired normal tissue. The relative abundances of these two bacterial species were inversely correlated in paired normal breast tissue but not in tumor tissue, indicating that dysbiosis is associated with breast cancer. Furthermore, the total bacterial DNA load was reduced in tumor versus paired normal and healthy breast tissue as determined by quantitative PCR. Interestingly, bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer. Lastly, we observed lower basal levels of antibacterial response gene expression in tumor versus healthy breast tissue. Taken together, these data indicate that microbial DNA is present in the breast and that bacteria or their components may influence the local immune microenvironment. Our findings suggest a previously unrecognized link between dysbiosis and breast cancer which has potential diagnostic and therapeutic implications.

  10. Oropharyngeal perinatal colonization by human papillomavirus.

    Science.gov (United States)

    Sánchez-Torices, María Soledad; Corrales-Millan, Rocío; Hijona-Elosegui, Jesús J

    2016-01-01

    Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery. The aim of our research was to study maternal-foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries. The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined. The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%. The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  11. Evaluation of a breast and colon cancer survivorship program.

    Science.gov (United States)

    McCollum, Kennon H; Wood, Felecia G; Auriemma, Kimberly

    2014-04-01

    This article describes a cancer survivorship program that addressed quality of life (QOL) changes related to chemotherapy. The program focused on adult breast and colon cancer survivors at a community oncology practice in the southeastern United States, and consisted of an educational visit designed to identify and address QOL changes that occurred as a result of chemotherapy. The QOL of Cancer Survivors (QOL-CS) survey administered before and after the visit analyzed QOL metrics, which were combined with program evaluation data to assess physical, psychosocial, social, and spiritual well-being changes that may have occurred as a result of program participation. Differences in QOL-CS scores did not represent statistically significant changes in QOL for program participants. However, program evaluation responses identified perceived changes in QOL as a result of participating in cancer treatment and a subsequent cancer survivorship program, which demonstrated clinical significance for program participants. Physical, psychosocial, social, and spiritual well-being measures were affected by program participation. Improvement in distress related to the initial cancer diagnosis and family distress were the most significant reported changes, and male gender and advanced age were associated with improved psychosocial well-being.

  12. Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jiten P. Kothadia

    2015-01-01

    Full Text Available Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures.

  13. Binding of chemical carcinogens to macromolecules in cultured human colon

    DEFF Research Database (Denmark)

    1977-01-01

    Metabolic activation of different chemical classes of carcinogens was studied in cultured human colon epithelia. Human colon epithelia were maintained in explant culture up to 4 days. Binding of benzo(a)pyrene, dimethylnitrosamine, and 1,2- dimethylhydrazine was found in both cell DNA and protein....... 1,2-Dimethylhydrazine methylated DNA at both N·7 and 0-6 positions of guanin....

  14. FasL EXPRESSION IN HUMAN COLON CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:The Fas and Fas ligand (FasL) play an important role in maintaining immune privilege on malignant tumors. In present study, we investigated the expression of FasL in SW480 and LS174 human colon carcinoma cell lines and twenty primary colon carcinoma specimens. Methods: The expression of FasL in human colon carcinoma cell lines and primary colon carcinomas specimens was detected by immunohistochemistry and Reverse Transcription-PCR (RT-PCR). Results: We found that all of detected human colon carcinoma cell lines and primary colon carcinoma specimens constitutively expressed FasL at the mRNA and protein level. However, the expression of FasL was not found in normal colon epithelial cells. Conclusion: The expression of FasL may occur during malignant transformation from normal colon epithelial cells to colon carcinoma cells. Our results suggest that tumor cells kill cytotoxic T lymphocytes (CTLS) and natural killer (NK) cells by expression of FasL. It may be a new mechanism for tumor cells to escape the host's immune surveillance. The expression of FasL may contribute to the formation of colon carcinomas.

  15. Lobular Breast Cancer Metastasis to the Colon, the Appendix and the Gallbladder

    Science.gov (United States)

    Molina-Barea, Rocio; Rios-Peregrina, Rosa M.; Slim, Mahmoud; Calandre, Elena P.; Hernández-García, Maria D.; Jimenez-Rios, José A.

    2014-01-01

    Summary Background Metastases of lobular breast cancer are commonly encountered at the level of lungs, bones, brain and liver, whereas lesions in the gastrointestinal tract are rarely seen. Case Report A case of a patient with metastases in the right colon and gallbladder originating from an invasive lobular carcinoma is described. Conclusion Adequate diagnostic procedures should be performed in patients with a history of breast cancer and who show gastrointestinal symptoms to rule out the potential presence of gastrointestinal metastases. PMID:25759626

  16. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  17. Colonic Fermentation: A Neglected Topic in Human Physiology Education

    Science.gov (United States)

    Valeur, Jorgen; Berstad, Arnold

    2010-01-01

    Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

  18. Colonic Fermentation: A Neglected Topic in Human Physiology Education

    Science.gov (United States)

    Valeur, Jorgen; Berstad, Arnold

    2010-01-01

    Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

  19. EXPRESSION OF Fas LIGAND IN HUMAN COLON CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁

    2001-01-01

    To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

  20. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni;

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... determined and found to be indistinguishable. Comparison of the vitronectin and the hemoglobin concentrations of the extracts showed that their vitronectin content was not derived from blood contamination. Vitronectin mRNA was undetectable in both carcinomas and normal tissue. We conclude that vitronectin...

  1. Strategies For Human Exploration Leading To Human Colonization of Space

    Science.gov (United States)

    Smitherman, David; Everett, Harmon

    2009-01-01

    Enabling the commercial development of space is key to the future colonization of space and key to a viable space exploration program. Without commercial development following in the footsteps of exploration it is difficult to justify and maintain public interest in the efforts. NASA's exploration program has suffered from the lack of a good commercial economic strategy for decades. Only small advances in commercial space have moved forward, and only up to Earth orbit with the commercial satellite industry. A way to move beyond this phase is to begin the establishment of human commercial activities in space in partnership with the human exploration program. In 2007 and 2008, the authors researched scenarios to make space exploration and commercial space development more feasible as part of their graduate work in the Space Architecture Program at the Sasakawa International Center for Space Architecture at the University of Houston, Houston, Texas. Through this research it became apparent that the problems facing future colonization are much larger than the technology being developed or the international missions that our space agencies are pursuing. These issues are addressed in this paper with recommendations for space exploration, commercial development, and space policy that are needed to form a strategic plan for human expansion into space. In conclusion, the authors found that the current direction in space as carried out by our space agencies around the world is definitely needed, but is inadequate and incapable of resolving all of the issues that inhibit commercial space development. A bolder vision with strategic planning designed to grow infrastructures and set up a legal framework for commercial markets will go a long way toward enabling the future colonization of space.

  2. Physical Activity and Sedentary Behavior in Breast and Colon Cancer Survivors Relative to Adults Without Cancer.

    Science.gov (United States)

    Shi, Joyce W; MacInnis, Robert J; Boyle, Terry; Vallance, Jeff K; Winkler, Elisabeth A H; Lynch, Brigid M

    2017-03-01

    To assess differences in accelerometer-assessed moderate- to vigorous-intensity physical activity (MVPA), light-intensity physical activity, and sedentary time between cancer survivors and adults without cancer. Accelerometer data collected from 241 breast cancer survivors (ACCEL-Breast study, 2013) and 171 colon cancer survivors (ACCEL-Colon study, 2012-2013) were pooled with data collected from adults without cancer (Australian Diabetes, Obesity and Lifestyle accelerometer substudy, 2011-2012). Linear regression was used to estimate differences in physical activity and sedentary behavior levels between cancer survivors and adults without cancer, adjusted for potential confounding factors. The mean MVPA was significantly higher among breast cancer survivors than among females who had not had cancer (29 vs 22 min/d; PColon cancer survivors had significantly lower levels of light activity than did adults without cancer (311 vs 338 min/d; Pcancer survivors engaged in more (breast) or equivalent (colon) MVPA compared with adults without cancer. Differences between colon cancer survivors and adults without cancer for light activity and sedentary behavior highlight the importance of considering the full activity spectrum in the context of cancer control. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  3. Coupled Two-Way Clustering Analysis of Breast Cancer and Colon Cancer Gene Expression Data

    CERN Document Server

    Getz, G; Kela, I; Domany, E; Notterman, D A; Getz, Gad; Gal, Hilah; Kela, Itai; Domany, Eytan; Notterman, Dan A.

    2003-01-01

    We present and review Coupled Two Way Clustering, a method designed to mine gene expression data. The method identifies submatrices of the total expression matrix, whose clustering analysis reveals partitions of samples (and genes) into biologically relevant classes. We demonstrate, on data from colon and breast cancer, that we are able to identify partitions that elude standard clustering analysis.

  4. Storage of Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Gamze Can

    2007-10-01

    Full Text Available Storage of human breast milk by freezing or refrigeration of milk has been recommended especially at some social circumstances of most mothers who are regularly separated from their infants because of work. The greatest fear that has hindered the prospects of in - vitro storage of breast milk for any considerable period of time is the possibility of bacterial contamination and growth of infectious pathogens in the stored milk, there by rendering them unsafe for human consumption. The storage container can influence the cell content of milk, as the cells adhere to the walls of a glass container but not to polyethylene or polypropylene containers. Bacteriological examination of refrigerated milks has proven their safety for human consumption for even up to 72 h. For a storage over longer periods up to 1 month, freezing at - 20 0C could be recommended, but the most preferred method, especially for longer storage would be fresh freezing at - 70 0C, if affordable or available. The nutrient value of human milk is essentially unchanged, but the immunological properties are reduced by various storage techniques. Boiling and microwave radiation have not been recommended. [TAF Prev Med Bull 2007; 6(5.000: 375-379

  5. Inactivation of the FoxO3a transcription factor is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated senescence in human colon cancer and breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seong-Yeol; Bae, Young-Seuk, E-mail: ysbae@knu.ac.kr

    2016-09-09

    We previously showed that protein kinase CK2 downregulation mediates senescence through the reactive oxygen species (ROS)–p53–p21{sup Cip1/WAF1} pathway in various human cells. In the present study, we investigated whether the FoxO3a transcription factor is associated with ROS production during CK2 downregulation-induced senescence in human colon cancer HCT116 and breast cancer MCF-7 cells. FoxO3a overexpression suppressed ROS production and p53 stabilization induced by a CK2α knockdown. CK2α downregulation induced nuclear export of FoxO3a through stimulation of AKT-mediated phosphorylation of FoxO3a and decreased transcription of its target genes (Cu/ZnSOD, MnSOD, and catalase). In contrast, CK2α overexpression inhibited AKT-mediated FoxO3a phosphorylation. This resulted in nuclear accumulation of FoxO3a, and elevated expression of its target genes. Therefore, these data indicate for the first time that CK2 downregulation stimulates ROS generation by inhibiting FoxO3a during premature senescence in human colon and breast cancer cells. - Highlights: • FoxO3a overexpression inhibited ROS production mediated by CK2α knockdown. • CK2α downregulation induced nuclear export of FoxO3a via AKT activation. • CK2α downregulation reduced transcription of FoxO3a target genes including SOD. • CK2α upregulation elevated nuclear import and target gene expression of FoxO3a. • This study indicates that CK2 can modulate the intracellular ROS level via FoxO3a.

  6. Dispersal time for ancient human migrations: Americas and Europe colonization

    Science.gov (United States)

    Flores, J. C.

    2007-07-01

    I apply the recently proposed intermittence strategy to investigate the ancient human migrations in the world. That is, the Americas colonization (Bering-bridge and Pacific-coast theories) and Neanderthal replacement in Europe around 45000 years before the present. Using a mathematical equation related to diffusion and ballistic motion, I calculate the colonization time in all these cases in good agreement with archeological data (including Neolithic transition in Europe). Moreover, to support these calculations, I obtain analytically the effective speed of colonization in Europe veff=0.62 [km/yr] and related to the Aurignacian culture propagation.

  7. Aluminium in human breast tissue.

    Science.gov (United States)

    Exley, Christopher; Charles, Lisa M; Barr, Lester; Martin, Claire; Polwart, Anthony; Darbre, Philippa D

    2007-09-01

    Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.

  8. CHANGES OF NUCLEAR MATRIX PROTEIN AND ITS RELATIONSHIP WITH c-erbB-2 IN HUMAN COLON ADENOCARCINOMA

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-lan; GAO Jing; LI Yuan-yuan

    2005-01-01

    Objective: Nuclear matrix protein is tissue, cell-type specific, and tumor-relative. It plays an important role in the regulation of intranuclear processes. Some researches also showed that a c-erbB-2 promoter-specific DNA-binding nuclear matrix protein is present only in malignant human breast tissues and induces mitogenesis and cell surface expression of the c-erbB-2 protein in resting NIH/3T3 cells. But it is not clear that how it in colon adenocarcinomas. Methods:Two-dimensional gel electrophoretic method was used for NMP identification and immunohistochemistry was used for c-erbB-2 detection in 12 cases of colon adenocarcinomas and matched adjacent normal colon tissues. Results: 5 different nuclear matrix proteins (named C1-C5) were identified in 12 colon adenocarcinoma specimens, but not in the matched adjacent normal colon tissues; 3 nuclear matrix proteins (named N1-N3) were identified in all 12 matched adjacent normal colon tissues, but not in colon adenocarcinoma specimens. A nuclear matrix protein (named N4) was detected in all of 9moderated-well differentiated adenocarcinomas and all 12 matched adjacent normal colon tissues, but not in 3poor-differentiated adenocarcinomas. All of the 10 colon adenocarcinomas which had the nuclear matrix protein C4 were c-erbB-2 expression positive. Conclusion: The data suggest that there are specific nuclear matrix proteins in colon adenocarcinomas and its subtypes, which maybe valuable to serve as markers of colon adenocarcinomas in future. Nuclear matrix protein C4 probably is a c-erbB-2 promotor-specific nuclear matrix protein in colon adenocarcinomas, and may induce the expression of c-erbB-2.

  9. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  10. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species.

    Directory of Open Access Journals (Sweden)

    Berlinda Verdoodt

    Full Text Available BACKGROUND: Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO and breast cancer cell lines (MCF-7, T47D, MDA-MB-453. METHODOLOGY/PRINCIPAL FINDINGS: We detected features of apoptosis in all cell lines tested, but the executor caspases 3 and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagy such as cytoplasmic vacuolization and LC3 processing. Caspase proficient cell lines activated autophagy at lower salinomycin concentrations and before the onset of caspase activation. Salinomycin also led to the formation of reactive oxygen species (ROS eliciting JNK activation and induction of the transcription factor JUN. Salinomycin mediated cell death could be partially inhibited by the free radical scavenger N-acetyl-cysteine, implicating ROS formation in the mechanism of salinomycin toxicity. CONCLUSIONS: Our data indicate that, in addition to its previously reported induction of caspase dependent apoptosis, the initiation of autophagy is an important and early effect of salinomycin in tumor cells.

  11. Diagnose human colonic tissues by terahertz near-field imaging

    Science.gov (United States)

    Chen, Hua; Ma, Shihua; Wu, Xiumei; Yang, Wenxing; Zhao, Tian

    2015-03-01

    Based on a terahertz (THz) pipe-based near-field imaging system, we demonstrate the capability of THz imaging to diagnose freshly surgically excised human colonic tissues. Through THz near-field scanning the absorbance of the colonic tissues, the acquired images can clearly distinguish cancerous tissues from healthy tissues fast and automatically without pathological hematoxylin and eosin stain diagnosis. A statistical study on 58 specimens (20 healthy tissues and 38 tissues with tumor) from 31 patients (mean age: 59 years; range: 46 to 79 years) shows that the corresponding diagnostic sensitivity and specificity on colonic tissues are both 100%. Due to its capability to perform quantitative analysis, our study indicates the potential of the THz pipe-based near-field imaging for future automation on human tumor pathological examinations.

  12. Human commensals producing a novel antibiotic impair pathogen colonization.

    Science.gov (United States)

    Zipperer, Alexander; Konnerth, Martin C; Laux, Claudia; Berscheid, Anne; Janek, Daniela; Weidenmaier, Christopher; Burian, Marc; Schilling, Nadine A; Slavetinsky, Christoph; Marschal, Matthias; Willmann, Matthias; Kalbacher, Hubert; Schittek, Birgit; Brötz-Oesterhelt, Heike; Grond, Stephanie; Peschel, Andreas; Krismer, Bernhard

    2016-07-28

    The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.

  13. Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yoshie Nakayama

    2013-01-01

    Full Text Available Background: Bevacizumab has been increasingly used in combination chemotherapy with paclitaxel for treatment of metastatic or recurrent breast cancer. The aim of this report is to underline possible risks associated with the new combination chemotherapy. Case Presentation: A 39-year-old woman with recurrent breast cancer was treated with bevacizumab and paclitaxel. Positron emission tomography revealed breast cancer metastasis to the left supraclavicular lymph nodes and right axillary lymph nodes, with no distant metastasis. Results: After the third cycle of bevacizumab and paclitaxel, the patient developed a bloody bowel discharge. Emergent colonoscopy demonstrated diverticular bleeding on one of the multiple diverticula in the ascending colon. The bleeding point was successfully clipped colonoscopically. Conclusion: The factors for diverticular bleeding are believed to be non-steroidal anti-inflammatory drugs, constipation, and bevacizumab. We recommend reviewing anamneses for diverticulitis, multiple prior abdominal surgeries, peritoneal carcinomatosis, and regular use of certain drugs.

  14. Trefoil factor-3 expression in human colon cancer liver metastasis.

    Science.gov (United States)

    Babyatsky, Mark; Lin, Jing; Yio, Xianyang; Chen, Anli; Zhang, Jie-yu; Zheng, Yan; Twyman, Christina; Bao, Xiuliang; Schwartz, Myron; Thung, Swan; Lawrence Werther, J; Itzkowitz, Steven

    2009-01-01

    Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.

  15. Dynamics of thymus organogenesis and colonization in early human development.

    Science.gov (United States)

    Farley, Alison M; Morris, Lucy X; Vroegindeweij, Eric; Depreter, Marianne L G; Vaidya, Harsh; Stenhouse, Frances H; Tomlinson, Simon R; Anderson, Richard A; Cupedo, Tom; Cornelissen, Jan J; Blackburn, C Clare

    2013-05-01

    The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45(+)CD34(int/-). Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients.

  16. Ultrastructure of interstitial cells in subserosa of human colon

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johannes; Vanderwinden, Jean-Marie; Hansen, Alastair;

    2013-01-01

    We studied the ultrastructure of interstitial cells in the subserosal/adventitial layer in human colon. An interstitial cell type with an ultrastructure intermediate between fibroblast-like cells (FLC) and interstitial cells of Cajal was identified (IC-SS). IC-SS had thin and flattened branching...

  17. Metastatic breast carcinoma uncovered in an otherwise unremarkable “random colon biopsy”

    Directory of Open Access Journals (Sweden)

    Mike Black

    2016-06-01

    Full Text Available Breast cancer is one of the most devastating cancers afflicting women, being a main cause of cancer related death. Approximately 50% of these patients have developed regional or distant metastases at the time of diagnosis; hence, an early diagnosis and surgery with indicated neoadjuvant therapy are crucial in eradicating this disease and improving patient survival. A significant percentage of patients, even after initial satisfactory tumor removal, still face the threat of metastatic diseases which could plague a wide spectrum of body sites such as bones, lungs, central nervous system, liver and gastrointestinal tract (mostly upper gastrointestinal locations. Colonic and anorectal involvement by metastatic breast cancer has been less frequently reported in disseminated diseases. Typically, metastatic disease presents as a mass, enteric stenosis, or obstruction. Rare cases, however, may not form an endoscopically or radiologically recognizable lesion, and thus could be overlooked. Here we report a unique case of random colon biopsies in a patient presenting with epigastric pain, whose stomach biopsy showed Helicobacter pylori-associated chronic active gastritis. No colonoscopic lesion was present; however, microscopic examination of the “random biopsy” revealed scattered single and small clusters of tumor cells involving the lamina propria of the colonic mucosa, morphologically and immunophenotypically consistent with metastatic disease from breast carcinoma. The clinical presentation and histopathology of the case were reviewed and compared with limited cases reported in the literature. We conclude that high levels of suspicion and alertness are essential to identify occult microscopic gastrointestinal metastatic breast cancer in the absence of a grossly appreciable lesion.

  18. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

    Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

  19. [Right Hemi-Colectomy for a Metastatic Transverse Colon Tumor from Breast Cancer Following Bilateral Breast Cancer Resection - A Case Report].

    Science.gov (United States)

    Okamura, Shu; Yanagisawa, Tetsu; Ohishi, Kazuhito; Murata, Kohei; Nushijima, Yoichiro; Hamano, Rie; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2016-11-01

    We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery. Colonoscopy revealed stenosis of the same lesion with an edematous mucosa and sclerosis. Using immunohistochemistry, a biopsy specimen from the lesion tested positive for CK AE1+AE3, and negative for CD20(-)and CD3 (-). As a result, the tumor was diagnosed as a poorly differentiated adenocarcinoma. We performed right hemicolectomy to avoid her intestinal obstruction. Tumor cells were mainly present at the subserosa, according to HEstaining. Using immunostaining, the cells were tested for the following markers: CDX2(-), GCDFP15(weakly positive), CK7(strongly positive), CD20(partially positive), E R(+), PgR(-), and HER2(1+), characterizing the tumor as metastasis of breast cancer. Although gastro-intestinal metastasis from breast cancer is rare, and colon metastasis is even rarer, it might be necessary to rule out the possibility of a metastatic colon tumor from breast cancer when treating patients with a colon tumor who have undergone surgery for breast cancer.

  20. Catabolism of coffee chlorogenic acids by human colonic microbiota.

    Science.gov (United States)

    Ludwig, Iziar A; Paz de Peña, Maria; Concepción, Cid; Alan, Crozier

    2013-01-01

    Several studies have indicated potential health benefits associated with coffee consumption. These benefits might be ascribed in part to the chlorogenic acids (CGAs), the main (poly)phenols in coffee. The impact of these dietary (poly)phenols on health depends on their bioavailability. As they pass along the gastrointestinal tract, CGAs are metabolized extensively and it is their metabolites rather than the parent compounds that predominate in the circulatory system. This article reports on a study in which after incubation of espresso coffee with human fecal samples, high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to monitor CGA breakdown and identify and quantify the catabolites produced by the colonic microflora. The CGAs were rapidly degraded by the colonic microflora and over the 6-h incubation period, 11 catabolites were identified and quantified. The appearance of the initial degradation products, caffeic and ferulic acids, was transient, with maximum quantities at 1 h. Dihydrocaffeic acid, dihydroferulic acid, and 3-(3'-hydroxyphenyl)propionic acid were the major end products, comprising 75-83% of the total catabolites, whereas the remaining 17-25% consisted of six minor catabolites. The rate and extent of the degradation showed a clear influence of the composition of the gut microbiota of individual volunteers. Pathways involved in colonic catabolism of CGAs are proposed and comparison with studies on the bioavailability of coffee CGAs ingested by humans helped distinguish between colonic catabolites and phase II metabolites of CGAs.

  1. Humans, water, and the colonization of Australia.

    Science.gov (United States)

    Bird, Michael I; O'Grady, Damien; Ulm, Sean

    2016-10-11

    The Pleistocene global dispersal of modern humans required the transit of arid and semiarid regions where the distribution of potable water provided a primary constraint on dispersal pathways. Here, we provide a spatially explicit continental-scale assessment of the opportunities for Pleistocene human occupation of Australia, the driest inhabited continent on Earth. We establish the location and connectedness of persistent water in the landscape using the Australian Water Observations from Space dataset combined with the distribution of small permanent water bodies (springs, gnammas, native wells, waterholes, and rockholes). Results demonstrate a high degree of directed landscape connectivity during wet periods and a high density of permanent water points widely but unevenly distributed across the continental interior. A connected network representing the least-cost distance between water bodies and graded according to terrain cost shows that 84% of archaeological sites >30,000 y old are within 20 km of modern permanent water. We further show that multiple, well-watered routes into the semiarid and arid continental interior were available throughout the period of early human occupation. Depletion of high-ranked resources over time in these paleohydrological corridors potentially drove a wave of dispersal farther along well-watered routes to patches with higher foraging returns.

  2. Epigenetic Effects of Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Elvira Verduci

    2014-04-01

    Full Text Available A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.

  3. Emigrating Beyond Earth Human Adaptation and Space Colonization

    CERN Document Server

    Smith, Cameron M

    2012-01-01

    For four million years humankind has been actively expanding geographically and in doing so has adapted to a wide variety of hostile environments. Now we are looking towards the ultimate adaptation - the colonization of space. Emigrating Beyond Earth illustrates that this is not a technocratic endeavor, but a natural continuation of human evolution; a journey not just for the engineer and rocket scientist, but for everyman. Based on the most current understanding of our universe, human adaptation and evolution, the authors explain why space colonization must be planned as an adaptation to, rather than the conquest of, space. Emigrating Beyond Earth argues that space colonization is an insurance policy for our species, and that it isn't about rockets and robots, it's about humans doing what we've been doing for four million years: finding new places and new ways to live. Applying a unique anthropological approach, the authors outline a framework for continued human space exploration and offer a glimpse of a po...

  4. Novel use of an air-filled breast prosthesis to allow radiotherapy to recurrent colonic cancer.

    LENUS (Irish Health Repository)

    O'Duffy, F

    2011-03-01

    AiM: The authors present the novel and successful use of an air-filled breast prosthesis for extra pelvic exclusion of small bowel to facilitate adjuvant radiotherapy following resection of recurrent adenocarcinoma of the ascending bowel. The therapeutic use of radiotherapy in colon cancer can cause acute or chronic radiation enteropathy. Mobile small bowel can be sequestered in \\'dead space\\' or by adhesions exposing it to adjuvant radiotherapy. A variety of pelvic partitioning methods have been described to exclude bowel from radiation fields using both native and prosthetic materials.

  5. STUDY ON NUCLEAR MATRIX PROTEINS FROM HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    HE Qian; ZHANG Shu-qun; CHU Yong-lie; JIA Xiao-li; JIANG Jian-tao

    2009-01-01

    Objective To investigate the marker protein of human breast carcinoma from nuclear matrix proteins (NMPs).Methods NMPs were injected subcutaneously into rabbit to get antiserum, which was used to detect the NMPs specificity for breast carcinoma.Results There was an apparent positive band (100kD) in the NMPs of breast carcinoma, which did not exist in normal breast and other tumors that were detected.Conclusion One or one group of 100kD NMPs were found to be related to human breast carcinoma, which may be involved in the carcinogenesis and development of human breast carcinoma and valuable for breast carcinoma diagnosis.

  6. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    Directory of Open Access Journals (Sweden)

    Ihab Shafek Atta

    2016-01-01

    Full Text Available We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner’s, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.

  7. Cloning and expression of human colon mast cell carboxypeptidase

    Institute of Scientific and Technical Information of China (English)

    Zhang-Quan Chen; Shao-Heng He

    2004-01-01

    AIM: To clone and express the human colon mast cell METHODS: Total RNA was extracted from colon tissue, and the cDNA encoding human colon mast cell carboxypeptidase was amplified by reverse-transcription PCR (RT-PCR). The product cDNA was subcloned into the prokaryotic expression vector pMAL-c2x and eukaryotic expression vector pPIC9K to conrtruct prokaryotic expression vector pMAL/human MC-CP (hMC-CP) and eukaryotic pPIC9K/hMC-CP. The recombinant fusion protein expressed in E.coli was induced with IPTG and purified by amylose affinity chromatography. After digestion with factor Xa, recombinant hMC-CP was purified by heparin agarose chromatography. The recombinant hMC-CP expressed in Pichia pastoris (P.pastoris) was induced with methanol and analyzed by SDS-PAGE, Western blot, N-terminal amino acid RESULTS: The cDNA encoding the human colon mast cell carboxypeptidase was cloned, which had five nucleotide variations compared with skin MC-CP cDNA. The recombinant hMC-CP protein expressed in E.coli was purified with amylose affinity chromatography and heparin agarose chromatogphy.SDS-PAGE and Western blot analysis showed that the recombinant protein expressed by E. coli had a molecular weight of 36 kDa and reacted to the anti-native hMC-CP monoclonal antibody (CA5). The N-terminal amino acid sequence confirmed further the product was hMC-CP. E. coli generated hMC-CP showed a very low level of enzymatic activity, but P. pastoris produced hMC-CP had a relatively high enzymatic activity towards a synthetic substrate hippuryl-L-phenylalanine.carboxypeptidase can be successfully cloned and expressed in E.coli and P. pastoris, which will contribute greatly to the fonctional study on hMC-CP.

  8. Butyrate-induced transcriptional changes in human colonic mucosa.

    Directory of Open Access Journals (Sweden)

    Steven A L W Vanhoutvin

    Full Text Available BACKGROUND: Fermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate. Butyrate modulates a wide range of processes, but its mechanism of action is mostly unknown. This study aimed to determine the effects of butyrate on the transcriptional regulation of human colonic mucosa in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Five hundred genes were found to be differentially expressed after a two week daily butyrate administration with enemas. Pathway analysis showed that the butyrate intervention mainly resulted in an increased transcriptional regulation of the pathways representing fatty acid oxidation, electron transport chain and oxidative stress. In addition, several genes associated with epithelial integrity and apoptosis, were found to be differentially expressed after the butyrate intervention. CONCLUSIONS/SIGNIFICANCE: Colonic administration of butyrate in concentrations that can be achieved by consumption of a high-fiber diet enhances the maintenance of colonic homeostasis in healthy subjects, by regulating fatty acid metabolism, electron transport and oxidative stress pathways on the transcriptional level and provide for the first time, detailed molecular insight in the transcriptional response of gut mucosa to butyrate.

  9. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  10. Microbiological toxicity of tilmicosin on human colonic microflora in chemostats.

    Science.gov (United States)

    Hao, Haihong; Yao, Junping; Wu, Qinghua; Wei, Yajing; Dai, Menghong; Iqbal, Zahid; Wang, Xu; Wang, Yulian; Huang, Lingli; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Yuan, Zonghui

    2015-10-01

    To evaluate the microbiological safety of tilmicosin on human intestinal microflora, four chemostat models of healthy human colonic ecosystems were exposed to tilmicosin (0, 0.436, 4.36, and 43.6 μg/mL) for 7 days. Prior to and during drug exposure, three microbiological endpoints were monitored daily including short-chain fatty acids, bacterial counts and macrolide susceptibility. Colonization resistance of each community was determined by 3 successive daily challenges of Salmonella typhimurium. Genes associated with virulence and macrolide resistance in Enterococcus faecalis were determined by PCR. Transcriptional expression of the virulence gene (gelE) in E. faecalis was determined by real-time RT-PCR. Our results showed that different concentrations of tilmicosin did not disrupt the colonization resistance in each chemostat. During exposure to 4.36 and 43.6 μg/mL tilmicosin, the Bacteroides fragilis population was significantly decreased while the proportion of resistant Enterococci increased. After long-term exposure to the highest concentration (43.6 μg/mL) of tilmicosin, the gelE gene was significantly up-regulated in the high-level macrolide resistant strains that also contained the ermB resistance gene. This study was the first of its kind to evaluate the microbiological toxicity of tilmicosin using a chemostat model. These findings also provide new insight into the co-occurrence of macrolide resistance and virulence in E. faecalis under tilmicosin selective pressure.

  11. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut.

    Science.gov (United States)

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

  12. Accidental endoscopic finding of Anisakis simplex in human colon

    Directory of Open Access Journals (Sweden)

    Aurelia Aloia

    2011-09-01

    Full Text Available Anisakidosis is a zoonotic disease caused by the ingestion of nematodes belonging to the family of Anisakidae. Human infection is caused by intake of raw or undercooked sea fish and cephalopods infested by Anisakis larvae. We present a case of accidental endoscopic finding of an alive nematode adhering to distal ascending colon in a 32 years old man, submitted to colonoscopy owing to recent onsets of rectal bleeding of likely hemorrhoidal origin. The nematode, removed from colon by means of biopsy forceps, has been identified as L3 larvae of A. simplex by a light microscope. Histological examination of intestinal mucosa showed a mild fibrosis of lamina propria, characterized by focal lymphocytic inflammation and scattered infiltration of eosinophils. The patient reported the intake of marinated anchovies 3 days before endoscopic examination.

  13. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...

  14. Simulated colon fiber metabolome regulates genes involved in cell cycle, apoptosis, and energy metabolism in human colon cancer cells.

    Science.gov (United States)

    Putaala, Heli; Mäkivuokko, Harri; Tiihonen, Kirsti; Rautonen, Nina

    2011-11-01

    High level of dietary fiber has been epidemiologically linked to protection against the risk for developing colon cancer. The mechanisms of this protection are not clear. Fermentation of dietary fiber in the colon results in production of for example butyrate that has drawn attention as a chemopreventive agent. Polydextrose, a soluble fiber that is only partially fermented in colon, was fermented in an in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse, and distal colon in sequence. The subsequent fermentation metabolomes were applied on colon cancer cells, and the gene expression changes studied. Polydextrose fermentation down-regulated gene ontology classes linked with cell cycle, and affected number of metabolically active cells. Furthermore, up-regulated effects on classes linked with apoptosis, with increased caspase 2 and 3 activity, implicate that polydextrose fermentation plays a role in induction of apoptosis in colon cancer cells. The up-regulated genes involved also key regulators of lipid metabolism, such as PPARα and PGC-1α. These results offer hypotheses for the mechanisms of two health benefits linked with consumption of dietary fiber, reducing risk of development of colon cancer, and dyslipidemia.

  15. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spink, Barbara C. [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Bloom, Michael S. [Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Wu, Susan [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Sell, Stewart; Schneider, Erasmus [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Ding, Xinxin [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Spink, David C., E-mail: spink@wadsworth.org [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States)

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  16. 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.

  17. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2...

  18. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kim Il-Han

    2009-06-01

    Full Text Available Abstract Background Peroxiredoxins (Prxs are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1 as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1. Methods We investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR and Western blot. Results Levels of messenger RNA (mRNA for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid. Among members of the Prx family (Prx I-VI and Trx family (Trx1, Trx2, Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue. Conclusion Prx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

  19. Chemical Biomarkers of Human Breast Milk Pollution

    Directory of Open Access Journals (Sweden)

    Benedetta Marchi

    2008-01-01

    Full Text Available Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics.In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed.In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

  20. Excretion of drugs in human breast milk

    Energy Technology Data Exchange (ETDEWEB)

    Welch, R.M.; Findlay, J.W.

    1981-01-01

    The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant.

  1. Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells.

    Science.gov (United States)

    Sahpazidou, Despina; Geromichalos, George D; Stagos, Dimitrios; Apostolou, Anna; Haroutounian, Serkos A; Tsatsakis, Aristidis M; Tzanakakis, George N; Hayes, A Wallace; Kouretas, Dimitrios

    2014-10-15

    A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC₅₀ values of 121-230 μg/ml (MCF-7), 121-184 μg/ml (MDA-MD-23), 175-309 μg/ml (HT29), 159-314 μg/ml (K1), 180-225 μg/ml (786-0) and 134->400 μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line.

    Science.gov (United States)

    Khanavi, Mahnaz; Gheidarloo, Razieh; Sadati, Nargess; Ardekani, Mohammad Reza Shams; Nabavi, Seyed Mohammad Bagher; Tavajohi, Shohreh; Ostad, Seyed Nasser

    2012-01-01

    Marine algae produce different secondary metabolites with a wide range of biological activities. Many studies have been achieved on the screening of biological effects of marine organisms and a lot of active compounds were isolated and characterized. In an attempt to find cytotoxic compound of hexane fraction, isolation, identification, and cytotoxicity of active compound of this fraction were performed. In this study, total methanolic (70%) extract and partition fractions of hexane, chloroform (CHCl(3)), ethyl acetate (EtOAc), and MeOH-H(2)O of Sargassum angustifolium, Chondria dasyphylla, and Ulva flexuosa, collected from coastlines of the Persian Gulf in south of Iran, were studied against colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), and Swiss mouse embryo fibroblast (NIH 3T3) cell lines by MTT assay. IC(50) (median growth inhibitory concentration) values were calculated by Sigmaplot (10) software. Hexane fraction of Chondria dasyphylla (IC(50) 82.26 ± 4.09 μg/ml) and MeOH-H(2)O fraction of Ulva flexuosa (IC(50) 116.92 ± 8.58 μg/ml) showed cytotoxic activity against proliferation of T47D cells. Hexane fraction of Sargassum angustifolium was also observed for cytotoxicity against T47D and HT-29 cell lines (IC(50) 166.42 ± 26.7 and 190.24 ± 52.8 μg/ml), respectively. An investigation of a component from the hexane fraction of Sargassum angustifolium yielded a steroidal metabolite, fucosterol, with cytotoxicity in T47D and HT29 (IC(50) 27.94 ± 9.3 and 70.41 ± 7.5 μg/ml). These results indicated that fucosterol, the most abundant phytosterol in brown algae, is responsible for cytotoxic effect of this extract against breast and colon carcinoma cell lines.

  3. Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line

    Science.gov (United States)

    Khanavi, Mahnaz; Gheidarloo, Razieh; Sadati, Nargess; Ardekani, Mohammad Reza Shams; Nabavi, Seyed Mohammad Bagher; Tavajohi, Shohreh; Ostad, Seyed Nasser

    2012-01-01

    Context: Marine algae produce different secondary metabolites with a wide range of biological activities. Many studies have been achieved on the screening of biological effects of marine organisms and a lot of active compounds were isolated and characterized. Aims: In an attempt to find cytotoxic compound of hexane fraction, isolation, identification, and cytotoxicity of active compound of this fraction were performed. Materials and Methods: In this study, total methanolic (70%) extract and partition fractions of hexane, chloroform (CHCl3), ethyl acetate (EtOAc), and MeOH–H2O of Sargassum angustifolium, Chondria dasyphylla, and Ulva flexuosa, collected from coastlines of the Persian Gulf in south of Iran, were studied against colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), and Swiss mouse embryo fibroblast (NIH 3T3) cell lines by MTT assay. Statistical Analysis Used: IC50 (median growth inhibitory concentration) values were calculated by Sigmaplot (10) software. Results: Hexane fraction of Chondria dasyphylla (IC50 82.26 ± 4.09 μg/ml) and MeOH-H2O fraction of Ulva flexuosa (IC50 116.92 ± 8.58 μg/ml) showed cytotoxic activity against proliferation of T47D cells. Hexane fraction of Sargassum angustifolium was also observed for cytotoxicity against T47D and HT-29 cell lines (IC50 166.42 ± 26.7 and 190.24 ± 52.8 μg/ml), respectively. An investigation of a component from the hexane fraction of Sargassum angustifolium yielded a steroidal metabolite, fucosterol, with cytotoxicity in T47D and HT29 (IC50 27.94 ± 9.3 and 70.41 ± 7.5 μg/ml). Conclusions: These results indicated that fucosterol, the most abundant phytosterol in brown algae, is responsible for cytotoxic effect of this extract against breast and colon carcinoma cell lines. PMID:22438665

  4. Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Mahnaz Khanavi

    2012-01-01

    Full Text Available Context: Marine algae produce different secondary metabolites with a wide range of biological activities. Many studies have been achieved on the screening of biological effects of marine organisms and a lot of active compounds were isolated and characterized. Aims: In an attempt to find cytotoxic compound of hexane fraction, isolation, identification, and cytotoxicity of active compound of this fraction were performed. Materials and Methods: In this study, total methanolic (70% extract and partition fractions of hexane, chloroform (CHCl 3 , ethyl acetate (EtOAc, and MeOH-H 2 O of Sargassum angustifolium, Chondria dasyphylla, and Ulva flexuosa, collected from coastlines of the Persian Gulf in south of Iran, were studied against colon carcinoma (HT-29, colorectal adenocarcinoma (Caco-2, breast ductal carcinoma (T47D, and Swiss mouse embryo fibroblast (NIH 3T3 cell lines by MTT assay. Statistical Analysis Used: IC 50 (median growth inhibitory concentration values were calculated by Sigmaplot (10 software. Results: Hexane fraction of Chondria dasyphylla (IC 50 82.26 ± 4.09 μg/ml and MeOH-H 2 O fraction of Ulva flexuosa (IC 50 116.92 ± 8.58 μg/ml showed cytotoxic activity against proliferation of T47D cells. Hexane fraction of Sargassum angustifolium was also observed for cytotoxicity against T47D and HT-29 cell lines (IC 50 166.42 ± 26.7 and 190.24 ± 52.8 μg/ml, respectively. An investigation of a component from the hexane fraction of Sargassum angustifolium yielded a steroidal metabolite, fucosterol, with cytotoxicity in T47D and HT29 (IC 50 27.94 ± 9.3 and 70.41 ± 7.5 μg/ml. Conclusions: These results indicated that fucosterol, the most abundant phytosterol in brown algae, is responsible for cytotoxic effect of this extract against breast and colon carcinoma cell lines.

  5. A simulation of microbial competition in the human colonic ecosystem.

    Science.gov (United States)

    Coleman, M E; Dreesen, D W; Wiegert, R G

    1996-10-01

    Many investigations of the interactions of microbial competitors in the gastrointestinal tract used continuous-flow anaerobic cultures. The simulation reported here was a deterministic 11-compartment model coded by using the C programming language and based on parameters from published in vitro studies and assumptions were data were unavailable. The resource compartments were glucose, lactose and sucrose, starch, sorbose, and serine. Six microbial competitors included indigenous nonpathogenic colonizers of the human gastrointestinal tract (Escherichia coli, Enterobacter aerogenes, Bacteroids ovatus, Fusobacterium varium, and Enterococcus faecalis) and the potential human enteropathogen Salmonella typhimurium. Flows of carbon from the resources to the microbes were modified by resource and space controls. Partitioning of resources to the competitors that could utilize them was calculated at each iteration on the basis of availability of all resources by feeding preference functions. Resources did not accumulate during iterations of the model. The results of the computer simulation of microbial competition model and for various modifications of the model. The results were based on few measured parameters but may be useful in the design of user-friendly software to aid researchers in defining and manipulating the microbial ecology of colonic ecosystems as relates to food-borne disease.

  6. In vitro anaerobic biofilms of human colonic microbiota.

    Science.gov (United States)

    Sproule-Willoughby, K M; Stanton, M Mark; Rioux, K P; McKay, D M; Buret, A G; Ceri, H

    2010-12-01

    The human gastrointestinal tract hosts a complex community of microorganisms that grow as biofilms on the intestinal mucosa. These bacterial communities are not well characterized, although they are known to play an important role in human health. This study aimed to develop a model for culturing biofilms (surface-adherent communities) of intestinal microbiota. The model utilizes adherent mucosal bacteria recovered from colonic biopsies to create multi-species biofilms. Culture on selective media and confocal microscopy indicated the biofilms were composed of a diverse community of bacteria. Molecular analyses confirmed that several phyla were represented in the model, and demonstrated stability of the community over 96 h when cultured in the device. This model is novel in its use of a multi-species community of mucosal bacteria grown in a biofilm mode of growth. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  8. Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.

    Science.gov (United States)

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer.

  9. Organizational change: a way to increase colon, breast and cervical cancer screening in primary care practices.

    Science.gov (United States)

    Arroyave, Ana Maria; Penaranda, Eribeth K; Lewis, Carmen L

    2011-04-01

    Screening tests for colon, cervical and breast cancer remain underutilized despite their proven effectiveness in reducing morbidity and mortality. Stone et al. concluded that cancer screening is most likely to improve when a health organization supports performance through organizational changes (OC) in staffing and clinical procedures. OC interventions include the use of separate clinics devoted to prevention, use of a planned care visit, designation of non-physician staff for specific prevention activities and continuous quality improvement interventions. To identify specific elements of OC interventions that increases the selected cancer screening rates. To determine to which extent practices bought into the interventions. Eleven randomized controlled trials from January 1990 to June 2010 that instituted OC to increase cancer screening completion were included. Qualitative data was analyzed by using a framework to facilitate abstraction of information. For quantitative data, an outcome of measure was determined by the change in the proportion of eligible individuals receiving cancer screening services between intervention and control practices. The health prevention clinic intervention demonstrated a large increase (47%) in the proportion of completed fecal occult blood test; having a non-physician staff demonstrated an increase in mammography (18.4%); and clinical breast examination (13.7%); the planned care visit for prevention intervention increased mammography (8.8%); continuous quality improvement interventions showed mixed results, from an increase in performance of mammography 19%, clinical breast examination (13%); Pap smear (15%) and fecal occult blood test (13%), to none or negative change in the proportion of cancer screening rates. To increase cancer screening completion goals, OC interventions should be implemented tailored to the primary care practice style. Interventions that circumvent the physicians were more effective. We could not conclude

  10. Colonic transit time relates to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencingand their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... on correlation analyses,we show that colonic transit time is associated with overall gutmicrobial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolismfrom carbohydrate fermentation to protein...

  11. Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... on correlation analyses, we show that colonic transit time is associated with overall gut microbial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolism from carbohydrate fermentation to protein...

  12. Gastric and colon metastasis from breast cancer: case report, review of the literature, and possible underlying mechanisms

    Science.gov (United States)

    Villa Guzmán, J Carlos; Espinosa, J; Cervera, R; Delgado, M; Patón, R; Cordero García, JM

    2017-01-01

    Gastrointestinal metastases from breast cancer are not common. We present a 58-year-old female diagnosed with lobular breast cancer some years before whose relapses were gastric and colonic mucosal. Simultaneous metastases are extremely rare. To our knowledge, no cases of initial dual affectation have been reported. The patient also showed gastritis by Helicobacter pylori. Invasive lobular breast carcinoma is the most frequent special type of breast cancer and carries some specific molecular alterations such as loss of expression of E-cadherin. Although underlying mechanisms of metastasization are not entirely known, chemokines as well as inflammatory events seem to be implicated in this process. Interaction between chemokines and their receptors frequently induces cell migration. We hypothesize that H. pylori, inflammatory cells, and chemokines may create a favorable environment attracting tumor cells. PMID:28096693

  13. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

    Science.gov (United States)

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Cimpean, Anca Maria; Nica, Cristian; Raica, Marius

    2016-06-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

  14. EXPRESSION OF FLIP IN HUMAN COLON CARCINOMAS:A NEW MECHANISM OF IMMUNE EVASION

    Institute of Scientific and Technical Information of China (English)

    XING Bao-cai; S. Wimmenauer; EH. Farthmann

    2005-01-01

    Objective: It has been proposed that Fas ligand (FasL) may play an important role in immune escape of tumors and FLIP is an important mediator of Fas/FasL pathway. In this study, the expression of FLIP was determined in human colon carcinoma cell lines and tissue to investigate the new mechanism of immune evasion of human colon carcinomas. Methods:RT-PCR and immunohistochemistry (IHC) were performed to investigate the expression of FLIP in human colon carcinoma cell lines SW480, LS174 and twenty human primary colon carcinoma specimens. Results: It was shown that SW480 cells,LS174 cells and primary colon carcinoma specimen constitutively expressed FLIP at the mRNA and protein level. The expression of FLIP was not found in the epithelial cells of normal colon mucosa. Conclusion: FLIP was expressed in human primary colon carcinoma specimens but not in the normal counterpart. It suggested that the expression of FLIP may occur during the malignant transformation from normal colon epithelial cells to colon carcinoma cells. Tumor cells might obtain the ability to resist the Fas-mediated apoptosis by expressing FLIP. The expression of FLIP might contribute to the formation of colon carcinomas.

  15. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden.

    Science.gov (United States)

    Baxter, Nielson T; Zackular, Joseph P; Chen, Grace Y; Schloss, Patrick D

    2014-01-01

    A growing body of evidence indicates that the gut microbiome plays a role in the development of colorectal cancer (CRC). Patients with CRC harbor gut microbiomes that are structurally distinct from those of healthy individuals; however, without the ability to track individuals during disease progression, it has not been possible to observe changes in the microbiome over the course of tumorigenesis. Mouse models have demonstrated that these changes can further promote colonic tumorigenesis. However, these models have relied upon mouse-adapted bacterial populations and so it remains unclear which human-adapted bacterial populations are responsible for modulating tumorigenesis. We transplanted fecal microbiota from three CRC patients and three healthy individuals into germ-free mice, resulting in six structurally distinct microbial communities. Subjecting these mice to a chemically induced model of CRC resulted in different levels of tumorigenesis between mice. Differences in the number of tumors were strongly associated with the baseline microbiome structure in mice, but not with the cancer status of the human donors. Partitioning of baseline communities into enterotypes by Dirichlet multinomial mixture modeling resulted in three enterotypes that corresponded with tumor burden. The taxa most strongly positively correlated with increased tumor burden were members of the Bacteroides, Parabacteroides, Alistipes, and Akkermansia, all of which are Gram-negative. Members of the Gram-positive Clostridiales, including multiple members of Clostridium Group XIVa, were strongly negatively correlated with tumors. Analysis of the inferred metagenome of each community revealed a negative correlation between tumor count and the potential for butyrate production, and a positive correlation between tumor count and the capacity for host glycan degradation. Despite harboring distinct gut communities, all mice underwent conserved structural changes over the course of the model. The

  16. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Han, Miaojun [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Wang, Hailun [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Zhang, Hua-Tang [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Han, Zhaozhong, E-mail: zhaozhong.han@vanderbilt.edu [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. Black-Right-Pointing-Pointer Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  17. Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

    Science.gov (United States)

    Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2014-01-01

    In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

  18. Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota

    DEFF Research Database (Denmark)

    Wahlström, Annika; Kovatcheva-Datchary, Petia; Ståhlman, Marcus

    2017-01-01

    The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study, we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR...... signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum...... of tauro-β-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized...

  19. Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors

    Institute of Scientific and Technical Information of China (English)

    Takahiro Nemoto; Shunichiro Kubota; Hideyuki Ishida; Nobuo Murata; Daijo Hashimoto

    2005-01-01

    AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

  20. Separation of water-soluble metabolites of benzo[a]pyrene formed by cultured human colon

    DEFF Research Database (Denmark)

    1979-01-01

    A method has been developed to separate conjugated metabolites of benzo[a]pyrene into three major fractions: sulfate esters, glucuronides and glutathione conjugates. In cultured human colon, formation of sulfate esters and glutathione conjugates is the major conjugation pathway, while formation o......-hydroxybenzo[a]pyrene were the major substrates for sulfotransferase in cultured human colon....

  1. Novel use of an air-filled breast prosthesis to allow radiotherapy to recurrent colonic cancer.

    LENUS (Irish Health Repository)

    O'Duffy, F

    2012-02-01

    AiM: The authors present the novel and successful use of an air-filled breast prosthesis for extra pelvic exclusion of small bowel to facilitate adjuvant radiotherapy following resection of recurrent adenocarcinoma of the ascending bowel. The therapeutic use of radiotherapy in colon cancer can cause acute or chronic radiation enteropathy. Mobile small bowel can be sequestered in \\'dead space\\' or by adhesions exposing it to adjuvant radiotherapy. A variety of pelvic partitioning methods have been described to exclude bowel from radiation fields using both native and prosthetic materials. METHOD: In this case a 68 year old presented with ascending colon adenocarcinoma invading the peritoneum and underwent en bloc peritoneal resection. Thirty-seven months later surveillance CT identified a local recurrence. Subsequent resection resulted in a large iliacus muscle defect which would sequester small bowel loops thus exposing the patient to radiation enteropathy. The lateral position of the defect precluded the use of traditional pelvic partitioning methods which would be unlikely to remain in place long enough to allow radiotherapy. A lightweight air-filled breast prosthesis (Allergan 133 FV 750 cms) secured in place with an omentoplasty was used to fill the defect. RESULTS: Following well tolerated radiotherapy the prosthesis was deflated under ultrasound guidance and removed via a 7-cm transverse incision above the right iliac crest. The patient is disease free 18 months later with no evidence of treatment related morbidity. CONCLUSION: The use of a malleable air-filled prosthesis for pelvic partitioning allows specific tailoring of the prosthesis size and shape for individual patient defects. It is also lightweight enough to be secured in place using an omentoplasty to prevent movement related prosthesis migration. In the absence of adequate omentum a mesh sling may be considered to allow fixation. In this case the anatomy of the prosthesis position allowed for its

  2. Breast cancer metastases to the stomach and colon mimicking primary gastrointestinal cancer: Four cases and literature review

    Directory of Open Access Journals (Sweden)

    Necdet Uskent

    2016-08-01

    Full Text Available Intraluminal gastric and colonic metastases of the breast cancer are very rare and may sometimes prove a  diagnostic dilemma to distinguish from primary gastric and colonic cancers. It is important to make the distinction in order to navigate the proper treatment approach, which is a systemic treatment rather than surgery if the disease is me- tastatic. The spread to the gastrointestinal (GI tract is more frequent in lobular histology and according to a number of investigators, it is related to a particular tropism of lobular cells toward gastrointestinal mucosa. Any region of GI tract may be involved, from the tongue to the anus. Over the last decade, among the 1,100 breast cancer cases registered at our institutions, we diagnosed four patients with breast cancer who had metastases to the stomach and/or colon and presented symptoms that simulated primary gastrointestinal cancer. A total of 84 out of the 1,100 patients experienced invasive lobular histology. Among the four patients with GI tract metastases, three were diagnosed with lobular histology – two of whom had the signet ring cell subtype. The remaining patient was diagnosed with triple negative invasive ductal carcinoma; however, it clinically resembled invasive lobular carcinoma. Clinical and pathological features of these cases, as well as the review of related literature are discussed in this report.

  3. Radiosensitivity of human colon cancer cell enhanced by immunoliposomal docetaxel

    Institute of Scientific and Technical Information of China (English)

    Qing-Wei Wang; Hui-Lan Lü; Chang-Cheng Song; Hong Liu; Cong-Gao Xu

    2005-01-01

    AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel.METHODS: Immunoliposomal docetaxel was prepared by coupling monodonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin.RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoliposomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dosedependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation,strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation,immunoliposomal docetaxel significantly increased the percentage of G2/M cells and induced apoptosis, but significantly decreased the percentage of cells in G2/G1 and S phase by comparison with liposomal docetaxel.Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells.Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased.CONCLUSION: Immunoliposomal docetaxel is strongly effective

  4. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

    Science.gov (United States)

    Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

    2016-01-19

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

  5. Diversity of the Lactobacillus group in breast milk and vagina of healthy women and potential role in the colonization of the infant gut

    NARCIS (Netherlands)

    Martin, R.; Heilig, G.H.J.; Zoetendal, E.G.; Smidt, H.; Rodriguez, J.M.

    2007-01-01

    Aims: To evaluate the diversity of the Lactobacillus group in breast milk and the vagina of healthy women and understand their potential role in the infant gut colonization using the 16S rRNA gene approaches. Methods and Results: Samples of breast milk, vaginal swabs and infant faeces were aseptical

  6. Estrogen Receptor Mutants/Variants in Human Breast Cancer.

    Science.gov (United States)

    1995-12-01

    Human breast tissues and cell lines. Normal breast tissues were obtained from reduction mammoplastv surgical specimens collected at the Necker Hospital ...mammoplasty specimens collected at the laboratory of F. Kuttenn, Necker Hospital , France (4 cases) and at the Manitoba Breast Tumor Bank (4 cases). Human...method for the identification of mutations and polymorphisms in the gene for glycoprotein IIIa. Blood 1993, 8:2281-2288 2 Ikonen E, Aula P, Gron K

  7. Prevalence and genotype identification of human JC virus in colon cancer in Taiwan.

    Science.gov (United States)

    Lin, Paul Yann; Fung, Chiung-Yau; Chang, Fang-Pei; Huang, Wen-Shih; Chen, Wen-Cheng; Wang, Jeng-Yi; Chang, Deching

    2008-10-01

    Although JC virus (JCV), a human polyomavirus, has been detected in colon cancers, the association between JCV and colon cancer remains controversial. In Taiwan, the prevalence of JCV infection in colon cancer patients has not been reported. Thus, the purpose of this study was to investigate JCV infection in colon cancers in Taiwan. Formalin-fixed, paraffin-embedded tissues from 22 colon cancer patients were examined in this study. Nested PCR was performed to detect viral genomic DNA. The product of the nested PCR flanking the JCV regulatory region was sequenced further. Viral large tumor protein, LT, and late capsid protein, VP1, were examined by immunohistochemistry (IHC). Nested PCR revealed JCV genomic DNA in 86.4% (19/22) of the colon cancer tissue samples. Both rearranged and archetypal genotypes of JCV were identified. Expression of JCV LT was positive in 63.6% (14/22) of the examined colon cancer tissue samples but not in any adjacent normal region. Expression of viral capsid protein VP1 was not detected in any of the tissues examined. The current study demonstrates that JCV genomic DNA was present in the examined colon cancer tissues. The genotypes of JCV in colon cancer tissues were also identified. Expression of viral early protein but not structural capsid protein was detected in the examined colon cancer tissues. Furthermore, a high prevalence of JCV infection in colon cancer tissues in Taiwan was also demonstrated.

  8. Modeling of human colonic blood flow for a novel artificial anal sphincter system

    Institute of Scientific and Technical Information of China (English)

    Peng ZAN; Guo-zheng YAN; Hua LIU

    2008-01-01

    A novel artificial anal sphincter system has been developed to simulate the normal physiology of the human anorectum. With the goal of engineering a safe and reliable device, the model of human colonic blood flow has been built and the relationship between the colonic blood flow rate and the operating occlusion pressure of the anorectum is achieved. The tissue ischemia is analyzed based on constitutive relations for human anorectum. The results suggest that at the planned operating occlusion pressure of less than 4 kPa the artificial anal sphincter should not risk the vaseularity of the human colon.

  9. Management of a case of Mucor colonization in breast tissue expander seroma pocket

    Directory of Open Access Journals (Sweden)

    Danielle N. Atwood

    2017-06-01

    Full Text Available Mucormycosis is a rare and potentially life-threatening opportunistic infection with approximately 500 cases per year in the United States (Spellberg et al., 2005. There are six major presentations, which include rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and uncommon (e.g. osteomyelitis, endocarditis Petrikkos et al. (2012.2 While not a prominent pathogen in immunocompetent patients, immunocompromised patients such as those with prolonged neutropenia, organ and/or bone marrow suppression, and diabetes mellitus are prone to dissemination resulting in rapid death without prompt intervention (Spellberg et al. 2005. With a mortality rate reaching 90% (Spellberg et al. 2005, it is imperative that therapy be initiated rapidly once a diagnosis is made. Successful treatment consists of management of underlying risk factors, surgical debridement, and antifungal therapies (Spellberg et al. 2005. The dilemma whether to pursue extensive debridement presents when the wound is cultured positive but the patient is not systemically ill. We present the first reported case of successful salvage of breast reconstruction with retention of tissue extender and acellular dermal matrix (ADM despite colonization of a recalcitrant seroma pocket by Mucor.

  10. Neutrophils support lung colonization of metastasis-initiating breast cancer cells.

    Science.gov (United States)

    Wculek, Stefanie K; Malanchi, Ilaria

    2015-12-17

    Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.

  11. Effect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor model.

    Science.gov (United States)

    Singletary, K W; Meline, B

    2001-01-01

    Cancers of the colon and breast are two of the most prevalent cancers in developed countries. The present experiments were conducted to determine the influence of several dietary doses of grape seed proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis and azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a dual-organ tumor model. In addition, the effects of the grape seed proanthocyanidins on liver cytochrome P-450 1A and 2E1 and glutathione S-transferase activities and on colonic ornithine decarboxylase activity were examined to determine possible mechanisms of action. Feeding female rats diets containing 0.1-1.0% grape seed proanthocyanidins was associated with a significant 72-88% inhibition of AOM-induced aberrant crypt foci formation and a 20-56% inhibition of ornithine decarboxylase activity in the distal third of the colon. Feeding the grape proanthocyanidins resulted in no significant effect on the activity of liver cytochrome P-450 2E1. There was no effect of feeding these doses of proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis. This lack of action on mammary tumorigenesis in part may be due to lack of effect of dietary proanthocyanidins on the liver carcinogen-metabolizing enzymes cytochrome P-450 1A and glutathione S-transferase. These results indicate that grape polyphenolics warrant further evaluation as potential colon cancer chemopreventive agents.

  12. Human Papilloma Viruses and Breast Cancer – Assessment of Causality

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

  13. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, L; Normark, M

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  14. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Normark, M;

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  15. Proteome of human colon cancer stem cells: A comparative analysis

    Institute of Scientific and Technical Information of China (English)

    Jian Zou; Xiao-Feng Yu; Zhi-Jun Bao; Jie Dong

    2011-01-01

    AIM: To isolate and identify the biological characteristics of human colon cancer stem cells (SW1116 cells) and further study their proteome. METHODS: SW1116 cells were isolated and cultured with a serum-free medium (SFM). Sphere formation was assayed to observe the formation of colon cancer stem cell spheres. SW1116 cells were inoculated into a serum-containing medium for observing their differentiation characteristics. Proliferation curve and cross-resistance of SW1116 cells to different drugs were detected by MTT. Percentage of SP cells in SW1116 cells was detected with Hoechst33342 staining. Telomerase activity in SW1116cells was checked by polymerase chain reaction (PCR)-enzyme linked immunosorbent assay. Expressions of stem cell relevant genes and proteins were detected by reverse transcription-PCR and Western blot, respectively. Total protein was isolated from SW1116 cells by two-dimensional gel electrophoresis (2-DE) and differentially expressed proteins were identified by tandem mass spectrometry (MALDI-TOF/TOF). RESULTS: The isolated SW1116 cells presented as spheroid and suspension growths in SFM with a strong self-renewal, proliferation, differentiation and drug-resistance ability. The percentage of SP cells in SW1116 cells was 38.9%. The SW1116 cells co-expressed the CD133 and CD29 proteins. The telomerase activity in SW1116 cells was increased. The expressions of different stem cell relevant genes and proteins were detected. The proteomic analysis showed that the 26 protein spots were differently expressed in SW1116 cells and 10 protein spots were identified as ubiquitin fusiondegradation 1-like protein, nuclear chloride channel protein, tubulin b, Raichu404X, stratifin, F-actin capping protein a-1 subunit, eukaryotic translation elongation factor 1 delta isoform 2, hypothetical protein, glyceraldehyde-3-phosphate dehydrogenase and guanine nucleotide binding protein b polypeptide 2-like 1, respectively. CONCLUSION: SW1116 cells are biologically

  16. Enhanced expression of resistin-like molecule beta in human colon cancer and its clinical significance.

    Science.gov (United States)

    Zheng, Li-Duan; Tong, Qiang-Song; Weng, Mi-Xia; He, Jun; Lv, Qing; Pu, Jia-Rui; Jiang, Guo-Song; Cai, Jia-Bin; Liu, Yuan; Hou, Xiao-Hua

    2009-02-01

    Previous studies have indicated that resistin-like molecule beta (RELM beta), an intestinal goblet cell-specific protein, is markedly increased in the intestinal tumors of min mice and over-expressed in a human colon cancer cell line. We hypothesized that RELM beta might be enhanced in human colon cancer. The aim of this study was to examine the clinical importance of RELM beta expression in colon cancer patients and to correlate its expression with various clinicopathological parameters, upstream regulatory molecule expression, tumor proliferative capacity, and patients' survival. Of the 80 colon cancer patients studied, 65 (81.25%) tested positive for RELM beta, mainly in the cytoplasm of colon mucosa. Contrasting sharply with the strongly RELM beta-positive tumors, normal colon mucous membrane was negative or weakly positive. RELM beta positivity in colon cancer was correlated with histological grade of differentiation and lymph node metastasis, but not with age, gender, tumor location and size, tumor infiltration, Dukes' stage, liver metastasis, and venous invasion. RELM beta expression was significantly correlated with the expression of transcription factor CDX-2 (P 0.05). The mean postoperative survival time (2.76 years) of RELM beta-positive patients was significantly longer than that (1.26 years) of RELM beta-negative patients (P = 0.032). These findings support evidence of the enhanced RELM beta expression in colon cancer patients and suggest that further investigation is warranted to explore the role of RELM beta in colon cancer.

  17. Gene transcriptional networks integrate microenvironmental signals in human breast cancer.

    Science.gov (United States)

    Xu, Ren; Mao, Jian-Hua

    2011-04-01

    A significant amount of evidence shows that microenvironmental signals generated from extracellular matrix (ECM) molecules, soluble factors, and cell-cell adhesion complexes cooperate at the extra- and intracellular level. This synergetic action of microenvironmental cues is crucial for normal mammary gland development and breast malignancy. To explore how the microenvironmental genes coordinate in human breast cancer at the genome level, we have performed gene co-expression network analysis in three independent microarray datasets and identified two microenvironment networks in human breast cancer tissues. Network I represents crosstalk and cooperation of ECM microenvironment and soluble factors during breast malignancy. The correlated expression of cytokines, chemokines, and cell adhesion proteins in Network II implicates the coordinated action of these molecules in modulating the immune response in breast cancer tissues. These results suggest that microenvironmental cues are integrated with gene transcriptional networks to promote breast cancer development.

  18. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

  19. Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma.

    Science.gov (United States)

    Bernardi, Stella; Zennaro, Cristina; Palmisano, Silvia; Velkoska, Elena; Sabato, Nicoletta; Toffoli, Barbara; Giacomel, Greta; Buri, Luigi; Zanconati, Fabrizio; Bellini, Giuseppe; Burrell, Louise M; De Manzini, Nicolò; Fabris, Bruno

    2012-03-01

    A new arm of the renin-angiotensin system (RAS) has been recently characterized; this includes angiotensin converting enzyme (ACE)2 and angiotensin (Ang)1-7, a heptapeptide acting through the Mas receptor (MasR). Recent studies show that Ang1-7 has an antiproliferative action on lung adenocarcinoma cells. The aim of this study was to characterize RAS expression in human colon adenocarcinoma and to investigate whether Ang1-7 exerts an antiproliferative effect on human colon adenocarcinoma cells. Gene, protein expression and enzymatic activity of the main components of the RAS were determined on non-neoplastic colon mucosa as well as on the tumor mass and the mucosa taken 5 cm distant from it, both collected from patients with colon adenocarcinoma. Two different human colon cancer cell lines were treated with AngII and Ang1-7. The novel finding of this study was that MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. However, AngII and Ang1-7 did not have any pro-/antiproliferative effects in the cell lines studied. The data suggest that upregulation of the MasR could be used as a diagnostic marker of colon adenocarcinoma.

  20. Lubricin in human breast tissue expander capsules.

    Science.gov (United States)

    Cheriyan, Thomas; Guo, Lifei; Orgill, Dennis P; Padera, Robert F; Schmid, Thomas M; Spector, Myron

    2012-10-01

    Capsular contraction is the most common complication of breast reconstruction surgery. While presence of the contractile protein alpha smooth muscle actin (α-SMA) is considered among the causes of capsular contraction, the exact etiology and pathophysiology is not fully understood. The objective of this study was to investigate the possible role of lubricin in capsular formation and contraction by determining the presence and distribution of the lubricating protein lubricin in human breast tissue expander capsules. Related aims were to evaluate select histopathologic features of the capsules, and the percentage of cells expressing α-SMA, which reflects the myofibroblast phenotype. Capsules from tissue expanders were obtained from eight patients. Lubricin, at the tissue-implant interface, in the extracellular matrix, and in cells, and α-SMA-containing cells were evaluated immunohistochemically. The notable finding was that lubricin was identified in all tissue expander capsules: as a discrete layer at the tissue-implant interface, extracellular, and intracellular. There was a greater amount of lubricin in the extracellular matrix in the intimal-subintimal zone when compared with the tissue away from the implant. Varying degrees of synovial metaplasia were seen at the tissue-implant interface. α-SMA-containing cells were also seen in all but one patient. The findings might help us better understand factors involved in capsule formation.

  1. Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

    NARCIS (Netherlands)

    Garcia, M.B.; Blankenstein, M.A.; Wall, E. van der; Nortier, J.W.R.; Schornagel, J.H.; Thijssen, J.H.H.

    1990-01-01

    The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen

  2. Expression of peripheral benzodiazepine receptor (PBR) in human tumors: relationship to breast, colorectal, and prostate tumor progression.

    Science.gov (United States)

    Han, Zeqiu; Slack, Rebecca S; Li, Wenping; Papadopoulos, Vassilios

    2003-01-01

    High levels of peripheral-type benzodiazepine receptor (PBR), the alternative-binding site for diazepam, are part of the aggressive human breast cancer cell phenotype in vitro. We examined PBR levels and distribution in normal tissue and tumors from multiple cancer types by immunohistochemistry. Among normal breast tissues, fibroadenomas, primary and metastatic adenocarcinomas, there is a progressive increase in PBR levels parallel to the invasive and metastatic ability of the tumor (p cancers, such as those of breast, colon-rectum and prostate tissues, where elevated PBR expression is associated with tumor progression. Thus, we propose that PBR overexpression could serve as a novel prognostic indicator of an aggressive phenotype in breast, colorectal and prostate cancers.

  3. Differential protein abundance and function of UT-B urea transporters in human colon.

    Science.gov (United States)

    Collins, D; Winter, D C; Hogan, A M; Schirmer, L; Baird, A W; Stewart, G S

    2010-03-01

    Facilitative UT-B urea transporters enable the passage of urea across cell membranes. Gastrointestinal urea transporters are thought to play a significant role in the urea nitrogen salvaging process that occurs between mammalian hosts and their gut bacteria. This study investigated the expression of UT-B urea transporters in different segments of human colon. Immunoblot analysis showed that human colon expressed a 35-kDa glycosylated UT-B protein in the colonic mucosa. The 35-kDa UT-B transporter was predominantly located in plasma membrane-enriched samples (P UT-B transporters were located throughout colonocytes situated in the upper portion of the colonic crypts. Bidirectional trans-epithelial urea transport was significantly greater in the ascending colon than the descending colon (P UT-B protein in different sections of the human colon, strongly correlating to regions that contain the largest populations of intestinal bacteria. This study suggests an important role for UT-B urea transporters in maintaining the symbiotic relationship between humans and their gut bacteria.

  4. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

    Science.gov (United States)

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  5. Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities.

    Science.gov (United States)

    Larrosa, Mar; González-Sarrías, Antonio; García-Conesa, María Teresa; Tomás-Barberán, Francisco A; Espín, Juan Carlos

    2006-03-08

    Urolithins A and B (hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives) are colonic microflora metabolites recently proposed as biomarkers of human exposure to dietary ellagic acid derivatives. Molecular models suggest that urolithins could display estrogenic and/or antiestrogenic activity. To this purpose, both urolithins and other known phytoestrogens (genistein, daidzein, resveratrol, and enterolactone) were assayed to evaluate the capacity to induce cell proliferation on the estrogen-sensitive human breast cancer MCF-7 cells as well as the ability to bind to alpha- and beta-estrogen receptors. Both urolithins A and B showed estrogenic activity in a dose-dependent manner even at high concentrations (40 microM), without antiproliferative or toxic effects, whereas the other phytoestrogens inhibited cell proliferation at high concentrations. Overall, urolithins showed weaker estrogenic activity than the other phytoestrogens. However, both urolithins displayed slightly higher antiestrogenic activity (antagonized the growth promotion effect of 17-beta-estradiol in a dose-dependent manner) than the other phytoestrogens. The IC(50) values for the ERalpha and ERbeta binding assays were 0.4 and 0.75 microM for urolithin A; 20 and 11 microM for urolithin B; 3 and 0.02 for genistein; and 2.3 and 1 for daidzein, respectively; no binding was detected for resveratrol and enterolactone. Urolithins A and B entered into MCF-7 cells and were metabolized to yield mainly urolithin-sulfate derivatives. These results, together with previous studies regarding absorption and metabolism of dietary ellagitannins and ellagic acid in humans, suggest that the gut microflora metabolites urolithins are potential endocrine-disrupting molecules, which could resemble other described "enterophytoestrogens" (microflora-derived metabolites with estrogenic/antiestrogenic activity). Further research is warranted to evaluate the possible role of ellagitannins and ellagic acid as dietary "pro-phytoestrogens".

  6. Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway.

    Science.gov (United States)

    Ha, Tae Kwun; Kim, Mi Eun; Yoon, Ju Hwa; Bae, Sung Jin; Yeom, Jihye; Lee, Jun Sik

    2013-09-01

    Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.

  7. Functional characterization and localization of AQP3 in the human colon

    Directory of Open Access Journals (Sweden)

    Silberstein C.

    1999-01-01

    Full Text Available Water channels or aquaporins (AQPs have been identified in a large variety of tissues. Nevertheless, their role in the human gastrointestinal tract, where their action is essential for the reabsorption and secretion of water and electrolytes, is still unclear. The purpose of the present study was to investigate the structure and function of water channels expressed in the human colon. A cDNA fragment of about 420 bp with a 98% identity to human AQP3 was amplified from human stomach, small intestine and colon by reverse transcription polymerase chain reaction (RT-PCR and a transcript of 2.2 kb was expressed more abundantly in colon than in jejunum, ileum and stomach as indicated by Northern blots. Expression of mRNA from the colon of adults and children but not from other gastrointestinal regions in Xenopus oocytes enhanced the osmotic water permeability, and the urea and glycerol transport in a manner sensitive to an antisense AQP3 oligonucleotide, indicating the presence of functional AQP3. Immunocytochemistry and immunofluorescence studies in human colon revealed that the AQP3 protein is restricted to the villus epithelial cells. The immunostaining within these cells was more intense in the apical than in the basolateral membranes. The presence of AQP3 in villus epithelial cells suggests that AQP3 is implicated in water absorption across human colonic surface cells.

  8. Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

    Science.gov (United States)

    Liévin-Le Moal, Vanessa

    2013-01-01

    SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses. PMID:24006470

  9. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  10. [Morphometric characteristics of human colon wall as anatomic basis for microsurgical anastomoses].

    Science.gov (United States)

    Konovalov, D Iu

    2007-01-01

    This article describes the morphometric characteristics and some peculiarities of microsurgical anatomy of human colon wall. The thickness of colon wall varied from 495 to 3501 microm in the areas between teniae and from 1103 to 4007 microm in the areas of teniae, the average values were equal to 1693+93.3 and 2602+85 microm, respectively. The width of teniae was 3.5-10.3 mm (6.2+0.3 mm on the average). The thickness of tunica muscularis along the colon prevailed over the thickness of other tunics and increased caudally, while the thickness of submucosa diminished. Marked variability and small thickness of both the colon wall and its layers, differences of these characteristics in the areas of teniae musculares and between them support the expediency of the application of microsurgical operative technique in the operations performed on the colon.

  11. Steady state and time-resolved autofluorescence studies of human colonic tissues

    Institute of Scientific and Technical Information of China (English)

    Buhong Li; Zhenxi Zhang; Shusen Xie

    2006-01-01

    Steady state and time-resolved autofluorescence spectroscopies are employed to study the autofluorescence characteristics of human colonic tissues in vitro. The excitation wavelength varies from 260 to 540 nm, and the corresponding fluorescence emission spectra are acquired from 280 to 800 nm. Significant difference in fluorescence intensity of excitation-emission matrices (EEMs) is observed between normal and tumor colonic tissues. Compared with normal colonic tissue, low nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), and high amino acids and protoporphyrin Ⅸ (PpⅨ) fluorescences characterize high-grade malignant tissue. Moreover, the autofluorescence lifetimes of normal and carcinomatous colonic tissues at 635 nm under 397-nm excitation are about 4.32±0.12 and 18.45±0.05 ns, respectively. The high accumulation of endogenous PpⅨ in colonic cancers is demonstrated in both steady state and time-resolved autofluorescence spectroscopies.

  12. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  13. Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells.

    Science.gov (United States)

    Gouyer, V; Fontaine, D; Dumont, P; de Wever, O; Fontayne-Devaud, H; Leteurtre, E; Truant, S; Delacour, D; Drobecq, H; Kerckaert, J-P; de Launoit, Y; Bracke, M; Gespach, C; Desseyn, J-L; Huet, G

    2008-07-03

    From the conditioned medium of the human colon carcinoma cells, HT-29 5M21 (CM-5M21), expressing a spontaneous invasive phenotype, tumor-associated trypsin inhibitor (TATI) was identified and characterized by proteomics, cDNA microarray approaches and functional analyses. Both CM-5M21 and recombinant TATI, but not the K18Y-TATI mutant at the protease inhibitor site, trigger collagen type I invasion by several human adenoma and carcinoma cells of the colon and breast, through phosphoinositide-3-kinase, protein kinase C and Rho-GTPases/Rho kinase-dependent pathways. Conversely, the proinvasive action of TATI in parental HT29 cells was alleviated by the TATI antibody PSKAN2 and the K18Y-TATI mutant. Stable expression of K18Y-TATI in HT-29 5M21 cells downregulated tumor growth, angiogenesis and the expression of several metastasis-related genes, including CSPG4 (13.8-fold), BMP-7 (9.7-fold), the BMP antagonist CHORDIN (5.2-fold), IGFBP-2 and IGF2 (9.6- and 4.6-fold). Accordingly, ectopic expression of KY-TATI inhibited the development of lung metastases from HT-29 5M21 tumor xenografts in immunodeficient mice. These findings identify TATI as an autocrine transforming factor potentially involved in early and late events of colon cancer progression, including local invasion of the primary tumor and its metastatic spread. Targeting TATI, its molecular partners and effectors may bring novel therapeutic applications for high-grade human solid tumors in the digestive and urogenital systems.

  14. Prevention of the Angiogenic Switch in Human Breast Cancer

    Science.gov (United States)

    2009-03-01

    chronic myeloid leukaemia | colorectal cancer | Down syndrome | infantile haemangiomas | multiple myeloma | non-small-cell lung cancer | rheumatoid...Human Breast Cancer PRINCIPAL INVESTIGATOR: Donald Ingber, M.D., Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital...From - To) 15 FEB 2004 - 14 FEB 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prevention of the Angiogenic Switch in Human Breast Cancer 5b

  15. Butyrate-induced transcriptional changes in human colonic mucosa

    NARCIS (Netherlands)

    Vanhoutvin, S.A.L.W.; Troost, F.J.; Hamer, H.M.; Lindsey, P.J.; Koek, G.H.; Jonkers, D.M.A.E.; Kodde, A.; Venema, K.; Brummer, R.J.M.

    2009-01-01

    Background: Fermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate). Butyrate modulates a wide range of processes, but its mechanism of action is mostly unknown. This study aimed to determine the effects of butyrate on

  16. Exploring human breast milk composition by NMR-based metabolomics.

    Science.gov (United States)

    Praticò, Giulia; Capuani, Giorgio; Tomassini, Alberta; Baldassarre, Maria Elisabetta; Delfini, Maurizio; Miccheli, Alfredo

    2014-01-01

    Breast milk is a complex fluid evolutionarily adapted to satisfy the nutritional requirements of growing infants. In addition, milk biochemical and immunological components protect newborns against infective agents in the new environment. Human milk oligosaccharides, the third most abundant component of breast milk, are believed to modulate the microbiota composition, thus influencing a wide range of physiological processes of the infant. Human milk also contains a number of other bioactive compounds, the functional role of which has not yet been clearly elucidated. In this scenario, NMR-based metabolic profiling can provide a rapid characterisation of breast milk composition, thus allowing a better understanding of its nutritional properties.

  17. T Cell Coinhibition and Immunotherapy in Human Breast Cancer

    OpenAIRE

    Janakiram, Murali; Abadi, Yael M.; Sparano, Joseph A.; Zang, Xingxing

    2012-01-01

    Costimulation and coinhibition generated by the B7 family and their receptor CD28 family have key roles in regulating T lymphocyte activation and tolerance. These pathways are very attractive therapeutic targets for human cancers including breast cancer. Gene polymorphisms of B7x (B7-H4/B7S1), PD-1 (CD279), and CTLA-4 (CD152) are associated with increased risk of developing breast cancer although the underlying mechanisms are unclear. In human breast cancer microenvironment, up-regulation of ...

  18. Human colon tissue in organ culture: calcium and multi-mineral-induced mucosal differentiation.

    Science.gov (United States)

    Dame, Michael K; Veerapaneni, Indiradevi; Bhagavathula, Narasimharao; Naik, Madhav; Varani, James

    2011-01-01

    We have recently shown that a multi-mineral extract from the marine red algae, Lithothamnion calcareum, suppresses colon polyp formation and inflammation in mice. In the present study, we used intact human colon tissue in organ culture to compare responses initiated by Ca(2+) supplementation versus the multi-mineral extract. Normal human colon tissue was treated for 2 d in culture with various concentrations of calcium or the mineral-rich extract. The tissue was then prepared for histology/immunohistochemistry, and the culture supernatants were assayed for levels of type I procollagen and type I collagen. At higher Ca(2+) concentrations or with the mineral-rich extract, proliferation of epithelial cells at the base and walls of the mucosal crypts was suppressed, as visualized by reduced Ki67 staining. E-cadherin, a marker of differentiation, was more strongly expressed at the upper third of the crypt and at the luminal surface. Treatment with Ca(2+) or with the multi-mineral extract influenced collagen turnover, with decreased procollagen and increased type I collagen. These data suggest that calcium or mineral-rich extract has the capacity to (1) promote differentiation in human colon tissue in organ culture and (2) modulate stromal function as assessed by increased levels of type I collagen. Taken together, these data suggest that human colon tissue in organ culture (supporting in vivo finding in mice) will provide a valuable model for the preclinical assessment of agents that regulate growth and differentiation in the colonic mucosa.

  19. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Ryuta Tobe

    2011-09-01

    Full Text Available Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins. Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15 may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.

  20. Classification of human colonic tissues using FTIR spectra and advanced statistical techniques

    Science.gov (United States)

    Zwielly, A.; Argov, S.; Salman, A.; Bogomolny, E.; Mordechai, S.

    2010-04-01

    One of the major public health hazards is colon cancer. There is a great necessity to develop new methods for early detection of cancer. If colon cancer is detected and treated early, cure rate of more than 90% can be achieved. In this study we used FTIR microscopy (MSP), which has shown a good potential in the last 20 years in the fields of medical diagnostic and early detection of abnormal tissues. Large database of FTIR microscopic spectra was acquired from 230 human colonic biopsies. Five different subgroups were included in our database, normal and cancer tissues as well as three stages of benign colonic polyps, namely, mild, moderate and severe polyps which are precursors of carcinoma. In this study we applied advanced mathematical and statistical techniques including principal component analysis (PCA) and linear discriminant analysis (LDA), on human colonic FTIR spectra in order to differentiate among the mentioned subgroups' tissues. Good classification accuracy between normal, polyps and cancer groups was achieved with approximately 85% success rate. Our results showed that there is a great potential of developing FTIR-micro spectroscopy as a simple, reagent-free viable tool for early detection of colon cancer in particular the early stages of premalignancy among the benign colonic polyps.

  1. The physiology of the normal human breast: an exploratory study.

    Science.gov (United States)

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  2. Anti-proliferation effects of benzimidazole derivatives on HCT-116 colon cancer and MCF-7 breast cancer cell lines.

    Science.gov (United States)

    Al-Douh, Mohammed Hadi; Sahib, Hayder B; Osman, Hasnah; Abd Hamid, Shafida; Salhimi, Salizawati M

    2012-01-01

    Benzimidazoles 1-4 were obtained using modified synthesis methods and studied for their ability to inhibit cell proliferation of colon cancer cell HCT-116 and breast cancer cell MCF-7 using MTT assays. In the HCT-116 cell line, benzimidazole 2 was found to have an IC50 value of 16.2 ± 3.85 μg/mL and benzimidazole 1 a value of 28.5 ± 2.91 μg/mL, while that for benzimidazole 4 was 24.08 ± 0.31 μg/mL. In the MCF-7 cell line, benzimidazole 4 had an IC50 value of 8.86 ± 1.10 μg/mL, benzimidazole 2 a value of 30.29 ± 6.39 μg/mL, and benzimidazole 1 a value of 31.2 ± 4.49 μg/mL. Benzimidazole 3 exerted no cytotoxicity in either of the cell lines, with IC50 values >50 μg/mL. The results suggest that benzimidazoles derivatives may have chemotherapeutic potential for treatment of both colon and breast cancers.

  3. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  4. Ultrastructure of interstitial cells of Cajal in myenteric plexus of human colon

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johannes; Vanderwinden, Jean-Marie; Rasmussen, Helle

    2009-01-01

    The role of the interstitial cells of Cajal (ICC) associated with the myenteric plexus (ICC-MP) as regulators of the motility of the colonic external muscle remains unclear. Ultrastructural studies of myenteric interstitial cells are lacking in human colon. We therefore characterized the distinct......The role of the interstitial cells of Cajal (ICC) associated with the myenteric plexus (ICC-MP) as regulators of the motility of the colonic external muscle remains unclear. Ultrastructural studies of myenteric interstitial cells are lacking in human colon. We therefore characterized...... and had myoid features such as scattered caveolae, prominent intermediate filaments, and cytoplasmic dense bodies. We found characteristic dense membrane-associated bands with a patchy basal lamina, invaginating cellular protrusions (peg and socket junctions) between ICC and between ICC and muscle cells...

  5. Src activity increases and Yes activity decreases during mitosis of human colon carcinoma cells.

    OpenAIRE

    Park, J.; Cartwright, C A

    1995-01-01

    Src and Yes protein-tyrosine kinase activities are elevated in malignant and premalignant tumors of the colon. To determine whether Src activity is elevated throughout the human colon carcinoma cell cycle as it is in polyomavirus middle T antigen- or F527 Src-transformed cells, and whether Yes activity, which is lower than that of Src in the carcinoma cells, is regulated differently, we measured their activities in cycling cells. We observed that the activities of both kinases were higher thr...

  6. FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

    Science.gov (United States)

    Bailey, Ann M; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L

    2014-01-01

    Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

  7. The utility of Apc-mutant rats in modeling human colon cancer

    Directory of Open Access Journals (Sweden)

    Amy A. Irving

    2014-11-01

    Full Text Available Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc and Kyoto Apc Delta (KAD strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  8. The utility of Apc-mutant rats in modeling human colon cancer

    Science.gov (United States)

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  9. Clinical impact of human breast milk metabolomics.

    Science.gov (United States)

    Cesare Marincola, Flaminia; Dessì, Angelica; Corbu, Sara; Reali, Alessandra; Fanos, Vassilios

    2015-12-01

    Metabolomics is a research field concerned with the analysis of metabolome, the complete set of metabolites in a given cell, tissue, or biological sample. Being able to provide a molecular snapshot of biological systems, metabolomics has emerged as a functional methodology in a wide range of research areas such as toxicology, pharmacology, food technology, nutrition, microbial biotechnology, systems biology, and plant biotechnology. In this review, we emphasize the applications of metabolomics in investigating the human breast milk (HBM) metabolome. HBM is the recommended source of nutrition for infants since it contains the optimal balance of nutrients for developing babies, and it provides a range of benefits for growth, immunity, and development. The molecular mechanisms beyond the inter- and intra-variability of HBM that make its composition unique are yet to be well-characterized. Although still in its infancy, the study of HBM metabolome has already proven itself to be of great value in providing insights into this biochemical variability in relation to mother phenotype, diet, disease, and lifestyle. The results of these investigations lay the foundation for further developments useful to identify normal and aberrant biochemical changes as well as to develop strategies to promote healthy infant feeding practices.

  10. Indoors forensic entomology: colonization of human remains in closed environments by specific species of sarcosaprophagous flies.

    Science.gov (United States)

    Pohjoismäki, Jaakko L O; Karhunen, Pekka J; Goebeler, Sirkka; Saukko, Pekka; Sääksjärvi, Ilari E

    2010-06-15

    Fly species that are commonly recovered on human corpses concealed in houses or other dwellings are often dependent on human created environments and might have special features in their biology that allow them to colonize indoor cadavers. In this study we describe nine typical cases involving forensically relevant flies on human remains found indoors in southern Finland. Eggs, larvae and puparia were reared to adult stage and determined to species. Of the five species found the most common were Lucilia sericata Meigen, Calliphora vicina Robineau-Desvoidy and Protophormia terraenovae Robineau-Desvoidy. The flesh fly Sarcophaga caerulescens Zetterstedt is reported for the first time to colonize human cadavers inside houses and a COI gene sequence based DNA barcode is provided for it to help facilitate identification in the future. Fly biology, colonization speed and the significance of indoors forensic entomological evidence are discussed.

  11. In vitro methods to culture primary human breast epithelial cells.

    Science.gov (United States)

    Raouf, Afshin; Sun, Yu Jia

    2013-01-01

    Current evidence suggests that much like leukemia, breast tumors are maintained by a small subpopulation of tumor cells that have stem cell properties. These cancer stem cells are envisaged to be responsible for tumor formation and relapse. Therefore, knowledge about their nature will provide a platform to develop therapies to eliminate these breast cancer stem cells. This concept highlights the need to understand the mechanisms that regulate the normal functions of the breast stem cells and their immediate progeny as alterations to these same mechanisms can cause these primitive cells to act as cancer stem cells. The study of the primitive cell functions relies on the ability to isolate them from primary sources of breast tissue. This chapter describes processing of discarded tissue from reduction mammoplasty samples as sources of normal primary human breast epithelial cells and describes cell culture systems to grow single-cell suspensions prepared from these reduction samples in vitro.

  12. Infrared absorption of human breast tissues in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu Chenglin [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Physics Department of Yancheng Teachers' College, Yancheng 224002 (China); Zhang Yuan [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Yan Xiaohui [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Zhang Xinyi [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China) and Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)]. E-mail: xy-zhang@fudan.edu.cn; Li Chengxiang [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Yang Wentao [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China); Shi Daren [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China)

    2006-07-15

    The spectral characteristics of human breast tissues in normal status and during different cancerous stages have been investigated by synchrotron radiation based Fourier transform infrared (SR-FTIR) absorption spectroscopy. Thanks to the excellent synchrotron radiation infrared (IR) source, higher resolving power is achieved in SR-FTIR absorption spectra than in conventional IR absorption measurements. Obvious variations in IR absorption spectrum of breast tissues were found as they change from healthy to diseased, or say in progression to cancer. On the other hand, some specific absorption peaks were found in breast cancer tissues by SR-FTIR spectroscopic methods. These spectral characteristics of breast tissue may help us in early diagnosis of breast cancer.

  13. Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

    OpenAIRE

    Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko; Gonzalez, Frank J.

    2014-01-01

    The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival r...

  14. Human colon carcinogenesis is associated with increased interleukin-17-driven inflammatory responses

    Directory of Open Access Journals (Sweden)

    Xie Z

    2015-03-01

    Full Text Available Zhaohui Xie,1 Yine Qu,2 Yanli Leng,2 Wenxiu Sun,2 Siqi Ma,2 Jingbo Wei,2 Jiangong Hu,3 Xiaolan Zhang1 1Department of Gastroenterology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Histology and Embryology, Hebei United University School of Basic Medicine, Tangshan, Hebei, People’s Republic of China; 3Department of Pathology, the Second Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China Abstract: Inflammation is known to contribute to carcinogenesis in human colorectal cancer. Proinflammatory cytokine interleukin-17 (IL-17 or IL-17A has been shown to play a critical role in colon carcinogenesis in mouse models. However, few studies have investigated IL-17A in human colon tissues. In the present study, we assessed IL-17-driven inflammatory responses in 17 cases of human colon adenocarcinomas, 16 cases of human normal colon tissues adjacent to the resected colon adenocarcinomas, ten cases of human ulcerative colitis tissues from biopsies, and eight cases of human colon polyps diagnosed as benign adenomas. We found that human colon adenocarcinomas contained the highest levels of IL-17A cytokine, which was significantly higher than the IL-17A levels in the adenomas, ulcerative colitis, and normal colon tissues (P<0.01. The levels of IL-17 receptor A (IL-17RA were also the highest in human colon adenocarcinomas, followed by adenomas and ulcerative colitis. The increased levels of IL-17A and IL-17RA were accompanied with increased IL-17-driven inflammatory responses, including activation of extracellular signal-regulated kinase (ERK1/2 and c-Jun N-terminal kinase (JNK pathways, increase in expression of matrix metalloproteinase (MMP9, MMP7, MMP2, B-cell lymphoma (Bcl-2, and cyclin D1, decrease in Bcl-2-associated X protein (BAX expression, and increase in vascular endothelial growth factor (VEGF and VEGF receptor (VEGFR expression that

  15. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.

  16. Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists.

    Science.gov (United States)

    He, Shao-Heng; Xie, Hua; Fu, Yi-Ling

    2005-03-01

    The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

  17. New Insights into the CD133 (Prominin-1) Expression in Mouse and Human Colon Cancer Cells.

    Science.gov (United States)

    Sgambato, Alessandro; Corbi, Maddalena; Svelto, Maria; Caredda, Emanuele; Cittadini, Achille

    2013-01-01

    Following its discovery as a cancer stem cell marker, CD133 has been widely studied for its role in colorectal tumorigenesis. Indeed, colon cancer remains one of the major causes of cancer-related disease and death worldwide, and there is a strong need for an improvement of current diagnostic, prognostic, and therapeutic strategies. Thus, efforts have been devoted to try to understand whether CD133 might play a role in human colorectal tumorigenesis and might contribute to a better management of colon cancer patients. This chapter reviews the current knowledge on CD133 expression in normal and cancer colon tissues, both in humans and mice, discussing apparently conflicting data reported in the two species. Moreover, a great attention is devoted to the available information regarding the functional role of CD133 in colon cancer cells. Finally, the proposed clinical applications of CD133, as a prognostic and/or predictive marker as well as a target for novel antineoplastic strategies in colorectal cancer, are discussed. Overall, the available data support a potential important role of CD133 as cancer stem cell marker in colon cancer cells and warrant future studies to verify its potential use in the routine clinical management of colon cancer patients.

  18. Overlapping expression of microRNAs in human embryonic colon and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    MicroRNAs (miRNAs) are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.

  19. Toward an increased understanding of the barriers to colonic drug absorption in humans: implications for early controlled release candidate assessment.

    Science.gov (United States)

    Tannergren, Christer; Bergendal, Anna; Lennernäs, Hans; Abrahamsson, Bertil

    2009-01-01

    The purpose of this study was to increase the understanding of in vivo colonic drug absorption in humans by summarizing and evaluating all regional in vivo human absorption data with focus on the interpretation of the colonic absorption data in relation to intestinal permeability and solubility. In addition, the usefulness of the Biopharmaceutics Classification System (BCS) in early assessment of the in vivo colonic absorption potential of controlled release drug candidates was investigated. Clinical regional absorption data (Cmax, Tmax, and AUC) of 42 drugs were collected from journal articles, abstracts, and internal reports, and the relative bioavailability in the colon (Frel(colon)) was obtained directly or calculated. Bioavailability, fraction dose absorbed, and information if the compounds were substrates for P-glycoprotein (P-gp) or cytochrome P450 3A (CYP3A) were also obtained. The BCS I drugs were well absorbed in the colon (Frel(colon) > 70%), although some drugs had lower values due to bacterial degradation in the colon. The low permeability drugs (BCS III/IV) had a lower degree of absorption in the colon (Frel(colon) colon), and atenolol and metoprolol may function as permeability markers for low and high colonic absorption, respectively. No obvious effect of P-gp on the colonic absorption of the drugs in this study was detected. There was insufficient data available to fully assess the impact of low solubility and slow dissolution rate. The estimated in vivo fractions dissolved of the only two compounds administered to the colon as both a solution and as solid particles were 55% and 92%, respectively. In conclusion, permeability and solubility are important barriers to colonic absorption in humans, and in vitro testing of these properties is recommended in early assessment of colonic absorption potential.

  20. Study on Invasion of Artesunate on Inhibiting Human Colon Cancer Cell SW620

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2013-09-01

    Full Text Available Objective: To observe the invasive effect of Chinese extraction artesunate on human colon cancer cell SW620 and explore its possible mechanisms. Methods: Colon cancer cell SW620 was managed by different concentrations of artesunate, and soft agar colony-cultivating trial was applied to detect anchorage independent proliferation of cancer cells, Boyden chamber model method to detect the invasive capability of cancer cells and Western blot method to detect the change of intercellular adhesion molecule-1 (ICAM-1 proteins. Results: Artesunate can effectively inhibit malignant proliferation and invasive capability of colon cancer cell SW620, and was dose-dependent (P < 0.01. Artesunate can effectively inhibit the expression of cancer cell ICAM-1 gene proteins, and was time- and concentration-dependant (P <0.01. Conclusion: Artesunate can significantly inhibit the invasion of colon cancer cell SW620, which can be related to down-regulation of ICAM-1 protein level.

  1. Study on Invasion of Artesunate on Inhibiting Human Colon Cancer Cell SW620

    Institute of Scientific and Technical Information of China (English)

    Fan Yu; Zhang Youli; Yao Guangtao; Li Yikui

    2013-01-01

    Objective:To observe the invasive effect of Chinese extraction artesunate on human colon cancer cell SW620 and explore its possible mechanisms. Methods:Colon cancer cell SW620 was managed by different concentrations of artesunate, and soft agar colony-cultivating trial was applied to detect anchorage independent proliferation of cancer cells, Boyden chamber model method to detect the invasive capability of cancer cells and Western blot method to detect the change of intercellular adhesion molecule-1 (ICAM-1) proteins. Results:Artesunate can effectively inhibit malignant proliferation and invasive capability of colon cancer cell SW620, and was dose-dependent (P Conclusion:Artesunate can signiifcantly inhibit the invasion of colon cancer cell SW620, which can be related to down-regulation of ICAM-1 protein level.

  2. The inhibition of Wnt/β-catenin signaling pathway in human colon cancer cells by sulindac.

    Science.gov (United States)

    Tai, Wei-Ping; Hu, Pin-Jin; Wu, Jing; Lin, Xiang-Chun

    2014-01-01

    The aberrant activation of Wnt/β-catenin signaling plays important roles in the initial development of colon cancer. Sulindac is a commonly used non-steroidal anti-inflammatory drug. We demonstrated the effects of sulindac on growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. Sulindac significantly inhibited proliferation of HT-29 colon cancer cells in a dose- and time-dependent manner. Sulindac was found to induce the apoptosis of HT-29 cells and inhibit the Wnt/β-catenin pathway. The inhibition was further confirmed by the decreased protein levels of β-catenin. The results indicate that sulindac may play a beneficial role in the comprehensive treatment of colon cancer.

  3. Abnormal colonic motility in mice overexpressing human wild-type alpha-synuclein.

    Science.gov (United States)

    Wang, Lixin; Fleming, Sheila M; Chesselet, Marie-Françoise; Taché, Yvette

    2008-05-28

    The presynaptic protein alpha-synuclein (alphaSyn) has been implicated in both familial and sporadic forms of Parkinson's disease. We examined whether human alphaSyn-overexpressing mice under Thy1 promoter (Thy1-alphaSyn) display alterations of colonic function. Basal fecal output was decreased in Thy1-alphaSyn mice fed ad libitum. Fasted/refed Thy1-alphaSyn mice had a slower distal colonic transit than the wild-type mice, as monitored by 2.2-fold increase in time to expel an intracolonic bead and 2.9-fold higher colonic fecal content. By contrast, Thy1-alphaSyn mice had an increased fecal response to novelty stress and corticotropin releasing factor injected intraperipherally. These results indicate that Thy1-alphaSyn mice display altered basal and stress-stimulated propulsive colonic motility and will be a useful model to study gut dysfunction associated with Parkinson's disease.

  4. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

    Science.gov (United States)

    Guillen-Ahlers, Hector; Tan, Jiangning; Castellino, Francis J; Ploplis, Victoria A

    2011-01-01

    Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+) colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  5. Characterization of AQPs in Mouse, Rat, and Human Colon and Their Selective Regulation by Bile Acids

    DEFF Research Database (Denmark)

    Yde, Jonathan; Keely, Stephen; Wu, Qi

    2016-01-01

    epithelial cells from rats (AQP1, 3, 4, 7, 8) and mice (AQP1, 4, 8). Several AQPs were also detected in human colon (AQP1, 3, 4, 7-9). Immunohistochemistry localized AQP1 to the apical plasma membrane of epithelial cells in the bottom of the crypts, whereas AQP3 (rat, human) and AQP4 (mice, human) were......In normal individuals, the epithelium of the colon absorbs 1.5-2 l of water a day to generate dehydrated feces. However, in the condition of bile acid malabsorption (BAM), an excess of bile acids in the colon results in diarrhea. Several studies have attempted to address the mechanisms contributing...... to BAM induced by various bile acids. However, none have addressed a potential dysregulation of aquaporin (AQP) water channels, which are responsible for the majority of transcellular water transport in epithelial cells, as a contributing factor to the onset of diarrhea and the pathogenesis of BAM...

  6. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

    Directory of Open Access Journals (Sweden)

    Hector Guillen-Ahlers

    Full Text Available Matrix metalloproteinase 7 (MMP7, a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  7. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  8. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Science.gov (United States)

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  9. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  10. Comprehensive molecular portraits of human breast tumours.

    Science.gov (United States)

    2012-10-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

  11. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data.

    Science.gov (United States)

    Kiarashi, Nooshin; Nolte, Adam C; Sturgeon, Gregory M; Segars, William P; Ghate, Sujata V; Nolte, Loren W; Samei, Ehsan; Lo, Joseph Y

    2015-07-01

    Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images

  12. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

    Energy Technology Data Exchange (ETDEWEB)

    Kiarashi, Nooshin [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Nolte, Adam C. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Sturgeon, Gregory M.; Ghate, Sujata V. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Segars, William P. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Nolte, Loren W. [Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Samei, Ehsan [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Department of Physics, Duke University, Durham, North Carolina 27708 (United States); and others

    2015-07-15

    Purpose: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. Methods: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. Results: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power

  13. Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

    Directory of Open Access Journals (Sweden)

    José J. Gaforio

    2011-10-01

    Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  14. Hydroxytyrosol protects against oxidative DNA damage in human breast cells.

    Science.gov (United States)

    Warleta, Fernando; Quesada, Cristina Sánchez; Campos, María; Allouche, Yosra; Beltrán, Gabriel; Gaforio, José J

    2011-10-01

    Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol's effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A) or breast cancer cells (MDA-MB-231 and MCF7). We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS) level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  15. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

    Science.gov (United States)

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

    The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Clinicopathological significance of PTPN12 expression in human breast cancer

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    Yuan, Xunyi [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China); Yuan, Zhentao [Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying Shandong Province (China); Jiang, Dandan; Li, Funian [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China)

    2012-10-15

    Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.

  17. Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

    Science.gov (United States)

    Raju, Jayadev; Roberts, Jennifer; Sondagar, Chandni; Kapal, Kamla; Aziz, Syed A.; Caldwell, Don; Mehta, Rekha

    2013-01-01

    Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters. PMID:24040114

  18. Effect of soy saponin on the growth of human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Cheng-Yu; Tsai; Yue-Hwa; Chen; Yi-Wen; Chien; Wen-Hsuan; Huang; Shyh-Hsiang; Lin

    2010-01-01

    AIM:To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells.METHODS:WiDr human colon cancer cells were treated with 150,300,600 or 1200 ppm of soy saponin to determine the effect on cell growth,cell morphology,alkaline phosphatase(AP) and protein kinase C(PKC) activities,and P53 protein,c-Fos and c-Jun gene expression.RESULTS:Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-Otetradecanol-phorbol-13-acetate-stimulated PKC ...

  19. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

    Science.gov (United States)

    Wu, Min; Jung, Lina; Cooper, Adrian B; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Richardson, Andrea; Bosenburg, Marcus; Naber, Stephen P; DePinho, Ronald A; Kuperwasser, Charlotte; Robinson, Murray O

    2009-04-28

    Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

  20. Nosocomial colonization due to imipenem-resistant Pseudomonas aeruginosa epidemiologically linked to breast milk feeding in a neonatal intensive care unit

    Institute of Scientific and Technical Information of China (English)

    Caterina MAMMINA; Paola DI CARLO; Domenico CIPOLLA; Alessandra CASUCCIO; Matilde TANTILLO; Maria Rosa Anna PLANO; Angela MAZZOLA; Giovanni CORSELLO

    2008-01-01

    Aim: We describe a one-year investigation of colonization by imipenem-resistant, metallo-β-1actamase (MBL) producing Pseudomonas aeruginosa in a neonatal intensive care unit (NICU) of the University Hospital of Palermo, Italy. Methods: A prospective epidemiological investigation was conducted in the period 2003 January to 2004 January. Rectal swabs were collected twice a week from all neonates throughout their NICU stay. MBL production by imipenem-resistant strains of P aeruginosa was detected by phenotypic and molecular methods. Pulsed field gel electrophoresis (PFGE) was carried out on all isolates of P aeruginosa. The association between risk factors and colonization by imipenem-resistant, imipenem-susceptible P aeruginosa isolates and other multidrug-resistant Gram negative (MDRGN) organisms was analyzed for variables present at admission and during the NICU stay. Data analysis was carried out by the Cox proportional hazards regression model. Results: Twenty-two of 210 neonates were colonized with imipenem-resistant, MBL-producing P aeruginosa isolates and 14 by imipenem-susceptible P aeruginosa isolates. A single pulsotype, named A, was shared by all imipenem-resistant isolates. Colonization by P aeruginosa of pulsotype A was positively correlated with breast milk feeding and administration of ampicillin-sulbactam, and inversely correlated with exclusive feeding by formula. In the Cox proportional hazards regression model, birthweight of more than 2500 g and breast milk feeding were independently associated with an increased risk of colonization by MBL-producing P aeruginosa. Conclusion: The results strongly support an association between colonization by a well-defined imipenem-resistant, MBL producing P aeruginosa strain and breast milk feeding. Such a study may highlight the need for implementation of strategies to prevent expressed breast milk from becoming a vehicle of health care-associated infections.

  1. Antiproliferative crude soy saponin extract modulates the expression of IkappaBalpha, protein kinase C, and cyclooxygenase-2 in human colon cancer cells.

    Science.gov (United States)

    Kim, Hwa-Young; Yu, Rina; Kim, Jeong-Sang; Kim, Young-Kyoon; Sung, Mi-Kyung

    2004-07-08

    Frequent consumption of soy and soy-based products is associated with reduced cancer incidence particularly for breast, colon, and prostate cancer. In this study, we examined the effect of crude soy saponin extract on PMA (phorbol 12-myristate 13-acetate)-induced inflammatory responses. Human adenocarcinoma cells (HT-29) were treated with various concentrations of saponin extract for 72 h. Cell growth was measured at 24, 48 and 72 h of incubation, and the PMA-induced expressions of cyclooxygenase-2 (COX-2), protein kinase C (PKC), and IkappaBalpha were determined. The results indicate that crude saponin extract decreased cell growth in a dose- and time-dependent manner. Crude soy saponin extract suppressed the degradation of IkappaBalpha in PMA-stimulated cells, while COX-2 and PKC expressions were significantly down-regulated. These findings support the hypothesis that the soy saponins reduce the risk of colon tumorigenesis possibly by suppressing inflammatory responses.

  2. Comparison of the effect of topical application of human milk and dry cord care on the bacterial colonization of umbilical cord in newborn infants

    Directory of Open Access Journals (Sweden)

    Fatemeh Abbaszadeh

    2014-04-01

    Full Text Available Background: Breast milk contains significant amounts of compounds that act as natural antimicrobial agents. This study was conducted to compare the effect of topical application of human milk and dry cord care on bacterial colonization in the umbilical cord of newborn infants. Methods: This clinical trial study was carried out on 174 infants in Kashan. The newborns were randomized to mother's milk group and dry cord care group from the birth. In group 1, the mother rubbed her own milk on the cord stump every 12 hours from 3 hours after birth to 2 days after the umbilical cord separation. In group 2, the mother was recommended not to use any material on the cord. Then, the cord samples were taken four times; 3hours after birth, at days 3 and 7, and 2 days after the umbilical cord separation. Results: The findings of the culture two days after umbilical cord separation indicated that low percentage of neonates in the breast milk (23.1% and dry cord care (28.8% groups had bacterial colonization. Moreover, no significant difference was found between the two groups in terms of growth of pathogenic organisms and normal flora of the skin (P>0.05. Conclusion: Given the low prevalence of pathogenic microorganisms in the two groups, it seems using breast milk and dry cord care are equally effective methods of taking care of umbilical cord.

  3. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats.

    Science.gov (United States)

    Patlolla, Jagan M R; Zhang, Yuting; Li, Qian; Steele, Vernon E; Rao, Chinthalapally V

    2012-01-01

    Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers and gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis induction in human colon cancer cells. Five-week-old male F344 rats were fed a control or experimental diet containing two doses of omeprazole (200 and 400 ppm). After one week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for two weeks). Rats continued on experimental diets for seven more weeks before being sacrificed. Colons were histopathologically evaluated for ACF. Human colon cancer HCT-116 and HCA-7 cells treated with omeprazole were evaluated for different markers associated with proliferation and apoptotic markers using Western blot technique. Rats fed with 200 and 400 ppm of omeprazole significantly suppressed total colonic ACF formation (~30%, Pcancer cell lines HCT-116 and HCA-7 cells resulted in induction of p21waf1/cip1 and decreased the expression of anti-apoptotic proteins Bcl-2, Bcl-XL and survivin in a dose-dependent manner. Anticancer properties observed in colon cancer cell lines suggest that omeprazole may induce key signaling molecules of antiproliferation and inhibition of anti-apoptotic proteins.

  4. Effect of Inulin on Proteome Changes Induced by Pathogenic Lipopolysaccharide in Human Colon

    Science.gov (United States)

    Guarino, Michele Pier Luca; Barera, Simone; Locato, Vittoria; Cocca, Silvia; Franchin, Cinzia; Arrigoni, Giorgio; Vannini, Candida; Grossi, Sarah; Campomenosi, Paola; Pasqualetti, Valentina; Bracale, Marcella; Alloni, Rossana; De Gara, Laura; Cicala, Michele

    2017-01-01

    In the present study, the protective role of inulin against lipopolysaccharide (LPS)-induced oxidative stress was evaluated on human colonic mucosa using a proteomic approach. Human colonic mucosa and submucosa were sealed between two chambers, with the luminal side facing upwards and overlaid with Krebs (control), LPS or LPS+ inulin IQ solution. The solutions on the submucosal side (undernatants) were collected following 30 min of mucosal exposure. iTRAQ based analysis was used to analyze the total soluble proteomes from human colonic mucosa and submucosa treated with different undernatants. Human colonic muscle strips were exposed to the undernatants to evaluate the response to acetylcholine. Inulin exposure was able to counteract, in human colonic mucosa, the LPS-dependent alteration of some proteins involved in the intestinal contraction (myosin light chain kinase (MLCK), myosin regulatory subunit (MYL)), to reduce the up-regulation of two proteins involved in the radical-mediated oxidative stress (the DNA-apurinic or apyrimidinic site) lyase) APEX1 and the T-complex protein 1 subunit eta (CCT7) and to entail a higher level of some detoxification enzymes (the metallothionein-2 MT2A, the glutathione–S-transferase K GSTk, and two UDP- glucuronosyltransferases UGT2B4, UGT2B17). Inulin exposure was also able to prevent the LPS-dependent intestinal muscle strips contraction impairment and the mucosa glutathione level alterations. Exposure of colonic mucosa to inulin seems to prevent LPS-induced alteration in expression of some key proteins, which promote intestinal motility and inflammation, reducing the radical-mediated oxidative stress. PMID:28068390

  5. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  6. On the relationship between sialomucin and sulfomucin expression and hydrogenotrophic microbes in the human colonic mucosa.

    Directory of Open Access Journals (Sweden)

    Jennifer A Croix

    Full Text Available The colonic mucus layer is comprised primarily of acidomucins, which provide viscous properties and can be broadly classified into sialomucins or sulfomucins based on the presence of terminating sialic acid or sulfate groups. Differences in acidomucin chemotypes have been observed in diseases such as colorectal cancer and inflammatory bowel disease, and variation in sialo- and sulfomucin content may influence microbial colonization. For example, sulfate derived from sulfomucin degradation may promote the colonization of sulfate-reducing bacteria (SRB, which through sulfate respiration generate the genotoxic gas hydrogen sulfide. Here, paired biopsies from right colon, left colon, and rectum of 20 subjects undergoing routine screening colonoscopies were collected to enable parallel histochemical and microbiological studies. Goblet cell sialo- and sulfomucins in each biopsy were distinguished histochemically and quantified. Quantitative PCR and multivariate analyses were used to examine the abundance of hydrogenotrophic microbial groups and SRB genera relative to acidomucin profiles. Regional variation was observed in sialomucins and sulfomucins with the greatest abundance of each found in the rectum. Mucin composition did not appear to influence the abundance of SRB or other hydrogenotrophic microbiota but correlated with the composition of different SRB genera. A higher sulfomucin proportion correlated with higher quantities of Desulfobacter, Desulfobulbus and Desulfotomaculum, relative to the predominant Desulfovibrio genus. Thus, acidomucin composition may influence bacterial sulfate respiration in the human colon, which may in turn impact mucosal homeostasis. These results stress the need to consider mucus characteristics in the context of studies of the microbiome that target intestinal diseases.

  7. Terahertz pulsed imaging of freshly excised human colonic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Caroline B; Gibson, Adam P [Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT (United Kingdom); Fitzgerald, Anthony; Wallace, Vincent P [School of Physics, University of Western Australia, Crawley 6009 (Australia); Reese, George; Tekkis, Paris [Division of Surgery, Chelsea and Westminster Campus, Imperial College London, London (United Kingdom); Goldin, Robert [Centre for Pathology, Imperial College London, St Mary' s Campus, London (United Kingdom); O' Kelly, P S [TeraView Ltd, Platinum Building, St John' s Innovation Park, Cowley Road, Cambridge, CB4 0WS (United Kingdom); Pickwell-MacPherson, Emma, E-mail: c.reid@medphys.ucl.ac.uk [Department of Electronic Engineering, Chinese University of Hong Kong, Shatin, NT (Hong Kong)

    2011-07-21

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  8. Proteogenomic characterization of human colon and rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri; Wang, Sean; Wang, Pei; Kinsinger, Christopher; Rivers, Robert; Rodriguez, Henry; Townsend, Reid; Ellis, Matthew; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert; Liebler, Daniel

    2014-09-18

    We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.

  9. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono

    2015-12-01

    Full Text Available MicroRNAs (miRNAs are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.

  10. CHL1 is involved in human breast tumorigenesis and progression

    Energy Technology Data Exchange (ETDEWEB)

    He, Li-Hong [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ma, Qin [Department of Oncology, The General Hospital of Tianjin Medical University, Tianjin (China); Shi, Ye-Hui [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie; Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Shu-Fen [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Tong, Zhong-Sheng, E-mail: 83352162@qq.com [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-08-23

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  11. Expression of the glioma-associated oncogene homolog (GLI 1 in human breast cancer is associated with unfavourable overall survival

    Directory of Open Access Journals (Sweden)

    Hartmann Arndt

    2009-08-01

    Full Text Available Abstract Background The transcription factor GLI1, a member of the GLI subfamily of Krüppel-like zinc finger proteins is involved in signal transduction within the hedgehog pathway. Aberrant hedgehog signalling has been implicated in the development of different human tumour entities such as colon and lung cancer and increased GLI1 expression has been found in these tumour entities as well. In this study we questioned whether GLI1 expression might also be important in human breast cancer development. Furthermore we correlated GLI1 expression with histopathological and clinical data to evaluate whether GLI1 could represent a new prognostic marker in breast cancer treatment. Methods Applying semiquantitative realtime PCR analysis and immunohistochemistry (IHC GLI1 expression was analysed in human invasive breast carcinomas (n = 229 in comparison to normal human breast tissues (n = 58. GLI1 mRNA expression was furthermore analysed in a set of normal (n = 3 and tumourous breast cell lines (n = 8. IHC data were statistically interpreted using SPSS version 14.0. Results Initial analysis of GLI1 mRNA expression in a small cohort of (n = 5 human matched normal and tumourous breast tissues showed first tendency towards GLI1 overexpression in human breast cancers. However only a small sample number was included into these analyses and values for GLI1 overexpression were statistically not significant (P = 0.251, two-tailed Mann-Whitney U-test. On protein level, nuclear GLI1 expression in breast cancer cells was clearly more abundant than in normal breast epithelial cells (P = 0.008, two-tailed Mann-Whitney U-test and increased expression of GLI1 protein in breast tumours significantly correlated with unfavourable overall survival (P = 0.019, but also with higher tumour stage (P P = 0.027. Interestingly, a highly significant correlation was found between GLI1 expression and the expression of SHH, a central upstream molecule of the hedgehog pathway that was

  12. Mutagens in human breast lipid and milk: the search for environmental agents that initiate breast cancer.

    Science.gov (United States)

    Phillips, David H; Martin, Francis L; Williams, J Andrew; Wheat, Luise M C; Nolan, Lisa; Cole, Kathleen J; Grover, Philip L

    2002-01-01

    Epidemiological studies indicate the involvement of environmental factors in the etiology of breast cancer, but have not provided clear indications of the nature of the agents responsible. Several environmental carcinogens are known to induce mammary tumors in rodents, and the abundance of adipose tissue in the human breast suggests that the epithelial cells, from which breast tumors commonly arise, could be exposed to lipid-soluble carcinogens sequestered by the adipose tissue. In this report we review our studies in which we have examined human mammary lipid, obtained from elective reduction mammoplasties from healthy donors, and human milk from healthy mothers, for the presence of components with genotoxic activity in several in vitro assays. A significant proportion of lipid extracts induced mutations in bacteria and micronuclei in mammalian cells. They also caused DNA damage, detected as single-strand breaks in the alkaline single-cell gel electrophoresis (comet) assay, in both the MCL-5 cell line and in primary cultures of human mammary epithelial cells. Genotoxic activity was also found in a significant proportion of extracts of human breast milk. Viable cells recovered from milk samples showed evidence of DNA damage and were susceptible to comet formation by genotoxic agents in vitro. Genotoxic activity was found to be less prevalent in milk samples from countries of lower breast cancer incidence (the Far East) compared with that in samples from the UK. The agents responsible for the activity in milk appear to be moderately polar lipophilic compounds and of low molecular weight. Identification of these agents and their sources may hold clues to the origins of breast cancer.

  13. Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

    Science.gov (United States)

    Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Armstrong, Georgina N.; Shete, Sanjay; Lau, Ching C.; Bainbridge, Matthew N.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Lai, Rose; Il'yasova, Dora; Houlston, Richard S.; Schildkraut, Joellen; Bernstein, Jonine L.; Olson, Sara H.; Jenkins, Robert B.; Lachance, Daniel H.; Wrensch, Margaret; Davis, Faith G.; Merrell, Ryan; Johansen, Christoffer; Sadetzki, Siegal; Bondy, Melissa L.; Melin, Beatrice S.; Adatto, Phyllis; Morice, Fabian; Payen, Sam; McQuinn, Lacey; McGaha, Rebecca; Guerra, Sandra; Paith, Leslie; Roth, Katherine; Zeng, Dong; Zhang, Hui; Yung, Alfred; Aldape, Kenneth; Gilbert, Mark; Weinberger, Jeffrey; Colman, Howard; Conrad, Charles; de Groot, John; Forman, Arthur; Groves, Morris; Levin, Victor; Loghin, Monica; Puduvalli, Vinay; Sawaya, Raymond; Heimberger, Amy; Lang, Frederick; Levine, Nicholas; Tolentino, Lori; Saunders, Kate; Thach, Thu-Trang; Iacono, Donna Dello; Sloan, Andrew; Gerson, Stanton; Selman, Warren; Bambakidis, Nicholas; Hart, David; Miller, Jonathan; Hoffer, Alan; Cohen, Mark; Rogers, Lisa; Nock, Charles J; Wolinsky, Yingli; Devine, Karen; Fulop, Jordonna; Barrett, Wendi; Shimmel, Kristen; Ostrom, Quinn; Barnett, Gene; Rosenfeld, Steven; Vogelbaum, Michael; Weil, Robert; Ahluwalia, Manmeet; Peereboom, David; Staugaitis, Susan; Schilero, Cathy; Brewer, Cathy; Smolenski, Kathy; McGraw, Mary; Naska, Theresa; Rosenfeld, Steven; Ram, Zvi; Blumenthal, Deborah T.; Bokstein, Felix; Umansky, Felix; Zaaroor, Menashe; Cohen, Avi; Tzuk-Shina, Tzeela; Voldby, Bo; Laursen, René; Andersen, Claus; Brennum, Jannick; Henriksen, Matilde Bille; Marzouk, Maya; Davis, Mary Elizabeth; Boland, Eamon; Smith, Marcel; Eze, Ogechukwu; Way, Mahalia; Lada, Pat; Miedzianowski, Nancy; Frechette, Michelle; Paleologos, Nina; Byström, Gudrun; Svedberg, Eva; Huggert, Sara; Kimdal, Mikael; Sandström, Monica; Brännström, Nikolina; Hayat, Amina; Tihan, Tarik; Zheng, Shichun; Berger, Mitchel; Butowski, Nicholas; Chang, Susan; Clarke, Jennifer; Prados, Michael; Rice, Terri; Sison, Jeannette; Kivett, Valerie; Duo, Xiaoqin; Hansen, Helen; Hsuang, George; Lamela, Rosito; Ramos, Christian; Patoka, Joe; Wagenman, Katherine; Zhou, Mi; Klein, Adam; McGee, Nora; Pfefferle, Jon; Wilson, Callie; Morris, Pagan; Hughes, Mary; Britt-Williams, Marlin; Foft, Jessica; Madsen, Julia; Polony, Csaba; McCarthy, Bridget; Zahora, Candice; Villano, John; Engelhard, Herbert; Borg, Ake; Chanock, Stephen K; Collins, Peter; Elston, Robert; Kleihues, Paul; Kruchko, Carol; Petersen, Gloria; Plon, Sharon; Thompson, Patricia; Johansen, C.; Sadetzki, S.; Melin, B.; Bondy, Melissa L.; Lau, Ching C.; Scheurer, Michael E.; Armstrong, Georgina N.; Liu, Yanhong; Shete, Sanjay; Yu, Robert K.; Aldape, Kenneth D.; Gilbert, Mark R.; Weinberg, Jeffrey; Houlston, Richard S.; Hosking, Fay J.; Robertson, Lindsay; Papaemmanuil, Elli; Claus, Elizabeth B.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Sloan, Andrew E.; Barnett, Gene; Devine, Karen; Wolinsky, Yingli; Lai, Rose; McKean-Cowdin, Roberta; Il'yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Yechezkel, Galit Hirsh; Bruchim, Revital Bar-Sade; Aslanov, Lili; Sadetzki, Siegal; Johansen, Christoffer; Kosteljanetz, Michael; Broholm, Helle; Bernstein, Jonine L.; Olson, Sara H.; Schubert, Erica; DeAngelis, Lisa; Jenkins, Robert B.; Yang, Ping; Rynearson, Amanda; Andersson, Ulrika; Wibom, Carl; Henriksson, Roger; Melin, Beatrice S.; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Merrell, Ryan; Lada, Patricia; Wrensch, Margaret; Wiencke, John; Wiemels, Joe; McCoy, Lucie; McCarthy, Bridget J.; Davis, Faith G.

    2014-01-01

    Background Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes. PMID:24723567

  14. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota

    Science.gov (United States)

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Safadi, Dima El; Certad, Gabriela; Delhaes, Laurence; Pereira, Bruno; Nourrisson, Céline; Poirier, Philippe; Wawrzyniak, Ivan; Delbac, Frédéric; Morelle, Christelle; Bastien, Patrick; Lachaud, Laurence; Bellanger, Anne-Pauline; Botterel, Françoise; Candolfi, Ermanno; Desoubeaux, Guillaume; Morio, Florent; Pomares, Christelle; Rabodonirina, Meja; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-01-01

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract. PMID:27147260

  15. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    Science.gov (United States)

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. © The Author(s) 2015.

  16. Dynamics of thymus organogenesis and colonization in early human development

    OpenAIRE

    Farley, Alison; Morris, Lucy; Vroegindeweij, Eric; Depreter, Marianne; Vaidya, Harsh; Stenhouse, Frances; Tomlinson, Simon; Anderson, Richard,; Cupedo, Tom; Cornelissen, Jan; Clare, Blackburn

    2013-01-01

    textabstractThe thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyng...

  17. Comprehensive molecular portraits of human breast tumours

    NARCIS (Netherlands)

    Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Schein, Jacqueline E.; Shafiei, Arash; Sipahimalani, Payal; Slobodan, Jared R.; Stoll, Dominik; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zeng, Thomas; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.; Cherniack, Andrew D.; Saksena, Gordon; Onofrio, Robert C.; Pho, Nam H.; Carter, Scott L.; Schumacher, Steven E.; Tabak, Barbara; Hernandez, Bryan; Gentry, Jeff; Nguyen, Huy; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Hoadley, Katherine A.; Auman, J. Todd; Fan, Cheng; Turman, Yidi J.; Shi, Yan; Li, Ling; Topal, Michael D.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Usary, Jerry; Berg, Jonathan S.; Adams, Michael; Booker, Jessica; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Malik, Simeen; Mahurkar, Swapna; Shen, Hui; Weisenberger, Daniel J.; Triche, Timothy; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Berman, Benjamin P.; Van den Berg, David J.; Baylin, Stephen B.; Laird, Peter W.; Creighton, Chad J.; Donehower, Lawrence A.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Sinha, Raktim; Park, Richard W.; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Reynolds, Sheila; Kreisberg, Richard B.; Bernard, Brady; Bressler, Ryan; Erkkila, Timo; Lin, Jake; Thorsson, Vesteinn; Zhang, Wei; Shmulevich, Ilya; Ciriello, Giovanni; Weinhold, Nils; Schultz, Nikolaus; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Sinha, Rileen; Aksoy, B. Arman; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Taylor, Barry S.; Ladanyi, Marc; Sander, Chris; Anur, Pavana; Spellman, Paul T.; Lu, Yiling; Liu, Wenbin; Verhaak, Roel R. G.; Mills, Gordon B.; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod D.; Wakefield, Chris; Unruh, Anna K.; Baggerly, Keith; Coombes, Kevin; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Scott, Gary K.; Yau, Christina; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Thusberg, Janita; Mooney, Sean; Ng, Sam; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian; Yan, Chunhua; Hu, Ying; Meerzaman, Daoud; Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron D.; Pyatt, Robert E.; White, Peter; Zmuda, Erik J.; Frick, Jessica; Lichtenberg, Taram.; Brookens, Robin; George, Myra M.; Gerken, Mark A.; Harper, Hollie A.; Leraas, Kristen M.; Wise, Lisa J.; Tabler, Teresa R.; McAllister, Cynthia; Barr, Thomas; Hart-Kothari, Melissa; Tarvin, Katie; Saller, Charles; Sandusky, George; Mitchell, Colleen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Dolzhansky, Oleg; Abramov, Mikhail; Voronina, Olga; Potapova, Olga; Marks, Jeffrey R.; Suchorska, Wiktoria M.; Murawa, Dawid; Kycler, Witold; Ibbs, Matthew; Korski, Konstanty; Spychala, Arkadiusz; Murawa, Pawel; Brzezinski, Jacek J.; Perz, Hanna; Lazniak, Radoslaw; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej; Van Le, Xuan; Kohl, Bernard; Viet Tien, Nguyen; Thorp, Richard; Van Bang, Nguyen; Sussman, Howard; Duc Phu, Bui; Hajek, Richard; Phi Hung, Nguyen; Viet The Phuong, Tran; Quyet Thang, Huynh; Khan, Khurram Zaki; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Ingle, James N.; Couch, Fergus J.; Lingle, Wilma L.; King, Tari A.; Gonzalez-Angulo, Ana Maria; Mills, Gordon B.; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto; Waldman, Frederic; Stoeppler, Hubert; Rathmell, W. Kimryn; Thorne, Leigh; Huang, Mei; Boice, Lori; Hill, Ashley; Morrison, Carl; Gaudioso, Carmelo; Bshara, Wiam; Daily, Kelly; Egea, Sophie C.; Pegram, Mark D.; Gomez-Fernandez, Carmen; Dhir, Rajiv; Bhargava, Rohit; Brufsky, Adam; Shriver, Craig D.; Hooke, Jeffrey A.; Campbell, Jamie Leigh; Mural, Richard J.; Hu, Hai; Somiari, Stella; Larson, Caroline; Deyarmin, Brenda; Kvecher, Leonid; Kovatich, Albert J.; Ellis, Matthew J.; King, Tari A.; Hu, Hai; Couch, Fergus J.; Mural, Richard J.; Stricker, Thomas; White, Kevin; Olopade, Olufunmilayo; Ingle, James N.; Luo, Chunqing; Chen, Yaqin; Marks, Jeffrey R.; Waldman, Frederic; Wiznerowicz, Maciej; Bose, Ron; Chang, Li-Wei; Beck, Andrew H.; Gonzalez-Angulo, Ana Maria; Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric; Pontius, Joan; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique; Nicholls, Matthew; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter; Alonso, Shelley; Sanbhadti, Rashmi; Barletta, Sean; Pot, David; Sheth, Margi; Demchok, John A.; Shaw, Kenna R. Mills; Yang, Liming; Eley, Greg; Ferguson, Martin L.; Tarnuzzer, Roy W.; Zhang, Jiashan; Dillon, Laura A. L.; Buetow, Kenneth; Fielding, Peter; Ozenberger, Bradley A.; Guyer, Mark S.; Sofia, Heidi J.; Palchik, Jacqueline D.

    2012-01-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression sub

  18. Comprehensive molecular portraits of human breast tumours

    NARCIS (Netherlands)

    Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Schein, Jacqueline E.; Shafiei, Arash; Sipahimalani, Payal; Slobodan, Jared R.; Stoll, Dominik; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zeng, Thomas; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.; Cherniack, Andrew D.; Saksena, Gordon; Onofrio, Robert C.; Pho, Nam H.; Carter, Scott L.; Schumacher, Steven E.; Tabak, Barbara; Hernandez, Bryan; Gentry, Jeff; Nguyen, Huy; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Hoadley, Katherine A.; Auman, J. Todd; Fan, Cheng; Turman, Yidi J.; Shi, Yan; Li, Ling; Topal, Michael D.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Usary, Jerry; Berg, Jonathan S.; Adams, Michael; Booker, Jessica; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Malik, Simeen; Mahurkar, Swapna; Shen, Hui; Weisenberger, Daniel J.; Triche, Timothy; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Berman, Benjamin P.; Van den Berg, David J.; Baylin, Stephen B.; Laird, Peter W.; Creighton, Chad J.; Donehower, Lawrence A.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Sinha, Raktim; Park, Richard W.; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Reynolds, Sheila; Kreisberg, Richard B.; Bernard, Brady; Bressler, Ryan; Erkkila, Timo; Lin, Jake; Thorsson, Vesteinn; Zhang, Wei; Shmulevich, Ilya; Ciriello, Giovanni; Weinhold, Nils; Schultz, Nikolaus; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Sinha, Rileen; Aksoy, B. Arman; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Taylor, Barry S.; Ladanyi, Marc; Sander, Chris; Anur, Pavana; Spellman, Paul T.; Lu, Yiling; Liu, Wenbin; Verhaak, Roel R. G.; Mills, Gordon B.; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod D.; Wakefield, Chris; Unruh, Anna K.; Baggerly, Keith; Coombes, Kevin; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Scott, Gary K.; Yau, Christina; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Thusberg, Janita; Mooney, Sean; Ng, Sam; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian; Yan, Chunhua; Hu, Ying; Meerzaman, Daoud; Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron D.; Pyatt, Robert E.; White, Peter; Zmuda, Erik J.; Frick, Jessica; Lichtenberg, Taram.; Brookens, Robin; George, Myra M.; Gerken, Mark A.; Harper, Hollie A.; Leraas, Kristen M.; Wise, Lisa J.; Tabler, Teresa R.; McAllister, Cynthia; Barr, Thomas; Hart-Kothari, Melissa; Tarvin, Katie; Saller, Charles; Sandusky, George; Mitchell, Colleen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Dolzhansky, Oleg; Abramov, Mikhail; Voronina, Olga; Potapova, Olga; Marks, Jeffrey R.; Suchorska, Wiktoria M.; Murawa, Dawid; Kycler, Witold; Ibbs, Matthew; Korski, Konstanty; Spychala, Arkadiusz; Murawa, Pawel; Brzezinski, Jacek J.; Perz, Hanna; Lazniak, Radoslaw; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej; Van Le, Xuan; Kohl, Bernard; Viet Tien, Nguyen; Thorp, Richard; Van Bang, Nguyen; Sussman, Howard; Duc Phu, Bui; Hajek, Richard; Phi Hung, Nguyen; Viet The Phuong, Tran; Quyet Thang, Huynh; Khan, Khurram Zaki; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Ingle, James N.; Couch, Fergus J.; Lingle, Wilma L.; King, Tari A.; Gonzalez-Angulo, Ana Maria; Mills, Gordon B.; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto; Waldman, Frederic; Stoeppler, Hubert; Rathmell, W. Kimryn; Thorne, Leigh; Huang, Mei; Boice, Lori; Hill, Ashley; Morrison, Carl; Gaudioso, Carmelo; Bshara, Wiam; Daily, Kelly; Egea, Sophie C.; Pegram, Mark D.; Gomez-Fernandez, Carmen; Dhir, Rajiv; Bhargava, Rohit; Brufsky, Adam; Shriver, Craig D.; Hooke, Jeffrey A.; Campbell, Jamie Leigh; Mural, Richard J.; Hu, Hai; Somiari, Stella; Larson, Caroline; Deyarmin, Brenda; Kvecher, Leonid; Kovatich, Albert J.; Ellis, Matthew J.; King, Tari A.; Hu, Hai; Couch, Fergus J.; Mural, Richard J.; Stricker, Thomas; White, Kevin; Olopade, Olufunmilayo; Ingle, James N.; Luo, Chunqing; Chen, Yaqin; Marks, Jeffrey R.; Waldman, Frederic; Wiznerowicz, Maciej; Bose, Ron; Chang, Li-Wei; Beck, Andrew H.; Gonzalez-Angulo, Ana Maria; Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric; Pontius, Joan; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique; Nicholls, Matthew; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter; Alonso, Shelley; Sanbhadti, Rashmi; Barletta, Sean; Pot, David; Sheth, Margi; Demchok, John A.; Shaw, Kenna R. Mills; Yang, Liming; Eley, Greg; Ferguson, Martin L.; Tarnuzzer, Roy W.; Zhang, Jiashan; Dillon, Laura A. L.; Buetow, Kenneth; Fielding, Peter; Ozenberger, Bradley A.; Guyer, Mark S.; Sofia, Heidi J.; Palchik, Jacqueline D.

    2012-01-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression sub

  19. In vitro degradation and fermentation of three dietary fiber sources by human colonic bacteria

    Science.gov (United States)

    Although clinical benefits of dietary fiber supplementation seem to depend in part on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of the type of supplemented fiber on bacterial metabolism. In an experiment using a non-adapted human bacterial...

  20. Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Petersen, Jørgen; Nielsen, Søren Jensby

    2010-01-01

    in the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images revealed...

  1. Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft tumors

    National Research Council Canada - National Science Library

    Cheng, Tzu-Chun; Lai, Ching-Shu; Chung, Min-Ching; Kalyanam, Nagabhushanam; Majeed, Muhammed; Ho, Chi-Tang; Ho, Yuan-Soon; Pan, Min-Hsiung

    2014-01-01

    ... (COLO 205, HCT-116, and HT-29) with measured IC50 values of 9.0, 40.2, and 70.9 µM, respectively. We found that HPSB effectively inhibited the growth of human colon cancer cells by inducing apoptosis and autophagy...

  2. Genetics of the pig tapeworm in Madagascar reveal a history of human dispersal and colonization

    Science.gov (United States)

    An intricate history of human dispersal and geographic colonization has strongly affected the distribution of obligate parasites circulating among people. Among these parasites, the pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serio...

  3. Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Petersen, Jørgen; Nielsen, Søren Jensby;

    2010-01-01

    in the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images revealed...

  4. The role of human innate immune factors in nasal colonization by Staphylococcus aureus

    NARCIS (Netherlands)

    van Belkum, Alex; Emonts, Marieke; Wertheim, Heiman; Bartels, Hans; Cole, Alexander; Lemmens-den Toom, Nicole; Snijders, Susan Susan; Verbrugh, Henri; van Leeuwen, Willem

    2007-01-01

    Slaphylococcus aureus colonization of the human nares predisposes to sometimes severe auto-infection. To investigate whether genetic polymorphism affects the S. aureus carriage status, sequence variation in alpha-defensin and beta-defensin, and mannose-binding lectin (MBL) genes were determined for

  5. Boletus edulis biologically active biopolymers induce cell cycle arrest in human colon adenocarcinoma cells.

    Science.gov (United States)

    Lemieszek, Marta Kinga; Cardoso, Claudia; Ferreira Milheiro Nunes, Fernando Hermínio; Ramos Novo Amorim de Barros, Ana Isabel; Marques, Guilhermina; Pożarowski, Piotr; Rzeski, Wojciech

    2013-04-25

    The use of biologically active compounds isolated from edible mushrooms against cancer raises global interest. Anticancer properties are mainly attributed to biopolymers including mainly polysaccharides, polysaccharopeptides, polysaccharide proteins, glycoproteins and proteins. In spite of the fact that Boletus edulis is one of the widely occurring and most consumed edible mushrooms, antitumor biopolymers isolated from it have not been exactly defined and studied so far. The present study is an attempt to extend this knowledge on molecular mechanisms of their anticancer action. The mushroom biopolymers (polysaccharides and glycoproteins) were extracted with hot water and purified by anion-exchange chromatography. The antiproliferative activity in human colon adenocarcinoma cells (LS180) was screened by means of MTT and BrdU assays. At the same time fractions' cytotoxicity was examined on the human colon epithelial cells (CCD 841 CoTr) by means of the LDH assay. Flow cytometry and Western blotting were applied to cell cycle analysis and protein expression involved in anticancer activity of the selected biopolymer fraction. In vitro studies have shown that fractions isolated from Boletus edulis were not toxic against normal colon epithelial cells and in the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells. The best results were obtained in the case of the fraction designated as BE3. The tested compound inhibited cancer cell proliferation which was accompanied by cell cycle arrest in the G0/G1-phase. Growth inhibition was associated with modulation of the p16/cyclin D1/CDK4-6/pRb pathway, an aberration of which is a critical step in the development of many human cancers including colon cancer. Our results indicate that a biopolymer BE3 from Boletus edulis possesses anticancer potential and may provide a new therapeutic/preventive option in colon cancer chemoprevention.

  6. The glutathione biotransformation system and colon carcinogenesis in human

    NARCIS (Netherlands)

    Grubben, M.J.A.L.; Nagengast, F.M.; Katan, M.B.; Peters, W.H.M.

    2001-01-01

    Evidence for a protective role of the glutathione biotransformation system in carcinogenesis is growing. However, most data on this system in relation to colorectal cancer originate from animal studies. Here we review the human data. In humans, a significant association was found between glutathione

  7. Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes.

    Science.gov (United States)

    Cotarelo, Cristina L; Schad, Arno; Kirkpatrick, Charles James; Sleeman, Jonathan P; Springer, Erik; Schmidt, Marcus; Thaler, Sonja

    2016-11-15

    Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities. As tumor initiation and progression of these breast cancer subtypes is triggered by diverse oncogenic stimuli, differences in the senescence secretomes within breast tumors might be responsible for tumor initiation, progression, metastasis and therapeutic response. Many studies have addressed the role of senescence as a barrier to tumor progression using murine xenograft models. However, few investigations have been performed to elucidate the degree to which senescent tumor cells are present within untreated human tumors, and if present, whether these senescent tumor cells may play a role in disease progression. In the present study we analysed the appearance of senescent cells within invasive breast cancers. Detection of cellular senescence by the use of SAβ-galactosidase (SAβ-gal) staining within invasive breast carcinoms from 129 untreated patients revealed differences in the amount of SAβ-gal+ tumor cells between breast cancer subtypes. The highest percentages of SAβ-gal+ tumor cells were found in HER2-positive and luminal A breast carcinomas whereas triple negative tumors showed either little or no positivity.

  8. Abnormal colonic motility in mice overexpressing human wild-type α-synuclein

    OpenAIRE

    2008-01-01

    The presynaptic protein α-synuclein (αSyn) has been implicated in both familial and sporadic forms of Parkinson’s disease. We examined whether human αSyn-overexpressing mice under Thy1 promoter (Thy1-αSyn) display alterations of colonic function. Basal fecal output was decreased in Thy1-αSyn mice fed ad libitum. Fasted/refed Thy1-αSyn mice had a slower distal colonic transit than the wild-type mice, as monitored by 2.2-fold increase in time to expel an intracolonic bead and 2.9-fold higher co...

  9. Human breast milk: A review on its composition and bioactivity.

    Science.gov (United States)

    Andreas, Nicholas J; Kampmann, Beate; Mehring Le-Doare, Kirsty

    2015-11-01

    Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely attuning it to the requirements of the infant. Breast milk contains many complex proteins, lipids and carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over lactation, to reflect the infant's needs. In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically active components. These molecules possess diverse roles, both guiding the development of the infants immune system and intestinal microbiota. Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis of which are determined by the maternal genotype. In this review, we discuss the composition of breast milk and the factors that affect it during the course of breast feeding. Understanding the components of breast milk and their functions will allow for the improvement of clinical practices, infant feeding and our understanding of immune responses to infection and vaccination in infants.

  10. Rapid change of fecal microbiome and disappearance of Clostridium difficile in a colonized infant after transition from breast milk to cow milk.

    Science.gov (United States)

    Davis, Manli Y; Zhang, Husen; Brannan, Lera E; Carman, Robert J; Boone, James H

    2016-10-07

    Clostridium difficile is the most common known cause of antibiotic-associated diarrhea. Upon the disturbance of gut microbiota by antibiotics, C. difficile establishes growth and releases toxins A and B, which cause tissue damage in the host. The symptoms of C. difficile infection disease range from mild diarrhea to pseudomembranous colitis and toxic megacolon. Interestingly, 10-50 % of infants are asymptomatic carriers of C. difficile. This longitudinal study of the C. difficile colonization in an infant revealed the dynamics of C. difficile presence in gut microbiota. Fifty fecal samples, collected weekly between 5.5 and 17 months of age from a female infant who was an asymptomatic carrier of C. difficile, were analyzed by 16S rRNA gene sequencing. Colonization switching between toxigenic and non-toxigenic C. difficile strains as well as more than 100,000-fold fluctuations of C. difficile counts were observed. C. difficile toxins were detected during the testing period in some infant stool samples, but the infant never had diarrhea. Although fecal microbiota was stable during breast feeding, a dramatic and permanent change of microbiota composition was observed within 5 days of the transition from human milk to cow milk. A rapid decline and eventual disappearance of C. difficile coincided with weaning at 12.5 months. An increase in the relative abundance of Bacteroides spp., Blautia spp., Parabacteroides spp., Coprococcus spp., Ruminococcus spp., and Oscillospira spp. and a decrease of Bifidobacterium spp., Lactobacillus spp., Escherichia spp., and Clostridium spp. were observed during weaning. The change in microbiome composition was accompanied by a gradual increase of fecal pH from 5.5 to 7. The bacterial groups that are less abundant in early infancy, and that increase in relative abundance after weaning, likely are responsible for the expulsion of C. difficile.

  11. Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect.

    Science.gov (United States)

    Huang, Liqun; Zhu, Caihua; Sun, Yu; Xie, Gang; Mackenzie, Gerardo G; Qiao, George; Komninou, Despina; Rigas, Basil

    2010-11-01

    Non-steroidal anti-inflammatory drugs such as sulindac are promising chemoprevention agents against colon cancer, but their weak potency and side effects limit their use for both chemoprevention and chemotherapy. Here, we evaluated the effect of a new sulindac derivative, phospho-sulindac or OXT-922, on the growth of human cancer cell lines and its mechanism of action. OXT-922 inhibited the growth of human cancer cell lines originating from colon, pancreas and breast ~11- to 30-fold more potently than sulindac. This effect was mediated by a strong cytokinetic effect. Compared with control, OXT-922 inhibited cell proliferation by up to 67%, induced apoptosis 4.1-fold over control and blocked the G(1) to S cell cycle phase transition. OXT-922 suppressed the levels of cell cycle regulating proteins, including cyclins D(1) and D(3) and Cyclin-dependent kinases (CDK) 4 and 6. The levels of intracellular reactive oxygen species (ROS), especially those of mitochondrial O₂ⁱ⁻, were markedly elevated (5.5-fold) in response to OXT-922. ROS collapsed the mitochondrial membrane potential and triggered apoptosis, which was largely abrogated by antioxidants. OXT-922 suppressed nuclear factor-kappaB activation and downregulated thioredoxin-1 expression. It also suppressed the production of prostaglandin E(2) and decreased cyclooxygenase-1 expression. Similar to sulindac, OXT-922 enhanced spermidine/spermine N(1)-acetyltransferase activity, reduced the cellular polyamine content and synergized with difluoromethylornithine to inhibit cancer cell proliferation and induce apoptosis. Our results suggest that OXT-922 possesses promising anticancer properties and deserves further evaluation.

  12. Pathological implications of Cx43 down-regulation in human colon cancer.

    Science.gov (United States)

    Ismail, Rehana; Rashid, Rabiya; Andrabi, Khurshid; Parray, Fazl Q; Besina, Syed; Shah, Mohd Amin; Ul Hussain, Mahboob

    2014-01-01

    Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (pcancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.

  13. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway.

    Science.gov (United States)

    Zhang, Xiang-An; Zhang, Shuangxi; Yin, Qing; Zhang, Jing

    2015-01-01

    Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases.

  14. Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

    Directory of Open Access Journals (Sweden)

    Caroline Vincent

    2015-07-01

    Full Text Available Clostridium difficile infection (CDI is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material.

  15. Vitamin D content in human breast milk

    DEFF Research Database (Denmark)

    Við Streym, Susanna; Højskov, Carsten S; Møller, Ulla Kristine

    2016-01-01

    BACKGROUND: Parents are advised to avoid the direct sun exposure of their newborns. Therefore, the vitamin D status of exclusively breastfed newborns is entirely dependent on the supply of vitamin D from breast milk. OBJECTIVES: We explored concentrations of ergocalciferol (vitamin D2......) and cholecalciferol (vitamin D3) (vitamin D) and 25-hydroxivitamin D2 plus D3 (25-hydroxyvitamin D [25(OH)D]) in foremilk and hindmilk during the first 9 mo of lactation and identified indexes of importance to the concentrations. DESIGN: We collected blood and breast-milk samples from mothers at 2 wk (n = 107), 4 mo......, (n = 90), and 9 mo (n = 48) postpartum. Blood samples from infants were collected 4 and 9 mo after birth. We measured concentrations of vitamin D metabolites in blood and milk samples with the use of liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of vitamin D and 25(OH)D...

  16. Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP‑7.

    Science.gov (United States)

    Gao, Fei; Zhang, Yuqin; Yang, Feng; Wang, Peng; Wang, Wenjun; Su, Yan; Luo, Weiren

    2014-03-01

    Increased expression levels of survivin are crucial for invasion activity in several types of human cancer, including colon carcinoma. However, the molecular mechanisms whereby survivin regulates cancer invasion have not been completely elucidated. To the best of our knowledge, this study is the first to investigate the role of matrix metalloprotease‑7 (MMP‑7) in cell invasion that is induced by survivin by using in vitro assays, including western blot, immunofluorescence and qPCR analyses. The results demonstrated that the ectopic expression of survivin significantly promoted the invasive activity of colon carcinoma cells (SW620 and HCT‑116) and resulted in increased levels of MMP‑7 activation. By contrast, the small interfering RNA (siRNA)‑based knockdown of survivin markedly reduced cell migration and led to a dose‑dependent decrease in MMP‑7 expression levels. Compared with the controls, knockdown of MMP‑7 by siRNA in colon carcinoma cells led to reduced invasion ability, whereas no obvious changes were observed when MMP‑7 expression was silenced in survivin‑overexpressing colon carcinoma cells. These findings demonstrate that MMP‑7 is crucial for survivin‑mediated invasiveness, suggesting that the survivin‑mediated MMP‑7 signaling pathway is a potential therapeutic target for the treatment of colon carcinoma.

  17. Plaque assay for human coronavirus NL63 using human colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Drosten Christian

    2008-11-01

    Full Text Available Abstract Background Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. Results 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2 replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2. CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4th day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. Conclusion CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

  18. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice.

    Science.gov (United States)

    Han, Miaojun; Wang, Hailun; Zhang, Hua-Tang; Han, Zhaozhong

    2012-05-25

    Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Modulation of histamine release from human colon mast cells by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of protease inhibitors to modulate histamine release from human colon mast cells.METHODS: Enzymatically dispersed cells from human colon were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of tryptase and chymase inhibitors, and histamine release was determined.RESULTS: IgE dependent histamine release from colon mast cells was inhibited by up to approximately 37%, 26% and 36.8% by chymase inhibitors Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPFM), N-Tosyl-L-phenylalanyl-chloromethyl ketone (TPCK), and α1-antitrypsin, respectively. Similarly, inhibitors of tryptase leupeptin, N-tosyl-L-lysine chloromethyl ketone (TLCK), lactoferrin and protamine were also able to inhibit anti-IgE induced histamine release by a maximum of some 48%, 37%, 40% and 34%, respectively. Preincubation of these inhibitors with cells for 20 min before challenged with anti-IgE had small effect on the inhibitory actions of these inhibitors on colon mast cells. A specific inhibitor of aminopeptidase amastatin had no effect on anti-IgE induced histamine release. The significant inhibition of calcium ionophore induced histamine release was also observed with the inhibitors of tryptase and chymase examined. Apart from leupeptin and protamine, the inhibitors tested by themselves did not stimulate colon mast cells.CONCLUSION: It was demonstrated that both tryptase and chymase inhibitors could inhibit IgE dependent and calcium ionophore induced histamine release from dispersed colon mast cells in a concentration dependent of manner, which suggest that they are likely to be developed as a novel class of anti-inflammatory drugs to treat chronic of colitis in man.

  20. Inhibition of tryptase release from human colon mast cells by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of protease inhibitors to modulate tryptase release from human colon mast cells.METHODS: Enzymatically dispersed cells from human colon were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of tryptase and chymase inhibitors,and tryptase release was determined.RESULTS: IgE dependent tryptase release from colon mast cells was inhibited by up to approximately 37%, 40% and 36.6% by chymase inhibitors Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPFM), N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK), and α1-antitrypsin, respectively. Similarly, the inhibitors of tryptase leupeptin, N-tosyl-L-lysine chloromethyl ketone (TLCK) and lactoferrin were also able to inhibit anti-IgE induced tryptase release by a maximum of 39.4%,47.6% and 36.6%, respectively. The inhibitory actions of chymase inhibitors, but not tryptase inhibitors on colon mast cells were enhanced by preincubation of them with cells for 20 min before challenged with anti-IgE. At a concentration of 10 μg/mL, protamine was able to inhibit anti-IgE and calcium ionophore induced tryptase release. However, at 100 μg/mL, protamine elevated tryptase levels in supernatants.A specific inhibitor of aminopeptidase amastatin had no effect on anti-IgE induced tryptase release. The significant inhibition of calcium ionophore induced tryptase release was also observed with the inhibitors of tryptase and chymase examined. The inhibitors tested by themselves did not stimulate tryptase release from colon mast cells.CONCLUSION: It was demonstrated for the first time that both tryptase and chymase inhibitors could inhibit IgE dependent and calcium ionophore induced tryptase release from dispersed colon mast cells in a concentration dependent of manner, which suggest that they are likely to be developed as a novel class of anti-inflammatory drugs to treat chronic of colitis in man.

  1. Detection of Volatile Metabolites of Garlic in Human Breast Milk.

    Science.gov (United States)

    Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

    2016-06-06

    The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography-mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO₂). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO₂ are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  2. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Laura Scheffler

    2016-06-01

    Full Text Available The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O, as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS, allyl methyl sulfoxide (AMSO and allyl methyl sulfone (AMSO2. Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  3. Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate.

    Directory of Open Access Journals (Sweden)

    Verena Natalie Schreier

    Full Text Available Targeted delivery of chemotherapeutic agents is a new approach for the treatment of cancer, which provides increased selectivity and decreased systemic toxicity. We have recently developed a promising drug delivery system, in which the anticancer drug daunorubicin (Dau was attached via oxime bond to a gonadotropin-releasing hormone-III (GnRH-III derivative used as a targeting moiety (Glp-His-Trp-Lys(Ac-His-Asp-Trp-Lys(Da  = Aoa-Pro-Gly-NH2; Glp = pyroglutamic acid, Ac = acetyl; Aoa = aminooxyacetyl. This bioconjugate exerted in vitro cytostatic/cytotoxic effect on human breast, prostate and colon cancer cells, as well as significant in vivo tumor growth inhibitory effect on colon carcinoma bearing mice. In our previous studies, H-Lys(Dau = Aoa-OH was identified as the smallest metabolite produced in the presence of rat liver lysosomal homogenate, which was able to bind to DNA in vitro. To get a deeper insight into the mechanism of action of the bioconjugate, changes in the protein expression profile of HT-29 human colon cancer cells after treatment with the bioconjugate or free daunorubicin were investigated by mass spectrometry-based proteomics. Our results indicate that several metabolism-related proteins, molecular chaperons and proteins involved in signaling are differently expressed after targeted chemotherapeutic treatment, leading to the conclusion that the bioconjugate exerts its cytotoxic action by interfering with multiple intracellular processes.

  4. Dynamics of thymus organogenesis and colonization in early human development

    NARCIS (Netherlands)

    A.M. Farley (Alison); L.X. Morris (Lucy); E.M. Vroegindeweij (Eric); M.L.G. Depreter (Marianne); H. Vaidya (Harsh); F.H. Stenhouse (Frances); S.R. Tomlinson (Simon); R.A. Anderson (Richard); T. Cupedo (Tom); J.J. Cornelissen (Jan); B.C. Clare (Blackburn)

    2013-01-01

    textabstractThe thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genet

  5. Beyond diversity: functional microbiomics of the human colon

    NARCIS (Netherlands)

    Egert, M.G.G.; Graaf, de A.; Smidt, H.; Vos, de W.M.; Venema, K.

    2006-01-01

    Molecular tools have revealed wide microbial diversity in the human alimentary tract. Most intestinal microorganisms have not been cultured and the in situ functions of distinct groups of the intestinal microbiota are largely unknown but pivotal to understanding the role of these microorganisms in h

  6. Therapeutic monoclonal antibodies in human breast milk: a case study.

    Science.gov (United States)

    Ross, Elle; Robinson, Steven E; Amato, Carol; McMillan, Colette; Westcott, Jay; Wolf, Tiffany; Robinson, William A

    2014-04-01

    Recently, therapeutic monoclonal antibodies have been introduced for the treatment of advanced melanoma and other diseases. It remains unclear whether these drugs can be safely administered to women who are breast feeding because of the potential hazardous side effects for nursing infants. One such therapy for metastatic melanoma is ipilimumab, a human monoclonal antibody that blocks cytotoxic T-lymphocyte-antigen-4, and is the preferred treatment for patients with metastatic melanoma when other molecular therapies are not viable. This study measured ipilimumab levels in the breast milk of a patient undergoing treatment that were enough to raise concerns for a nursing infant exposed to ipilimumab.

  7. Depth-dependent differences in community structure of the human colonic microbiota in health.

    Directory of Open Access Journals (Sweden)

    Aonghus Lavelle

    Full Text Available OBJECTIVE: The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes. DESIGN: A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota. RESULTS: Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples. CONCLUSION: These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities.

  8. Secreted human adipose leptin decreases mitochondrial respiration in HCT116 colon cancer cells.

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, pobese subjects. We conclude that secreted products from the adipose tissue of obese subjects inhibit mitochondrial respiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues.

  9. Secreted human adipose leptin decreases mitochondrial respiration in HCT116 colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Einav Yehuda-Shnaidman

    Full Text Available Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration and extracellular acidification rate (ECAR, mostly lactate production via glycolysis were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese subjects decreased basal (40%, p<0.05 and maximal (50%, p<0.05 OCR and gene expression of mitochondrial proteins and Bax without affecting cell viability or expression of glycolytic enzymes. Similar changes could be recapitulated by incubating cells with leptin, whereas, leptin-receptor specific antagonist inhibited the reduced OCR induced by conditioned media from obese subjects. We conclude that secreted products from the adipose tissue of obese subjects inhibit mitochondrial respiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues.

  10. Expression of connexins 26, 32 and 43 in the human colon--an immunohistochemical study.

    Directory of Open Access Journals (Sweden)

    Maria Sobaniec-Lotowska

    2005-02-01

    Full Text Available Gap junctional intercellular communication (GJIC is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions (GJs, which consist of proteins called connexins (Cxs. GJIC plays a critical role in tissue development and differentiation and is important in maintenance of tissue homeostasis. The purpose of the study was to evaluate the expression of Cx26, Cx32 and Cx43 in the human colon. Surgical specimens were obtained from patients who underwent surgical resection of colorectal tumours. Tissue samples (50 cases were collected from normal colon, at the maximum distance from the tumor. Using antibodies for Cx26, Cx32 and Cx43, immunohistochemical detection was made. In epithelial cells, strong Cx26 immunoreactivity was found, whereas Cx32 and Cx43 were sparsely distributed. Strong Cx43 immunostaining in muscularis mucosae was observed. In the circular layer of muscularis externa, expression of Cx43 and Cx26 was seen, but only in the portion closest to the submucosa. No immunoreactivity was found in the longitudinal muscle layer. Small vessels stained positively only for Cx43. Furthermore, there was no difference in staining between samples derived from various sections of the colon. This study showed immunohistochemically for the first time the expression of Cx26 in human colon mucosa.

  11. Expression of connexins 26, 32 and 43 in the human colon--an immunohistochemical study.

    Science.gov (United States)

    Kanczuga-Koda, Luiza; Sulkowski, Stanislaw; Koda, Mariusz; Sobaniec-Lotowska, Maria; Sulkowska, Mariola

    2004-01-01

    Gap junctional intercellular communication (GJIC) is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions (GJs), which consist of proteins called connexins (Cxs). GJIC plays a critical role in tissue development and differentiation and is important in maintenance of tissue homeostasis. The purpose of the study was to evaluate the expression of Cx26, Cx32 and Cx43 in the human colon. Surgical specimens were obtained from patients who underwent surgical resection of colorectal tumours. Tissue samples (50 cases) were collected from normal colon, at the maximum distance from the tumor. Using antibodies for Cx26, Cx32 and Cx43, immunohistochemical detection was made. In epithelial cells, strong Cx26 immunoreactivity was found, whereas Cx32 and Cx43 were sparsely distributed. Strong Cx43 immunostaining in muscularis mucosae was observed. In the circular layer of muscularis externa, expression of Cx43 and Cx26 was seen, but only in the portion closest to the submucosa. No immunoreactivity was found in the longitudinal muscle layer. Small vessels stained positively only for Cx43. Furthermore, there was no difference in staining between samples derived from various sections of the colon. This study showed immunohistochemically for the first time the expression of Cx26 in human colon mucosa.

  12. A piglet model for studying Candida albicans colonization of the human oro-gastrointestinal tract.

    Science.gov (United States)

    Hoeflinger, Jennifer L; Coleman, David A; Oh, Soon-Hwan; Miller, Michael J; Hoyer, Lois L

    2014-08-01

    Pigs from a variety of sources were surveyed for oro-gastrointestinal (oro-GIT) carriage of Candida albicans. Candida albicans-positive animals were readily located, but we also identified C. albicans-free pigs. We hypothesized that pigs could be stably colonized with a C. albicans strain of choice, simply by feeding yeast cells. Piglets were farrowed routinely and remained with the sow for 4 days to acquire a normal microbiota. Piglets were then placed in an artificial rearing environment and fed sow milk replacer. Piglets were inoculated orally with one of three different C. albicans strains. Piglets were weighed daily, and culture swabs were collected to detect C. albicans orally, rectally and in the piglet's environment. Stable C. albicans colonization over the course of the study did not affect piglet growth. Necropsy revealed mucosally associated C. albicans throughout the oro-GIT with the highest abundance in the esophagus. Uninoculated control piglets remained C. albicans-negative. These data establish the piglet as a model to study C. albicans colonization of the human oro-GIT. Similarities between oro-GIT colonization in humans and pigs, as well as the ease of working with the piglet model, suggest its adaptability for use among investigators interested in understanding C. albicans-host commensal interactions.

  13. Flux analysis of the human proximal colon using anaerobic digestion model 1.

    Science.gov (United States)

    Motelica-Wagenaar, Anne Marieke; Nauta, Arjen; van den Heuvel, Ellen G H M; Kleerebezem, Robbert

    2014-08-01

    The colon can be regarded as an anaerobic digestive compartment within the gastro intestinal tract (GIT). An in silico model simulating the fluxes in the human proximal colon was developed on basis of the anaerobic digestion model 1 (ADM1), which is traditionally used to model waste conversion to biogas. Model calibration was conducted using data from in vitro fermentation of the proximal colon (TIM-2), and, amongst others, supplemented with the bio kinetics of prebiotic galactooligosaccharides (GOS) fermentation. The impact of water and solutes absorption by the host was also included. Hydrolysis constants of carbohydrates and proteins were estimated based on total short chain fatty acids (SCFA) and ammonia production in vitro. Model validation was established using an independent dataset of a different in vitro model: an in vitro three-stage continuous culture system. The in silico model was shown to provide quantitative insight in the microbial community structure in terms of functional groups, and the substrate and product fluxes between these groups as well as the host, as a function of the substrate composition, pH and the solids residence time (SRT). The model confirms the experimental observation that methanogens are washed out at low pH or low SRT-values. The in silico model is proposed as useful tool in the design of experimental setups for in vitro experiments by giving insight in fermentation processes in the proximal human colon.

  14. Crude extracts of marine-derived and soil fungi of the genus Neosartorya exhibit selective anticancer activity by inducing cell death in colon, breast and skin cancer cell lines

    Directory of Open Access Journals (Sweden)

    Alice Abreu Ramos

    2016-01-01

    Full Text Available Background: The crude ethyl acetate extracts of marine-derived fungi Neosartorya tsunodae KUFC 9213 (E1 and N. laciniosa KUFC 7896 (E2, and soil fungus N. fischeri KUFC 6344 (E3 were evaluated for their in vitro anticancer activities on a panel of seven human cancer cell lines. Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay was performed, after 48 h treatments with different concentrations of extracts, to determine their concentration of the extract or Dox that inhibits cell viability by 50% for each cell line. The effects of the crude extracts on DNA damage, clonogenic potential and their ability to induce cell death were also assessed. Results: E1 was found to the void of anti-proliferative effects. E2 was shown to decrease the clonogenic potential in human colorectal carcinoma cell line (HCT116, human malignant melanoma cell line (A375, human breast adenocarcinoma cell line (MCF7, and human caucasian colon adenocarcinoma Grade II cell line (HT29 cells, whereas E3 showed such effect only in HCT116 and MCF7 cells. Both extracts were found to increase DNA damage in some cell lines. E2 was found to induce cell death in HT29, HCT116, MCF7, and A375 cells while extract E3 increased cell death in MCF7 and HCT116 cell lines. Conclusion: The results reveal that E2 and E3 possess anticancer activities in human colon carcinoma, breast adenocarcinoma, and melanoma cells, validating the interest for an identification of molecular targets involved in the anticancer activity.

  15. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    Directory of Open Access Journals (Sweden)

    van Erk Marjan J

    2004-05-01

    Full Text Available Abstract Background Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling. Methods Gene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours. Gene expression changes after short-term exposure (3 or 6 hours to curcumin were also studied in a second cell type, Caco-2 cells. Results Gene expression changes (>1.5-fold were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis. Conclusions This study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase

  16. Modulation of tryptase secretion from human colon mast cells by histamine

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of histamine to modulate tryptase release from human colon mast cells and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with histamine, anti-IgE or calcium ionophore A23187 (CI), and the cell supernatants after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure.able to induce a "bell" shape dose related release of tryptase from colon mast cells. The maximum release of tryptase was approximately 3.5 fold more than spontaneous release. As little as 10 ng/mL histamine showed a similar potency to 10 μg/mL anti-IgE in induction of tryptase release. Histamine induced release of tryptase initiated at 10 s when histamine (100 ng/mL) was added to cells, gradually increased thereafter, and completed at 5 min, Both pertussis toxin or metabolic inhibitors were able to inhibit histamine induced tryptase release. When histamine and anti-IgE were added to colon mast cells at the same time, the quantity of tryptase released was similar to that induced by anti-IgE alone. The similar results were observed with CI. However, when various concentrations of histamine were incubated with cells for 20 min before adding anti-IgE or CI, the quantity of tryptase released was similar to that was induced by histamine alone.CONCLUSION: Histamine is a potent activator of human colon mast cells, which represents a novel and pivotal selfamplification mechanism of mast cell degranulation.

  17. Life expectancy of colon, breast, and testicular cancer patients: an analysis of US-SEER population-based data.

    Science.gov (United States)

    Capocaccia, R; Gatta, G; Dal Maso, L

    2015-06-01

    Cancer survivorship is an increasingly important issue in cancer control. Life expectancy of patients diagnosed with breast, colon, and testicular cancers, stratified by age at diagnosis and time since diagnosis, is provided as an indicator to evaluate future mortality risks and health care needs of cancer survivors. The standard period life table methodology was applied to estimate excess mortality risk for cancer patients diagnosed in 1985-2011 from SEER registries and mortality data of the general US population. The sensitivity of life expectancy estimates on different assumptions was evaluated. Younger patients with colon cancer showed wider differences in life expectancy compared with that of the general population (11.2 years in women and 10.7 in men at age 45-49 years) than older patients (6.3 and 5.8 at age 60-64 years, respectively). Life expectancy progressively increases in patients surviving the first years, up to 4 years from diagnosis, and then starts to decrease again, approaching that of the general population. For breast cancer, the initial drop in life expectancy is less marked, and again with wider differences in younger patients, varying from 8.7 at age 40-44 years to 2.4 at ages 70-74 years. After diagnosis, life expectancy still decreases with time, but less than that in the general population, slowly approaching that of cancer-free women. Life expectancy of men diagnosed with testicular cancer at age 30 years is estimated as 45.2 years, 2 years less than cancer-free men of the same age. The difference becomes 1.3 years for patients surviving the first year, and then slowly approaches zero with increasing survival time. Life expectancy provides meaningful information on cancer patients, and can help in assessing when a cancer survivor can be considered as cured. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Light- and electron microscopical studies of interstitial cells of Cajal and muscle cells at the submucosal border of human colon

    DEFF Research Database (Denmark)

    Rumessen, J J; Peters, S; Thuneberg, L

    1993-01-01

    It has been suggested that interstitial cells of Cajal (ICC) at the submucosal border of the colonic circular muscle are pacemaker cells. We studied smooth muscle cells and ICC at the submucosal surface of the circular muscle layer of the normal human colon....

  19. Identification of the Virulence Landscape Essential for Entamoeba histolytica Invasion of the Human Colon

    Science.gov (United States)

    Hon, Chung-Chau; Dillies, Marie-Agnès; Avé, Patrick; Coppée, Jean-Yves; Labruyère, Elisabeth; Guillén, Nancy

    2013-01-01

    Entamoeba histolytica is the pathogenic amoeba responsible for amoebiasis, an infectious disease targeting human tissues. Amoebiasis arises when virulent trophozoites start to destroy the muco-epithelial barrier by first crossing the mucus, then killing host cells, triggering inflammation and subsequently causing dysentery. The main goal of this study was to analyse pathophysiology and gene expression changes related to virulent (i.e. HM1:IMSS) and non-virulent (i.e. Rahman) strains when they are in contact with the human colon. Transcriptome comparisons between the two strains, both in culture conditions and upon contact with human colon explants, provide a global view of gene expression changes that might contribute to the observed phenotypic differences. The most remarkable feature of the virulent phenotype resides in the up-regulation of genes implicated in carbohydrate metabolism and processing of glycosylated residues. Consequently, inhibition of gene expression by RNA interference of a glycoside hydrolase (β-amylase absent from humans) abolishes mucus depletion and tissue invasion by HM1:IMSS. In summary, our data suggest a potential role of carbohydrate metabolism in colon invasion by virulent E. histolytica. PMID:24385905

  20. The colon-selective spasmolytic otilonium bromide inhibits muscarinic M3 receptor-coupled calcium signals in isolated human colonic crypts

    Science.gov (United States)

    Lindqvist, Susanne; Hernon, James; Sharp, Paul; Johns, Neil; Addison, Sarah; Watson, Mark; Tighe, Richard; Greer, Shaun; Mackay, Jean; Rhodes, Michael; Lewis, Michael; Stebbings, William; Speakman, Chris; Evangelista, Stefano; Johnson, Ian; Williams, Mark

    2002-01-01

    Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB. Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M3 receptor subtype (CHO-M3). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques. The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC50 of 14 μM. The muscarinic receptor antagonists 4-DAMP, AF-DX 384, pirenzepine and methroctamine inhibited the ACh-induced calcium signal with the following respective IC50 (pKb) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8). Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M3 receptor subtype expression at the crypt-base. Otilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC50=880 nM). In CHO-M3 cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine-induced colonic crypt calcium signals. The present studies have demonstrated that OB inhibited M3 receptor-coupled calcium signals in human colonic crypts and CHO-M3 cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M3 receptor-coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti-secretory action in IBS patients suffering with diarrhoea. PMID

  1. The colon-selective spasmolytic otilonium bromide inhibits muscarinic M(3) receptor-coupled calcium signals in isolated human colonic crypts.

    Science.gov (United States)

    Lindqvist, Susanne; Hernon, James; Sharp, Paul; Johns, Neil; Addison, Sarah; Watson, Mark; Tighe, Richard; Greer, Shaun; Mackay, Jean; Rhodes, Michael; Lewis, Michael; Stebbings, William; Speakman, Chris; Evangelista, Stefano; Johnson, Ian; Williams, Mark

    2002-12-01

    1. Otilonium bromide (OB) is a smooth muscle relaxant used in the treatment of irritable bowel syndrome. Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated. We identified the muscarinic receptor subtype coupled to calcium signals in colonic crypt derived from the human colonic epithelium and evaluated the inhibitory effects of OB. 2. Calcium signals were monitored by fluorescence imaging of isolated human colonic crypts and Chinese hamster ovary cells stably expressing the cloned human muscarinic M(3) receptor subtype (CHO-M(3)). Colonic crypt receptor expression was investigated by pharmacological and immunohistochemical techniques. 3. The secretagogue acetylcholine (ACh) stimulated calcium mobilization from intracellular calcium stores at the base of human colonic crypts with an EC(50) of 14 micro M. The muscarinic receptor antagonists 4-DAMP, AF-DX 384, pirenzepine and methroctamine inhibited the ACh-induced calcium signal with the following respective IC(50) (pK(b)) values: 0.78 nM (9.1), 69 nM (7.2), 128 nM (7.1), and 2510 nM (5.8). 4. Immunohistochemical analyses of muscarinic receptor expression demonstrated the presence of M(3) receptor subtype expression at the crypt-base. 5. Otilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC(50)=880 nM). 6. In CHO-M(3) cells, OB inhibited calcium signals induced by ACh, but not ATP. In addition, OB did not inhibit histamine-induced colonic crypt calcium signals. 7. The present studies have demonstrated that OB inhibited M(3) receptor-coupled calcium signals in human colonic crypts and CHO-M(3) cells, but not those induced by stimulation of other endogenous receptor types. We propose that the M(3) receptor-coupled calcium signalling pathway is directly targeted by OB at the level of the colonic epithelium, suggestive of an anti-secretory action

  2. Inhibition of transfected PTEN on human colon cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Shui Xu; Wen-Lu Shen; Song-Ying Ouyang

    2004-01-01

    AIM: To study the inhibitory effect of transfected PTEN on LoVo cells.METHODS: Human PTEN cDNA was transferred into LoVo cells via lipofectin and PTEN mRNA levels and its expression were analyzed by Western blot and flow cytometry. Before or after transfection, the effects of 5-Fu on inhibiting cell proliferation and inducing apoptosis were measured by flow cytometry, DNA bands and MTT.RESULTS: PTEN transfection significantly up-regulated PTEN expression in LoVo cells. 5-Fu inhibited cell proliferation and induced apoptosis in transfected LoVo cells.CONCLUSION: Transfected PTEN can remark ably up-regulate PTEN expression in LoVo cells and promote the apoptosis.PTEN transfection is associated with 5-Fu treatment effect and has a cooperatively cytotoxic effect.

  3. Evolution of Staphylococcus aureus during human colonization and infection.

    Science.gov (United States)

    Fitzgerald, J Ross

    2014-01-01

    The diversification of bacterial pathogens during infection is central to their capacity to adapt to different anatomical niches, evade the host immune system, and overcome therapeutic challenges. For example, antimicrobial treatment may fail due to the development of resistance during infection, which is often accompanied by transition to a less virulent state during chronic, persistent infection. In this review, the adaptation of the major human pathogen Staphylococcus aureus to its host environment during infection will be discussed, particularly in the context of new sequencing technologies which have opened a gateway towards understanding of the molecular processes underlying those adaptations. We now have the capacity to address previously intractable questions regarding bacterial diversification during infection which will ultimately lead to enhanced understanding of pathogenesis and the nature of epidemics, and will inform the design of effective therapeutic measures.

  4. Formation of propionate and butyrate by the human colonic microbiota.

    Science.gov (United States)

    Louis, Petra; Flint, Harry J

    2017-01-01

    The human gut microbiota ferments dietary non-digestible carbohydrates into short-chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health-promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.

  5. Colonization of plants by human pathogenic bacteria in the course of organic vegetable production

    Directory of Open Access Journals (Sweden)

    Andreas eHofmann

    2014-05-01

    Full Text Available In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system or via agricultural soil amended with spiked organic fertilizers (soil system. In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4x10CFU/ml in the axenic system or 4x105CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in

  6. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

    Directory of Open Access Journals (Sweden)

    Mingquan Chen

    Full Text Available FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10 human hepatocellular carcinoma, 66.7% (6/9 liver cancer cell lines and 100% (6/6 colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza, indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

  7. KiSS-1 expression in human breast cancer.

    Science.gov (United States)

    Martin, Tracey A; Watkins, Gareth; Jiang, Wen G

    2005-01-01

    The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using beta-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3,124+/-1,262 vs 2,397+/-1,181) and significantly increased in node positive tumours compared to node negative (3,637+/-1,719 vs 2,653+/-1,994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4,631+/-3,024 vs 2,280+/-1,403) whereas expression of the receptor was reduced (480+/-162 vs 195+/-134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.

  8. Matrix Stiffness Corresponding to Strictured Bowel Induces a Fibrogenic Response in Human Colonic Fibroblasts

    Science.gov (United States)

    Johnson, Laura A.; Rodansky, Eva S.; Sauder, Kay L.; Horowitz, Jeffrey C.; Mih, Justin D.; Tschumperlin, Daniel J.; Higgins, Peter D.

    2013-01-01

    Background Crohn’s disease is characterized by repeated cycles of inflammation and mucosal healing which ultimately progress to intestinal fibrosis. This inexorable progression towards fibrosis suggests that fibrosis becomes inflammation-independent and auto-propagative. We hypothesized that matrix stiffness regulates this auto-propagation of intestinal fibrosis. Methods The stiffness of fresh ex vivo samples from normal human small intestine, Crohn’s disease strictures, and the unaffected margin were measured with a microelastometer. Normal human colonic fibroblasts were cultured on physiologically normal or pathologically stiff matrices corresponding to the physiological stiffness of normal or fibrotic bowel. Cellular response was assayed for changes in cell morphology, α-smooth muscle actin (αSMA) staining, and gene expression. Results Microelastometer measurements revealed a significant increase in colonic tissue stiffness between normal human colon and Crohn’s strictures as well as between the stricture and adjacent tissue margin. In Ccd-18co cells grown on stiff matrices corresponding to Crohn’s strictures, cellular proliferation increased. Pathologic stiffness induced a marked change in cell morphology and increased αSMA protein expression. Growth on a stiff matrix induced fibrogenic gene expression, decreased matrix metalloproteinase and pro-inflammatory gene expression, and was associated with nuclear localization of the transcriptional cofactor MRTF-A. Conclusions Matrix stiffness, representative of the pathological stiffness of Crohn’s strictures, activates human colonic fibroblasts to a fibrogenic phenotype. Matrix stiffness affects multiple pathways suggesting the mechanical properties of the cellular environment are critical to fibroblast function and may contribute to autopropagation of intestinal fibrosis in the absence of inflammation, thereby contributing to the intractable intestinal fibrosis characteristic of Crohn’s disease. PMID

  9. Expression of connexins 26, 32 and 43 in the human colon--an immunohistochemical study.

    OpenAIRE

    Maria Sobaniec-Lotowska; Mariusz Koda; Stanislaw Sulkowski; Luiza Kanczuga-Koda; Mariola Sulkowska

    2005-01-01

    Gap junctional intercellular communication (GJIC) is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions (GJs), which consist of proteins called connexins (Cxs). GJIC plays a critical role in tissue development and differentiation and is important in maintenance of tissue homeostasis. The purpose of the study was to evaluate the expression of Cx26, Cx32 and Cx43 in the human colon. Surgical specimens were obtained from patients who underwent surgical resection of c...

  10. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation

    OpenAIRE

    Le Rolle, Anne-France; Chiu, Thang K; ZENG, ZHAOSHI; Shia, Jinru; Weiser, Martin R; Paty, Philip B.; Chiu, Vi K

    2016-01-01

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut ) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer i...

  11. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    OpenAIRE

    Reyhan Akhtar; Mohd Ali; Safrannisa Mahmood; Sankar Nath Sanyal

    2014-01-01

    Background: Silibinin a flavonoid from milk thistle (Silybum marianum) exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml) for 24, 48 or 72 h showed a progressive decline in cell viability. Res...

  12. Carriers of human mitochondrial DNA macrohaplogroup M colonized India from southeastern Asia

    OpenAIRE

    Marrero, Patricia; Abu-Amero, Khaled K.; Larruga, Jose M; Cabrera, Vicente M

    2016-01-01

    Background From a mtDNA dominant perspective, the exit from Africa of modern humans to colonize Eurasia occurred once, around 60 kya, following a southern coastal route across Arabia and India to reach Australia short after. These pioneers carried with them the currently dominant Eurasian lineages M and N. Based also on mtDNA phylogenetic and phylogeographic grounds, some authors have proposed the coeval existence of a northern route across the Levant that brought mtDNA macrohaplogroup N to A...

  13. Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Larsen, Sylvester; Linnemann, Dorte

    2015-01-01

    of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal...... epithelial cells (IECs) was increased at the wound edge after 24 h (P

  14. Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

  15. Antitumor Effects of Fucoidan on Human Colon Cancer Cells via Activation of Akt Signaling.

    Science.gov (United States)

    Han, Yong-Seok; Lee, Jun Hee; Lee, Sang Hun

    2015-05-01

    We identified a novel Akt signaling mechanism that mediates fucoidan-induced suppression of human colon cancer cell (HT29) proliferation and anticancer effects. Fucoidan treatment significantly inhibited growth, induced G1-phase-associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin-dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan treatment activated the Akt signaling pathway, which was inhibited by treatment with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan-induced decrease in cell proliferation, the induction of G1-phase-associated p21WAF1 expression, and the reduction in cell cycle regulatory protein expression. Intraperitoneal injection of fucoidan reduced tumor volume; this enhanced antitumor efficacy was associated with induction of apoptosis and decreased angiogenesis. These data suggest that the activation of Akt signaling is involved in the growth inhibition of colon cancer cells treated with fucoidan. Thus, fucoidan may serve as a potential therapeutic agent for colon cancer.

  16. Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Inoue-Yamauchi, Akane, E-mail: ainoyama@research.twmu.ac.jp [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Oda, Hideaki [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer DRP1 is required for mitochondrial fission in colon cancer cells. Black-Right-Pointing-Pointer DRP1 participates in inhibition of colon cancer cell apoptosis. Black-Right-Pointing-Pointer DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.

  17. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro.

    Science.gov (United States)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang; Dong, Wei-Guo

    2012-05-11

    Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC(50)=75 μM). This cytotoxicity was reflected by cell cycle arrest at G(2)/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  18. Assessing the potential for raw meat to influence human colonization with Staphylococcus aureus.

    Science.gov (United States)

    Carrel, Margaret; Zhao, Chang; Thapaliya, Dipendra; Bitterman, Patrick; Kates, Ashley E; Hanson, Blake M; Smith, Tara C

    2017-09-07

    The role of household meat handling and consumption in the transfer of Staphylococcus aureus (S. aureus) from livestock to consumers is not well understood. Examining the similarity of S. aureus colonizing humans and S. aureus in meat from the stores in which those individuals shop can provide insight into the role of meat in human S. aureus colonization. S. aureus isolates were collected from individuals in rural and urban communities in Iowa (n = 3347) and contemporaneously from meat products in stores where participants report purchasing meat (n = 913). The staphylococcal protein A (spa) gene was sequenced for all isolates to determine a spa type. Morisita indices and Permutational Multivariate Analysis of Variance Using Distance Matrices (PERMANOVA) were used to determine the relationship between spa type composition among human samples and meat samples. spa type composition was significantly different between households and meat sampled from their associated grocery stores. spa types found in meat were not significantly different regardless of the store or county in which they were sampled. spa types in people also exhibit high similarity regardless of residential location in urban or rural counties. Such findings suggest meat is not an important source of S. aureus colonization in shoppers.

  19. The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells.

    Science.gov (United States)

    Jaramillo, Sara; Lopez, Sergio; Varela, Lourdes M; Rodriguez-Arcos, Rocio; Jimenez, Ana; Abia, Rocio; Guillen, Rafael; Muriana, Francisco J G

    2010-10-27

    The aim of this study was to determine whether isorhamnetin, an immediate 3'-O-methylated metabolite of quercetin, affects proliferation, cell death, and the cell cycle of human colon carcinoma (HCT-116) cells. Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner, with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay. Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis. Isorhamnetin also increased the number of cells in G2/M phase. Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase. These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells, leading to apoptotic and necrotic death. These antiproliferative, apoptotic, necrotic, and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities. To our knowledge, this is the first report of the effect of isorhamnetin on human colon cancer cells.

  20. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    Institute of Scientific and Technical Information of China (English)

    Hua-Jiang Wei; Da Xing; Jian-Jun Lu; Huai-Min Gu; Guo-Yong Wu; Ying Jin

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integratingsphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength,and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength.There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa,and there

  1. Potential Factors Enabling Human Body Colonization by Animal Streptococcus dysgalactiae subsp. equisimilis Strains.

    Science.gov (United States)

    Ciszewski, Marcin; Szewczyk, Eligia M

    2017-05-01

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a pyogenic, Lancefield C or G streptococcal pathogen. Until recently, it has been considered as an exclusive animal pathogen. Nowadays, it is responsible for both animal infections in wild animals, pets, and livestock and human infections often clinically similar to the ones caused by group A streptococcus (Streptococcus pyogenes). The risk of zoonotic infection is the most significant in people having regular contact with animals, such as veterinarians, cattlemen, and farmers. SDSE is also prevalent on skin of healthy dogs, cats, and horses, which pose a risk also to people having contact with companion animals. The main aim of this study was to evaluate if there are features differentiating animal and human SDSE isolates, especially in virulence factors involved in the first stages of pathogenesis (adhesion and colonization). Equal groups of human and animal SDSE clinical strains were obtained from superficial infections (skin, wounds, abscesses). The presence of five virulence genes (prtF1, prtF2, lmb, cbp, emm type) was evaluated, as well as ability to form bacterial biofilm and produce BLIS (bacteriocin-like inhibitory substances) which are active against human skin microbiota. The study showed that the presence of genes coding for fibronectin-binding protein and M protein, as well as BLIS activity inhibiting the growth of Corynebacterium spp. strains might constitute the virulence factors which are necessary to colonize human organism, whereas they are not crucial in animal infections. Those virulence factors might be horizontally transferred from human streptococci to animal SDSE strains, enabling their ability to colonize human organism.

  2. Human breast milk and the gastrointestinal innate immune system.

    Science.gov (United States)

    Jakaitis, Brett M; Denning, Patricia W

    2014-06-01

    The gastrointestinal (GI) tract is a large potential portal for multiple infectious agents to enter the human body. The GI system performs multiple functions as part of the neonate's innate immune system, providing critical defense during a vulnerable period. Multiple mechanisms and actions are enhanced by the presence of human breast milk. Bioactive factors found in human milk work together to create and maintain an optimal and healthy environment, allowing the intestines to deliver ideal nutrition to the host and afford protection by a variety of mechanisms.

  3. Human exposure to endocrine disruptors and breast milk.

    Science.gov (United States)

    Stefanidou, M; Maravelias, C; Spiliopoulou, C

    2009-09-01

    Endocrine system is one of the most sensitive communication networks of the human body which influences all aspects of human health and well-being, including reproductive potential, cognitive functions, thyroid and metabolism, digestion and hormonal balance. In recent years basic laboratory research has been focused on the potential relationship between environmental contaminants and cellular endocrine function. Environmental contaminants are ubiquitous in the environment, alter endocrine physiology and produce endocrine disruption without acting as classic toxicants. These endocrine disruptors (EDCs) are lipophilic and stored for long periods of time in the adipose tissue. Maternal exposure to EDCs during pregnancy and lactation has as a result the exposure of the fetus and neonate through placenta and breast milk. It has been recognized that human milk is the best natural food for neonates providing immunologic, developmental and practical advantages throughout childhood. However, contamination of human milk by the presence of environmental toxicants is widespread through the past decades due to inadequately controlled pollution. Persistent pesticides, chemical solvents and others tend to invade slowly the environment, to bioaccumulate in the food chain and to have long half-lives in animals and humans. During the past fifteen years, the scientific interest has been focused on xenoestrogens, i.e.,environmental chemicals with estrogen disrupting activity. Certain adverse health and reproductive outcomes are attributed to these chemicals in wildlife, in laboratory animals, as well as in humans. Although most toxic agents are hazardous in high doses, the human health risks associated with EDCs concern exposure to low doses. The human health risks that may be associated with these low-level but constant exposures are still largely unknown and highly controversial. In this paper, we review available data on environmental chemicals present in breast milk that may

  4. BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo.

    Science.gov (United States)

    Cheng, Shujie; Castillo, Victor; Welty, Matt; Alvarado, Mark; Eliaz, Isaac; Temm, Constance J; Sandusky, George E; Sliva, Daniel

    2017-02-16

    Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry. Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer. BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.

  5. Effect of Age on the Enteric Nervous System of the Human Colon

    Science.gov (United States)

    Bernard, Cheryl E.; Gibbons, Simon J.; Gomez-Pinilla, Pedro J.; Lurken, Matthew S.; Schmalz, Philip F.; Roeder, Jaime L.; Linden, David; Cima, Robert R.; Dozois, Eric J.; Larson, David W.; Camilleri, Michael; Zinsmeister, Alan R; Pozo, Maria J; Hicks, Gareth A.; Farrugia, Gianrico

    2009-01-01

    The effect of age on the anatomy and function of the human colon is incompletely understood. The prevalence of disorders in adults such as constipation increase with age but it is unclear if this is due to confounding factors or age-related structural defects. The aim of this study was to determine number and subtypes of enteric neurons and neuronal volumes in the human colon of different ages. Normal colon (descending and sigmoid) from 16 patients (9 male) was studied; ages 33–99. Antibodies to HuC/D, ChAT, nNOS, and PGP9.5 were used. Effect of age was determined by testing for linear trends using regression analysis. In the myenteric plexus, number of Hu-positive neurons declined with age (slope = −1.3 neurons/mm/10yrs, p =0.03). The number of ChAT-positive neurons also declined with age (slope = −1.1 neurons/mm/10yrs of age, p=0.02). The number of nNOS-positive neurons did not decline with age. As a result, the ratio of nNOS to Hu increased (slope= 0.03 per 10yrs of age, p=0.01). In the submucosal plexus, the number of neurons did not decline with age (slope = − 0.3 neurons/mm/10 yrs, p =0.09). Volume of nerve fibers in the circular muscle and volume of neuronal structures in the myenteric plexus did not change with age. In conclusion, the number of neurons in the human colon declines with age with sparing of nNOS- positive neurons. This change was not accompanied by changes in total volume of neuronal structures suggesting compensatory changes in the remaining neurons. PMID:19220755

  6. Disentangling hybridization and host colonization in parasitic roundworms of humans and pigs.

    Science.gov (United States)

    Criscione, Charles D; Anderson, Joel D; Sudimack, Dan; Peng, Weidong; Jha, Bharat; Williams-Blangero, Sarah; Anderson, Timothy J C

    2007-11-07

    Knowledge of cross-transmission and hybridization between parasites of humans and reservoir hosts is critical for understanding the evolution of the parasite and for implementing control programmes. There is now a consensus that populations of pig and human Ascaris (roundworms) show significant genetic subdivision. However, it is unclear whether this has resulted from a single or multiple host shift(s). Furthermore, previous molecular data have not been sufficient to determine whether sympatric populations of human and pig Ascaris can exchange genes. To disentangle patterns of host colonization and hybridization, we used 23 microsatellite loci to conduct Bayesian clustering analyses of individual worms collected from pigs and humans. We observed strong differentiation between populations which was primarily driven by geography, with secondary differentiation resulting from host affiliation within locations. This pattern is consistent with multiple host colonization events. However, there is low support for the short internal branches of the dendrograms. In part, the relationships among clusters may result from current hybridization among sympatric human and pig roundworms. Indeed, congruence in three Bayesian methods indicated that 4 and 7% of roundworms sampled from Guatemala and China, respectively, were hybrids. These results indicate that there is contemporary cross-transmission between populations of human and pig Ascaris.

  7. GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast.

    Science.gov (United States)

    Scaling, Allison L; Prossnitz, Eric R; Hathaway, Helen J

    2014-06-01

    17β-Estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the mammary gland, promoting ductal elongation and morphogenesis. In addition to a developmental role, estrogen promotes proliferation in tumorigenic settings, particularly breast cancer. The proliferative effects of estrogen in the normal breast and breast tumors are attributed to estrogen receptor α. Although in vitro studies have demonstrated that the G protein-coupled estrogen receptor (GPER, previously called GPR30) can modulate proliferation in breast cancer cells both positively and negatively depending on cellular context, its role in proliferation in the intact normal or malignant breast remains unclear. Estrogen-induced GPER-dependent proliferation was assessed in the immortalized nontumorigenic human breast epithelial cell line, MCF10A, and an ex vivo organ culture model employing human breast tissue from reduction mammoplasty or tumor resections. Stimulation by estrogen and the GPER-selective agonist G-1 increased the mitotic index in MCF10A cells and proportion of cells in the cell cycle in human breast and breast cancer explants, suggesting increased proliferation. Inhibition of candidate signaling pathways that may link GPER activation to proliferation revealed a dependence on Src, epidermal growth factor receptor transactivation by heparin-bound EGF and subsequent ERK phosphorylation. Proliferation was not dependent on matrix metalloproteinase cleavage of membrane-bound pro-HB-EGF. The contribution of GPER to estrogen-induced proliferation in MCF10A cells and breast tissue was confirmed by the ability of GPER-selective antagonist G36 to abrogate estrogen- and G-1-induced proliferation, and the ability of siRNA knockdown of GPER to reduce estrogen- and G-1-induced proliferation in MCF10A cells. This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant

  8. A Gene Regulatory Program in Human Breast Cancer.

    Science.gov (United States)

    Li, Renhua; Campos, John; Iida, Joji

    2015-12-01

    Molecular heterogeneity in human breast cancer has challenged diagnosis, prognosis, and clinical treatment. It is well known that molecular subtypes of breast tumors are associated with significant differences in prognosis and survival. Assuming that the differences are attributed to subtype-specific pathways, we then suspect that there might be gene regulatory mechanisms that modulate the behavior of the pathways and their interactions. In this study, we proposed an integrated methodology, including machine learning and information theory, to explore the mechanisms. Using existing data from three large cohorts of human breast cancer populations, we have identified an ensemble of 16 master regulator genes (or MR16) that can discriminate breast tumor samples into four major subtypes. Evidence from gene expression across the three cohorts has consistently indicated that the MR16 can be divided into two groups that demonstrate subtype-specific gene expression patterns. For example, group 1 MRs, including ESR1, FOXA1, and GATA3, are overexpressed in luminal A and luminal B subtypes, but lowly expressed in HER2-enriched and basal-like subtypes. In contrast, group 2 MRs, including FOXM1, EZH2, MYBL2, and ZNF695, display an opposite pattern. Furthermore, evidence from mutual information modeling has congruently indicated that the two groups of MRs either up- or down-regulate cancer driver-related genes in opposite directions. Furthermore, integration of somatic mutations with pathway changes leads to identification of canonical genomic alternations in a subtype-specific fashion. Taken together, these studies have implicated a gene regulatory program for breast tumor progression.

  9. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China); Dong, Wei-Guo, E-mail: dongwg1966@yahoo.com.cn [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  10. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota.

    Science.gov (United States)

    Li, Min; Monaco, Marcia H; Wang, Mei; Comstock, Sarah S; Kuhlenschmidt, Theresa B; Fahey, George C; Miller, Michael J; Kuhlenschmidt, Mark S; Donovan, Sharon M

    2014-08-01

    The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.4 g l(-1)) (PRE) (n=19-21 per group) for 15 days. Piglets (n=7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO- and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection.

  11. Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells

    DEFF Research Database (Denmark)

    Perner, A; Andresen, L; Pedersen, G

    2003-01-01

    Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells.......Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells....

  12. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  13. FT-Raman spectroscopy study of human breast tissue

    Science.gov (United States)

    Bitar Carter, Renata A.; Martin, Airton A.; Netto, Mario M.; Soares, Fernando A.

    2004-07-01

    Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool to provide information about the chemical and morphologic structure of tissue. Raman Spectroscpy is an inelastic scattering process that can provide a wealth of spectral features that can be related to the specific molecular structure of the sample. This article reports results of an in vitro study of the FT-Raman human breast tissue spectra. An Nd:YAG laser at 1064nm was used as the excitation source in the FT-Raman Spectrometer. The neoplastic human breast samples, both Fibroadenoma and ICD, were obtained during therapeutical routine medical procedures required by the primary disease, and the non-diseased human tissue was obtained in plastic surgery. No sample preparation was needed for the FT-Raman spectra collection. The FT-Raman spectra were recorded from normal, benign (Fibroadenomas) and malignant (IDC-Intraductal Carcinoma) samples, adding up 51 different areas. The main spectral differences of a typical FT-Raman spectra of a Normal (Non-diseased), Fibroadenoma, and Infiltrating Ductal Carcinoma (IDC) breast tissue at the interval of 600 to 1800cm-1, which may differentiate diagnostically the sample, were found in the bands of 1230 to 1295cm-1, 1440 to 1460 cm-1 and 1650 to 1680 cm-1, assigned to the vibrational bands of the carbohydrate-amide III, proteins and lipids, and carbohydrate-amide I, respectively.

  14. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  15. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    Science.gov (United States)

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  16. Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Ying-Xuan Chen; Jing-Yuan Fang; Hong-Yin Zhu; Rong Lu; Zhong-Hua Cheng; De-Kai Qiu

    2004-01-01

    AIM: To investigate the effect of histone acetylation on regulation of p21WAF1 gene expression in human colon cancer cell lines.METHODS: Two cell lines, Colo-320 and SW1116 were treated with either trichostatin or sodium butyrate. Expressions of p21WAF1 mRNA and protein were detected by real-time RT-PCR and Western blotting, respectively. Acetylation of two regions of p21WAF1 gene-associated histones and total cellular histones were examined by chromatin immunoprecipitation assay and Western blotting. RESULTS: Trichostatin or sodium butyrate re-activated p21WAF1 transcription resulted in up-regulated p21WF1 protein level in colon cancer cell lines. Those effects were accompanied by an accumulation of acetylated histones in total cellular chromatin and p21WAF1 gene-associated region of chromatin.CONCLUSION: Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines, Colo-320 and SW1116.

  17. Retroviral endostatin gene transfer inhibits human colon cancer cell growth in vivo

    Institute of Scientific and Technical Information of China (English)

    陈卫昌; 傅建新; 刘强; 阮长耿; 萧树东

    2003-01-01

    Objective To investigate the therapeutic effect of retroviral endostatin gene transfer on the human colon cancer cell line, LoVo.Methods A retroviral vector pLESSN expressing secretable endostatin was constructed and packaged with a titer of 8.2×105 CFU/ml. A LoVo cell line was subjected to retrovirus-mediated endostatin gene transfer. The proviral integration of endostatin was analyzed with PCR. The function of endostatin was tested by MTT assay in vitro and a mouse xenograft model in vivo.Results After transfection and superinfection, amphotropic retrovirus was collected, and transduction with amphotropic retroviruses resulted in endostatin proviral integration. The endostatin secreted by transduced LoVo cells markedly inhibited endothelial cell growth up to 67% (P<0.001), compared with the control cells. The gene expression of endostatin in LoVo colon tumor cells significantly inhibited tumor growth in vivo. There was an 86% reduction in tumor size in the endostatin-transduced group, accompanied by a reduction in vessels, compared with the control group (P<0.01). Conclusion Retroviruses can allow functional expression of the endostatin gene in human colon tumors, showing promise for an antitumor strategy using antiangiogenesis.

  18. Peroxisome proliferator-activated receptor gamma overexpression suppresses proliferation of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@shinshu-u.ac.jp [Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Haniu, Hisao [Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer We examined the correlation between PPAR{gamma} expression and cell proliferation. Black-Right-Pointing-Pointer PPAR{gamma} overexpression reduces cell viability. Black-Right-Pointing-Pointer We show the synergistic effect of cell growth inhibition by a PPAR{gamma} agonist. -- Abstract: Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) plays an important role in the differentiation of intestinal cells and tissues. Our previous reports indicate that PPAR{gamma} is expressed at considerable levels in human colon cancer cells. This suggests that PPAR{gamma} expression may be an important factor for cell growth regulation in colon cancer. In this study, we investigated PPAR{gamma} expression in 4 human colon cancer cell lines, HT-29, LOVO, DLD-1, and Caco-2. Real-time polymerase chain reaction (PCR) and Western blot analysis revealed that the relative levels of PPAR{gamma} mRNA and protein in these cells were in the order HT-29 > LOVO > Caco-2 > DLD-1. We also found that PPAR{gamma} overexpression promoted cell growth inhibition in PPAR{gamma} lower-expressing cell lines (Caco-2 and DLD-1), but not in higher-expressing cells (HT-29 and LOVO). We observed a correlation between the level of PPAR{gamma} expression and the cells' sensitivity for proliferation.

  19. Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications

    Science.gov (United States)

    O’Connell, Malaney; Shubhashish, Sarkar

    2016-01-01

    Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation. The unopposed activation of Wnt/β-catenin pathways, either due to loss of APC function or up-regulation of related stimulatory pathways, results in unopposed hyperproliferation of colonic crypts, considered the single most important risk factor for colon carcinogenesis. Hypermethylation of CpG islands within the promoters of specific genes can potentially inactivate DNA repair genes and/or critical tumor suppressor genes. Recently, CpG methylation of the 5’ promoter of human (h) DCLK1 gene was reported in many human epithelial cancers, including colorectal cancers (CRCs), resulting in the loss of expression of the canonical long isoform of DCLK1 (DCLK1-L) in hCRCs. Instead, a shorter isoform of DCLK1 (DCLK1-S) was discovered to be expressed in hCRCs, from an alternate β promoter of DCLKL1-gene; the clinical and biological implications of these novel findings, in relation to recent publications is discussed. PMID:27777940

  20. Two-photon imaging and spectroscopy of fresh human colon biopsies

    Science.gov (United States)

    Cicchi, R.; Sturiale, A.; Nesi, G.; Tonelli, F.; Pavone, F. S.

    2012-03-01

    Two-photon fluorescence (TPEF) microscopy is a powerful tool to image human tissues up to 200 microns depth without any exogenously added probe. TPEF can take advantage of the autofluorescence of molecules intrinsically contained in a biological tissue, as such NADH, elastin, collagen, and flavins. Two-photon microscopy has been already successfully used to image several types of tissues, including skin, muscles, tendons, bladder. Nevertheless, its usefulness in imaging colon tissue has not been deeply investigated yet. In this work we have used combined two-photon excited fluorescence (TPEF), second harmonic generation microscopy (SHG), fluorescence lifetime imaging microscopy (FLIM), and multispectral two-photon emission detection (MTPE) to investigate different kinds of human ex-vivo fresh biopsies of colon. Morphological and spectroscopic analyses allowed to characterize both healthy mucosa, polyp, and colon samples in a good agreement with common routine histology. Even if further analysis, as well as a more significant statistics on a large number of samples would be helpful to discriminate between low, mild, and high grade cancer, our method is a promising tool to be used as diagnostic confirmation of histological results, as well as a diagnostic tool in a multiphoton endoscope or colonoscope to be used in in-vivo imaging applications.

  1. Capsaicin Modulates the Immune Cross Talk Between Human Mononuclears and Cells from Two Colon Carcinoma Lines.

    Science.gov (United States)

    Bessler, Hanna; Djaldetti, Meir

    2017-01-01

    Capsaicin, the pungent alkaloid of the chili peppers, has gained a worldwide reputation. In addition to its culinary assets, capsaicin possesses analgesic, anti-inflammatory, antimicrobial, and even carcinopreventive properties. Considering the linkage between chronic inflammation and tumorigenesis, the aim of the study was to evaluate the role of capsaicin in the immune interplay between human peripheral blood mononuclear cells (PBMCs) and HT-29 or RKO cells from human colon carcinoma lines. PBMCs were incubated for 24 hours with either HT-29 or RKO cells and concentrations of capsaicin ranging between 10 and 200 µM. Subsequently, the generation of the following cytokines was examined: tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, IL-1ra, and IL-10. Capsaicin caused a concentration-dependent inhibition of colon cancer cells proliferation but had no effect on PBMC viability. 200 µM of capsaicin suppressed the production of all cytokines tested. At lower concentrations, the secretion of TNF-α, IL-1β, IFN-γ, IL-10, and IL-1ra was inhibited concentration-dependently, whereas that of IL-6 was stimulated. Capsaicin causes a concentration-dependent alteration of the immune balance between PBMC and colon carcinoma cells expressed as an inhibited generation of inflammatory cytokines. These findings indicate the existence of an additional immunomodulatory mechanism by which this alkaloid may prevent tumor development.

  2. Analyzing the regulation of metabolic pathways in human breast cancer

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    Schramm Gunnar

    2010-09-01

    Full Text Available Abstract Background Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer. Methods For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors. Results Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway. Conclusion We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.

  3. Natural variation in populations of persistently colonizing bacteria affect human host cell phenotype.

    Science.gov (United States)

    Aras, Rahul A; Lee, Yongchan; Kim, Sung-Kook; Israel, Dawn; Peek, Richard M; Blaser, Martin J

    2003-08-15

    The highly diverse bacterium Helicobacter pylori, which persistently colonizes the human stomach, provides models to study the role of genome plasticity in host adaptation. Within H. pylori populations from 2 colonized individuals, intragenomic recombination between cagA DNA repeat sequences leads to deletion or duplication of tyrosine phosphorylation sites in the CagA protein, which is injected by a type IV secretion system into host cells. Experimental coculture of gastric epithelial cells with the strains containing these naturally occurring CagA phosphorylation site variants induced markedly divergent host cell morphologic responses. Mutants were constructed in which a phosphorylation site was either added or deleted in the expressed CagA protein; coculture studies confirmed that the naturally occurring differences in CagA phosphorylation are responsible for the observed phenotypic variation. These findings indicate that within an individual host, intragenomic recombination between H. pylori repetitive DNA produces strain variants differing in their signals to host cells.

  4. Modeling microRNA-mRNA Interactions Using PLS Regression in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Li Xiaohong

    2011-05-01

    Full Text Available Abstract Background Changes in microRNA (miRNA expression patterns have been extensively characterized in several cancers, including human colon cancer. However, how these miRNAs and their putative mRNA targets contribute to the etiology of cancer is poorly understood. In this work, a bioinformatics computational approach with miRNA and mRNA expression data was used to identify the putative targets of miRNAs and to construct association networks between miRNAs and mRNAs to gain some insights into the underlined molecular mechanisms of human colon cancer. Method The miRNA and mRNA microarray expression profiles from the same tissues including 7 human colon tumor tissues and 4 normal tissues, collected by the Broad Institute, were used to identify significant associations between miRNA and mRNA. We applied the partial least square (PLS regression method and bootstrap based statistical tests to the joint expression profiles of differentially expressed miRNAs and mRNAs. From this analysis, we predicted putative miRNA targets and association networks between miRNAs and mRNAs. Pathway analysis was employed to identify biological processes related to these miRNAs and their associated predicted mRNA targets. Results Most significantly associated up-regulated mRNAs with a down-regulated miRNA identified by the proposed methodology were considered to be the miRNA targets. On average, approximately 16.5% and 11.0% of targets predicted by this approach were also predicted as targets by the common prediction algorithms TargetScan and miRanda, respectively. We demonstrated that our method detects more targets than a simple correlation based association. Integrative mRNA:miRNA predictive networks from our analysis were constructed with the aid of Cytoscape software. Pathway analysis validated the miRNAs through their predicted targets that may be involved in cancer-associated biological networks. Conclusion We have identified an alternative bioinformatics

  5. Genetic evidence of paleolithic colonization and neolithic expansion of modern humans on the tibetan plateau.

    Science.gov (United States)

    Qi, Xuebin; Cui, Chaoying; Peng, Yi; Zhang, Xiaoming; Yang, Zhaohui; Zhong, Hua; Zhang, Hui; Xiang, Kun; Cao, Xiangyu; Wang, Yi; Ouzhuluobu; Basang; Ciwangsangbu; Bianba; Gonggalanzi; Wu, Tianyi; Chen, Hua; Shi, Hong; Su, Bing

    2013-08-01

    Tibetans live on the highest plateau in the world, their current population size is approximately 5 million, and most of them live at an altitude exceeding 3,500 m. Therefore, the Tibetan Plateau is a remarkable area for cultural and biological studies of human population history. However, the chronological profile of the Tibetan Plateau's colonization remains an unsolved question of human prehistory. To reconstruct the prehistoric colonization and demographic history of modern humans on the Tibetan Plateau, we systematically sampled 6,109 Tibetan individuals from 41 geographic populations across the entire region of the Tibetan Plateau and analyzed the phylogeographic patterns of both paternal (n = 2,354) and maternal (n = 6,109) lineages as well as genome-wide single nucleotide polymorphism markers (n = 50) in Tibetan populations. We found that there have been two distinct, major prehistoric migrations of modern humans into the Tibetan Plateau. The first migration was marked by ancient Tibetan genetic signatures dated to approximately 30,000 years ago, indicating that the initial peopling of the Tibetan Plateau by modern humans occurred during the Upper Paleolithic rather than Neolithic. We also found evidences for relatively young (only 7-10 thousand years old) shared Y chromosome and mitochondrial DNA haplotypes between Tibetans and Han Chinese, suggesting a second wave of migration during the early Neolithic. Collectively, the genetic data indicate that Tibetans have been adapted to a high altitude environment since initial colonization of the Tibetan Plateau in the early Upper Paleolithic, before the last glacial maximum, followed by a rapid population expansion that coincided with the establishment of farming and yak pastoralism on the Plateau in the early Neolithic.

  6. MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

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    Christoph Campregher

    Full Text Available BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient and primary human colon epithelial cells (HCEC, MSH3-wildtype were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4 at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50, apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon

  7. Human beta-defensin-2 increases cholinergic response in colon epithelium.

    Science.gov (United States)

    Himmerkus, Nina; Vassen, Veit; Sievers, Birte; Goerke, Boeren; Shan, Qixian; Harder, Jürgen; Schröder, Jens-Michael; Bleich, Markus

    2010-06-01

    The human beta-defensin-2 (hBD-2) is expressed in epithelial cells of skin and respiratory and gastrointestinal tracts. Defensins are arginine-rich small cationic peptides with six intramolecular disulfide bonds and are antimicrobially active against a broad spectrum of pathogens. In addition, they have cytokine-like immunomodulatory properties. We hypothesized that hBD-2 also might influence epithelial cells themselves, thereby altering fluid composition in the gastrointestinal tract. We therefore tested its impact on electrogenic ion transport properties of distal colon in Ussing chamber experiments. Application of hBD-2 did not affect transepithelial voltage or resistance in cAMP-stimulated distal colon. However, it increased cholinergic Ca(2+)-dependent Cl(-) secretion. After 20 min of incubation with hBD-2, the effect of carbachol (CCh) on the equivalent short circuit current (I'(sc)) was enhanced twofold compared to vehicle-treated colon. Modulation of Ca(2+) signaling by hBD-2 was validated by Fura-2 measurements in human colon carcinoma HT29 cells. Twenty-minute incubation with hBD-2 increased the CCh-induced Ca(2+) transient by 20-30% compared to either vehicle-treated cells or cells treated with the defensins hBD-1, hBD-3, or HD-5. This effect was concentration-dependent, with an EC(50) of 0.043 microg/ml, and still present in the absence of extracellular Ca(2+). Also, the ionomycin-induced Ca(2+) transient was increased by hBD-2 treatment. We conclude that hBD-2 facilitates cholinergic Ca(2+)-regulated epithelial Cl(-) secretion. These findings contribute to the concept of a specific interaction of antimicrobial peptides with epithelial function.

  8. Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines.

    Science.gov (United States)

    Taylor, C W; Kim, Y S; Childress-Fields, K E; Yeoman, L C

    1992-02-29

    Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.

  9. Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

    Science.gov (United States)

    Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko

    2014-01-01

    The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR–dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor κ-light-chain-enhancer of activated B cells–mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. PMID:25277138

  10. Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer.

    Science.gov (United States)

    Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko; Gonzalez, Frank J

    2014-12-01

    The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR-dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor κ-light-chain-enhancer of activated B cells-mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events.

  11. Benzyl Isothiocyanate Inhibits Epithelial-Mesenchymal Transition in Cultured and Xenografted Human Breast Cancer Cells

    OpenAIRE

    Sehrawat, Anuradha; Singh, Shivendra V.

    2011-01-01

    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells, and suppresses mammary cancer development in a transgenic mouse model. We now demonstrate, for the first time, that BITC inhibits epithelial-to-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell ...

  12. The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway.

    Science.gov (United States)

    Pan, Li; Zhang, Yuming; Zhao, Wanlu; Zhou, Xia; Wang, Chunxia; Deng, Fan

    2017-07-01

    Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells. The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively. Apoptosis was determined by staining cells with annexin V-FITC and propidium iodide, followed by flow cytometry. Intracellular Ca(2+) was determined using Fluo-3 AM,glutathione (GSH) levels were measured using a GSH detection kit,and the activity of caspase-3, -9 was measured using a peptide substrate. BAX, pro-caspase-3, -9, cytochrome C and BCL-2 expression were determined by Western blotting. Oleandrin significantly decreased cell viabilities in SW480, HCT116 and RKO cells. The IC50 for SW480 cells was 0.02 µM, whereas for NCM460 cells 0.56 µM. More interestingly, the results of flow cytometry showed that oleandrin potently induced apoptosis in SW480 and RKO cells. Oleandrin downregulated protein expression of pro-caspase-3, -9, but enhanced caspase-3, -9 activities. These effects were accompanied by upregulation of protein expression of cytochrome C and BAX, and downregulation of BCL-2 protein expression in a concentration-dependent manner. Furthermore, oleandrin increased intracellular Ca(2+) concentration, but decreased GSH concentration in the cells. The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin.

  13. Effect of otilonium bromide on contractile patterns in the human sigmoid colon.

    Science.gov (United States)

    Gallego, D; Aulí, M; Aleu, J; Martínez, E; Rofes, L; Martí-Ragué, J; Jiménez, M; Clavé, P

    2010-06-01

    The mechanism of action of the spasmolytic compound otilonium bromide (OB) on human colonic motility is not understood. The aim of our study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon. Circular sigmoid strips were studied in organ baths. Isolated smooth muscle cells from human sigmoid colon were examined using the calcium imaging technique. Otilonium bromide inhibited by 85% spontaneous non-neural rhythmic phasic contractions (RPCs), (IC(50) = 49.9 nmol L(-1)) and stretch-induced tone (IC(50) = 10.7 nmol L(-1)) with maximum effects at micromolar range. OB also inhibited by 50% both on- (IC(50) = 38.0 nmol L(-1)) and off-contractions induced by electrical stimulation of excitatory motor neurons. In contrast, the inhibitory latency period prior to off-contractions was unaffected by OB. OB inhibited acetylcholine-, substance P-, and neurokinin A-induced contractions. The L-type Ca(2+) channel agonist BayK8644 reversed the effects of OB on RPCs, on- and off-contractions. Hexamethonium, atropine, the NK(2) antagonist, or depletion of intracellular Ca(2+) stores by thapsigargin did not prevent the inhibitory effect of OB on RPCs and electrical contractions. KCl-induced calcium transients in isolated smooth muscle cells were also inhibited by OB (IC(50) = 0.2 micromol L(-1)). Otilonium bromide strongly inhibited the main patterns of human sigmoid motility in vitro by blocking calcium influx through L-type calcium channels on smooth muscle cells. This pharmacological profile may mediate the clinically observed effects of the drug in patients with irritable bowel syndrome.

  14. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

    Directory of Open Access Journals (Sweden)

    Ann-Marie Baker

    2014-08-01

    Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

  15. Engineering targeted chromosomal amplifications in human breast epithelial cells.

    Science.gov (United States)

    Springer, Simeon; Yi, Kyung H; Park, Jeenah; Rajpurohit, Anandita; Price, Amanda J; Lauring, Josh

    2015-07-01

    Chromosomal amplifications are among the most common genetic alterations found in human cancers. However, experimental systems to study the processes that lead to specific, recurrent amplification events in human cancers are lacking. Moreover, some common amplifications, such as that at 8p11-12 in breast cancer, harbor multiple driver oncogenes, which are poorly modeled by conventional overexpression approaches. We sought to develop an experimental system to model recurrent chromosomal amplification events in human cell lines. Our strategy is to use homologous-recombination-mediated gene targeting to deliver a dominantly selectable, amplifiable marker to a specified chromosomal location. We used adeno-associated virus vectors to target human MCF-7 breast cancer cells at the ZNF703 locus, in the recurrent 8p11-12 amplicon, using the E. coli inosine monophosphate dehydrogenase (IMPDH) enzyme as a marker. We applied selective pressure using IMPDH inhibitors. Surviving clones were found to have increased copy number of ZNF703 (average 2.5-fold increase) by droplet digital PCR and FISH. Genome-wide array comparative genomic hybridization confirmed that amplifications had occurred on the short arm of chromosome 8, without changes on 8q or other chromosomes. Patterns of amplification were variable and similar to those seen in primary human breast cancers, including "sawtooth" patterns, distal copy number loss, and large continuous regions of copy number gain. This system will allow study of the cis- and trans-acting factors that are permissive for chromosomal amplification and provide a model to analyze oncogene cooperativity in amplifications harboring multiple candidate driver genes.

  16. Study on trace elements behaviour in cancerous and healthy tissues of colon, breast and stomach: Total reflection X-ray fluorescence applications

    Science.gov (United States)

    Magalhães, T.; Carvalho, M. L.; Von Bohlen, A.; Becker, M.

    2010-06-01

    In this work Total-reflection X-ray fluorescence (TXRF) was used to analyse healthy and cancerous tissues of the same individual along several contiguous thin sections of each tissue. Thirty two samples (16 pairs) of breast tissue, 30 samples (15 pairs) of intestine tissue and 10 samples (5 pairs) of stomach tissue were analysed. The samples were obtained in Civil Hospitals of Germany (Dortmund) and Portugal (Lisbon). The elemental distribution of P, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, Rb, Sr and Pb in these samples was studied. Descriptive statistics based on bar graphics and hypotheses tests and also an automatic classification based on hierarchical grouping analysis was used for the several analysed tissues. It was shown that the behaviour of the elements is tissue dependent. Some elements, like P and K exhibit the same behaviour in all the analysed tissue types. They have increased concentrations in all cancerous tissues. Unlike, other elements like Br show completely different behaviour depending on the tissue: similar concentration in healthy and cancerous stomach, decreased levels in colon cancerous tissues and enhanced concentrations in breast was observed. Moreover cancer tissues present decreased Se concentrations on colon and increased on breast.

  17. Carbon nanotube electron field emitters for X-ray imaging of human breast cancer

    OpenAIRE

    Gidcumb, Emily; Gao, Bo; Shan, Jing; Inscoe, Christy; Lu, Jianping; Zhou, Otto

    2014-01-01

    For imaging human breast cancer, digital breast tomosynthesis (DBT) has been shown to improve image quality and breast cancer detection in comparison to 2D mammography. Current DBT systems have limited spatial resolution and lengthy scan times. Stationary digital breast tomosynthesis (s-DBT), utilizing an array of carbon nanotube (CNT) field emission X-ray sources, provides increased spatial resolution and potentially faster imaging than current DBT systems. This study presents...

  18. Sodium Butyrate Induces Apoptosis of Human Colon Cancer Cells by Modulating ERK and Sphingosine Kinase 2

    Institute of Scientific and Technical Information of China (English)

    XIAO Min; LIU Yun Gang; ZOU Meng Chen; ZOU Fei

    2014-01-01

    Objective To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the U0126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.

  19. Effect of human isolated probiotic bacteria on preventing Campylobacter jejuni colonization of poultry.

    Science.gov (United States)

    Cean, Ada; Stef, Lavinia; Simiz, Eliza; Julean, Calin; Dumitrescu, Gabi; Vasile, Aida; Pet, Elena; Drinceanu, Dan; Corcionivoschi, Nicolae

    2015-02-01

    This study was performed in order to determine whether human isolated probiotic bacteria can be effective in reducing Campylobacter jejuni infection of chicken intestinal cells, in vitro, and in decreasing its colonization abilities within the chicken gut. Our results show that the probiotic strains Lactobacillus paracasei J. R, L. rhamnosus 15b, L. lactis Y, and L. lactis FOa had a significant effect on C. jejuni invasion of chicken primary cells, with the strongest inhibitory effect detected when a combination of four was administered. In regard to the in vivo effect, using all four strains in one combination prevented mucus colonization in the duodenum and cecum. Moreover, the pathogen load in the lumen of these two compartments was significantly reduced. When probiotics were introduced during the early growth period, the presence of the pathogen in feces was increased (p>0.05), but when they were given during the last week of growth, there was no significant effect. In conclusion, our data indicate that these four new probiotic strains are able to cause modifications in the chicken intestinal mucosa and can reduce the ability of C. jejuni to invade, in vitro, and to colonize, in vivo. These probiotics are now proven to be effective even when introduced in broiler's feed 7 days before slaughter, which makes them cost-effective for the producers.

  20. Patterns of Early-Life Gut Microbial Colonization during Human Immune Development: An Ecological Perspective

    Directory of Open Access Journals (Sweden)

    Isabelle Laforest-Lapointe

    2017-07-01

    Full Text Available Alterations in gut microbial colonization during early life have been reported in infants that later developed asthma, allergies, type 1 diabetes, as well as in inflammatory bowel disease patients, previous to disease flares. Mechanistic studies in animal models have established that microbial alterations influence disease pathogenesis via changes in immune system maturation. Strong evidence points to the presence of a window of opportunity in early life, during which changes in gut microbial colonization can result in immune dysregulation that predisposes susceptible hosts to disease. Although the ecological patterns of microbial succession in the first year of life have been partly defined in specific human cohorts, the taxonomic and functional features, and diversity thresholds that characterize these microbial alterations are, for the most part, unknown. In this review, we summarize the most important links between the temporal mosaics of gut microbial colonization and the age-dependent immune functions that rely on them. We also highlight the importance of applying ecology theory to design studies that explore the interactions between this complex ecosystem and the host immune system. Focusing research efforts on understanding the importance of temporally structured patterns of diversity, keystone groups, and inter-kingdom microbial interactions for ecosystem functions has great potential to enable the development of biologically sound interventions aimed at maintaining and/or improving immune system development and preventing disease.

  1. Antitumor Activity of Human Hydatid Cyst Fluid in a Murine Model of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Edgardo Berriel

    2013-01-01

    Full Text Available This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P=0.01. In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P=0.05. This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines.

  2. Antitumor Activity of Human Hydatid Cyst Fluid in a Murine Model of Colon Cancer

    Science.gov (United States)

    Russo, Sofía; Berois, Nora; Fernández, Gabriel; Freire, Teresa; Osinaga, Eduardo

    2013-01-01

    This study evaluates the antitumor immune response induced by human hydatic cyst fluid (HCF) in an animal model of colon carcinoma. We found that anti-HCF antibodies were able to identify cell surface and intracellular antigens in CT26 colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination was found to be protective against tumor formation for 40% of the mice (P = 0.01). In the therapeutic setting, HCF vaccination induced tumor regression in 40% of vaccinated mice (P = 0.05). This vaccination generated memory immune responses that protected surviving mice from tumor rechallenge, implicating the development of an adaptive immune response in this process. We performed a proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze the immune cross-reactivity between E. granulosus (HCF) and CT26 colon cancer cells. We identified two proteins: mortalin and creatine kinase M-type. Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In conclusion, our data demonstrate the capacity of HCF vaccination to induce antitumor immunity which protects from tumor growth in an animal model. This new antitumor strategy could open new horizons in the development of highly immunogenic anticancer vaccines. PMID:24023528

  3. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jian-Yong [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Huang, Yi [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi' an (China); Li, Ji-Peng [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Xiang; Wang, Lei [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Meng, Yan-Ling [Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Yan, Bo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Bian, Yong-Qian [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Wang, Wei-Zhong, E-mail: weichang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); and others

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.

  4. Sulforaphane Preconditioning Sensitizes Human Colon Cancer Cells towards the Bioreductive Anticancer Prodrug PR-104A.

    Directory of Open Access Journals (Sweden)

    Melanie M Erzinger

    Full Text Available The chemoprotective properties of sulforaphane (SF, derived from cruciferous vegetables, are widely acknowledged to arise from its potent induction of xenobiotic-metabolizing and antioxidant enzymes. However, much less is known about the impact of SF on the efficacy of cancer therapy through the modulation of drug-metabolizing enzymes. To identify proteins modulated by a low concentration of SF, we treated HT29 colon cancer cells with 2.5 μM SF. Protein abundance changes were detected by stable isotope labeling of amino acids in cell culture. Among 18 proteins found to be significantly up-regulated, aldo-keto reductase 1C3 (AKR1C3, bioactivating the DNA cross-linking prodrug PR-104A, was further characterized. Preconditioning HT29 cells with SF reduced the EC50 of PR-104A 3.6-fold. The increase in PR-104A cytotoxicity was linked to AKR1C3 abundance and activity, both induced by SF in a dose-dependent manner. This effect was reproducible in a second colon cancer cell line, SW620, but not in other colon cancer cell lines where AKR1C3 abundance and activity were absent or barely detectable and could not be induced by SF. Interestingly, SF had no significant influence on PR-104A cytotoxicity in non-cancerous, immortalized human colonic epithelial cell lines expressing either low or high levels of AKR1C3. In conclusion, the enhanced response of PR-104A after preconditioning with SF was apparent only in cancer cells provided that AKR1C3 is expressed, while its expression in non-cancerous cells did not elicit such a response. Therefore, a subset of cancers may be susceptible to combined food-derived component and prodrug treatments with no harm to normal tissues.

  5. Proanthocyanidin metabolites associated with dietary fibre from in vitro colonic fermentation and proanthocyanidin metabolites in human plasma.

    Science.gov (United States)

    Saura-Calixto, Fulgencio; Pérez-Jiménez, Jara; Touriño, Sonia; Serrano, José; Fuguet, Elisabet; Torres, Josep Lluis; Goñi, Isabel

    2010-07-01

    Proanthocyanidins (PAs) or condensed tannins, a major group of dietary polyphenols, are oligomers and polymers of flavan-3-ol and flavan-3, 4-diols widely distributed in plant foods. Most literature data on PAs' metabolic fate deal with PAs that can be extracted from the food matrix by aqueous-organic solvents ( extractable proanthocyanidins). However, there are no data on colonic fermentation of non-extractable proanthocyanidins (NEPAs), which arrive almost intact to the colon, mostly associated to dietary fibre (DF). The aim of the present work was to examine colonic fermentation of NEPAs associated with DF, using a model of in vitro small intestine digestion and colonic fermentation. Two NEPA-rich materials obtained from carob pod (Ceratonia siliqua L. proanthocyanidin) and red grapes (grape antioxidant dietary fibre) were used as test samples. The colonic fermentation of these two products released hydroxyphenylacetic acid, hydroxyphenylvaleric acid and two isomers of hydroxyphenylpropionic acid, detected by HPLC-ESI-MS/MS. Differences between the two products indicate that DF may enhance the yield of metabolites. In addition, the main NEPA metabolite in human plasma was 3,4-dihydroxyphenyl acetic acid. The presence in human plasma of the same metabolites as were detected after in vitro colonic fermentation of NEPAs suggests that dietary NEPAs would undergo colonic fermentation releasing absorbable metabolites with potential healthy effects.

  6. Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhu; Bao-Ming Yu; Yu-Bao Ji; Ming-Hua Zheng; Dong-Hua Li

    2002-01-01

    AIM: To evaluate the effect of reactive oxygen species suchas hydrogen peroxide on the progression of human coloncancer.METHODS: Human colon carcinoma cell lines, LS174T andHCT8, were treated respectively with 10- 5,10- 7 or 10- 9 mol@L- 1 hydrogen peroxide for 24h, and co-cultured with humanendothelial cell line ECV-304. The migration of ECV-304induced by cancer cells was calculated and the expressionlevel of vascular endothelial growth factor in cancer cellswas determined by RT-PCR analysis and ELISA.Dactinomycin of 1.5mg@ L-1 which could block transcriptionof cancer cells was applied to observe the effects of H2O2 ontranscriptional activity and the relative half-life of VEGFmRNA. Finally, to evaluate the effect H2O2 on NF-κB activityin colon cancer cells, NF-κB in cytoplasm and nucleus of thecells were detected with FITC-tagged antibody and itspresence in the nucleus (Fn ) Vs cytoplasm ( Fc ) wasmonitored by measuring the green fluorescence integratedover the nucleus by laser scanning cytometry(LSC).RESULTS: Exogenouse hydrogen peroxide of lowconcentration increased the migration of endothelial cellsinduced by colon cancer cells. When cancer cells weretreated with 10-5 mol@ L-1 H2O2, the migration number ofendothelial cells induced by LS174T cells was 203 ± 70, andthe number induced by HCT8 cells was 145 ± 65. The twovalues were significantly higher than those treated with otherconcentrations of h2O2 ( P < 0.01 ). The expression ofvascular endothelial growth factor in cancer cells, whichcould be blocked by dactinomycin, were increased to acertain degree, while the relative half-life of VEGF mRNAwas not prolonged after treatment with hydrogen peroxide.The activity of NF-κB in colon cells rose after the cells wereexposed to hydrogen peroxide for 24h. The Fn values inHCT8 cells were 91 ± 13 (0 mol@ L- 1 h2O2) and 149 ± 40( 10-5mol@L-1 h2O2) ( P< 0.05), in LS174T cells were 127 ± 35(0mol@L-1 H2O2) and 192± 11(10-5 mol@L-1 h2O2) (P< 0.05).lt is similar

  7. Evodiamine induces caspase-dependent apoptosis and S phase arrest in human colon lovo cells.

    Science.gov (United States)

    Zhang, Chun; Fan, Xia; Xu, Xiang; Yang, Xue; Wang, Xi; Liang, Hua-Ping

    2010-09-01

    Evodiamine, one of the major bioactive components derived from Wu-Chu-Yu, a long-standing Chinese herb, was reported to possess anticancer activity. In this study, we investigated the in-vitro and in-vivo anticancer effects of evodiamine on human colon lovo cells and their potential mechanisms. The 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the in-vitro proliferation of lovo cells was inhibited by evodiamine of various concentrations. Flow cytometry showed a time-dependent increase in the percentage of apoptotic cells and cells arrested in the S phase after treatment with 60 micromol/l evodiamine. Western blot indicated that evodiamine treatment decreased the expression of procaspase-8, procaspase-9, and procaspase-3 in lovo cells, accompanied by the activation of caspase-8, caspase-9, and caspase-3. However, the translocation of apoptosis-inducing factor and endonuclease G was not affected by evodiamine. Moreover, western blot assay also suggested that evodiamine-induced S phase arrest in lovo cells was associated with a marked decrease in the protein expression of cyclinA, cyclinA-dependent kinase 2, and cdc25c. In-vivo antineoplastic characteristics of evodiamine were examined in a human colon carcinoma lovo xenograft model and results showed that evodiamine increased the number of TUNEL-positive cells accompanied by the downregulated expression of procaspase-8, procaspase-9, and procaspase-3. In conclusion, these findings indicated that evodiamine could inhibit the in-vitro and in-vivo proliferation of human colon lovo cells by inducing caspase-dependent apoptosis and S phase arrest.

  8. Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiang-Liang Zhang; An-Bin Hu; Shu-Zhong Cui; Hong-Bo Wei

    2012-01-01

    AIM:To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells.METHODS:The human colon adenocarcinoma cell line Lovo was obtained from Sun Yat-Sen University.Cells were sealed with parafilm and placed in a circulating water bath,and was maintained within 0.01 ℃ of the desired temperature (37 ℃,39 ℃,41 ℃,43 ℃ and 45 ℃).Thermal therapy was given alone to the negarive control group while oxaliplatin was administered to the treatment group at doses of 12.5 μg/mL and 50 μg/mL.Identification of morphological changes,3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,flow cytometry and Western blotting were used to investigate the effect of thermochemotherapy on human colon adenocarcinoma Lovo cells,including changes in the signal pathway related to apoptosis.RESULTS:A temperature-dependent inhibition of cell growth was observed after oxaliplatin exposure,while a synergistic interaction was detected preferentially with sequential combination.Thermochemotherapy changed the morphology of Lovo cells,increased the inhibition rate of the Lovo cells (P < 0.05) and enhanced cellular population in the G0/G1 phase (16.7%± 4.8 % in phase S plus 3.7% ± 2.4 % in phase G2/M,P < 0.05).Thermochemotherapy increased apoptosis through upregulating p53,Bax and downregulating Bcl-2.Protein levels were elevated in p53,Bax/Bcl-2in thermochemotherapy group as compared with the control group (P < 0.05).CONCLUSION:Thermochemotherapy may play an important role in apoptosis via the activation of p53,Bax and the repression of Bcl-2 in Lovo cells.

  9. Deciphering the colon cancer genes--report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010

    DEFF Research Database (Denmark)

    Kohonen-Corish, Maija R J; Macrae, Finlay; Genuardi, Maurizio;

    2011-01-01

    The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP...... Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.liacs.nl/LOVD2/colon_cancer...

  10. Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells.

    Science.gov (United States)

    Kang, Soo-Young; Seeram, Navindra P; Nair, Muraleedharan G; Bourquin, Leslie D

    2003-05-08

    Anthocyanins, which are bioactive phytochemicals, are widely distributed in plants and especially enriched in tart cherries. Based on previous observations that tart cherry anthocyanins and their respective aglycone, cyanidin, can inhibit cyclooxygenase enzymes, we conducted experiments to test the potential of anthocyanins to inhibit intestinal tumor development in Apc(Min) mice and growth of human colon cancer cell lines. Mice consuming the cherry diet, anthocyanins, or cyanidin had significantly fewer and smaller cecal adenomas than mice consuming the control diet or sulindac. Colonic tumor numbers and volume were not significantly influenced by treatment. Anthocyanins and cyanidin also reduced cell growth of human colon cancer cell lines HT 29 and HCT 116. The IC(50) of anthocyanins and cyanidin was 780 and 63 microM for HT 29 cells, respectively and 285 and 85 microM for HCT 116 cells, respectively. These results suggest that tart cherry anthocyanins and cyanidin may reduce the risk of colon cancer.

  11. Activation of human colon mast cells through proteinase activated receptor-2

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Yong-Song He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of agonists of PAR-2 to rtimulate release of tryptase and histamine from human colon mast cells and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with tc-LIGRLO, tc-OLRGIL, SLIGKV,VKGILS, trypsin, anti-IgE or calcium ionophore A23187, and the cell supernatante after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured using a glass fibrebased fluorometric assay.RESULTS: Both PAR-2 agonists tc-LIGRLO-NH2 and SLIGKVNH2 were able to induce dose dependent release of tryptase and histamine from colon mast cells. More than 2.5 fold increase in both tryptase and histamine release was provoked by 100 μmol/mL tc-LIGRLO-NH2, in compariSon with only 2.0 fold increase being stimulated by SLIGKV-NH2. The reverse peptides tc-OLRGIL-NH2 and VKGILS -NH2 at the concentrations tested had no effect on the release of these two mediators. The maximum tryptase release elicited by tc-LIGRLO-NH2 was similar to that induced by anti-IgE(10 μg/mL) or calcium ionophore (1 μg/mL), though the latter was a more potent stimulus for histamine release. Both histamine and tryptase release in response to tc-LIGRLONH2 were completed within 3 min. Trypsin at concentrations from 1.0 to 100 μg/mL was capable of provoking a dose dependent release of tryptase as well as histamine with a maximum of 16 ng/mL tryptase and 14 ng/mL histamine release being achieved. An approximately 80% and 70% inhibition of trypsin induced release of tryptase and histamine were observed with SBTI, respectively. Pretreatment of cells with metabolic inhibitors or pertussis toxin abolished the actions of tc-LIGRLO-NH2, SLIGKV-NH2 and trypsin.CONCLUSION: The agonists of PAR-2 and trypsin are potent secretagogues of human colon mast cells, which are likely to contribute to the development of inflammatory disorders in human gut.

  12. Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi, Maria Lauda [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); Ryoo, Minjung; Skay, Anna [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); Tomasi, Ivan; Giordano, Pasquale [Department of Colorectal Surgery, Whipps Cross University Hospital, London E11 1NR (United Kingdom); Mato, José M. [CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia (Spain); Lu, Shelly C., E-mail: shellylu@usc.edu [Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States); The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033 (United States)

    2013-07-15

    Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70–75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100 pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell. -- Highlights: • MAT2A knockdown depletes putrescine and leads to apoptosis. • Putrescine attenuates MAT2A knockdown-induced apoptosis and growth

  13. Characterization of galactosyl glycerolipids in the HT29 human colon carcinoma cell line.

    Science.gov (United States)

    Påhlsson, P; Spitalnik, S L; Spitalnik, P F; Fantini, J; Rakotonirainy, O; Ghardashkhani, S; Lindberg, J; Konradsson, P; Larson, G

    2001-12-15

    Glycoglycerolipids constitute a family of glycolipids with apparently very restricted expression in human tissues. They have previously been detected only in the testis and the nervous system. In the present study, two glycoglycerolipids were isolated from the HT29 human colon carcinoma cell line. The glycoglycerolipids were structurally characterized as a monogalactosylglycerolipid (1-O-alkyl-2-O-acyl-3-O-(beta-galactosyl)-sn-glycerol) and a digalactosylglycerolipid (1-O-alkyl-2-O-acyl-3-O-(beta-galactosyl(1-4)alpha-galactosyl)-sn-glycerol) using NMR and mass spectrometry. This digalactosylglycerolipid has not previously been structurally characterized. When HT29 cells were allowed to differentiate into more enterocyte-like cells by culture in glucose-free medium, expression of both of these glycoglycerolipids was greatly diminished. The presence of glycoglycerolipids in a human colon carcinoma cell line indicates that expression of this family of glycolipids may not be as restricted as previously thought. Instead this class of glycolipids may serve as differentiation antigens in various normal tissues and in tumor development. The Galalpha1-4Gal epitope was previously identified as a receptor for bacterial adhesins and toxins. The finding that this epitope is also linked to a glycerolipid moiety opens up new possible roles for this carbohydrate receptor in intracellular signaling.

  14. Current and Potential Treatments for Reducing Campylobacter Colonization in Animal Hosts and Disease in Humans

    Science.gov (United States)

    Johnson, Tylor J.; Shank, Janette M.; Johnson, Jeremiah G.

    2017-01-01

    Campylobacter jejuni is the leading cause of bacteria-derived gastroenteritis worldwide. In the developed world, Campylobacter is usually acquired by consuming under-cooked poultry, while in the developing world it is often obtained through drinking contaminated water. Once consumed, the bacteria adhere to the intestinal epithelium or mucus layer, causing toxin-mediated inhibition of fluid reabsorption from the intestine and invasion-induced inflammation and diarrhea. Traditionally, severe or prolonged cases of campylobacteriosis have been treated with antibiotics; however, overuse of these antibiotics has led to the emergence of antibiotic-resistant strains. As the incidence of antibiotic resistance, emergence of post-infectious diseases, and economic burden associated with Campylobacter increases, it is becoming urgent that novel treatments are developed to reduce Campylobacter numbers in commercial poultry and campylobacteriosis in humans. The purpose of this review is to provide the current status of present and proposed treatments to combat Campylobacter infection in humans and colonization in animal reservoirs. These treatments include anti-Campylobacter compounds, probiotics, bacteriophage, vaccines, and anti-Campylobacter bacteriocins, all of which may be successful at reducing the incidence of campylobacteriosis in humans and/or colonization loads in poultry. In addition to reviewing treatments, we will also address several proposed targets that may be used in future development of novel anti-Campylobacter treatments. PMID:28386253

  15. Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.

    Science.gov (United States)

    Toh, Michael C; Goodyear, Mara; Daigneault, Michelle; Allen-Vercoe, Emma; Van Raay, Terence J

    2013-06-01

    The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

  16. Mechanism of Alternariol monomethyl ether-induced mitochondrial apoptosis in human colon carcinoma cells.

    Science.gov (United States)

    Bensassi, Fatma; Gallerne, Cindy; el Dein, Ossama Sharaf; Hajlaoui, Mohamed Rabeh; Bacha, Hassen; Lemaire, Christophe

    2011-12-18

    Alternariol monomethyl ether (AME) is a major mycotoxin produced by fungi of the genus Alternaria and a common contaminant of food products such as fruits and cereals worldwide. AME can cause serious health problems for animals as well as for humans. In this study, human colon carcinoma cells (HCT116) were used to explore the mechanisms of cell death induced by AME. Exposure of HCT116 cells to AME resulted in significant cytotoxicity manifested by a loss in cell viability mainly mediated by activation of apoptotic process. AME activated the mitochondrial apoptotic pathway evidenced by the opening of the mitochondrial permeability transition pore (PTP), loss of the mitochondrial transmembrane potential (ΔΨm) downstream generation of O(2)(-), cytochrome c release and caspase 9 and 3 activation. Experiments conducted on isolated organelles indicated that AME does not directly target mitochondria to induce PTP-dependent permeabilization of mitochondrial membranes. Moreover, no difference was observed in Bax-KO cells in comparison to parental cells, suggesting that the pro-apoptotic protein Bax is not involved in AME-induced mitochondrial apoptosis. Our findings demonstrate for the first time that AME induces cell death in human colon carcinoma cells by activating the mitochondrial pathway of apoptosis.

  17. Carriers of human mitochondrial DNA macrohaplogroup M colonized India from southeastern Asia.

    Science.gov (United States)

    Marrero, Patricia; Abu-Amero, Khaled K; Larruga, Jose M; Cabrera, Vicente M

    2016-11-10

    From a mtDNA dominant perspective, the exit from Africa of modern humans to colonize Eurasia occurred once, around 60 kya, following a southern coastal route across Arabia and India to reach Australia short after. These pioneers carried with them the currently dominant Eurasian lineages M and N. Based also on mtDNA phylogenetic and phylogeographic grounds, some authors have proposed the coeval existence of a northern route across the Levant that brought mtDNA macrohaplogroup N to Australia. To contrast both hypothesis, here we reanalyzed the phylogeography and respective ages of mtDNA haplogroups belonging to macrohaplogroup M in different regions of Eurasia and Australasia. The macrohaplogroup M has a historical implantation in West Eurasia, including the Arabian Peninsula. Founder ages of M lineages in India are significantly younger than those in East Asia, Southeast Asia and Near Oceania. Moreover, there is a significant positive correlation between the age of the M haplogroups and its longitudinal geographical distribution. These results point to a colonization of the Indian subcontinent by modern humans carrying M lineages from the east instead the west side. The existence of a northern route, previously proposed for the mtDNA macrohaplogroup N, is confirmed here for the macrohaplogroup M. Both mtDNA macrolineages seem to have differentiated in South East Asia from ancestral L3 lineages. Taking this genetic evidence and those reported by other disciplines we have constructed a new and more conciliatory model to explain the history of modern humans out of Africa.

  18. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an a

  19. Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium

    DEFF Research Database (Denmark)

    Barrow, Hannah; Guo, Xiuli; Wandall, Hans H

    2011-01-01

    Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells...... to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion....

  20. INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

    1996-01-01

    Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

  1. Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    YAN Chen; TENG Zhi Ping; CHEN Yun Xin; SHEN Dan Hua; LI Jin Tao; ZENG Yi

    2016-01-01

    ObjectiveTo explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. MethodsPCR was used to screen HPV16 and HPV18 oncogenesE6 andE7 in the SKBR3 cell line andin 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18E6 andE7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. ResultsHPV18 oncogenesE6 andE7 were amplified and sequenced from the SKBR3 cells. Ofthe patient samples, 6.58% and 23.68% were tested to bepositivefor HPV18E6 and HPV18E7. In the cell culture models, the knockdown of HPV18E6 andE7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. ConclusionHPV was a contributor to virus causedhuman breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.

  2. Mathematical analysis of mammary ducts in lactating human breast.

    Science.gov (United States)

    Mortazavi, S Negin; Geddes, Donna; Hassiotou, Foteini; Hassanipour, Fatemeh

    2014-01-01

    This work studies a simple model for milk transport through lactating human breast ducts, and describes mathematically the mass transfer from alveolar sacs through the mammary ducts to the nipple. In this model both the phenomena of diffusion in the sacs and conventional flow in ducts have been considered. The ensuing analysis reveals that there is an optimal range of bifurcation numbers leading to the easiest milk flow based on the minimum flow resistance. This model formulates certain difficult-to-measure values like diameter of the alveolar sacs, and the total length of the milk path as a function of easy-to-measure properties such as milk fluid properties and macroscopic measurements of the breast. Alveolar dimensions from breast tissues of six lactating women are measured and reported in this paper. The theoretically calculated alveoli diameters for optimum milk flow (as a function of bifurcation numbers) show excellent match with our biological data on alveolar dimensions. Also, the mathematical model indicates that for minimum milk flow resistance the glandular tissue must be within a short distance from the base of the nipple, an observation that matches well with the latest anatomical and physiological research.

  3. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  4. Cigarette smoke extracts induced the colon cancer migration via regulating epithelial mesenchymal transition and metastatic genes in human colon cancer cells.

    Science.gov (United States)

    Kim, Cho-Won; Go, Ryeo-Eun; Lee, Hae-Miru; Hwang, Kyung-A; Lee, Kyuhong; Kim, Bumseok; Lee, Moo-Yeol; Choi, Kyung-Chul

    2017-02-01

    There was considerable evidence that exposure to cigarette smoke is associated with an increased risk for colon cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and colon cancer remains unclear. Moreover, there were only a few studies on effects of complexing substance contained in cigarette smoke on colon cancer. Thus, we further investigated whether cigarette smoke extract (CSE) affects the cell cycle, apoptosis and migration of human metastatic colon cancer cells, SW-620. MTT assay revealed that SW-620 cell proliferation was significantly inhibited following treatments with all CSEs, 3R4F, and two-domestic cigarettes, for 9 days in a concentration-dependent manner. Moreover, CSE treatments decreased cyclin D1 and E1, and increased p21 and p27 proteins by Western blot analysis in SW-620 cells. Additionally, the treatment of the cells with CSE contributed to these effects expressing by apoptosis-related proteins. An increased migration or invasion ability of SW-620 cells following CSE treatment was also confirmed by a scratch or fibronectin invasion assay in vitro. In addition, the protein levels of E-cadherin as an epithelial maker were down-regulated, while the mesenchymal markers, N-cadherin, snail, and slug, were up-regulated in a time-dependent manner. A metastatic marker, cathepsin D, was also down-regulated by CSE treatment. Taken together, these results indicate that CSE exposure in colon cancer cells may deregulate the cell growth by altering the expression of cell cycle-related proteins and pro-apoptotic protein, and stimulate cell metastatic ability by altering epithelial-mesenchymal transition (EMT) markers and cathepsin D expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 690-704, 2017.

  5. Models of Human Metastatic Colon Cancer in Nude Mice Orthotopically Constructed by Using Histologically Intact Patient Specimens

    Science.gov (United States)

    Fu, Xinyu; Besterman, Jeffrey M.; Monosov, Ann; Hoffman, Robert M.

    1991-10-01

    There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.

  6. MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hisataka Ogawa

    Full Text Available Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.

  7. Novel snail1 target proteins in human colon cancer identified by proteomic analysis.

    Directory of Open Access Journals (Sweden)

    María Jesús Larriba

    Full Text Available BACKGROUND: The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT, a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT. METHODOLOGY/PRINCIPAL FINDINGS: We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4 that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6 and the Splicing factor proline/glutamine-rich (SFPQ, was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3epsilon, 14-3-3tau, 14-3-3zeta and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3sigma and Snail1 expression in human colorectal tumors. CONCLUSIONS/SIGNIFICANCE: We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.

  8. Orexin A induces autophagy in HCT-116 human colon cancer cells through the ERK signaling pathway.

    Science.gov (United States)

    Wen, Jing; Zhao, Yuyan; Guo, Lei

    2016-01-01

    Orexins are a class of peptides which have a potent influence on a broad variety of cancer cells. Autophagy is closely associated with tumors; however, its function is not yet completely understood. In this study, we aimed to determine whether orexin A induces autophagy in HCT‑116 human colon cancer cells and to elucidate the molecular mechanisms involved. For this purpose, HCT‑116 cells were treated with orexin A, and cell viability was then measured by MTT assay, and apoptosis was determined by flow cytometry. The expression levels of autophagy‑related proteins were measured by western blot analysis. Quantitative analysis of autophagy following acridine orange (AO) staining was performed using fluorescence microscopy, and cellular morphology was observed under a transmission electron microscope. In addition, the HCT‑116 cells were treated with the extracellular signal‑regulated kinase (ERK) inhibitor, U0126, or the autophagy inhibitor, chloroquine, in combination with orexin A in order to examine the activation of ERK. We found that orexin A significantly inhibited the viability of the HCT‑116 cells. Both autophagy and apoptosis were activated during the orexin A‑induced death of HCT‑116 cells. When the HCT‑116 cells were treated with orexin A for 24 h, an accumulation of punctate microtubule-associated protein-1 light chain 3 (LC3) and an increase in LC3‑Ⅱ protein levels were also detected, indicating the activation of autophagy. Moreover, orexin A upregulated ERK phosphorylation; however, U0126 or chloroquine abrogated ERK phosphorylation and decreased autophagy, compared to treatment with orexin A alone. Therefore, our findings demonstratedm that orexin A induced autophagy through the ERK pathway in HCT‑116 human colon cancer cells. The inhibition of autophagy may thus prove to be an effective strategy for enhancing the antitumor potential of orexin A as a treatment for colon cancer.

  9. Stereospecific ligands and their complexes. Part XII. Synthesis, characterization and in vitro antiproliferative activity of platinum(IV) complexes with some O,O‧-dialkyl esters of (S,S)-ethylenediamine-N,N‧-di-2-propanoic acid against colon cancer (HCT-116) and breast cancer (MDA-MB-231) cell lines

    Science.gov (United States)

    Stojković, Danijela Lj.; Jevtić, Verica V.; Radić, Gordana P.; Đačić, Dragana S.; Ćurčić, Milena G.; Marković, Snežana D.; Ðinović, Vesna M.; Petrović, Vladimir P.; Trifunović, Srećko R.

    2014-03-01

    Synthesis of three new platinum(IV) complexes C1-C3, with bidentate N,N‧-ligand precursors, O,O‧-dialkyl esters (alkyl = propyl, butyl and pentyl), of (S,S)-ethylenediamine-N,N‧-di-2-propanoic acid, H2-S,S-eddp were reported. The reported platinum(IV) complexes characterized by elemental analysis and their structures were discussed on the bases of their infrared, 1H and 13C NMR spectroscopy. In vitro antiproliferative activity was determined on tumor cell lines: human colon carcinoma HCT-116 and human breast carcinoma MDA-MB-231, using MTT test.

  10. Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic factor associated with estrogen receptor.

    Science.gov (United States)

    Sase, Tomohiko; Suzuki, Takashi; Miura, Koh; Shiiba, Kenichi; Sato, Ikuro; Nakamura, Yasuhiro; Takagi, Kiyoshi; Onodera, Yoshiaki; Miki, Yasuhiro; Watanabe, Mika; Ishida, Kazuyuki; Ohnuma, Shinobu; Sasaki, Hiroyuki; Sato, Ryuichiro; Karasawa, Hideaki; Shibata, Chikashi; Unno, Michiaki; Sasaki, Iwao; Sasano, Hironobu

    2012-11-15

    Runt-related transcription factor 2 (RUNX2) belongs to the RUNX family of heterodimeric transcription factors, and is mainly associated with osteogenesis. Previous in vitro studies demonstrated that RUNX2 increased the cell proliferation of mouse and rat colon carcinoma cells but the status of RUNX2 has remained unknown in human colon carcinoma. Therefore, we examined clinical significance and biological functions of RUNX2 in colon carcinoma. RUNX2 immunoreactivity was examined in 157 colon carcinoma tissues using immunohistochemistry. RUNX2 immunoreactivity was evaluated as percentage of positive carcinoma cells [i.e., labeling index (LI)]. We used SW480 and DLD-1 human colon carcinoma cells, expressing estrogen receptor-β (ER) in subsequent in vitro studies. RUNX2 immunoreactivity was detected in colon carcinoma cells, and the median value of RUNX2 LI was 67%. RUNX2 LI was significantly associated with Dukes' stage, liver metastasis and ERβ status. In addition, RUNX2 LI was significantly associated with adverse clinical outcome of the colon carcinoma patients, and turned out an independent prognostic factor following multivariate analysis. Results of in vitro studies demonstrated that both SW480 and DLD-1 cells transfected with small interfering RNA against RUNX2 significantly decreased their cell proliferation, migration and invasive properties. In addition, RUNX2 mRNA level was significantly decreased by ER antagonist in these two cells. These findings all suggest that RUNX2 is a potent prognostic factor in human colon carcinoma patients through the promotion of cell proliferation and invasion properties, and is at least partly upregulated by estrogen signals through ERβ of carcinoma cells.

  11. Nonlinear fractal dynamics of human colonic pressure activity based upon the box-counting method.

    Science.gov (United States)

    Yan, Rongguo; Guo, Xudong

    2013-01-01

    The computational fractal dimension of human colonic pressure activity acquired by a telemetric capsule robot under normal physiological conditions was studied using the box-counting method. The fractal dimension is a numeric value that quantifies to measure how rough the signal is from nonlinear dynamics, rather than its amplitude or other linear statistical features. The colonic pressure activities from the healthy subject during three typical periods were analysed. The results showed that the activity might be fractal with a non-integer fractal dimension after it being integrated over time using the cumsum method, which was never revealed before. Moreover, the activity (after it being integrated) acquired soon after wakening up was the roughest (also the most complex one) with the largest fractal dimension, closely followed by that acquired during sleep with that acquired long time after awakening up (in the daytime) ranking third with the smallest fractal dimension. Fractal estimation might provide a new method to learn the nonlinear dynamics of human gastrointestinal pressure recordings.

  12. Use of Mueller polarimetric imaging for the staging of human colon cancer

    Science.gov (United States)

    Pierangelo, Angelo; Manhas, Sandeep; Benali, Abdelali; Antonelli, Maria Rosaria; Novikova, Tatiana; Validire, Pierre; Gayet, Brice; De Martino, Antonello

    2011-03-01

    In this paper we show the results of multi-spectral Mueller Imaging applied to the analysis of human colon cancer in a backscattering configuration with diffuse light illumination. The analyzed sample behaves as a pure depolarizer. The depolarization power, for both healthy and cancerous zones, is lower for linearly than for circularly polarized incident light for all used wavelengths and increases with increasing wavelength. Based on their visual staging and polarimetric responses, we chose specific zones which we correlated to the histology of the corresponding cuts. The histological examination shows that we see a multilayer interaction in both healthy and abnormal zones, if the light penetration depth is sufficient. The measured depolarization depends on several factors: the presence or absence of tumor, the microscopic structure of cancer (ratio between cellular density and stroma), its exophytic (budding) or endophytic (penetrating) nature, its thickness, the degree of cancer penetration in deeper layers and the nature of healthy tissue left under abnormal layers. These results demonstrate that multi-spectral Mueller imaging can provide useful contrasts for the quick staging of human colon cancer ex-vivo, with additional information about cancerous zones with different microscopic structures.

  13. In vitro radiosensitization by oxaliplatin and 5-fluorouracil in a human colon cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kjellstroem, Johan; Kjellen, Elisabeth; Johnsson, Anders [Univ. Hospital, Lund (Sweden). Dept. of Oncology

    2005-10-01

    The current study was designed to compare the radiosensitizing effects of oxaliplatin and 5-fluorouracil (5FU) in a human colon cancer cell line. A human colon cancer cell line (S1) was treated with various doses of oxaliplatin, 5FU, radiation, and combinations thereof. Various clinically used schedules were mimicked. 5FU was either incubated during 1 h ('bolus') or 24 h ('continuous infusion'). When combining oxaliplatin and 5FU, an isobologram analysis revealed synergistic effects, regardless of 5FU schedule. The IC{sub 10} and IC{sub 50}-doses for the drugs where then combined with radiotherapy. With equitoxic drug doses (IC{sub 50}), radiosensitization was observed in the following order: oxaliplatin>5FU 24 h>5FU 1 h exposure. The degree of potentiation corresponded to approximately 0.8 Gy, 0.7 Gy, and 0.2 Gy, respectively. In this experimental setting, oxaliplatin seemed to be a better radiosensitizer than 5FU, and longer incubation time with 5FU was better than short exposure.

  14. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Hae-Jeong Park; Sung-Vin Yim; Joo-Ho Chung; Seon-Pyo Hong; Seo-Hyun Yoon; Long-Shan Han; Long-Tai Zheng; Kyung-Hee Jung; Yoon-Kyung Uhm; Je-Hyun Lee; Ji-Seon Jeong; Woo-Sang Joo

    2005-01-01

    AIM: The genes were divided into seven categories according to biological function; apoptosis-reiated, immune response-related, signal transduction-related, cell cyclerelated, cell growth-related, stress response-related and transcription-related genes.METHODS: We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated (5 mg/mL,24 h) and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT-PCR. RESULTS: Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F, member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE114), topoisomerase (DNA) I (TOP1), and FK506 binding protein 12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells.CONCLUSION: These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells,and might be used for therapeutic anticancer drug.

  15. In Vitro Degradation and Fermentation of Three Dietary Fiber Sources by Human Colonic Bacteria

    Science.gov (United States)

    Bliss, Donna Z.; Weimer, Paul J.; Jung, Hans-Joachim G.; Savik, Kay

    2013-01-01

    Although clinical benefits of dietary fiber supplementation seem to depend partially on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of supplemental fiber type on bacterial metabolism. In an experiment using a non-adapted human bacterial population from three normal subjects, extent of in vitro fermentation was greater for gum arabic (GA) than for psyllium (PSY), which was greater than that for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation with feces from 52 subjects with fecal incontinence, before and after random assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements or a placebo for 20-21d, indicated that prior consumption of a specific fiber source did not increase its degradation by fecal bacteria. Results suggest that the colonic microbial community enriched on a particular fiber substrate can rapidly adapt to the presentation of a new fiber substrate. Clinical implications of the findings are that intake of a fiber source by humans is not expected to result in bacterial adaptation that would require continually larger and eventually intolerable amounts of fiber to achieve therapeutic benefits. PMID:23556460

  16. Apoptosis of human colon carcinoma HT-29 cells induced by ceramide

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Zhang; Bai-Xiang Li; Chun-Yan Dong; Rui Ren

    2006-01-01

    AIM: To investigate the effect of exogenous ceramideinduced apoptosis on human colon carcinoma HT-29cells.METHODS: Light microscope, transmission electron microscope and fluorescence microscope were used to observe the morphology change of apoptosis in HT-29cells. Agarose gel electrophoresis was performed to detect the DNA fragment. Mitochondrial function was detected by MTT assay. mRNA expression of Bcl-2 family gene members was determined by reverse transcription polymerase chain reaction (RT-PCR) assay.RESULTS: After C2-ceramide treatment, typical characteristics of apoptosis, such as nuclear chromatin breakage, apoptotic body and DNA ladder, could be observed. After exposure to 50 μmol/L C2-ceramide for 12 and 24 h, cell apoptosis was 64.1% and 81.3% respectively, which had a time-and dose-effect relationship. Mitochondrial function started to decrease from 6 h after exposure to ceramide. Meanwhile,ceramide up-regulated or down-regulated the mRNA expression of Bcl-2 family gene members.CONCLUSION: Ceramide induces apoptosis of human colon carcinoma HT-29 cells by affecting the expression of Bcl-2 family gene members and impacting the mitochondrial function.

  17. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells.

    Science.gov (United States)

    Park, Hae-Jeong; Yoon, Seo-Hyun; Han, Long-Shan; Zheng, Long-Tai; Jung, Kyung-Hee; Uhm, Yoon-Kyung; Lee, Je-Hyun; Jeong, Ji-Seon; Joo, Woo-Sang; Yim, Sung-Vin; Chung, Joo-Ho; Hong, Seon-Pyo

    2005-09-07

    The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cycle-related, cell growth-related, stress response-related and transcription-related genes. We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated (5 mg/mL, 24 h) and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT-PCR. Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F, member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE11A), topoisomerase (DNA) I (TOP1), and FK506 binding protein 12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug.

  18. Electroporation-assisted penetration of zinc oxide nanoparticles in ex vivo normal and cancerous human colon tissue

    Science.gov (United States)

    Zhou, L. P.; Wu, G. Y.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; He, Y. H.; Xie, S. S.

    2015-11-01

    In this study, we presented the research of the penetration of zinc oxide nanoparticles (ZnO NPs) (30 and 90 nm), and electroporation (EP) assisted penetration of the ZnO NPs in the human normal colon (NC) and adenomatous colon (AC) tissues studied with optical coherence tomography (OCT) and diffuse reflectance (DR) measurement. The results have shown that the attenuation coefficient of colon tissue after the application of 30 or 90 nm ZnO NPs alone decreased approximately by 28% and 14% for NC tissue, 35% and 22% for AC tissue, respectively; while the attenuation coefficient of colon tissue after combined application of 30 or 90 nm ZnO NPs/EP decreased approximately by 46% and 30% for NC tissue, and 53% and 42% for AC tissue, respectively. The results illustrate EP can significantly increase the penetration of ZnO NPs in the colon tissue, especially in AC tissue. Through the analysis of attenuation coefficient and reflectance intensity of the colon tissue, we find that the accumulation of the ZnO NPs in the colon tissue greatly influenced the tissue optical properties.

  19. High risk human papillomavirus and Epstein Barr virus in human breast milk

    Directory of Open Access Journals (Sweden)

    Glenn Wendy K

    2012-09-01

    Full Text Available Abstract Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid and in situ polymerase chain reaction (PCR techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15% from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%. Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.

  20. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  1. Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids.

    Science.gov (United States)

    Déprez, S; Brezillon, C; Rabot, S; Philippe, C; Mila, I; Lapierre, C; Scalbert, A

    2000-11-01

    Polymeric proanthocyanidins are common constituents of many foods and beverages. Their fate in the human body remains largely unknown. Their metabolism by human colonic microflora incubated in vitro in anoxic conditions has been investigated using nonlabeled and (14)C-labeled purified proanthocyanidin polymers. Polymers were almost totally degraded after 48 h of incubation. Phenylacetic, phenylpropionic and phenylvaleric acids, monohydroxylated mainly in the meta or para position, were identified as metabolites by gas chromatography coupled to mass spectrometry (GC-MS). Yields were similar to those previously reported for flavonoid monomers. These results provide the first evidence of degradation of dietary phenolic polymers into low-molecular-weight aromatic compounds. To understand the nutritional properties of proanthocyanidins, it is therefore essential to consider the biological properties of these metabolites.

  2. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    Science.gov (United States)

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

  3. The potent microtubule-stabilizing agent (+)-discodermolide induces apoptosis in human breast carcinoma cells--preliminary comparisons to paclitaxel.

    Science.gov (United States)

    Balachandran, R; ter Haar, E; Welsh, M J; Grant, S G; Day, B W

    1998-01-01

    (+)-Discodermolide, a sponge-derived natural product, stabilizes microtubules more potently than paclitaxel despite the lack of any obvious structural similarities between the drugs. It competitively inhibits the binding of paclitaxel to tubulin polymers, hypernucleates microtubule assembly more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant ovarian and colon carcinoma cells. Because paclitaxel shows clinical promise for breast cancer treatment, its effects in a series of human breast cancer cells were compared to those of (+)-discodermolide. Growth inhibition, cell and nuclear morphological, and electrophoretic and flow cytometric analyses were performed on (+)-discodermolide-treated MCF-7 and MDA-MB231 cells. (+)-Discodermolide potently inhibited the growth of both cell types (IC50 Discodermolide-treated cells exhibited condensed and highly fragmented nuclei. Flow cytometric comparison of cells treated with either drug at 10 nM, a concentration well below that achieved clinically with paclitaxel, showed both caused cell cycle perturbation and induction of a hypodiploid cell population. (+)-Discodermolide caused these effects more extensively and at earlier time points. The timing and type of high molecular weight DNA fragmentation induced by the two agents was consistent with induction of apoptosis. The results suggest that (+)-discodermolide has promise as a new chemotherapeutic agent against breast and other cancers.

  4. Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.

    Science.gov (United States)

    Rao, C V; Desai, D; Kaul, B; Amin, S; Reddy, B S

    1992-11-16

    Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems.

  5. Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo

    Institute of Scientific and Technical Information of China (English)

    Ying-Fang Fan; Zong-Hai Huang

    2002-01-01

    AIM: To study the effect of angiogenesis inhibitor TNP-470on peritoneal dissemination of colon cancer in nude mice,METHODS: The MTT assay was used to evaluate theinhibitory effect of TNP-470 on human colon cancer cell lineLovo. Lovo cells were injected into the peritoneal cavity ofBABL/C nu/nu mice and the models of peritonealdissemination were developed. Thirty nude mice wererandomly divided into control and TNP-470-treated group.In TNP-470-treated group, TNP-470 was injectedsubcutaneously every other day from day 1 until sacrifice ordeath (30 mg.kg-1). The control group received a shaminjection of the same volume saline solutionRESULTS: In vltro, TNP-470 inhibited the growth of Lovocells, with its IC50 at 2.14x102μg.L-1 In vivo, TNP-470demonstrated growth inhibition of tumors. Mice body weightand abdominal circumferences were significantly differentbetween TNP-470-treated group (24.5±3.2 g, 7.0±1.1 cm)and control group (29.5±2.1 g, 10.3±1.5 cm), P=0.005 andP=0.001. The number of disseminated foci was significantlydifferent between the control group (92.1±20.6) and theTNP-470-treated group (40.3±12.3), P<0.001. The maximalsize of foci was significantly smaller in TNP-470-treated group(3.3±0.7 mm) than that of control (7.3±2.3 mm), P=0.004.Mean survival time was significantly longer in TNP-470-treated group(98.00±12.06 d) than that in control group(41.86±9.51 d), P<0.001.CONCLUSION: Angiogenesis inhibitor TNP-470 might beeffective in treating peritoneal dissemination of colon cancerand improve the survival rate of nude mice.

  6. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

    Directory of Open Access Journals (Sweden)

    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  7. Differentiation between human normal colon mucosa and colon cancer tissue using ToF-SIMS imaging technique and principal component analysis

    Science.gov (United States)

    Park, Ji-Won; Shon, Hyun Kyong; Yoo, Byong Chul; Kim, In Hoo; Moon, Dae Won; Lee, Tae Geol

    2008-12-01

    Human normal colon mucosa and colon cancer tissue were studied using the time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and principal component analysis (PCA) techniques. The surfaces of the tissues were successfully cleaned by C 602+ cluster-ion beams before the ToF-SIMS images were obtained. A PCA on the spectra and images were performed to compare differences in the peaks and images of normal and cancer tissues. Significant differences in principal component 1 (PC 1) score values for normal and cancer tissues were observed, and each PC 1 loadings had a specific peak profile of proteins. In addition, the PC images obtained from the ToF-SIMS images for normal and cancer tissues were clearly distinguishable, and the amino acid fragments associated with normal and cancer tissues were found to have originated from the lamina propria region and the epithelium cells, respectively. Based on the PCA results, structural distortion of the crypts in the cancer colon tissue could be attributed to the proliferation of the cancerous epithelium cells. This work shows that the application of the ToF-SIMS imaging technique with PCA could be a useful method of obtaining valuable information for cancer analysis.

  8. Genetics of the pig tapeworm in madagascar reveal a history of human dispersal and colonization.

    Directory of Open Access Journals (Sweden)

    Tetsuya Yanagida

    Full Text Available An intricate history of human dispersal and geographic colonization has strongly affected the distribution of human pathogens. The pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serious neglected tropical diseases. Discrete genetic lineages of T. solium in Asia and Africa/Latin America are geographically disjunct; only in Madagascar are they sympatric. Linguistic, archaeological and genetic evidence has indicated that the people in Madagascar have mixed ancestry from Island Southeast Asia and East Africa. Hence, anthropogenic introduction of the tapeworm from Southeast Asia and Africa had been postulated. This study shows that the major mitochondrial haplotype of T. solium in Madagascar is closely related to those from the Indian Subcontinent. Parasitological evidence presented here, and human genetics previously reported, support the hypothesis of an Indian influence on Malagasy culture coinciding with periods of early human migration onto the island. We also found evidence of nuclear-mitochondrial discordance in single tapeworms, indicating unexpected cross-fertilization between the two lineages of T. solium. Analyses of genetic and geographic populations of T. solium in Madagascar will shed light on apparently rapid evolution of this organism driven by recent (<2,000 yr human migrations, following tens of thousands of years of geographic isolation.

  9. Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ke ZOU; Ji-hang JU; Hong XIE

    2007-01-01

    Aim: To investigate the effects of insulin on enhancing 5-fluorouracil (5-FU) anti-cancer functions and its mechanisms in the human esophageal cancer cell line (Eca 109) and human colonic cancer cell line (Ls-174-t). Methods: The effect of insulin/5-FU combination treatment on the growth of Eca 109 and Ls-174-t cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. After insulin treatment or insulin/5-FU treatment, cell cycle distri-bution of both cell lines was analyzed by flow cytometry. Western blot assay was used to assess the expression of caspase-3 and thymidylate synthase (TS).Apoptosis was detected by flow cytometry, DNA fragmentation assay, and termi-nal transferase dUTP nick end labeling assay (TUNEL). Moreover, the changes of 5-FU uptake after insulin pretreatment were detected by HPLC assay and Western blot analysis. Results: We found that insulin enhanced the inhibitory effect of 5-FU on cell proliferation when Eca 109 cells and Ls- 174-t cells were pretreated with insulin for the appropriate time. Insulin increased the cell number of the S phase and the uptake of 5-FU. Insulin/5-FU treatment enhanced apoptosis of tumor cells and upregulated the expression of cleaved caspase-3 compared with 5-FU treatment.Moreover, insulin/5-FU treatment induced the changes of free TS and the TS ternary complex level compared with 5-FU treatment in Eca 109 and Ls-174-t cells.Conclusion: These data suggest that insulin enhances anticancer functions of 5-FU when it is treated before 5-FU for the appropriate time in human esophageal and colonic cancer cell lines.

  10. Systematic analysis of human oncogenic viruses in colon cancer revealed EBV latency in lymphoid infiltrates.

    Science.gov (United States)

    Fiorina, Loretta; Ricotti, Mattia; Vanoli, Alessandro; Luinetti, Ombretta; Dallera, Elena; Riboni, Roberta; Paolucci, Stefania; Brugnatelli, Silvia; Paulli, Marco; Pedrazzoli, Paolo; Baldanti, Fausto; Perfetti, Vittorio

    2014-01-01

    Environmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results. We undertook a systematic DNA analysis of 44 consecutive, prospectively collected primary tumor samples by real time and qualitative PCR for viruses of known or potential oncogenic role in humans, including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and EBV. Negative controls consisted of surgical resection margins. No evidence of genomic DNA fragments from tested virus were detected, except for EBV, which was found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that EBV DNA was present at a highly variable content (median 258 copies in 10(5) cells, range 15-4837). Presence of EBV DNA had a trend to be associated with high lymphocyte infiltration (p = 0.06, χ2 test), and in situ hybridization with EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just a few scattered plasma cells positive for BZLF-1, an immediate early protein expressed during lytic replication. LMP-1 expression was undetectable by immunohistochemistry. These results argue against a significant involvement of the tested oncogenic viruses in established colon cancer.

  11. Escherichia albertii, a novel human enteropathogen, colonizes rat enterocytes and translocates to extra-intestinal sites

    Science.gov (United States)

    Yamamoto, Denise; Hernandes, Rodrigo T.; Liberatore, Ana Maria A.; Abe, Cecilia M.; de Souza, Rodrigo B.; Romão, Fabiano T.; Sperandio, Vanessa; Koh, Ivan H.

    2017-01-01

    Diarrhea is the second leading cause of death of children up to five years old in the developing countries. Among the etiological diarrheal agents are atypical enteropathogenic Escherichia coli (aEPEC), one of the diarrheagenic E. coli pathotypes that affects children and adults, even in developed countries. Currently, genotypic and biochemical approaches have helped to demonstrate that some strains classified as aEPEC are actually E. albertii, a recently recognized human enteropathogen. Studies on particular strains are necessary to explore their virulence potential in order to further understand the underlying mechanisms of E. albertii infections. Here we demonstrated for the first time that infection of fragments of rat intestinal mucosa is a useful tool to study the initial steps of E. albertii colonization. We also observed that an E. albertii strain can translocate from the intestinal lumen to Mesenteric Lymph Nodes and liver in a rat model. Based on our finding of bacterial translocation, we investigated how E. albertii might cross the intestinal epithelium by performing infections of M-like cells in vitro to identify the potential in vivo translocation route. Altogether, our approaches allowed us to draft a general E. albertii infection route from the colonization till the bacterial spreading in vivo. PMID:28178312

  12. γ-Tocotrienol induces paraptosis-like cell death in human colon carcinoma SW620 cells.

    Directory of Open Access Journals (Sweden)

    Jing-Shu Zhang

    Full Text Available Colorectal cancer is one of the most serious illnesses among diagnosed cancer. As a new type of anti-cancer composition from tocotrienol-rich fraction of palm oil, γ-tocotrienol is widely used in anti-cancer research. The objectives of this study were to investigate the effects of γ-tocotrienol on human colon cancer SW620 and HCT-8 cells. We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth. Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells. Real-time RT-PCR and western blot analyses showed that γ-tocotrienol inhibited the expression level of β-catenin, cyclin D1 and c-jun. These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

  13. Inhibitor of fatty acid synthase induced apoptosis in human colonic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Pei Lin Huang; Zhen Sheng Dai; Yue Lin Jin; Shi Neng Zhu; Shi Lun Lu

    2000-01-01

    @@INTRODUCTION The treatment of human epithelial malignancies is limited by drug resistance and toxic and side effects,which results in the failure in the treatment of majority of advanced cancer victims. To seek for a new, and specific antineoplastic therapy will provide hope for tumor treatment. Although disordered intermediary metabolism in cancer cells has been known for many years, much of the work focused on abnormal glucose catabolism. At the same time, little attention has been paid to fatty acid synthasis in tumor tissues, dispite of the significance of fatty acid synthase (FAS) in some clinical human ovarian[1], breast[2], colorectal[3],and prostatic cancers[4,5]. Tumor cells which express high levels of fatty acid synthesizing enzymes use endogeneously synthesized fatty acids for membrance biosynthesis and appear to export large amounts of lipid. In contrast, normal cells preferentially utilize diary lipid.

  14. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

    Science.gov (United States)

    Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

    2014-01-01

    Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Peroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

  15. α-TEA inhibits the growth and motility of human colon cancer cells via targeting RhoA/ROCK signaling.

    Science.gov (United States)

    Yao, Jialin; Gao, Peng; Xu, Yang; Li, Zhaozhu

    2016-09-01

    Colon or colorectal cancer is a common type of human cancer, which originates in the intestine crassum or the rectum. In the United States, colorectal cancer has one of the highest rates of cancer‑related mortality. Investigating novel chemotherapeutic approaches is significant in the treatment of cancers, such as colorectal cancer. α-tocopherol ether-linked acetic acid (α-TEA) is a potent anticancer agent in multiple types of human cancer. However, its effect remains to be determined in colon cancer. In this study, HCT116 and SW480 human colon cancer cells were used to investigate the anticancer role of α-TEA. It was demonstrated that α-TEA inhibited cell proliferation, migration and invasion in colon cancer cells. Furthermore, it was shown that α-TEA downregulated the activity of RhoA and phosphorylated Rho-associated protein kinase (ROCK) substrate myosin light chain (MLC) using a pull-down assay and western blotting, respectively, implying that the RhoA/ROCK pathway is involved in α-TEA-mediated cell growth and motility inhibition. In order to confirm this hypothesis a RhoA inhibitor (clostridium botulinum C3 exoenzyme), a ROCK inhibitor (Y27632) and RhoA small interfering (si)RNA were applied to block RhoA/ROCK signaling. This resulted in the attenuation of MLC phosphorylation, and augmentation of α-TEA-mediated growth and motility inhibition in colon cancer cells. In conclusion, these results indicate that α-TEA inhibits growth and motility in colon cancer cells possibly by targeting RhoA/ROCK signaling. Moreover, combined with RhoA or ROCK inhibitors, α-TEA may exhibit a more effective inhibitory role in colon cancer.

  16. Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Khanitta Srimuangwong; Chainarong Tocharus; Pornphrom Yoysungnoen Chintana; Apichart Suksamrarn; Jiraporn Tocharus

    2012-01-01

    AIM:To investigate the ability of hexahydrocurcumin (HHC) to enhance 5-fluorouracil (5-FU) in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase (COX)-2 expression.METHODS:Antiproliferative effects of HHC and 5-FU,alone and in combination,on growth of HT-29 human colon cancer cells were assessed using 5-diphenyltetrazolium bromide (MTT) reduction assay.In combination treatment,low doses of 5-FU were used combined with various concentrations of HHC to minimize the toxicity and side effects of 5-FU.The therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein expression were examined using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis.RESULTS:MTT reduction assay indicated that HHC alone markedly decreased the viability of HT-29 human colon cancer cells compared to control.Semi-quantitative RT-PCR analysis indicated that HHC is a selective COX-2 inhibitor.This finding was supported by the observation that HHC significantly down-regulates COX-2 mRNA expression compared to the control (control:100.05% ± 0.03% vs HHC:61.01% ± 0.35%,P < 0.05)but does not alter COX-1 mRNA.In combined treatment,addition of HHC to a low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by markedly reducing cell viability to a greater degree than monotherapy.Semi-quantitative RT-PCR indicated that 5-FU at the concentration of 5 μmol/L in combination with HHC at the concentration of 25 μmol/L significantly down-regulates COX-2 mRNA expression when compared with values in cells treated with 5-FU or HHC alone (HHC + 5-FU:31.93% ± 5.69%,5-FU:100.66%± 4.52% vs HHC:61.01% ± 0.35%,P < 0.05).CONCLUSION:HHC together with 5-FU exerts a synergistic effect and may prove chemotherapeutically useful in treating human colon cancer.

  17. Can we colonize the solar system? Human biology and survival in the extreme space environment.

    Science.gov (United States)

    Launius, Roger D

    2010-09-01

    Throughout the history of the space age the dominant vision for the future has been great spaceships plying the solar system, and perhaps beyond, moving living beings from one planet to another. Spacesuited astronauts would carry out exploration, colonization, and settlement as part of a relentlessly forward looking movement of humanity beyond Earth. As time has progressed this image has not changed appreciably even as the full magnitude of the challenges it represents have become more and more apparent. This essay explores the issues associated with the human movement beyond Earth and raises questions about whether humanity will ever be able to survive in the extreme environment of space and the other bodies of the solar system. This paper deals with important historical episodes as well as wider conceptual issues about life in space. Two models of expansion beyond Earth are discussed: (1) the movement of microbes and other types of life on Earth that can survive the space environment and (2) the modification of humans into cyborgs for greater capability to survive in the extreme environments encountered beyond this planet.

  18. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

    Science.gov (United States)

    Ritter, G; Cohen, L S; Williams, C; Richards, E C; Old, L J; Welt, S

    2001-09-15

    Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.

  19. Anti-proliferative effect of a compound isolated from Cassia auriculata against human colon cancer cell line HCT 15.

    Science.gov (United States)

    Esakkirajan, M; Prabhu, N M; Arulvasu, C; Beulaja, M; Manikandan, R; Thiagarajan, R; Govindaraju, K; Prabhu, D; Dinesh, D; Babu, G; Dhanasekaran, G

    2014-01-01

    The compound was isolated from leaves of Cassia auriculata and its structure was characterized using high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology and lactate dehydrogenase assay of isolated compound was tested against human colon cancer cell line HCT 15. The isolated compound, 4-(4-chlorobenzyl)-2,3,4,5,6,7-hexahydro-7-(2-ethoxyphenyl)benzo[h][1,4,7]triazecin-8(1H)-one at 25μg/ml concentration and by 48h showed 50% inhibition of human colon cancer cells (HCT 15). The results suggest that isolated compound from C. auriculata has potential to prevent colon cancer cell line.

  20. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.

    Science.gov (United States)

    Barr, L; Metaxas, G; Harbach, C A J; Savoy, L A; Darbre, P D

    2012-03-01

    The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).

  1. E durans strain M4-5 isolated from human colonic flora attenuates intestinal inflammation

    DEFF Research Database (Denmark)

    Avram-Hananel, Liraz; Stock, Julia; Parlesak, Alexandr;

    2010-01-01

    effects, mediated by regulation of pro- and anti-inflammatory immune factors as well as preservation of intestine epithelial integrity, suggesting that this novel anti-inflammatory bacterium may be preferentially a useful prophylactic treatment to avoid inflammatory bowel disease.......PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model...... was used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia coli-stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-α) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used...

  2. Candida albicans is not always the preferential yeast colonizing humans: a study in Wayampi Amerindians.

    Science.gov (United States)

    Angebault, Cécile; Djossou, Félix; Abélanet, Sophie; Permal, Emmanuelle; Ben Soltana, Mouna; Diancourt, Laure; Bouchier, Christiane; Woerther, Paul-Louis; Catzeflis, François; Andremont, Antoine; d'Enfert, Christophe; Bougnoux, Marie-Elisabeth

    2013-11-15

    In industrialized countries Candida albicans is considered the predominant commensal yeast of the human intestine, with approximately 40% prevalence in healthy adults. We discovered a highly original colonization pattern that challenges this current perception by studying in a 4- year interval a cohort of 151 Amerindians living in a remote community (French Guiana), and animals from their environment. The prevalence of C. albicans was persistently low (3% and 7% of yeast carriers). By contrast, Candida krusei and Saccharomyces cerevisiae were detected in over 30% of carriers. We showed that C. krusei and S. cerevisiae carriage was of food or environmental origin, whereas C. albicans carriage was associated with specific risk factors (being female and living in a crowded household). We also showed using whole-genome sequence comparison that C. albicans strains can persist in the intestinal tract of a healthy individual over a 4-year period.

  3. Effects of inositol hexaphosphate on proliferation of HT-29 human colon carcinoma cell line

    Science.gov (United States)

    Tian, Ying; Song, Yang

    2006-01-01

    AIM: To investigate the effects of inositol hexaphosphate (IP6) on proliferation of HT-29 human colon carcinoma cell line. METHODS: Cells were exposed to various concen-trations (0, 1.8, 3.3, 5.0, 8.0, 13.0 mmol/L) of IP6 for a certain period of time. Its effect on growth of HT-29 cells was measured by MTT assay. The expressions of cell cycle regulators treated with IP6 for 2 d were detected by immunocytochemistry. RESULTS: IP6 inhibited the HT-29 cell growth in a dose- and time-dependent manner. Analysis of cell cycle regulator expression revealed that IP6 reduced the abnormal expression of P53 and PCNA and induced the expression of P21. CONCLUSION: IP6 has potent inhibitory effect on proliferation of HT-29 cells by modulating the expression of special cell cycle regulators. PMID:16830361

  4. Effects of inositol hexaphosphate on proliferation of HT-29 human colon carcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    Ying Tian; Yang Song

    2006-01-01

    AIM: To investigate the effects of inositol hexaphosphate (IP6) on proliferation of HT-29 human colon carcinoma cell line.METHODS: Cells were exposed to various concentrations (0, 1.8, 3.3, 5.0, 8.0, 13.0 mmol/L) of IP6 for a certain period of time. Its effect on growth of HT-29 cells was measured by MTT assay. The expressions of cell cycle regulators treated with IP6 for 2 d were detected by immunocytochemistry.RESULTS: IP6 inhibited the HT-29 cell growth in a dose- and time-dependent manner. Analysis of cell cycle regulator expression revealed that IP6 reduced the abnormal expression of P53 and PCNA and induced the expression of P21.CONCLUSION: IP6 has potent inhibitory effect on proliferation of HT-29 cells by modulating the expression of special cell cycle regulators.

  5. Temporal Changes of Human Breast Milk Lipids of Chinese Mothers

    Directory of Open Access Journals (Sweden)

    Francesca Giuffrida

    2016-11-01

    Full Text Available Fatty acids (FA, phospholipids (PL, and gangliosides (GD play a central role in infant growth, immune and inflammatory responses. The aim of this study was to determine FA, PL, and GD compositional changes in human milk (HM during lactation in a large group of Chinese lactating mothers (540 volunteers residing in Beijing, Guangzhou, and Suzhou. HM samples were collected after full expression from one breast and while the baby was fed on the other breast. FA were assessed by direct methylation followed by gas chromatography (GC analysis. PL and GD were extracted using chloroform and methanol. A methodology employing liquid chromatography coupled with an evaporative light scattering detector (ELSD and with time of flight (TOF mass spectrometry was used to quantify PL and GD classes in HM, respectively. Saturated FA (SFA, mono-unsaturated FA (MUFA, and PL content decreased during lactation, while polyunsaturated FA (PUFA and GD content increased. Among different cities, over the lactation time, HM from Beijing showed the highest SFA content, HM from Guangzhou the highest MUFA content and HM from Suzhou the highest n-3PUFA content. The highest total PL and GD contents were observed in HM from Suzhou. In order to investigate the influence of the diet on maternal milk composition, a careful analyses of dietary habits of these population needs to be performed in the future.

  6. Expression of Axl and its prognostic significance in human breast cancer

    OpenAIRE

    Jin, Gaoyuan; Wang, Zhenzhen; Wang, Jianguang; Zhang, Like; CHEN Yanbin; Yuan, Pengfei; Liu, Dechun

    2016-01-01

    Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 ...

  7. Siah1 proteins enhance radiosensitivity of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Engenhart-Cabillic Rita

    2010-08-01

    Full Text Available Abstract Background Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1ΔR on radiosensitization of human breast cancer cells. Methods The status of Siah1 and Siah1L was analysed in five breast cancer cell lines. To establish stable cells, SKBR3 cells were transfected with Siah1, Siah-1L and Siah1ΔR. Siah1 function was suppressed by siRNA in MCF-7 cells. The impact of Siah1 overexpression and silencing on apoptosis, proliferation, survival, invasion ability and DNA repair was assessed in SKBR3 and MCF-7 cells, also in regards to radiation. Results Siah1 and Siah1L mRNA expression was absent in four of five breast cancer cells lines analysed. Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable transfected SKBR3 cells, while Siah1ΔR failed to show this effect. In addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and 4.0 for clonogenic survival and proliferation, respectively, pointing to a highly cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells. Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred by increased levels of DNA double-strand breaks in irradiated SKBR3 cells. Conclusion Our results reveal for the first time how overexpression of Siah1L and Siah1 can determine radiosensitivity of breast cancer cells. These findings suggest that development of drugs augmenting Siah1 and Siah1L activity could be a novel approach in improving tumor cell kill.

  8. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing, E-mail: wangstella5@163.com [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Yang, Qifeng, E-mail: qifengy@gmail.com [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Haffty, Bruce G., E-mail: hafftybg@umdnj.edu [Department of Radiation Oncology, UMDNJ-Robert Wood Johnson School of Medicine, Cancer Institute of New Jersey, NB (United States); Li, Xiaoyan, E-mail: xiaoyanli1219@gmail.com [Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Moran, Meena S., E-mail: meena.moran@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2013-02-08

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  9. Effects of menthol on circular smooth muscle of human colon: analysis of the mechanism of action.

    Science.gov (United States)

    Amato, Antonella; Liotta, Rosa; Mulè, Flavia

    2014-10-05

    Menthol is the major constituent of peppermint oil, an herbal preparation commonly used to treat nausea, spasms during colonoscopy and irritable bowel disease. The mechanism responsible for its spasmolytic action remains unclear. The aims of this study were to investigate the effects induced by menthol on the human distal colon mechanical activity in vitro and to analyze the mechanism of action. The spontaneous or evoked-contractions of the circular smooth muscle were recorded using vertical organ bath. Menthol (0.1 mM-30 mM) reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. The inhibitory effect was not affected by 5-benzyloxytryptamine (1 μM), a transient receptor potential-melastatin8 channel antagonist, or tetrodotoxin (1 μM), a neural blocker, or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (10 µM), inhibitor of nitric oxide (NO)-sensitive soluble guanylyl cyclase, or tetraethylammonium (10 mM), a blocker of potassium (K+)-channels. On the contrary, nifedipine (3 nM), a voltage-activated L-type Ca2+ channel blocker, significantly reduced the inhibitory menthol actions. Menthol also reduced in a concentration-dependent manner the contractile responses caused by exogenous application of Ca2+ (75-375 μM) in a Ca2+-free solution, or induced by potassium chloride (KCl; 40 mM). Moreover menthol (1-3 mM) strongly reduced the electrical field stimulation (EFS)-evoked atropine-sensitive contractions and the carbachol-contractile responses. The present results suggest that menthol induces spasmolytic effects in human colon circular muscle inhibiting directly the gastrointestinal smooth muscle contractility, through the block of Ca2+ influx through sarcolemma L-type Ca2+ channels.

  10. High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.

    Science.gov (United States)

    O'Neill, Ann Marie; Burrington, Christine M; Gillaspie, Erin A; Lynch, Darin T; Horsman, Melissa J; Greene, Michael W

    2016-12-01

    Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1(tm1Mom) mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells.

    Science.gov (United States)

    Jung, Soo-A; Lee, Dae-Hee; Moon, Jai-Hee; Hong, Seung-Woo; Shin, Jae-Sik; Hwang, Ih Yeon; Shin, Yu Jin; Kim, Jeong Hee; Gong, Eun-Yeung; Kim, Seung-Mi; Lee, Eun Young; Lee, Seul; Kim, Jeong Eun; Kim, Kyu-Pyo; Hong, Yong Sang; Lee, Jung Shin; Jin, Dong-Hoon; Kim, TaeWon; Lee, Wang Jae

    2016-06-01

    Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor, which is an effective clinical therapy for patients with wild-type KRAS. Numerous combinatorial therapies have been tested to overcome the resistance to cetuximab. However, no combinations have been found that can be used as effective therapeutic strategies. In this study, we demonstrate that L-ascorbic acid partners with cetuximab to induce killing effects, which are influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human colon cancer cells with a mutant KRAS. L-Ascorbic acid treatment of human colon cancer cells that express a mutant KRAS differentially and synergistically induced cell death with cetuximab in a SVCT-2-dependent manner. The ectopic expression of SVCT-2 induced sensitivity to L-ascorbic acid treatment in human colon cancer cells that do not express SVCT-2, whereas the knockdown of endogenous SVCT-2 induced resistance to L-ascorbic acid treatment in SVCT-2-positive cells. Moreover, tumor regression via the administration of L-ascorbic acid and cetuximab in mice bearing tumor cell xenografts corresponded to SVCT-2 protein levels. Interestingly, cell death induced by the combination of L-ascorbic acid and cetuximab resulted in both apoptotic and necrotic cell death. These cell death mechanisms were related to a disruption of the ERK pathway and were represented by the impaired activation of RAFs and the activation of the ASK-1-p38 pathway. Taken together, these results suggest that resistance to cetuximab in human colon cancer patients with a mutant KRAS can be bypassed by L-ascorbic acid in an SVCT-2-dependent manner. Furthermore, SVCT-2 in mutant KRAS colon cancer may act as a potent marker for potentiating L-ascorbic acid co-treatment with cetuximab.

  12. Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Wang; Fan-Rong Qiu; Guo-Zhen Liu; Rui-Fen Chen

    2005-01-01

    AIM: To investigate the correlation between dinicopathology and expression of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human colonic carcinoma.METHODS: The expression of HSP70 and grp94 was studied in 80 human colonic cancers with or without metastasis as well as in their adjacent mucous membrane by way of immunohistochemistry and pathology photograph analysis.RESULTS: The expression of HSP70 and grp94 was significantly higher in cancer than that in adjacent mucous membrane (92.5%, 85.0% vs 56.3%, 42.5%, P<0.01).HSP70 and grp94 expressed higher in moderately- and poorly-differentiated colonic cancers than that in their adjacent tissues (93.7%, 87.5%; 100%, 90% vs 56.3%,42.5%; P<0.01). Dukes C and D stages of colonic cancers showed higher positive rates than Dukes A and B stage groups (97.1%, 91.2%; 100%, 90.9%; vs 80%, 70%;78.6%, 71.4%; P<0.05). There were definite differences in HSP70 and grp94 expression between metastasis groups and non-metastasis groups (100% vs75%, 100%vs 50%, P<0.05).CONCLUSION: The HSP70 and grp94 expression rates in colonic cancer groups are significantly higher than that in their adjacent mucous membrane. The HSP70 and grp94expression in poorly-differentiated colonic cancers with metastasis is significantly higher than well-differentiated cancers without metastasis. The overexpression of HSP70and grp94 can be used as diagnostic or prognostic markers for colonic cancer.

  13. Lactose in human breast milk an inducer of innate immunity with implications for a role in intestinal homeostasis.

    Science.gov (United States)

    Cederlund, Andreas; Kai-Larsen, Ylva; Printz, Gordana; Yoshio, Hiroyuki; Alvelius, Gunvor; Lagercrantz, Hugo; Strömberg, Roger; Jörnvall, Hans; Gudmundsson, Gudmundur H; Agerberth, Birgitta

    2013-01-01

    Postpartum, infants have not yet established a fully functional adaptive immune system and are at risk of acquiring infections. Hence, newborns are dependent on the innate immune system with its antimicrobial peptides (AMPs) and proteins expressed at epithelial surfaces. Several factors in breast milk are known to confer immune protection, but which the decisive factors are and through which manner they work is unknown. Here, we isolated an AMP-inducing factor from human milk and identified it by electrospray mass spectrometry and NMR to be lactose. It induces the gene (CAMP) that encodes the only human cathelicidin LL-37 in colonic epithelial cells in a dose- and time-dependent manner. The induction was suppressed by two different p38 antagonists, indicating an effect via the p38-dependent pathway. Lactose also induced CAMP in the colonic epithelial cell line T84 and in THP-1 monocytes and macrophages. It further exhibited a synergistic effect with butyrate and phenylbutyrate on CAMP induction. Together, these results suggest an additional function of lactose in innate immunity by upregulating gastrointestinal AMPs that may lead to protection of the neonatal gut against pathogens and regulation of the microbiota of the infant.

  14. Lactose in human breast milk an inducer of innate immunity with implications for a role in intestinal homeostasis.

    Directory of Open Access Journals (Sweden)

    Andreas Cederlund

    Full Text Available Postpartum, infants have not yet established a fully functional adaptive immune system and are at risk of acquiring infections. Hence, newborns are dependent on the innate immune system with its antimicrobial peptides (AMPs and proteins expressed at epithelial surfaces. Several factors in breast milk are known to confer immune protection, but which the decisive factors are and through which manner they work is unknown. Here, we isolated an AMP-inducing factor from human milk and identified it by electrospray mass spectrometry and NMR to be lactose. It induces the gene (CAMP that encodes the only human cathelicidin LL-37 in colonic epithelial cells in a dose- and time-dependent manner. The induction was suppressed by two different p38 antagonists, indicating an effect via the p38-dependent pathway. Lactose also induced CAMP in the colonic epithelial cell line T84 and in THP-1 monocytes and macrophages. It further exhibited a synergistic effect with butyrate and phenylbutyrate on CAMP induction. Together, these results suggest an additional function of lactose in innate immunity by upregulating gastrointestinal AMPs that may lead to protection of the neonatal gut against pathogens and regulation of the microbiota of the infant.

  15. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Klijn Jan GM

    2009-07-01

    Full Text Available Abstract Background Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Methods Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. Results The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. Conclusion The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines.

  16. Utility of CK7 and CK20 immunohistochemistry in the detection of synchronous breast and colon carcinoma in a pleural effusion: a case report and supporting survey of archival material

    DEFF Research Database (Denmark)

    Stopyra, G A; Warhol, M J; Multhaupt, H A

    2001-01-01

    which demonstrated two strikingly different populations of malignant cells by immunohistochemical study of cell block material. One cell population demonstrated a cytokeratin (CK)7+/CK20-/ER+ phenotype, while the other demonstrated a CK7-/CK20+/ER- phenotype, consistent with breast and colon origin...

  17. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  18. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer.

    Science.gov (United States)

    Cotter, Kristina; Liberman, Rachel; Sun-Wada, GeHong; Wada, Yoh; Sgroi, Dennis; Naber, Stephen; Brown, Dennis; Breton, Sylvie; Forgac, Michael

    2016-07-19

    The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that acidify intracellular compartments and transport protons across the plasma membrane. Previous work has demonstrated that plasma membrane V-ATPases are important for breast cancer invasion in vitro and that the V-ATPase subunit a isoform a3 is upregulated in and critical for MDA-MB231 and MCF10CA1a breast cancer cell invasion. It has been proposed that subunit a3 is present on the plasma membrane of invasive breast cancer cells and is overexpressed in human breast cancer. To test this, we used an a3-specific antibody to assess localization in breast cancer cells. Subunit a3 localizes to the leading edge of migrating breast cancer cells, but not the plasma membrane of normal breast epithelial cells. Furthermore, invasive breast cancer cells express a3 throughout all intracellular compartments tested, including endosomes, the Golgi, and lysosomes. Moreover, subunit a3 knockdown in MB231 breast cancer cells reduces in vitro migration. This reduction is not enhanced upon addition of a V-ATPase inhibitor, suggesting that a3-containing V-ATPases are critical for breast cancer migration. Finally, we have tested a3 expression in human breast cancer tissue and mRNA prepared from normal and cancerous breast tissue. a3 mRNA was upregulated 2.5-47 fold in all breast tumor cDNA samples tested relative to normal tissue, with expression generally correlated to cancer stage. Furthermore, a3 protein expression was increased in invasive breast cancer tissue relative to noninvasive cancer and normal breast tissue. These studies suggest that subunit a3 plays an important role in invasive human breast cancer.

  19. The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

    OpenAIRE

    James Ryan; Curran, Catherine E.; Emer Hennessy; John Newell; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M

    2011-01-01

    INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), t...

  20. Role of cytokines in promoting immune escape of FasL-expressing human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Tong Xu; Bao-Cun Sun; Qiang Li; Xi-Shan Hao

    2005-01-01

    -cultured with the Jurkat T lymphocytes. The cytotoxicity was significantly enhancedby PMA+ionomycin or TNF-α.CONCLUSION: The FasL expressed in human colon cancer cells may be regulated by endogenous factors in the microenvironment of the host and facilitate the escape of tumor cells from the host immune system.

  1. Complete Genome Sequences of Two Methicillin-Sensitive Staphylococcus aureus Isolates Representing a Population Subset Highly Prevalent in Human Colonization

    Science.gov (United States)

    Weber, Robert E.; Layer, Franziska; Fuchs, Stephan; Bender, Jennifer K.; Fiedler, Stefan; Werner, Guido

    2016-01-01

    Here, we report the high-quality draft genome sequences of two methicillin-susceptible Staphylococcus aureus isolates, 08-02119 and 08-02300. Belonging to sequence type 582 (ST582) and ST7, both isolates are representatives of clonal lineages often associated with asymptomatic colonization of humans. PMID:27469954

  2. New model of in-situ xenograft lymphangiogenesis by a human colonic adenocarcinoma cell line in nude mice.

    Science.gov (United States)

    Sun, Jian-Jun; Jing, Wei; Ni, Yan-Yan; Yuan, Xiao-Jian; Zhou, Hai-Hua; Fan, Yue-Zu

    2012-01-01

    To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenografts in-situ than in the negative control group (both Pconformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

  3. Deciphering the Colon Cancer Genes-Report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010

    NARCIS (Netherlands)

    Kohonen-Corish, Maija R. J.; Macrae, Finlay; Genuardi, Maurizio; Aretz, Stefan; Bapat, Bharati; Bernstein, Inge T.; Burn, John; Cotton, Richard G. H.; den Dunnen, Johan T.; Frebourg, Thierry; Greenblatt, Marc S.; Hofstra, Robert; Holinski-Feder, Elke; Lappalainen, Ilkka; Lindblom, Annika; Maglott, Donna; Moller, Pal; Morreau, Hans; Moeslein, Gabriela; Sijmons, Rolf; Spurdle, Amanda B.; Tavtigian, Sean; Tops, Carli M. J.; Weber, Thomas K.; de Wind, Niels; Woods, Michael O.

    2011-01-01

    The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP Integrat

  4. Livestock-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) as Causes of Human Infection and Colonization in Germany

    NARCIS (Netherlands)

    Koeck, Robin; Schaumburg, Frieder; Mellmann, Alexander; Koeksal, Mahir; Jurke, Annette; Becker, Karsten; Friedrich, Alexander W.

    2013-01-01

    Pigs, cattle and poultry are colonized with MRSA and the zoonotic transmission of such MRSA to humans via direct animal contact, environmental contaminations or meat are a matter of concern. Livestock-associated (LA) MRSA are mostly belonging to clonal complex (CC) 398 as defined by multilocus seque

  5. The Effect of Various Inulins and Clostridium difficile on the Metabolic Activity of the Human Colonic Microbiota in vitro

    NARCIS (Netherlands)

    Nuenen, M.H.M.C. van; Meyer, P.D.; Venema, K.

    2003-01-01

    The influence of inulins with different average degree of polymerization (ranging from 3 to 25) on the metabolic activity of the human colonic microbiota with or without the addition of Clostridium difficile was investigated in vitro. The in vitro system used was a dynamic, computer-controlled model

  6. Regulation of deleted in liver cancer-1 gene domains on the proliferation of human colon cancer HT29 cell

    Institute of Scientific and Technical Information of China (English)

    吴平平

    2013-01-01

    Objective To study the role of deleted in liver cancer-1(DLC-1) gene main domains on the regulation of hu-man colon cancer HT29 cell proliferation. Methods Subcloning recombinant plasmid vectors with Rho GTPase activating protein(RhoGAP),sterile alpha motif(SAM)

  7. The Effect of Various Inulins and Clostridium difficile on the Metabolic Activity of the Human Colonic Microbiota in vitro

    NARCIS (Netherlands)

    Nuenen, M.H.M.C. van; Meyer, P.D.; Venema, K.

    2003-01-01

    The influence of inulins with different average degree of polymerization (ranging from 3 to 25) on the metabolic activity of the human colonic microbiota with or without the addition of Clostridium difficile was investigated in vitro. The in vitro system used was a dynamic, computer-controlled model

  8. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation.

    Science.gov (United States)

    Duo, Jian; Ying, Guo-Guang; Wang, Guo-Wen; Zhang, Li

    2012-06-01

    Breast cancer is a disease in which cancer cells form in the tissues of the breast. The present study aimed to explore the effect of the flavonoid compound quercetin on the growth and apoptosis of human breast cancer cells. Varying concentrations (12.5, 25, 50, 100, 200 µM) of quercetin were applied to cultured MCF-7 human breast cancer cells for defined lengths of time. At 50 to 200 µM doses, quercetin significantly inhibited the proliferation of MCF-7 cells assessed by MTT colorimetry, in both dose- and time-dependent manners (Papoptosis after 48 h of exposure (Pquercetin treatment Bcl-2 expression decreased significantly while Bax expression increased significantly (Pquercetin inhibits cell growth and induces apoptosis in MCF-7 human breast cancer cells. The mechanisms behind these effects may stem from the downregulation of Bcl-2 protein expression and upregulation of Bax expression.

  9. The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue.

    Science.gov (United States)

    Thibeaux, Roman; Avé, Patrick; Bernier, Michèle; Morcelet, Marie; Frileux, Pascal; Guillén, Nancy; Labruyère, Elisabeth

    2014-10-07

    Intestinal invasion by the protozoan parasite Entamoeba histolytica is characterized by remodelling of the extracellular matrix (ECM). The parasite cysteine proteinase A5 (CP-A5) is thought to cooperate with human matrix metalloproteinases (MMPs) involved in ECM degradation. Here, we investigate the role CP-A5 plays in the regulation of MMPs upon mucosal invasion. We use human colon explants to determine whether CP-A5 activates human MMPs. Inhibition of the MMPs' proteolytic activities abolishes remodelling of the fibrillar collagen structure and prevents trophozoite invasion of the mucosa. In the presence of trophozoites, MMPs-1 and -3 are overexpressed and are associated with fibrillar collagen remodelling. In vitro, CP-A5 performs the catalytic cleavage needed to activate pro-MMP-3, which in turn activates pro-MMP-1. Ex vivo, incubation with recombinant CP-A5 was enough to rescue CP-A5-defective trophozoites. Our results suggest that MMP-3 and/or CP-A5 inhibitors may be of value in further studies aiming to treat intestinal amoebiasis.

  10. Specific binding of benzodiazepines to human breast cancer cell lines.

    Science.gov (United States)

    Beinlich, A; Strohmeier, R; Kaufmann, M; Kuhl, H

    1999-01-01

    Binding of [3H]Ro5-4864, a peripheral benzodiazepine receptor (PBR) agonist, to BT-20 human, estrogen- (ER) and progesterone- (PR) receptor negative breast cancer cells was characterized. It was found to be specific, dose-dependent and saturable with a single population of binding sites. Dissociation constant (K(D)) was 8.5 nM, maximal binding capacity (Bmax) 339 fM/10(6) cells. Ro5-4864 (IC50 17.3 nM) and PK 11195 (IC50 12.3 nM) were able to compete with [3H]Ro5-4864 for binding, indicating specificity of interaction with PBR. Diazepam was able to displace [3H]Ro5-4864 from binding only at high concentrations (>1 microM), while ODN did not compete for PBR binding. Thymidine-uptake assay showed a biphasic response of cell proliferation. While low concentrations (100 nM) of Ro5-4864, PK 11195 and diazepam increased cell growth by 10 to 20%, higher concentrations (10-100 microM) significantly inhibited cell proliferation. PK 11195, a potent PBR ligand, was able to attenuate growth of BT-20 cells stimulated by 100 nM Ro5-4864 and to reverse growth reduction caused by 1 and 10 microM Ro5-4864, but not by 50 microM and 100 microM. This indicates that the antimitotic activity of higher concentrations of Ro5-4864 is independent of PBR binding. It is suggested, that PBR are involved in growth regulation of certain human breast cancer cell lines, possibly by supplying proliferating cells with energy, as their endogenous ligand is a polypeptide transporting Acyl-CoA.

  11. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  12. Human Progesterone A-Form as a Target for New Drug Discovery in Human Breast Cancer

    Science.gov (United States)

    2001-07-01

    Voltz et al’(ii 3 altered recycling, and impaired regulation of the PDGFR TR4 chloride transporter by hormones. Most recent studies suggest that CFTR ...growth transporters, and other proteins localized at or near the factor receptor and ion transporters such as CFTR , plasma membrane. Consistent with this...overexpression in human breast cancers cytoskeleton. This review will focus on the signaling and mutations in NHERF targets, such as CFTR and paradigms

  13. Garcinia benzophenones inhibit the growth of human colon cancer cells and synergize with sulindac sulfide and turmeric.

    Science.gov (United States)

    Einbond, Linda Saxe; Mighty, Jason; Kashiwazaki, Ryota; Figueroa, Mario; Jalees, Filza; Acuna, Ulyana Munoz; Le Gendre, Onica; Foster, David A; Kennelly, Edward J

    2013-12-01

    Previous studies indicate that extracts and purified components from Garcinia species inhibit the growth of human colon cancer cells. Garcinia benzophenones activate the expression of genes in the endoplasmic reticulum and cellular energy stress (mTOR) pathways. This study examines the growth inhibitory and synergistic effects of Garcinia benzophenones, alone or combined with chemopreventive agents, on human colon cancer cells. To find optimal combination treatments, HT29 colon cancer cells were treated with benzophenones alone, or combined with chemopreventive agents, and cell growth measured using the MTT assay. To reveal effects on signaling pathways, we assessed effects of the MEK inhibitor U0126 and the ER IP3 receptor antagonist heparin, as well as effects on the phosphorylation of 4E-BP-1 (mTOR pathway), using Western blot analysis. New and known benzophenones from Garcinia intermedia inhibited the growth of human colon cancer cells; an alcohol extract of Garcinia xanthochymus, as well as purified guttiferones (guttiferone E and xanthochymol), preferentially inhibited the growth of colon cancer versus nonmalignant intestinal epithelial cells. Guttiferone E exhibited synergy with the NSAID sulindac sulfide and xanthochymol, with the spice turmeric. Guttiferone A did not alter phosphorylation of 4E-BP-1, indicating that the mTORC1 pathway is not involved in its action. The effects of xanthochymol were enhanced by U0126, at low doses, and were blocked by heparin, indicating that the MEK pathway is involved, while the ER IP3 receptor is critical for its action. These studies indicate the potential of benzophenones, alone or combined with sulindac sulfide or turmeric, to prevent and treat colon cancer.

  14. DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast

    NARCIS (Netherlands)

    Graham, J. Dinny; Mote, Patricia A.; Salagame, Usha; van Dijk, Jessica H.; Balleine, Rosemary L.; Huschtscha, Lily I.; Reddel, Roger R.; Clarke, Christine L.

    2009-01-01

    Proliferation in the nonpregnant human breast is highest in the luteal phase of the menstrual cycle when serum progesterone levels are high, and exposure to progesterone analogues in hormone replacement therapy is known to elevate breast cancer risk, yet the proliferative effects of progesterone in

  15. The nude mouse as an in vivo model for human breast cancer invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Boysen, B; Rømer, J;

    1993-01-01

    Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains...

  16. Effects of Down-regulation of Integrin-β_1 Expression on Migration and Hepatic Metastasis of Human Colon Carcinoma

    Institute of Scientific and Technical Information of China (English)

    张建立; 高军; 谭晓杰; 王敏; 秦仁义

    2010-01-01

    Organ-specific tumor cell adhesion to extracellular matrix (ECM) components and cell migration into host organs often involve integrin-mediated cellular processes. Direct integrin-mediated cell adhesion to ECM components in the space of Disse appears to be required for the successful liver metastatic formation of colon cancer. In the present study, human colon cancer HT-29 cells were transfected by liposome with integrin-β1 antisense oligodeoxynucleotide (ASODN). The integrin-β1 gene expression in HT-29 cel...

  17. Multivariate meta-analysis of proteomics data from human prostate and colon tumours

    Directory of Open Access Journals (Sweden)

    Lehtiö Janne

    2010-09-01

    Full Text Available Abstract Background There is a vast need to find clinically applicable protein biomarkers as support in cancer diagnosis and tumour classification. In proteomics research, a number of methods can be used to obtain systemic information on protein and pathway level on cells and tissues. One fundamental tool in analysing protein expression has been two-dimensional gel electrophoresis (2DE. Several cancer 2DE studies have reported partially redundant lists of differently expressed proteins. To be able to further extract valuable information from existing 2DE data, the power of a multivariate meta-analysis will be evaluated in this work. Results We here demonstrate a multivariate meta-analysis of 2DE proteomics data from human prostate and colon tumours. We developed a bioinformatic workflow for identifying common patterns over two tumour types. This included dealing with pre-processing of data and handling of missing values followed by the development of a multivariate Partial Least Squares (PLS model for prediction and variable selection. The variable selection was based on the variables performance in the PLS model in combination with stability in the validation. The PLS model development and variable selection was rigorously evaluated using a double cross-validation scheme. The most stable variables from a bootstrap validation gave a mean prediction success of 93% when predicting left out test sets on models discriminating between normal and tumour tissue, common for the two tumour types. The analysis conducted in this study identified 14 proteins with a common trend between the tumour types prostate and colon, i.e. the same expression profile between normal and tumour samples. Conclusions The workflow for meta-analysis developed in this study enabled the finding of a common protein profile for two malign tumour types, which was not possible to identify when analysing the data sets separately.

  18. Anticancer activity of Nelumbo nucifera stamen extract in human colon cancer HCT-116 cells in vitro

    Science.gov (United States)

    Zhao, Xin; Feng, Xia; Wang, Cun; Peng, Deguang; Zhu, Kai; Song, Jia-Le

    2017-01-01

    The aim of the present study was to investigate the anticancer activities of Nelumbo nucifera (Ba lotus) stamen ethanol crude extract (BLSEE) in human colon carcinoma HCT-116 cells. MTT assay, flow cytometry analysis and reverse transcription-polymerase chain reaction assay were employed to investigate the anticancer mechanisms of BLSEE (100, 200 and 400 µg/ml) in HCT-116 cells. BLSEE reduced HCT-116 cell proliferation in a dose-dependent manner. BLSEE treatment also significantly increased the sub-G1 population in HCT-116 cells (P=0.0020 at 400 µg/ml), as shown by flow cytometry assay. Following treatment with BLSEE, the mRNA levels of the apoptosis-associated factors Fas, Fas ligand, tumor necrosis factor-related apoptosis-inducing ligand, death receptor 4 (DR4), death receptor 5 (DR5), caspases 3, 8 and 9, and B-cell lymphoma-2 (Bcl-2) associated X protein were increased, and the expression of anti-apoptotic Bcl-2 and Bcl-extra large was decreased in HCT-116 cells. The mRNA levels of matrix metalloproteinase (MMP)-2, MMP-9, TIMP metallopeptidase inhibitor 1 and TIMP metallopeptidase inhibitor 2 were also regulated by BLSEE treatment. In addition, BLSEE was able to modulate the expression of inflammation-associated nuclear factor-κB, inhibitory κBα, inducible nitric oxide synthase and cyclooxygenase 2 in HCT-116 cells. The present study clearly indicated the cytotoxicity of BLSEE in HCT-116 cells through induced cellular apoptosis. These results also suggested the BLSEE may be a powerful agent against colon cancer cells. PMID:28454279

  19. Exposure to Anisakis extracts can induce inflammation on in vitro cultured human colonic cells.

    Science.gov (United States)

    Speciale, Antonio; Trombetta, Domenico; Saija, Antonella; Panebianco, Antonio; Giarratana, Filippo; Ziino, Graziella; Minciullo, Paola Lucia; Cimino, Francesco; Gangemi, Sebastiano

    2017-07-12

    Anisakis spp. is a parasitic nematode whose infective third-stage larvae may be found within the flesh of fish species commonly consumed by humans. Thorough cooking or freezing should render the fish safe for consumption; furthermore, marinating solutions containing biocidal agents might have a significant action against Anisakis larvae. Some studies suggest a relationship between some parasitic infections and development of inflammatory bowel disorders, and Anisakis infection might be a risk factor for stomach or colon cancer. The aim of our study was to investigate if crude extracts (CEs) obtained from Anisakis larvae marinated in a solution with added allyl isothiocyanate (ACE-AITC) and frozen, or from frozen only Anisakis larvae (ACE), can induce an inflammatory effect on in vitro differentiated colonic Caco-2 cells exposed or not to LPS. Caco-2 exposure to the two CEs induced a marked COX-2 expression and potentiated LPS-induced COX-2 overexpression, confirming that substances present in Anisakis larvae can induce an inflammatory response in the intestinal epithelium, possibly also exacerbating the effects of other inflammatory stimuli. ACE induced a marked decrease in caspase-3 activation, while AITC-ACE increased its activation. However, LPS-induced caspase-3 activation appeared lower in cells treated with ACE and with the lower concentration of AITC-ACE. Thus, it is evident that Anisakis CEs may affect various cell pathways crucial not only in the inflammatory process but also in cell growth and death. Thus, CEs obtained from nonviable Anisakis larvae retain or are otherwise provided with noxious properties able to induce a strong inflammation response in intestinal epithelial cells. Furthermore, their influence may persist also following pretreatment with the biocidal agent AITC, indicating that the harmful substances contained in crude extracts from Anisakis larvae are resistant to the thermal or biocidal agent treatments.

  20. Hypertonic stress induces VEGF production in human colon cancer cell line Caco-2: inhibitory role of autocrine PGE₂.

    Directory of Open Access Journals (Sweden)

    Luciana B Gentile

    Full Text Available Vascular Endothelial Growth Factor (VEGF is a major regulator of angiogenesis. VEGF expression is up regulated in response to micro-environmental cues related to poor blood supply such as hypoxia. However, regulation of VEGF expression in cancer cells is not limited to the stress response due to increased volume of the tumor mass. Lipid mediators in particular arachidonic acid-derived prostaglandin (PGE₂ are regulators of VEGF expression and angiogenesis in colon cancer. In addition, increased osmolarity that is generated during colonic water absorption and feces consolidation seems to activate colon cancer cells and promote PGE₂ generation. Such physiological stimulation may provide signaling for cancer promotion. Here we investigated the effect of exposure to a hypertonic medium, to emulate colonic environment, on VEGF production by colon cancer cells. The role of concomitant PGE₂ generation and MAPK activation was addressed by specific pharmacological inhibition. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked VEGF and PGE₂ production. VEGF production was inhibited by selective inhibitors of ERK 1/2 and p38 MAPK pathways. To address the regulatory role of PGE₂ on VEGF production, Caco-2 cells were treated with cPLA₂ (ATK and COX-2 (NS-398 inhibitors, that completely block PGE₂ generation. The Caco-2 cells were also treated with a non selective PGE₂ receptor antagonist. Each treatment significantly increased the hypertonic stress-induced VEGF production. Moreover, addition of PGE₂ or selective EP₂ receptor agonist to activated Caco-2 cells inhibited VEGF production. The autocrine inhibitory role for PGE₂ appears to be selective to hypertonic environment since VEGF production induced by exposure to CoCl₂ was decreased by inhibition of concomitant PGE₂ generation. Our results indicated that hypertonicity stimulates VEGF production in colon cancer cell lines. Also PGE

  1. A native outer membrane vesicle vaccine confers protection against meningococcal colonization in human CEACAM1 transgenic mice.

    Science.gov (United States)

    Pajon, Rolando; Buckwalter, Carolyn M; Johswich, Kay O; Gray-Owen, Scott D; Granoff, Dan M

    2015-03-10

    The effect of protein-based meningococcal vaccines on prevention of nasopharyngeal colonization has been difficult to investigate experimentally because a reliable animal colonization model did not exist. Human CEACAM1 transgenic mice, which can be colonized by meningococci, were immunized IP with one of two meningococcal native outer membrane vesicle (NOMV) vaccines prepared from mutants with attenuated endotoxin (lpxL1 knockout) and over-expressed sub-family B Factor H-binding proteins (FHbp). Animals were challenged intranasally two weeks after the third dose with wild-type strain H44/76, or were treated IP with anti-NOMV serum before and during the bacterial challenge. The NOMV-1 vaccine, prepared from the serogroup B H44/76 mutant, elicited ∼40-fold higher serum bactericidal antibody titers against the wild-type H44/76 challenge strain than the NOMV-2 vaccine prepared from a heterologous serogroup W mutant strain with different PorA and FHbp amino acid sequence variants. Compared to aluminum hydroxide-immunized control mice, the efficacy for prevention of any H44/76 colonization was 93% (95% confidence interval, 52-99, P<0.0001) for the NOMV-1 vaccine, and 19% (-3-36, P=0.23) for NOMV-2. NOMV-2-vaccinated mice had a 5.6-fold decrease in geometric mean CFU of bacteria per animal in tracheal washes compared to control mice (P=0.007). The efficacy of passive administration of serum from NOMV-1-vaccinated mice to immunologically naïve mice against colonization was 44% (17-61; P=0.002). Both NOMV vaccines protected against meningococcal colonization but there was greater protection by the NOMV-1 vaccine with antigens matched with the challenge strain. Meningococcal vaccines that target protein antigens have potential to decrease colonization. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families

    Directory of Open Access Journals (Sweden)

    Jamile Abud

    2012-12-01

    Full Text Available CONTEXT: CHEK2 encodes a cell cycle checkpoint kinase that plays an important role in the DNA damage repair pathway, activated mainly by ATM (Ataxia Telangiectasia Mutated in response to double-stranded DNA breaks. A germline mutation in CHEK2, 1100delC, has been described as a low penetrance allele in a significant number of families with breast and colorectal cancer in certain countries and is also associated with increased risk of contralateral breast cancer in women previously affected by the disease. About 5%-10% of all breast and colorectal cancers are associated with hereditary predisposition and its recognition is of great importance for genetic counseling and cancer risk management. OBJECTIVES: Here, we have assessed the frequency of the CHEK2 1100delC mutation in the germline of 59 unrelated Brazilian individuals with clinical criteria for the hereditary breast and colorectal cancer syndrome. METHODS: A long-range PCR strategy followed by gene sequencing was used. RESULTS: The 1100delC mutation was encountered in the germline of one (1.7% individual in this high risk cohort. This indicates that the CHEK2 1100delC is not commonly encountered in Brazilian families with multiple diagnoses of breast and colorectal cancer. CONCLUSION: These results should be confirmed in a larger series of families and further testing should be undertaken to investigate the molecular mechanisms underlying the hereditary breast and colorectal cancer phenotype.

  3. In Vitro Utilization of Amylopectin and High-Amylose Maize (Amylomaize) Starch Granules by Human Colonic Bacteria

    OpenAIRE

    Wang, Xin; Conway, Patricia Lynne; Brown, Ian Lewis; Evans, Anthony John

    1999-01-01

    It has been well established that a certain amount of ingested starch can escape digestion in the human small intestine and consequently enters the large intestine, where it may serve as a carbon source for bacterial fermentation. Thirty-eight types of human colonic bacteria were screened for their capacity to utilize soluble starch, gelatinized amylopectin maize starch, and high-amylose maize starch granules by measuring the clear zones on starch agar plates. The six cultures which produced ...

  4. Analysis of the Chaotic Characteristics of Human Colonic Activities and Comparison of Healthy Participants to Costive Subjects.

    Science.gov (United States)

    Lu, Li; Yan, Guozheng; Zhao, Kai; Xu, Fei

    2016-01-01

    Constipation is a common yet distressing disease that has high rates of morbidity and impacts patients' quality of life. However, there is no perfect method to distinguish costive patients from healthy subjects. Is there chaos in human colonic activities? Are there any differences for the chaos indicators of colonic activities between healthy and costive subjects? Can these indicators distinguish patients with constipation from healthy subjects? To answer these questions, colonic pressure data from 16 healthy subjects and 48 patients with constipation were analyzed using the chaos theory. Three chaotic indicators [i.e., the largest Lyapunov exponent (LyE), correlation dimension (CorDim), and Kolmogorov entropy (KoEn)] were calculated and compared between groups with the Wilcoxon rank sum test. As a result, the LyE was greater than zero and the CorDim was fractioned, which showed that human colonic activities have clear chaotic characteristics. Statistically significant differences were observed between groups for CorDim (p chaotic indicator of CorDim was able to differentiate between patients with constipation and healthy subjects. The chaos theory provides a new method for learning the nonlinear dynamics of human gastrointestinal activities.

  5. Bacteroides intestinalis DSM 17393, a member of the human colonic microbiome, upregulates multiple endoxylanases during growth on xylan

    Science.gov (United States)

    Wang, Kui; Pereira, Gabriel V.; Cavalcante, Janaina J. V.; Zhang, Meiling; Mackie, Roderick; Cann, Isaac

    2016-01-01

    Many human diets contain arabinoxylan, and the ease of genome sequencing coupled with reduced cost have led to unraveling the arsenal of genes utilized by the colonic Bacteroidetes to depolymerize this polysaccharide. The colonic Bacteroidetes with potential to ferment arabinoxylans include Bacteroides intestinalis. In this study, we analyzed the hydrolytic activities of members of a xylan degradation cluster encoded on the genome of Bacteroides intestinalis DSM 17393. Here, it is demonstrated that a cocktail of the xylanolytic enzymes completely hydrolyze arabinoxylans found in human diets. We show that this bacterium and relatives have evolved and secrete a unique bifunctional endoxylanase/arabinofuranosidase in the same polypeptide. The bifunctional enzyme and other secreted enzymes attack the polysaccharides extracellularly to remove the side-chains, exposing the xylan backbone for cleavage to xylo-oligosaccharides and xylose. These end products are transported into the cell where a β-xylosidase cleaves the oligosaccharides to fermentable sugars. While our experiments focused on B. intestinalis, it is likely that the extracellular enzymes also release nutrients to members of the colonic microbial community that practice cross-feeding. The presence of the genes characterized in this study in other colonic Bacteroidetes suggests a conserved strategy for energy acquisition from arabinoxylan, a component of human diets. PMID:27681607

  6. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2.

    Directory of Open Access Journals (Sweden)

    Chen Wang

    Full Text Available A better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo.To study the reciprocal effects of adipocytes and cancer cells, we co-cultured human mature adipocytes and breast cancer cells in a system devoid of heterogeneous cell-cell contact. To analyze the factors that were secreted from adipocytes and that affected the invasive abilities of breast cancer cells, we detected different cytokines in various co-culture media. To study the communication of mature adipocytes and breast cancer cells in vivo, we chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to do immunostaining.The co-culture media of human MCF-7 breast cancer cells and human mature adipocytes increased motility of MCF-7 cells. In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells. Based on our co-culture medium chip results, we chose four candidate cytokines and tested their influence on metastasis individually. We found that IGFBP-2 enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors. In vivo, metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors.IGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.

  7. Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa

    DEFF Research Database (Denmark)

    Parlesak, Alexandr

    2005-01-01

    BACKGROUND: Despite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four...... representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon. METHODS: Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined...... to the descending colon. CONCLUSION: The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon....

  8. The challenge of preserving cardiorespiratory fitness in physically inactive patients with colon or breast cancer during adjuvant chemotherapy: a randomised feasibility study

    DEFF Research Database (Denmark)

    Møller, Tom; Lillelund, Christian; Andersen, Christina

    2015-01-01

    Introduction Anti-neoplastic treatment is synonymous with an inactive daily life for a substantial number of patients. It remains unclear what is the optimal setting, dosage and combination of exercise and health promoting components that best facilitate patient adherence and symptom management...... in order to support cardio-respiratory fitness and lifestyle changes in an at-risk population of pre-illness physically inactive cancer patients.Methods Patients with breast or colon cancer referred to adjuvant chemotherapy and by the oncologists pre-screening verified as physically inactive were eligible...... to enter a randomised three-armed feasibility study comparing a 12-week supervised hospital-based moderate to high intensity exercise intervention or alternate an instructive home-based12-week pedometer intervention, with usual care.Results Using a recommendation based physical activity screening...

  9. Metabolic fate of ochratoxin A as a coffee contaminant in a dynamic simulator of the human colon.

    Science.gov (United States)

    Ouethrani, Minale; Van de Wiele, Tom; Verbeke, Ellen; Bruneau, Aurélia; Carvalho, Maryline; Rabot, Sylvie; Camel, Valérie

    2013-12-15

    Ochratoxin A (OTA) is a mycotoxin frequently encountered in coffee. The relevance of this contaminant in the colon upon digestion necessitates a study on its interaction with colon microbiota. Here, the fate of OTA during colon digestion was investigated using a dynamic simulator of the human gut. The influence of coffee as a food matrix was taken into account, as it may affect the colonic microbial ecosystem and, consequently, the fate of OTA. Biodegradation was followed by measuring OTA concentration over time, and by screening for several possible metabolites, using LC-ESI-MS and HRMS. The descending colon was found to be the main site of OTA biodegradation. Two metabolites, ochratoxin α and ochratoxin B, were identified, suggesting that biodegradation by gut microbiota is beneficial for the host, as they are considered less toxic than OTA. The extent of biodegradation was reduced in the presence of the coffee matrix, possibly due to competition for available carbon sources. Effects of OTA and the coffee matrix on the microbial ecosystem were contrasting. While OTA caused a specific, but lasting loss, of the beneficial species Lactobacillus reuteri, coffee temporarily altered the fermentation pattern towards lower ammonia and higher acetate and propionate production, likely due to its dietary fibre content.

  10. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xiaolan, E-mail: huxiaolan1998@yahoo.com.cn [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Zhang, Xianqi [The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou (China); Qiu, Shuifeng [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Yu, Daihua; Lin, Shuxin [Fourth Military Medical University, Xi' an (China)

    2010-07-16

    Research highlights: {yields} Salidroside inhibits the growth of human breast cancer cells. {yields} Salidroside induces cell-cycle arrest of human breast cancer cells. {yields} Salidroside induces apoptosis of human breast cancer cell lines. -- Abstract: Recently, salidroside (p-hydroxyphenethyl-{beta}-D-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

  11. Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon.

    Science.gov (United States)

    Louis, Petra; Duncan, Sylvia H; McCrae, Sheila I; Millar, Jacqueline; Jackson, Michelle S; Flint, Harry J

    2004-04-01

    The final steps in butyrate synthesis by anaerobic bacteria can occur via butyrate kinase and phosphotransbutyrylase or via butyryl-coenzyme A (CoA):acetate CoA-transferase. Degenerate PCR and enzymatic assays were used to assess the presence of butyrate kinase among 38 anaerobic butyrate-producing bacterial isolates from human feces that represent three different clostridial clusters (IV, XIVa, and XVI). Only four strains were found to possess detectable butyrate kinase activity. These were also the only strains to give PCR products (verifiable by sequencing) with degenerate primer pairs designed within the butyrate kinase gene or between the linked butyrate kinase/phosphotransbutyrylase genes. Further analysis of the butyrate kinase/phosphotransbutyrylase genes of one isolate, L2-50, revealed similar organization to that described previously from different groups of clostridia, along with differences in flanking sequences and phylogenetic relationships. Butyryl-CoA:acetate CoA-transferase activity was detected in all 38 strains examined, suggesting that it, rather than butyrate kinase, provides the dominant route for butyrate formation in the human colonic ecosystem that contains a constantly high concentration of acetate.

  12. TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells.

    Science.gov (United States)

    Mitrovic, Sandra; Nogueira, Cristina; Cantero-Recasens, Gerard; Kiefer, Kerstin; Fernández-Fernández, José M; Popoff, Jean-François; Casano, Laetitia; Bard, Frederic A; Gomez, Raul; Valverde, Miguel A; Malhotra, Vivek

    2013-05-28

    Mucin 5AC (MUC5AC) is secreted by goblet cells of the respiratory tract and, surprisingly, also expressed de novo in mucus secreting cancer lines. siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line (HT29-18N2) revealed new proteins, including a Ca(2+)-activated channel TRPM5, for MUC5AC secretion. TRPM5 was required for PMA and ATP-induced secretion of MUC5AC from the post-Golgi secretory granules. Stable knockdown of TRPM5 reduced a TRPM5-like current and ATP-mediated Ca(2+) signal. ATP-induced MUC5AC secretion depended strongly on Ca(2+) influx, which was markedly reduced in TRPM5 knockdown cells. The difference in ATP-induced Ca(2+) entry between control and TRPM5 knockdown cells was abrogated in the absence of extracellular Ca(2+) and by inhibition of the Na(+)/Ca(2+) exchanger (NCX). Accordingly, MUC5AC secretion was reduced by inhibition of NCX. Thus TRPM5 activation by ATP couples TRPM5-mediated Na(+) entry to promote Ca(2+) uptake via an NCX to trigger MUC5AC secretion. DOI:http://dx.doi.org/10.7554/eLife.00658.001.

  13. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells.

    Science.gov (United States)

    de Vasconcelos, Alana; Campos, Vinicius Farias; Nedel, Fernanda; Seixas, Fabiana Kömmling; Dellagostin, Odir A; Smith, Kevin R; de Pereira, Cláudio Martin Pereira; Stefanello, Francieli Moro; Collares, Tiago; Barschak, Alethéa Gatto

    2013-06-01

    Recent studies report that chalcones exhibit cytotoxicity to human cancer cell lines. Typically, the form of cell death induced by these compounds is apoptosis. In the context of the discovery of new anticancer agents and in light of the antitumour potential of several chalcone derivatives, in the present study, we synthesized and tested the cytotoxicity of six chalcone derivatives on human colon adenocarcinoma cells. Six derivatives of 3-phenyl-1-(thiophen-2-yl) prop-2-en-1-one were prepared and characterized on the basis of their (1) H and (13) C NMR spectra. HT-29 cells were treated with synthesized chalcones on two concentrations by three different incubation times. Cells were evaluated by cell morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry (annexin V) and gene expression analyses to determine the cytotoxic way. Chalcones 3-(4-bromophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C06) and 3-(2-nitrophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C09) demonstrated higher cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay. These data were confirmed by a decreased expression of anti-apoptotic genes and increased pro-apoptotic genes. Our findings indicate in summary that the cytotoxic activity of chalcone C06 on colorectal carcinoma cells occurs by apoptosis.

  14. c-MYC is a radiosensitive locus in human breast cells.

    Science.gov (United States)

    Wade, M A; Sunter, N J; Fordham, S E; Long, A; Masic, D; Russell, L J; Harrison, C J; Rand, V; Elstob, C; Bown, N; Rowe, D; Lowe, C; Cuthbert, G; Bennett, S; Crosier, S; Bacon, C M; Onel, K; Scott, K; Scott, D; Travis, L B; May, F E B; Allan, J M

    2015-09-17

    Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.

  15. Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer

    OpenAIRE

    Costa, C; SOARES, R.; Reis-Filho, J S; Leitão, D; Amendoeira, I; Schmitt, F C

    2002-01-01

    Aims: Cyclo-oxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis. COX-2 is induced by a wide variety of stimuli, and present during inflammation. COX-2 overexpression has been observed in colon, head and neck, lung, prostate, stomach, and breast cancer. In colon and gastric cancer, COX-2 expression was associated with angiogenesis. The aim of this study was to determine the relation between COX-2 expression and angiogenesis in breast cancer, and to correlate the ...

  16. How Does a Shared Decision-Making (SDM) Intervention for Oncologists Affect Participation Style and Preference Matching in Patients with Breast and Colon Cancer?

    Science.gov (United States)

    Bieber, Christiane; Nicolai, Jennifer; Gschwendtner, Kathrin; Müller, Nicole; Reuter, Katrin; Buchholz, Angela; Kallinowski, Birgit; Härter, Martin; Eich, Wolfgang

    2016-12-13

    The aims of this study are to assess patients' preferred and perceived decision-making roles and preference matching in a sample of German breast and colon cancer patients and to investigate how a shared decision-making (SDM) intervention for oncologists influences patients' preferred and perceived decision-making roles and the attainment of preference matches. This study is a post hoc analysis of a randomised controlled trial (RCT) on the effects of an SDM intervention. The SDM intervention was a 12-h SDM training program for physicians in combination with decision board use. For this study, we analysed a subgroup of 107 breast and colon cancer patients faced with serious treatment decisions who provided data on specific questionnaires with regard to their preferred and perceived decision-making roles (passive, SDM or active). Patients filled in questionnaires immediately following a decision-relevant consultation (t1) with their oncologist. Eleven of these patients' 27 treating oncologists had received the SDM intervention within the RCT. A majority of cancer patients (60%) preferred SDM. A match between preferred and perceived decision-making roles was reached for 72% of patients. The patients treated by SDM-trained physicians perceived greater autonomy in their decision making (p < 0.05) with more patients perceiving SDM or an active role, but their preference matching was not influenced. A SDM intervention for oncologists boosted patient autonomy but did not improve preference matching. This highlights the already well-known reluctance of physicians to engage in explicit role clarification.

  17. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt

    2014-01-01

    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  18. Carob fibre compounds modulate parameters of cell growth differently in human HT29 colon adenocarcinoma cells than in LT97 colon adenoma cells.

    Science.gov (United States)

    Klenow, S; Glei, M; Haber, B; Owen, R; Pool-Zobel, B L

    2008-04-01

    An extract of the Mediterranean carob (Ceratonia siliqua L.) pod (carob fibre extract), products formed after its fermentation by the gut flora and the major phenolic ingredient gallic acid (GA), were comparatively investigated for their influence on survival and growth parameters of colon adenocarcinoma HT29 cells and adenoma LT97 cells. Hydrogen peroxide (H2O2) formation in the cell culture media was quantified. After 1h 97+/-4 microM or 70+/-15 microM were found in HT29 medium and 6+/-1 microM or 3+/-3 microM in LT97 medium for carob fibre extract or GA, respectively. After 72 h carob fibre extract reduced survival of rapidly proliferating HT29 cells (by 76.4+/-12.9%) whereas metabolic activity and DNA-synthesis were only transiently impaired. Survival of slower growing LT97 cells was less decreased (by 21.5+/-12.9%), but there were marked effects on DNA-synthesis (reduction by 95.6+/-7%, 72 h). GA and fermented carob fibre did not have comparable effects. Thus, carob fibre extract resulted in H2O2 formation, which, however, could not explain impairment of cell growth. The differently modulated growth of human colon cell lines was more related to proliferation rates and impairment of DNA-synthesis than to H2O2 formation.

  19. Hybrids of Iron-Filled Multiwall Carbon Nanotubes and Anticancer Agents as Potential Magnetic Drug Delivery Systems: In Vitro Studies against Human Melanoma, Colon Carcinoma, and Colon Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sławomir Boncel

    2017-01-01

    Full Text Available Cell type, morphology, and functioning are key variables in the construction of efficient “drug-vehicle” hybrids in magnetic drug delivery. Iron-encapsulated multiwall carbon nanotubes (Fe@MWCNTs appear as promising candidates for theranostics due to in situ chemical catalytic vapor deposition (c-CVD synthesis, straightforward organic functionalization, and nanoneedle (1D behavior. Here, model hybrids were synthesized by exploring C-sp2 chemistry ((1+2-cycloaddition of nitrenes and amidation of the outer MWCNT walls combined with anticancer agents, that is, 5-fluorouracil (5FU, purpurin (Purp, and 1,8-naphthalimide DNA intercalators (NIDIs, via linkers. Analyses of the Fe@MWCNT vehicles by SEM, TEM, and Raman spectroscopy revealed their morphology while Mössbauer spectroscopy confirmed the presence of encapsulated ferromagnetic iron-based nanodomains. Cytotoxicity of the hybrids was studied using a 24 h MTS assay combined with the apoptosis and life cycle assays against human melanoma (Me45, colon carcinoma (HCT116+, and colon adenocarcinoma (Caco-2. The cells had different sensitivity to the vehicles themselves as well as to the hybrids. MWCNT-based covalent hybrids of 5FU and Purp emerged as the most promising systems against Me45 and HCT116+ cell lines with the highest in vitro cytotoxicity and proapoptotic activity. Furthermore, nanotubes bearing 4-nitro- and 4-(N-morpholinyl-1,8-naphthalimide DNA intercalators appear as a promising candidate for the treatment of Caco-2.

  20. Extravirgin olive oil up-regulates CB₁ tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms.

    Science.gov (United States)

    Di Francesco, Andrea; Falconi, Anastasia; Di Germanio, Clara; Micioni Di Bonaventura, Maria Vittoria; Costa, Antonio; Caramuta, Stefano; Del Carlo, Michele; Compagnone, Dario; Dainese, Enrico; Cifani, Carlo; Maccarrone, Mauro; D'Addario, Claudio

    2015-03-01

    Extravirgin olive oil (EVOO) represents the typical lipid source of the Mediterranean diet, an eating habit pattern that has been associated with a significant reduction of cancer risk. Diet is the more studied environmental factor in epigenetics, and many evidences suggest dysregulation of epigenetic pathways in cancer. The aim of our study was to investigate the effects of EVOO and its phenolic compounds on endocannabinoid system (ECS) gene expression via epigenetic regulation in both human colon cancer cells (Caco-2) and rats exposed to short- and long-term dietary EVOO. We observed a selective and transient up-regulation of CNR1 gene - encoding for type 1 cannabinoid receptor (CB₁) - that was evoked by exposure of Caco-2 cells to EVOO (100 ppm), its phenolic extracts (OPE, 50 μM) or authentic hydroxytyrosol (HT, 50 μM) for 24 h. None of the other major elements of the ECS (i.e., CB₂; GPR55 and TRPV1 receptors; and NAPE-PLD, DAGL, FAAH and MAGL enzymes) was affected at any time point. The stimulatory effect of OPE and HT on CB₁ expression was inversely correlated to DNA methylation at CNR1 promoter and was associated with reduced proliferation of Caco-2 cells. Interestingly, CNR1 gene was less expressed in Caco-2 cells when compared to normal colon mucosa cells, and again this effect was associated with higher level of DNA methylation at CNR1. Moreover, in agreement with the in vitro studies, we also observed a remarkable (~4-fold) and selective increase in CB₁ expression in the colon of rats receiving dietary EVOO supplementation for 10 days. Consistently, CpG methylation of rat Cnr1 promoter, miR23a and miR-301a, previously shown to be involved in the pathogenesis of colorectal cancer and predicted to target CB₁ mRNA, was reduced after EVOO administration down to ~50% of controls. Taken together, our findings demonstrating CB₁ gene expression modulation by EVOO or its phenolic compounds via epigenetic mechanism, both in vitro and in vivo, may

  1. 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.

  2. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-08-12

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

  3. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Roberto Madeddu

    2013-08-01

    Full Text Available Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd, which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

  4. Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Fabjani Gerhild

    2008-01-01

    Full Text Available Abstract Background Many cancer cells produce interleukin-6 (IL-6, a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E2, 17β-estradiol, and 1,25-dihydroxyvitamin D3, on expression and synthesis of the cytokine at different stages of tumour progression. Methods We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. Results IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10-7 M reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10-8 M 1,25-dihydroxyvitamin D3. Conclusion In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally

  5. Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction.

    Directory of Open Access Journals (Sweden)

    Sujatha Ramasamy

    Full Text Available Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski and colon (HT-29 cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50 values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10. PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8. PPWH-7 possessed greatest cytotoxicity (IC(50 values ranged from 0.66-0.83 µg/mL and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.

  6. Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gui-Ping Li; Yong-Xian Wang; Kai Huang; Hui Zhang; Chun-Fu Zhang

    2005-01-01

    AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti

  7. Tropomyosin-1, A Putative Tumor-Suppressor and a Biomarker of Human Breast Cancer

    Science.gov (United States)

    2004-10-01

    cDNA. Lobular carcinoma - 2 A polyclonal pan-TM antibody that recognizes multiple TM Phyllodes tumor - 1 Not determined from the initial pathology...AD Award Number: DAMD17-98-1-8162 TITLE: Tropomyosin-1, A Putative Tumor -Suppressor and a Biomarker of Human Breast Cancer PRINCIPAL INVESTIGATOR...4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Tropomyosin-l, A Putative Tumor -Suppressor and a Biomarker DAMD17-98-1-8162 of Human Breast Cancer 6. A UTHOR

  8. Kinase Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0009 TITLE: PRINCIPAL INVESTIGATOR: John Cleveland CONTRACTING ORGANIZATION: H. Lee Moffitt Cancer Center...so designated by other documentation. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer REPORT DOCUMENTATION PAGE Form...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0009 5c

  9. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0008 TITLE: Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer PRINCIPAL INVESTIGATOR...Jan 2017 4. TITLE AND SUBTITLE Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...Investigator [PI], Scripps) and John Cleveland (Collaborating/Partnering PI, Moffitt Cancer Center) seek to validate 40S ribosome assembly as a therapeutic

  10. Role of COX-2 in the regulation of the metastatic potential of human breast tumor cells

    Directory of Open Access Journals (Sweden)

    M. A. Taipov

    2014-01-01

    Full Text Available The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105, and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

  11. Iron sufficiency in breast-fed infants and the availability of iron from human milk.

    Science.gov (United States)

    McMillan, J A; Landaw, S A; Oski, F A

    1976-11-01

    Four infants were studied who had been exclusively breast-fed for periods varying from 8 to 18 months. All had grown sufficiently to have exhausted their prenatally acquired iron endowment with respect to meeting current needs for maintaining normal hemoglobin levels. All infants had normal hemoglobin values and normal serum iron values. Studies of iron absorption from breast milk and cow's milk were performed in ten normal adults. The absorption of iron from the human milk was significantly higher. These findings suggest that the iron present in human milk is sufficient to meet the iron requirements of the exclusively breast-fed infant until he approximately triples his birthweight.

  12. Colonic fermentation may play a role in lactose intolerance in humans

    NARCIS (Netherlands)

    He, T; Priebe, MG; Harmsen, HJM; Stellaard, F; Sun, XH; Welling, GW; Vonk, RJ

    2006-01-01

    The results of our previous study suggested that in addition to the small intestinal lactase activity and transit time, colonic processing of lactose may play a role in lactose intolerance. We investigated whether colonic fermentation of lactose is correlated with lactose intolerance. After 28 Chine

  13. Dissection of a stem cell hierarchy in the human breast

    DEFF Research Database (Denmark)

    Rubner Fridriksdottir, Agla Jael

    and apoptosis during each menstrual cycle. These changes are most prominent during pregnancy, lactation and involution after breast feeding. These highly dynamic changes are thought to rely on the presence of a breast epithelial stem cell population (reviewed in (Fridriksdottir et al. 2005)). Nevertheless...... al. 2006) is highly warranted as this may lead to identification of those long-term breast resident(s) that accumulate enough genetic hits for clonal expansion and tumor development, i.e. the cellular origin(s) of breast cancer....

  14. Microbial dysbiosis is associated with human breast cancer

    National Research Council Canada - National Science Library

    Xuan, Caiyun; Shamonki, Jaime M; Chung, Alice; Dinome, Maggie L; Chung, Maureen; Sieling, Peter A; Lee, Delphine J

    2014-01-01

    .... In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae...

  15. Distributed human intelligence for colonic polyp classification in computer-aided detection for CT colonography.

    Science.gov (United States)

    Nguyen, Tan B; Wang, Shijun; Anugu, Vishal; Rose, Natalie; McKenna, Matthew; Petrick, Nicholas; Burns, Joseph E; Summers, Ronald M

    2012-03-01

    To assess the diagnostic performance of distributed human intelligence for the classification of polyp candidates identified with computer-aided detection (CAD) for computed tomographic (CT) colonography. This study was approved by the institutional Office of Human Subjects Research. The requirement for informed consent was waived for this HIPAA-compliant study. CT images from 24 patients, each with at least one polyp of 6 mm or larger, were analyzed by using CAD software to identify 268 polyp candidates. Twenty knowledge workers (KWs) from a crowdsourcing platform labeled each polyp candidate as a true or false polyp. Two trials involving 228 KWs were conducted to assess reproducibility. Performance was assessed by comparing the area under the receiver operating characteristic curve (AUC) of KWs with the AUC of CAD for polyp classification. The detection-level AUC for KWs was 0.845 ± 0.045 (standard error) in trial 1 and 0.855 ± 0.044 in trial 2. These were not significantly different from the AUC for CAD, which was 0.859 ± 0.043. When polyp candidates were stratified by difficulty, KWs performed better than CAD on easy detections; AUCs were 0.951 ± 0.032 in trial 1, 0.966 ± 0.027 in trial 2, and 0.877 ± 0.048 for CAD (P = .039 for trial 2). KWs who participated in both trials showed a significant improvement in performance going from trial 1 to trial 2; AUCs were 0.759 ± 0.052 in trial 1 and 0.839 ± 0.046 in trial 2 (P = .041). The performance of distributed human intelligence is not significantly different from that of CAD for colonic polyp classification. © RSNA.

  16. Antigen binding of human IgG Fabs mediate ERK-associated proliferation of human breast cancer cells.

    Science.gov (United States)

    Wen, Yue-Jin; Mancino, Anne; Pashov, Anastas; Whitehead, Tracy; Stanley, Joseph; Kieber-Emmons, Thomas

    2005-02-01

    Serum-circulating antibody can be linked to poor outcomes in some cancer patients. To investigate the role of human antibodies in regulating tumor cell growth, we constructed a recombinant cDNA expression library of human IgG Fab from a patient with breast cancer. Clones were screened from the library with breast tumor cell lysate. Sequence analysis of the clones showed somatic hypermutations when compared to their closest VH/VL germ-line genes. Initial characterizations focused on five clones. All tested clones displayed stronger binding to antigen derived from primary breast cancers and established breast cancer cell lines than to normal breast tissues. In vitro functional studies showed that four out of five tested clones could stimulate the growth of MDA-MB-231 breast cancer cell lines, and one out of five was able to promote MCF-7 cell growth as well. Involvement of ERK2 pathway was observed. By 1H-NMR spectra and Western blot analysis, it was evident that two tested antibody Fabs are capable of interacting with sialic acid. Our study suggests a possible role for human antibody in promoting tumor cell growth by direct binding of IgG Fab to breast tumor antigen. Such studies prompt speculation regarding the role of serum antibodies in mediating tumor growth as well as their contribution to disease progression.

  17. Simulated lesion, human observer performance comparison between thin-section dedicated breast CT images versus computed thick-section simulated projection images of the breast

    Science.gov (United States)

    Chen, L.; Boone, J. M.; Abbey, C. K.; Hargreaves, J.; Bateni, C.; Lindfors, K. K.; Yang, K.; Nosratieh, A.; Hernandez, A.; Gazi, P.

    2015-04-01

    The objective of this study was to compare the lesion detection performance of human observers between thin-section computed tomography images of the breast, with thick-section (>40 mm) simulated projection images of the breast. Three radiologists and six physicists each executed a two alterative force choice (2AFC) study involving simulated spherical lesions placed mathematically into breast images produced on a prototype dedicated breast CT scanner. The breast image data sets from 88 patients were used to create 352 pairs of image data. Spherical lesions with diameters of 1, 2, 3, 5, and 11 mm were simulated and adaptively positioned into 3D breast CT image data sets; the native thin section (0.33 mm) images were averaged to produce images with different slice thicknesses; average section thicknesses of 0.33, 0.71, 1.5 and 2.9 mm were representative of breast CT; the average 43 mm slice thickness served to simulate simulated projection images of the breast. The percent correct of the human observer’s responses were evaluated in the 2AFC experiments. Radiologists lesion detection performance was significantly (p physicist observer, however trends in performance were similar. Human observers demonstrate significantly better mass-lesion detection performance on thin-section CT images of the breast, compared to thick-section simulated projection images of the breast.

  18. A Human Volunteer Study to Determine the Prebiotic Effects of Lactulose Powder on Human Colonic Microbiota

    OpenAIRE

    2011-01-01

    The prebiotic effects of lactulose were monitored in a human feeding study. Prebiotics are dietary carbohydrates that have a selective microbial metabolism in the gut, directed towards bacteria seen as beneficial, examples being bifidobacteria and/or lactobacilli. The study was conducted in a double blind, placebo controlled manner. A dose of 10 g per day, half the pharmacological dose, was fed to 10 healthy adult volunteers. In parallel, 10 persons were fed a placebo (glucose/lactose). Both ...

  19. The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer

    DEFF Research Database (Denmark)

    Brunner, N; Spang-Thomsen, M; Cullen, K

    1996-01-01

    Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen recepto...

  20. Human papilloma virus identification in breast cancer patients with previous cervical neoplasia

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2016-01-01

    Full Text Available Purpose: Women with human papilloma virus (HPV associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i identify high risk for cancer HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii determine if these HPVs were biologically active.Methods: A range of polymerase chain reaction (PCR and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. Results: The same high risk HPV types were identified in both the cervical and breast specimens in 13 (46% of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001. Conclusions: These findings indicate that high risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of 2 similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  1. A feasibility study of soft embalmed human breast tissue for preclinical trials of HIFU- preliminary results

    Science.gov (United States)

    Joy, Joyce; Yang, Yang; Purdie, Colin; Eisma, Roos; Melzer, Andreas; Cochran, Sandy; Vinnicombe, Sarah

    2017-03-01

    Breast cancer is the commonest cancer in women in the UK, accounting for 30% of all new cancers in women, with an estimated 49,500 new cases in 20101. With the widespread negative publicity around over-diagnosis and over-treatment of low risk breast cancers, interest in the application of non-invasive treatments such as magnetic resonance imaging (MRI) guided high intensity focused ultrasound (HIFU) has increased. Development has begun of novel US transducers and platforms specifically designed for use with breast lesions, so as to improve the range of breast lesions that can be safely treated. However, before such transducers can be evaluated in patients in clinical trials, there is a need to establish their efficacy. A particular issue is the accuracy of temperature monitoring of FUS with MRI in the breast, since the presence of large amounts of surrounding fat can hinder temperature measurement. An appropriate anatomical model that imposes similar physical constraints to the breast and that responds to FUS in the same way would be extremely advantageous. The aim of this feasibility study is to explore the use of Thiel embalmed cadaveric tissue for these purposes. We report here the early results of laboratory-based experiments sonicating dissected breast samples from a Thiel embalmed soft human cadaver with high body mass index (BMI). A specially developed MRI compatible chamber and sample holder was developed to secure the sample and ensure reproducible sonications at the transducer focus. The efficacy of sonication was first studied with chicken breast and porcine tissue. The experiments were then repeated with the dissected fatty breast tissue samples from the soft-embalmed human cadavers. The sonicated Thiel breast tissue was examined histopathologically, which confirmed the absence of any discrete lesion. To investigate further, fresh chicken breast tissue was embalmed and the embalmed tissue was sonicated with the same parameters. The results confirmed the

  2. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer

    Science.gov (United States)

    Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. Methods RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. Results A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast

  3. Combined photoacoustic and ultrasound imaging of human breast in vivo in the mammographic geometry

    Science.gov (United States)

    Xie, Zhixing; Lee, Won-Mean; Hooi, Fong Ming; Fowlkes, J. Brian; Pinsky, Renee W.; Mueller, Dean; Wang, Xueding; Carson, Paul L.

    2013-03-01

    This photoacoustic volume imaging (PAVI) system is designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3D ultrasound (AUS). The good penetration of near-infrared (NIR) light and high receiving sensitivity of a broad bandwidth, 572 element, 2D PVDF array at a low center-frequency of 1MHz were utilized with 20 channel simultaneous acquisition. The feasibility of this system in imaging optically absorbing objects in deep breast tissues was assessed first through experiments on ex vivo whole breasts. The blood filled pseudo lesions were imaged at depths up to 49 mm in the specimens. In vivo imaging of human breasts has been conducted. 3D PAVI image stacks of human breasts were coregistered and compared with 3D ultrasound image stacks of the same breasts. Using the designed system, PAVI shows satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides with mild compression in the mammographic geometry. With its unique soft tissue contrast and excellent sensitivity to the tissue hemodynamic properties of fractional blood volume and blood oxygenation, PAVI, as a complement to 3D ultrasound and digital tomosynthesis mammography, might well contribute to detection, diagnosis and prognosis for breast cancer.

  4. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles

    Directory of Open Access Journals (Sweden)

    Tchou Julia

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2 of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. Methods To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC and six Her2+. Results We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER + cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer. Conclusions These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer.

  5. Screening and analysis of breast cancer genes regulated by the human mammary microenvironment in a humanized mouse model

    Science.gov (United States)

    Zheng, Mingjie; Wang, Jue; Ling, Lijun; Xue, Dandan; Wang, Shui; Zhao, Yi

    2016-01-01

    Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells. It was demonstrated that breast cancer cells showed improved growth in the human mammary microenvironment compared with a conventional subcutaneous mouse model. In the present study, the novel mouse model and microarray technology was used to analyze changes in the expression of genes in breast cancer cells that are regulated by the human mammary microenvironment. Humanized breast and conventional subcutaneous mouse models were established, and orthotopic tumor cells were obtained from orthotopic tumor masses by primary culture. An expression microarray using Illumina HumanHT-12 v4 Expression BeadChip and database analyses were performed to investigate changes in gene expression between tumors from each microenvironment. A total of 94 genes were differentially expressed between the primary cells cultured from the humanized and conventional mouse models. Significant upregulation of genes that promote cell proliferation and metastasis or inhibit apoptosis, such as SH3-domain binding protein 5 (BTK-associated), sodium/chloride cotransporter 3 and periostin, osteoblast specific factor, and genes that promote angiogenesis, such as KIAA1618, was also noted. Other genes that restrain cell proliferation and accelerate cell apoptosis, including tripartite motif containing TRIM36 and NES1, were downregulated. The present results revealed differences in various aspects of tumor growth and metabolism between the two model groups and indicated the functional

  6. ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells.

    Science.gov (United States)

    Condello, Maria; De Berardis, Barbara; Ammendolia, Maria Grazia; Barone, Flavia; Condello, Giancarlo; Degan, Paolo; Meschini, Stefania

    2016-09-01

    Zinc Oxide (ZnO) nanoparticles are widely used both in the industry and in biomedical applications for their chemical and physical nanomaterial properties. It is therefore essential to go in depth into the cytotoxicity mechanisms and interactions between nanomaterials and cells. The aim of this work was to evaluate the dissolution of ZnO nanoparticles and their uptake, from a few minutes after treatments up to 24h. ZnO nanoparticles routes of entry into the human colon carcinoma cells (LoVo) were followed at different times by a thorough ultrastructural investigation and semiquantitative analysis. The intracellular release of Zn(2+) ions by Zinquin fluorescent dye, and phosphorylated histone H2AX (γ-H2AX) expression were evaluated. The genotoxic potential of ZnO nanoparticles was also investigated by determining the levels of 8-hydroxyl-2'-deoxyguanosine (8-oxodG). The experimental data show that ZnO nanoparticles entered LoVo cells by either passive diffusion or endocytosis or both, depending on the agglomeration state of the nanomaterial. ZnO nanoparticles coming into contact with acid pH of lysosomes altered organelles structure, resulting in the release of Zn(2+) ions. The simultaneous presence of ZnO nanoparticles and Zn(2+) ions in the LoVo cells determined the formation of reactive oxygen species at the mitochondrial and nuclear level, inducing severe DNA damage.

  7. Tectorigenin inhibits Caco-2 human colon cells via NF-κB pathway suppression

    Directory of Open Access Journals (Sweden)

    Xiao-Yu Dai

    2015-12-01

    Full Text Available Effective immunomodulator and pro-inflammatory cytokine, Tumor necrosis factor-α (TNF-α are considered to be responsible for connecting autoimmune pathological process and contagious diseases. TNF-α stimulates the C-X-C motif chemokine 10 (CXCL10 expression that is participated in migration of tumor, metastasis, and invasion. Tectorigenin, an o-methylated isoflavone, is present as a major portion in the Iris tectorum rhizomes. In this study, we investigated the tectorigenin effects as an anticancer drug. The obtained results showed that tectorigenin hinders the invasion of human colon cancer cells (Caco-2. We used reverse transcription PCR, q-PCR and enzyme linked immunosorbent assays to test whether the tectorigenin is involved in the inhibition of TNF-α induced CXCL-10 expression in the Caco-2 cell lines. Further, we tested TNF-α induced NF-κB activity using the tectorigenin. Collective results showed that tectorigenin inhibits the CXCL10 production by using TNF-α via NF-κB inhibition.

  8. Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells.

    Science.gov (United States)

    Wang, Bo; Zhao, Xin-Huai

    2017-02-01

    Apigenin is one of the plant-originated flavones with anticancer activities. In this study, apigenin was assessed for its in vitro effects on a human colon carcinoma line (HCT‑116 cells) in terms of anti-proliferation, cell cycle progression arrest, apoptosis and intracellular reactive oxygen species (ROS) generation, and then outlined its possible apoptotic mechanism for the cells. Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase, and decreased mitochondrial membrane potential of the treated cells. Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells. Apigenin shows apoptosis induction towards the cells, resulting in enhanced portion of apoptotic cells. A mechanism involved ROS generation and endoplasmic reticulum stress was outlined for the apigenin-mediated apoptosis via both intrinsic mitochondrial and extrinsic pathways, based on the assayed mRNA and protein expression levels in the cells. With this mechanism, apigenin resulted in the HCT-116 cells with enhanced intracellular ROS generation and Ca2+ release together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.

  9. Evaluation of lignan (-)-cubebin extracted from Piper cubeba on human colon adenocarcinoma cells (HT29).

    Science.gov (United States)

    Niwa, Andressa Megumi; de Paula, Natalia Aparecida; Vesenick, Diogo Campos; Sartori, Daniele; Maistro, Edson Luis; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2016-01-01

    The dibenzylbutyrolactone lignan (-)-cubebin, which is extracted from the seeds of the pepper Piper cubeba, has shown promise as an anti-inflammatory, analgesic, leishmanicidal, antiproliferative, and trypanocidal compound. Given the therapeutic potential of (-)-cubebin, this study aimed to investigate its safety profile by analyzing cytotoxicity, mutagenicity, cell proliferation kinetics, induction of apoptosis, and expression of pro-apoptotic genes in human colon adenocarcinoma cells (HT29) exposed to (-)-cubebin. MTT cytotoxicity assays demonstrated that (-)-cubebin was cytotoxic only at 280 µM, whereas it was not cytotoxic at 2.8, 14, or 28 µM. Data demonstrated that (-)-cubebin was not mutagenic as evidenced by a micronucleus (MN) assay, did not alter cell-growth kinetics over 4 d, and showed absence of induced apoptosis after 24 h. Further, CASP8 and CASP9 gene expression was not markedly changed in HT29 cells exposed to 28 µM or 70 µM (-)-cubebin for 12 h. Based on our observations, (-)-cubebin was cytotoxic at a concentration of 280 µM, suggesting that the use of this concentration should be avoided. However, lower concentrations exerted no apparent damaging effects, indicating that this lignan is safe to use for pharmacological purposes at certain concentrations.

  10. Anti-proliferative effect of Melissa officinalis on human colon cancer cell line.

    Science.gov (United States)

    Encalada, Manuel Alejandro; Hoyos, Kelly Melissa; Rehecho, Sheyla; Berasategi, Izaskun; de Ciriano, Mikel García-Íñiguez; Ansorena, Diana; Astiasarán, Iciar; Navarro-Blasco, Iñigo; Cavero, Rita Yolanda; Calvo, María Isabel

    2011-11-01

    Melissa officinalis L. (Lamiaceae) is consumed as a traditional herbal tea in the Mediterranean region. The cytotoxic effect of the 50% ethanolic and aqueous extract, determined by the MTT and NR assays, was evaluated in vitro on Human Colon Cancer Cell Line (HCT-116), using Triton 10% as positive control. The 50% ethanolic extract showed significant differences after 72 h of treatment, reducing cell proliferation to values close to 40%, even the lowest dose tested (5 μg/ml). In the MTT assay, the same extract caused the lowest cell viability with 13% at a concentration of 1,000 μg/ml after 72 h of treatment, being a value lower than Triton 10%. The antioxidant activity was also confirmed evaluating the capacity of the extracts to scavenge ABTS and DPPH radicals, and IC(50) values were highly correlated with the total phenolic and flavonoid content. Bioassay guided fractionation led to the isolation of an anti-proliferative compound, rosmarinic acid. Its structural elucidation was performed by HPLC/DAD/ESI/MS analysis. High dose of rosmarinic acid (1,000 μg/ml) was clearly cytotoxic against HCT-116 cells, with a significant decrease in cell number since the earliest time point (24 h).

  11. Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hong Sun; Juan Ren; Qing Zhu; Fan-Zhong Kong; Lei Wu; Bo-Rong Pan

    2009-01-01

    AIM: To study the effects of lysophosphatidic acid (LPA) on proliferation, adhesion, migration, and apoptosisin the human colon cancer cell line, SW480, and its mechanisms of action. METHODS: Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transwell migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol.RESULTS: LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group (P < 0.05) while the mitogen-activated protein kinase (MAPK) inhibitor,PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner (P < 0.05). Rho kinase inhibitor,Y-27632, significantly inhibited the up-regulatory effect of LPA on adhesion and migration (P < 0.05). LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU (P < 0.05),but the phosphoinositide 3-kinase (PI3K) inhibitor,LY294002, significantly blocked the protective effect of LPA on apoptosis.CONCLUSION: LPA stimulated proliferation, adhesion,migration of SW480 cells, and protected from apoptosis.The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3KAKT/ PKB signal pathways may be involved.

  12. Laminarin induces apoptosis of human colon cancer LOVO cells through a mitochondrial pathway.

    Science.gov (United States)

    Ji, Yu Bin; Ji, Chen Feng; Zhang, He

    2012-08-20

    Many scientific studies have shown that laminarin has anti-tumor effects, but the anti-tumor mechanism was unclear. The purpose of this study was to investigate the effect of laminarin on the induction of apoptosis in human colon cancer LOVO cells and the molecular mechanism involved. LOVO cells were treated with different concentrations of laminarin at different times. Morphology observations were performed to determine the effects of laminarin on apoptosis of LOVO cells. Flow cytometry (FCM) was used to detect the level of intracellular reactive oxygen species (ROS) and pH. Laser scanning confocal microscope (LSCM) was used to analyze intracellular calcium ion concentration, mitochondrion permeability transition pore (MPTP) and mitochondrial membrane potential (MMP). Western blotd were performed to analyze the expressions of Cyt-C, Caspase-9 and -3. The results showed the apoptosis mo