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Cancer Biology Commons

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2009

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Articles 1 - 21 of 21

Full-Text Articles in Cancer Biology

Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski Dec 2009

Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski

Goldi A Kozloski

The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or signaling mechanisms. In particular, Muc4/MUC4 can serve as a ligand/modulator of the receptor tyrosine kinase ErbB2, regulating its phosphorylation and the phosphorylation of its partner ErbB3, with or without the involvement of the ErbB3 ligand neuregulin. Muc4/MUC4 can also modulate cell apoptosis via multiple mechanisms, both ErbB2 dependent and independent. Muc4/MUC4 expression is regulated by multiple ...


Lymphatic Pump Treatment Enhances Pulmonary Immunity And Inhibits Solid Tumor Formation In The Lung, Mayela Pedrueza Dec 2009

Lymphatic Pump Treatment Enhances Pulmonary Immunity And Inhibits Solid Tumor Formation In The Lung, Mayela Pedrueza

Theses and Dissertations

No abstract provided.


Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr Nov 2009

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.


Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr Oct 2009

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Maria Cekanova MS, RNDr, PhD

No abstract provided.


Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle Oct 2009

Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle

Open Dartmouth: Faculty Open Access Scholarship

Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.


Conformational Changes In Receptor Tyrosine Kinase Signaling: An Erbb Garden Of Delights., Goldi Kozloski Sep 2009

Conformational Changes In Receptor Tyrosine Kinase Signaling: An Erbb Garden Of Delights., Goldi Kozloski

Goldi A Kozloski

The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors.



Mechanisms Of Notch1 Mediated Leukemogenesis: A Dissertation, Kathleen J. Cullion Sep 2009

Mechanisms Of Notch1 Mediated Leukemogenesis: A Dissertation, Kathleen J. Cullion

GSBS Dissertations and Theses

Gain of function NOTCH1 mutations are common in both patients with T-ALL and in mouse models of the disease. Inhibiting the Notch pathway in T-ALL cell lines results in growth arrest and/or apoptosis in vitro, suggesting a requirement for Notch signaling in T-ALL. Therefore, we sought to examine the role of Notch1 signaling in both premalignancy and in the maintenance of leukemic growth. Using a murine model of T-ALL, in which expression of the Tal1 and Lmo2 oncogenes arrests thymocyte development, our preleukemic studies reveal that Notch1 mutations are early events that contribute to the clonal expansion of DN3 ...


Survivin As A Global Target Of Intrinsic Tumor Suppression Networks, Minakshi Guha, Dario C. Altieri Sep 2009

Survivin As A Global Target Of Intrinsic Tumor Suppression Networks, Minakshi Guha, Dario C. Altieri

Open Access Articles

Despite the constant exposure to genomic insults that may lead to malignancy, cancer is surprisingly a relatively rare occurrence, and this is largely credited to an elaborate network of endogenous tumor suppression. Many effectors of tumor suppression have been identified, and their functions when activated in damaged cells have in large part been elucidated. What is less clear is whether there are common target gene(s) of tumor suppression, whose expression must be ablated in order to block transformation and preserve cellular homeostasis. Fresh experimental evidence suggests that silencing of the mitotic regulator and cell death inhibitor, survivin, is a ...


Expression Of An Alternate Splice Form Of Bmi-1 In Multiple Myeloma, Adam Austin, Kristine Veys, Debbie Wong, James Tung Aug 2009

Expression Of An Alternate Splice Form Of Bmi-1 In Multiple Myeloma, Adam Austin, Kristine Veys, Debbie Wong, James Tung

Undergraduate Research Opportunities Program (UROP)

The concept of “tumor stem cells” has garnered much attention in the last few years. Tumor stem cells are believed to exist among a heterogeneous group of cells that constitute a tumor. These tumor stem cells often express genes that are important for stem cell function, cell division, and maintenance of pluripotent state in stem cells. Stem cell or stem cell maintenance genes such as SALL 4 and Bmi-1 are often seen in these cancer cells and contribute to self-renewing divisions and cancer cell survival. In particular, high expression of Bmi-1 (B lymphoma mouse Moloney leukemia virus insertion region), a ...


Pdest Fg12-Cmv Dsred Vector, Jarod Wolffis, Sheri L. Holmen Aug 2009

Pdest Fg12-Cmv Dsred Vector, Jarod Wolffis, Sheri L. Holmen

Undergraduate Research Opportunities Program (UROP)

Melanoma is the most rapidly increasing malignancy among young people in the United States. If detected early, the disease is easily treated; however, once the disease has metastasized it is largely refractory to conventional therapies and is associated with a high mortality rate. The development of human cancer from a pre-malignant primary tumor to a metastatic lesion that develops at secondary sites is thought to be a multi-step process, requiring many genetic and epigenetic events that provide a growth advantage to cells. It is still unclear which of the many genetic changes in human cancers are required for metastasis. Therefore ...


Nod2, Rip2 And Irf5 Play A Critical Role In The Type I Interferon Response To Mycobacterium Tuberculosis, Amit K. Pandey, Yibin Yang, Zhaozhao Jiang, Sarah M. Fortune, Francois Coulombe, Marcel A. Behr, Katherine A. Fitzgerald, Christopher M. Sassetti, Michelle A. Kelliher Jul 2009

Nod2, Rip2 And Irf5 Play A Critical Role In The Type I Interferon Response To Mycobacterium Tuberculosis, Amit K. Pandey, Yibin Yang, Zhaozhao Jiang, Sarah M. Fortune, Francois Coulombe, Marcel A. Behr, Katherine A. Fitzgerald, Christopher M. Sassetti, Michelle A. Kelliher

Open Access Articles

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNalpha and IFNbeta, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds ...


Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, Maria Cekanova, Seong-Ho Lee, Robert Donnell, M Sukhthankar, Te Eling, Sm Fischer, Seung Baek Apr 2009

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, Maria Cekanova, Seong-Ho Lee, Robert Donnell, M Sukhthankar, Te Eling, Sm Fischer, Seung Baek

Maria Cekanova MS, RNDr, PhD

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6 background). In the present study, we investigated whether the NAG-1 protein would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB background (NAG-1(Tg+/FVB)). NAG-1(Tg+/FVB) mice had both decreased number and size of urethane-induced tumors, compared with control littermates (NAG-1(Tg+/FVB) = 16 +/- 4 per mouse versus control = 20 +/- 7 per mouse, P < 0.05). Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control mice; however, only pulmonary adenomas were observed in NAG-1(Tg+/FVB) mice. Urethane-induced tumors from control littermates and NAG-1(Tg+/FVB) mice highly expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2, prostaglandin E synthase, and prostaglandin E(2) receptor) and highly activated several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation was decreased in NAG-1(Tg+/FVB) mice. Furthermore, significantly increased apoptosis in tumors of NAG-1(Tg+/FVB) mice compared with control mice was observed as assessed by caspase-3/7 activity. In addition, fewer inflammatory cells were observed in the lung tissue isolated from urethane-treated NAG-1(Tg+/FVB) mice compared with control mice. These results paralleled in vitro assays using human A549 pulmonary carcinoma cells. Less phosphorylated p38 MAPK was observed in cells overexpressing NAG-1 compared with control cells. Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer chemoprevention.


Soy Isoflavones Have An Antiestrogenic Effect And Alter Mammary Promoter Hypermethylation In Healthy Premenopausal Women1, Wenyi Qin, Weizhu Zhu, Huidong Shi, John E. Hewett, Rachel L. Ruhlen, Ruth S. Macdonald, George E. Rottinghaus, Yin-Chieh Chien, Edward R. Sauter Feb 2009

Soy Isoflavones Have An Antiestrogenic Effect And Alter Mammary Promoter Hypermethylation In Healthy Premenopausal Women1, Wenyi Qin, Weizhu Zhu, Huidong Shi, John E. Hewett, Rachel L. Ruhlen, Ruth S. Macdonald, George E. Rottinghaus, Yin-Chieh Chien, Edward R. Sauter

Food Science and Human Nutrition Publications

We hypothesized that soy isoflavones would have dose related estrogenic and methylation effects. 34 healthy premenopausal women were prospectively enrolled and randomized in double-blind fashion to receive either 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific (NAF) and systemic (serum) estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, while methylation effects were evaluated in mammary ductoscopy (MD) specimens using methylation specific PCR assessment of five genes (p16, RASSF1A, RARβ2, ER, and CCND2) associated with breast carcinogenesis. Serum genistein significantly increased post treatment in women consuming both isoflavone doses ...


Mmtv-Wnt1 And -Dn89b-Catenin Induce Canonical Signaling In Distinct Progenitors And Differentially Activate Hedgehog Signaling Within Mammary Tumors, Brigitte Teissedre, Alicia Pinderhughes, Angela Incassati, Sarah J. Hatsell, Minoti Hiremath, Pamela Cowin Feb 2009

Mmtv-Wnt1 And -Dn89b-Catenin Induce Canonical Signaling In Distinct Progenitors And Differentially Activate Hedgehog Signaling Within Mammary Tumors, Brigitte Teissedre, Alicia Pinderhughes, Angela Incassati, Sarah J. Hatsell, Minoti Hiremath, Pamela Cowin

Minoti Hiremath

Canonical Wnt/b-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTVWnt1 and MMTV-DN89b-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DN89b-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DN89b-catenin activate canonical Wnt signaling within distinct cell-types. DN89b-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18+ER2PR2CD24highCD49flow profile and ...


Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash Jan 2009

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell ...


The Effect Of Sex And Background On Doxorubicin-Induced Cardiotoxicity In Carbonyl Reductase 1 +/- Mice: A Comparative Study, Megan M. Freeland Jan 2009

The Effect Of Sex And Background On Doxorubicin-Induced Cardiotoxicity In Carbonyl Reductase 1 +/- Mice: A Comparative Study, Megan M. Freeland

Undergraduate Honors Theses

Doxorubicin has long been used clinically to treat a variety of cancers. Unfortunately, its success is limited due to its cardiotoxic side effects, restricting the cumulative dose that can be given to patients. It is known that the enzyme carbonyl reductase 1 (Cbr1) metabolizes this cancer drug in vivo, leading to the production of its toxic alcohol metabolite, doxorubicinol. A previous study has indicated that decreasing the expression level of carbonyl reductase 1 in male Cbr1+/- mice provided them with significant protection from doxorubicin-induced cardiotoxicity when compared to their wild type littermates. With the intent to identify whether the protection ...


Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro Jan 2009

Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling ...


Repressive Effects Of Resveratrol On Androgen Receptor Transcriptional Activity, Wenfeng Shi, Melanie Leong, Ellen Cho, Joseph Farrell, Hanchun Chen, Jun Tian, Dianzheng Zhang Jan 2009

Repressive Effects Of Resveratrol On Androgen Receptor Transcriptional Activity, Wenfeng Shi, Melanie Leong, Ellen Cho, Joseph Farrell, Hanchun Chen, Jun Tian, Dianzheng Zhang

PCOM Scholarly Papers

Background: The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity. Methodology: The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of ARnegative HeLa cells to generate the AR(+) cells. The constitutively expressed AR was characterized by monitoring hormonestimulated nuclear translocation, DNA binding, and transcriptional activation ...


Overexpression Of Truncated Erg From Tmprss2-Erg Fusion And Prostate Cancer Development , Melanie Leong, Wenfeng Shi, Jun Tian, Ellen Cho, Abbas Raza, Saquib A. Siddiqi, Abdulhafez Selim, Hanchun Chen, Dianzheng Zhang Jan 2009

Overexpression Of Truncated Erg From Tmprss2-Erg Fusion And Prostate Cancer Development , Melanie Leong, Wenfeng Shi, Jun Tian, Ellen Cho, Abbas Raza, Saquib A. Siddiqi, Abdulhafez Selim, Hanchun Chen, Dianzheng Zhang

PCOM Scholarly Papers

No abstract provided.


Targeted Inhibition Of The Egfr Pathways Enhances Zn-Bc-Am Pdt-Induced Apoptosis In Well-Differentiated Nasopharyngeal Carcinoma Cells, Hk Koon, Ps Chan, Rns Wong, Zg Wu, Ml Lung, Ck Chang, N.K. Mak Dec 2008

Targeted Inhibition Of The Egfr Pathways Enhances Zn-Bc-Am Pdt-Induced Apoptosis In Well-Differentiated Nasopharyngeal Carcinoma Cells, Hk Koon, Ps Chan, Rns Wong, Zg Wu, Ml Lung, Ck Chang, N.K. Mak

Professor MAK, Nai Ki

No abstract provided.


Oncogenesis And Cancer Stem Cells: Current Opinions And Future Directions., Xiaoyu Cheng, Helen O'Neill Dec 2008

Oncogenesis And Cancer Stem Cells: Current Opinions And Future Directions., Xiaoyu Cheng, Helen O'Neill

Helen O'Neill

There is increasing evidence to show that only a subset of cancer cells drives the growth and progression of a tumour. These cells share similar properties with normal stem cells and are termed 'cancer stem cells'. Cancer stem cells have been identified in acute myeloid leukaemia and in some solid tumours by their distinct expression of cell surface antigens. Their long-term, self-renewing capacity is thought to be a determining factor in the maintenance and regrowth of the tumour. Studies on haematopoietic cancers show that important signalling pathways and genes for normal haematopoiesis, such as Wnt, NF-kappaB, Notch, hedgehog (Hh) and ...