Life Sciences Commons^™

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

David Turay, MD

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Franklin D. Shuler

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K2 (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation of …

Erbeta Regulation Of Nf-Kb Activation In Prostate Cancer Is Mediated By Hif-1, Paul Mak, Jiarong Li, Sanjoy Samanta, Arthur M. Mercurio

Arthur M. Mercurio

We examined the regulation of NF-kappaB in prostate cancer by estrogen receptor beta (ERbeta) based on the inverse correlation between p65 and ERbeta expression that exists in prostate carcinomas and reports that ERbeta can inhibit NF-kappaB activation, although the mechanism is not known. We demonstrate that ERbeta functions as a gate-keeper for NF-kappaB p65 signaling by repressing its expression and nuclear translocation. ERbeta regulation of NF-kappaB signaling is mediated by HIF-1. Loss of ERbeta or hypoxia stabilizes HIF-1alpha, which we found to be a direct driver of IKKbeta transcription through a hypoxia response element present in the promoter of the …

Oncology Section Edge Task Force On Breast Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Mary Insana Fisher, Jeannette Lee, Claire Davies, Hannah Geyer, Genevieve Colon, Lucinda Pfalzer

Mary Insana Fisher

Background: Breast cancer treatments in women with breast cancer often result in physical impairments that lead to activity limitations and participation restrictions. These limitations and restrictions manifest in impaired functional mobility skills that may impact survivorship. Thus, evaluation of functional mobility is an important part of survivorship care. Purpose: To identify functional mobility outcome measures that possess strong psychometric properties and are clinically useful for examination of women treated for breast cancer. Methods: Multiple electronic databases were searched for articles published after 1995. Studies were included if they reported psychometric properties, used clinically feasible methods, were performed on adults, and …

Breast Cancer Rehabilitation: Clinical Examination And Outcomes Assessment, Nicole L. Stout, Shana Harrington, Lucinda Pfalzer, Mary Insana Fisher

Mary Insana Fisher

Breast cancer is the most commonly diagnosed cancer in women in the United States. The treatment for breast cancer occurs along a protracted time period and includes many different disease treatment modalities. These treatments carry with them a large number of adverse effects that negatively impact function in both the short term and long term. It is necessary for rehabilitation providers to interface with patients being treated for breast cancer throughout the continuum of care so that interval assessments can be conducted to identify emerging impairments and alleviate disability. To achieve this, the rehabilitation provider must have an understanding of …

Oncology Section Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Clinical Measures Of Strength And Muscular Endurance, Mary Insana Fisher, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer

Mary Insana Fisher

Background: Strength deficits are a common morbidity following treatment for prostate cancer. Accurate assessment of strength and muscular endurance following prostate cancer treatments is essential to identify deficits and plan rehabilitation. Purpose: To identify strength and muscular endurance outcome measures that possess strong psychometric properties and are clinically useful for examination of men treated for prostate cancer. Methods: Multiple electronic databases were searched for articles published after 1995. Studies of tools used to assess strength and muscular endurance were included if they reported psychometric properties, were clinically feasible methods, performed on adults, and published in the English language. Each outcome …

A Comparison Of Upper Extremity Function Between Female Breast Cancer Survivors And Healthy Controls: Typical Self-Report Of Function, Motion, Strength, And Muscular Endurance, Mary Insana Fisher

Mary Insana Fisher

Many women who have experienced breast cancer (BC) report continued impairments in upper extremity (UE) function beyond the time required for normal healing after surgical treatment. Most research supporting this has not made comparisons between survivors of breast cancer (BCS) to a sample of healthy women. This lack of comparison to a healthy cohort prevents an understanding of whether continued deficits in UE function are due to normal aging or the BC treatment. The purpose of this research was to compare quality of life (QOL) and UE function among long term breast cancer survivors and similar aged women without cancer. …

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Zijian Xie

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Joseph I Shapiro MD

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Mary Insana Fisher

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Breast Cancer Edge Task Force Outcomes - Clinical Measures Of Strength And Muscular Endurance: A Systematic Review, Mary Insana Fisher, Claire Davies, Christine Beuthin, Genevieve Colon, Brittany Zoll, Lucinda Pfalzer

Mary Insana Fisher

Background: Muscular strength deficits are a common morbidity following treatment for breast cancer. Accurate assessment of strength and muscular endurance following breast cancer treatments is essential in identifying deficits and planning rehabilitation strategies.

Purpose: The purpose of this systematic review was to identify strength and muscular endurance outcome measures for use with women treated for breast cancer that possess strong psychometric properties and are clinically useful.

Methods: Multiple electronic databases were searched between February and June 2013. Included studies of tools used to assess strength and muscular endurance met the following criteria: reported psychometric properties, clinically feasible methods, adults (preferably …

Oncology Section Task Force On Breast Cancer Outcomes: An Introduction To The Edge Task Force And Clinical Measures Of Upper Extremity Function, Pamela K. Levangie, Mary Insana Fisher

Mary Insana Fisher

With the proliferation of outcome measures in the literature, many of which lack documentation of sufficient psychometric properties to justify use, it is difficult to document patient change or demonstrate effectiveness of interventions. The goal of the Section on Research’s EDGE (Evaluation Database to Guide Effectiveness) Task Force is to facilitate identification of valid and reliable tests and measures that reflect clinically important outcomes and are responsive to change for standard use across selected patient groups. This paper lays the groundwork for understanding the work of the Oncology Section’s Breast Cancer EDGE Task Force on clinical measures of shoulder function …

The Power Of Empowerment: An Icf-Based Model To Improve Self-Efficacy And Upper Extremity Function Of Survivors Of Breast Cancer, Mary Insana Fisher, Dana Howell

Mary Insana Fisher

Breast cancer is one of the most frequently diagnosed cancers among women. Breast cancer treatments often negatively impact the function of the arm, and quality of life and upper extremity function does not always return to a prediagnosis level. Survivors of breast cancer may also experience feelings of diminished self-efficacy related to functional deficits resulting from their physical limitations. The International Classification of Functioning (ICF) provides a framework for rehabilitation practitioners to address physical and psychological impairments, activity limitations, and participation restrictions. Patient outcomes may be improved by fostering self-efficacy through empowerment. This paper explores how the ICF model and …

Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong

Gyongyi Szabo

Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Betsy Donahoe-Fillmore

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold Merriman

Harold L. Merriman

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Goran Boskovic

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald Primerano, Richard Niles

James Denvir

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Elaine Hardman Ph.D.

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Donald A. Primerano

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Richard M. Niles

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Richard M. Niles

Background Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Richard M. Niles

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …

Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun Iyer, Keinosuke Ryu, Edwin Choi, Francis Hornicek, Henry Mankin, Lara Milane, Mansoor Amiji, Zhenfeng Duan

Arun Iyer

Background: The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients’ average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy. Methodology/Principal Findings: In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy …

Decarboxylation Of L-Dopa And 5-Hydroxytryptophan In Dispersed Rat Pancreas Acinar Cells, E. Yu, L. Stern, A. Tenenhouse

Edward Yu

Amino acid decarboxylation activity in dispersed rat pancreas acinar cells and fractions derived by differential centrifugation of homogenate of these cells was studied. The rate of decarboxylation was measured by determining the rate of production of the [3H]-amine from [3H]-amino acid or the rate of production of 14CO2 from the [14C]-carboxy-labelled amino acid. Only the hydroxylated amino acids L-dopa and 5-hydroxytryptophan are decarboxylated by intact dispersed pancreas acinar cells or cell homogenates at all pH values and amino acid concentrations tested. The decarboxylase activity is located exclusively in the cell cytosol. Each substrate competitively inhibits the decarboxylation of the other …

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 …

Collaborative Roles For C-Jun N-Terminal Kinase, C-Jun, Serum Response Factor, And Sp1 In Calcium-Regulated Myocardial Gene Expression, Patrick M. Mcdonough, Deanna S. Hanford, Amy B. Sprenkle, Noel R. Mellon, Christopher C. Glembotski

Amy Sprenkle