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Articles 481 - 510 of 579

Full-Text Articles in Medical Specialties

Unilateral Thalamic Infarction Presenting As Vertical Gaze Palsy: A Case Report, Muhib Khan, Christos Sidiropoulos, Panayiotis Mitsias Jan 2011

Unilateral Thalamic Infarction Presenting As Vertical Gaze Palsy: A Case Report, Muhib Khan, Christos Sidiropoulos, Panayiotis Mitsias

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction.

Case presentation

We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation.

Conclusions

This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze …


Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou Jan 2011

Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. …


Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved Jan 2011

Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods

We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real …


The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White Jan 2011

The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White

Wayne State University Dissertations

Post-operative adhesion development occurs in the vast majority of patients following abdominal surgery and is a natural occurrence of peritoneal-wound healing. These fibrous bands may form within the first 5-7 days post-surgery and have the ability to cause a distortion in the normal anatomical positioning of abdominal organs. Consequently, adhesions are major contributors to small bowel obstruction, infertility, and severe pelvic and abdominal pain. Physiological processes responsible for adhesion formation remain obscure though it is believed to involve cell migration, proliferation, and differentiation of several cell types including mesothelial cells, fibroblasts, and inflammatory and immune cells. Substances released from these …


Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Edwin Choy, Francis J. Hornicek, Henry Mankin, Lara Milane, Mansoor M. Amiji, Zhenfeng Duan May 2010

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

Pharmaceutical Sciences Faculty Publications

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 …


Spermine Oxidase (Smo) Activity In Breast Tumor Tissues And Biochemical Analysis Of The Anticancer Spermine Analogues Benspm And Cpenspm, Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A. Casero Jr, Paolo Mariottini Jan 2010

Spermine Oxidase (Smo) Activity In Breast Tumor Tissues And Biochemical Analysis Of The Anticancer Spermine Analogues Benspm And Cpenspm, Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A. Casero Jr, Paolo Mariottini

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.

Methods

BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT …


Antioxidant Rich Grape Pomace Extract Suppresses Postprandial Hyperglycemia In Diabetic Mice By Specifically Inhibiting Alpha-Glucosidase, Shelly Hogan, Lei Zhang, Jianrong Li, Shi Sun, Corene Canning, Kequan Zhou Jan 2010

Antioxidant Rich Grape Pomace Extract Suppresses Postprandial Hyperglycemia In Diabetic Mice By Specifically Inhibiting Alpha-Glucosidase, Shelly Hogan, Lei Zhang, Jianrong Li, Shi Sun, Corene Canning, Kequan Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo.

Methods

The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An …


Angiogenesis Inhibitors In The Treatment Of Prostate Cancer, Clara Hwang, Elisabeth I. Heath Jan 2010

Angiogenesis Inhibitors In The Treatment Of Prostate Cancer, Clara Hwang, Elisabeth I. Heath

Wayne State University Associated BioMed Central Scholarship

Abstract

Prostate cancer remains a significant public health problem, with limited therapeutic options in the setting of castrate-resistant metastatic disease. Angiogenesis inhibition is a relatively novel antineoplastic approach, which targets the reliance of tumor growth on the formation of new blood vessels. This strategy has been used successfully in other solid tumor types, with the FDA approval of anti-angiogenic agents in breast, lung, colon, brain, and kidney cancer. The application of anti-angiogenic therapy to prostate cancer is reviewed in this article, with attention to efficacy and toxicity results from several classes of anti-angiogenic agents. Ultimately, the fate of anti-angiogenic agents …


Vaccination With A Plasmid Dna Encoding Her-2/Neu Together With Low Doses Of Gm-Csf And Il-2 In Patients With Metastatic Breast Carcinoma: A Pilot Clinical Trial, Hã¥Kan Norell, Isabel Poschke, Jehad Charo, Wei Z. Wei, Courtney Erskine, Marie P. Piechocki, Keith L. Knutson, Jonas Bergh, Elisabet Lidbrink, Rolf Kiessling Jan 2010

Vaccination With A Plasmid Dna Encoding Her-2/Neu Together With Low Doses Of Gm-Csf And Il-2 In Patients With Metastatic Breast Carcinoma: A Pilot Clinical Trial, Hã¥Kan Norell, Isabel Poschke, Jehad Charo, Wei Z. Wei, Courtney Erskine, Marie P. Piechocki, Keith L. Knutson, Jonas Bergh, Elisabet Lidbrink, Rolf Kiessling

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Adjuvant trastuzumab (Herceptin) treatment of breast cancer patients significantly improves their clinical outcome. Vaccination is an attractive alternative approach to provide HER-2/neu (Her2)-specific antibodies and may in addition concomitantly stimulate Her2-reactive T-cells. Here we report the first administration of a Her2-plasmid DNA (pDNA) vaccine in humans.

Patients and Methods

The vaccine, encoding a full-length signaling-deficient version of the oncogene Her2, was administered together with low doses of GM-CSF and IL-2 to patients with metastatic Her2-expressing breast carcinoma who were also treated with trastuzumab. Six of eight enrolled patients completed all three vaccine cycles. In the remaining two patients …


Sulforaphane Induces Cell Cycle Arrest By Protecting Rb-E2f-1 Complex In Epithelial Ovarian Cancer Cells, Christopher S. Bryant, Sanjeev Kumar, Sreedhar Chamala, Jay Shah, Jagannath Pal, Mahdi Haider, Shelly Seward, Aamer M. Qazi, Robert Morris, Assaad Semaan, Masood A. Shammas, Christopher Steffes, Ravindra B. Potti, Madhu Prasad, Donald W. Weaver, Ramesh B. Batchu Jan 2010

Sulforaphane Induces Cell Cycle Arrest By Protecting Rb-E2f-1 Complex In Epithelial Ovarian Cancer Cells, Christopher S. Bryant, Sanjeev Kumar, Sreedhar Chamala, Jay Shah, Jagannath Pal, Mahdi Haider, Shelly Seward, Aamer M. Qazi, Robert Morris, Assaad Semaan, Masood A. Shammas, Christopher Steffes, Ravindra B. Potti, Madhu Prasad, Donald W. Weaver, Ramesh B. Batchu

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.

Results

SFN at concentrations of 5 - 20 …


Elevated Csf Outflow Resistance Associated With Impaired Lymphatic Csf Absorption In A Rat Model Of Kaolin-Induced Communicating Hydrocephalus, Gurjit Nagra, Mark E. Wagshul, Shams Rashid, Jie Li, J Pat Mcallister Ii, Miles Johnston Jan 2010

Elevated Csf Outflow Resistance Associated With Impaired Lymphatic Csf Absorption In A Rat Model Of Kaolin-Induced Communicating Hydrocephalus, Gurjit Nagra, Mark E. Wagshul, Shams Rashid, Jie Li, J Pat Mcallister Ii, Miles Johnston

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance).

Methods

Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging …


Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh Jan 2010

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …


Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv Jan 2010

Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor.

Methods

Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was …


Adaptive Radiation Therapy Of Prostate Cancer, Ning Wen Jan 2010

Adaptive Radiation Therapy Of Prostate Cancer, Ning Wen

Wayne State University Dissertations

ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT.

The dose from CBCT was measured in phantom using TLD and ion chamber techniques …


Identification Of Neuroblastoma And Its Prognostic Markers Using Raman Spectroscopy, Rachel Kast Jan 2010

Identification Of Neuroblastoma And Its Prognostic Markers Using Raman Spectroscopy, Rachel Kast

Wayne State University Dissertations

Introduction: Neuroblastoma is the most common cancer of infancy. It is one of several peripheral nervous system tumors, including ganglioneuroma, peripheral nerve sheath tumor, and pheochromocytoma. It is commonly situated on the adrenal gland. It displays similar histology to other small round blue cell tumors, including non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma. One method of judging neuroblastoma aggressiveness uses tumor histology factors, including mitosis-karyorrhexis index, Schwannian stromal development, degree of differentiation, and patient age. Tumor aggressiveness can also be judged based on the amplification of certain genes, including MYCN. Raman spectroscopy is a physics-based method which identifies the biochemical …


Egfr/Met Association Regulates Egfr Tki Resistance In Breast Cancer, Kelly L. Mueller, Zeng-Quan Yang, Ramsi Haddad, Stephen P. Ethier, Julie L. Boerner Jan 2010

Egfr/Met Association Regulates Egfr Tki Resistance In Breast Cancer, Kelly L. Mueller, Zeng-Quan Yang, Ramsi Haddad, Stephen P. Ethier, Julie L. Boerner

Wayne State University Associated BioMed Central Scholarship

Abstract

Breast cancers show a lack of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), despite 30% of tumors expressing EGFR. The mechanism of this resistance is unknown; however, we have recently shown that Met kinase activity compensates for loss of EGFR kinase activity in cell culture models. Met has been implicated in the pathogenesis of breast tumors and therefore may cooperate with EGFR for tumor growth. Here we have found that EGFR phosphorylation and cell proliferation is in part regulated by Met expression. In addition, we found that Met constitutive phosphorylation occurred independent of the Met …


Synergistic Effects Of Garcinol And Gemcitabine In Enhancing Therapeutic Efficacy In Pancreatic Adenocarcinoma Cells And Its Effect On Microrna Profile, Mansi Anand Parasramka Jan 2010

Synergistic Effects Of Garcinol And Gemcitabine In Enhancing Therapeutic Efficacy In Pancreatic Adenocarcinoma Cells And Its Effect On Microrna Profile, Mansi Anand Parasramka

Wayne State University Dissertations

SYNERGISTIC EFFECTS OF GARCINOL AND GEMCITABINE IN ENHANCING THERAPEUTIC EFFICACY IN PANCREATIC ADENOCARCINOMA CELLS AND ITS EFFECT ON MICRORNA PROFILE

By

MANSI PARASRAMKA

ADVISOR: DR. SMITI V. GUPTA

MAJOR: NUTRITION AND FOOD SCIENCE

DEGREE: DOCTOR OF PHILOSPHY

Human Pancreatic Cancer (PaCa) is one of the most hostile and fourth leading cause of cancer deaths in the United States. Current standard chemotherapeutic agent for advanced PaCa is gemcitabine, a cytotoxic nucleoside analogue which results in modest response due to high degree of inherent and acquired chemo resistance. Forthcoming evidence strongly supports that non-nutritive food components have therapeutic benefits attributable to pleiotropic …


Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka Jan 2010

Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka

Wayne State University Dissertations

Myelin is a multilamellar membrane structure surrounding axons in both the CNS and PNS that facilitates nerve conduction. In the CNS, myelin is synthesized by oligodendrocytes, while in the PNS, myelin is synthesized by Schwann cells. In the CNS, Proteolipid protein 1 (PLP1), an integral membrane protein, is the major protein component of myelin, constituting ~50% of myelin protein. Mutations of the PLP1 gene in man cause a spectrum of neurological disease, ranging from the severe Pelizaeus-Merzbacher disease (PMD), that typically begins during infancy with nystagmus, seizures and hypotonia and evolves into spastic quadriparesis, cognitive impairment and ataxia, to ¡¥pure¡¦ …


I-Kappa-Kinase-2 (Ikk-2) Inhibition Potentiates Vincristine Cytotoxicity In Non-Hodgkin's Lymphoma, Ayad Al-Katib, Alan A. Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N. Mohamed, Frances W. Beck, Ramzi M. Mohammad Jan 2010

I-Kappa-Kinase-2 (Ikk-2) Inhibition Potentiates Vincristine Cytotoxicity In Non-Hodgkin's Lymphoma, Ayad Al-Katib, Alan A. Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N. Mohamed, Frances W. Beck, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma.

Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), …


The Wnt/Β-Catenin Pathway Regulates Growth And Maintenance Of Colonospheres, Shailender S. Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B. Patel, Adhip Pn Majumdar Jan 2010

The Wnt/Β-Catenin Pathway Regulates Growth And Maintenance Of Colonospheres, Shailender S. Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B. Patel, Adhip Pn Majumdar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Recent evidence suggests that epithelial cancers, including colorectal cancer are driven by a small sub-population of self-renewing, multi-potent cells termed cancer stem cells (CSCs) which are thought to be responsible for recurrence of cancer. One of the characteristics of CSCs is their ability to form floating spheroids under anchorage-independent conditions in a serum-free defined media. The current investigation was undertaken to examine the role of Wnt/β-catenin pathway in regulating the growth and maintenance of colonospheres. Human colon cancer cells HCT-116 (p53 wild type; K-ras mutant), HCT-116 (p53 null; K-ras mutant) and HT-29 (p53 mutant) were used.

Results

Colonospheres …


A Novel Mechanism Of Cell Growth Regulation By Cell Cycle And Apoptosis Regulatory Protein (Carp)-1, Yan Jiang, Vineshkumar T. Puliyappadamba, Liyue Zhang, Wenjuan Wu, Anil Wali, Michael B. Yaffe, Joseph A. Fontana, Arun K. Rishi Jan 2010

A Novel Mechanism Of Cell Growth Regulation By Cell Cycle And Apoptosis Regulatory Protein (Carp)-1, Yan Jiang, Vineshkumar T. Puliyappadamba, Liyue Zhang, Wenjuan Wu, Anil Wali, Michael B. Yaffe, Joseph A. Fontana, Arun K. Rishi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

CARP-1/CCAR1, a perinuclear phospho-protein, regulates signaling by adriamycin, steroids, or growth factors. However, intracellular events that regulate CARP-1-dependent cell growth are not fully understood.

Results

Here we investigated whether CARP-1 is involved in signaling induced by the protein kinase A inhibitor H89. Treatments of human breast cancer cells with H89 resulted in apoptosis that involved enhanced CARP-1 threonine phosphorylation and expression. Depletion of CARP-1, on the other hand, abrogates apoptosis induced by H89. CARP-1 binds with signal transducer TAZ and over-expression of TAZ inhibits apoptosis by CARP-1. CARP-1 (651-759) interacts with a novel, N-terminal epitope of TAZ. H89 …


Acute Subarachnoid Hemorrhage And Cardiac Abnormalities: Takotsubo Cardiomyopathy Or Neurogenic Stunned Myocardium? A Case Report, C Franco, B Khaled, L Afonso, M Raufi Jan 2010

Acute Subarachnoid Hemorrhage And Cardiac Abnormalities: Takotsubo Cardiomyopathy Or Neurogenic Stunned Myocardium? A Case Report, C Franco, B Khaled, L Afonso, M Raufi

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Cardiac abnormalities can be seen with subarachnoid hemorrhage. To date, there have been isolated case reports of transient left ventricular apical ballooning cardiomyopathy, also known as Takotsubo cardiomyopathy in patients suffering from subarachnoid hemorrhage.

Case presentation

An adult female was brought to the emergency department with somnolence. A 3 × 3 mm ruptured basilar aneurysm was found and successfully embolized. Two days after the patient developed acute heart failure. Troponin-I was elevated to 4.2 (normal <0.4). On ECG, new symmetric T wave inversion in V3, V4, V5 with prolonged QT were evident. Transthoracic echocardiogram showed severe systolic dysfunction with an ejection fraction of 20% and akinetic apex along with the distal left ventricular segments, consistent with Takotsubo cardiomyopathy. Myocardial contrast echocardiography showed a decrease in capillary blood flow and volume in the akinetic areas with delayed contrast replenishment, sparing the basal segments. A repeat study 2 weeks later showed near normalization of the perfusion parameters. The patient improved with medical management. A repeat echocardiogram, a month later revealed an ejection fraction of 45% with no identifiable wall motion abnormality.

Conclusion

Our case, as well as others reported previously, supports the diagnosis of Takotsubo cardiomyopathy in patients with Subarachnoid Hemorrhage who fulfill the …


Utility Of Immunohistochemical Markers In Differentiating Benign From Malignant Follicular-Derived Thyroid Nodules, Husain A. Saleh, Bo Jin, John Barnwell, Opada Alzohaili Jan 2010

Utility Of Immunohistochemical Markers In Differentiating Benign From Malignant Follicular-Derived Thyroid Nodules, Husain A. Saleh, Bo Jin, John Barnwell, Opada Alzohaili

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Thyroid nodules are common among adults though only a small percentage is malignant, which can histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management.

Methods

We investigated immunoexpression in 98 surgically removed benign thyroid nodules including 52 hyperplastic nodules (HN) and 46 follicular/Hurthle cell adenomas (FA), and 54 malignant tumors including 22 follicular carcinoma (FC), 20 classic papillary carcinoma (PTC), and 12 follicular variant papillary carcinoma (FVPC).

Results

The staining results showed that malignant tumors express galectin-3, HBME-1, CK19 and Ret oncoprotein significantly more than benign nodules. The sensitivity of …


Activation Of Tumor Cell Death Program By Targeting The Ubiquitin-Proteasome Pathway: Significance In Cancer Treatment And Prevention, Michael Joseph Frezza Jan 2010

Activation Of Tumor Cell Death Program By Targeting The Ubiquitin-Proteasome Pathway: Significance In Cancer Treatment And Prevention, Michael Joseph Frezza

Wayne State University Dissertations

ACTIVATION OF TUMOR CELL DEATH PROGRAM BY TARGETING THE UBIQUITIN-PROTEASOME PATHWAY: SIGNIFICANCE IN CANCER TREATMENT AND PREVENTION

by

MICHAEL FREZZA

August 2010

Advisor: Dr. Q. Ping Dou

Major: Cancer Biology

Degree: Doctor of Philosophy

The ubiquitin-proteasome pathway serves as a quality control mechanism to regulate the degradation of intracellular proteins involved in a wide array of cellular processes including tumorigeneis. Thus targeting key features of protein turnover responsible for the growth and proliferation of cancer have emerged as a favorable approach in cancer therapy. Both in vitro and in vivo experimental and clinical results have demonstrated the potential use of …


Defensins In Ocular Immunity, Minhao Wu Jan 2010

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …


Hepatic Failure, Neonatal Hemochromatosis And Porto-Pulmonary Hypertension In A Newborn With Trisomy 21 - A Case Report, Erin Neil, Josef Cortez, Aparna Joshi, Erawati V. Bawle, Janet Poulik, Mark Zilberman, Mohammad F. El-Baba, Beena G. Sood Jan 2010

Hepatic Failure, Neonatal Hemochromatosis And Porto-Pulmonary Hypertension In A Newborn With Trisomy 21 - A Case Report, Erin Neil, Josef Cortez, Aparna Joshi, Erawati V. Bawle, Janet Poulik, Mark Zilberman, Mohammad F. El-Baba, Beena G. Sood

Wayne State University Associated BioMed Central Scholarship

Abstract

Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis. A less commonly recognized cause of liver failure in neonates with Trisomy 21 is neonatal hemochromatosis (NH); this association has been reported in nine cases of Trisomy 21 in literature. NH is a rare, severe liver disease of intra-uterine onset that is characterized by neonatal …


Novel Cis-Trans Interactions Are Involved In Post-Transcriptional Regulation Of Cyclin-Dependent Kinase Inhibitor P21Waf1/Cip1 Mrna, Liyue Zhang, Anil Wali, Joseph A. Fontana, Marcia I. Dawson, Arun K. Rishi Jan 2010

Novel Cis-Trans Interactions Are Involved In Post-Transcriptional Regulation Of Cyclin-Dependent Kinase Inhibitor P21Waf1/Cip1 Mrna, Liyue Zhang, Anil Wali, Joseph A. Fontana, Marcia I. Dawson, Arun K. Rishi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

A variety of pathways target CDKI p21WAF1/CIP1 expression at transcriptional, post-transcriptional as well as translational levels. We previously found that cell growth suppressing retinoid CD437 enhanced expression of p21WAF1/CIP1 and DNA damage inducible GADD45 proteins in part by elevating their mRNA stability.

Results

Here, we investigated molecular mechanisms of CD437-dependent post-transcriptional regulation of p21WAF1/CIP1 expression. By utilizing MDA-MB-468 HBC cells expressing chimeric rabbit β-globin-p21WAF1/CIP1 transcripts we mapped multiple CD437-responsive sequences located within positions 1195 to 1795 of the 3'-untranslated region of p21WAF1/CIP1 mRNA. Several cytoplasmic proteins present in MDA-MB-468, MCF-7 HBC as well …


Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis J. Hornicek, Henry Mankin, Mansoor M. Amiji, Zhenfeng Duan Nov 2009

Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis J. Hornicek, Henry Mankin, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the …


Emerging Role Of Garcinol, The Antioxidant Chalcone From Garcinia Indica Choisy And Its Synthetic Analogs, Subhash Padhye, Aamir Ahmad, Nikhil Oswal, Fazlul H. Sarkar Jan 2009

Emerging Role Of Garcinol, The Antioxidant Chalcone From Garcinia Indica Choisy And Its Synthetic Analogs, Subhash Padhye, Aamir Ahmad, Nikhil Oswal, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed …


A Unique Case Of Urinary Bladder Simple Melanosis: A Case Report And Review Of The Literature, Bo Jin, Syed Y. Zaidi, Melvin Hollowell, Christopher Hollowell, Husain Saleh Jan 2009

A Unique Case Of Urinary Bladder Simple Melanosis: A Case Report And Review Of The Literature, Bo Jin, Syed Y. Zaidi, Melvin Hollowell, Christopher Hollowell, Husain Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Melanosis refers to abnormal or excessive deposition of melanin pigment in the cells and/or tissue, which can be seen in any organ but commonly in skin and oral mucosa. Melanosis of the urinary bladder is an extremely rare benign condition and only a handful of cases been reported in the English literature before. In this article, we report a new case of urinary melanosis, describe the differential diagnostic features from pseudomelanosis and offer clues for correct diagnosis. We also provide comprehensive review of the literature on the subject.