Medicine and Health Sciences Commons^™

Comparison Of Mitotic Cell Death By Chromosome Fragmentation To Premature Chromosome Condensation, Joshua B. Stevens, Batoul Y. Abdallah, Sarah M. Regan, Guo Liu, Steven W. Bremer, Christine J. Ye, Henry H. Heng

Wayne State University Associated BioMed Central Scholarship

Abstract

Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost …

Loss Of The Sin3 Transcriptional Corepressor Results In Aberrant Mitochondrial Function, Valerie L. Barnes, Bethany S. Strunk, Icksoo Lee, Maik Hüttemann, Lori A. Pile

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

SIN3 is a transcriptional repressor protein known to regulate many genes, including a number of those that encode mitochondrial components.

Results

By monitoring RNA levels, we find that loss of SIN3 inDrosophilacultured cells results in up-regulation of not only nuclear encoded mitochondrial genes, but also those encoded by the mitochondrial genome. The up-regulation of gene expression is accompanied by a perturbation in ATP levels in SIN3-deficient cells, suggesting that the changes in mitochondrial gene expression result in altered mitochondrial activity. In support of the hypothesis that SIN3 is necessary for normal mitochondrial function, yeastsin3null mutants exhibit very poor …

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 …

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 …

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 …

The Globin Gene Family Of The Cephalochordate Amphioxus: Implications For Chordate Globin Evolution, Bettina Ebner, Georgia Panopoulou, Serge N. Vinogradov, Laurent Kiger, Michael C. Marden, Thorsten Burmester, Thomas Hankeln

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The lancelet amphioxus (Cephalochordata) is a close relative of vertebrates and thus may enhance our understanding of vertebrate gene and genome evolution. In this context, the globins are one of the best studied models for gene family evolution. Previous biochemical studies have demonstrated the presence of an intracellular globin in notochord tissue and myotome of amphioxus, but the corresponding gene has not yet been identified. Genomic resources of Branchiostoma floridae now facilitate the identification, experimental confirmation and molecular evolutionary analysis of its globin gene repertoire.

Results

We show that B. floridae harbors at least fifteen paralogous globin genes, …

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 …

Mapping Haplotype-Haplotype Interactions With Adaptive Lasso, Ming Li, Roberto Romero, Wenjiang J. Fu, Yuehua Cui

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it …

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), …

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 p21^WAF1/CIP1 expression at transcriptional, post-transcriptional as well as translational levels. We previously found that cell growth suppressing retinoid CD437 enhanced expression of p21^WAF1/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 p21^WAF1/CIP1 expression. By utilizing MDA-MB-468 HBC cells expressing chimeric rabbit β-globin-p21^WAF1/CIP1 transcripts we mapped multiple CD437-responsive sequences located within positions 1195 to 1795 of the 3'-untranslated region of p21^WAF1/CIP1 mRNA. Several cytoplasmic proteins present in MDA-MB-468, MCF-7 HBC as well …

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 …

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 …

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 …

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 …

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

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 …

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 …

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

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

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 …