Medicine and Health Sciences Commons^™

Network Insights On Oxaliplatin Anti-Cancer Mechanisms, Osama M. Alian, Asfar S. Azmi, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Oxaliplatin has been a crucial component of combination therapies since admission into the clinic causing modest gains in survival across multiple malignancies. However, oxaliplatin functions in a non-targeted manner, posing a difficulty in ascertaining precise efficacy mechanisms. While previously thought to only affect DNA repair mechanisms, Platinum-protein adducts (Pt-Protein) far outnumber Pt-DNA adducts leaving a big part of oxaliplatin function unknown. Through preliminary network modeling of high throughput data, this article critically reviews the efficacy of oxaliplatin as well as proposes a better model for enhanced efficacy based on a network approach. In our study, not only oxaliplatin’s function …

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …

Acr Appropriateness Criteria®  Resectable Rectal Cancer, William E. Jones Iii, Charles R. Thomas Jr, Joseph M. Herman, May Abdel-Wahab, Nilofer Azad, William Blackstock, Prajnan Das, Karyn A. Goodman, Theodore S. Hong, Salma K. Jabbour, Andre A. Konski, Albert C. Koong, Miguel Rodriguez-Bigas, William Small Jr, Jennifer Zook, W Suh

Wayne State University Associated BioMed Central Scholarship

Abstract

The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The …

In Ovo Serial Skeletal Muscle Diffusion Tractography Of The Developing Chick Embryo Using Dti: Feasibility And Correlation With Histology, Zien Zhou, Zachary Delproposto, Lianming Wu, Jianrong Xu, Jia Hua, Yan Zhou, Yongquan Ye, Zishu Zhang, Jiani Hu, E Mark Haacke

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Magnetic resonance imaging is a noninvasive method of evaluating embryonic development. Diffusion tensor imaging (DTI), based on the directional diffusivity of water molecules, is an established method of evaluating tissue structure. Yet embryonic motion degrades the in vivo acquisition of long-duration DTI. We used a dual-cooling technique to avoid motion artifact and aimed to investigate whether DTI can be used to monitor chick embryonic skeletal muscle development in ovo, and to investigate the correlation between quantitative DTI parameters fractional anisotropy (FA) and fiber length and quantitative histologic parameters fiber area percentage (FiberArea%) and limb length.

Results

From 84 …

Tracking Of In-111-Labeled Human Umbilical Tissue-Derived Cells (Hutc) In A Rat Model Of Cerebral Ischemia Using Spect Imaging, Ali S. Arbab, Christine Thiffault, Bradford Navia, Stephen J. Victor, Klaudyne Hong, Li Zhang, Quan Jiang, Nadimpalli Rs Varma, Asm Iskander, Michael Chopp

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available in vivo cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT).

Methods

Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals …

Expression Of Mir-34 Is Lost In Colon Cancer Which Can Be Re-Expressed By A Novel Agent Cdf, Sanchita Roy, Edi Levi, Adhip Pn Majumdar, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Colorectal Cancer (CRC) is one of the leading causes of death worldwide. Numerous cellular events, including deregulated expression of microRNAs (miRNAs), specifically the family of miR-34 consisting of miR-34a, b and c, is known to regulate the processes of growth and metastasis.

Methods

We evaluated the expression of miR-34 in formalin-fixed paraffin-embedded (FFPE) human colon cancer tissue specimens compared to normal colonic mucosa. Moreover, we also assessed the expression of miR-34 in colon cancer cell lines treated with our newly developed synthetic analogue of curcumin referred as difluorinated curcumin (CDF) compared to well known inhibitor of methyl transferase. …

Signaling In Colon Cancer Stem Cells, Sanchita Roy, Adhip Pn Majumdar

Wayne State University Associated BioMed Central Scholarship

Abstract

Bickerstaff’S Brainstem Encephalitis, Miller Fisher Syndrome And Guillain-Barré Syndrome Overlap In An Asthma Patient With Negative Anti-Ganglioside Antibodies, Chongyu Han, Yuan Wang, Jianping Jia, Xunming Ji, Vance Fredrickson, Yuchuan Ding, Wei Sun, Jia Xu, Yong-Xin Sun

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Bickerstaff’s brainstem encephalitis (BBE), together with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) were considered to form a continuous clinical spectrum. An anti-GQ1b antibody syndrome has been proposed to underlie the common pathophysiology for the three disorders; however, other studies have found a positive anti-GM1 instead of anti-GQ1b antibody.

Case presentation

Here we report a 20-year-old male patient with overlapping BBE, MFS and GBS. The patient had a positive family history of bronchial asthma and had suffered from the condition for over 15 years. He developed BBE symptoms nine days after an asthma exacerbation. During the course …

Fibroblast-Secreted Hepatocyte Growth Factor Mediates Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance In Triple-Negative Breast Cancers Through Paracrine Activation Of Met, Kelly L. Mueller, Julie M. Madden, Gina L. Zoratti, Charlotte Kuperwasser, Karin List, Julie L. Boerner

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic cancers. In lung cancer, resistance to EGFR TKIs correlates with amplification of the hepatocyte growth factor (HGF) receptor tyrosine kinase Met. Breast cancers do not respond to EGFR TKIs, even though EGFR is overexpressed. This intrinsic resistance to EGFR TKIs in breast cancer does not correlate with Met amplification. In several tissue monoculture models of human breast cancer, Met, although expressed, is not phosphorylated, suggesting a requirement for a paracrine-produced ligand. In fact, HGF, the ligand for Met, is not …

Genetic Variation In Glutathione S-Transferase Omega-1, Arsenic Methyltransferase And Methylene-Tetrahydrofolate Reductase, Arsenic Exposure And Bladder Cancer: A Case–Control Study, Jennifer L. Beebe-Dimmer, Priyanka T. Iyer, Jerome O. Nriagu, Greg R. Keele, Shilpin Mehta, Jaymie R. Meliker, Ethan M. Lange, Ann G. Schwartz, Kimberly A. Zuhlke, David Schottenfeld, Kathleen A. Cooney

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer.

Methods

Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a …

Segmentation Of Corpus Callosum Using Diffusion Tensor Imaging: Validation In Patients With Glioblastoma, Mohammad-Reza Nazem-Zadeh, Sona Saksena, Abbas Babajani-Fermi, Quan Jiang, Hamid Soltanian-Zadeh, Mark Rosenblum, Tom Mikkelsen, Rajan Jain

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma.

Methods

Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the …

Augmented Annotation And Orthologue Analysis For Oryctolagus Cuniculus: Better Bunny, Douglas B. Craig, Sujatha Kannan, Alan A. Dombkowski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The rabbit is an important model organism used in a wide range of biomedical research. However, the rabbit genome is still sparsely annotated, thus prohibiting extensive functional analysis of gene sets derived from whole-genome experiments. We developed a web-based application that provides augmented annotation and orthologue analysis for rabbit genes. Importantly, the application allows comprehensive functional analysis through the use of orthologous relationships.

Results

Using data extracted from several public bioinformatics repositories we created Better Bunny, a database and query tool that extensively augments the available functional annotation for rabbit genes. Using the complete set of target genes …

Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several important biological processes through regulation of genes post-transcriptionally. Carcinogenesis is one of the key biological processes where miRNAs play important role in the regulation of genes. The miRNAs elicit their effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNA, depending on the degree of complementary base pairing. To-date more than 1,000 miRNAs are postulated to exist, although the field is moving rapidly. Currently, miRNAs are becoming the center of interest in a …

Using Learned Under-Sampling Pattern For Increasing Speed Of Cardiac Cine Mri Based On Compressive Sensing Principles, Pooria Zamani, Mohammad Kayvanrad, Hamid Soltanian-Zadeh

Wayne State University Associated BioMed Central Scholarship

Abstract

This article presents a compressive sensing approach for reducing data acquisition time in cardiac cine magnetic resonance imaging (MRI). In cardiac cine MRI, several images are acquired throughout the cardiac cycle, each of which is reconstructed from the raw data acquired in the Fourier transform domain, traditionally called k-space. In the proposed approach, a majority, e.g., 62.5%, of the k-space lines (trajectories) are acquired at the odd time points and a minority, e.g., 37.5%, of the k-space lines are acquired at the even time points of the cardiac cycle. Optimal data acquisition at the even time points is learned …

The Cyclin-Like Protein Spy1/Ringo Promotes Mammary Transformation And Is Elevated In Human Breast Cancer, Mohammad Al Sorkhy, Rosa-Maria Ferraiuolo, Espanta Jalili, Agnes Malysa, Andreea R. Fratiloiu, Bonnie F. Sloane, Lisa A. Porter

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.

Methods

Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.

Results

We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. …

Does Cerclage Improve Neonatal Outcomes In A Molar Pregnancy And A Coexistent Fetus? A Case Report, Eduardo Aguin, Victor Aguin, Ligia Cisneros, Tina Aguin, Cosmas Van De Ven, Ray Bahado-Singh

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Complete hydatiform mole and coexistent viable fetus is very rare. The use of a cervical cerclage for cervical indications in the presence of this condition has never been reported. Although the diagnosis was made postnatal, the objective is to present a case with good neonatal outcome.

Case presentation

A patient presented with vaginal spotting around 23 weeks. She has a history of four preterm deliveries. Her cervix was dilated and a cerclage was placed. She presented again with PPROM around 25 weeks. She went into spontaneous preterm labor and delivered a viable fetus that is a healthy girl …

Evaluation Of Age-Related Changes In Translocator Protein (Tspo) In Human Brain Using 11C-[R]-Pk11195 Pet, Ajay Kumar, Otto Muzik, Varun Shandal, Diane Chugani, Pulak Chakraborty, Harry T. Chugani

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We studied the distribution and expression of translocator protein in the human brain using ¹¹C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.

Methods

A dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as …

Hdm2 Antagonist Mi-219 (Spiro-Oxindole), But Not Nutlin-3 (Cis-Imidazoline), Regulates P53 Through Enhanced Hdm2 Autoubiquitination And Degradation In Human Malignant B-Cell Lymphomas, Angela M. Sosin, Angelika M. Burger, Aisha Siddiqi, Judith Abrams, Ramzi M. Mohammad, Ayad M. Al-Katib

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma …

A Case–Control Study Of Occupation/Industry And Renal Cell Carcinoma Risk, Sara Karami, Joanne S. Colt, Kendra Schwartz, Faith G. Davis, Julie J. Ruterbusch, Stella S. Munuo, Sholom Wacholder, Patricia A. Stewart, Barry I. Graubard, Nathanial Rothman, Wong-Ho Chow, Mark P. Purdue

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The role of occupation in the etiology of renal cell carcinoma (RCC) is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC).

Methods

Between 2002 and 2007, a population-based case–control study of Caucasians and African Americans (1,217 cases; 1,235 controls) was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating occupation and industry to RCC …

Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.

Methods

We established the MCF10A-ERLIN2 …

Norepinephrine: The Next Therapeutics Frontier For Parkinson's Disease, Peter A. Lewitt

Wayne State University Associated BioMed Central Scholarship

Abstract

Tissue concentrations of norepinephrine (NE) are markedly decreased in various regions of the Parkinson's disease (PD) brain. As in the substantia nigra pars compacta, neuronal dropout and Lewy bodies are prominent changes affecting the locus coeruleus, which is the source of ascending NErgic projections. Despite the major roles of NE throughout the brain, there has been only minimal exploration of pharmacological intervention with NErgic neurotransmission. Cognitive operations, "freezing" of gait, tremor, dyskinesia, REM sleep regulation, and other aspects of brain function are tied into signaling by NE, and there is also evidence that it may have a role in …