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Distinct Transcriptome Profiles Of Gag-Specific Cd8+ T Cells Temporally Correlated With The Protection Elicited By Sivδnef Live Attenuated Vaccine, Wuxun Lu, Yanmin Wu, Fangrui Ma, R. Paul Johnson, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3±5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) …

Chloroviruses Have A Sweet Tooth, James L. Van Etten, Irina V. Agarkova, David D. Dunigan, Michela Tonetti, Cristina De Castro, Garry A. Duncan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large double-stranded DNA (dsDNA) viruses that infect certain isolates of chlorella-like green algae. They contain up to approximately 400 protein-encoding genes and 16 transfer RNA (tRNA) genes. This review summarizes the unexpected finding that many of the chlorovirus genes encode proteins involved in manipulating carbohydrates. These include enzymes involved in making extracellular polysaccharides, such as hyaluronan and chitin, enzymes that make nucleotide sugars, such as GDP-L-fucose and GDP-D-rhamnose and enzymes involved in the synthesis of glycans attached to the virus major capsid proteins. This latter process differs from that of all other glycoprotein containing viruses that traditionally use …

Tryptophan 375 Stabilizes The Outer-Domain Core Of Gp120 For Hiv Vaccine Immunogen Design, Duoyi Hu, Dane Bowder, Wenzhong Wei, Jesse Thompson, Mark A. Wilson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a …

Chronic Inflammation And Apoptosis Propagate In Ischemic Cerebellum And Heart Of Non-Human Primates, Sandra A. Acosta, Sherwin Mashkouri, Diana Nwokoye, Jea Y. Lee, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

The major pathological consequences of cerebral ischemia are characterized by neurological deficits commonly ascribed to the infarcted tissue and its surrounding region, however, brain areas, as well as peripheral organs, distal from the original injury may manifest as subtle disease sequelae that can increase the risks of co-morbidities complicating the disease symptoms. To evaluate the vulnerability of the cerebellum and the heart to secondary injuries in the late stage of transient global ischemia (TGI) model in non-human primates (NHP), brain and heart tissues were collected at six months post-TGI. Unbiased stereological analyses of immunostained tissues showed significant Purkinje cells loss …

How To Explain Cancer To A Child And The Effects Of Coloring Therapy In Children With Cancer, Alexandra Mauer

Undergraduate Honors Thesis Collection

Did you know that doodling or coloring in a book can have significant therapeutic effects? It has been studied and proven that art therapy can help with anxiety, depression, and even some diseases such as cancer.1 Although coloring may not be able to cure cancer, it can make coping with it more manageable.1 When a child who has cancer is waiting to be seen in a doctor’s office or at the hospital, a coloring book can keep his or her mind off of the diagnosis, provide entertainment, and elicit a relaxing mindset. This coloring book could also have a storyline …

Assessment Of Coronary Artery Outward Remodeling In Consequence Of Excision Of Epicardial Adipose Tissue In Ossabaw Swine, Kelly Coderre

Undergraduate Honors Thesis Collection

Background

Coronary artery disease (CAD) results from the buildup of cholesterol, inflammatory factors, and proliferating smooth muscle cells within a vessel wall. This plaque impedes on the vessel lumen, decreasing the space through which blood can flow, leading to an array of complications in the human body. To offset these effects, the arterial wall undergoes outward remodeling, a compensatory physiologic phenomenon that blood vessels undertake when burdened with a blockage, such as CAD. In a previously conducted study, a coronary epicardial adipose tissue excision (cEATx) surgery was performed above the left anterior descending (LAD) in Ossabaw swine to investigate the …

Safety And Feasibility Of Minimally Invasive Inguinal Lymph Node Dissection In Patients With Melanoma (Safe-Milnd): Report Of A Prospective Multi-Institutional Trial., James W Jakub, Alicia M Terando, Amod Sarnaik, Charlotte E Ariyan, Mark Faries, Sabino Zani, Heather B Neuman, Nabil Wasif, Jeffrey M Farma, Bruce J Averbook, Karl Y Bilimoria, Travis E Grotz, Jacob B Jake Allred, Vera J Suman, Mary Sue Brady, Douglas Tyler, Jeffrey D Wayne, Heidi Nelson

Articles, Abstracts, and Reports

BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure.

METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria …

Mechanical Loading As Potential Treatment For Wnt Inhibitor Induced Bone Loss, Juraj Zahatnansky Md, Daniel Dick, Gabrielle Foxa, Robert Baker, Bart Williams Phd

Research Day

The Wnt signaling pathway has been shown to play a role in bone homeostasis and carcinogenesis. On the one hand, a decrease in signaling has been associated with a decrease in bone mass, on the other, an increase in signaling with cancer development. LGK974 is a Wnt signaling inhibitor currently being investigated as a potential cancer therapeutic agent. This molecule inhibits Porcupine, a transmembrane protein necessary for Wnt ligand secretion. In light of the above and based on our preliminary data, treatment with LGK974 leads to bone mass loss. Our investigation aims to address whether such bone loss can be …

A Novel Design Of A Phase Iii Trial Of Isradipine In Early Parkinson Disease (Steady-Pd Iii), Kevin M. Biglan, David Oakes, Anthony E. Lang, Robert A. Hauser, Karen Hodgeman, Brittany Greco, Jillian Lowell, Rebecca Rockhill, Ira Shoulson, Charles Venuto, Diony Young, Tanya Simuni

Neurology Faculty Publications

Objectives To describe the rationale for a novel study design and baseline characteristics of a disease-modifying trial of isradipine 10 mg daily in early Parkinson disease (PD).

Methods STEADY-PDIII is a 36-month, Phase 3, parallel group, placebo-controlled study of the efficacy of isradipine 10 mg daily in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I-III score in the practically defined ON state. Secondary outcome measures include clinically meaningful measures of disability progression in early PD: (1) Time to initiation and utilization of dopaminergic therapy; (2) Time to onset …

Hippocampal Cholinergic Neurostimulating Peptide As A Possible Modulating Factor Against Glutamatergic Neuronal Disability By Amyloid Oligomers, Toyohiro Sato, Yoshiaki Ohi, Daisuke Kato, Masayuki Mizuno, Hiroshi Takase, Tetsuko Kanamori, Cesar V. Borlongan, Akira Haji, Noriyuki Matsukawa

Neurosurgery and Brain Repair Faculty Publications

Despite having pathological changes in the brain associated with Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown. Previous reports have demonstrated that enriched environments prevent the impairment of hippocampal long-term potentiation (LTP) through β2-adrenergic signals, when LTP is incompletely suppressed by synthetic amyloid-β (Aβ) oligomers. The cholinergic network from the medial septal nucleus (MSN) is also a …

Genetic And Histological Alterations Reveal Key Role Of Prostaglandin Synthase And Cyclooxygenase 1 And 2 In Traumatic Brain Injury–Induced Neuroinflammation In The Cerebral Cortex Of Rats Exposed To Moderate Fluid Percussion Injury, Hideki Shojo, Cesar V. Borlongan, Tadashi Mabuchi

Neurosurgery and Brain Repair Faculty Publications

After the initial insult in traumatic brain injury (TBI), secondary neurodegeneration occurs that is intimately associated with neuroinflammation. Prostaglandin (PG) synthases and cyclooxygenase (COX) 1 and 2 may contribute to inflammation in the brain. Temporal and spatial expression features of PG and COX1 and 2 following trauma may guide the development of antineuroinflammation strategies. Here, we examined PG synthase signaling and COX1 and 2 gene expression levels and COX-1- and 2-positive cell types and their temporal localization in TBI-induced brain in an effort to reveal their participation in the disease’s evolving neuroinflammation. Using brain samples from the cerebral cortex of …

Electrosensitization Increases Antitumor Effectiveness Of Nanosecond Pulsed Electric Fields In Vivo, Claudia Muratori, Andrei G. Pakhomov, Loree Heller, Maura Casciola, Elena Gianulis, Sergey Grigoryev, Shu Xiao, Olga N. Pakhomova

Bioelectrics Publications

Nanosecond pulsed electric fields are emerging as a new modality for tissue and tumor ablation. We previously reported that cells exposed to pulsed electric fields develop hypersensitivity to subsequent pulsed electric field applications. This phenomenon, named electrosensitization, is evoked by splitting the pulsed electric field treatment in fractions (split-dose treatments) and causes in vitro a 2- to 3-fold increase in cytotoxicity. The aim of this study was to show the benefit of split-dose treatments for in vivo tumor ablation by nanosecond pulsed electric field. KLN 205 squamous carcinoma cells were embedded in an agarose gel or grown subcutaneously as tumors …

Impact Of Diabetes In The Friedreich Ataxia Clinical Outcome Measures Study, Ashley Mccormick, Jennifer Farmer, Susan Perlman, Martin Delatycki, George Wilmot, Katherine Matthews, Grace Yoon, Chad Hoyle, Sub H. Subramony, Theresa Zesiewicz, David R. Lynch, Shana E. Mccormack

Neurology Faculty Publications

Objective Friedreich ataxia (FA) is a progressive neuromuscular disorder caused by GAA triplet repeat expansions or point mutations in the FXN gene. FA is associated with increased risk of diabetes mellitus (DM). This study assessed the age-specific prevalence of FA-associated DM and its impact on neurologic outcomes.

Research Design and Methods Participants were 811 individuals with FA from 12 international sites in a prospective natural history study (FA Clinical Outcome Measures Study, FACOMS). Physical function was assessed, using validated instruments. Multivariable regression analyses examined the independent association of DM with outcomes.

Results Mean age of participants was 30.1 years (SD …

Thyroid Hormone As A Method Of Reducing Damage To Donor Hearts After Circulatory Arrest, William P. Adams

Theses and Dissertations

There is a chronic lack of donor hearts to meet the need for heart transplant both in the US and worldwide. Further, the use of available hearts is limited by the short period between collection and implantation during which the heart can be safely preserved ex vivo. Using mid-thermic Langendorff machine perfusion, we have been able to preserve the metabolic function of a healthy heart for up to 8 hours, twice the limit for current static cold storage. We have also been able to preserve the metabolic function of a damaged DCD Heart collected 30 minutes after cardiac arrest …

Role Of Epigenetic Modification And Immunomodulation In A Murine Prostate Cancer Model, Jay E. Sulek, Samuel P. Robinson, Albert A. Petrossian, Shaoqing Zhou, Ekaterine Goliadze, Masoud H. Manjili, Amir Toor, Georgi Guruli

Surgery Publications

INTRODUCTION. Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC).

MATERIALS AND METHODS. Gene microarrays were performed to compare expression of several CTA in murine …

Operative And Nonoperative Management Of Blunt Liver Injuries, Jill Peysha, Paula Ferrada

Surgery Publications

Purpose of Review

The purpose of this review is to discuss the indications for operative and nonoperative management in patients with blunt liver injuries.

Recent Findings

Over the past several years, research has begun to show that nonoperative management in blunt liver injuries is feasible and has favorable outcomes over immediate operations in patients who are hemodynamically stable. This includes high-grade injuries who were previously taken to the operating room, in the absence of peritoneal signs or instability, for washout and packing. This trend in management is likely multifactorial and includes improved quality of critical care medicine, advances in imaging …

Insights Into Local Tumor Microenvironment Immune Factors Associated With Regression Of Cutaneous Melanoma Metastases By, Junbao Yang, Maris S Jones, Romela Irene Ramos, Alfred A Chan, Agnes F Lee, Leland J Foshag, Peter A Sieling, Mark Faries, Delphine J Lee

Articles, Abstracts, and Reports

No abstract provided.

Different Ret Gene Mutation-Induced Multiple Endocrine Neoplasia Type 2a In 3 Chinese Families, Qiuli Liu, Dali Tong, Wenqiang Yuan, Gaolei Liu, Gang Yuan, Weihua Lan, Dianzheng Zhang, Jun Zhang, Zaoming Huang, Yao Zhang, Jun Jiang

PCOM Scholarly Works

BACKGROUD: Multiple endocrine neoplasia type 2A (MEN2A) is a condition with inherited autosomal dominant mutations in RET (rearranged during transfection) gene that predisposes the carrier to extremely high risk of medullary thyroid cancer (MTC) and other MEN2A-associated tumors such as parathyroid cancer and/or pheochromocytoma. Little is reported about MEN2A syndrome in the Chinese population.

METHODS: All members of the 3 families along with specific probands of MEN2A were analyzed for their clinical, laboratory, and genetic characteristics. Exome sequencing was performed on the 3 probands, and specific mutation in RET was further screened on each of the family members.

RESULTS: Different …

A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboob Qureshi

College of Osteopathic Medicine (TUN) Publications and Research

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and interaction …

New Mechanism Based Approaches For Treating Prostate Cancer, Rayna Rosati

Wayne State University Dissertations

Prostate cancer (PC) is generally dependent on the androgen signaling axis for tumor growth. PC is managed by androgen deprivation therapy (ADT). The tumors then frequently progress by restoring ADT-resistant AR signaling through mechanisms such as intratumoral androgen synthesis, overexpression of AR, expression of splice variants of AR and alteration in the balance of AR co-regulators. This stage of progression is termed castrate recurrent prostate cancer (CRPC). Moreover, ADT has many major undesirable acute and chronic side effects on various normal tissues. Therefore a more strategic therapy approach is one that would disrupt a functional arm of AR signaling critical …

Preoperative Immunonutrition And Elective Colorectal Resection Outcomes., Lucas W Thornblade, Thomas K Varghese, Xu Shi, Eric K Johnson, Amir Bastawrous, Richard P Billingham, Richard Thirlby, Alessandro Fichera, David R Flum

Articles, Abstracts, and Reports

BACKGROUND: Randomized controlled trials demonstrate the efficacy of arginine-enriched nutritional supplements (immunonutrition) in reducing complications after surgery. The effectiveness of preoperative immunonutrition has not been evaluated in a community setting.

OBJECTIVE: This study aims to determine whether immunonutrition before elective colorectal surgery improves outcomes in the community at large.

DESIGN: This is a prospective cohort study with a propensity score-matched comparative effectiveness evaluation.

SETTINGS: This study was conducted in Washington State hospitals in the Surgical Care Outcomes Assessment Program from 2012 to 2015.

PATIENTS: Adults undergoing elective colorectal surgery were selected.

INTERVENTIONS: Surgeons used a preoperative checklist that recommended that …

The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky

Legacy Theses & Dissertations (2009 - 2024)

Altered carbohydrate and lipid metabolism are increasingly well characterized hallmarks of aggressive breast cancers. While aerobic glycolysis, or “the Warburg effect”, is a well-established metabolic adaptation exploited by tumor cells, the understanding of unique aspects of cancer lipid metabolism lags behind. This is especially true regarding the coordination of complex lipid synthesis and trafficking pathways, which remains poorly understood. N-Myc Downstream Regulated Gene1 (NDRG1) is overexpressed in many solid tumors, but its function is unclear. The importance of NDRG1 is best exemplified by the effect of null mutations on human physiology: inactivating mutations give rise to the severe autosomal recessive …

Characterization Of A New Chlorovirus Type With Permissive And Non-Permissive Features On Phylogenetically Related Algal Strains, Cristian F. Quispe, Ahmed Esmael, Olivia Sonderman, Michelle Mcquinn, Irina Agarkova, Mohammed Battah, Garry A. Duncan, David D. Dunigan, Timothy P. L. Smith, Cristina Decastro, Immacolata Speciale, Fangrui Ma, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

A previous report indicated that prototype chlorovirus PBCV-1 replicated in two Chlorella variabilis algal strains, NC64A and Syngen 2-3, that are ex-endosymbionts isolated from the protozoan Paramecium bursaria. Surprisingly, plaque-forming viruses on Syngen 2-3 lawns were often higher than on NC64A lawns from indigenous water samples. These differences led to the discovery of viruses that exclusively replicate in Syngen 2-3 cells, named Only Syngen (OSy) viruses. OSy-NE5, the prototype virus for the proposed new species, had a linear dsDNA genome of 327 kb with 44-nucleotide-long, incompletely base-paired, covalently closed hairpin ends. Each hairpin structure was followed by an identical …

Understanding Zoonotic Enteric Disease In Minnesota: A Spatio Temporal Analysis And Causal Theory Approach, Suchismita Swain

All Graduate Theses, Dissertations, and Other Capstone Projects

With 75 percent of diseases in humans having origin in animals or animal products, zoonotic diseases have an enormous impact on the global disease burden. A significant portion of this can be attributed to bacterial zoonotic enteric pathogens. This study was designed to locate clusters of bacterial zoonotic enteric outbreaks in the State of Minnesota and study the seasonality of these outbreaks. In addition to identifying hot spots for zoonotic enteric outbreaks in Minnesota, the study also aimed to design a causal model to improve understanding of risk factors. This thesis considered only the bacterial zoonotic pathogens with significant disease …

Predicting Tacrolimus Concentrations In Children Receiving A Heart Transplant Using A Population Pharmacokinetic Model, Joseph E. Rower, Chris Stockmann, Matthew W. Linakis, Shaun S. Kumar, Xiaoxi Liu, E. Kent Korgenski, Catherine M.T. Sherwin, Kimberly M. Molina

Pediatrics Faculty Publications

Objective Immunosuppressant therapy plays a pivotal role in transplant success and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to exhibit significant pharmacological interpatient and intrapatient variability. This variability necessitates the collection of serial trough concentrations to ensure that the drug remains within therapeutic range. The objective of this study was to build a population pharmacokinetic (PK) model and use it to determine the minimum number of trough samples needed to guide the prediction of an individual’s future concentrations.

Design, setting and patients Retrospective data from 48 children who received tacrolimus as inpatients at Primary Children’s Hospital in Salt …

The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown

Theses and Dissertations--Neuroscience

The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. …

Factors Regulating Features Of Metabolic Syndrome, Sonja S. Pijut

Theses and Dissertations--Pharmacy

The collective presence of central obesity, low HDL-cholesterol, and elevated triglycerides, blood pressure, and fasting blood glucose constitutes Metabolic Syndrome (MetS), a disease state that increases the risk of cardiovascular disease (CVD) and Type 2 Diabetes Mellitus (T2DM). Nonalcoholic fatty liver disease (NAFLD), present in up to 90% of obese adults, is also linked to MetS. As in CVD, disruptions in cholesterol metabolism play a contributing role in the development of T2DM and NAFLD. Genes involved in cholesterol synthesis, secretion, and catabolism are diurnally regulated in the liver and adipose. Disruptions in the sleep-wake cycle are thought to potentiate metabolic …

The Development Of Bsn272 From Prevention Of Diet-Induced Hyperlipidemia In Mice To A Potential Therapy For Prader-Willi Syndrome In Humans, Jarrod B. Williams

Theses and Dissertations--Pharmacy

While type 2 diabetes mellitus (T2DM) is distinguished as a disorder of blood glucose homeostasis, the vast majority of patients afflicted with this disease in the US present with the entire complement of the metabolic syndrome: abdominal obesity, hypertriglyceridemia, low HDL levels, elevated blood pressure, and elevated fasting plasma glucose. Current guidelines aim to treat each of these disorders, but do so individually even though they are manifestations of common pathologies. In other words, a patient will be prescribed different medications for diabetes, blood pressure, CVD prevention, etc., while the only single treatment aimed at the myriad of disorders together …

New Insights Into Post-Sepsis Muscle Weakness Elucidated Using A Novel Animal Model, Allison M. Steele

Theses and Dissertations--Physiology

Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild …

Anti-Proliferative Role Of Recombinant Lethal Toxin Of Bacillus Anthracis On Primary Mammary Ductal Carcinoma Cells Revealing Its Therapeutic Potential, Rekha Khandia, Bramhadev Pattnaik, Katherikamem Rajukumar, Atul Pateriya, Sandeep Bhatia, Harshad Murugkar, Anil Prakash, Hare Krishna Pradhan, Kildeep Dhama, Ashol Munjal, Sunil K. Joshi

Bioelectrics Publications

Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ±1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = …