Medicine and Health Sciences Commons^™

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Postural Responses To Perturbations Of The Vestibular System During Walking In Healthy Young And Older Adults, Jung Hung Chien

Theses & Dissertations

It has been shown that approximate one-third of US adults aged 40 years and older (69 million US citizens) have some type of vestibular problems. These declining abilities of the vestibular system affect quality of life. Difficulties in performing daily activities (dressing, bathing, getting in and out of the bed and etc.) have been highly correlated to loss of balance due to vestibular disorders. The exact number of people affected by vestibular disorders is still difficult to quantify. This might be because symptoms are difficult to describe and differences exist in the qualifying criteria within and across studies. Thus, it …

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

Evaluation Of Upper Airway Changes Following Surgical Removal Of The Adenoids Using 3-D Cone Beam Ct, Christopher C. Schultz

Theses & Dissertations

Purpose: The purpose of this study was to evaluate the changes in volume, cross-sectional area and depth of the upper airway following the surgical removal of the adenoids.

Materials and Methods: 16 patients were diagnosed with hypertrophic adenoids and referred for surgical removal. Pre-surgical and post-surgical CBCT scans were taken on each patient. Volume measurements of the total airway, oropharynx and nasopharynx were recorded. In addition, cross-sectional areas and airway depths at the posterior nasal spine (PNS) and cervical vertebrae 2 were recorded. 15 patients diagnosed with no or mild adenoid hypertrophy were treated as the control group. The controls …

Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang

Theses & Dissertations

Hepatitis C Virus (HCV) is recognized as a major burden in global public health, which can be further exacerbated by several cofactors such as human immunodeficiency virus (HIV). Currently, there is no vaccine for HCV. The emergence of potent and highly specific direct-acting antivirals (DAA) has marked a new era in HCV therapy, however, the remaining issues like affordability, genotype dependency, and potential resistance still necessitate the development of additional therapeutic approaches to be used instead or in combination with DAA.

Recently, the antiviral peptide C5A (in our studies designated as p1) and its cationic derivative p41 have been identified …

Biodegradable Hybrid Nanogels For Combination Chemotherapy, Swapnil Desale

Theses & Dissertations

Combination chemotherapy is commonly used to treat cancer, because such a therapy regimens usually involve sequential administration of multiple drugs and allow targeting different cell signaling pathway. The co-delivery of drug combination at a controlled ratio via the same vehicle is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and suppression of drug resistance. Undoubtedly, there are several molecular and pharmacological factors that determine the effectiveness of drug combinations. A rationally designed drug combination is required since certain drug ratios and the definitive exposure to the targets of interest can only be synergistic while others …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

The Role Of Genetic Alterations In Tumor Initiation, Progression And Transformation, Weiwei Zhang

Theses & Dissertations

Follicular lymphoma (FL) is the second most common lymphoma in the United States. Although it is generally an indolent lymphoma, FL is not curable, and, in about 30% of patients, the FL undergoes transformation into an aggressive lymphoma (tFL) with marked worsening of prognosis. To identify mutations preferentially present in tFL, we performed whole exome sequencing (WES) on paired FL and tFL arising in the same patients and developed a mutational analysis pipeline. After we identified potentially important genes that have been found to be mutated in our paired FL and tFL study, we constructed a custom capture platform including …

Association Between Recipient’S Preexisting Antibodies And Allograft Vasculopathy And Mortality In Heart Transplant Patients, Hoang Tran, Lorena Baccaglini, Jane L. Meza, Brian D. Lowes

Theses & Dissertations

Objectives: To evaluate the role of preexisting Angiotensin II receptor type I antibodies (AT1RAb) and anti-HLA antibodies in predicting mortality and cardiac allograft vasculopathy (CAV) among heart transplant patients.

Methods: In this retrospective cohort study, we included 114 adults who received heart transplant from January 1^st, 2007 to December 31, 2014 and were followed up at Nebraska Medicine. 48 hours pre-transplant sera sample were used to detect antibodies. A cutoff of 10UL/ml was used for AT1RAb positive and mean fluorescence intensity of 3,000 and 1,500 were used for anti HLA class I and class II, respectively. Patients were …

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

Examining Employee Knowledge Of The Jennie Edmundson Hospital Active Shooter Policy, Mallory W. Darais

Theses & Dissertations

Nationally, there has been a large increase in the number of active shooter events within healthcare facilities such as hospitals. Due to this increase, government organizations have recently released documents to guide healthcare facilities on implementing active shooter policies and updating emergency operation plans. Currently, recommendations from government entities such as the Federal Bureau of Investigation and the Department of Homeland Security suggest the “Run, Hide, Fight” approach during an active shooter incident. Jennie Edmundson Hospital, located in Council Bluffs, Iowa, and affiliated with the Methodist Health System, currently has an active shooter policy in place. Data was collected from …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

Regulatory Roles Of Mical-L1 And Ehd1 In Cell Signaling And Mitosis, James B. Reinecke

Theses & Dissertations

Membrane trafficking is a basic cell biological process that controls the distribution of proteins and lipids. Our lab is particularly interested in delineating the cellular functions as well as the molecular mechanisms that regulate the C-terminal Eps15 Homology Domain (EHD) protein family of adenosine-5’-triphosphatases in mammalian cells. EHD1-4 are ubiquitously expressed in mammalian tissues and serve partially overlapping but also distinct functions in regulating membrane shaping and fission along the endocytic pathway. Specifically, EHD1 is recruited to tubular recycling endosomes (TREs) by Molecule Interacting with CasL Like-1 (MICAL-L1) and facilitates TRE fission and release of cargo from the perinuclear endocytic …

Squamous Cell Carcinoma Response To Cisplatin Exposure, Khanh V. Luong

Theses & Dissertations

Purpose: This thesis attempted to quantitatively analyze the individual cell fate choice in resistant head and neck UM-SCC38 cells exposed to cisplatin using the most current techniques available.

Methods: UM-SCC-38 cells were grown in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS). They were treated with cisplatin and ATM/ATR inhibitors of known dosages. Using live cell imaging, one hundred cells were tracked in each experiment and their behaviors were analyzed and entered into Microsoft Excel Spreadsheet to generate cell profile graphs. HaCaT cells, non-tumorigenic keratinocyte cell line, were also analyzed using live cell imaging and their …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

Vanishing Retinal Arterial Aneurysms With Anti-Tubercular Treatment In A Patient Presenting With Idiopathic Retinal Vasculitis, Aneurysms, And Neuroretinitis., Ramandeep Singh, Kusum Sharma, Aniruddha Agarwal, Mohit Dogra, Vishali Gupta, Aman Sharma, Mangat R. Dogra

Journal Articles: Ophthalmology

BACKGROUND: Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome presents with characteristic clinical manifestations such as aneurysms at arteriolar bifurcations and optic nerve and retinal vascular inflammation. Regression of such features on treatment with anti-tubercular therapy (ATT) combined with corticosteroids has not been reported in literature.

FINDINGS: A 30-year-old female with sudden painless decreased vision in the left eye was referred with a diagnosis of presumed tuberculous retinal vasculitis and a positive tuberculin skin test. Based on the clinical and angiographic features of the right eye, a diagnosis of IRVAN syndrome was made. In the left eye, the patient had …

Silibinin-Mediated Metabolic Reprogramming Attenuates Pancreatic Cancer-Induced Cachexia And Tumor Growth., Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua J. Souchek, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Nagarajan, Nina V. Chaika, Fang Yu, Surendra K. Shukla

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic …

Combined Systemic And Ocular Chemotherapy For Anterior Segment Metastasis Of Systemic Mantle Cell Lymphoma., Aniruddha Agarwal, Mohammad Ali Sadiq, William R. Rhoades, Loren S. Jack, Mostafa Hanout, Philip J. Bierman, William W. West, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature.

FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and …

Outcomes With As-Needed Ranibizumab After Initial Monthly Therapy: Long-Term Outcomes Of The Phase Iii Ride And Rise Trials., David S. Boyer, Quan Dong Nguyen, David M. Brown, Karen Basu, Jason S. Ehrlich

Journal Articles: Ophthalmology

PURPOSE: To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment.

DESIGN: Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330).

PARTICIPANTS: Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE.

METHODS: All patients participating in the OLE were eligible to receive 0.5 mg ranibizumab according to predefined re-treatment criteria: Treatment was administered when DME was identified by the investigator on optical coherence tomography or when best-corrected visual acuity (BCVA) worsened by …

Enormous, Rapidly Growing Breast Mass., Vivek Verma, Sanjay Muttineni, Rajesh R. Kulkarni, Edibaldo Silva, William W. West, Robert B. Thompson

Journal Articles: Oncology and Hematology

BACKGROUND: Signs and symptoms of a rapidly enlarging breast mass are not only important for all clinicians to recognize and assess, but also are not uncommon occurrences. We describe a similar but unique case that developed into an enormous, 36 cm exophytic mass.

CASE PRESENTATION: A 51-year-old woman with history of psychiatric conditions presented for signs and symptoms of sepsis. It was determined that the source was an enormous 36 cm mass originating from the breast/chest wall. After stabilizing the patient with antibiotics, she underwent successful resection. Surgical margins were positive, and histopathology demonstrated bland spindle cells with stromal overgrowth. …

Role Of Micrornas In Alcohol-Induced Multi-Organ Injury., Sathish Kumar Natarajan, Joseph M. Pachunka, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, …

Active Yap Promotes Pancreatic Cancer Cell Motility, Invasion And Tumorigenesis In A Mitotic Phosphorylation-Dependent Manner Through Lpar3., Shuping Yang, Lin Zhang, Vinee Purohit, Surendra K. Shukla, Xingcheng Chen, Fang Yu, Kai Fu, Yuanhong Chen, Joyce C. Solheim, Surendra K. Shukla, Wei Song, Jixin Dong

Journal Articles: Eppley Institute

The transcriptional co-activator Yes-associated protein, YAP, is a main effector in the Hippo tumor suppressor pathway. We recently defined a mechanism for positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here, we show that active YAP promotes pancreatic cancer cell migration, invasion and anchorage-independent growth in a mitotic phosphorylation-dependent manner. Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP reduction significantly impairs cell migration and invasion. Immunohistochemistry shows significant upregulation and nuclear localization of YAP in metastases when compared with primary tumors and normal tissue in human. Mitotic phosphorylation of YAP controls a unique transcriptional program in pancreatic cells. …

Endogenous Endophthalmitis: Diagnosis, Management, And Prognosis., Mohammad Ali Sadiq, Muhammad Hassan, Aniruddha Agarwal, Salman Sarwar, Shafak Toufeeq, Mohamed K. Soliman, Mostafa Hanout, Yasir Jamal Sepah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

Endogenous endophthalmitis is an ophthalmic emergency that can have severe sight-threatening complications. It is often a diagnostic challenge because it can manifest at any age and is associated with a number of underlying predisposing factors. Microorganisms associated with this condition vary along a broad spectrum. Depending upon the severity of the disease, both medical and surgical interventions may be employed. Due to rarity of the disease, there are no guidelines in literature for optimal management of these patients. In this review, treatment guidelines based on clinical data and microorganism profile have been proposed.

Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker

Journal Articles: Cellular & Integrative Physiology

Increased central angiotensin II (Ang II) levels contribute to sympathoexcitation in cardiovascular disease states such as chronic heart failure and hypertension. One mechanism by which Ang II increases neuronal excitability is through a decrease in voltage-gated, rapidly inactivating K(+) current (IA); however, little is known about how Ang II signaling results in reduced IA. Brain-derived neurotrophic factor (BDNF) has also been demonstrated to decrease IA and has signaling components common to Ang II. Therefore, we hypothesized that Ang II-mediated suppression of voltage-gated K(+) currents is due, in part, to BDNF signaling. Differentiated CATH.a, catecholaminergic cell line treated with BDNF for …

Neuroinflammatory Paradigms In Lysosomal Storage Diseases., Megan Bosch, Tammy Kielian

Journal Articles: Pathology and Microbiology

Lysosomal storage diseases (LSDs) include approximately 70 distinct disorders that collectively account for 14% of all inherited metabolic diseases. LSDs are caused by mutations in various enzymes/proteins that disrupt lysosomal function, which impairs macromolecule degradation following endosome-lysosome and phagosome-lysosome fusion and autophagy, ultimately disrupting cellular homeostasis. LSDs are pathologically typified by lysosomal inclusions composed of a heterogeneous mixture of various proteins and lipids that can be found throughout the body. However, in many cases the CNS is dramatically affected, which may result from heightened neuronal vulnerability based on their post-mitotic state. Besides intrinsic neuronal defects, another emerging factor common to …

Apobec3g Interacts With Ssdna By Two Modes: Afm Studies., Luda S. Shlyakhtenko, Samrat Dutta, Jaspreet Banga, Ming Li, Reuben S. Harris, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

APOBEC3G (A3G) protein has antiviral activity against HIV and other pathogenic retroviruses. A3G has two domains: a catalytic C-terminal domain (CTD) that deaminates cytidine, and a N-terminal domain (NTD) that binds to ssDNA. Although abundant information exists about the biological activities of A3G protein, the interplay between sequence specific deaminase activity and A3G binding to ssDNA remains controversial. We used the topographic imaging and force spectroscopy modalities of Atomic Force Spectroscopy (AFM) to characterize the interaction of A3G protein with deaminase specific and nonspecific ssDNA substrates. AFM imaging demonstrated that A3G has elevated affinity for deaminase specific ssDNA than for …

Mortality-Related Resource Utilization In The Inpatient Care Of Hypoplastic Left Heart Syndrome., David A. Danford, Quentin Karels, Aparna Kulkarni, Aysha Hussain, Yunbin Xiao, Shelby Kutty

Journal Articles: Pediatrics

BACKGROUND: Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF).

METHODS: A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children's hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of …

Naturally Occurring Deletion Mutants Of The Pig-Specific, Intestinal Crypt Epithelial Cell Protein Clca4b Without Apparent Phenotype., Stephanie Plog, Nikolai Klymiuk, Stefanie Binder, Matthew J. Van Hook, Wallace B. Thoreson, Achim D. Gruber, Lars Mundhenk

Journal Articles: Ophthalmology

The human CLCA4 (chloride channel regulator, calcium-activated) modulates the intestinal phenotype of cystic fibrosis (CF) patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological …

Invariant Characteristics Of Carcinogenesis., Simon Sherman, Nirosha Rathnayake, Tengiz Mdzinarishvili

Journal Articles: Eppley Institute

Carcinogenic modeling is aimed at mathematical descriptions of cancer development in aging. In this work, we assumed that a small fraction of individuals in the population is susceptible to cancer, while the rest of the population is resistant to cancer. For individuals susceptible to cancer we adopted methods of conditional survival analyses. We performed computational experiments using data on pancreatic, stomach, gallbladder, colon and rectum, liver, and esophagus cancers from the gastrointestinal system collected for men and women in the SEER registries during 1975-2009. In these experiments, we estimated the time period effects, the birth cohort effects, the age effects …