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Tumor-Associated Antigen Prediction Using A Single-Sample Gene Expression State Inference Algorithm, Xinpei Yi, Hongwei Zhao, Shunjie Hu, Liangqing Dong, Yongchao Dou, Jing Li, Qiang Gao, Bing Zhang Nov 2024

Tumor-Associated Antigen Prediction Using A Single-Sample Gene Expression State Inference Algorithm, Xinpei Yi, Hongwei Zhao, Shunjie Hu, Liangqing Dong, Yongchao Dou, Jing Li, Qiang Gao, Bing Zhang

Faculty, Staff and Students Publications

We developed a Bayesian-based algorithm to infer gene expression states in individual samples and incorporated it into a workflow to identify tumor-associated antigens (TAAs) across 33 cancer types using RNA sequencing (RNA-seq) data from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA). Our analysis identified 212 candidate TAAs, with 78 validated in independent RNA-seq datasets spanning seven cancer types. Eighteen of these TAAs were further corroborated by proteomics data, including 10 linked to liver cancer. We predicted that 38 peptides derived from these 10 TAAs would bind strongly to HLA-A02, the most common HLA allele. Experimental validation confirmed …


Nusap4 Regulates Chromosome Segregation In Trypanosoma Brucei By Promoting Bipolar Spindle Assembly, Qing Zhou, Ziyin Li Nov 2024

Nusap4 Regulates Chromosome Segregation In Trypanosoma Brucei By Promoting Bipolar Spindle Assembly, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

Faithful chromosome segregation in eukaryotes requires the assembly of a bipolar spindle and the faithful attachment of kinetochores to spindle microtubules, which are regulated by various spindle-associated proteins (SAPs) that play distinct functions in regulating spindle dynamics and microtubule-kinetochore attachment. The protozoan parasite Trypanosoma brucei employs evolutionarily conserved and kinetoplastid-specific proteins, including some kinetoplastid-specific nucleus- and spindle-associated proteins (NuSAPs), to regulate chromosome segregation. Here, we characterized NuSAP4 and its functional interplay with diverse SAPs in promoting chromosome segregation in T. brucei. NuSAP4 associates with the spindle during mitosis and concentrates at spindle poles where it interacts with SPB1 and MAP103. …


Tumor-Infiltrating Mast Cells Confer Resistance To Immunotherapy In Pancreatic Cancer, Ying Ma, Xiangqin Zhao, Jingyan Feng, Suimin Qiu, Baoan Ji, Lu Huang, Patrick Hwu, Craig D Logsdon, Huamin Wang Nov 2024

Tumor-Infiltrating Mast Cells Confer Resistance To Immunotherapy In Pancreatic Cancer, Ying Ma, Xiangqin Zhao, Jingyan Feng, Suimin Qiu, Baoan Ji, Lu Huang, Patrick Hwu, Craig D Logsdon, Huamin Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast cells infiltrating the PDAC TME foster this immunosuppression and desmoplasia. Mast cell infiltration correlated with human PDAC progression, and genetic or pharmacological mast cell depletion reduced tumor growth and desmoplasia while enhancing survival in mouse PDAC models. Mechanistically, mast cell-derived IL-10 promoted PDAC progression. Strikingly, combining an agonistic anti-OX40 immunotherapy with mast cell blockade synergistically elicited durable anti-tumor immunity, marked by increased infiltration of CD8


Assessing Mechanical Agency During Apical Apoptotic Cell Extrusion, Sommer Anjum, Llaran Turner, Youmna Atieh, George T Eisenhoffer, Lance A Davidson Nov 2024

Assessing Mechanical Agency During Apical Apoptotic Cell Extrusion, Sommer Anjum, Llaran Turner, Youmna Atieh, George T Eisenhoffer, Lance A Davidson

Faculty, Staff and Student Publications

Homeostasis is necessary for epithelia to maintain barrier function and prevent the accumulation of defective cells. Unfit, excess, and dying cells in the larval zebrafish tail fin epidermis are removed via controlled cell death and extrusion. Extrusion coincides with oscillations of cell area, both in the extruding cell and its neighbors. Here, we develop a biophysical model of this process to explore the role of autonomous and non-autonomous mechanics. We vary biophysical properties and oscillatory behaviors of extruding cells and their neighbors along with tissue-wide cell density and viscosity. We find that cell autonomous processes are major contributors to the …


Epigenome Reprogramming Through H3k27 And H3k4 Trimethylation As A Resistance Mechanism To Dna Methylation Inhibition In Brafv600e-Mutated Colorectal Cancer, Hey Min Lee, Ajay Kumar Saw, Van K Morris, Stefania Napolitano, Christopher Bristow, Sanjana Srinivasan, Micheal Peoples, Alexey Sorokin, Preeti Kanikarla Marie, Jonathan Schulz, Anand K Singh, Christopher Terranova, Oluwadara Coker, Abhinav Jain, Scott Kopetz, Kunal Rai Nov 2024

Epigenome Reprogramming Through H3k27 And H3k4 Trimethylation As A Resistance Mechanism To Dna Methylation Inhibition In Brafv600e-Mutated Colorectal Cancer, Hey Min Lee, Ajay Kumar Saw, Van K Morris, Stefania Napolitano, Christopher Bristow, Sanjana Srinivasan, Micheal Peoples, Alexey Sorokin, Preeti Kanikarla Marie, Jonathan Schulz, Anand K Singh, Christopher Terranova, Oluwadara Coker, Abhinav Jain, Scott Kopetz, Kunal Rai

Faculty, Staff and Student Publications

Purpose: BRAFV600E-mutated colorectal cancer exhibits a strong correlation with DNA hypermethylation, suggesting that this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E colorectal cancer in vivo.

Experimental design: We randomized and treated mice implanted with patient-derived tumor xenografts harboring BRAFV600E mutation with control, 5-azacitidine, vemurafenib (BRAF inhibitor), or the combination. Comprehensive epigenomic profiling was conducted on control and 5-azacitidine-treated tumor samples, including DNA methylation, histone modifications, chromatin accessibility, and gene expression. Combinations of epigenetic agents were explored in preclinical BRAFV600E colorectal cancer models.

Results: A profound reduction of DNA …


Association Of Clonal Hematopoiesis And Mosaic Chromosomal Alterations With Solid Malignancy Incidence And Mortality, Pinkal Desai, Ying Zhou, Justin Grenet, Samuel K Handelman, Cynthia M Crispino, Laura N Tarbay, Eric A Whitsel, Gail Roboz, Ana Barac, Michael Honigberg, Alexander Bick, Garnet Anderson, Jean Wactawski-Wende, Yasminka A Jakubek Swartzlander, Jason Bacon, Justin Wong, Xiaolong Ma, Paul Scheet, Zichan Li, Pashtoon Kasi, Ross Prentice, Paul Auer, Joann E Manson, Alexander Reiner, Michael Simon Nov 2024

Association Of Clonal Hematopoiesis And Mosaic Chromosomal Alterations With Solid Malignancy Incidence And Mortality, Pinkal Desai, Ying Zhou, Justin Grenet, Samuel K Handelman, Cynthia M Crispino, Laura N Tarbay, Eric A Whitsel, Gail Roboz, Ana Barac, Michael Honigberg, Alexander Bick, Garnet Anderson, Jean Wactawski-Wende, Yasminka A Jakubek Swartzlander, Jason Bacon, Justin Wong, Xiaolong Ma, Paul Scheet, Zichan Li, Pashtoon Kasi, Ross Prentice, Paul Auer, Joann E Manson, Alexander Reiner, Michael Simon

Faculty, Staff and Student Publications

Background: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways.

Methods: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers.

Results: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or …


Disease Site Specialization In The Academic Radiation Oncology Workforce: Evidence Of Gender Differences, Kelsey L Corrigan, Mikaela E Bankston, Emma B Holliday, Simona F Shaitelman, Anna Lee, Chelain R Goodman, C David Fuller, Fumiko L Chino, Charles R Thomas, Reshma Jagsi, Ethan B Ludmir Nov 2024

Disease Site Specialization In The Academic Radiation Oncology Workforce: Evidence Of Gender Differences, Kelsey L Corrigan, Mikaela E Bankston, Emma B Holliday, Simona F Shaitelman, Anna Lee, Chelain R Goodman, C David Fuller, Fumiko L Chino, Charles R Thomas, Reshma Jagsi, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Because some stakeholders within medicine seek to diversify and attain greater workforce equity, it is critical to understand gender-based divisions within specialization. Radiation oncology (RO) has one of the smallest proportions of women representation of all specialties, and to our knowledge, no prior studies have investigated gender differences in all the disease site specializations within RO. Thus, we analyzed the relationship between gender and disease site(s) treated in academic RO (ARO).

Methods and materials: Faculty gender and disease site(s) treated by faculty from ARO departments were collected via publicly available department websites in January 2020. X2 analyses were conducted …


Low-Molecular Weight Cyclin E Confers A Vulnerability To Pkmyt1 Inhibition In Triple-Negative Breast Cancer, Mi Li, Amriti R Lulla, Yan Wang, Spyros Tsavaschidis, Fuchenchu Wang, Cansu Karakas, Tuyen D T Nguyen, Tuyen N Bui, Marc A Pina, Mei-Kuang Chen, Sofia Mastoraki, Asha S Multani, Natalie W Fowlkes, Aysegul Sahin, C Gary Marshall, Kelly K Hunt, Khandan Keyomarsi Nov 2024

Low-Molecular Weight Cyclin E Confers A Vulnerability To Pkmyt1 Inhibition In Triple-Negative Breast Cancer, Mi Li, Amriti R Lulla, Yan Wang, Spyros Tsavaschidis, Fuchenchu Wang, Cansu Karakas, Tuyen D T Nguyen, Tuyen N Bui, Marc A Pina, Mei-Kuang Chen, Sofia Mastoraki, Asha S Multani, Natalie W Fowlkes, Aysegul Sahin, C Gary Marshall, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin E is a regulatory subunit of CDK2 that mediates S phase entry and progression. The cleavage of full-length cyclin E (FL-cycE) to low-molecular weight isoforms (LMW-E) dramatically alters substrate specificity, promoting G1-S cell cycle transition and accelerating mitotic exit. Approximately 70% of triple-negative breast cancers (TNBC) express LMW-E, which correlates with poor prognosis. PKMYT1 also plays an important role in mitosis by inhibiting CDK1 to block premature mitotic entry, suggesting it could be a therapeutic target in TNBC expressing LMW-E. In this study, analysis of tumor samples of patients with TNBC revealed that coexpression of LMW-E and PKMYT1-catalyzed CDK1 …


Personalized Composite Dosimetric Score-Based Machine Learning Model Of Severe Radiation-Induced Lymphopenia Among Patients With Esophageal Cancer, Yan Chu, Cong Zhu, Brian P Hobbs, Yiqing Chen, Peter S N Van Rossum, Clemens Grassberger, Degui Zhi, Steven H Lin, Radhe Mohan Nov 2024

Personalized Composite Dosimetric Score-Based Machine Learning Model Of Severe Radiation-Induced Lymphopenia Among Patients With Esophageal Cancer, Yan Chu, Cong Zhu, Brian P Hobbs, Yiqing Chen, Peter S N Van Rossum, Clemens Grassberger, Degui Zhi, Steven H Lin, Radhe Mohan

Faculty, Staff and Student Publications

Purpose: Radiation-induced lymphopenia (RIL) is common among patients undergoing radiation therapy (RT)' Severe RIL has been linked to adverse outcomes. The severity and risk of RIL can be predicted from baseline clinical characteristics and dosimetric parameters. However, dosimetric parameters, e.g. dose-volume (DV) indices, are highly correlated with one another and are only weakly associated with RIL. Here we introduce the novel concept of "composite dosimetric score" (CDS) as the index that condenses the dose distribution in immune tissues of interest to study the dosimetric dependence of RIL. We derived an improved multivariate classification scheme for risk of grade 4 RIL …


Clonal Hematopoiesis And Solid Tumor Risk: New Insights From The Women's Health Initiative, Nehali Shah, Koichi Takahashi Nov 2024

Clonal Hematopoiesis And Solid Tumor Risk: New Insights From The Women's Health Initiative, Nehali Shah, Koichi Takahashi

Faculty, Staff and Student Publications

No abstract provided.


Update On Recommendations For Cancer Screening And Surveillance In Children With Genomic Instability Disorders, Yoshiko Nakano, Roland P Kuiper, Kim E Nichols, Christopher C Porter, Harry Lesmana, Julia Meade, Christian P Kratz, Lucy A Godley, Luke D Maese, Maria Isabel Achatz, Payal P Khincha, Sharon A Savage, Andrea S Doria, Mary-Louise C Greer, Vivian Y Chang, Lisa L Wang, Sharon E Plon, Michael F Walsh Nov 2024

Update On Recommendations For Cancer Screening And Surveillance In Children With Genomic Instability Disorders, Yoshiko Nakano, Roland P Kuiper, Kim E Nichols, Christopher C Porter, Harry Lesmana, Julia Meade, Christian P Kratz, Lucy A Godley, Luke D Maese, Maria Isabel Achatz, Payal P Khincha, Sharon A Savage, Andrea S Doria, Mary-Louise C Greer, Vivian Y Chang, Lisa L Wang, Sharon E Plon, Michael F Walsh

Center for Medical Ethics and Health Policy Staff Publications

Genomic instability disorders are characterized by DNA or chromosomal instability, resulting in various clinical manifestations, including developmental anomalies, immunodeficiency, and increased risk of developing cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop, where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article discusses childhood cancer risks and surveillance recommendations for the group …


Therapeutic Effect Of Recombinant Echinococcus Granulosus Antigen B Subunit 2 Protein On Sepsis In A Mouse Model, Ya-Yun Qian, Fei-Fei Huang, Si-Yu Chen, Wei-Xiao Zhang, Yin Wang, Peng-Fei Du, Gen Li, Wen-Bo Ding, Lei Qian, Bin Zhan, Liang Chu, Dong-Hui Jiang, Xiao-Di Yang, Rui Zhou Nov 2024

Therapeutic Effect Of Recombinant Echinococcus Granulosus Antigen B Subunit 2 Protein On Sepsis In A Mouse Model, Ya-Yun Qian, Fei-Fei Huang, Si-Yu Chen, Wei-Xiao Zhang, Yin Wang, Peng-Fei Du, Gen Li, Wen-Bo Ding, Lei Qian, Bin Zhan, Liang Chu, Dong-Hui Jiang, Xiao-Di Yang, Rui Zhou

Faculty, Staff and Students Publications

BACKGROUND: Sepsis is a potentially fatal systemic inflammatory response syndrome (SIRS) that threatens millions of lives worldwide. Echinococcus granulosus antigen B (EgAgB) is a protein released by the larvae of the tapeworm. This protein has been shown to play an important role in modulating host immune response. In this study we expressed EgAgB as soluble recombinant protein in E. coli (rEgAgB) and explored its protective effect on sepsis.

METHODS: The sepsis model was established by cecal ligation and puncture (CLP) procedure in BALB/c mice. The therapeutic effect of rEgAgB on sepsis was performed by interperitoneally injecting 5 µg rEgAgB in …


Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner Nov 2024

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …


Isolation, Discrimination, And Feeling “Constant Guilt”: A Mixed-Methods Analysis Of Female Physicians’ Experience With Fertility, Family Planning, And Oncology Careers, Sarah Marion, Shraddha M Dalwadi, Aleksandra Kuczmarska-Haas, Erin F Gillespie, Michelle S Ludwig, Emma B Holliday, Bridgette Thom, Fumiko Chino, Anna Lee Nov 2024

Isolation, Discrimination, And Feeling “Constant Guilt”: A Mixed-Methods Analysis Of Female Physicians’ Experience With Fertility, Family Planning, And Oncology Careers, Sarah Marion, Shraddha M Dalwadi, Aleksandra Kuczmarska-Haas, Erin F Gillespie, Michelle S Ludwig, Emma B Holliday, Bridgette Thom, Fumiko Chino, Anna Lee

Faculty, Staff and Students Publications

Introduction: Family planning among female physicians is harmed by high risks of infertility, workload burden, poor family leave policies, and gender discrimination. Many women report feeling unsupported in the workplace, despite national policies to protect against unfair treatment.

Methods: This secondary analysis applied a modified version of the rigorous and accelerated data reduction technique to conduct a thematic analysis of comments to an open-ended prompt. Comments were coded by multiple trained researchers then grouped and merged into illustrative themes via qualitative techniques.

Results: Of 1004 responses to the quantitative survey, 162 physicians completed the open-ended prompt. Initial codes (n = …


Alternatively Spliced Map4 Isoforms Have Key Roles In Maintaining Microtubule Organization And Skeletal Muscle Function, Lathan Lucas, Larissa Nitschke, Brandon Nguyen, James A Loehr, George G Rodney, Thomas A Cooper Nov 2024

Alternatively Spliced Map4 Isoforms Have Key Roles In Maintaining Microtubule Organization And Skeletal Muscle Function, Lathan Lucas, Larissa Nitschke, Brandon Nguyen, James A Loehr, George G Rodney, Thomas A Cooper

Faculty, Staff and Students Publications

Skeletal muscle cells (myofibers) are elongated non-mitotic, multinucleated syncytia that have adapted a microtubule lattice. Microtubule-associated proteins (MAPs) play roles in regulating microtubule architecture. The most abundant MAP in skeletal muscle is MAP4. MAP4 consists of a ubiquitous MAP4 isoform (uMAP4), expressed in most tissues, and a striated-muscle-specific alternatively spliced isoform (mMAP4) that includes a 3,180-nucleotide exon (exon 8). To determine the role of mMAP4 in skeletal muscle, we generated mice that lack mMAP4 and express only uMAP4 due to genomic deletion of exon 8. We demonstrate that loss of mMAP4 leads to disorganized microtubule architecture and intrinsic loss of …


Sample Multiplexing For Retinal Single-Cell Rna Sequencing, Justin Ma, Ting-Kuan Chu, Maria Polo-Prieto, Yong H Park, Yumei Li, Rui Chen, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran Nov 2024

Sample Multiplexing For Retinal Single-Cell Rna Sequencing, Justin Ma, Ting-Kuan Chu, Maria Polo-Prieto, Yong H Park, Yumei Li, Rui Chen, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran

Faculty, Staff and Students Publications

Rare cell populations can be challenging to characterize using microfluidic single-cell RNA sequencing (scRNA-seq) platforms. Typically, the population of interest must be enriched and pooled from multiple biological specimens for efficient collection. However, these practices preclude the resolution of sample origin together with phenotypic data and are problematic in experiments in which biological or technical variation is expected to be high (e.g., disease models, genetic perturbation screens, or human samples). One solution is sample multiplexing whereby each sample is tagged with a unique sequence barcode that is resolved bioinformatically. We have established a scRNA-seq sample multiplexing pipeline for mouse retinal …


Going Against The Family: Perturbation Of A Greenbeard Pathway Leads To Falsebeard Cheating, Peter Lehmann, Mariko Katoh-Kurasawa, Peter Kundert, Gad Shaulsky Nov 2024

Going Against The Family: Perturbation Of A Greenbeard Pathway Leads To Falsebeard Cheating, Peter Lehmann, Mariko Katoh-Kurasawa, Peter Kundert, Gad Shaulsky

Faculty, Staff and Students Publications

Greenbeards facilitate cooperation by encoding a perceptible signal, the ability to detect it, and a tendency to help others that display it. Falsebeards are hypothetical cheaters that display the signal without being altruistic. Despite many examples of greenbeards, evidence for falsebeards is scarce. The Dictyostelium discoideum tgrB1-tgrC1 allorecognition pathway encodes a greenbeard. It allows development, which yields fruiting bodies with altruistic stalks that increase spore dispersal. Here we show that cells lacking rapgapB, a tgrB1-tgrC1 signaling element, cheat by avoiding the stalk fate and generating more spores in chimeras than in pure populations. rapgapB– cells cheat only on …


Pulmonary Alveolar Microlithiasis And Interstitial Pneumonitis: A Case Report Of The West Of Iran, Mazaher Ramezani, Zahra Aminparast, Masoud Sadeghi Nov 2024

Pulmonary Alveolar Microlithiasis And Interstitial Pneumonitis: A Case Report Of The West Of Iran, Mazaher Ramezani, Zahra Aminparast, Masoud Sadeghi

BioMedicine

Pulmonary alveolar microlithiasis (PAM) is a rare disease with autosomal recessive inheritance. Herein, a 20-year-old lady referred to the hospital with a dry cough for two years. The chest X-ray findings were bilateral reticulonodular opacities in both lungs and honeycomb appearance suspicious for miliary tuberculosis and idiopathic pulmonary fibrosis. A wedge biopsy of lung showed that there were several intraalveolar laminated concretions in the pathology report compatible with pulmonary alveolar microlithiasis and interstitial infiltration of lymphocytes and neutrophils compatible with interstitial pneumonitis. PAM is a rare progressive disease with the production of microliths in pulmonary alveoli. The pathologist, radiologist, and …


Epigenetic Profiling Of Mutyh, Klf6, Wnt1 And Klf4 Genes In Carcinogenesis And Tumorigenesis Of Colorectal Cancer, Kosar Babaei, Roya Khaksar, Tahereh Zeinali, Hossein Hemmati, Ahmadreza Bandegi, Pirouz Samidoust, Mohammad Taghi Ashoobi, Hooman Hashemian, Kourosh Delpasand, Fereshteh Talebinasab, Hoora Naebi, Seyed Hossein Mirpour, Arman Keymoradzadeh, Seyedeh Elham Norollahi Nov 2024

Epigenetic Profiling Of Mutyh, Klf6, Wnt1 And Klf4 Genes In Carcinogenesis And Tumorigenesis Of Colorectal Cancer, Kosar Babaei, Roya Khaksar, Tahereh Zeinali, Hossein Hemmati, Ahmadreza Bandegi, Pirouz Samidoust, Mohammad Taghi Ashoobi, Hooman Hashemian, Kourosh Delpasand, Fereshteh Talebinasab, Hoora Naebi, Seyed Hossein Mirpour, Arman Keymoradzadeh, Seyedeh Elham Norollahi

BioMedicine

Colorectal cancer (CRC) is distinguished by epigenetic elements like DNA methylation, histone modification, histone acetylation and RNA remodeling which is related with genomic instability and tumor initiation. Correspondingly, as a main epigenetic regulation, DNA methylation has an impressive ability in order to be used in CRC targeted therapy. Meaningly, DNA methylation is identified as one of most important epigenetic regulators in gene expression and is considered as a notable potential driver in tumorigenesis and carcinogenesis through gene-silencing of tumor suppressors genes. Abnormal methylation situation, even in the level of promoter regions, does not essentially change the gene expression levels, particularly …


The Rna Degradation Pathway Is Involved In Pparα-Modulated Anti-Oral Tumorigenesis, Nai-Wen Chang, Yi-Ping Huang Nov 2024

The Rna Degradation Pathway Is Involved In Pparα-Modulated Anti-Oral Tumorigenesis, Nai-Wen Chang, Yi-Ping Huang

BioMedicine

Background: The activation of peroxisome proliferator-activated receptor alpha (PPARα) has been shown to reprogram tumor metabolism and exhibits great potential for treating anti-oral tumorigenesis.

Methods: In this study, we used a pathway-based strategy to explore possible functional pathways involved in the anticancer activity of PPARα in oral cancer cells through next-generation sequencing (NGS) and bioinformatic approaches.

Results: We found that 3919 genes were upregulated and 1060 genes were downregulated through PPARα activation. These genes were mainly involved in the proteasomal, mRNA surveillance, spliceosomal, RNA transport, and RNA degradation pathways, as indicated by GO and KEGG enrichment analysis. Importantly, a total …


Oral Acute And Sub-Acute Toxic Effects Of HydroalcoholicTerminalia ChebulaRetz AndAchillea WilhelmsiiExtracts In Balb/C Mice, Mahnaz Jafari, Kourosh Manochehri Naeini, Zahra Lorigooini, Rasool Namjoo Nov 2024

Oral Acute And Sub-Acute Toxic Effects Of HydroalcoholicTerminalia ChebulaRetz AndAchillea WilhelmsiiExtracts In Balb/C Mice, Mahnaz Jafari, Kourosh Manochehri Naeini, Zahra Lorigooini, Rasool Namjoo

BioMedicine

Background: This study examined the acute and sub-acute toxic effects ofTerminalia chebulaandAchillea wilhelmsiiextracts on the murine model.

Methods: In both phases, mice were assigned to intervention and control groups. At the end of study, the liver, kidney, and heart tissues were collected for histopathological studies.

Results: In the acute phase of the study, the safe dose was ≤5000 mg/kg for both extracts. In sub-acute phase, LD50 (95% CI) ofAchillea wilhelmsiiextract was determined ≥5000 mg/kg and that ofTerminalia chebulaextract 2754.436 (2438-3114) mg/kg. The highest dose ofT. chebulaextract induced few histopathological changes.

Conclusion: It will be useful to gain information on the …


The Potential Therapeutic Effect For Melatonin And Mesenchymal Stem Cells On Hepatocellular Carcinoma, Yasser Mohamed, Mohamed A. Basyony, Nabila I. El-Desouki, Walied S. Abdo, Mohammed A. El-Magd Nov 2024

The Potential Therapeutic Effect For Melatonin And Mesenchymal Stem Cells On Hepatocellular Carcinoma, Yasser Mohamed, Mohamed A. Basyony, Nabila I. El-Desouki, Walied S. Abdo, Mohammed A. El-Magd

BioMedicine

Background/aim: Herein, we investigated the potential therapeutic effect of Melatonin (Mel) and/or mesenchymal stem cells (MSCs) on rat model of HCC.

Materials and Methods: Female mature rats were divided into 5 groups (n= 10/group): normal (Nor), HCC group intraperitoneally injected with 200 mg/kg DEN, and 3 treated groups; HCC + Mel (Mel) group given Mel intraperitoneally 20 mg/kg, twice a week, HCC + MSCs (MSCs) group intravenously injected by 1 × 106 cells, and HCC + MSCs (Mel +MSCs) group.

Results: Rats in HCC group showed most deteriorated effect in form of increased mortality and relative liver weight, elevated …


Immunohistochemical Expression Of P53, Ki-67, And Cd34 In Psoriasis And Psoriasiform Dermatitis, Mazaher Ramezani, Atefeh Shamshiri, Elisa Zavattaro, Sedigheh Khazaei, Mansour Rezaei, Rozhano Mahmoodi, Masoud Sadeghi Nov 2024

Immunohistochemical Expression Of P53, Ki-67, And Cd34 In Psoriasis And Psoriasiform Dermatitis, Mazaher Ramezani, Atefeh Shamshiri, Elisa Zavattaro, Sedigheh Khazaei, Mansour Rezaei, Rozhano Mahmoodi, Masoud Sadeghi

BioMedicine

Background: Psoriasis is the prime example of psoriasiform tissue pattern and should be differentiated from other psoriasiform dermatoses both clinically and histopathologically.

Aim: To evaluate immunohistochemical expression of P53, Ki-67, and CD34 in psoriasis and psoriasiform dermatitis for diagnostic purposes.

Methods: An analytical cross-sectional study was performed on the paraffin blocks of 60 psoriasis and 31 psoriasiform dermatitis patients between 2014 and 2017. The selected formalin-fixed paraffin-embedded tissues from each biopsy specimen were cut into 4-micron sections. Initial sections were stained by hematoxylin and eosin staining. Primary antihuman antibodies against P53, Ki-67, and CD34 were applied. Positive control samples for …


Cohort Study Of Microelement Status In “Healthy” Population Of Russian Megapolis, Andrew K. Martusevich, Konstantin A. Karuzin Nov 2024

Cohort Study Of Microelement Status In “Healthy” Population Of Russian Megapolis, Andrew K. Martusevich, Konstantin A. Karuzin

BioMedicine

The aim of the study was at the cohort assessment of microelement status in large city residents classified as “apparently healthy people”. The population study included 2,025 randomly selected middle-aged (2045 years) persons without chronic diseases or acute infectious pathologies. The set of subjects was standardized by age and gender. A blood sample was taken once from each person to determine concentrations of microelements. The level of peripheral blood microelements were determined by atomic absorption spectrometry using «Shimadzu AA7000» device (Japan). The study of a large population of city residents demonstrated inhomogeneity in their microelement status. Deficit conditions were found …


Evaluation Of The Serum Β2 Microglobulin Level In Patients With Systemic Lupus Erythematosus And Its Correlation With Disease Activity, Miramir Aghdashi, Simak Salami, Ahmad Nezhadisalami Nov 2024

Evaluation Of The Serum Β2 Microglobulin Level In Patients With Systemic Lupus Erythematosus And Its Correlation With Disease Activity, Miramir Aghdashi, Simak Salami, Ahmad Nezhadisalami

BioMedicine

Background: Designation of disease activity is serious for the management of systemic lupus erythematosus (SLE). Serum level of β2 microglobulin (β2M) may be associated with illness activity in SLE disease. Since the role of β2M for assessing of illness activity in SLE is not completely clear, the current study aimed to discern evaluation of β2M in patients with SLE and its correlation with sickness activity.

Materials and Methods: In this case-control study, 50 patients with SLE disease and 25 healthy individuals were selected in Imam Khomeini Hospital in central of Urmia.

Blood samples were collected safely from patients, serum was …


Development Of Broad Spectrum Mycosporine Loaded Sunscreen Formulation From Ulva Fasciata Delile, Saurabh Bhatia, Satish Sardana, Ajay Sharma, Celia Bertha Vargas De La Cruz, Bhupal Chaugule, Laleh Khodaie Nov 2024

Development Of Broad Spectrum Mycosporine Loaded Sunscreen Formulation From Ulva Fasciata Delile, Saurabh Bhatia, Satish Sardana, Ajay Sharma, Celia Bertha Vargas De La Cruz, Bhupal Chaugule, Laleh Khodaie

BioMedicine

Ba.ckground: Sunscreen formulations primarily offer protection against UV induced damages however nowadays it also maintains skin natural physiological conditions. Current global market is flooded with numerous sunscreen products which offer protection to skin against several UV induced damages. However most of these sunscreen formulations offers narrow spectrum protection against UV and also suffer from stability as well as toxicity related issues.

Methods: Present work aims to isolate mycosporine amino acid (Mgy) from green alga namelyUlva fasciata (U. fasciata)and study its sunscreen potential against widely used domestic marketed formulation. Stability evaluations were also performed for almost 90 days.

Results: Results demonstrated …


Fascioliasis Mimicking Malignancy In An Old Patient, Mazaher Ramezani, Farhad Amirian, Masoud Sadeghi Nov 2024

Fascioliasis Mimicking Malignancy In An Old Patient, Mazaher Ramezani, Farhad Amirian, Masoud Sadeghi

BioMedicine

No abstract provided.


Protective Effect OfGlycyrrhiza GlabraRoots Extract On Bone Mineral Density Of Ovariectomized Rats, Dimitrios Galanis, Konstantinos Soultanis, Pavlos Lelovas, Alexandros Zervas, Panagiotis Papadopoulos, Antonis Galanos, Katerina Argyropoulou, Maria Makropoulou, Anastasia Patsaki, Christina Passali, Anastasia Tsingotjidou, Stavros Kourkoulis, Sofia Mitakou, Ismene Dontas Nov 2024

Protective Effect OfGlycyrrhiza GlabraRoots Extract On Bone Mineral Density Of Ovariectomized Rats, Dimitrios Galanis, Konstantinos Soultanis, Pavlos Lelovas, Alexandros Zervas, Panagiotis Papadopoulos, Antonis Galanos, Katerina Argyropoulou, Maria Makropoulou, Anastasia Patsaki, Christina Passali, Anastasia Tsingotjidou, Stavros Kourkoulis, Sofia Mitakou, Ismene Dontas

BioMedicine

Objective: The aim of this study was to evaluate the potential effect of the methanolic extract of plantGlycyrrhiza glabraroots on bone mineral density and femoral bone strength of ovariectomized rats.

Methods: Thirty 10-month-old Wistar rats were randomly separated into three groups of ten, Control, Ovariectomy and Ovariectomy-plus-Glycyrrhiza in their drinking water. Total and proximal tibial bone mineral density was measured in all groups before ovariectomy (baseline) and after 3 and 6 months post ovariectomy. Three-point-bending of the femurs and uterine weight and histology were examined at the end of the study.

Results: No significant difference was noted in bone density …


Addressing Statistical Challenges In The Analysis Of Proteomics Data With Extremely Small Sample Size: A Simulation Study, Kyung Hyun Lee, Shervin Assassi, Chandra Mohan, Claudia Pedroza Nov 2024

Addressing Statistical Challenges In The Analysis Of Proteomics Data With Extremely Small Sample Size: A Simulation Study, Kyung Hyun Lee, Shervin Assassi, Chandra Mohan, Claudia Pedroza

Faculty, Staff and Student Publications

Background: One of the most promising approaches for early and more precise disease prediction and diagnosis is through the inclusion of proteomics data augmented with clinical data. Clinical proteomics data is often characterized by its high dimensionality and extremely limited sample size, posing a significant challenge when employing machine learning techniques for extracting only the most relevant information. Although there is a wide array of statistical techniques and numerous analysis pipelines employed in proteomics data analysis, it is unclear which of these methods produce the most efficient, reproducible, and clinically meaningful results.

Results: In this study, we compared 9 unique …


The Relationship Between Spectral Signals And Retinal Sensitivity In Dendrobatid Frogs, Whitney G. Walkowski, Corinne L. Richards-Zawacki, William C. Gordon, Nicolas G. Bazan, Hamilton E. Farris Nov 2024

The Relationship Between Spectral Signals And Retinal Sensitivity In Dendrobatid Frogs, Whitney G. Walkowski, Corinne L. Richards-Zawacki, William C. Gordon, Nicolas G. Bazan, Hamilton E. Farris

School of Graduate Studies Faculty Publications

Research on visually driven behavior in anurans has often focused on Dendrobatoidea, a clade with extensive variation in skin reflectance, which is perceived to range from cryptic to conspicuous coloration. Because these skin patterns are important in intraspecific and interspecific communication, we hypothesized that the visual spectral sensitivity of dendrobatids should vary with conspecific skin spectrum. We predicted that the physiological response of frog retinas would be tuned to portions of the visible light spectrum that match their body reflectance. Using wavelength-specific electroretinograms (ERGs; from 350-650 nm), spectrometer measurements, and color-calibrated photography of the skin, we compared retinal sensitivity and …