Medicine and Health Sciences Commons^™

Survival With Axicabtagene Ciloleucel In Large B-Cell Lymphoma, Jason R Westin, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: In an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes.

METHODS: In this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had …

Conditional Metastasis Of Uveal Melanoma In 8091 Patients Over Half-Century (51 Years) By Age Group: Assessing The Entire Population And The Extremes Of Age, Carol L. Shields, Annika Samuelson, Glenn Oh, Joseph D. Desimone, Zaynab Sajjadi, Zeynep Bas, Nicholas E Kalafatis, Sara E. Lally, Jerry A. Shields, Philip W. Dockery

Wills Eye Hospital Papers

PURPOSE: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age).

METHODS: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific …

Definitive Treatment And Risk Of Death Among Men Diagnosed With Metastatic Prostate Cancer At The Veterans Health Administration, Bettina F Drake, Saira Khan, Mei Wang, Veronica Hicks, Kate Nichols, Meghan Taylor, Eric H Kim, Su-Hsin Chang

2020-Current year OA Pubs

PURPOSE: To assess the potential survival benefit associated with receipt of definitive treatment (radical prostatectomy or radiation), compared to non-definitive treatment (hormonal therapy or chemotherapy) among men with metastatic prostate cancer.

METHODS: A cohort of men diagnosed with metastatic (T4/M1/N1 or T4/M1) prostate cancer from 1999 to 2013 in the Veterans Health Administration were identified and followed to December 28, 2014. All-cause and prostate cancer-specific mortality were evaluated at 10 years for the T4/M1/N1 cohort and 8 years for the T4/M1/ cohort. The association of definitive treatment (radical prostatectomy or radiation), compared to non-definitive (hormonal therapy or chemotherapy) with both …

Impact Of Timing To Initiate Adjuvant Therapy On Survival Of Elderly Glioblastoma Patients Using The Seer-Medicare And National Cancer Databases, Ping Zhu, Xianglin L Du, Lu-Yu Hwang, David Lairson, Ruosha Li, Yoshua Esquenazi, Jay-Jiguang Zhu

Journal Articles

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 …

A Flexible-Hazards Cure Model With Application To Patients With Soft Tissue Sarcoma, Can Xie, Xuelin Huang, Ruosha Li, Peter W T Pisters

Journal Articles

In medical research, it is often of great interest to have an accurate estimation of cure rates by different treatment options and for different patient groups. If the follow-up time is sufficiently long and the sample size is large, the proportion of cured patients will make the Kaplan-Meier estimator of survival function have a flat plateau at its tail, whose value indicates the overall cure rate. However, it may be difficult to estimate and compare the cure rates for all the subsets of interest in this way, due to the limit of sample sizes and curse of dimensionality. In the …

Mixture Models For Interval Censored Outcomes, Yibai Zhao

Doctoral Dissertations

Silent events such as the first detectable HIV infection, the onset of Type 2 diabetes and prostate cancer progression are often ascertained by diagnostic tests and/or self-reports that are scheduled periodically. In such applications, we only observe the time to the event of interest to lie between the times of last negative and the first positive tests, resulting in interval-censored observations. In addition, in some medical studies, a substantial proportion of participants may experience the events before the study, so-called prevalent cases, or participants may never experience the event, that is regarded as non-susceptible cases (or indolent cancer or long-term …

Overall Survival With Brentuximab Vedotin In Stage Iii Or Iv Hodgkin's Lymphoma, Stephen M Ansell, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has …

The Medicaid Expansion: Modeling Of Important Factors In State Decision Making, Augustus M. White

Haslam Scholars Projects

No abstract provided.

Predictive Biomarkers For 5-Fluorouracil And Oxaliplatin-Based Chemotherapy In Gastric Cancers Via Profiling Of Patient-Derived Xenografts., Deukchae Na, Jeesoo Chae, Sung-Yup Cho, Wonyoung Kang, Ahra Lee, Seoyeon Min, Jinjoo Kang, Min Jung Kim, Jaeyong Choi, Woochan Lee, Dongjin Shin, Ahrum Min, Yu-Jin Kim, Kyung-Hun Lee, Tae-Yong Kim, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, Woo-Ho Kim, Hansoo Park, Seock-Ah Im, Han-Kwang Yang, Charles Lee, Jong-Il Kim

Faculty Research 2021

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both …

Quality-Adjusted Time Without Symptoms Of Disease Or Toxicity (Q-Twist) Analysis Of Cpx-351 Versus 7 + 3 In Older Adults With Newly Diagnosed High-Risk/Secondary Aml, Jorge E Cortes, Tara L Lin, Geoffrey L Uy, Robert J Ryan, Stefan Faderl, Jeffrey E Lancet

2020-Current year OA Pubs

BACKGROUND: CPX-351 (United States: Vyxeos

METHODS: Patients were randomized 1:1 between December 20, 2012 and November 11, 2014 to receive induction with CPX-351 or 7 + 3. Survival time for each patient was partitioned into 3 health states: TOX (time with any grade 3 or 4 toxicity or prior to remission), TWiST (time in remission without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Within each treatment arm, Q-TWiST was calculated by adding the mean time spent in each health state weighted by its respective quality-of-life, represented by health utility. The relative Q-TWiST gain, calculated as …

Investigating The Relevance Of Major Signaling Pathways In Cancer Survival Using A Biologically Meaningful Deep Learning Model, Jiarui Feng, Heming Zhang, Fuhai Li

2020-Current year OA Pubs

BACKGROUND: Survival analysis is an important part of cancer studies. In addition to the existing Cox proportional hazards model, deep learning models have recently been proposed in survival prediction, which directly integrates multi-omics data of a large number of genes using the fully connected dense deep neural network layers, which are hard to interpret. On the other hand, cancer signaling pathways are important and interpretable concepts that define the signaling cascades regulating cancer development and drug resistance. Thus, it is important to investigate potential associations between patient survival and individual signaling pathways, which can help domain experts to understand deep …

Utilization Of Target Lesion Heterogeneity For Treatment Efficacy Assessment In Late Stage Lung Cancer, Dung-Tsa Chen, Wenyaw Chan, Zachary J Thompson, Ram Thapa, Amer A Beg, Andreas N Saltos, Alberto A Chiappori, Jhanelle E Gray, Eric B Haura, Trevor A Rose, Ben Creelan

Journal Articles

RATIONALE: Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.g., 29 trials so far listed in clinicaltrials.gov for cancer patients with oligometastasis). Some of the trials have shown survival benefit by tailored treatment strategies. This evidence presents the unmet need to incorporate lesion heterogeneity to improve …

Longitudinal Care Cascade Outcomes Among People Eligible For Antiretroviral Therapy Who Are Newly Linking To Care In Zambia: A Multistate Analysis, Aaloke Mody, David V Glidden, Ingrid Eshun-Wilson, Kombatende Sikombe, Sandra Simbeza, Njekwa Mukamba, Paul Somwe, Laura K Beres, Jake Pry, Carolyn Bolton-Moore, Nancy Padian, Charles B Holmes, Izukanji Sikazwe, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Retention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time.

METHODS: We analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last …

Prognostic Gene Expression Signature For High-Grade Serous Ovarian Cancer., J Millstein, T Budden, E L Goode, M S Anglesio, A Talhouk, M P Intermaggio, H S Leong, S Chen, W Elatre, B Gilks, T Nazeran, M Volchek, R C Bentley, C Wang, D S Chiu, S Kommoss, S C Y Leung, J Senz, A Lum, V Chow, H Sudderuddin, R Mackenzie, Joshy George, Aocs Group, S Fereday, J Hendley, N Traficante, H Steed, J M Koziak, M Köbel, I A Mcneish, T Goranova, D Ennis, G Macintyre, D Silva De Silva, T Ramón Y Cajal, J García-Donas, S Hernando Polo, G C Rodriguez, K L Cushing-Haugen, H R Harris, C S Greene, R A Zelaya, S Behrens, R T Fortner, P Sinn, E Herpel, J Lester, J Lubiński, O Oszurek, A Tołoczko, C Cybulski, J Menkiszak, C L Pearce, M C Pike, C Tseng, J Alsop, V Rhenius, H Song, M Jimenez-Linan, A M Piskorz, A Gentry-Maharaj, C Karpinskyj, M Widschwendter, N Singh, C J Kennedy, R Sharma, P R Harnett, B Gao, S E Johnatty, R Sayer, J Boros, S J Winham, G L Keeney, S H Kaufmann, M C Larson, H Luk, B Y Hernandez, P J Thompson, L R Wilkens, M E Carney, B Trabert, J Lissowska, L Brinton, M E Sherman, C Bodelon, S Hinsley, L A Lewsley, R Glasspool, S N Banerjee, E A Stronach, P Haluska, I Ray-Coquard, S Mahner, B Winterhoff, D Slamon, D A Levine, L E Kelemen, J Benitez, J Chang-Claude, J Gronwald, A H Wu, U Menon, M T Goodman, J M Schildkraut, N Wentzensen, R Brown, A Berchuck, G Chenevix-Trench, A Defazio, S A Gayther, M J García, M J Henderson, M A Rossing, A Beeghly-Fadiel, P A Fasching, S Orsulic, B Y Karlan, G E Konecny, D G Huntsman, D D Bowtell, J D Brenton, J A Doherty, P D P Pharoah, S J Ramus

Faculty Research 2020

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.

PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for …

Beyond An Updated Graded Prognostic Assessment (Breast Gpa): A Prognostic Index And Trends In Treatment And Survival In Breast Cancer Brain Metastases From 1985 To Today, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Journal Articles

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 …

Safety And Efficacy Of Tocilizumab In The Treatment Of Severe Acute Respiratory Syndrome Coronavirus-2 Pneumonia: A Retrospective Cohort Study, Atul Patel, Kinjal Shah, Mitkumar Dharsandiya, Ketan Patel, Tushar Patel, Mukesh Patel, Tea Reljic, Ambuj Kumar

All publications

Background: Cytokine release storm (CRS) in severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is thought to be the cause for organ damage and death which is independent of the actual viral burden. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is approved for the treatment of CRS. We describe the efficacy and safety of TCZ in SARS CoV-2 pneumonia. Methods: This retrospective study was conducted at a tertiary care hospital from April 20 2020 to May 21 2020. The primary endpoint was the cumulative incidence of a composite of either need for admission to the intensive care unit (ICU) with invasive mechanical …

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

A Technique For Approximating Transition Rates From Published Survival Analyses, Markian A. Pahuta, Joel Werier, Eugene K. Wai, Roy A. Patchell, Doug Coyle

Neurology Faculty Publications

Background: Quality-adjusted-life-years (QALYs) are used to concurrently quantify morbidity and mortality within a single parameter. For this reason, QALYs can facilitate the discussion of risks and benefits during patient counseling regarding treatment options. QALYs are often calculated using partitioned-survival modelling. Alternatively, QALYs can be calculated using more flexible and informative state-transition models populated with transition rates estimated using multistate modelling (MSM) techniques. Unfortunately the latter approach is considered not possible when only progression-free survival (PFS) and overall survival (OS) analyses are reported.

Methods: We have developed a method that can be used to estimate approximate transition rates from published PFS …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Commonly Integrated Epigenetic Modifications Of Differentially Expressed Genes Lead To Adaptive Resistance In Cancer., Abdullah Al Emran, Diego M Marzese, Dinoop R Menon, Heinz Hammerlindl, Farzana Ahmed, Erika Richtig, Pascal Duijf, Dave Hoon, Helmut Schaider

Articles, Abstracts, and Reports

Aim: To investigate the integrated epigenetic regulation of acquired drug resistance in cancer. Materials & methods: Our gene expression data of five induced drug-tolerant cell models, one resistant cell line and one publicly available drug-resistant dataset were integrated to identify common differentially expressed genes and pathways. ChIP-seq and DNA methylation by HM450K beadchip were used to study the epigenetic profile of differential expressed genes. Results & conclusion: Integrated transcriptomic analysis identified a common 'viral mimicry' related gene signature in induced drug-tolerant cells and the resistant state. Analysis of the epigenetic regulation revealed a common set of down-regulated genes, which are …

Comparative Effectiveness Of Intensity Modulated Radiation Therapy To 3-Dimensional Conformal Radiation In Locally Advanced Lung Cancer: Pathological And Clinical Outcomes., Sarit Appel, Jair Bar, Alon Ben-Nun, Marina Perelman, Dror Alezra, Damien Urban, Maoz Ben-Ayun, Nir Honig, Efrat Ofek, Tamar Katzman, Amir Onn, Sumit Chatterji, Sergey Dubinski, Lev Tsvang, Shira Felder, Judith Kraitman, Ory Haisraely, Tatiana Rabin Alezra, Sivan Lieberman, Edith M. Marom, Nir Golan, David Simansky, Zvi Symon, Yaacov Richard Lawrence

Department of Radiation Oncology Faculty Papers

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy.

METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) …

Epigenetic Silencing Rna Methylation Machinery Fto And Mettl3 Associate With Patient Survival In Renal Clear Cell Carcinoma, Jiaxun Zhao

Public Health Theses

Purpose: RNA methylation eraser FTO and writer METTL3 play important roles in human diseases by regulating gene expression. However, the potential of FTO and METTL3 as markers in renal clear cell carcinoma (CCRCC) is still unknown. The purpose of this study is to investigate differential expression of FTO and METTL3 in CCRCC vs. normal kidney tissues, the association of FTO and METTL3 expression and methylation with and their interaction of FTO and METTL3 expression in patient survival in CCRCC.

Method: FTO and METTL3 expression and methylation, the clinicopathologic data were retrieved from a publicly accessed dataset of The Cancer Genome …

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO₂) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO₂ exposure (i.e., the effects of nTiO₂-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO₂ (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …

Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived …

Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival In Acute Lymphoblastic Leukemia: A Cibmtr Analysis., William A. Wood, Ruta Brazauskas, Zhen-Huan Hu, Hisham Abdel-Azim, Ibrahim A. Ahmed, Mahmoud Aljurf, Sherif Badawy, Amer Beitinjaneh, Biju George, David Buchbinder, Jan Cerny, Laurence Dedeken, Miguel Angel Diaz, Cesar O. Freytes, Siddhartha Ganguly, Usama Gergis, David Gomez Almaguer, Ashish Gupta, Gregory Hale, Shahrukh K. Hashmi, Yoshihiro Inamoto, Rammurti T. Kamble, Kehinde Adekola, Tamila Kindwall-Keller, Jennifer Knight, Lalit Kumar, Yachiyo Kuwatsuka, Jason Law, Hillard M. Lazarus, Charles Lemaistre, Richard F. Olsson, Michael A. Pulsipher, Bipin N. Savani, Kirk R. Schultz, Ayman A. Saad, Matthew Seftel, Sachiko Seo, Thomas C. Shea, Amir Steinberg, Keith Sullivan, David Szwajcer, Baldeep Wirk, Jean Yared, Agnes Yong, Jignesh Dalal, Theresa Hahn, Nandita Khera, Carmem Bonfim, Yoshiko Atsuta, Wael Saber

Manuscripts, Articles, Book Chapters and Other Papers

For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed …

Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg

Shu-Ching Chang, PhD, MS

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 …

Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 …

Prostate Cancer Survival Among Hispanics: A Surveillance, Epidemiology, And End Results (Seer) Population-Based Cohort Study, David Rivas

UNLV Theses, Dissertations, Professional Papers, and Capstones

Hispanics are now the youngest, largest, and fastest growing minority group in the U.S. Prostate cancer (PC) is the most commonly diagnosed cancer in men and is the second-leading cause of cancer deaths among Hispanics. For the first time, we examined PC-specific survival among distinct Hispanic groups that include Mexicans, Cubans, Dominicans, Puerto Ricans, as well as Central and South Americans. We compared these groups to the main reference population in the U.S., non-Hispanic Whites (NHW), after adjustment for prognostic factor risk categories (prostate-specific antigen (PSA) level, Gleason score, and tumor stage), as well as sociodemographic covariates (e.g., health insurance, …

Comorbidities In Aging Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) in general and sickle cell anemia in particular is a highly complex disorder both at the molecular and clinical levels. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Moreover, despite the fact that SCD is a chronic malady, its manifestations are both acute and chronic. The former include, among other things, the recurrent vaso-occlusive crises (its hallmark) and acute chest syndrome. The chronic complications include most commonly avascular necrosis and leg ulcers. Currently, survival of patients with …

Data-Driven Modeling For Decision Support Systems And Treatment Management In Personalized Healthcare, Milad Zafar Nezhad

Wayne State University Dissertations

Massive amount of electronic medical records (EMRs) accumulating from patients and populations motivates clinicians and data scientists to collaborate for the advanced analytics to create knowledge that is essential to address the extensive personalized insights needed for patients, clinicians, providers, scientists, and health policy makers. Learning from large and complicated data is using extensively in marketing and commercial enterprises to generate personalized recommendations. Recently the medical research community focuses to take the benefits of big data analytic approaches and moves to personalized (precision) medicine. So, it is a significant period in healthcare and medicine for transferring to a new paradigm. …