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Full-Text Articles in Medicine and Health Sciences

Scaling Of Computed Tomography Body Composition To Height: Relevance Of Height-Normalized Indices In Patients With Colorectal Cancer, Justin C. Brown, Steven B. Heymsfield, Bette J. Caan Nov 2021

Scaling Of Computed Tomography Body Composition To Height: Relevance Of Height-Normalized Indices In Patients With Colorectal Cancer, Justin C. Brown, Steven B. Heymsfield, Bette J. Caan

School of Medicine Faculty Publications

Background: Body weight scales to height with a power of ≈2 (weight/height2), forming the basis of body mass index (BMI). The corresponding scaling of body composition measured by abdominal computed tomography (CT) to height has not been established. The objective of this analysis was to quantify the scaling of body composition measured by a single-slice axial abdominal CT image (skeletal muscle, and visceral, subcutaneous, and total adipose tissue) to height in patients with colorectal cancer (CRC). Methods: This cross-sectional study included non-Hispanic white males and females, aged 18–80 years, who were diagnosed with stage I–III CRC at an integrated health …


A Phase Ib Dose Escalation Trial Of Ro4929097 (A Γ-Secretase Inhibitor) In Combination With Exemestane In Patients With Er + Metastatic Breast Cancer (Mbc), Julie A. Means-Powell, Ingrid A. Mayer, Roohi Ismail-Khan, Luis Del Valle, Debra Tonetti, Vandana G. Abramson, Melinda S. Sanders, Richard M. Lush, Claudia Sorrentino, Samarpan Majumder, Lucio Miele Oct 2021

A Phase Ib Dose Escalation Trial Of Ro4929097 (A Γ-Secretase Inhibitor) In Combination With Exemestane In Patients With Er + Metastatic Breast Cancer (Mbc), Julie A. Means-Powell, Ingrid A. Mayer, Roohi Ismail-Khan, Luis Del Valle, Debra Tonetti, Vandana G. Abramson, Melinda S. Sanders, Richard M. Lush, Claudia Sorrentino, Samarpan Majumder, Lucio Miele

School of Medicine Faculty Publications

Preclinical studies: have demonstrated a complex cross-talk between Notch and estrogen signaling in ERα-positive breast cancer. Gamma-secretase inhibitors (GSIs) are investigational agents that block the cleavage and activation of Notch receptors. In animal models of endocrine-resistant breast cancer, combinations of tamoxifen and GSIs produce additive or synergistic efficacy, while decreasing the intestinal toxicity of GSIs. However, results of a clinical trial of a GSI-endocrine therapy combination in the metastatic setting have not been published to date, nor had the safety of such combinations been investigated with longer term treatment. We conducted a phase 1b dose escalation trial (NCT01149356) of GSI …


Artificial Image Objects For Classification Of Breast Cancer Biomarkers With Transcriptome Sequencing Data And Convolutional Neural Network Algorithms, Xiangning Chen, Daniel G. Chen, Zhongming Zhao, Justin M. Balko, Jingchun Chen Oct 2021

Artificial Image Objects For Classification Of Breast Cancer Biomarkers With Transcriptome Sequencing Data And Convolutional Neural Network Algorithms, Xiangning Chen, Daniel G. Chen, Zhongming Zhao, Justin M. Balko, Jingchun Chen

School of Medicine Faculty Publications

Background: Transcriptome sequencing has been broadly available in clinical studies. However, it remains a challenge to utilize these data effectively for clinical applications due to the high dimension of the data and the highly correlated expression between individual genes. Methods: We proposed a method to transform RNA sequencing data into artificial image objects (AIOs) and applied convolutional neural network (CNN) algorithms to classify these AIOs. With the AIO technique, we considered each gene as a pixel in an image and its expression level as pixel intensity. Using the GSE96058 (n = 2976), GSE81538 (n = 405), and GSE163882 (n = …


Palliative Care And Life-Sustaining/Local Procedures In Colorectal Cancer In The United States Hospitals: A Ten-Year Perspective, Zahra Mojtahedi, Ja Seol Koo, Ji Yoo, Pearl Kim, Hee-Taik Kang, Jinwook Hwang, Moon Kyung Joo, Jay J. Shen Oct 2021

Palliative Care And Life-Sustaining/Local Procedures In Colorectal Cancer In The United States Hospitals: A Ten-Year Perspective, Zahra Mojtahedi, Ja Seol Koo, Ji Yoo, Pearl Kim, Hee-Taik Kang, Jinwook Hwang, Moon Kyung Joo, Jay J. Shen

School of Medicine Faculty Publications

Background: In recent years, palliative care utilization has been increasing while life-sustaining/local procedures have been declining at the end of life. Palliative care utilization widely varies based on tumor type. Limited information is available on inpatient palliative care in colorectal cancer. Aims: This study investigated inpatient palliative care utilization and its association with patient demographics, hospital charges, and procedures among colorectal cancer patients admitted to US hospitals between 2008 and 2017. Receipt of life-sustaining and local procedures and surgeries were also investigated during the ten years. Methods: Data were extracted from the National inpatient sample (NIS) database containing de-identified information …


How I Treat Neuroendocrine Tumors, Aasems Jacob, Gaby Gabriel, Robert A. Ramirez, Yi Zarn Wang, Lowell Anthony, Aman Chauhan Oct 2021

How I Treat Neuroendocrine Tumors, Aasems Jacob, Gaby Gabriel, Robert A. Ramirez, Yi Zarn Wang, Lowell Anthony, Aman Chauhan

School of Medicine Faculty Publications

No abstract provided.


Obesity Modulates The Gut Microbiome In Triple-Negative Breast Cancer, Fokhrul Hossain, Samarpan Majumder, Justin David, Bruce A. Bunnell, Lucio Miele Oct 2021

Obesity Modulates The Gut Microbiome In Triple-Negative Breast Cancer, Fokhrul Hossain, Samarpan Majumder, Justin David, Bruce A. Bunnell, Lucio Miele

School of Medicine Faculty Publications

Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous sub-type of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflam-mation, and failure of cancer immunotherapy. However, the debate on what constitutes a “healthy” gut microbiome is ongoing, and the connection among …


Facilitators And Barriers To Clinical Practice Guideline-Consistent Supportive Care At Pediatric Oncology Institutions: A Children's Oncology Group Study, Aaron J. Sugalski, Tammy Lo, Melissa Beauchemin, Allison C. Grimes, Paula D. Robinson, Alexandra M. Walsh, Nancy Santesso, Ha Dang, Brian T. Fisher, Andrea Rothfus Wrightson, Lolie C. Yu, Lillian Sung, L Lee Dupuis Sep 2021

Facilitators And Barriers To Clinical Practice Guideline-Consistent Supportive Care At Pediatric Oncology Institutions: A Children's Oncology Group Study, Aaron J. Sugalski, Tammy Lo, Melissa Beauchemin, Allison C. Grimes, Paula D. Robinson, Alexandra M. Walsh, Nancy Santesso, Ha Dang, Brian T. Fisher, Andrea Rothfus Wrightson, Lolie C. Yu, Lillian Sung, L Lee Dupuis

School of Medicine Faculty Publications

Background Clinical practice guideline (CPG)-consistent care improves patient outcomes, but CPG implementation is poor. Little is known about CPG implementation in pediatric oncology. This study aimed to understand supportive care CPG implementation facilitators and barriers at pediatric oncology National Cancer Institute (NCI) Community Oncology Research Program (NCORP) institutions. Methods Healthcare professionals at 26 pediatric, Children's Oncology Group-member, NCORP institutions were invited to participate in face-to-face focus groups. Serial focus groups were held until saturation of ideas was reached. Supportive care CPG implementation facilitators and barriers were solicited using nominal group technique (NGT), and implementation of specific supportive care CPG recommendations …


Does Low Income Effects 5-Year Mortality Of Hepatocellular Carcinoma Patients?, Dong Jun Kim, Ji Won Yoo, Jong Wha Chang, Takashi Yamashita, Eun-Cheol Park, Kyu-Tae Han, Seung Ju Kim, Sun Jung Kim Sep 2021

Does Low Income Effects 5-Year Mortality Of Hepatocellular Carcinoma Patients?, Dong Jun Kim, Ji Won Yoo, Jong Wha Chang, Takashi Yamashita, Eun-Cheol Park, Kyu-Tae Han, Seung Ju Kim, Sun Jung Kim

School of Medicine Faculty Publications

Background: In Korea, the universal health system offers coverage to all members of society. Despite this, it is unclear whether risk of death from hepatocellular carcinoma (HCC) varies depending on income. We evaluated the impact of low income on HCC mortality. Methods: The Korean National Health Insurance sampling cohort was used to identify new HCC cases (n = 7325) diagnosed between 2004 and 2008, and the Korean Community Health Survey data were used to investigate community-level effects. The main outcome was 5-year all-cause mortality risk, and Cox proportional hazard models were applied to investigate the individual- and community-level factors associated …


Precision Medicine And Triple-Negative Breast Cancer: Current Landscape And Future Directions, Fokhrul Hossain, Samarpan Majumder, Justin David, Lucio Miele Jul 2021

Precision Medicine And Triple-Negative Breast Cancer: Current Landscape And Future Directions, Fokhrul Hossain, Samarpan Majumder, Justin David, Lucio Miele

School of Medicine Faculty Publications

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer associated with a high recurrence and metastasis rate that affects African-American women disproportionately. The recent approval of targeted therapies for small subgroups of TNBC patients by the US ‘Food and Drug Administration’ is a promising development. The advancement of next-generation sequencing, particularly somatic exome panels, has raised hopes for more individualized treatment plans. However, the use of precision medicine for TNBC is a work in progress. This review will discuss the potential benefits and challenges of precision medicine for TNBC. A recent clinical trial designed to target …


Severe Covid-19 Is Characterized By An Impaired Type I Interferon Response And Elevated Levels Of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells, Matthew J. Dean, Juan B. Ochoa, Maria Dulfary Sanchez-Pino, Jovanny Zabaleta, Jone Garai, Luis Del Valle, Dorota Wyczechowska, Lyndsey Buckner Baiamonte, Phaethon Philbrook, Rinku Majumder, Richard S. Vander Heide, Logan Dunkenberger, Ramesh Puttalingaiah Thylur, Bobby Nossaman, W. Mark Roberts, Andrew G. Chapple, Jiande Wu, Chindo Hicks, Jack Collins, Brian Luke Jul 2021

Severe Covid-19 Is Characterized By An Impaired Type I Interferon Response And Elevated Levels Of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells, Matthew J. Dean, Juan B. Ochoa, Maria Dulfary Sanchez-Pino, Jovanny Zabaleta, Jone Garai, Luis Del Valle, Dorota Wyczechowska, Lyndsey Buckner Baiamonte, Phaethon Philbrook, Rinku Majumder, Richard S. Vander Heide, Logan Dunkenberger, Ramesh Puttalingaiah Thylur, Bobby Nossaman, W. Mark Roberts, Andrew G. Chapple, Jiande Wu, Chindo Hicks, Jack Collins, Brian Luke

School of Medicine Faculty Publications

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen …


Oridonin And Its Derivatives For Cancer Treatment And Overcoming Therapeutic Resistance, Xi Liu, Jimin Xu, Jia Zhou, Qiang Shen Jul 2021

Oridonin And Its Derivatives For Cancer Treatment And Overcoming Therapeutic Resistance, Xi Liu, Jimin Xu, Jia Zhou, Qiang Shen

School of Medicine Faculty Publications

Cancer is one of the diseases with high morbidity and mortality on a global scale. Chemotherapy remains the primary treatment option for most cancer patients, including patients with progressive, metastatic, and recurrent diseases. To date, hundreds of chemotherapy drugs are used to treat various cancers, however, the anti-cancer efficacy and outcomes are largely hampered by chemotherapy-associated toxicity and acquired therapeutic resistance. The natural product (NP) oridonin has been extensively studied for its anti-cancer efficacy. More recently, oridonin has been shown to overcome drug resistance through multiple mechanisms, with yet-to-be-defined bona fide targets. Hundreds of oridonin derivative analogs (oridonalogs) have been …


Diagnosis-To-Surgery Interval And Survival For Different Histologies Of Stage I-Iia Lung Cancer, Lu Zhang, Mei Chin Hsieh, Lior Rennert, Paige Neroda, Xiao Cheng Wu, Chindo Hicks, Jiande Wu, Ronald Gimbel Jul 2021

Diagnosis-To-Surgery Interval And Survival For Different Histologies Of Stage I-Iia Lung Cancer, Lu Zhang, Mei Chin Hsieh, Lior Rennert, Paige Neroda, Xiao Cheng Wu, Chindo Hicks, Jiande Wu, Ronald Gimbel

School of Medicine Faculty Publications

Background: Guidelines on timeliness of lung cancer surgery are inconsistent. Lung cancer histologic subtypes have different prognosis and treatment. It is important to understand the consequences of delayed surgery for each lung cancer histologic subtype. This study aimed to examine the association between diagnosis-to-surgery time interval and survival for early stage lung cancer and selected histologic subtypes. Methods: Patients diagnosed with stage I-IIA lung cancer between 2004 and 2015 receiving definitive surgery and being followed up until Dec. 31, 2018, were identified from Surveillance, Epidemiology, and End Results database. Histologic subtypes included adenocarcinoma, squamous or epidermoid carcinoma, bronchioloalveolar carcinoma, large …


Upregulation Of Endogenous Trail-Elicited Apoptosis Is Essential For Metformin-Mediated Antitumor Activity Against Tnbc And Nsclc, Shuang Liu, Erik V. Polsdofer, Lukun Zhou, Sanbao Ruan, Hui Lyu, Defu Hou, Hao Liu, Ann D. Thor, Zhimin He, Bolin Liu Jun 2021

Upregulation Of Endogenous Trail-Elicited Apoptosis Is Essential For Metformin-Mediated Antitumor Activity Against Tnbc And Nsclc, Shuang Liu, Erik V. Polsdofer, Lukun Zhou, Sanbao Ruan, Hui Lyu, Defu Hou, Hao Liu, Ann D. Thor, Zhimin He, Bolin Liu

School of Medicine Faculty Publications

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promising antitumor activity in preclinical studies. However, the efficacy of recombinant TRAIL in clinical trials is compromised by its short serum half-life and low in vivo stability. Induction of endogenous TRAIL may overcome the limitations and become a new strategy for cancer treatment. Here, we discovered that metformin increased TRAIL expression and induced apoptosis in triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) cells. Metformin did not alter the expression of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). Metformin-upregulated TRAIL was secreted into conditioned medium (CM) and found to be functional, since the …


Disruption Of Foxo3a-Mirna Feedback Inhibition Of Igf2/Igf-1r/Irs1 Signaling Confers Herceptin Resistance In Her2-Positive Breast Cancer, Liyun Luo, Zhijie Zhang, Ni Qiu, Li Ling, Xiaoting Jia, Ying Song, Hongsheng Li, Jiansheng Li, Hui Lyu, Hao Liu, Zhimin He, Bolin Liu, Guopei Zheng May 2021

Disruption Of Foxo3a-Mirna Feedback Inhibition Of Igf2/Igf-1r/Irs1 Signaling Confers Herceptin Resistance In Her2-Positive Breast Cancer, Liyun Luo, Zhijie Zhang, Ni Qiu, Li Ling, Xiaoting Jia, Ying Song, Hongsheng Li, Jiansheng Li, Hui Lyu, Hao Liu, Zhimin He, Bolin Liu, Guopei Zheng

School of Medicine Faculty Publications

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 …


Advanced Bioinformatic Analysis And Pathway Prediction Of Nsclc Cells Upon Cisplatin Resistance, A. K.M.Nawshad Hossian, Fatema Tuz Zahra, Sagun Poudel, Camille F. Abshire, Paula Polk, Jone Garai, Jovanny Zabaleta, Constantinos M. Mikelis, George Mattheolabakis Apr 2021

Advanced Bioinformatic Analysis And Pathway Prediction Of Nsclc Cells Upon Cisplatin Resistance, A. K.M.Nawshad Hossian, Fatema Tuz Zahra, Sagun Poudel, Camille F. Abshire, Paula Polk, Jone Garai, Jovanny Zabaleta, Constantinos M. Mikelis, George Mattheolabakis

School of Medicine Faculty Publications

This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of …


Cancer Survivorship In Hematologic Malignancies: Lifestyle Changes After Diagnosis, Pannaga Malalur, Manas Agastya, Sandhya Wahi-Gururaj, Chad L. Cross, Delva Deauna-Limayo, Edwin C. Kingsley Feb 2021

Cancer Survivorship In Hematologic Malignancies: Lifestyle Changes After Diagnosis, Pannaga Malalur, Manas Agastya, Sandhya Wahi-Gururaj, Chad L. Cross, Delva Deauna-Limayo, Edwin C. Kingsley

School of Medicine Faculty Publications

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Background: Studies show that patients make lifestyle changes soon after certain solid tumor diagnoses, suggesting that this may be a teachable moment to motivate and promote healthy behaviors. There is a paucity of data regarding changes made after a diagnosis of a hematologic malignancy. Methods: A cross-sectional study of 116 patients at a community oncology center who completed anonymous questionnaires was performed. Questions addressed lifestyle choices made with respect to smoking, alcohol consumption, recreational drug use, diet, and exercise habits before and after diagnosis of a hematologic …


Characteristic Pancreatic And Splenic Immune Cell Infiltration Patterns In Mouse Acute Pancreatitis, Baibing Yang, Joy M. Davis, Thomas H. Gomez, Mamoun Younes, Xiurong Zhao, Qiang Shen, Run Wang, Tien C. Ko, Yanna Cao Feb 2021

Characteristic Pancreatic And Splenic Immune Cell Infiltration Patterns In Mouse Acute Pancreatitis, Baibing Yang, Joy M. Davis, Thomas H. Gomez, Mamoun Younes, Xiurong Zhao, Qiang Shen, Run Wang, Tien C. Ko, Yanna Cao

School of Medicine Faculty Publications

Background: A systemic evaluation of immune cell infiltration patterns in experimental acute pancreatitis (AP) is lacking. Using multi-dimensional flow cytometry, this study profiled infiltrating immune cell types in multiple AP mouse models. Methods: Three AP models were generated in C57BL/6 mice via cerulein (CAE) injection, alcohol and palmitoleic acid (EtOH + POA) injection, and alcohol diet feeding and cerulein (EtOH + CAE) injection. Primary pancreatic cells and splenocytes were prepared, and multi-dimensional flow cytometry was performed and analyzed by manual gating and computerized PhenoGraph, followed by visualization with t-distributed stochastic neighbor embedding (t-SNE). Results: CAE treatment induced a time-dependent increase …


Short- And Long-Term Outcomes For Single-Port Risk-Reducing Salpingo-Oophorectomy With And Without Hysterectomy For Women At Risk For Gynecologic Cancer, Caitlin E. Carr, Laura Chambers, Amelia Marie Jernigan, Lindsey Freeman, Pedro F. Escobar, Chad M. Michener Feb 2021

Short- And Long-Term Outcomes For Single-Port Risk-Reducing Salpingo-Oophorectomy With And Without Hysterectomy For Women At Risk For Gynecologic Cancer, Caitlin E. Carr, Laura Chambers, Amelia Marie Jernigan, Lindsey Freeman, Pedro F. Escobar, Chad M. Michener

School of Medicine Faculty Publications

Introduction Risk-reducing salpingo-oophorectomy has been established as one of the most effective strategies in risk reduction for ovarian and breast cancers among women at increased genetic risk. However, there are limited data regarding the single-port laparoscopic platform in the field of risk-reducing surgery. Our objective was to describe outcomes after single-port risk-reducing salpingo-oophorectomy with or without hysterectomy for reduction of ovarian, breast, or endometrial cancer risk. Methods A retrospective, single institution (Canadian Task Force Classification II.2) analysis was performed in women at high genetic or familial risk for ovarian/tubal/primary peritoneal cancer or with personal history of breast cancer who underwent …