Medicine and Health Sciences Commons^™

Identifying Personalized Metabolic Signatures In Breast Cancer., Priyanka Baloni, Wikum Dinalankara, John C Earls, Theo A Knijnenburg, Donald Geman, Luigi Marchionni, Nathan D Price

Articles, Abstracts, and Reports

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino …

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland J Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

Upper And Lower Limb Movement Kinematics In Aging, Zheng Wang, Callie Lane, Matthew Terza, Pravin Khemani, Su Lui, Walker S Mckinney, Matthew W Mosconi

Articles, Abstracts, and Reports

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation cytosine-guanine-guanine (CGG) trinucleotide repeat expansion of the FMR1 gene. FXTAS is estimated to be the most common single-gene form of ataxia in the aging population. Gait ataxia and intention tremor are the primary behavioral symptoms of FXTAS, though clinical evaluation of these symptoms often is subjective, contributing to difficulties in reliably differentiating individuals with FXTAS and asymptomatic premutation carriers. This study aimed to clarify the extent to which quantitative measures of gait and upper limb kinematics may serve as biobehavioral markers of FXTAS degeneration. Nineteen premutation carriers …

Development And Preliminary Clinical Activity Of Pd-1-Guided Ctla-4 Blocking Bispecific Dart Molecule., Alexey Berezhnoy, Bradley J Sumrow, Kurt Stahl, Kalpana Shah, Daorong Liu, Jonathan Li, Su-Shin Hao, Anushka De Costa, Sanjeev Kaul, Johanna Bendell, Gregory M Cote, Jason J Luke, Rachel E Sanborn, Manish R Sharma, Francine Chen, Hua Li, Gundo Diedrich, Ezio Bonvini, Paul A Moore

Articles, Abstracts, and Reports

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner.

Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …

Erratum: Viswanathan, A., Et Al. Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor With Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation)., Anisha Viswanathan, Aliyu Musa, Akshaya Murugesan, João R Vale, Carlos A M Afonso, Saravanan Konda Mani, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

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Sitc Cancer Immunotherapy Resource Document: A Compass In The Land Of Biomarker Discovery., Siwen Hu-Lieskovan, Srabani Bhaumik, Kavita Dhodapkar, Jean-Charles J B Grivel, Sumati Gupta, Brent A Hanks, Sylvia Janetzki, Thomas O Kleen, Yoshinobu Koguchi, Amanda W Lund, Cristina Maccalli, Yolanda D Mahnke, Ruslan D Novosiadly, Senthamil R Selvan, Tasha Sims, Yingdong Zhao, Holden T Maecker

Articles, Abstracts, and Reports

Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in …

The Authors Reply., Mindy M Pike, Aseel Alsouqi, Samuel A E Headley, Katherine Tuttle, Elizabeth Elspeth Evans, Charles M Milch, Kelsey Anne Moody, Michael Germain, Thomas G Stewart, Loren Lipworth, Jonathan Himmelfarb, T Alp Ikizler, Cassianne Robinson-Cohen

Articles, Abstracts, and Reports

No abstract provided.

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume Ii-Practical Challenges., Alessandra Cesano, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Sergio Rutella

Articles, Abstracts, and Reports

The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated …

A Rare Case Of Idiopathic Pyometra In A Premenopausal Patient., Kristina M Mori, Howard D Epstein, Michael C Roossin, Bram H Goldstein

Articles, Abstracts, and Reports

Pyometra is a very uncommon disease principally occurring in postmenopausal women. It is characterized by the accumulation of purulent material within the uterine cavity. This paper presents the clinical history of a 35-year-old premenopausal woman with otherwise normal menstruation who developed heavy menstruation and was diagnosed with a benign pyometra of indeterminate etiology in March 2017. The patient underwent repeated ultrasound-guided drainage, dilation and curettage, and antibiotic therapy. Biopsies of the pelvic sidewall revealed endometriosis in June 2017. The heavy menstruation and suppurative fluid in the uterus of the patient persisted in which intramuscular leuprolide acetate was prescribed to address …

Salvage Of Failed Femoral Neck Fracture Fixation With Conversion Total Hip Arthroplasty Using The Direct Anterior Approach., Andrew G Yun, Marilena Qutami, Kory B Dylan Pasko

Articles, Abstracts, and Reports

Purpose: Failed femoral neck fracture (FNF) fixation with

Materials and Methods: Medical records for 42 patients with a prior history of FNF fixation who underwent conversion THA with hardware removal between 2009 and 2019 were retrospectively reviewed. Surgery was performed by a single surgeon at a single institution. All patients underwent hardware removal followed by direct anterior approach (DAA) THA using two separate incisions. Clinical outcomes, radiographic findings, and perioperative morbidity and mortality are reported.

Results: Clinically, there were no postoperative dislocations, periprosthetic fractures, or infections at follow-up. After a mean follow-up of 4 years, the mean hip disability and …

Conversion From Knee Arthrodesis Back To Arthroplasty: A Particular Challenge In Combination With Fungal Periprosthetic Joint Infection., Sven Frieler, Emre Yilmaz, Ryan Goodmanson, Yannik Hanusrichter, Thomas A Schildhauer, Hinnerk Baecker

Articles, Abstracts, and Reports

A 58-year-old female treated at an outside facility with knee arthrodesis due to persistent periprosthetic joint infection fulfilled all prerequisites for a conversion back to arthroplasty, as part of a 2-stage revision. Owing to the detection of Candida parapsilosis, the treatment concept was converted to a three-stage procedure. A scheduled spacer exchange with additional amphotericin B-loaded polymethylmethacrylate was conducted as an intermediate revision before reimplantation. Conversion in the setting of fungal periprosthetic joint infection presents a challenge, and successful treatment hinges on the use of proper antifungal and antimicrobial protocols, advanced surgical techniques, and a multidisciplinary team approach. At …

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

New Beginnings., Jeffrey C Wang, Jens R Chapman, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.

Predicting Breast Cancer Response To Neoadjuvant Treatment Using Multi-Feature Mri: Results From The I-Spy 2 Trial., Wen Li, David C Newitt, Jessica Gibbs, Lisa J Wilmes, Ella F Jones, Vignesh A Arasu, Fredrik Strand, Natsuko Onishi, Alex Anh-Tu Nguyen, John Kornak, Bonnie N Joe, Elissa R Price, Haydee Ojeda-Fournier, Mohammad Eghtedari, Kathryn W Zamora, Stefanie A Woodard, Heidi Umphrey, Wanda Bernreuter, Michael Nelson, An Ly Church, Patrick Bolan, Theresa Kuritza, Kathleen Ward, Kevin Morley, Dulcy Wolverton, Kelly Fountain, Dan Lopez-Paniagua, Lara Hardesty, Kathy Brandt, Elizabeth S Mcdonald, Mark Rosen, Despina Kontos, Hiroyuki Abe, Deepa Sheth, Erin P Crane, Charlotte Dillis, Pulin Sheth, Linda Hovanessian-Larsen, Dae Hee Bang, Bruce Porter, Karen Y Oh, Neda Jafarian, Alina Tudorica, Bethany L Niell, Jennifer Drukteinis, Mary S Newell, Michael A Cohen, Marina Giurescu, Elise Berman, Constance Lehman, Savannah C Partridge, Kimberly A Fitzpatrick, Marisa H Borders, Wei T Yang, Basak Dogan, Sally Goudreau, Thomas Chenevert, Christina Yau, Angela Demichele, Don Berry, Laura J Esserman, Nola M Hylton

Articles, Abstracts, and Reports

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and …

The Effect Of Mock Code Blue Simulations And Dedicated Advanced Cardiac Life Support Didactics On Resident Perceived Competency., Dallis Q Ngo, Christina Vu, Thien Nguyen, Patricia Sotolongo, Manika Talati, Nikki Zahabi, Katrina Platt

Articles, Abstracts, and Reports

In-hospital cardiac or pulmonary arrest is associated with high mortality. In the USA, approximately 200,000 of these events occur and are associated with overall survival rates of 18%-20%. Despite advances in resuscitative methods, the probability of intact survival also remains unfavorable. Though many factors play a role, we believe a large portion of a patient's survival is dependent on the competency of the leader of the code blue or resuscitative team's efforts. Newly minted physicians who enter medical training in their respective residencies are equipped with a wide range of clinical competency in regards to hands-on experience and aptitude with …

Breast Cancer Distant Recurrence Lead Time Interval By Detection Method In An Institutional Cohort., Henry G Kaplan, Judith A Malmgren, Mary K Atwood

Articles, Abstracts, and Reports

BACKGROUND: Lead time, the interval between screen detection and when a disease would have become clinically evident, has been cited to explain longer survival times in mammography detected breast cancer cases (BC).

METHODS: An institutional retrospective cohort study of BC outcomes related to detection method (mammography (MamD) vs. patient (PtD)). Cases were first primary invasive stage I-III BC, age 40-74 years (n = 6603), 1999-2016. Survival time was divided into 1) distant disease-free interval (DDFI) and 2) distant disease-specific survival (DDSS) as two separate time interval outcomes. We measured statistical association between detection method and diagnostic, treatment and outcome variables …

Metabolic Network Analysis Reveals Altered Bile Acid Synthesis And Metabolism In Alzheimer's Disease., Priyanka Baloni, Cory C Funk, Jingwen Yan, James T Yurkovich, Alexandra Kueider-Paisley, Kwangsik Nho, Almut Heinken, Wei Jia, Siamak Mahmoudiandehkordi, Gregory Louie, Andrew J Saykin, Matthias Arnold, Gabi Kastenmüller, William J Griffiths, Ines Thiele, Alzheimer’S Disease Metabolomics Consortium, Rima Kaddurah-Daouk, Nathan D Price

Articles, Abstracts, and Reports

Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. …

Safety And Tolerability Of Srx246, A Vasopressin 1a Antagonist, In Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial., Michael J Brownstein, Neal G Simon, Jeffrey D Long, Jon Yankey, Hilda T Maibach, Merit Cudkowicz, Christopher Coffey, Robin A Conwit, Codrin Lungu, Karen E Anderson, Steven M Hersch, Dixie J Ecklund, Eve M Damiano, Debra E Itzkowitz, Shifang Lu, Marianne K Chase, Jeremy M Shefner, Andrew Mcgarry, Brenda Thornell, Catherine Gladden, Michele Costigan, Padraig O'Suilleabhain, Frederick J Marshall, Amy M Chesire, Paul Deritis, Jamie L Adams, Peter Hedera, Kelly Lowen, H Diana Rosas, Amie L Hiller, Joseph Quinn, Kellie Keith, Andrew P Duker, Christina Gruenwald, Angela Molloy, Cara Jacob, Stewart Factor, Elaine Sperin, Danny Bega, Zsazsa R Brown, Lauren C Seeberger, Victor W Sung, Melanie Benge, Sandra K Kostyk, Allison M Daley, Susan Perlman, Valerie Suski, Patricia Conlon, Matthew J Barrett, Stephanie Lowenhaupt, Mark Quigg, Joel S Perlmutter, Brenton A Wright, Elaine Most, Guy J Schwartz, Jessica Lamb, Rosalind S Chuang, Carlos Singer, Karen Marder, Joyce A Moran, John R Singleton, Meghan Zorn, Paola V Wall, Richard M Dubinsky, Carolyn Gray, Carolyn Drazinic

Articles, Abstracts, and Reports

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic …

A Pilot Study Comparing The Efficacy Of Lactate Dehydrogenase Levels Versus Circulating Cell-Free Micrornas In Monitoring Responses To Checkpoint Inhibitor Immunotherapy In Metastatic Melanoma Patients., Matias A Bustos, Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T Tran, Kevin Tran, Ling Takeshima, Stacey L Stern, Steven O'Day, Dave Hoon

Articles, Abstracts, and Reports

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 …

Fall Prevention In A Neurosurgery Clinic, Beth Ann Bremer, Brenda Senger, Jonathan Dennis Carlson, Teresa Bigand, Deborah Smith

Articles, Abstracts, and Reports

No abstract provided.

Discovery Of Driver Non-Coding Splice-Site-Creating Mutations In Cancer., Song Cao, Daniel Cui Zhou, Clara Oh, Reyka G Jayasinghe, Yanyan Zhao, Christopher J Yoon, Matthew A Wyczalkowski, Matthew H Bailey, Terrence Tsou, Qingsong Gao, Andrew Malone, Sheila Reynolds, Ilya Shmulevich, Michael C Wendl, Feng Chen, Li Ding

Articles, Abstracts, and Reports

Non-coding mutations can create splice sites, however the true extent of how such somatic non-coding mutations affect RNA splicing are largely unexplored. Here we use the MiSplice pipeline to analyze 783 cancer cases with WGS data and 9494 cases with WES data, discovering 562 non-coding mutations that lead to splicing alterations. Notably, most of these mutations create new exons. Introns associated with new exon creation are significantly larger than the genome-wide average intron size. We find that some mutation-induced splicing alterations are located in genes important in tumorigenesis (ATRX, BCOR, CDKN2B, MAP3K1, MAP3K4, MDM2, SMAD4, STK11, TP53 etc.), often leading …

Semiautomated Glasgow-Blatchford Bleeding Score Helps Direct Bed Placement For Patients With Upper Gastrointestinal Bleeding., Drew B Schembre, Robson E Ely, Janice M Connolly, Kunjali T Padhya, Rohit Sharda, John J Brandabur

Articles, Abstracts, and Reports

OBJECTIVE: The Glasgow-Blatchford Bleeding Score (GBS) was designed to identify patients with upper gastrointestinal bleeding (UGIB) who do not require hospitalisation. It may also help stratify patients unlikely to benefit from intensive care.

DESIGN: We reviewed patients assigned a GBS in the emergency room (ER) via a semiautomated calculator. Patients with a score ≤7 (low risk) were directed to an unmonitored bed (UMB), while those with a score of ≥8 (high risk) were considered for MB placement. Conformity with guidelines and subsequent transfers to MB were reviewed, along with transfusion requirement, rebleeding, length of stay, need for intervention and death. …

Heroism And Hypocrisy: Seeing Our Reflection With 2020 Vision., Ira Byock

Articles, Abstracts, and Reports

No abstract provided.

An Atypical Case Of Necrotizing Fasciitis Secondary To Perforated Cecal Cancer., Laura S Heidelberg, Erica Pettke, Teresa E Wagner, Lauren Angotti

Articles, Abstracts, and Reports

Necrotizing fasciitis is an aggressive, life threatening soft tissue infection that requires high index of suspicion for diagnosis. Diagnosis is clinical with management including broad spectrum antibiotics and emergent operative debridement. The majority of cases are secondary to underlying medical processes, local tissue damage, abscess, or inciting procedure, with a paucity of data correlating causation with colon cancer. We describe the case of an 84-year-old man presenting with sepsis of unknown origin who was diagnosed with an atypical presentation of necrotizing fasciitis secondary to a perforated cecal malignancy. His case is unique in that a less virulent polymicrobial infection was …

Cardio-Renal-Metabolic Care Models: Toward Achieving Effective Interdisciplinary Care., Janani Rangaswami, Katherine Tuttle, Muthiah Vaduganathan

Articles, Abstracts, and Reports

No abstract provided.

An Exploratory Pilot Study With Plasma Protein Signatures Associated With Response Of Patients With Depression To Antidepressant Treatment For 10 Weeks., Eun Young Kim, Hee-Sung Ahn, Min Young Lee, Jiyoung Yu, Jeonghun Yeom, Hwangkyo Jeong, Hophil Min, Hyun Jeong Lee, Kyunggon Kim, Yong Min Ahn

Articles, Abstracts, and Reports

Major depressive disorder (MDD) is a leading cause of global disability with a chronic and recurrent course. Recognition of biological markers that could predict and monitor response to drug treatment could personalize clinical decision-making, minimize unnecessary drug exposure, and achieve better outcomes. Four longitudinal plasma samples were collected from each of ten patients with MDD treated with antidepressants for 10 weeks. Plasma proteins were analyzed qualitatively and quantitatively with a nanoflow LC-MS/MS technique. Of 1153 proteins identified in the 40 longitudinal plasma samples, 37 proteins were significantly associated with response/time and clustered into six according to time and response by …

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml., Jayakumar Vadakekolathu, Catherine Lai, Stephen Reeder, Sarah E Church, Tressa Hood, Anbarasu Lourdusamy, Michael P Rettig, Ibrahim Aldoss, Anjali S Advani, John E Godwin, Matthew J Wieduwilt, Martha Arellano, John Muth, Tung On Yau, Farhad Ravandi, Kendra Sweet, Heidi Altmann, Gemma A Foulds, Friedrich Stölzel, Jan Moritz Middeke, Marilena Ciciarello, Antonio Curti, Peter J M Valk, Bob Löwenberg, Ivana Gojo, Martin Bornhäuser, John F Dipersio, Jan K Davidson-Moncada, Sergio Rutella

Articles, Abstracts, and Reports

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) …

Targeting Breast Cancer Metabolism With A Novel Inhibitor Of Mitochondrial Atp Synthesis., Myoung Sook Kim, Ramkishore Gernapudi, Yessenia Cedeño Cedeño, Brian M Polster, Ramon Martinez, Paul Shapiro, Santosh Kesari, Elmar Nurmemmedov, Antonino Passaniti

Articles, Abstracts, and Reports

Inhibitors of mitochondrial respiration and ATP synthesis may promote the selective killing of respiration-competent cancer cells that are critical for tumor progression. We previously reported that CADD522, a small molecule inhibitor of the RUNX2 transcription factor, has potential for breast cancer treatment. In the current study, we show that CADD522 inhibits mitochondrial oxidative phosphorylation by decreasing the mitochondrial oxygen consumption rate (OCR) and ATP production in human breast cancer cells in a RUNX2-independent manner. The enzyme activity of mitochondrial ATP synthase was inhibited by CADD522 treatment. Importantly, results from cellular thermal shift assays that detect drug-induced protein stabilization revealed that …