Digital Commons Network^™

Tumor Targeting With Peptide-Drug Conjugates: Showcasing Key Progress And Hurdles, Keykavous Parang, Thuy Do, Clare Dinh, Dorna Davanidavari, Max Foroughi, Troy Khong, Mahsa Moazen, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss …

Montana Kaimin, February 12, 2026, Students Of The University Of Montana, Missoula

Montana Kaimin, 1898-present

Student newspaper of the University of Montana, Missoula.

Insights Into The Influence Of The Greenland Ice Sheet On Oceanic Macronutrient Dynamics From Decades Of Historical Data, Xin Huang, Yuanyuan Gu, Hilde Oliver, Dustin Carroll, Thomas Juul-Pedersen, Lorenz Meire, Mark J. Hopwood

Faculty Research, Scholarly, and Creative Activity

Increasing freshwater discharge from the cryosphere has the potential to affect mechanisms that regulate the supply of macronutrients to primary producers in the ocean. Although numerous studies have characterized the biogeochemical effects of freshwater discharge from the Greenland Ice Sheet within fjords, it is unclear to what extent these effects propagate offshore and whether or not seasonal macronutrient availability in Greenland's shelf seas has changed since annual freshwater discharge increased in the mid-1990s. Here, we collate and scrutinize extensive work undertaken over the past century to constrain macronutrient distributions in Greenland's coastal seas. From 1929 to 2022, over 38,000 publicly …

Mandibular Extension As A Trigger Of The Proprioceptive Trigeminocardiac Reflex, Massimo Conti, Giovanna Traina, Daniele Tonlorenzi

Turkish Journal of Medical Sciences

The trigeminocardiac reflex (TCR) is a physiological response characterized by a reduction in heart rate and arterial blood pressure following stimulation of any branch of the fifth cranial nerve. This review presents a novel mechanism of TCR induction through proprioceptive activation of the trigeminal nerve via mandibular extension (ME). Accordingly, it is referred to as the “proprioceptive trigeminocardiac reflex” (pTCR). An overview of the existing literature on ME-evoked TCR in humans and animals is presented, with particular emphasis on evidence of cerebral microcirculatory alterations. The magnitude of cardiovascular responses appears to depend on the duration of ME, with repeated applications …

Canakinumab Treatment In Patients With Colchicine-Resistant Familial Mediterranean Fever: A Multicenter Observational Study, Emrah Koç, Mete Pekdi̇ker, Mete Kara

Turkish Journal of Medical Sciences

Background/aim: Anti-interleukin-1 agents have known beneficial effects in the treatment of colchicine-resistant familial Mediterranean fever (cr-FMF); however, studies to date have tended to have small sample sizes and to be based on pooled data. The present study investigates the efficacy of Canakinumab (CAN) in a homogeneous cohort of cr-FMF cases.

Materials and methods: The study included patients who underwent treatment in three tertiary rheumatology departments, whose electronic medical records were reviewed retrospectively. The inclusion criteria were presence of colchicine resistant disease activity or persistent proteinuria secondary to AA-amyloidosis, and treatment with CAN for at least 6 months. Clinical and laboratory …

Retrospective Evaluation Of Treatment Outcomes Of Gasserian Ganglion Radiofrequency Thermocoagulation In Trigeminal Neuralgia Patients With Multiple Sclerosis, Emel Başar, Nevci̇han Şahutoğlu Bal, Erkan Yavuz Akçaboy

Turkish Journal of Medical Sciences

Background/aim: Trigeminal neuralgia (TN) secondary to multiple sclerosis (MS) is a rare but debilitating condition. Aside from two case reports, there are limited data on the use of Gasserian ganglion radiofrequency interventions in this patient population. This study aims to evaluate the outcomes of combined radiofrequency thermocoagulation (RFT) and pulsed radiofrequency (PRF) treatment targeting the Gasserian ganglion in patients with MS-related TN.

Materials and methods: We retrospectively analyzed 12 patients with MS-associated TN who underwent combined Gasserian ganglion RFT and PRF treatment between 1 January 2021 and 1 January 2025. Patients were followed for six months. Visual analog scale (VAS) …

Preoperative Inflammatory And Molecular Marker Changes In 125 Supratentorial Glioma Cases, Semi̇h Can Çeti̇ntaş, Burak Tahmazoğlu, Tufan Agah Kartum, Rahşan Kemerdere, Taner Tanriverdi̇

Turkish Journal of Medical Sciences

Background/aim: To determine whether there is a possible link between selected preoperative systemic inflammatory markers and molecular pathological indices.Material and methods: For this retrospective study, 125 patients served as subjects. Preoperative systemic inflammatory markers, namely neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR), and postoperative pathological indices, namely mitosis, Ki-67 labeling index (LI), isocitrate dehydrogenase-1 (IDH1) mutation, and 1p/19q codeletion, were obtained from the electronic database.

Results: Results showed that NLR positively correlated with PLR (p = 0.00001), mitotic activity (p = 0.001), and Ki-67 LI (p = 0.00001). On the other …

Proximal Fragment Perfusion Following Hip Arthroplasty With Subtrochanteric Shortening Osteotomy In Patients With Severe Developmental Dysplasia Of The Hip, Vedat Bi̇çi̇ci̇, Hi̇lmi̇ Alkan, Enejd Vei̇zi̇, Şahan Güven, Serkan Ünlü, Eli̇f Özdemi̇r, Tural Talibli, Ahmet Firat

Turkish Journal of Medical Sciences

Background/aim: The changes in proximal femoral blood flow occurring after reconstructive surgery for Crowe types III– IV developmental dysplasia of the hip (DDH) and their impact on healing remain unclear. In the present study, blood flow around the osteotomy site is evaluated with particular focus on the proximal segment in patients who underwent subtrochanteric shortening osteotomy and hip arthroplasty. To this end, single-photon emission computed tomography (SPECT/CT) scans were conducted to evaluate changes in proximal blood flow and to assess the impact on union rates and potential complications.

Materials and methods: A retrospective analysis was conducted of 26 hips from …

Radial Peripapillary Capillary Changes And Retinal Nerve Fiber Layer Alterations In Diabetic Foot Ulcers With Mild-To-Moderate Nonproliferative Diabetic Retinopathy: An Octa Study, Eyüpcan Şensoy, Hi̇kmet Erhan Güven, Mehmet Çitirik

Turkish Journal of Medical Sciences

Background/aim: This study aimed to evaluate the impact of diabetic foot ulcers (DFUs) on retinal microvascular changes, specifically the radial peripapillary capillary (RPC) vessel density and retinal nerve fiber layer (RNFL) thickness in patients with mild-to-moderate nonproliferative diabetic retinopathy (NPDR).

Materials and methods: Ninety participants were enrolled and divided into three groups: 30 patients with DFUs and mild-to-moderate NPDR, 30 patients with NPDR but without DFUs, and 30 healthy controls. RPC density and RNFL thickness were evaluated using optical coherence tomography angiography (OCTA), a noninvasive imaging method. Comparisons between groups were made with statistical adjustments, including optic disc area.

Results: …

Evaluation Of Colonization With Multidrug-Resistant Microorganisms And The Incidence Of Attributable Infections In Patients Undergoing Hematopoietic Stem Cell Transplantation, Burcu Çalişkan Demi̇rkiran, Gülşen İskender, İpek Mumcuoğlu, Duygu Mert, Si̇nan Dal, Tuba Dal, Semra Tunçbi̇lek, Mustafa Ertek, Fevzi̇ Altuntaş

Turkish Journal of Medical Sciences

Background/aim: The global rise in multidrug-resistant organisms (MDROs) has led to an increased incidence of MDRO infections following hematopoietic stem cell transplantation (HSCT), particularly during the preengraftment period. The objective of this study was to evaluate the relationship between pretransplant colonization by MDROs or carbapenem-resistant Enterobacterales (CRE) and the occurrence of infections caused by phenotypically similar microorganisms during the preengraftment period, as well as to assess the clinical outcomes of patients colonized with MDROs prior to transplantation.

Materials and methods: This prospective cohort study included patients diagnosed with hematological malignancies who underwent HSCT at the bone marrow transplant unit of …

Levothyroxine Poisoning In Children: A Multicenter Study From Türkiye, Kübra Şen Küçük, Şule Demi̇r, Reyhan Deveci̇ Sevi̇m, Fatma Akgül, Gülşen Yalçin, Öznur Eser, Alkan Bal, Eli̇f Ergi̇n, Sercan Öztürk, Ahmet Anik

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the clinical features, laboratory findings, treatment approaches, and follow-up strategies employed in the management of pediatric patients with levothyroxine poisoning.

Materials and methods: This multicenter retrospective study included patients aged ≤18 years who presented with acute, single-episode levothyroxine ingestion to the pediatric emergency departments of six tertiary care centers between 2010 and 2023. Clinical data, laboratory findings, symptom onset and severity, and treatment modalities were extracted from medical records. Thyroid function tests (TFTs) were interpreted according to the age-specific reference ranges of each center. Treatment decisions, including gastric decontamination and pharmacologic therapy, were evaluated …

Effects Of Transversus Abdominis And Erector Spinae Plane Blocks On Postoperative Pain Control And Postpartum Depression After Cesarean Section: A Randomized Prospective Study, Hi̇lal Bi̇radli, Feyza Çalişir, Alev Özer

Turkish Journal of Medical Sciences

Background/aim: Effective postoperative pain management after cesarean section is essential for maternal recovery. Poor pain control can lead to complications, including postpartum depression. This study aimed to compare the postoperative analgesic efficacy of erector spinae plane (ESP) and transversus abdominis plane (TAP) blocks following cesarean section, with a particular focus on their potential impact on postpartum depression.

Materials and methods: Sixty patients were randomly assigned to receive either an ESP block (Group E, n = 30) or a TAP block (Group T, n = 30) after cesarean section. Pain severity was assessed using a visual analog scale (VAS), and the …

Cd20 Molecule Deficiency And Carrier Frequency: A Village-Based Screening Study, Ebru Sümen, Mehmet Ali̇ Karaselek, Serkan Küççüktürk, Tuğçe Duran, Büşra Yüksel, Mustafa Gençeli̇, Ayşe Sümeyra Engi̇n, Muhammed Furkan Erden, Tuğba Esra Pekcandanoğlu, Bi̇lal Bostan, Mahmut Esad Yurtseven, Nazi̇re Nur Onat, Şükrü Nai̇l Güner, Sevgi̇ Keleş, İsmai̇l Rei̇sli̇

Turkish Journal of Medical Sciences

Background/aim: CD20 deficiency is an autosomal recessive inborn error of immunity (IEI), and the only known affected individual worldwide has been under follow-up in our clinic. Because the consanguineous parents of the index patient are putative carriers, we hypothesized that additional individuals with reduced CD20 expression might exist within their village population. This study aimed to evaluate clinical features associated with IEI and to identify individuals displaying CD20 mean fluorescence intensity (MFI) patterns consistent with putative carrier status, while also providing appropriate genetic counseling.

Materials and methods: This cross-sectional screening study was conducted in December 2024 in Çukurbağ village. Participants …

Association Between Frailty Status And Pain, Balance, And Quality Of Life In Patients With Lumbar Spinal Stenosis, Musa Güneş, Aydin Si̇nan Apaydin

Turkish Journal of Medical Sciences

Background/aim: Frailty is a clinical syndrome that affects individuals physically and psychosocially. However, the association between lumbar spinal stenosis (LSS) and frailty remains unclear. This study aimed to compare pain, balance, disability, fear of falling, and quality of life between patients with LSS with and without frailty.

Materials and methods: This cross-sectional study included 43 frail and 48 nonfrail patients with LSS according to the frailty criteria of Fried et al. Pain intensity (numeric rating scale [NRS]), static balance (single leg stance test [SLST]), dynamic balance (Timed Up and Go test [TUG]), disability (Oswestry Disability Index [ODI]), fear of falling …

Developing Liposomal And Ethosomal Formulations With Potent Antioxidant And Cytotoxic Effects: Unleashing The Power Of Achillea Millefolium L., Esra Akkol, Sena Akçakaya Mutlu, Gökçe Şeker Karatoprak, Çi̇ğdem Yücel, Selen İlgün, Esra Köngül Şafak, Murat Koç

Turkish Journal of Medical Sciences

Background/aim: Achillea millefolium L., a plant rich in phenolics and flavonoids, has been shown to possess strong antioxidant and cytotoxic properties. However, no pharmaceutical formulations have yet been developed for this plant. This study aimed to create and characterize an A. millefolium extract with high antioxidant and cytotoxic activities.

Materials and methods: A total of 10 extracts were prepared from the plant’s aerial parts using ethanol concentrations ranging from 10% to 99.9%. The DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging tests were used to assess the antioxidant properties of the extracts. Cytotoxic effects were assessed using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium …

Oleanolic Acid–Chitosan Compound Inhibits Mitochondrial Autophagy And Malignant Transformation Of Lung Cancer Through The Pten/Akt Pathway, Abuli̇mi̇ti̇ Abulai̇ti̇, Xi̇aohong Sun, Waresijiang Yibulayin, Dan He, Kemi̇ng Xu, Xi̇ayi̇mai̇erdan Yi̇bulayi̇n

Turkish Journal of Medical Sciences

Background/aim: Oleanolic acid–chitosan compound (OAC) shows potent antinonsmall cell lung cancer (NSCLC) activity, but its mechanisms remain unclear. This study elucidates how OAC modulates autophagy and apoptosis via the Phosphatase and Tensin Homolog/Protein Kinase B (PTEN/AKT) signaling pathway.

Materials and methods: Oleanolic acid was coupled with chitosan to synthesize OAC. A549 and MRC-5 cells were cultured in Dulbecco’s Modified Eagle Medium and Minimum Essential Medium, respectively, supplemented with 10% fetal bovine serum and penicillin–streptomycin. Cells were pretreated with chloroquine before OAC treatment. Cell viability was assessed using the CCK- 8 assay, while 5-bromo-2′-deoxyuridine (BrdU) and colony formation tests were employed …

Neuroendocrine Effects Of Exogenous Adropin Administration On The Hypothalamic Pituitary Testicular Axis In Male Rats, Ersen Eraslan, Ayhan Tanyeli̇, Mustafa Can Güler, Asli Özbek Bi̇lgi̇n, Fazi̇le Nur Eki̇nci̇ Akdemi̇r, Eli̇f Polat, Seli̇m Çomakli, Nezahat Kurt, Tuğba Bal Taştan

Turkish Journal of Medical Sciences

Background/aim: Obesity impairs male fertility through metabolic dysfunction, oxidative stress, and disruption of the hypothalamic– pituitary–testicular (HPT) axis. Adropin (ADR), a peptide hormone whose circulating levels are reduced in obesity, plays emerging roles in metabolic homeostasis; however, its involvement in reproductive endocrine regulation remains unclear. The present study was conducted in healthy, nonobese male rats and aimed to investigate the neuroendocrine and testicular effects of exogenous ADR administration, focusing on circulating reproductive hormones, hypothalamic regulatory peptides, and testicular antioxidant pathways.

Materials and methods: Thirty-two male Wistar rats were randomized into control, sham, low-dose ADR (4 μg/kg/day), and high-dose ADR (40 …

Fitness Cost And Biofilm Formation In Fosfomycin-Resistant Clinical Escherichia Coli And Klebsiella Pneumoniae Isolates, Mustafa Ökeer, Sabi̇re Şöhret Aydemi̇r, Bayri Eraç

Turkish Journal of Medical Sciences

Background/aim: Fosfomycin has regained importance owing to its unique mechanism of action and effectiveness against extended-spectrum β-lactamase-producing Gram-negative bacteria. This study aimed to evaluate the biological fitness cost associated with fosfomycin resistance and its impact on biofilm formation in clinical Enterobacteriaceae isolates.

Materials and methods: A total of 78 Escherichia coli and 34 Klebsiella pneumoniae strains isolated from urine samples at Ege University Hospital were analyzed. Fosfomycin minimum inhibitory concentrations (MICs) were determined using the reference agar dilution method. Resistance was induced by exposing two K. pneumoniae strains with a fosfomycin MIC of 4 μg/mL and two E. coli strains …

Association Of Mir-34a With Metastatic Progression Through The Foxo3a–Sirt1 Regulatory Axis In Breast Cancer, Banu Şahi̇n, İlker Batuhan Bural, Hüseyi̇n Özcan, Sendegül Yildirim, Gamze Tanriöver, Şükran Burçak Yoldaş

Turkish Journal of Medical Sciences

Background/aim: Breast cancer represents the foremost cause of cancer-related mortality among women worldwide and is characterized by a markedly high metastatic potential, contributing substantially to its clinical severity and poor prognosis. This study aimed to evaluate the interrelationship among silent information regulator (SIRT1), Forkhead box O3a (FoxO3a), and microRNA-34a (miR- 34a), the latter of which promotes apoptosis by suppressing the proliferation, migration, and invasion of breast cancer cells. Specifically, we investigated the tumor microenvironment associated with metastatic progression of malignant primary tumors, the influence of nonmetastatic (benign) tumors, and the potential roles of these proteins in both primary tumor development …

Contribution Of Adenosine A2a Receptor Agonist And Antagonist On Ovarian Ischemia/Reperfusion Injury In Rats, Azad Mammadov, Abdullah Tuncay Demi̇ryürek, Ahmet Saracaloğlu, Cahi̇t Demi̇rkiran, İsmai̇l Tuncer Deği̇m, Ömer Eronat, Şeni̇z Demi̇ryürek

Turkish Journal of Medical Sciences

Background/aim: To determine the effects of an A2A receptor agonist regadenoson, an A2A receptor antagonist istradefylline, and istradefylline nanosuspension on ovarian ischemia/reperfusion (I/R) injury in rats.

Materials and methods: A total of 80 female rats were divided into 10 groups: sham, ovarian I/R, blank nanosuspension + ovarian I/R, regadenoson (3 μg/kg) + ovarian I/R, regadenoson (30 μg/kg) + ovarian I/R, istradefylline (0.3 mg/kg) + ovarian I/R, istradefylline (3 mg/kg) + ovarian I/R, istradefylline-loaded nanosuspension (3 mg/kg) + ovarian I/R, istradefylline (3 mg/kg) + regadenoson (30 μg/kg) + ovarian I/R, and istradefylline-loaded nanosuspension (3 mg/kg) + regadenoson (30 μg/kg) + ovarian …

A Study Of The Intellectual Property Rights Of Farmers With Special Reference To The Protection Of Plant Variety And The Farmers' Rights Act, 2001, Gomathi R Ms

Theses and Dissertations

Intellectual Property Rights (IPR) confer exclusive rights on individuals over the creations of their minds. Intellectual property is protected through patents, trademarks, copyrights, industrial designs, geographical indications, and other legal rights, enabling inventors to obtain economic benefits and legal recognition from their innovations. These rights provide exclusive usage for a prescribed period and have evolved significantly over the years, sharing similarities with ownership rights over tangible property. As intangible rights, IPR primarily consist of the property element and the object to which that property relates. Among the various forms of IPR, Plant Variety Protection (PVP) rights recognize the creativity and …

A Rare And Challenging Polymicrobial Pleural Infection Involving Cupriavidus Pauculus In A Patient With Rheumatoid Arthritis And Multiple Complications, Moiz Ahmed Khan, Syeda Samiya Kamal, Muhammad Muneeb, Summaya Zafar

The University of Louisville Journal of Respiratory Infections

A 58-year-old female with a 15-year history of rheumatoid arthritis (RA) and a history of treatment consisting of methotrexate, hydroxychloroquine, leflunomide, and chronic prednisolone therapy, presented with fever, productive cough, dyspnea, and left leg cellulitis. She developed septic shock complicated by tension pneumothorax requiring emergency thoracostomy and non-ST-elevation myocardial infarction (NSTEMI). Pleural fluid culture grew Cupriavidus pauculus, a rare environmental gram-negative bacillus, alongside Burkholderia cepacia and Candida parapsilosis, indicating polymicrobial infection which was most likely predisposed by patient's immunosuppressed state from RA and prolonged steroid use. Treatment consisted of trimethoprim/sulfamethoxazole, meropenem, fluconazole, and cardiopulmonary support, and culminated in …

Data And Code From: Rapid Scavenging Of Avian Carcasses In The Desert Southwest: Implications For Mortality Surveys Not Associated With Infrastructure, Thomas Huycke, Dylan M. Osterhaus, Kelley C. Boland, Fitsum Abadi, Martha J. Desmond

Fish, Wildlife, & Conservation Ecology: Datasets

No abstract provided.

The Perk Signaling Pathway As A Marker Of The Unfolded Protein Response In Patients With Acute Myeloid Leukemia, Nergi̇z Erkut, Turhan Köksal, Seli̇m Demi̇r, Ahmet Menteşe, Özlen Balta, Mehmet Sönmez

Turkish Journal of Medical Sciences

Background/aim: The protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway plays a critical role in preventing the accumulation of misfolded or unfolded proteins within the endoplasmic reticulum. In this study, the role of the PERK signaling pathway was evaluated in newly diagnosed, treatment-naïve patients with acute myeloid leukemia (AML).

Materials and methods: Plasma levels of eukaryotic translation initiation factor 2-alpha kinase 3 (eIF2AK3), glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), hypoxia-inducible factor-1 alpha (HIF-1α), and caspase 3 were measured by enzyme-linked immunosorbent assay in peripheral blood samples obtained from AML patients and healthy …

Comment On “Survival Of Patients With 2014 Figo Stage Iiic High‑Grade Serous Ovarian Cancer Treated With Platinum‑Based Adjuvant Chemotherapy”, Abdullah Saad, Syeda Abeeha Hasan, Syeda Aki̇fa Sajid

Turkish Journal of Medical Sciences

No abstract provided.

Albumin-Binding Domains In Therapeutic Protein Engineering: A Structural And Computational Perspective On Rational Design, Matthew Argyle, Dallin M. Chipman, Anna Claire Woolley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

Therapeutic proteins face a critical pharmacokinetic challenge: rapid clearance from circulation limits their clinical efficacy. Albumin-binding domains (ABDs) offer an elegant solution by enabling therapeutic proteins to “hitchhike” on serum albumin’s favorable 19-day half-life through FcRn-mediated recycling. Clinical validation through approved therapeutics like ozoralizumab demonstrates the success of this approach, with preclinical studies showing fusion to an ABD extended half-life to 18 days. This review provides an analysis of ABD-fusion protein design, integrating structural biology, computational prediction, and rational engineering principles. We catalog the major classes of albumin-binding modalities, including bacterial three-helix bundle domains, engineered peptides, antibody-derived binders, and alternative …

Spartan Daily, February 12, 2026, San Jose State University, School Of Journalism And Mass Communications

Spartan Daily, 2026

Volume 166, Issue 10

Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán

Faculty, Staff and Student Publications

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …

Primary Tumor Size And Tumor-Vessel Interface Following Capecitabine And Temozolomide For Pancreatic Neuroendocrine Tumor, Jin Guo, Kever A Lewis, Laura Prakash, Priya Bhosale, Ajaykumar Morani, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Rebecca Snyder, Michael P Kim, Chandrikha Chandrasekharan, Arvind Dasari, James C Yao, Jeffrey E Lee, Jessica E Maxwell, Daniel M Halperin

Faculty, Staff and Student Publications

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. …

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …