2,740 results match your criteria: "Siteman Cancer Center[Affiliation]"

Background: Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients.

Objectives: This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC.

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  • Pexidartinib is a drug used for treating tenosynovial giant cell tumor (TGCT) in patients where surgery isn't an option, and this study looked at the effects of stopping and then restarting the medication.
  • It was a phase 4 global study involving patients who had benefited from pexidartinib, allowing them to either continue treatment or stop with the option to restart later, monitoring their tumor progression and quality of life.
  • Results showed that while about 54.5% of patients who stopped the drug experienced disease progression, none of those who continued treatment saw their condition worsen over a 24-month period.
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Targeting dendritic cells to drive PDAC immunotherapy response.

Trends Pharmacol Sci

December 2024

Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA. Electronic address:

Pancreatic adenocarcinoma (PDAC) has been historically unresponsive to immunotherapy, predominantly due to lower antigen loads and a lack of tumor-infiltrating dendritic cells (DCs) and T cells. A recent study by Mahadevan and colleagues demonstrates that increasing DC infiltration through use of an engineered DC1 vaccine can sensitize PDAC to immunotherapy.

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  • * The increase in lung cancer survival rates highlights the urgent need to better understand and minimize the cardiovascular complications of radiotherapy, yet current clinical trials have inadequately reported on these cardiac effects due to inconsistent definitions and endpoints.
  • * This review aims to consolidate existing knowledge on cardiotoxicity from conventional radiotherapy in lung cancer, addressing ongoing clinical gaps and recommending advanced evaluations involving oncology and cardiology to improve patient care.
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Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass.

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The evolving role of checkpoint inhibitors in the treatment of Hodgkin lymphoma.

Front Oncol

October 2024

Washington University School of Medicine, Siteman Cancer Center, St. Louis, MO, United States.

Since their initial approval as single agent therapy for multiply relapsed/refractory Hodgkin lymphoma (HL), the PD-1 inhibitors nivolumab and pembrolizumab have been incorporated into second-line salvage regimens, and they are being investigated in upfront therapy of newly diagnosed patients. As second-line therapy in combination with brentuximab vedotin or multi-agent chemotherapy, nivolumab and pembrolizumab provide high complete remission rates and durable progression-free survival after consolidative autologous stem cell transplant. Incorporation of these agents into frontline chemotherapy regimens is feasible, and early results from a Phase III trial of nivolumab-AVD compare favorably with the existing standard for advanced stage HL, brentuximab vedotin plus AVD.

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Background/objectives: Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options.

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  • Multiple Myeloma (MM) is an incurable cancer affecting plasma cells, with over 35,000 new cases diagnosed each year in the U.S., leading to frequent relapses and limited treatment options.
  • Researchers used transcriptome sequencing to compare newly diagnosed MM patients with short progression-free survival (PFS) to those with longer PFS, identifying 157 lncRNAs associated with poor outcomes, particularly focusing on one specific lncRNA.
  • The study found that the overexpression of this lncRNA enhances cell viability and decreases apoptosis, while its knockdown has the opposite effect, and targeted therapies using antisense oligonucleotides showed potential in reducing cell viability and promoting apoptosis in MM cells.
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To study the spatial interactions among cancer and non-cancer cells, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined 'tumour microregions' as spatially distinct cancer cell clusters separated by stromal components.

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  • Analyzing somatic evolution in tumors over time and space is crucial for cancer research, and CalicoST is introduced as a new algorithm that enhances understanding by inferring copy number aberrations (CNAs) from spatially resolved transcriptomics (SRT) data.
  • CalicoST identifies types of CNAs, such as copy-neutral loss of heterozygosity and mirrored subclonal CNAs, which are often overlooked in traditional total copy number analysis, achieving an impressive average accuracy of 86% using data from nine patients.
  • This algorithm successfully reconstructs the phylogeography of tumors in three-dimensional space, illustrating mirrored subclonal CNAs in a prostate cancer study, highlighting the genetic and physical complexity of tumor evolution.
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  • Breast cancer (BC) has distinct molecular subtypes influenced by different cell origins, yet the transcriptional networks for these subtypes are not well understood.
  • This study utilized advanced techniques on 61 samples from 37 BC patients to reveal how gene expression and chromatin accessibility connect BC subtypes to their likely cells of origin.
  • Key transcription factors BHLHE40 and KLF5 were found to play crucial roles in luminal and basal-like tumors, respectively, and exhausted CD8 T cells were linked to immune dysfunction in basal-like BC, showcasing the potential of single-cell level analysis in understanding cancer lineages.
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Predictors of Progressing Toward Lifestyle Change Among Participants of an Interprofessional Lifestyle Medicine Program.

Am J Lifestyle Med

December 2023

Department of Orthopaedic Surgery, Division of Physical Medicine and Rehabilitation, Washington University in St. Louis School of Medicine, St. Louis, MO, USA (ALC, MED, AM, CGL, DEF, KHB, DMH).

Background: Therapeutic lifestyle change can be challenging, and not every attempt is successful.

Purpose: To identify predictors of making progress toward lifestyle change among patients who participate in a lifestyle medicine program.

Methods: This was a single-center, retrospective cohort study of 205 adults who enrolled in a goal-directed, individualized, interprofessional lifestyle medicine program.

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Mammographic density is a strong risk factor for breast cancer and is reported clinically as part of Breast Imaging Reporting and Data System (BI-RADS) results issued by radiologists. Automated assessment of density is needed that can be used for both full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) as both types of exams are acquired in standard clinical practice. We trained a deep learning model to automate the estimation of BI-RADS density from a prospective Washington University clinic-based cohort of 9,714 women, entering into the cohort in 2013 with follow-up through October 31, 2020.

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An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex ( = 0.

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is often resistant to therapy. An immune suppressive tumor microenvironment (TME) and oncogenic mutations in have both been implicated as drivers of resistance to therapy. Mitogen-activated protein kinase (MAPK) inhibition has not yet shown clinical efficacy, likely because of rapid acquisition of tumor-intrinsic resistance.

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Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT).

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Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes.

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Arthritogenic alphaviruses cause disease characterized by fever, rash, and incapacitating joint pain. Alphavirus infection stimulates robust inflammatory responses in infected hosts, leading to the upregulation of several cytokines, including granulocyte colony-stimulating factor (G-CSF). G-CSF is secreted by endothelial cells, fibroblasts, macrophages, and monocytes and binds to colony stimulating factor 3 receptor (CSF3R, also known as G-CSFR) on the surface of myeloid cells.

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Obesity induces diverse changes in host immunity, resulting in worse disease outcomes following infection with various pathogens, including arthritogenic alphaviruses. However, the impact of obesity on the functional landscape of immune cells during arthritogenic alphavirus infection remains unexplored. Here, we used single-cell RNA sequencing (scRNA-seq) to dissect the blood and tissue immune responses to Mayaro virus (MAYV) infection in lean and obese mice.

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Article Synopsis
  • - The NCCN Guidelines outline a comprehensive approach to diagnosing, staging, and treating ovarian, fallopian tube, and primary peritoneal cancers.
  • - Recent developments in the use of PARP inhibitors, both as maintenance therapy and standalone treatments, have significantly influenced the recommendations in these guidelines.
  • - These insights highlight the collaborative effort among experts to continuously update treatment protocols based on the latest research in ovarian cancer therapies.
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  • - The NCCN Guidelines for acute lymphoblastic leukemia (ALL) offer management recommendations that prioritize classifying ALL subtypes using immunophenotype and cytogenetic/molecular markers.
  • - The guidelines emphasize risk assessment and stratification to tailor therapy for both Ph-positive and Ph-negative ALL, specifically addressing treatment for adolescent, young adult, and adult patients.
  • - This excerpt highlights treatment recommendations specifically for adults newly diagnosed with Ph-negative ALL, grounded in the latest evidence-based research.
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Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma.

N Engl J Med

October 2024

From City of Hope Comprehensive Cancer Center, Duarte (A.F.H., M.G.M., J.Y.S.), University of California Davis Comprehensive Cancer Center, Sacramento (J.M.T.), and Children's Hospital Los Angeles, Los Angeles (C.F., A.D., A.K.) - all in California; SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, (M.L., H.L.) and Seattle Children's Hospital (A.L.) - both in Seattle; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta (S.M.C.), and Winship Cancer Institute and Emory University Hospital (K.A.B.), Atlanta; Weill Cornell Medicine (S.C.R., J.P.L.), Memorial Sloan Kettering Cancer Center (P.T.), and New York University Langone (L.K.S.), New York, Wilmot Cancer Institute, University of Rochester, Rochester (C.C., L.S.C., J.W.F.), and Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo (K.M.K.) - all in New York; Rutgers Cancer Institute of New Jersey, New Brunswick (A.M.E.); McGill University Health Centre, Montreal (K.D.), and SickKids Hospital (Angela Punnett) and Princess Margaret Cancer Centre (D.H., Anca Prica, M.C.), Toronto - all in Canada; Reid R. Sacco AYA Cancer Program, Tufts Medical Center (S.K.P.), and Dana-Farber Cancer Institute (M.A.S.) - both in Boston; M.D. Anderson Cancer Center, Houston (S.A.), and University of Texas Health Science Center at San Antonio, San Antonio (S.K.) - both in Texas; Siteman Cancer Center, Washington University, St. Louis (N.L.B., B.K.); Medical University of South Carolina, Charleston (B.T.H.), and Prisma Health Cancer Institute - Eastside, Greenville (S.C.) - both in South Carolina; Carolinas Medical Center, Levine Cancer Institute, Charlotte, NC (R.J.); Moffitt Cancer Center, Tampa (H.S.), and Sylvester Comprehensive Cancer Center, University of Miami, Miami (C.M.) - both in Florida; Huntsman Cancer Institute, University of Utah, Salt Lake City (B.H.); University of Alabama at Birmingham, Birmingham (G.G.); Illinois CancerCare, Peoria (P.K.), and University of Chicago, Chicago (S.M.S.); Cancer and Hematology Centers of Western Michigan, Grand Rapids (B.B.), and University of Michigan, Ann Arbor (A.M.P.); the Department of Hematology and Oncology, Geisinger Community Medical Center, Scranton, PA (N.S.); Fairview Ridges Hospital, Minnesota Oncology, Burnsville (A.S.); SWOG Cancer Research Network, Teaneck, NJ (H.D.); and the National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD (R.F.L.).

Article Synopsis
  • Brentuximab vedotin has been shown to improve outcomes in treating advanced classic Hodgkin's lymphoma, but it also causes more toxic side effects in adults, while many pediatric patients still need radiation therapy and face challenges with relapse.
  • A phase 3 trial involving patients aged 12 and older tested two treatment combinations: brentuximab vedotin with standard chemotherapy (BV+AVD) versus nivolumab with standard chemotherapy (N+AVD), aiming to assess progression-free survival.
  • Results indicated that N+AVD significantly enhances progression-free survival compared to BV+AVD, with a 2-year survival rate of 92% for N+AVD versus 83% for BV
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68 Ga-DOTATATE and 18 F-FDG PET/CT in a Rapidly Progressing Lymphoma.

Clin Nucl Med

January 2025

From the Mallinckrodt Institute of Radiology and Siteman Cancer Center, Washington University School of Medicine, St Louis, MO.

68 Ga-DOTATATE PET/CT targeting somatostatin receptors is commonly utilized in the imaging of neuroendocrine tumors. However, other malignancies such as lymphomas (both Hodgkin and non-Hodgkin) also have expression of somatostatin receptors, albeit to a lesser degree compared with the neuroendocrine tumors, and thus can be positive on a 68 Ga-DOTATATE PET/CT. We describe an atypical presentation of an aggressive large B-cell lymphoma mimicking a metastatic neuroendocrine tumor at initial presentation with high somatostatin receptor expression demonstrated on the 68 Ga-DOTATATE PET/CT and a rapidly progressing course on the subsequent 18 F-FDG PET/CT.

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Activation of PKR by a short-hairpin RNA.

Sci Rep

October 2024

Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, MO, 63110, USA.

Article Synopsis
  • Recognition of viral infection often involves detecting double-stranded RNA (dsRNA) using proteins like MDA5 and RIG-I, but these proteins can have trouble telling viral dsRNA apart from the body's own.
  • A study shows that using shRNA to knock down DDX54 can activate PKR, a crucial immune response protein, even when DDX54 levels are high, pointing to a possible off-target effect.
  • The activation of PKR by the shRNA was further boosted by reducing ADAR1, a protein that normally inhibits PKR, suggesting that this activation happens through a dsRNA-dependent mechanism.
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