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Application of 7T MRS to High-Grade Gliomas.

AJNR Am J Neuroradiol 2022 May 26. Epub 2022 May 26.

From the Department of Neurosurgery (L.M., C.G.H.), Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York.

MRS, including single-voxel spectroscopy and MR spectroscopic imaging, captures metabolites in high-grade gliomas. Emerging evidence indicates that 7T MRS may be more sensitive to aberrant metabolic activity than lower-field strength MRS. However, the literature on the use of 7T MRS to visualize high-grade gliomas has not been summarized. Read More

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Diffusion-Weighted Imaging to Assess HPV-Positive versus HPV-Negative Oropharyngeal Squamous Cell Carcinoma: The Importance of b-Values.

AJNR Am J Neuroradiol 2022 May 26. Epub 2022 May 26.

From the Divisions of Radiology (V.L., B.M.A.D., Y.M., T.d.P., M.B.)

Background And Purpose: Controversy exists as to whether ADC histograms are capable to distinguish human papillomavirus-positive (HPV+) from human papillomavirus-negative (HPV-) oropharyngeal squamous cell carcinoma. We investigated how the choice of b-values influences the capability of ADC histograms to distinguish between the two tumor types.

Materials And Methods: Thirty-four consecutive patients with histologically proved primary oropharyngeal squamous cell carcinoma (11 HPV+ and 23 HPV-) underwent 3T MR imaging with a single-shot EPI DWI sequence with 6 b-values (0, 50, 100, 500, 750, 1000 s/mm). Read More

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Frequent somatic gene conversion as a mechanism for loss of heterozygosity in tumor suppressor genes.

Genome Res 2022 May 26. Epub 2022 May 26.

SOKENDAI, The Graduate University for Advanced Studies

The major processes to carcinogenesis include inactivation of tumor suppressor genes (TSGs). While Knudson's two-hit model requires two independent inactivating mutations, perhaps more frequently, inactivation of a TSG can occur through loss of heterozygosity (LOH) of one inactivating mutation. Deletion and uniparental disomy (UPD) have been well documented as the mechanisms of LOH, but the role of gene conversion is poorly understood. Read More

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Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillance.

Genes Dev 2022 May 26. Epub 2022 May 26.

Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.

Senescence is a stress-responsive tumor suppressor mechanism associated with expression of the senescence-associated secretory phenotype (SASP). Through the SASP, senescent cells trigger their own immune-mediated elimination, which if evaded leads to tumorigenesis. Senescent parenchymal cells are separated from circulating immunocytes by the endothelium, which is targeted by microenvironmental signaling. Read More

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Mechanism of effective combination radio-immunotherapy against 9464D-GD2, an immunologically cold murine neuroblastoma.

J Immunother Cancer 2022 May;10(5)

Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA

Background: Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( ombination daptive- nnate immunotherapy egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. Read More

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Tumor-associated Tregs obstruct antitumor immunity by promoting T cell dysfunction and restricting clonal diversity in tumor-infiltrating CD8+ T cells.

J Immunother Cancer 2022 May;10(5)

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

Background: Accumulation of regulatory T cells (Treg) has been described to often correlate with poor prognosis in many solid tumors. How Treg presence impinges on limited functionality and clonal composition of tumor-associated CD8 +T cells has important implications for their therapeutic targeting in the tumor microenvironment. In the present study, we investigated how accumulation of Tregs contributes to T cell dysfunction and clonal constriction of tumor-infiltrating CD8 +T cells. Read More

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Spatial transcriptomics of macrophage infiltration in non-small cell lung cancer reveals determinants of sensitivity and resistance to anti-PD1/PD-L1 antibodies.

J Immunother Cancer 2022 May;10(5)

Department of Medecine, Institut Bergonié, Bordeaux, France

Background: Tumor-associated macrophages (TAMs) having immunosuppressive properties are one of the most abundant immune cells in the tumor microenvironment (TME). Preclinical studies have highlighted the potential role of TAMs in resistance to immune checkpoint blockers (ICBs). Here, we investigated the predictive value of TAM infiltration in patients with non-small cell lung cancer (NSCLC) treated with ICBs and characterized their transcriptomic profiles. Read More

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Bufalin stimulates antitumor immune response by driving tumor-infiltrating macrophage toward M1 phenotype in hepatocellular carcinoma.

J Immunother Cancer 2022 May;10(5)

Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China

Background: Immunotherapy for hepatocellular carcinoma (HCC) exhibits limited clinical efficacy due to immunosuppressive tumor microenvironment (TME). Tumor-infiltrating macrophages (TIMs) account for the major component in the TME, and the dominance of M2 phenotype over M1 phenotype in the TIMs plays the pivotal role in sustaining the immunosuppressive character. We thus investigate the effect of bufalin on promoting TIMs polarization toward M1 phenotype to improve HCC immunotherapy. Read More

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Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial.

J Immunother Cancer 2022 May;10(5)

Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Cancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP. Read More

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Design and application of DNA nanostructures for organelle-targeted delivery of anticancer drugs.

Expert Opin Drug Deliv 2022 May 26. Epub 2022 May 26.

Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 305108, China.

Introduction: DNA nanostructures targeting organelles are of great significance for the early diagnosis and precise therapy of human cancers. This review is expected to promote the development of DNA nanostructure-based cancer treatment with organelle-level precision in the future.

Areas Covered: In this review, we introduce the different principles for targeting organelles, summarize the progresses in the development of organelle-targeting DNA nanostructures, highlight their advantages and applications in disease treatment, and discuss current challenges and future prospects. Read More

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The Supportive Care Clinic: a novel model of embedded pediatric palliative oncology care.

J Pain Symptom Manage 2022 May 23. Epub 2022 May 23.

Aflac Cancer & Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA, USA; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Emory University. Atlanta, GA, USA.

Context: Pediatric palliative care (PPC) improves quality of life and end-of-life outcomes for children with cancer, but often occurs late in the disease course. The Supportive Care Clinic (SCC) was launched in 2017 to expand outpatient PPC access.

Objectives: To describe the inaugural four years (2017-2021) of an academic, consultative, embedded SCC within pediatric oncology. Read More

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The Applications of Plasma Cell-free DNA in Cancer Detection: Implications in the Management of Breast Cancer Patients.

Crit Rev Oncol Hematol 2022 May 23:103725. Epub 2022 May 23.

Department of Surgery, Cedars-Sinai Medical Center, West Hollywood, CA, 90048, USA; Samuel Oschin Comprehensive Cancer Institute and Cedars-Sinai Medical Center, West Hollywood, CA, 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, West Hollywood, CA, 90048, USA.

Liquid biopsy probes DNA, RNA, and proteins in body fluids for cancer detection and is one of the most rapidly developing areas in oncology. Tumor-derived DNA (circulating tumor DNA, ctDNA) in the context of cell-free DNA (cfDNA) in blood has been the main target for its potential utilities in cancer detection. Liquid biopsy can report tumor burden in real-time without invasive interventions, and would be feasible for screening tumor types that lack standard-of-care screening approaches. Read More

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Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy.

Brain Behav Immun 2022 May 23. Epub 2022 May 23.

Department of Psychological Medicine, King's College London (Institute of Psychiatry, Psychology and Neuroscience); South London and Maudsley NHS Foundation Trust, London, UK. Electronic address:

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. Read More

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Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer.

Clin Immunol 2022 May 23:109045. Epub 2022 May 23.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China. Electronic address:

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Read More

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Ser392 phosphorylation modulated a switch between p53 and transcriptional condensates.

Biochim Biophys Acta Gene Regul Mech 2022 May 23:194827. Epub 2022 May 23.

Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong Province 510006, PR China; Guangdong Provincial Key Laboratory of New and Renewable Energy Research and Development, Guangzhou 510640, PR China. Electronic address:

Human p53 is a transcription factor regulating the transcription of a variety of target genes. Under various stresses, its tumor suppressor function was activated by the phosphorylation of p53. In this study, we found that full-length wild-type p53 could form phase-separated condensates with the aggregation tendency in vitro and in vivo. Read More

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Fluorinated diselenide nanoparticles for radiosensitizing therapy of cancer.

Free Radic Biol Med 2022 May 23. Epub 2022 May 23.

Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovsky Sq.2, 162 06, Prague 6, Czech Republic.

Radiation resistance of cancer cells represents one of the major challenges in cancer treatment. The novel self-assembled fluoralkylated diselenide nanoparticles (fluorosomes) based on seleno-l-cystine (17FSe) possess redox-active properties that autocatalytically decompose hydrogen peroxide (HO) and oxidize the intracellular glutathione (GSH) that results in regulation of cellular oxidative stress. Alkylfluorinated diselenide nanoparticles showed a significant cytotoxic and radiosensitizing effect on cancer cells. Read More

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Halofuginone micelle nanoparticles eradicate Nrf2-activated lung adenocarcinoma without systemic toxicity.

Free Radic Biol Med 2022 May 23. Epub 2022 May 23.

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan. Electronic address:

The Keap1-Nrf2 system is the master regulator of the cellular response against oxidative and xenobiotic stresses. Constitutive activation of Nrf2 is frequently observed in various types of cancers. Nrf2 hyperactivation induces metabolic reprogramming in cancer cells, which supports the increased energy demand required for rapid proliferation and confers high-level resistance against anticancer radio/chemotherapy. Read More

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Exposure to greenspace and cancer incidence, prevalence, and mortality: A systematic review and meta-analyses.

Sci Total Environ 2022 May 23:156180. Epub 2022 May 23.

Univ Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, F-35000 Rennes, France. Electronic address:

We conducted a systematic review and meta-analysis of the available literature on the association between greenspace exposure and all-sites and site-specific cancer incidence, prevalence, and mortality in adults. We searched PubMed, Scopus, and Web of Science for original articles published, without language restriction until September 2021. We assessed the risk of bias in each study and the overall quality of evidence for exposure-outcome pairs that were reported in two or more studies. Read More

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Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

Radiother Oncol 2022 May 23. Epub 2022 May 23.

CRUK & UCL Cancer Trials Centre, London, United Kingdom.

Background: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival.

Patients And Method: SCORAD is a randomised trial of 686 patients comparing a single dose of 8Gy radiotherapy with 20Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). Read More

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Structural characterization and immunomodulatory activity of a mannan from Helvella leucopus.

Int J Biol Macromol 2022 May 23. Epub 2022 May 23.

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China; Key Laboratory of Modern Biomanufacturing of Anhui Province, Hefei 230601, Anhui, China. Electronic address:

A new polysaccharide fraction HLP-1 (2.55 × 10 Da) was obtained from the fruiting bodies of Helvella leucopus. Structural characterization of HLP-1 was elucidated by infrared spectroscopy, monosaccharide composition analysis, methylation analysis, nuclear magnetic resonance spectroscopy, scanning electron microscopy and Congo red assay. Read More

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Gastrointest Endosc 2022 May 23. Epub 2022 May 23.

Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita Salute San Raffaele University, Milan, Italy.

Background And Aims: Pancreatic Cystic Neoplasms (PCNs) represent a difficult preoperative diagnosis despite imaging improvement. In this study, we compare preoperative and final pathological diagnosis in a large cohort of resected PCNs, evaluating diagnostic accuracy with a specific focus on the value of Endoscopic Ultrasound (EUS).

Methods: A retrospective analysis of patients undergoing resection between 2009 and 2019 for presumed PCNs was performed. Read More

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A Novel LncRNA PTH-AS Upregulates Interferon-Related DNA damage resistance Signature genes and Promotes Metastasis in Human Breast Cancer Xenografts.

J Biol Chem 2022 May 23:102065. Epub 2022 May 23.

Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.

Long non-coding RNAs (lncRNAs) are important tissue-specific regulators of gene expression, and their dysregulation can induce aberrant gene expression leading to various pathological conditions, including cancer. Although many lncRNAs have been discovered by computational analysis, most of these are as yet unannotated. Herein, we describe the nature and function of a novel lncRNA detected downstream of the human parathyroid hormone (PTH) gene in both extremely rare ectopic PTH-producing retroperitoneal malignant fibrous histiocytoma and parathyroid tumors with PTH overproduction. Read More

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A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent anti-tumor activity against non-small cell lung cancers.

J Biol Chem 2022 May 23:102063. Epub 2022 May 23.

Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address:

Tumor angiogenesis is closely associated with the metastasis and progression of non-small cell lung cancer (NSCLC), a highly vascularized solid tumor. However, novel therapeutics are lacking for the treatment of this cancer. Here, we developed a series of 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazol analogs (6a-6x) as colchicine binding site-tubulin inhibitors, aiming to find a novel promising drug candidate for NSCLC treatment. Read More

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Ginsenoside CK induces apoptosis in triple-negative breast cancer cells by targeting glutamine metabolism.

Biochem Pharmacol 2022 May 23:115101. Epub 2022 May 23.

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China. Electronic address:

Breast cancer (BC) has replaced lung cancer as the most common cancer worldwide. Ginsenoside CK (CK) can effectively inhibit triple-negative breast cancer (TNBC), the occurrence and development of which are associated with glutamine addiction. However, the connection between CK and glutamine metabolism in TNBC proliferation and the mechanism of cell death induction remains unclear. Read More

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LAT1, a novel pharmacological target for the treatment of glioblastoma.

Biochem Pharmacol 2022 May 23:115103. Epub 2022 May 23.

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology (ISMIB), University of Liverpool, Liverpool, United Kingdom.

The L-Type Amino Acid transporter, LAT1 (SLC7A5), has a crucial role in mediating amino acid uptake into the cells, thus modulating cell growth and proliferation as well as other intracellular functions. Different studies have reported a central role of LAT1 in glioblastoma development and progression, suggesting that the modulation of its activity could be a novel therapeutic strategy. LAT1 also has an important role in the peripheral immune system, by regulating the activation status of several immune cells through modulation of the mechanistic target of rapamycin kinase. Read More

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Decreased HMGB1 expression contributed to cutaneous toxicity caused by lapatinib.

Biochem Pharmacol 2022 May 23:115105. Epub 2022 May 23.

Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou 310018, Zhejiang, P.R. China; Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, P.R. China. Electronic address:

The application of lapatinib, a widely used dual inhibitor of human epidermal growth factor receptor 1 (EGFR/ERBB1) and 2 (HER2/ERBB2), has been seriously limited due to cutaneous toxicity. However, the specific mechanism of lapatinib-induced cutaneous toxicity has not been clarified, leading to the lack of an effective strategy to improve clinical safety. Here, we found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and ultimately cause apoptosis of keratinocytes. Read More

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Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study.

Lancet Gastroenterol Hepatol 2022 May 23. Epub 2022 May 23.

Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Unresectable solitary very early to early stage hepatocellular carcinoma is managed with ablation for curative intent. Radiation segmentectomy is a treatment option that delivers radioactive yttrium (Y)-bound microspheres transarterially to a segment of liver. The aim of this study was to assess the safety and efficacy of radiation segmentectomy in patients with unresectable hepatocellular carcinoma deemed unfavourable for ablation. Read More

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Dendritic cells can prime anti-tumor CD8 T cell responses through major histocompatibility complex cross-dressing.

Immunity 2022 May 23. Epub 2022 May 23.

Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA. Electronic address:

Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigen on major histocompatibility class I (MHC-I) molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8 T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentation pathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules, is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8 T cell activation in two subcutaneous tumor models. Read More

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Genetic changes associated with relapse in favorable histology Wilms tumor: A Children's Oncology Group AREN03B2 study.

Cell Rep Med 2022 May 25:100644. Epub 2022 May 25.

Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Robert H. Lurie Cancer Center, Northwestern University, 225 East Chicago Avenue, Box 17, Chicago, IL 60611, USA. Electronic address:

Over the last decade, sequencing of primary tumors has clarified the genetic underpinnings of Wilms tumor but has not affected therapy, outcome, or toxicity. We now sharpen our focus on relapse samples from the umbrella AREN03B2 study. We show that over 40% of relapse samples contain mutations in SIX1 or genes of the MYCN network, drivers of progenitor proliferation. Read More

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Engineered colorectal cancer tissue recapitulates key attributes of a patient-derived xenograft tumor line.

Biofabrication 2022 May 26. Epub 2022 May 26.

Department of Chemical Engineering Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL 36849-5127 , USA, Auburn, Alabama, 36849-5412, UNITED STATES.

The development of physiologically relevant in vitro colorectal cancer (CRC) models is vital for advancing understanding of tumor biology. Although CRC patient-derived xenografts (PDX) recapitulate key patient tumor characteristics and demonstrate high concordance with clinical outcomes, the use of this in vivo model is costly and low-throughput. Here we report the establishment and in-depth characterization of an in vitro tissue-engineered CRC model using PDX cells. Read More

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