Oncotarget is a peer-reviewed, open-access biomedical journal dedicated to publishing high-quality, primarily oncology-focused research.

On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget published this research paper in Volume 13, entitled, “Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis" by researchers from Department of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan; Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

DOI - https://doi.org/10.18632/oncotarget.28306

Correspondence to - Yuji Morine - ymorine@tokushima-u.ac.jp 

Abstract

Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis–time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. Our results reveal striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identify the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.

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Keywords - metabolomics, essential amino acid, hepatocellular carcinoma, diagnostic biomarker

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Essential Amino Acids as Diagnostic Biomarkers of Hepatocellular Carcinoma

Oncotarget published this review in Volume 13, entitled, Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more" by researchers from Department of Comprehensive Cancer Treatment and Research at Aizu, Fukushima Medical University, Fukushima, Japan; Department of Surgery, Cancer Treatment Center, Aizu Chuo Hospital, Fukushima, Japan; Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan; Aizu Oncology Consortium, Fukushima, Japan; Department of Surgery, Nippon Medical School, Tokyo, Japan; Department of Surgery, Bange Kousei General Hospital, Fukushima, Japan; Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima, Japan; Department of Breast Surgery, Fukushima Medical University, Fukushima, Japan; Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan; Department of Radiation Oncology, Fukushima Medical University, Fukushima, Japan; Department of Colorectoanal Surgery, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan; Fukushima Medical University, Fukushima, Japan.

DOI - https://doi.org/10.18632/oncotarget.28303

Correspondence to - Masahiko Shibata - mshibata@fmu.ac.jp

Abstract

Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies. We reviewed the perspective of MDSCs with emerging evidence in this review.

Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs.

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Keywords - MDSC, immunosuppression, Treg, TAM, cancer

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Myeloid-Derived Suppressor Cells: Cancer, Autoimmune Diseases, and More

Oncotarget published this trending research perspective in Volume 13, entitled, "Treasures from trash in cancer research" by researchers from Núcleo de Pesquisas em Oncologia/Universidade Federal do Pará, Belém, Pará, Brazil; Instituto Metrópole Digital/Universidade Federal do Rio Grande do Norte, Natal, Brazil; Instituto de Ciências Biológicas/Universidade Federal do Pará, Belém, Pará, Brazil.

DOI - https://doi.org/10.18632/oncotarget.28308

Correspondence to - Paulo Pimentel de Assumpção - assumpcaopp@gmail.com

Abstract

Introduction: Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets.

Materials and Methods: Metagenomic tools were used to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated.

Results: In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found.

Conclusions: These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.

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Keywords - cancer metagenomics, cancer sncRNA expression, RNA-Seq variant calling

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Treasures From Trash in Cancer Research

Oncotarget published this research paper in Volume 13, entitled, "Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention" by researchers from Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR; School of Nursing, Oregon Health and Science University, Portland, OR; Department of Radiation Medicine, Oregon Health and Science University, Portland, OR; Department of Radiation Oncology, Dartmouth-Hitchcock’s Dartmouth Cancer Center, Lebanon, NH; Knight Cancer Institute, Oregon Health and Science University, Portland, OR; Department of Neurology and Division of Neuroscience, ONPRC, Oregon Health and Science University, Portland, OR.

DOI - https://doi.org/10.18632/oncotarget.28310

Correspondence to - Jacob Raber - raberj@ohsu.edu

Abstract

Purpose/Objectives: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention.

Materials and Methods: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments.

Results: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not.

Conclusions: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.

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Keywords - apoE, breast cancer, exercise intervention, fall rate, functional status

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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APOE Genotype Determines Cancer Patients Most Likely to Benefit From Exercise

Oncotarget published this trending research paper in Volume 13, entitled, "Mutation analysis performed on tumor biopsies from patients with newly-diagnosed germinal center aggressive B cell lymphomas" by researchers from the Department of Medicine University of Pennsylvania, Philadelphia, PA.
#openaccess #research #germinalcancer #lymphoma #cancer #oncologyresearch #peerreview #openscience #chemotherapy

DOI - https://doi.org/10.18632/oncotarget.28309

Correspondence to - Daniel J. Landsburg - daniel.landsburg@pennmedicine.upenn.edu 

Abstract

Comprehensive genomic analyses of tumor biopsies from patients with newly-diagnosed germinal center B cell (GCB) diffuse large B cell/high grade B cell lymphoma (DLBCL/HGBL) have identified molecular subtypes predictive of inferior survival, which are characterized by somatic mutations that can be detected through clinical laboratory mutation analysis (CLMA). To determine the frequency and predictive value of individual genetic mutations associated with these experimentally-defined poor-risk subgroups, we reviewed the findings from CLMA performed on tumors from patients with newly-diagnosed GCB DLBCL/HGBL who were previously treated at our institution. CLMA was successfully performed on 58/59 patient tumor biopsies with a median turnaround time of 16 days, and 51 on which CLMA was routinely performed with adequate clinical follow-up were analyzed. Patients whose tumors demonstrated CREBBP mutation experienced a lower estimated rate of 2-year disease free survival (DFS) as compared to those whose tumors did not (45% [95% CI 18–68%] vs. 67% [95% CI 44–83%], P = 0.045). CREBBP mutations may be frequent and predict for inferior DFS in patients with newly-diagnosed GCB DLBCL/HGBL. Furthermore, CLMA may be practically-applied to translate experimental findings into those with more direct application to risk stratification and clinical trial design in subsets of patients with DLBCL/HGBL.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-mutation-analysis-performed-on-tumor-biopsies-from-patients-with-newly-diagnosed-germinal-center-aggressive-b-cell-lymphomas/

Keywords - diffuse large B cell lymphoma, high grade B cell lymphoma, mutation analysis, next generation sequencing, chemotherapy

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Mutation Analysis of Newly-Diagnosed Germinal Center Aggressive B Cell Lymphomas

Oncotarget published this trending research paper in Volume 13, entitled, "MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway" by researchers from Thoracic Oncology, Department of Medicine, University of California, San Francisco, CA; Touro University, College of Osteopathic Medicine, Vallejo, CA.

DOI - https://doi.org/10.18632/oncotarget.28305

Correspondence to - Jen-Chieh Lee - jenchieh.lee@ucsf.edu , Shu Liu - shu.liu@ucsf.edu 

Abstract

Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. We sought to examine the anticancer effect of MK256 on AML. In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation. Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.

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Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-mk-is-novel-cdk-inhibitor-with-potent-antitumor-activity-in-aml-through-downregulation-of-stat-pathway

Keywords - AML, CDK8, kinase inhibitor, STAT pathway, xenograft

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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