Oncotarget

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About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 10), titled, "Inhibitory effects of Tomivosertib in acute myeloid leukemia," researchers based out of Chicago, Illinois, U.S., from Northwestern University’s Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, and Jesse Brown Veterans Affairs Medical Center conducted a new study to assess the efficacy of Tomivosertib to regulate the eIF4E binding protein in AML.

In this study, the researchers purchased Tomivosertib (and Venetoclax) from TargetMol. They cultured AML cell lines, used clonogenic leukemic progenitor assays in methylcellulose, cell viability assays, cell lysis and immunoblotting, co-immunoprecipitation assays, plasmids and transfections, and conducted proteomics immunoprecipitation analysis using liquid-chromatography-tandem mass spectrometry, gene annotation and protein function enrichment analysis, and statistical analysis.

“We demonstrate that Tomivosertib suppresses eIF4E phosphorylation in AML cells and decreases leukemic cell survival and proliferation.”

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DOI - https://doi.org/10.18632/oncotarget.27952

Full text - https://www.oncotarget.com/article/27952/text/

Correspondence to - Leonidas C. Platanias - [email protected]

Keywords - MNK, Tomivosertib, acute myeloid leukemia, eIF4E

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 10.

View the complete issue: https://www.oncotarget.com/archive/v12/i10/

COVER PAPER:

“Inhibitory effects of Tomivosertib in acute myeloid leukemia” https://doi.org/10.18632/oncotarget.27952

EDITORIAL:

“Raman spectroscopy determination of the mineral characteristics of microcalcifications in breast cancer, a way towards an improved screening approach” https://doi.org/10.18632/oncotarget.27912 (PDF Download)

EDITORIAL:

“Reactive oxygen species in leukemias: maintaining cancer cell proliferation via redox signaling and changing metabolic homeostasis” https://doi.org/10.18632/oncotarget.27913 (PDF Download)

RESEARCH PAPER:

“Genome wide DNA methylation landscape reveals glioblastoma’s influence on epigenetic changes in tumor infiltrating CD4+ T cells” https://doi.org/10.18632/oncotarget.27955

RESEARCH PAPER:

“Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity” https://doi.org/10.18632/oncotarget.27953

RESEARCH PAPER:

“Perioperative changes in the plasma metabolome of patients receiving general anesthesia for pancreatic cancer surgery” https://doi.org/10.18632/oncotarget.27956

RESEARCH PAPER:

“Transcriptome analyses of urine RNA reveal tumor markers for human bladder cancer: validated amplicons for RT-qPCR-based detection” https://doi.org/10.18632/oncotarget.27954

Keywords - acute myeloid leukemia, breast cancer, bladder cancer, leukemia, DNA methylation, tumor, glioblastoma, miRNA, skin toxicity, pancreatic cancer, cancer, science, research, oncology

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget published this trending research paper on April 13, 2021, entitled, “Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib,” by researchers from the University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, and Harvard Medical School.

The majority of circulating insulin–like growth factor (IGF) is synthesized and secreted by the liver, and levels of IGF dramatically decrease in chronic liver disease and HCC. IGF can be a helpful tool to determine the prognosis of patients with advanced HCC while undergoing treatment with sorafenib. Researchers also use the Child-Turcotte-Pugh (CTP) qualitative scoring system to assess severity of liver cirrhosis, hepatic reserve, guide treatment decisions, and to stratify patients with HCC into three groups (A, B, and C). CTP class A has a better prognosis compared to classes B and C.

“Assessing liver reserve in HCC is of a great value as a tool for stratification of patients in clinical trials as well as to predict HCC outcome and guide therapy decisions in routine practice.”

In the researchers’ prospective study, 171 patients with HCC from the University of Texas MD Anderson Cancer Center were screened and included in this study. Of the patients, 116 were classified in CTP group A. Patient IGF/CTP scores were calculated and the researchers used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. Based on CTP and the IGF/CTP scores, researchers reclassified group A patients into AA and AB risk groups, which differed significantly in terms of OS and PFS. The researchers followed up with all patients in the study until disease progression or death. Unfortunately, during the follow-up period, 100 patients passed away.

“After IGF/CTP scoring, 87 of 116 CTP class A patients were reclassified as IGF/CTP-A (AA) and 29 patients were reclassified as IGF/CTP-B (AB).”

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DOI - https://doi.org/10.18632/oncotarget.27924

Full text - https://www.oncotarget.com/article/27924/text/

Correspondence to - Ahmed O. Kaseb - [email protected]

Keywords - IGF-1, Child-Pugh, sorafenib, liver reserve, hepatocellular carcinoma

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 9), titled, "Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore," researchers conducted a study to create mibefradil analogs as superior radiosensitizers for glioblastomas.

In the current study, based on their previous findings, the researchers from Yale University used structure activity relationship analysis and EJ-DR assays to create, synthesize, and profile a series of 140 mibefradil analogs. Their goal was to develop superior mibefradil analogues, with reduced off-target effects and improved potency.

After successfully reducing the known off-target liabilities of mibefradil, the team selected the top 12 analogues for further in vitro and in vivo pharmacokinetic studies. These analogs were tested in vivo to verify that they cross the blood-brain barrier and accumulate in mouse brain tissue.

“We then tested the pharmacokinetic parameters of the synthesized analogues and validated their ability to cross the blood-brain barrier (BBB) and accumulate in mouse brain tissue, at levels similar to that observed with mibefradil.”

DOI - https://doi.org/10.18632/oncotarget.27933

Full text - https://www.oncotarget.com/article/27933/text/

Correspondence to - Yulia V. Surovtseva - [email protected] and Ranjit S. Bindra - [email protected]

Keywords - glioblastoma, radiosensitizers, mibefradil, DNA repair, alternative non-homologous end joining

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 9.

View the complete issue: https://www.oncotarget.com/archive/v12/i9/

Oncotarget Volume 12, Issue 9 features:

COVER PAPER:

“Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore” https://doi.org/10.18632/oncotarget.27933

EDITORIAL:

“Is there a role for CDK 4/6 inhibitors in breast cancer brain metastases?” https://doi.org/10.18632/oncotarget.27904 (PDF Download)

EDITORIAL:

“Epigenetic effects of pharmacologic ascorbate” https://doi.org/10.18632/oncotarget.27911 (PDF Download)

RESEARCH PAPER:

“Activation of plasmacytoid dendritic cells promotes AML-cell fratricide” https://doi.org/10.18632/oncotarget.27949

RESEARCH PAPER:

“Piperlongumine promotes death of retinoblastoma cancer cells” https://doi.org/10.18632/oncotarget.27947

RESEARCH PAPER:

“A higher De Ritis ratio (AST/ALT) is a risk factor for progression in high-risk non-muscle invasive bladder cancer” https://doi.org/10.18632/oncotarget.27944

RESEARCH PAPER:

“Down regulation of lactate dehydrogenase initiates apoptosis in HeLa and MCF-7 cancer cells through increased voltage-dependent anion channel protein and inhibition of BCL2” https://doi.org/10.18632/oncotarget.27950

REVIEW:

“Multigene tests for breast cancer: the physician’s perspective” https://doi.org/10.18632/oncotarget.27948

Keywords - breast cancer, bladder cancer, glioblastoma, plasmacytoid dendritic cells, pharmacologic ascorbate, retinoblastoma, cancer cells, cancer, science, research, oncology

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget published this trending paper on July 21, 2020, entitled, “Genomic markers of midostaurin drug sensitivity in FLT3 mutated and FLT3 wild-type acute myeloid leukemia patients,” by researchers from Knight Cancer Institute, Oregon Health and Science University; Division of Hematology and Medical Oncology, Oregon Health and Science University; Howard Hughes Medical Institute; Department of Cell, Developmental, and Cancer Biology, Oregon Health and Science University.

The researchers conducted a study to identify features that may predict response to midostaurin in FLT3 mutant and wild-type samples. They performed an ex vivo drug sensitivity screen on primary and relapsed AML samples, with corresponding targeted sequencing and RNA sequencing.

In order to understand the impact that different genomic alterations have on midostaurin response, the researchers identified 214 patients with AML and annotated for their FLT3 status. Of these patients, 193 were primary and 21 were relapse AML samples from the Beat AML publicly available dataset. Risk groups within the cohort were as follows: 73 samples were favorable risk, 59 samples were intermediate, and 68 were adverse. The median age of patients in the cohort was 61, with 52% male and 48% female.

“We hypothesized that there are additional genomic alterations and gene expression changes outside of FLT3-ITD mutations that can influence AML sample resistance or sensitivity to midostaurin and aimed to further characterize these factors.”

To date, this research paper has generated an Altmetric Attention score of 54. Altmetric Attention scores, located at the top-left of trending Oncotarget papers, provide an at-a-glance indication of the volume and type of online attention the research has received.

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DOI - https://doi.org/10.18632/oncotarget.27656

Full text - https://www.oncotarget.com/article/27656/text/

Correspondence to - Mara W. Rosenberg - [email protected]

Keywords - acute myeloid leukemia, drug sensitivity, midostaurin, drug resistance, FLT3

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 8), titled, "Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas," researchers examined five potential biomarkers across 18 different histologic subtypes of sarcoma in 163 tissue samples. Immunohistochemical staining, statistical analysis, and correlation-based network analysis revealed promising results.

Researchers from the University of Iowa, University of Alabama at Birmingham, and the Mayo Clinic, report the need for additional prognostic and therapeutic biomarkers to predict clinical behavior across different histological types of sarcoma.

“Although the French (FNCLCC) and NCI grading schemes have been adopted for many sarcomas, there is a substantial subset of sarcomas for which the grading scheme does not adequately predict clinical behavior.”

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DOI: https://doi.org/10.18632/oncotarget.27928

Full text: https://www.oncotarget.com/article/27928/text/

Correspondence to: Munir R. Tanas - [email protected]

About Oncotarget:

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Listen to short summaries of the latest oncology-focused research published in this week's issue of Oncotarget. https://www.oncotarget.com/archive/v12/i8/

Oncotarget Volume 12, Issue 8 features:

COVER PAPER:

“Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas” https://doi.org/10.18632/oncotarget.27928

NEWS:

“Immunotherapy and fatigue: what we know and what we don’t know” https://doi.org/10.18632/oncotarget.27946 (PDF Download)

EDITORIAL:

“Drug exposure: still relevant after all these years” https://doi.org/10.18632/oncotarget.27899 (PDF Download)

EDITORIAL:

“Up to your NEK2 in CIN” https://doi.org/10.18632/oncotarget.27918 (PDF Download)

RESEARCH PAPER:

“Analytic validation and clinical utilization of the comprehensive genomic profiling test, GEM ExTra®” https://doi.org/10.18632/oncotarget.27945

RESEARCH PAPER:

“Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib” https://doi.org/10.18632/oncotarget.27924

RESEARCH PAPER:

“Controlling for cellular heterogeneity using single-cell deconvolution of gene expression reveals novel markers of colorectal tumors exhibiting microsatellite instability” https://doi.org/10.18632/oncotarget.27935

RESEARCH PAPER:

“Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens” https://doi.org/10.18632/oncotarget.27941

RESEARCH PAPER:

“The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations” https://doi.org/10.18632/oncotarget.27943

RESEARCH PAPER:

“Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer” https://doi.org/10.18632/oncotarget.27932

RESEARCH PAPER:

“Carcinoma cells that have undergone an epithelial-mesenchymal transition differentiate into endothelial cells and contribute to tumor growth” https://doi.org/10.18632/oncotarget.27940

RESEARCH PAPER:

“Predicting clinical outcomes using cancer progression associated signatures” https://doi.org/10.18632/oncotarget.27934

RESEARCH PAPER:

“High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC” https://doi.org/10.18632/oncotarget.27930

About Oncotarget:

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget published this trending paper on March 30, 2021, entitled, “Differential expression of Vitamin D binding protein in thyroid cancer health disparities,” researchers from Harbor-UCLA Medical Center, Loma Linda University School of Medicine, and Riverside University Health System compared the expression of DBP in patients with thyroid cancer from Filipino Americans and European Americans.

Filipino Americans are disproportionately affected by thyroid cancer, and the goal of this research was to further elucidate the functional implications of DBP in different stages of thyroid cancer across ethnicities.

“Although DBP is an essential protein with multifunctional properties, very few studies are available on its contribution to thyroid cancer oncogenesis.”

Read the full study: https://www.oncotarget.com/article/27920/text/

The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels.

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DOI: https://doi.org/10.18632/oncotarget.27920

Full text: https://www.oncotarget.com/article/27920/text/

Correspondence to: Salma Khan - [email protected]

About Oncotarget:

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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