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

Our mission is to make scientific results rapidly and widely available. We seek to maximize the impact of research via insightful review, to enable exceptional discoveries to be shared quickly, to eliminate the border between specialties, to link different fields of biomedical science, and to foster application of basic and clinical science to fight disease.

On June 2020, Scopus released their 2019 Journal Rankings on Oncology, and Oncotarget is among their highest rated (Q1) journals and ranked number one in total citations in oncology.

Oncotarget

Oncotarget published this research paper on August 11, 2020, entitled, “Survival after resection of brain metastases with white light microscopy versus fluorescence-guidance: A matched cohort analysis of the Metastasys study data,” by researchers from the University of Medicine Goettingen, Goettingen, Germany; University Medical Center Leipzig, Leipzig, Germany; University Hospital Muenster, Muenster, Germany.

The cover for issue 32 of Oncotarget features Figure 2, "This figure depicts overall survival and local in-brain recurrence-free survival in the study's subgroups," by Hussein, et al. which reported that the aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection.

Two groups were compared:
In the “white light” group, resection was performed with conventional microscopy.
In the 5-ALA group, fluorescence guided peritumoral resection was additionally performed after standard microscopic resection.
Local in-brain recurrence occurred in 21/175 patients with a rate of 15/119 in the white light and 6/56 in the 5-ALA group.

The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy.

Dr. Bawarjan Schatlo from the Department of Neurosurgery at The University of Medicine Goettingen said, "Metastatic brain disease is more common than primary brain tumors."

Another group made the case for extending tumor resection 5 millimeters into peritumoral tissue to perform a so-called supramarginal resection.

Its aim is to prolong progression-free survival through radical resection and improved local tumor control.

In a series of 52 patients, Kamp and colleagues detected positive fluorescence in 62% of resected cerebral metastases.

Thus, the utility and importance of using methods to improve local control of brain metastases remains an unresolved issue.

The aim of the current study was to compare survival and local recurrence in a cohort of patients who underwent surgery for brain metastases with 5-ALA fluorescence microscopy to one that was operated using microscopic white light only.

The Schatlo Research Team concluded in their Oncotarget research paper, "the present study confirmed that regardless of surgical adjunct, radiotherapy is strongly associated with improved survival."

To date, this research paper has generated an Altmetric Attention Score of 48. The Altmetric Attention Score provides 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.27688

Full text - https://www.oncotarget.com/article/27688/text/

Correspondence to - Bawarjan Schatlo - bawarjan.schatlo@med.uni-goettingen.de

Keywords - brain tumor, brain metastasis, fluorescence-guided surgery, 5-ALA

About Oncotarget

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Top-Performer: White Light Versus 5-ALA Fluorescence Guided Resection

Oncotarget published this trending research paper on February 2, 2021, entitled, "Testosterone deficiency in men receiving immunotherapy for malignant melanoma" by researchers from the University of Iowa.

Abstract:
Immunotherapy has been established as a standard of care for patients with malignant melanoma, however, the long-term side-effects of immunotherapy are still emerging. Studies over the last decade have documented increasing reports of endocrine dysfunction following the initiation of immunotherapy. Our study aimed to detect the proportion of men who have low testosterone before, during, and or/after receiving immunotherapy for malignant melanoma, and to determine the proportion of men who receive testosterone replacement therapy after detection of low testosterone. We performed retrospective chart review of patients with malignant melanoma treated with immunotherapy. Low testosterone was identified in 34 out of 49 patients at some point during their treatment with immunotherapy. Despite low testosterone levels in two-thirds of patients, only three patients were treated with testosterone replacement therapy. In addition to laboratory evidence of low testosterone, patients were also symptomatic as 43 out of 49 patients reported fatigue to their providers. Four patients developed hypophysitis and subsequent hypopituitarism, all of whom were receiving Ipilimumab. We conclude that patients with stage 3 or 4 melanoma treated with immunotherapy appear to be at an increased risk of developing testosterone deficiency during their treatment.

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DOI - https://doi.org/10.18632/oncotarget.27876

Full text - https://www.oncotarget.com/article/27876/text/

Correspondence to - Madeline Peters - madeline-peters@uiowa.edu

Keywords - cancer, melanoma, immunotherapy, testosterone deficiency, androgens, skin cancer

About Oncotarget

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

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Trending with Impact: Melanoma, Immunotherapy, and Testosterone Deficiency

The cover paper for Oncotarget Volume 12, Issue 12 is entitled, "Frame-shift mediated reduction of gain-of-function p53 R273H and deletion of the R273H C-terminus in breast cancer cells result in replication-stress sensitivity," by researchers from the Department of Biological Sciences Hunter College, Belfer Building, City University of New York, NY; The Graduate Center Biology and Biochemistry Programs of City University of New York, NY; Department of Biological Sciences, Columbia University, NY; Department of Cell and Developmental Biology, Weill Cornell Medical College, NY.

Abstract:
We recently documented that gain-of-function (GOF) mutant p53 (mtp53) R273H in triple negative breast cancer (TNBC) cells interacts with replicating DNA and PARP1. The missense R273H GOF mtp53 has a mutated central DNA binding domain that renders it unable to bind specifically to DNA, but maintains the capacity to interact tightly with chromatin. Both the C-terminal domain (CTD) and oligomerization domain (OD) of GOF mtp53 proteins are intact and it is unclear whether these regions of mtp53 are responsible for chromatin-based DNA replication activities. We generated MDA-MB-468 cells with CRISPR-Cas9 edited versions of the CTD and OD regions of mtp53 R273H. These included a frame-shift mtp53 R273Hfs387, which depleted mtp53 protein expression; mtp53 R273HΔ381-388, which had a small deletion within the CTD; and mtp53 R273HΔ347-393, which had both the OD and CTD regions truncated. The mtp53 R273HΔ347-393 existed exclusively as monomers and disrupted the chromatin interaction of mtp53 R273H. The CRISPR variants proliferated more slowly than the parental cells and mt53 R273Hfs387 showed the most extreme phenotype. We uncovered that after thymidine-induced G1/S synchronization, but not hydroxyurea or aphidicholin, R273Hfs387 cells displayed impairment of S-phase progression while both R273HΔ347-393 and R273HΔ381-388 displayed only moderate impairment. Moreover, reduced chromatin interaction of MCM2 and PCNA in mtp53 depleted R273Hfs387 cells post thymidine-synchronization revealed delayed kinetics of replisome assembly underscoring the slow S-phase progression. Taken together our findings show that the CTD and OD domains of mtp53 R273H play critical roles in mutant p53 GOF that pertain to processes associated with DNA replication.

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DOI -  https://doi.org/10.18632/oncotarget.27975

Full text - https://www.oncotarget.com/article/27975/text/

Correspondence to - Jill Bargonetti - bargonetti@genectr.hunter.cuny.edu

Keywords - mutant p53, gain-of-function, oligomerization, DNA replication, frame-shift, breast cancer

About Oncotarget

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

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CRISPR Used in Triple Negative Breast Cancer Research

View the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 12.
https://www.oncotarget.com/archive/v12/i12/

Cover Paper - “Frame-shift mediated reduction of gain-of-function p53 R273H and deletion of the R273H C-terminus in breast cancer cells result in replication-stress sensitivity” 
https://doi.org/10.18632/oncotarget.27975

News - “LY6 gene family presents a novel class of potential biomarkers associated with overall survival outcome of pancreatic ductal adenocarcinoma”
https://doi.org/10.18632/oncotarget.27968 (PDF Download)

Editorial - “Neoantigen evolution in head and neck cancer progression: Where do we go from here?” 
https://doi.org/10.18632/oncotarget.27942 (PDF Download)

Editorial - “Unexpected zinc dependency of ferroptosis – what is in a name?” https://doi.org/10.18632/oncotarget.27951 (PDF Download)

Research Paper - “Role for Fgr and Numb in retinoic acid-induced differentiation and G0 arrest of non-APL AML cells” 
https://doi.org/10.18632/oncotarget.27969

Research Paper - “Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy” 
https://doi.org/10.18632/oncotarget.27974

Research Paper - “Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type” https://doi.org/10.18632/oncotarget.27978

Research Paper - “Deep learning with deep convolutional neural network using FDG-PET/CT for malignant pleural mesothelioma diagnosis” 
https://doi.org/10.18632/oncotarget.27979

Keywords - mutant p53, DNA replication, head and neck cancer, biomarker, ferroptosis, retinoic acid(RA), hypoxia, thymic epithelial tumor, mesothelioma, AML, breast cancer, 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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Table of Contents - Volume 12, Issue 12

Oncotarget published "Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens" which reported that the current study examines urine samples from 66 subjects, comprising of 31 Urology clinic controls and 35 bladder cancer patients, using a Luminex based screening platform.

ELISA validation was carried out for the top 4 prospective urine biomarkers using an independent cohort of 20 Urology clinic controls and 60 bladder cancer subjects.

Eight of these urine proteins were able to differentiate BC from control urine with ROC AUC values exceeding 0.70 at p < 0.0001, with specificity values exceeding 0.9. Upon ELISA validation, urine IL-1α, IL-1ra, and IL-8 were able to distinguish control urine from urine drawn from various bladder cancer stages, with IL-8 being the best discriminator.

These Oncotarget findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer.

Urine IL-8 not only distinguishes bladder cancer from controls, it also discriminates high grade from low grade disease, and the successive clinical stages of bladder cancer.

Dr. Chandra Mohan from The University of Houston said, "Bladder cancer (BC) is the sixth most common cancer diagnosis in the United States and is over four times more common in men than women."

Urine biomarkers could potentially provide preliminary confirmation of low-grade BC before invasive procedures are performed and facilitate surveillance of BC, as reviewed.

The present study implements a Luminex based screening platform with a cytokine/chemokine panel that simultaneously interrogates 16 urine biomarkers, followed by ELISA validation of 4 prospective urine biomarkers.

Of the 16 proteins screened by Luminex, 12 were within the detectable range and among these, 10 urine biomarkers showed significant elevation in BC compared to the controls.

ELISA validation for these 4 urine biomarkers was carried out using an independent cohort of 20 urology clinic controls and 60 BC subjects.

Of these 4 proteins, IL-8 displayed the highest significance in discriminating between controls and BC patients and discriminating highly advanced stages/grades of BC from less advanced stages/grades of BC.

The Mohan Research Team concluded in their Oncotarget Research Output that these studies indicate that urine IL-1α, IL-1ra, and IL-8 are potential biomarkers of BC, two of which re-affirm previous reports.

These studies shed additional light on the potential utility of these markers, since some of them also exhibit the ability to discriminate T1 and/or T2-T4 from Ta BC, as well as high grade from low grade BC.

Looking forward, systematic studies in larger patient cohorts are warranted to establish the specific clinical contexts in which these markers may be used, including the following: for initial diagnosis of BC, for surveillance of tumor recurrence, and/or for assessing treatment response following BCG therapy or other therapeutic modalities.

Finally, these newer urine biomarkers need to be compared against the performance of current yardsticks such as the Bladderchek and UroVysion FISH assay.

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DOI - https://doi.org/10.18632/oncotarget.27941

Full text - https://www.oncotarget.com/article/27941/text/

Correspondence to - Chandra Mohan - cmohan@central.uh.edu

Keywords - urothelial, proteomics, targeted screens, interleukins, inflammation

About Oncotarget

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

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Trending with Impact: Novel Urine Protein Biomarkers in Bladder Cancer

Oncotarget published this priority research paper on June 9, 2020, entitled, “MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma,” by researchers from the United Kingdom’s University of Sheffield, Institute of Cancer Research, Royal Marsden NHS Trust, Sheffield Children’s Hospital, and University of Cambridge.

Abstract:
This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, MYCN amplification or MYCN expression resulted in increased cell death in response to a range of PARP inhibitors (niraparib, veliparib, talazoparib and olaparib) compared to the response seen in non-expressing/amplified cells. MYCN expression slowed replication fork speed and increased replication fork stalling, an effect that was amplified by PARP inhibition or PARP1 depletion. Increased DNA damage seen was specifically induced in S-phase cells. Importantly, PARP inhibition caused a significant increase in the survival of mice bearing MYCN expressing tumours in a transgenic murine model of MYCN expressing neuroblastoma. Olaparib also sensitized MYCN expressing cells to camptothecin- and temozolomide-induced cell death to a greater degree than non-expressing cells. In summary, MYCN expression leads to increased replication stress in neuroblastoma cells. This effect is exaggerated by inhibition of PARP, resulting in S-phase specific DNA damage and ultimately increased tumour cell death. PARP inhibition alone or in combination with classical chemotherapeutics is therefore a potential therapeutic strategy for neuroblastoma and may be more effective in MYCN expressing tumours.

To date, this priority research paper has generated an Altmetric Attention Score of 58. The Altmetric Attention Score provides an at-a-glance indication of the volume and type of online attention the research has received. 

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Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27329

DOI - https://doi.org/10.18632/oncotarget.27329

Full text - https://www.oncotarget.com/article/27329/text/

Correspondence to - Helen E. Bryant - h.bryant@sheffield.ac.uk and Louis Chesler - louis.chesler@icr.ac.uk

Keywords - PARP inhibitor, neuroblastoma, MYCN, replication stress, replication fork stalling

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

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